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Liu P, Li G, Yang Q, Cao K, Wang J. Risk factors for gastrointestinal complications during glucocorticoid therapy in internal medicine inpatients: a real-world retrospective analysis. BMC Pharmacol Toxicol 2025; 26:37. [PMID: 39979942 PMCID: PMC11841309 DOI: 10.1186/s40360-025-00871-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/08/2025] [Accepted: 02/17/2025] [Indexed: 02/22/2025] Open
Abstract
BACKGROUND The risk factors for gastrointestinal complications during glucocorticoid therapy in internal medicine inpatients are rarely reported. This study aimed to investigate the risk factors for gastrointestinal complications in internal medicine patients using glucocorticoids. METHODS Internal medicine inpatients receiving glucocorticoid therapy from February 2023 to September 2023 were included. Gastrointestinal complications were identified by careful review of the electronic medical records of these patients. The risk factors for gastrointestinal complications during glucocorticoid therapy were analyzed by univariable and multivariable logistic regression. Receiver operating characteristic (ROC) curve with Youden's index was used to determine the best cutoff point of the identified continuous variables. RESULTS Of the 960 inpatients included, 88 had gastrointestinal complications, with the most common complications including 27 (30.7%) with abdominal discomfort, 26 (29.5%) with acid regurgitation and heartburn, and 14 (15.9%) with asymptomatic positive fecal occult blood. Multiple logistic regression analysis showed that age ≥ 65 years [OR = 2.014, 95% CI (1.096, 3.703), p = 0.024], history of gastroesophageal reflux disease (GERD) [OR = 1.810, 95% CI (1.009, 3.250), p = 0.047], history of peptic ulcer (PU) [OR = 5.636, 95% CI (1.505, 21.102), p = 0.010], maximum dose of glucocorticoids [OR = 1.003, 95% CI (1.001, 1.004), p = 0.001], and nonsteroidal anti-inflammatory drugs (NSAIDs) [OR = 2.788, 95% CI (1.023, 7.597), p = 0.045] were associated with more gastrointestinal complications during glucocorticoid therapy in internal medicine inpatients. ROC curve analysis revealed that when the maximum dose of glucocorticoids was greater than 160 mg, gastrointestinal complications were more likely to occur. CONCLUSIONS The study shows that age ≥ 65 years, history of GERD, history of PU, maximum dose of glucocorticoids, and NSAIDs are associated with more gastrointestinal complications during glucocorticoid therapy in internal medicine inpatients. Multidisciplinary teams, including physicians, pharmacists, and nurses, should consider increased monitoring to inpatients with high-risk factors.
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Affiliation(s)
- Pengpeng Liu
- Department of Pharmacy, Beijing Tongren Hospital, Capital Medical University, 1 Dongjiaominxiang Street, Dongcheng District, Beijing, 100730, China
| | - Guangyao Li
- Department of Pharmacy, Beijing Tongren Hospital, Capital Medical University, 1 Dongjiaominxiang Street, Dongcheng District, Beijing, 100730, China
| | - Qinglin Yang
- Department of Neurology, Beijing Tongren Hospital, Capital Medical University, Beijing, China
| | - Kai Cao
- Beijing Institute of Ophthalmology, Beijing Tongren Hospital, Capital Medical University, Beijing, China
| | - Jiawei Wang
- Department of Pharmacy, Beijing Tongren Hospital, Capital Medical University, 1 Dongjiaominxiang Street, Dongcheng District, Beijing, 100730, China.
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2
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Grymonprez M, Capiau A, Steurbaut S, Boussery K, Mehuys E, Somers A, Petrovic M, De Backer TL, Lahousse L. Pharmacodynamic Drug-Drug Interactions and Bleeding Outcomes in Patients with Atrial Fibrillation Using Non-Vitamin K Antagonist Oral Anticoagulants: a Nationwide Cohort Study. Cardiovasc Drugs Ther 2025; 39:133-143. [PMID: 37930588 DOI: 10.1007/s10557-023-07521-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 10/23/2023] [Indexed: 11/07/2023]
Abstract
PURPOSE Pharmacodynamic drug-drug interactions (PD DDIs) may influence the safety of non-vitamin K antagonist oral anticoagulants (NOACs), but the extent to which PD DDIs increase bleeding risks, remains unclear. Therefore, the impact of PD DDIs on bleeding outcomes in NOAC-treated patients with atrial fibrillation (AF) was investigated. METHODS Using Belgian nationwide data, NOAC-treated AF patients were included between 2013-2019. Concomitant use of PD interacting drugs when initiating NOAC treatment was identified. RESULTS Among 193,072 patients, PD DDIs were identified in 114,122 (59.1%) subjects. After multivariable adjustment, concomitant use of PD interacting drugs was associated with significantly higher risks of major or clinically-relevant non-major bleeding (adjusted hazard ratio (aHR) 1.19, 95% confidence interval (CI) (1.13-1.24)), gastrointestinal (aHR 1.12, 95%CI (1.03-1.22)), urogenital (aHR 1.21, 95%CI (1.09-1.35)) and other bleeding (aHR 1.28, 95%CI (1.20-1.36)), compared to NOAC-treated AF patients without PD interacting drug use. Increased bleeding risks were most pronounced with P2Y12 inhibitors (aHR 1.62, 95%CI (1.48-1.77)) and corticosteroids (aHR 1.53, 95%CI (1.42-1.66)), followed by selective serotonin or serotonin and norepinephrine reuptake inhibitors (SSRI/SNRI, aHR 1.26, 95%CI (1.17-1.35)), low-dose aspirin (aHR 1.14, 95%CI (1.08-1.20)) and non-steroidal anti-inflammatory drugs (NSAID, aHR 1.10, 95%CI (1.01-1.21)). Significantly higher intracranial bleeding risks in NOAC users were observed with SSRI/SNRIs (aHR 1.50, 95%CI (1.25-1.81)) and corticosteroids (aHR 1.49, 95%CI (1.21-1.84)). CONCLUSION Concomitant use of PD interacting drugs, especially P2Y12 inhibitors and corticosteroids, was associated with higher major, gastrointestinal, urogenital, and other bleeding risks in NOAC-treated AF patients. Remarkably, higher intracranial bleeding risks were observed with SSRI/SNRIs and corticosteroids.
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Affiliation(s)
- Maxim Grymonprez
- Department of Bioanalysis, Pharmaceutical Care Unit, Faculty of Pharmaceutical Sciences, Ghent University, Ottergemsesteenweg 460, 9000, Ghent, Belgium
| | - Andreas Capiau
- Department of Bioanalysis, Pharmaceutical Care Unit, Faculty of Pharmaceutical Sciences, Ghent University, Ottergemsesteenweg 460, 9000, Ghent, Belgium
- Department of Pharmacy, Ghent University Hospital, C. Heymanslaan 10, 9000, Ghent, Belgium
| | - Stephane Steurbaut
- Centre for Pharmaceutical Research, Research Group of Clinical Pharmacology and Clinical Pharmacy, Vrije Universiteit Brussel, Laarbeeklaan 103, 1090, Jette, Belgium
- Department of Hospital Pharmacy, UZ Brussel, Laarbeeklaan 101, 1090, Jette, Belgium
| | - Koen Boussery
- Department of Bioanalysis, Pharmaceutical Care Unit, Faculty of Pharmaceutical Sciences, Ghent University, Ottergemsesteenweg 460, 9000, Ghent, Belgium
| | - Els Mehuys
- Department of Bioanalysis, Pharmaceutical Care Unit, Faculty of Pharmaceutical Sciences, Ghent University, Ottergemsesteenweg 460, 9000, Ghent, Belgium
| | - Annemie Somers
- Department of Bioanalysis, Pharmaceutical Care Unit, Faculty of Pharmaceutical Sciences, Ghent University, Ottergemsesteenweg 460, 9000, Ghent, Belgium
- Department of Pharmacy, Ghent University Hospital, C. Heymanslaan 10, 9000, Ghent, Belgium
| | - Mirko Petrovic
- Department of Geriatrics, Ghent University Hospital, C. Heymanslaan 10, 9000, Ghent, Belgium
| | - Tine L De Backer
- Department of Cardiology, Ghent University Hospital, C. Heymanslaan 10, 9000, Ghent, Belgium
| | - Lies Lahousse
- Department of Bioanalysis, Pharmaceutical Care Unit, Faculty of Pharmaceutical Sciences, Ghent University, Ottergemsesteenweg 460, 9000, Ghent, Belgium.
- Department of Epidemiology, Erasmus Medical Center, PO Box 2040, Rotterdam, 3000, CA, the Netherlands.
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3
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Shu CP, Nwegbu CG, Ginette DYA, Brown JA. Kissing duodenal ulcer in a young adult presenting as upper gastrointestinal bleeding in a resource-limited setting: A case report and literature review. Int J Surg Case Rep 2025; 127:110942. [PMID: 39930643 PMCID: PMC11864163 DOI: 10.1016/j.ijscr.2025.110942] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/12/2024] [Revised: 01/22/2025] [Accepted: 01/23/2025] [Indexed: 03/01/2025] Open
Abstract
INTRODUCTION Upper gastrointestinal bleeding from kissing duodenal ulcers has been reported frequently in elderly patients taking non-steroidal anti-inflammatory drugs (NSAIDs) and steroids but rarely reported in young adults. We reviewed the literature and discussed the management. PRESENTATION OF CASE We report a case of a 29-year-old Cameroonian male on over-the-counter NSAIDs and steroids, who presented with fatigue, acute abdominal pain, melena, and hematemesis. After resuscitation, esophagogastroduodenoscopy (EGD) revealed a Forest IIB duodenal bulb ulcer. Bleeding could not be controlled locally, necessitating laparotomy, at which time, anterior and posterior perforated duodenal ulcers sealed against the liver and pancreas were found, with active bleeding of the posterior ulcer. The bleeding vessel was over-sewn, followed by an antrectomy and Billroth II gastrojejunostomy. The patient was discharged on the eighth postoperative day and was followed up two weeks later with a satisfactory outcome. DISCUSSION Kissing duodenal ulcers may present in young adults with a history of NSAIDS and steroid use. Perforation may not always be apparent especially if sealed. Urgent EGD does not decrease mortality. CONCLUSION As demonstrated in this index case report, early diagnosis and surgical intervention could be lifesaving in a resource-limited setting.
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Affiliation(s)
- Chinonso Paul Shu
- Pan-African Academy of Christian Surgeons, Mbingo Baptist Hospital, Cameroon.
| | | | - Djomo Y A Ginette
- Pan-African Academy of Christian Surgeons, Mbingo Baptist Hospital, Cameroon
| | - James Allen Brown
- Pan-African Academy of Christian Surgeons, Mbingo Baptist Hospital, Cameroon
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Fujiwara M, Ikesue H, Yamaoka K, Uchida M, Uesawa Y, Muroi N, Shimizu T. Disproportionality Analysis of Hepatotoxic and Gastrointestinal Adverse Events Associated With Nintedanib Using the Japanese Adverse Drug Event Report (JADER) Database. In Vivo 2025; 39:396-403. [PMID: 39740899 PMCID: PMC11705104 DOI: 10.21873/invivo.13841] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/07/2024] [Revised: 09/24/2024] [Accepted: 09/25/2024] [Indexed: 01/02/2025]
Abstract
BACKGROUND/AIM Nintedanib may cause adverse events such as elevated liver enzyme levels, diarrhea, and decreased appetite. These adverse events should be managed appropriately as they affect the quality of life of patients. This study has aimed to analyze patient characteristics and time-to-onset of adverse events caused by nintedanib using the Japanese Adverse Drug Event Report (JADER) database. PATIENTS AND METHODS Data from April 2004 to June 2023 were extracted from the JADER database and the patient characteristics of nintedanib administration were evaluated using reported odds ratio (ROR) and 95% confidence interval (95%CI). The data were analyzed for time-to-onset and patient characteristics such as age, sex, body mass index (BMI), and the presence or absence of prednisolone. RESULTS The JADER database included 1,419 adverse event reports in which nintedanib was suspected. The number (%) and ROR of adverse events known to occur with the use of nintedanib were 72 (5.07%) cases of decreased appetite [ROR=7.09 (95%CI=5.59-8.99)], and 79 (5.57%) cases of diarrhea [ROR=6.52 (5.19-8.18)]. The median days until onset were 19.5 (IQR=6.25-50.5) days for hepatotoxicity, 119.5 (IQR=24.5-258.5) days for diarrhea, and 131.5 (IQR=20.5-334.5) days for decreased appetite. CONCLUSION Nintedanib is more likely to cause elevated liver enzyme levels, diarrhea, and decreased appetite than other drugs. These events occurred within approximately 3-4 months. The concomitant use of prednisolone may also be associated with gastrointestinal hemorrhage.
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Affiliation(s)
- Masaki Fujiwara
- Department of Pharmacy, Kobe City Medical Center General Hospital, Kobe, Japan
- School of Pharmacy, Hyogo Medical University, Kobe, Japan
| | - Hiroaki Ikesue
- Department of Pharmacy, Kobe City Medical Center General Hospital, Kobe, Japan
| | - Kenta Yamaoka
- Department of Pharmacy, Kobe City Medical Center General Hospital, Kobe, Japan
- School of Pharmacy, Hyogo Medical University, Kobe, Japan
| | - Mayako Uchida
- Department of Education and Research Center for Pharmacy Practice, Faculty of Pharmaceutical Sciences, Doshisha Women's College of Liberal Arts, Kyotanabe, Japan
| | - Yoshihiro Uesawa
- Department of Medical Molecular Informatics, Meiji Pharmaceutical University, Tokyo, Japan
| | - Nobuyuki Muroi
- Department of Pharmacy, Kobe City Medical Center General Hospital, Kobe, Japan
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5
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La VP, Tong HD, La VP, Le Thanh NM, Tran QM, Dang CP, Doan AV. Simultaneous triple peptic perforations: a report of an extremely rare case. J Surg Case Rep 2025; 2025:rjae800. [PMID: 39726568 PMCID: PMC11670774 DOI: 10.1093/jscr/rjae800] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/04/2024] [Accepted: 12/03/2024] [Indexed: 12/28/2024] Open
Abstract
Peptic ulcer perforations are common in surgical emergencies, whereas double perforations are rare, and triple peptic perforations are even exceedingly rare, with only a few cases documented. While undetected perforation during surgery can be fatal, the absence of standardized procedures for managing multiple perforations remains an ongoing challenge for surgeons. Herein, we describe a rare case of simultaneous triple peptic perforations in an elderly man with a prolonged history of analgesic and corticosteroid use. This case underscores the importance of screening multiple peptic perforations intraoperatively. Subtotal gastrectomy is suggested as an effective option when simple closure of perforations is infeasible.
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Affiliation(s)
- Van Phu La
- Department of Surgery, Can Tho City General Hospital, 04 Chau Van Liem Street, Tan An Ward, Ninh Kieu Disctrict, Can Tho 900000, Vietnam
- Faculty of Medicine, Can Tho University of Medicine and Pharmacy, 179 Nguyen Van Cu Street, An Khanh Ward, Ninh Kieu District, Can Tho 900000, Vietnam
| | - Hai Duong Tong
- Department of Surgery, Can Tho City General Hospital, 04 Chau Van Liem Street, Tan An Ward, Ninh Kieu Disctrict, Can Tho 900000, Vietnam
| | - Vinh Phuc La
- Faculty of Medicine, Can Tho University of Medicine and Pharmacy, 179 Nguyen Van Cu Street, An Khanh Ward, Ninh Kieu District, Can Tho 900000, Vietnam
| | - Nhat Minh Le Thanh
- Faculty of Medicine, Can Tho University of Medicine and Pharmacy, 179 Nguyen Van Cu Street, An Khanh Ward, Ninh Kieu District, Can Tho 900000,Vietnam
| | - Quan Minh Tran
- Faculty of Medicine, Can Tho University of Medicine and Pharmacy, 179 Nguyen Van Cu Street, An Khanh Ward, Ninh Kieu District, Can Tho 900000, Vietnam
| | - Cong Phi Dang
- Faculty of Medical Laboratory Science, Da Nang University of Medical Technology and Pharmacy, 99 Hung Vuong Street, Hai Chau 1 Ward, Hai Chau Disctrict, Da Nang 550000, Vietnam
| | - Anh Vu Doan
- Faculty of Medicine, Can Tho University of Medicine and Pharmacy, 179 Nguyen Van Cu Street, An Khanh Ward, Ninh Kieu District, Can Tho 900000, Vietnam
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Piedepalumbo FV, Motos A, Blasi F, Torres A. Safety of steroids in severe community-acquired pneumonia. Eur Respir Rev 2025; 34:240131. [PMID: 39778921 PMCID: PMC11707601 DOI: 10.1183/16000617.0131-2024] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/12/2024] [Accepted: 11/05/2024] [Indexed: 01/11/2025] Open
Abstract
The systemic use of corticosteroids for patients with severe community-acquired pneumonia (sCAP) remains controversial in clinical practice, particularly in terms of the safety profile of these drugs. This narrative review aims to analyse the available literature data concerning the safety of short-term steroid use in the treatment of sCAP, while also highlighting potential future research directions. Several trials and meta-analyses have evaluated corticosteroid therapy as an adjuvant treatment for sCAP, yielding heterogeneous results regarding its efficacy and safety. Despite the wide variability in results, it is generally accepted that steroids are not associated with a significant risk of healthcare-associated infections, gastrointestinal bleeding or acute kidney injury in patients with sCAP in the short term. Nevertheless, such drugs are linked to hyperglycaemia, necessitating regular monitoring and appropriate management. The influence of steroids on long-term outcomes and their potential risks in viral sCAP still needs to be investigated.
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Affiliation(s)
- Federica Viola Piedepalumbo
- Respiratory Unit and Cystic Fibrosis Adult Center, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy
- Department of Pathophysiology and Transplantation, Università degli studi di Milano, Milan, Italy
- These authors contributed equally to this work
| | - Ana Motos
- Hospital Clínic, Cellex Laboratory, CIBERES (Center for Networked Biomedical Research Respiratory Diseases, 06/06/0028), FCRB-Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), School of Medicine, University of Barcelona, Barcelona, Spain
- Center for Research in Transplantation and Translational Immunology, UMR 1064, Nantes Université, Nantes, France
- These authors contributed equally to this work
| | - Francesco Blasi
- Respiratory Unit and Cystic Fibrosis Adult Center, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy
- Department of Pathophysiology and Transplantation, Università degli studi di Milano, Milan, Italy
| | - Antoni Torres
- Hospital Clínic, Cellex Laboratory, CIBERES (Center for Networked Biomedical Research Respiratory Diseases, 06/06/0028), FCRB-Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), School of Medicine, University of Barcelona, Barcelona, Spain
- Respiratory Intensive Care Unit, Pneumology Department, Hospital Clínic, Barcelona, Spain
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7
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Vakil N. Peptic Ulcer Disease: A Review. JAMA 2024; 332:1832-1842. [PMID: 39466269 DOI: 10.1001/jama.2024.19094] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 10/29/2024]
Abstract
Importance In the US, peptic ulcer disease affects 1% of the population and approximately 54 000 patients are admitted to the hospital annually for bleeding peptic ulcers. Observations Approximately 10% of patients presenting with upper abdominal pain in a primary care setting have a peptic ulcer as the cause of their symptoms. The principal causes of peptic ulcer disease are Helicobacter pylori infection, which affects approximately 42% of patients with peptic ulcer disease, and aspirin or nonsteroidal anti-inflammatory drug (NSAID) use, which are etiologic factors in approximately 36% of people with peptic ulcer disease. Complications of peptic ulcer include bleeding (73% of patients), perforation (9% of patients), and pyloric obstruction (3% of patients). Annually, 10 000 people die of peptic ulcer disease in the US. Endoscopy definitively diagnoses peptic ulcer disease. Acid blockers, such as omeprazole, can heal peptic ulcers in approximately 80% to 100% of patients within 4 weeks, but gastric ulcers larger than 2 cm may require 8 weeks of treatment. Eradication of H pylori decreases peptic ulcer recurrence rates from approximately 50% to 60% to 0% to 2%. Discontinuing NSAIDs heals 95% of ulcers identified on endoscopy and reduces recurrence from 40% to 9%. When discontinuing an NSAID is not desirable, changing the NSAID (eg, from ketorolac to ibuprofen), adding a proton pump inhibitor such as omeprazole or lansoprazole, and eradicating H pylori with treatment such as bismuth, metronidazole, and tetracycline combined with omeprazole can reduce recurrence rates. Conclusions and Relevance Peptic ulcer disease is associated with increased hospitalization rates and mortality. Acid blocking with proton pump inhibitors, such as omeprazole or lansoprazole, is the primary treatment. Recurrence of ulcers can be prevented by eradicating H pylori if present and discontinuing aspirin or NSAIDs if applicable.
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Affiliation(s)
- Nimish Vakil
- University of Wisconsin School of Medicine and Public Health, Madison
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8
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Aldiabat M, Aleyadeh W, Muzammil T, Adewuyi K, Alahmad M, Jabri A, Alhuneafat L, Kilani Y, Alsakarneh S, Bilal M. Rates, Risk Factors, and Outcomes of Nonvariceal Upper Gastrointestinal Bleeding in Patients Hospitalized for COVID-19 in the United States. Curr Med Sci 2024; 44:1202-1209. [PMID: 39673580 DOI: 10.1007/s11596-024-2838-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/15/2023] [Accepted: 12/11/2023] [Indexed: 12/16/2024]
Abstract
OBJECTIVE This study aimed to investigate the incidence and predictors of non-variceal upper gastrointestinal bleeding (NVUGIB) in hospitalized patients with coronavirus disease 2019 (COVID-19), as well as the inpatient outcomes associated with this complication. METHODS This was an analysis of the National Inpatient Sample Database from January to December 2020. Adult COVID-19 patients were categorized into two groups based on NVUGIB development during hospitalization. Multivariate logistic analysis was performed to identify predictors and outcomes associated with NVUGIB in hospitalized COVID-19 patients in the US, after adjusting for age, sex, race, and Charlson Comorbidity Index (CCI) score, using Stata/BE 17.0. RESULTS Among 1 050 045 hospitalized patients, 1.87% developed NVUGIB. Asian Americans had the highest risk, followed by Native Americans, Hispanics, and African Americans, with odds ratios (ORs) of 1.70, 1.59, 1.40, and 1.14, respectively. Patients with higher CCI scores were also at greater risk (with ORs of 1.47, 2.09, and 3.45 for CCI scores of 1, 2, and 3, respectively). COVID-19 patients with NVUGIB had a higher risk of inpatient mortality (OR=3.84), acute kidney injury (OR=3.12), hypovolemic shock (OR=13.7), blood transfusion (OR=7.02), and in-hospital cardiac arrest (OR=4.02). CONCLUSION NVUGIB occurred in 1.87% of hospitalized COVID-19 patients and was associated with a threefold increase in mortality. Further research is necessary to identify strategies for reducing its incidence in COVID-19 patients with multiple risk factors.
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Affiliation(s)
- Mohammad Aldiabat
- Harvard T.H. Chan School of Public Health, Harvard University, Boston, 02115, USA.
| | - Wesam Aleyadeh
- Department of Medicine, Cleveland Clinic Akron General, Akron, 44307, USA
| | - Taimur Muzammil
- Department of Medicine, Allegheny Health Network, Pittsburgh, 15212, USA
| | - Kemi Adewuyi
- Department of Medicine, Allegheny Health Network, Pittsburgh, 15212, USA
| | - Majd Alahmad
- Department of Medicine, University of Pittsburgh, Pittsburgh, 15261, USA
| | - Ahmad Jabri
- Heart and Vascular Center, MetroHealth Medical Center, Cleveland, 44109, USA
| | - Laith Alhuneafat
- Department of Medicine, Allegheny Health Network, Pittsburgh, 15212, USA
| | - Yassine Kilani
- Department of Medicine, Lincoln Medical Center/Weil Cornell Medicine, Bronx, 10451, USA
| | - Saqr Alsakarneh
- Department of Medicine, University of Missouri-Kansas City, Kansas City, 64108, USA
| | - Mohammad Bilal
- Department of Medicine, University of Minnesota/Minneapolis VA Medical Center, Minneapolis, 55417, USA
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9
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Sephien A, Lozano M, Prince SP, Dayto DC, Minton C, Kumar A, Nerella N, Shah G. Comparison of Standard and Extended Dexamethasone Duration on Mortality in Patients with Severe COVID-19. South Med J 2024; 117:701-704. [PMID: 39622519 DOI: 10.14423/smj.0000000000001760] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/19/2024]
Abstract
OBJECTIVES Current guidelines recommend dexamethasone 6 mg/day for up to 10 days in patients with severe coronavirus disease 2019 (COVID-19) requiring supplemental oxygenation or mechanical ventilation. The practice has significant variation, however, and dexamethasone has been used for >10 days for many patients with severe COVID-19. The aim of this study was to assess the benefits and risks associated with standard versus extended use of dexamethasone in patients with severe COVID-19. METHODS A multicenter retrospective cohort study was conducted from January 2021 to December 2021. All of the consecutive patients with severe COVID-19 receiving 6 mg/day dexamethasone were eligible for inclusion. The primary outcome was the incidence of in-hospital mortality for patients treated with dexamethasone 6 mg/day for the standard duration of 10 days versus an extended duration of >10 days. RESULTS A total of 1294 patients met the inclusion criteria: 803 received the standard duration of dexamethasone and 491 received the extended duration. The incidence of in-hospital mortality was significantly higher (P = 0.003) in the extended duration group (36.5%) compared with the standard duration group (28.5%), with no significant difference in in-hospital major adverse cardiac events (16.1% for extended vs 13.2% for the standard duration; P = 0.15). CONCLUSIONS The results show that extended duration of dexamethasone compared with standard duration is associated with a significant increase in in-hospital mortality in patients with severe COVID-19. These findings need to be confirmed in well-designed and performed randomized controlled trials.
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Affiliation(s)
- Andrew Sephien
- From the Division of Cardiovascular Disease, University of Miami/Jackson Memorial Hospital, Miami, FL
| | - Marc Lozano
- Department of Internal Medicine, HCA Healthcare/University of South Florida (USF) Morsani GME Consortium: HCA Florida Citrus Hospital, Inverness
| | - Sean-Patrick Prince
- Department of Internal Medicine, HCA Healthcare/University of South Florida (USF) Morsani GME Consortium: HCA Florida Citrus Hospital, Inverness
| | - Denisse Camille Dayto
- Department of Hepatology and Liver Transplantation, Rutgers Health New Jersey Medical School, Newark, NJ
| | - Caroline Minton
- Department of Internal Medicine, HCA Healthcare/University of South Florida (USF) Morsani GME Consortium: HCA Florida Citrus Hospital, Inverness
| | - Ambuj Kumar
- Research Methodology and Biostatistics Core, Office of Research, Department of Internal Medicine, USF, Tampa
| | - Nishant Nerella
- Department of Cardiology, HCA Healthcare/USF Morsani GME Consortium: HCA Florida Citrus Hospital, Inverness
| | - Guarav Shah
- Department of Pulmonology, HCA Healthcare/USF Morsani GME Consortium: HCA Florida Citrus Hospital, Inverness
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10
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Loubani L, Bartlett JW, Mothner B, Asaithambi R, Lee S. Evaluation of Stress Ulcer Prophylaxis in Pediatric General Medicine Patients After Transfer From the Intensive Care Unit and at Discharge. J Pediatr Pharmacol Ther 2024; 29:630-635. [PMID: 39659854 PMCID: PMC11627567 DOI: 10.5863/1551-6776-29.6.630] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/17/2023] [Accepted: 02/06/2024] [Indexed: 12/12/2024]
Abstract
OBJECTIVES The primary aim of this study was to determine continuation rates of stress ulcer prophylaxis (SUP) upon transfer from a pediatric intensive care unit (PICU) to a general medicine unit and upon hospital discharge. The secondary aim was to identify patient characteristics or concomitant medications that were associated with continuation of SUP at transfer from the PICU. METHODS This retrospective chart review included patients who were initiated on acid suppression for SUP in the PICU between June 2021 and May 2022 and subsequently transferred to a general medicine unit prior to discharge. Patients were excluded if they were receiving acid suppressant therapy prior to admission or were started on acid suppressants for an indication other than SUP. RESULTS Two hundred three patients (median age, 3.3 years) were included. The rates of SUP continuation at the time of transfer from the PICU to a general medicine unit and at hospital discharge were 61.6% and 9.9%, respectively. Patients continued on SUP at the time of transfer from the PICU were more likely to be prescribed concomitant corticosteroids (p < 0.01), anticoagulants or antiplatelet medications (p < 0.01). CONCLUSIONS The continuation of SUP from the PICU to the general medicine unit is common at our institution and calls into question the appropriateness of this practice. Future research is warranted to investigate the appropriateness of the continuation of SUP at transitions of care. Additionally, implementation of institutional protocols standardizing review of SUP may help reduce unnecessary prescribing of acid suppressants in general medicine units and at discharge.
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Affiliation(s)
- Lamees Loubani
- Department of Pharmacy (LL, SL, JWB), Texas Children’s Hospital, Houston, TX
| | - Jenna W. Bartlett
- Department of Pharmacy (LL, SL, JWB), Texas Children’s Hospital, Houston, TX
| | - Brent Mothner
- Department of Pediatrics (BM, RA), Division of Pediatric Hospital Medicine, Baylor College of Medicine, Houston, TX
| | - Rathi Asaithambi
- Department of Pediatrics (BM, RA), Division of Pediatric Hospital Medicine, Baylor College of Medicine, Houston, TX
| | - Surin Lee
- Department of Pharmacy (LL, SL, JWB), Texas Children’s Hospital, Houston, TX
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11
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Sobolewska J, Dzialach L, Kuca P, Witek P. Critical illness-related corticosteroid insufficiency (CIRCI) - an overview of pathogenesis, clinical presentation and management. Front Endocrinol (Lausanne) 2024; 15:1473151. [PMID: 39574948 PMCID: PMC11580036 DOI: 10.3389/fendo.2024.1473151] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/30/2024] [Accepted: 10/22/2024] [Indexed: 11/24/2024] Open
Abstract
According to the Society of Critical Care Medicine, critical illness-related corticosteroid insufficiency (CIRCI) characterizes hypothalamic-adrenal axis insufficiency following acute medical conditions of various causes, i.e., sepsis, septic shock, acute respiratory distress syndrome, community-acquired pneumonia, and status after major surgical procedures. Due to highly variable etiology, understanding the pathomechanism and management of CIRCI assumes relevance for all centers providing intensive care. During CIRCI, multiple peripheral adaptations develop, and cortisol distribution volume increases due to hypothalamic-adrenal axis dysregulation, alterations in cortisol metabolism, and tissue resistance to corticosteroids. The proper diagnosis and treatment of CIRCI may be challenging in many cases. Although we have been acquainted with CIRCI since 2008, it remains a difficult condition with widely variable approaches among clinicians due to inconsistent high-quality study results determining the effect of corticosteroids on mortality. Corticosteroids are widely used in acutely ill patients, highlighting the necessity for reliable knowledge to support crucial clinicians' decisions in daily medical practice. In this review, we provide an overview of the clinical management of patients with CIRCI based on current recommendations and selected studies.
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Affiliation(s)
- Joanna Sobolewska
- Department of Internal Medicine, Endocrinology and Diabetes, Medical University of Warsaw, Warsaw, Poland
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12
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El Hajj W, Nahon S, Fares E, Quentin V, Grasset D, Arpurt JP, Skinazi F, Vitte RL, Costes L, Remy AJ, Locher C, Macaigne G. Prophylactic Proton Pump Inhibitors in Upper Gastrointestinal Bleeding: Impact and Underprescription in a French Multicentric Cohort. Dig Dis Sci 2024; 69:4053-4062. [PMID: 39395925 DOI: 10.1007/s10620-024-08663-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/24/2024] [Accepted: 09/22/2024] [Indexed: 10/14/2024]
Abstract
BACKGROUND Appropriate prescription of Proton pump inhibitors (PPIs) remains an important concern amid the rising overuse. A gap exists in the literature regarding the benefit of PPI prophylaxis and the consequences of underprescription in patients at risk for upper gastrointestinal bleeding (UGIB). AIMS This study aims to describe the characteristics of hemorrhage in relation to PPI use in patients experiencing UGIB, with a focus on high-risk individuals requiring gastroprotection. METHODS Data from a French multicentric cohort of patients experiencing UGIB were analyzed. Patients using PPI were compared to those without PPI considering bleeding etiologies and outcomes of peptic ulcer disease (PUD)-related hemorrhage. The rate of PPI use and its effect on bleeding characteristics in high-risk populations, defined based on international guidelines, were also assessed. RESULTS Among 2497 included patients, 31.1% were on PPI at bleeding onset. PPI users exhibited a significantly lower rate of PUD-related bleeding in comparison with those without PPI (24.7 vs 40.8%, respectively, p < 0.0001). Similar difference was observed in high-risk populations, of whom, only 40.3% had gastroprotection with PPI before bleeding onset. PPI prophylaxis, however, did not influence the severity of bleeding in the general study population or in high-risk groups. Multivariate analysis identified age, comorbidities, and having more than two anti-thrombotic agents as predictors of severe bleeding. CONCLUSIONS PPI users appear to have a lower rate of bleeding ulcers compared to non-users. However, underprescription in high-risk groups raises the need for standardized care to ensure appropriate PPI use.
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Affiliation(s)
- Weam El Hajj
- Groupe Hosptalier Intercommunal Le Raincy - Montfermeil, Montfermeil, France
| | - Stéphane Nahon
- Groupe Hosptalier Intercommunal Le Raincy - Montfermeil, Montfermeil, France
| | - Eddy Fares
- Groupe Hosptalier Intercommunal Le Raincy - Montfermeil, Montfermeil, France
| | | | - Denis Grasset
- Centre Hospitalier Bretagne-Atlantique, Vannes, France
| | | | | | | | - Laurent Costes
- Centre Hospitalier Intercommunal de Créteil, Créteil, France
| | | | | | - Gilles Macaigne
- Groupe Hosptalier Intercommunal Le Raincy - Montfermeil, Montfermeil, France.
- Gastroenterology and hepatology department, Groupe Hospitalier Intercommunal Le Raincy-Montfermeil, 10 avenue du Général Leclerc, 93370, Montfermeil, France.
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13
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Milic T, Shah K, Mitra A, Stabler S. Outcomes Associated with the use of High Dose Corticosteroids and IL-6 Inhibitors for the Treatment of Acute Respiratory Distress Syndrome Secondary to SARS COV-2. J Intensive Care Med 2024:8850666241287514. [PMID: 39429028 DOI: 10.1177/08850666241287514] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/22/2024]
Abstract
BACKGROUND During the COVID-19 pandemic, treatment strategies evolved rapidly. The RECOVERY trial established corticosteroids as the standard care for reducing mortality in COVID-19 patients. However, some critical care clinicians began using doses higher than those recommended in RECOVERY. OBJECTIVE To characterize the use of high-dose corticosteroids and IL-6 inhibitors in critically ill COVID-19 patients and examine their association with adverse drug events (ADEs). METHODS A retrospective cohort study of 320 electronic health records (January 1, 2020 - June 30, 2022) was conducted on COVID-19 patients requiring high-flow oxygen or mechanical ventilation. Patients were categorized based on corticosteroid dose: "high dose dexamethasone" (daily dose greater than 12 mg and/or for longer than 10 days), "low dose dexamethasone" (daily dose 12 mg or less for 10 days or less), and "no dexamethasone" (no corticosteroid therapy). Subgroups were created based on IL-6 inhibitor use. RESULTS High-dose dexamethasone was associated with increased odds of ADEs compared to low dose (OR 2.55, 95% CI 1.45 to 4.49) and no dexamethasone (OR 6.29, 95% CI 2.08 to 19.03). No additional efficacy benefit was observed in patients receiving high dose corticosteroids when compared to low dose corticosteroids. Patients receiving both an IL-6 inhibitor and high-dose dexamethasone had further increased odds of ADEs. High-dose dexamethasone was also associated with increased mortality compared to low dose (OR 3.78, 95% CI 1.97-7.25) and no dexamethasone (OR 15.22, 95% CI 3.27-70.74). CONCLUSIONS Acknowledging the risk for residual confounding, higher doses of dexamethasone were associated with increased ADEs and mortality. These findings highlight the need for careful consideration of the use of high-dose dexamethasone.
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Affiliation(s)
- Tessa Milic
- Lower Mainland Pharmacy Services, Fraser Health Authority, Royal Columbian Hospital, New Westminster, British Columbia, Canada
| | - Kieran Shah
- Lower Mainland Pharmacy Services, Fraser Health Authority, Surrey Memorial Hospital, Surrey, British Columbia, Canada
| | - Anish Mitra
- Lower Mainland Pharmacy Services, Fraser Health Authority, Surrey Memorial Hospital, Surrey, British Columbia, Canada
| | - Sarah Stabler
- Lower Mainland Pharmacy Services, Fraser Health Authority, Surrey Memorial Hospital, Surrey, British Columbia, Canada
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14
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Gomez‐Lumbreras A, Brendle M, Moorman‐Bishir K, Tan M, Malone DC. Nonvitamin K Anticoagulants: Risk of Bleeding When Interacting With Other Medications: A Cohort Study From Medicare. Clin Cardiol 2024; 47:e70023. [PMID: 39360666 PMCID: PMC11447635 DOI: 10.1002/clc.70023] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/22/2024] [Revised: 08/12/2024] [Accepted: 09/10/2024] [Indexed: 10/04/2024] Open
Abstract
INTRODUCTION Patients on nonvitamin K antagonist (NVKA) are usually taking other drugs. Potential interaction may increase the gastrointestinal (GI) bleeding risk associated with NVKA. METHODS Observational cohort study using Medicare data from 2017 to 2020. Participants receiving a NVKA were included. A concomitant overlapping period while on NVKA was assessed for nonsteroidal anti-inflammatory drugs (NSAIDS), selective serotonin reuptake inhibitors (SSRI), antiplatelets, glucocorticoids, aspirin and proton pump inhibitors (PPI). A logistic regression predicting either any bleeding or GI bleeding was conducted estimating the odds ratio (OR) and 95% confidence interval (CI). RESULTS A total of 102 531 people on NVKA with mean age 77 years (SD = 9.8) and 55% females (N = 56 671) were included. Previous history of GI bleeding occurred in 2 908 (2.8%) participants, concomitant exposure to PPI occurred in 38 713 (38%), SSRI in 16 487 (16%), clopidogrel in 15 795 (15.4%), NSAIDs in 13 715 (13.4%) and glucocorticoids in 13 715 (13.4%). Risk for any bleeding was shown for clopidogrel (OR: 1.37, 95% CI: 1.30, 1.44), prasugrel/ticagrelor (OR: 1.36, 95% CI: 1.18, 1.58), glucocorticoids (OR: 1.26, 95% CI: 1.19, 1.34), and SSRIs (OR: 1.13, 95% CI: 1.07, 1.19). GI bleeding risk was shown for clopidogrel (OR: 1.44, 95% CI: 1.34, 1.55), prasugrel/ticagrelor (OR: 1.47, 95% CI: 1.20, 1.79), SSRIs (OR: 1.09, 95% CI: 1.01, 1.17) and glucocorticoids (OR: 1.33, 95% CI: 1.23, 1.44). PPI use was correlated with both NSAID (r = 0.07, p ≤ 0.0001) and SSRI use (r = 0.09, p ≤ 0.0001). CONCLUSION NVKA concomitantly taken with antiplatelets, glucocorticoids, and SSRIs showed an increased risk for any bleeding and GI bleeding.
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Affiliation(s)
| | - Madeline Brendle
- Department of Health Outcomes, College of PharmacyThe University of Texas at AustinAustinTexasUSA
| | | | - Malinda Tan
- Real World Evidence, Open HealthBethesdaMarylandUSA
| | - Daniel C. Malone
- Department of PharmacotherapyUniversity of UtahSalt Lake CityUtahUSA
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15
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Saeki K, Nakagama H, Tanaka Y, Goto Y, Kaneshiro K, Kono H, Yanai K, Yamamoto H, Yoneda R, Shimakawa T, Ueki T. Rectum necrosis in a patient with severe COVID19 infection after CAR-T therapy: a case report. Surg Case Rep 2024; 10:227. [PMID: 39325308 PMCID: PMC11427651 DOI: 10.1186/s40792-024-02026-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/02/2024] [Accepted: 09/14/2024] [Indexed: 09/27/2024] Open
Abstract
BACKGROUND Coronavirus disease 2019 (COVID19) can cause gastrointestinal complications as well as respiratory tract disease. Coagulation abnormalities and thrombosis frequently occur in COVID19, especially in cases with severe clinical outcome. The relationship between gastrointestinal perforation and coagulopathy due to COVID19 remains unclear. CASE PRESENTATION A 49-year-old female received Chimeric antigen receptor T (CAR-T) therapy for an early recurrence of diffuse large B-cell lymphoma (DLBCL) that was refractory to chemotherapy. She was diagnosed with cytokine release syndrome (CRS) because of a fever and oxygen desaturation, and administered tocilizumab. Forty days after completing CAR-T therapy, she was infected with COVID19 and transferred to our hospital. Her general condition worsened and she developed COVID19 pneumonia, and then steroid pulse therapy was started. While her respiratory condition improved, she experienced pain in the anal region and computed tomography (CT) revealed a rectal perforation. An emergency surgery was undertaken, and the lower rectum wall was found to be completely necrotic. Removal of the necrotic part of the rectum tissue, and drainage and lavage of necrotic tissue in the pelvic cavity were performed. The remaining rectum was resected with partial sigmoidectomy, but we could not make the anal stump closed. In addition, an end colostomy in the sigmoid colon was performed. Histopathological findings showed thromboses in the rectal mesentery veins. After the first surgery, the pelvic abscess cavity persisted and her high-grade fever continued. Reoperation was laparoscopically performed, and she underwent a resection of anal canal with residual necrotic rectal and mesorectal tissue, and a drainage of the pelvic abscess. After the reoperation, her general condition improved and CT showed that the abscess cavity had significantly improved. CONCLUSIONS Gastrointestinal perforation, especially rectal necrosis due to coagulopathy caused by severe COVID19 infection, is a rare but life-threatening complication. Physicians should have a high degree of clinical suspicion for timely diagnosis and management, and surgical intervention is necessary in cases of rectal necrosis.
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Affiliation(s)
- Kiyoshi Saeki
- Department of Surgery, Hamanomachi General Hospital, 3-3-1, Nagahama, Fukuoka, 810-8539, Japan.
| | - Hidenobu Nakagama
- Department of Surgery, Hamanomachi General Hospital, 3-3-1, Nagahama, Fukuoka, 810-8539, Japan
| | - Yuichi Tanaka
- Department of Surgery, Hamanomachi General Hospital, 3-3-1, Nagahama, Fukuoka, 810-8539, Japan
| | - Yoshitaka Goto
- Department of Surgery, Hamanomachi General Hospital, 3-3-1, Nagahama, Fukuoka, 810-8539, Japan
| | - Kazuhisa Kaneshiro
- Department of Surgery, Hamanomachi General Hospital, 3-3-1, Nagahama, Fukuoka, 810-8539, Japan
| | - Hiroshi Kono
- Department of Surgery, Hamanomachi General Hospital, 3-3-1, Nagahama, Fukuoka, 810-8539, Japan
| | - Kosuke Yanai
- Department of Surgery, Hamanomachi General Hospital, 3-3-1, Nagahama, Fukuoka, 810-8539, Japan
| | - Hirofumi Yamamoto
- Department of Surgery, Hamanomachi General Hospital, 3-3-1, Nagahama, Fukuoka, 810-8539, Japan
| | - Reiko Yoneda
- Department of Pathology, Hamanomachi General Hospital, Fukuoka, Japan
| | - Takashi Shimakawa
- Department of Hematology, Hamanomachi General Hospital, Fukuoka, Japan
| | - Takashi Ueki
- Department of Surgery, Hamanomachi General Hospital, 3-3-1, Nagahama, Fukuoka, 810-8539, Japan
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16
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Brito-Dellan N, Franco-Vega MC, Ruiz JI, Lu M, Sahar H, Rajapakse P, Lin HY, Peterson C, Leal-Alviarez D, Altay H, Tomy S, Manzano JGM. Optimizing inpatient care for lung cancer patients with immune checkpoint inhibitor-related pneumonitis using a clinical care pathway algorithm. Support Care Cancer 2024; 32:661. [PMID: 39283351 DOI: 10.1007/s00520-024-08867-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/03/2024] [Accepted: 09/09/2024] [Indexed: 09/25/2024]
Abstract
PURPOSE Immune checkpoint inhibitor-related pneumonitis (ICI-P) is a condition associated with high mortality, necessitating prompt recognition and treatment initiation. This study aimed to assess the impact of implementing a clinical care pathway algorithm on reducing the time to treatment for ICI-P. METHODS Patients with lung cancer and suspected ICI-P were enrolled, and a multimodal intervention promoting algorithm use was implemented in two phases. Pre- and post-intervention analyses were conducted to evaluate the primary outcome of time from ICI-P diagnosis to treatment initiation. RESULTS Of the 82 patients admitted with suspected ICI-P, 73.17% were confirmed to have ICI-P, predominantly associated with non-small cell lung cancer (91.67%) and stage IV disease (95%). Pembrolizumab was the most commonly used immune checkpoint inhibitor (55%). The mean times to treatment were 2.37 days in the pre-intervention phase, 3.07 days (p = 0.46), and 1.27 days (p = 0.40) in the post-intervention phases 1 and 2, respectively. Utilization of the immunotoxicity order set significantly increased from 0 to 27.27% (p = 0.04) after phase 2. While there were no significant changes in ICU admissions or inpatient mortality, outpatient pulmonology follow-ups increased statistically significantly, demonstrating enhanced continuity of care. The overall mortality for patients with ICI-P was 22%, underscoring the urgency of optimizing management strategies. Notably, all patients discharged on high-dose corticosteroids received appropriate gastrointestinal prophylaxis and prophylaxis against Pneumocystis jirovecii pneumonia infections at the end of phase 2. CONCLUSION Implementing a clinical care pathway algorithm for managing severe ICI-P in hospitalized lung cancer patients standardizes practices, reducing variability in management.
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MESH Headings
- Humans
- Immune Checkpoint Inhibitors/adverse effects
- Immune Checkpoint Inhibitors/administration & dosage
- Male
- Algorithms
- Lung Neoplasms/drug therapy
- Female
- Aged
- Critical Pathways
- Middle Aged
- Pneumonia/etiology
- Aged, 80 and over
- Hospitalization/statistics & numerical data
- Carcinoma, Non-Small-Cell Lung/drug therapy
- Antibodies, Monoclonal, Humanized/administration & dosage
- Antibodies, Monoclonal, Humanized/therapeutic use
- Antibodies, Monoclonal, Humanized/adverse effects
- Antibodies, Monoclonal, Humanized/pharmacology
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Affiliation(s)
- Norman Brito-Dellan
- Department of Hospital Medicine, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd., Unit 1465, Houston, TX, 77030-40098, USA.
| | - Maria Cecilia Franco-Vega
- Department of Hospital Medicine, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd., Unit 1465, Houston, TX, 77030-40098, USA
| | - Juan Ignacio Ruiz
- Department of Health Services Research, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Maggie Lu
- Pharmacy Clinical Programs, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Hadeel Sahar
- Department of Hospital Medicine, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd., Unit 1465, Houston, TX, 77030-40098, USA
| | | | - Heather Y Lin
- Department of Biostatistics, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Christine Peterson
- Department of Biostatistics, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Daniel Leal-Alviarez
- Department of Hospital Medicine, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd., Unit 1465, Houston, TX, 77030-40098, USA
| | - Haider Altay
- Department of Hematology and Medical Oncology, The University of Texas Health Science Center at Tyler, Tyler, TX, USA
| | - Sophy Tomy
- Department of Hospital Medicine, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd., Unit 1465, Houston, TX, 77030-40098, USA
| | - Joanna-Grace Mayo Manzano
- Department of Hospital Medicine, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd., Unit 1465, Houston, TX, 77030-40098, USA
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17
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Hussen NHA, Qadir SH, Rahman HS, Hamalaw YY, Kareem PSS, Hamza BA. Long-term toxicity of fluoroquinolones: a comprehensive review. Drug Chem Toxicol 2024; 47:795-806. [PMID: 37501614 DOI: 10.1080/01480545.2023.2240036] [Citation(s) in RCA: 7] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/23/2022] [Revised: 07/11/2023] [Accepted: 07/14/2023] [Indexed: 07/29/2023]
Abstract
Fluoroquinolones (FQs) are highly potent bactericidal antibiotics with broad-spectrum activity against Gram-negative/positive bacteria. The Food and Drug Administration (FDA) anticipated the presence of a long-lasting incapacity of Fluoroquinolone Associated Toxicity (FQAT), which is not officially documented yet. This review aimed to précis the existing information on FQA long-term toxicity, such as cardiotoxicity, aortic aneurysm, tendon rupture, nephrotoxicity, hepatotoxicity, peripheral neuropathy, vagus nervous dysfunction, reactive oxygen species (ROS), phototoxicity, glucose hemostasis, and central nervous system (CNS) toxicity. We are focused on the CNS toxicity of FQs, either due to the direct action of the FQs on CNS receptors or by other drug co-administration, including nonsteroidal anti-inflammatory disease (NSAIDs) and theophylline. Due to the nature of the R7 side chain, FQs containing unsubstituted 7-piperazine and 7-pyrrolidine have the most significant effect. The gamma-aminobutyric acid-A (GABAA) receptor and CNS effects are inhibited through at least three possible mechanisms. Firstly, by the pharmacological action of the quinolone directly. Secondly, FQ-NSAIDs interact pharmacodynamically in which the interaction between the FQ and a receptor is significantly altered by the presence of another drug that interacts with the same receptor. An example may be the interaction between NSAIDs and some FQs. Thirdly, a pharmacokinetic drug-drug interaction leads to a higher concentration of quinolone or the other drug. An example may be the interaction between theophylline and benzodiazepines with some FQs.
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Affiliation(s)
- Narmin Hama Amin Hussen
- Department of Pharmacognosy and Pharmaceutical Chemistry, College of Pharmacy, University of Sulaimani, Sulaimaniyah, Iraq
| | - Shnyar Hamid Qadir
- Department of Biochemistry and Clinical Chemistry, College of Pharmacy, University of Sulaimani, Sulaimaniyah, Iraq
| | - Heshu Sulaiman Rahman
- Department of Physiology, College of Medicine, University of Sulaimani, Sulaimaniyah, Iraq
- Department of Medical Laboratory Sciences, Komar University of Science and Technology, Sulaimaniyah, Iraq
| | - Yusra Yassin Hamalaw
- Department of Pharmacognosy and Pharmaceutical Chemistry, College of Pharmacy, University of Sulaimani, Sulaimaniyah, Iraq
| | - Parsan Siyamand Shekh Kareem
- Department of Pharmacognosy and Pharmaceutical Chemistry, College of Pharmacy, University of Sulaimani, Sulaimaniyah, Iraq
| | - Botan Aziz Hamza
- Department of Pharmacognosy and Pharmaceutical Chemistry, College of Pharmacy, University of Sulaimani, Sulaimaniyah, Iraq
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18
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Eftimie Spitz R, Popa SL, Grad S, Dumitrascu DL, Ismaiel A, Surdea-Blaga T. The Use of Proton Pump Inhibitors in Patients with Liver Cirrhosis: Real Life Experience. J Clin Med 2024; 13:5155. [PMID: 39274368 PMCID: PMC11396469 DOI: 10.3390/jcm13175155] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/22/2024] [Revised: 08/12/2024] [Accepted: 08/28/2024] [Indexed: 09/16/2024] Open
Abstract
(1) Background: Proton pump inhibitors (PPIs) are commonly prescribed for gastric disorders. In patients with liver cirrhosis, PPI use is associated with an increased risk of spontaneous bacterial peritonitis and increased mortality rates; therefore, they should be used with caution. This study aims to evaluate the appropriateness of PPI prescriptions in hospitalized cirrhotic patients against current clinical guidelines to identify patterns of misuse and guide better prescribing practices. (2) Methods: A retrospective study was conducted on liver cirrhosis inpatients in an internal medicine department from January 2022 to May 2023. The primary measure was the proportion of PPI prescriptions aligned with clinical guidelines. Medical files were entirely reviewed by researchers to assess the appropriateness of PPI prescriptions using the current guidelines. Outcomes included the identification of common reasons for PPI prescription and the rate of inappropriate PPI use among the study population. (3) Results: The study included 189 cirrhotic patients, with PPIs prescribed to 95 (50.2%) patients during hospitalization and 75 (39.7%) patients at discharge. Among those, 47.4% of the inpatients and 34.7% at discharge had no valid indication for PPI administration. The most common reason for PPI prescription during hospital stays was gastritis, followed by antiplatelet use in high-risk patients, ulcers, and upper gastrointestinal bleeding. The most common inappropriate indication was portal hypertensive gastropathy (PHG), followed by treatment with corticosteroids and anticoagulants alone. We did not find an association between PPI administration during hospital stays and infections. Only in 4% of cases patients should have received PPIs and did not. (4) Conclusions: There is a concerning overprescription of PPIs in cirrhotic patients, often deviating from established guidelines. It subjects patients to unnecessary risks. There is an urgent need for increased awareness and adherence to clinical guidelines regarding PPI prescriptions in cirrhotic patients.
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Affiliation(s)
- Raphaël Eftimie Spitz
- Faculty of Medicine, "Iuliu Hatieganu" University of Medicine and Pharmacy, 400000 Cluj-Napoca, Romania
| | - Stefan Lucian Popa
- Faculty of Medicine, "Iuliu Hatieganu" University of Medicine and Pharmacy, 400000 Cluj-Napoca, Romania
- 2nd Department of Internal Medicine, Emergency County Hospital, 400003 Cluj-Napoca, Romania
| | - Simona Grad
- Faculty of Medicine, "Iuliu Hatieganu" University of Medicine and Pharmacy, 400000 Cluj-Napoca, Romania
- 2nd Department of Internal Medicine, Emergency County Hospital, 400003 Cluj-Napoca, Romania
| | - Dan Lucian Dumitrascu
- Faculty of Medicine, "Iuliu Hatieganu" University of Medicine and Pharmacy, 400000 Cluj-Napoca, Romania
- 2nd Department of Internal Medicine, Emergency County Hospital, 400003 Cluj-Napoca, Romania
| | - Abdulrahman Ismaiel
- Faculty of Medicine, "Iuliu Hatieganu" University of Medicine and Pharmacy, 400000 Cluj-Napoca, Romania
- 2nd Department of Internal Medicine, Emergency County Hospital, 400003 Cluj-Napoca, Romania
| | - Teodora Surdea-Blaga
- Faculty of Medicine, "Iuliu Hatieganu" University of Medicine and Pharmacy, 400000 Cluj-Napoca, Romania
- 2nd Department of Internal Medicine, Emergency County Hospital, 400003 Cluj-Napoca, Romania
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19
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Acton EK, Hennessy S, Gelfand MA, Leonard CE, Bilker WB, Shu D, Willis AW, Kasner SE. Thinking Three-Dimensionally: A Self- and Externally-Controlled Approach to Screening for Drug-Drug-Drug Interactions Among High-Risk Populations. Clin Pharmacol Ther 2024; 116:448-459. [PMID: 38860403 PMCID: PMC11262479 DOI: 10.1002/cpt.3310] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/05/2024] [Accepted: 05/06/2024] [Indexed: 06/12/2024]
Abstract
The global rise in polypharmacy has increased both the necessity and complexity of drug-drug interaction (DDI) assessments, given the growing potential for interactions involving more than two drugs. Leveraging large-scale healthcare claims data, we piloted a semi-automated, high-throughput case-crossover-based approach for drug-drug-drug interaction (3DI) screening. Cases were direct-acting oral anticoagulant (DOAC) users with either a major bleeding event during ongoing dispensings for potentially interacting, enzyme-inhibiting antihypertensive drugs (AHDs) (Study 1), or a thromboembolic event during ongoing dispensings for potentially interacting, enzyme-inducing antiseizure medications (ASMs) (Study 2). 3DI detection was based on screening for additional drug exposures that served as acute outcome triggers. To mitigate direct effects and confounding by concomitant drugs, self-controlled estimates were adjusted using negative cases (external "control" DOAC users with the same outcomes but co-dispensings for non-interacting AHDs or ASMs). Signal thresholds were set based on P-values and false discovery rate q-values to address multiple comparisons. Study 1: 285 drugs were examined among 3,306 episodes. Self-controlled assessments with q-value thresholds yielded 9 3DI signals (cases) and 40 DDI signals (negative cases). External adjustment generated 10 3DI signals from the P-value threshold and no signals from the q-value threshold. Study 2: 126 drugs were examined among 604 episodes. Assessments with P-value thresholds yielded 3 3DI and 26 DDI signals following self-control, as well as 4 3DI signals following adjustment. No 3DI signals met the q-value threshold. The presented self- and externally-controlled approach aimed to advance paradigms for real-world higher order drug interaction screening among high-susceptibility populations with pre-existent DDI risk.
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Affiliation(s)
- Emily K. Acton
- Center for Real-World Effectiveness and Safety of Therapeutics, Department of Biostatistics, Epidemiology, and Informatics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, US
- Translational Center of Excellence for Neuroepidemiology and Neurology Outcomes Research, Department of Neurology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, US
| | - Sean Hennessy
- Center for Real-World Effectiveness and Safety of Therapeutics, Department of Biostatistics, Epidemiology, and Informatics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, US
- Leonard Davis Institute of Health Economics, University of Pennsylvania, Philadelphia, PA, US
- Department of Systems Pharmacology and Translational Therapeutics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, US
| | - Michael A. Gelfand
- Department of Neurology, University of Pennsylvania, Philadelphia, PA, US
| | - Charles E. Leonard
- Center for Real-World Effectiveness and Safety of Therapeutics, Department of Biostatistics, Epidemiology, and Informatics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, US
- Leonard Davis Institute of Health Economics, University of Pennsylvania, Philadelphia, PA, US
| | - Warren B. Bilker
- Center for Real-World Effectiveness and Safety of Therapeutics, Department of Biostatistics, Epidemiology, and Informatics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, US
- Department of Psychiatry, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, US
| | - Di Shu
- Center for Real-World Effectiveness and Safety of Therapeutics, Department of Biostatistics, Epidemiology, and Informatics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, US
| | - Allison W. Willis
- Center for Real-World Effectiveness and Safety of Therapeutics, Department of Biostatistics, Epidemiology, and Informatics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, US
- Translational Center of Excellence for Neuroepidemiology and Neurology Outcomes Research, Department of Neurology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, US
- Leonard Davis Institute of Health Economics, University of Pennsylvania, Philadelphia, PA, US
- Department of Neurology, University of Pennsylvania, Philadelphia, PA, US
| | - Scott E. Kasner
- Department of Neurology, University of Pennsylvania, Philadelphia, PA, US
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20
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Nagaraju N, Varma A, Meshram RJ. Steroids in the Management of Ionotropic-Resistant Septic Shock: A Comprehensive Review of Efficacy and Outcomes. Cureus 2024; 16:e67795. [PMID: 39323670 PMCID: PMC11423274 DOI: 10.7759/cureus.67795] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/03/2024] [Accepted: 08/26/2024] [Indexed: 09/27/2024] Open
Abstract
Septic shock is a critical condition characterized by persistent hypotension despite adequate fluid resuscitation and the use of vasopressors, often accompanied by multi-organ dysfunction. A challenging subset, ionotropic-resistant septic shock, persists despite ionotropic support. Steroids have been explored as a treatment for septic shock due to their anti-inflammatory properties and potential to improve hemodynamic stability. This review aims to evaluate the efficacy and outcomes of steroid therapy in managing ionotropic-resistant septic shock, assessing its impact on mortality, hemodynamic parameters, and adverse effects. A comprehensive review of the current literature, including randomized controlled trials, observational studies, and clinical guidelines, was conducted. Key studies, such as the CORTICUS and ADRENAL trials, were analyzed to determine the effectiveness of steroid regimens, specifically low-dose hydrocortisone, in patients with septic shock resistant to ionotropic agents. Evidence from recent trials indicates that low-dose hydrocortisone therapy can improve hemodynamic stability and reduce mortality in patients with septic shock, including those with ionotropic resistance. However, the benefits may vary depending on the timing of intervention, patient characteristics, and the presence of contraindications. Steroid therapy is associated with potential adverse effects, including secondary infections, glucose dysregulation, and gastrointestinal issues. Steroid therapy, particularly low-dose hydrocortisone, appears to be an effective adjunctive treatment for ionotropic-resistant septic shock, offering improved shock reversal and reduced mortality. Nonetheless, careful consideration of the risks and benefits is essential, and ongoing research is needed to refine treatment protocols and optimize patient outcomes. This review provides a detailed synthesis of current evidence and offers recommendations for clinical practice and future research in the management of septic shock resistant to ionotropic agents.
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Affiliation(s)
- Nimmanagoti Nagaraju
- Paediatrics, Jawaharlal Nehru Medical College, Datta Meghe Institute of Higher Education and Research, Wardha, IND
| | - Ashish Varma
- Paediatrics, Jawaharlal Nehru Medical College, Datta Meghe Institute of Higher Education and Research, Wardha, IND
| | - Revat J Meshram
- Paediatrics, Jawaharlal Nehru Medical College, Datta Meghe Institute of Higher Education and Research, Wardha, IND
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21
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Bliźniak F, Chęciński M, Chęcińska K, Lubecka K, Kamińska M, Szuta M, Chlubek D, Sikora M. Non-Steroidal Anti-Inflammatory Drugs Administered Intra-Articularly in Temporomandibular Joint Disorders: A Systematic Review and Meta-Analysis. J Clin Med 2024; 13:4056. [PMID: 39064095 PMCID: PMC11278433 DOI: 10.3390/jcm13144056] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/25/2024] [Revised: 07/04/2024] [Accepted: 07/09/2024] [Indexed: 07/28/2024] Open
Abstract
Objectives: This systematic review was designed to summarize randomized controlled trials of intra-articular administration of non-steroidal anti-inflammatory drugs (NSAIDs) for temporomandibular disorders. Methods: Randomized controlled trials regarding intra-articular injections of non-steroidal anti-inflammatory drugs for temporomandibular disorders were included in the review. The final search was conducted on 16 June 2024 in the Bielefeld Academic Search Engine, PubMed, and Scopus databases. Results: Of the 173 identified studies, 6 were eligible for review. In trials comparing arthrocentesis alone to arthrocentesis with NSAIDs, slight differences in joint pain were noted. For tenoxicam, differences were under 1 point on a 0-10 scale after 4 weeks, with inconsistent results. Piroxicam showed no significant difference, and pain levels were minimal in both groups. For maximum mouth opening (MMO), tenoxicam showed no significant difference. Piroxicam increased MMO by nearly 5 mm, based on one small trial with bias concerns. Conclusions: Currently, there is no strong scientific evidence supporting the injection of NSAIDs into the temporomandibular joint to relieve pain or increase jaw movement. Preliminary reports on piroxicam with arthrocentesis and tenoxicam or diclofenac without rinsing justify further research.
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Affiliation(s)
- Filip Bliźniak
- Department of Oral Surgery, Preventive Medicine Center, Komorowskiego 12, 30-106 Kraków, Poland; (F.B.); (M.C.); (K.L.)
| | - Maciej Chęciński
- Department of Oral Surgery, Preventive Medicine Center, Komorowskiego 12, 30-106 Kraków, Poland; (F.B.); (M.C.); (K.L.)
| | - Kamila Chęcińska
- Department of Glass Technology and Amorphous Coatings, Faculty of Materials Science and Ceramics, AGH University of Science and Technology, Mickiewicza 30, 30-059 Kraków, Poland;
| | - Karolina Lubecka
- Department of Oral Surgery, Preventive Medicine Center, Komorowskiego 12, 30-106 Kraków, Poland; (F.B.); (M.C.); (K.L.)
| | - Monika Kamińska
- Provincial Hospital in Kielce, ul. Grunwaldzka 45, 25-736 Kielce, Poland;
| | - Mariusz Szuta
- Department of Oral Surgery, Medical College, Jagiellonian University, Montelupich 4, 31-155 Kraków, Poland;
| | - Dariusz Chlubek
- Department of Biochemistry and Medical Chemistry, Pomeranian Medical University, Powstańców Wielkopolskich 72, 70-111 Szczecin, Poland;
| | - Maciej Sikora
- Department of Biochemistry and Medical Chemistry, Pomeranian Medical University, Powstańców Wielkopolskich 72, 70-111 Szczecin, Poland;
- Department of Maxillofacial Surgery, Hospital of the Ministry of Interior, Wojska Polskiego 51, 25-375 Kielce, Poland
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22
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LeVine DN, Goggs R, Kohn B, Mackin AJ, Kidd L, Garden OA, Brooks MB, Eldermire ERB, Abrams-Ogg A, Appleman EH, Archer TM, Bianco D, Blois SL, Brainard BM, Callan MB, Fellman CL, Haines JM, Hale AS, Huang AA, Lucy JM, O'Marra SK, Rozanski EA, Thomason JM, Walton JE, Wilson HE. ACVIM consensus statement on the treatment of immune thrombocytopenia in dogs and cats. J Vet Intern Med 2024; 38:1982-2007. [PMID: 38779941 PMCID: PMC11256181 DOI: 10.1111/jvim.17079] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/29/2024] [Accepted: 04/04/2024] [Indexed: 05/25/2024] Open
Abstract
Management of immune thrombocytopenia (ITP) in dogs and cats is evolving, but there are no evidence-based guidelines to assist clinicians with treatment decisions. Likewise, the overall goals for treatment of ITP have not been established. Immunosuppressive doses of glucocorticoids are the first line treatment, but optimal treatment regimens beyond glucocorticoids remain uncertain. Additional options include secondary immunosuppressive drugs such as azathioprine, modified cyclosporine, and mycophenolate mofetil, usually selected based on clinician preference. Vincristine, human IV immunoglobulin (hIVIg), and transfusion of platelet or red blood cell-containing products are often used in more severe cases. Splenectomy and thrombopoietin receptor agonists are usually reserved for refractory cases, but when and in which patient these modalities should be employed is under debate. To develop evidence-based guidelines for individualized treatment of ITP patients, we asked 20 Population Intervention Comparison Outcome (PICO) format questions. These were addressed by 17 evidence evaluators using a literature pool of 288 articles identified by a structured search strategy. Evidence evaluators, using panel-designed templates and data extraction tools, summarized evidence and created guideline recommendations. These were integrated by treatment domain chairs and then refined by iterative Delphi survey review to reach consensus on the final guidelines. In addition, 19 non-PICO questions covering scenarios in which evidence was lacking or of low quality were answered by expert opinion using iterative Delphi surveys with panelist integration and refinement. Commentary was solicited from multiple relevant professional organizations before finalizing the consensus. The rigorous consensus process identified few comparative treatment studies, highlighting many areas of ITP treatment requiring additional studies. This statement is a companion manuscript to the ACVIM Consensus Statement on the Diagnosis of Immune Thrombocytopenia in Dogs and Cats.
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Affiliation(s)
- Dana N LeVine
- Department of Clinical Sciences, College of Veterinary Medicine, Auburn University, Auburn, Alabama, USA
| | - Robert Goggs
- Department of Clinical Sciences, College of Veterinary Medicine, Cornell University, Ithaca, New York, USA
| | - Barbara Kohn
- Small Animal Clinic, School of Veterinary Medicine, Freie Universität Berlin, Berlin, Germany
| | - Andrew J Mackin
- Department of Clinical Sciences, College of Veterinary Medicine, Mississippi State University, Mississippi State, Mississippi, USA
| | - Linda Kidd
- Linda Kidd Veterinary Internal Medicine Consulting, Carlsbad, California, USA
| | - Oliver A Garden
- School of Veterinary Medicine, Louisiana State University, Baton Rouge, Louisiana, USA
| | - Marjory B Brooks
- Department of Population Medicine and Diagnostic Sciences, College of Veterinary Medicine, Cornell University, Ithaca, New York, USA
| | - Erin R B Eldermire
- Flower-Sprecher Veterinary Library, College of Veterinary Medicine, Cornell University, Ithaca, New York, USA
| | - Anthony Abrams-Ogg
- Department of Clinical Studies, Ontario Veterinary College, University of Guelph, Guelph, Ontario, Canada
| | - Elizabeth H Appleman
- Department of Internal Medicine, The Animal Medical Center, New York, New York, USA
| | - Todd M Archer
- Bluff City Veterinary Specialists, Memphis, Tennessee, USA
| | - Domenico Bianco
- College of Veterinary Medicine, Western University of Health Sciences, Pomona, California, USA
| | - Shauna L Blois
- Department of Clinical Studies, Ontario Veterinary College, University of Guelph, Guelph, Ontario, Canada
| | - Benjamin M Brainard
- Department of Small Animal Medicine and Surgery, College of Veterinary Medicine, University of Georgia, Athens, Georgia, USA
| | - Mary Beth Callan
- Department of Clinical Sciences and Advanced Medicine, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA
| | - Claire L Fellman
- Department of Clinical Sciences, Cummings School of Veterinary Medicine, Tufts University, North Grafton, Massachusetts, USA
| | - Jillian M Haines
- Department of Veterinary Clinical Sciences, College of Veterinary Medicine, Washington State University, Pullman, Washington, USA
| | - Anne S Hale
- Zia Pet Hospital, Rio Rancho, New Mexico, USA
| | | | - John M Lucy
- Oradell Animal Hospital, Paramus, New Jersey, USA
| | - Shana K O'Marra
- Northwest Veterinary Critical Care Services, Vancouver, Washington, USA
| | - Elizabeth A Rozanski
- Department of Clinical Sciences, Cummings School of Veterinary Medicine, Tufts University, North Grafton, Massachusetts, USA
| | - John M Thomason
- Department of Clinical Sciences, College of Veterinary Medicine, Mississippi State University, Mississippi State, Mississippi, USA
| | - Jenny E Walton
- Veterinary Apheresis Service UK, Washington, Tyne and Wear, United Kingdom
| | - Helen E Wilson
- Langford Vets, University of Bristol, Langford, Somerset, United Kingdom
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Johnson A, Piplani S, Akpan E, Zinobia K, Bachan M, Radulovic M. Impact of connective tissue diseases on inpatient outcomes in gastrointestinal bleeding: insights from a national database analysis. Transl Gastroenterol Hepatol 2024; 9:35. [PMID: 39091649 PMCID: PMC11292097 DOI: 10.21037/tgh-24-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/10/2024] [Accepted: 04/18/2024] [Indexed: 08/04/2024] Open
Abstract
Background Connective tissue diseases (CTDs) are characterized by immune system dysregulation, which can profoundly impact the gastrointestinal (GI) system. While GI bleeding is a well-recognized cause of mortality and morbidity in the USA, its occurrence in patients with CTD remains documented but underexplored in terms of inpatient outcomes. GI bleeding in CTD is attributed to factors such as vasculopathy and drug-related risks, notably steroids and non-steroidal anti-inflammatory drugs (NSAIDs). This research seeks to conduct a comprehensive national-level analysis, utilizing the National Inpatient Sample (NIS), to compare GI bleeding outcomes between patients with CTD and those without this condition. Methods Utilizing the extensive NIS database covering 2020, we conducted a retrospective analysis of GI bleeding patients with CTD, identified through the International Classification of Diseases, 10th Revision (ICD-10). The primary outcome was in-hospital mortality. The secondary outcomes included rate of urgent esophagogastroduodenoscopy (EGD) and colonoscopy-endoscopy in 1 day or less, total rate of EGD and colonoscopy, rate of EGD and Colonoscopy with intervention, rate of complications including acute kidney injury (AKI), blood transfusion, sepsis, pneumonia, pulmonary embolism (PE) and healthcare utilization. Employing Stata software, we utilized multivariate logistic and linear regression analyses to adjust for confounders. Results There were 455,494 hospitalizations for GI bleeding and 19,874 involved patients with CTDs. The in-hospital mortality rate was significantly lower for CTD patients at 2.1%, compared to 2.4% for non-CTD patients [adjusted odds ratio (aOR): 0.79, 95% confidence interval (CI): 0.63-0.99, P=0.04]. CTD patients showed increased odds of total EGD, urgent colonoscopy, and total colonoscopy; however, these changes were not statistically significant. CTD patients had higher odds of complications, including PE (6.87% vs. 4.12%, P=0.009). However, there were no significant differences in mean length of hospital stay and total hospital charges (THCs) compared to non-CTD patients. Conclusions Patients with CTD exhibited a lower in-hospital mortality rate compared to those without CTD. The elevated risk of PE underscores the importance of implementing prophylactic measures for these patients.
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Affiliation(s)
- Adejoke Johnson
- Department of Internal Medicine, Jacobi Medical Center/North Central Bronx Hospital, New York, NY, USA
| | - Shobhit Piplani
- Department of Internal Medicine, Jacobi Medical Center/North Central Bronx Hospital, New York, NY, USA
| | - Ezekiel Akpan
- Department of Internal Medicine, Jacobi Medical Center/North Central Bronx Hospital, New York, NY, USA
| | - Khan Zinobia
- Department of Internal Medicine, James J Peters VA Medical Center, New York, NY, USA
| | - Moses Bachan
- Department of Internal Medicine, James J Peters VA Medical Center, New York, NY, USA
| | - Miroslav Radulovic
- Department of Internal Medicine, Jacobi Medical Center/North Central Bronx Hospital, New York, NY, USA
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24
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Piplani S, Jelic V, Johnson A, Shah U, Kolli S, Kong S, Tanasijevic N, Bejugam VR, Goguri SR, Mogga P, Kasire SP, Chaturvedi S, Jain P. Prevalence, Causes and Outcomes of Acute Gastrointestinal Bleeding in Rheumatoid Arthritis: A Systematic Review and Meta-Analysis. Mediterr J Rheumatol 2024; 35:210-219. [PMID: 39211013 PMCID: PMC11350423 DOI: 10.31138/mjr.230324.pca] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/23/2024] [Revised: 05/18/2024] [Accepted: 05/20/2024] [Indexed: 09/04/2024] Open
Abstract
Aim The present study aims to investigate the prevalence, causes and outcomes of acute gastrointestinal (GI) bleeding in Rheumatoid arthritis (RA). Methods A systemic search was conducted from electronic databases (PubMed/Medline, Cochrane Library, and Google Scholar) from inception to 14th November 2023. All statistical analyses were conducted in Review Manager 5.4.1. Studies meeting inclusion criteria were selected. A random-effect model was used when heterogeneity was seen to pool the studies, and the result was reported in prevalence and their corresponding 95% confidence interval (CI). Other outcomes were assessed using qualitative analysis. Results A total of eight studies (six observational studies and 2 trials were used to conduct this systematic review and meta-analysis. A total population of 138,041 patients was used. Pooled analysis showed a statistically significant risk of GI bleeding in RA patients receiving NSAIDs (prevalence = 2% (1%, 3%); P < 0.00001; I2 = 98%). Qualitatively, causes and outcomes were discussed. Conclusion Our study showed that 2% RA patients were subjected to GI bleeding, when they used NSAIDs. Other causes of GI bleeding were age-related factors, cardiovascular events, history of GI complications, and peptic ulcers. Outcome varied by the use of specific NSAIDs and the presence of comorbidities. Recent guidelines for the management of RA may mention GI bleeding as a potential complication, but the level of emphasis placed on this issue varies. Some guidelines provide comprehensive recommendations for its prevention and management, while others offer limited guidance.
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Affiliation(s)
- Shobhit Piplani
- Jacobi Medical Centre/North Central Bronx, Albert Einstein College of Medicine, NYC Health and Hospitals, New York, New York, United States
| | - Vladimir Jelic
- Jacobi Medical Centre/North Central Bronx, Albert Einstein College of Medicine, NYC Health and Hospitals, New York, New York, United States
| | - Adejoke Johnson
- Jacobi Medical Centre/North Central Bronx, Albert Einstein College of Medicine, NYC Health and Hospitals, New York, New York, United States
| | - Usman Shah
- Jacobi Medical Centre/North Central Bronx, Albert Einstein College of Medicine, NYC Health and Hospitals, New York, New York, United States
| | - Shiny Kolli
- Jacobi Medical Centre/North Central Bronx, Albert Einstein College of Medicine, NYC Health and Hospitals, New York, New York, United States
| | - Steve Kong
- Jacobi Medical Centre/North Central Bronx, Albert Einstein College of Medicine, NYC Health and Hospitals, New York, New York, United States
| | - Nikola Tanasijevic
- Jacobi Medical Centre/North Central Bronx, Albert Einstein College of Medicine, NYC Health and Hospitals, New York, New York, United States
| | - Vishal Reddy Bejugam
- Jacobi Medical Centre/North Central Bronx, Albert Einstein College of Medicine, NYC Health and Hospitals, New York, New York, United States
| | - Sumaja Reddy Goguri
- Frank H. Netter MD School of Medicine/St. Vincent’s Medical Centre, Connecticut, United States
| | - Phanidhar Mogga
- Frank H. Netter MD School of Medicine/St. Vincent’s Medical Centre, Connecticut, United States
| | - Sripada Preetham Kasire
- Jacobi Medical Centre/North Central Bronx, Albert Einstein College of Medicine, NYC Health and Hospitals, New York, New York, United States
| | - Salil Chaturvedi
- Jacobi Medical Centre/North Central Bronx, Albert Einstein College of Medicine, NYC Health and Hospitals, New York, New York, United States
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25
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Yao Y, Ba T, Bao B, Zhang S, Kong L. Sepsis as a Potential Risk Factor for Upper Gastrointestinal Bleeding in Critically Ill Patients: A Systematic Review and Meta-analysis. J Intensive Care Med 2024:8850666241252048. [PMID: 38813775 DOI: 10.1177/08850666241252048] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 05/31/2024]
Abstract
Purpose: Sepsis is a common and critical condition in intensive care units (ICUs) known to complicate patient outcomes. Previous studies have indicated an association between sepsis and various ICU morbidities, including upper gastrointestinal bleeding (UGIB). However, the extent of this relationship and its implications in ICU settings remain inadequately quantified. This study aims to elucidate the association between sepsis and the risk of UGIB in ICU patients. Methods: A comprehensive meta-analysis was conducted, encompassing nine studies with a total of nearly 9000 participants. These studies reported events for both sepsis and nonsepsis patients separately. Pooled odds ratios (ORs) were calculated to assess the risk of UGIB in septic versus nonseptic ICU patients. Subgroup analyses were conducted based on age and study design, and both unadjusted and adjusted ORs were examined. Results: The pooled OR indicated a significant association between sepsis and UGIB (OR = 3.276, 95% CI: 1.931 to 5.557). Moderate heterogeneity was observed (I² = 43.9%). The association was significant in adults (pooled OR = 4.083) but not in children. No difference in association was found based on the study design. Unadjusted and adjusted ORs differed slightly, indicating the influence of confounding factors. Conclusion: This meta-analysis reveals a significant association between sepsis and an increased risk of UGIB in ICU patients, particularly in adults. These findings highlight the need for vigilant monitoring and proactive management of septic ICU patients to mitigate the risk of UGIB. Future research should focus on understanding the underlying mechanisms and developing tailored preventive strategies.
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Affiliation(s)
- Yanfen Yao
- Department of Intensive Care Medicine, Shandong Provincial Third Hospital, Shandong University, Jinan, China
- The First Clinical Medical College, Shandong University of Traditional Chinese Medicine, Jinan, China
| | - Tejin Ba
- Department of Emergency, International Mongolian Hospital of Inner Mongolia, Hohhot, China
| | - Bagenna Bao
- Department of Emergency, International Mongolian Hospital of Inner Mongolia, Hohhot, China
| | - Shuanglin Zhang
- Department of Emergency, International Mongolian Hospital of Inner Mongolia, Hohhot, China
| | - Li Kong
- The First Clinical Medical College, Shandong University of Traditional Chinese Medicine, Jinan, China
- Department of Emergency Center, Shandong University of Traditional Chinese Medicine Affiliated Hospital, Jinan, China
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26
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Butt N, Usmani MT, Mehak N, Mughal S, Qazi-Arisar FA, Mohiuddin G, Khan G. Risk factors and outcomes of peptic ulcer bleed in a Pakistani population: A single-center observational study. World J Gastrointest Pharmacol Ther 2024; 15:92305. [PMID: 38846968 PMCID: PMC11151881 DOI: 10.4292/wjgpt.v15.i3.92305] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/22/2024] [Revised: 04/24/2024] [Accepted: 05/20/2024] [Indexed: 05/27/2024] Open
Abstract
BACKGROUND Peptic ulcer disease (PUD) remains a significant healthcare burden, contributing to morbidity and mortality worldwide. Despite advancements in therapies, its prevalence persists, particularly in regions with widespread nonsteroidal anti-inflammatory drugs (NSAIDs) use and Helicobacter pylori infection. AIM To comprehensively analyse the risk factors and outcomes of PUD-related upper gastrointestinal (GI) bleeding in Pakistani population. METHODS This retrospective cohort study included 142 patients with peptic ulcer bleeding who underwent upper GI endoscopy from January to December 2022. Data on demographics, symptoms, length of stay, mortality, re-bleed, and Forrest classification was collected. RESULTS The mean age of patients was 53 years, and the majority was men (68.3%). Hematemesis (82.4%) and epigastric pain (75.4%) were the most common presenting symptoms. Most patients (73.2%) were discharged within five days. The mortality rates at one week and one month were 10.6% and 14.8%, respectively. Re-bleed within 24 h and seven days occurred in 14.1% and 18.3% of patients, respectively. Most ulcers were Forrest class (FC) III (72.5%). Antiplatelet use was associated with higher mortality at 7 and 30 d, while alternative medications were linked to higher 24-hour re-bleed rates. NSAID use was associated with more FC III ulcers. Re-bleed at 24 h and 7 d was strongly associated with one-week or one-month mortality. CONCLUSION Antiplatelet use and rebleeding increase the risk of early mortality in PUD-related upper GI bleeding, while alternative medicines are associated with early rebleeding.
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Affiliation(s)
- Nazish Butt
- Department of Gastroenterology, Jinnah Postgraduate Medical Centre, Karachi 75505, Sindh, Pakistan
| | - Muhammad Tayyab Usmani
- National Institute of Liver & GI Diseases, Dow University of Health Sciences, Karachi 75330, Sindh, Pakistan
| | - Nimrah Mehak
- Department of Gastroenterology, Jinnah Postgraduate Medical Centre, Karachi 75505, Sindh, Pakistan
| | - Saba Mughal
- School of Public Health, Dow University of Health Sciences, Karachi 75330, Sindh, Pakistan
| | - Fakhar Ali Qazi-Arisar
- National Institute of Liver & GI Diseases, Dow University of Health Sciences, Karachi 75330, Sindh, Pakistan
| | - Ghulam Mohiuddin
- Department of Gastroenterology, Jinnah Postgraduate Medical Centre, Karachi 75505, Sindh, Pakistan
| | - Gulzar Khan
- Department of Gastroenterology, Jinnah Postgraduate Medical Centre, Karachi 75505, Sindh, Pakistan
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Maria Medeiros de Ataides Bezerra M, Cristina de Farias Andrade I, Cesar Dias de Melo Silva J, Clara Santos Costa A, Ricardo Costa da Silva R, Richardison Silva Vasconcelos L, de Fátima Cavalcanti Toscano Barreto M, Maria Moreira Beltrão Pereira L, Wanessa Santos Rocha S. Hepatic expression of tumor necrosis factor-α and evaluation of MAPK-p38 and NFκB signaling pathways in autoimmune hepatitis. Cytokine 2024; 177:156541. [PMID: 38368696 DOI: 10.1016/j.cyto.2024.156541] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/23/2023] [Revised: 01/12/2024] [Accepted: 02/06/2024] [Indexed: 02/20/2024]
Abstract
OBJECTIVES Autoimmune hepatitis (AIH) is a necroinflammatory disease that occurs when genetically susceptible individuals are exposed to an environmental trigger. It is a rare disease, and its epidemiological aspects are nearly unknown in Northeast Brazil. In the literature, the activation of components of the inflammatory cascade pathways, including interleukins such as TNF-α and signaling factors like MAPK-p38 and NFκB, in the pathogenesis of AIH is well described in animal models. This study evaluated, for the first time, the immunostaining of TNF-α, MAPK-p38, and NFκB in immunohistochemical analysis of liver biopsies from AIH patients. The activation of the MAPK-p38 pathway was also studied through immunoassay analysis in the peripheral blood of AIH patients. METHODS AND RESULTS Data from medical records of 25 AIH patients were analyzed. Histological and immunohistochemical analysis of liver tissue obtained from biopsies was performed to detect NFκB, MAPK-p38, and TNF-α. Immunoassay analysis of the MAPK-p38 pathway was performed in peripheral blood from 18 AIH patients and 8 healthy volunteers. Medical record analysis showed an average age of 33.3 years, with a female predominance in a ratio of 7.3:1. Concomitance with other autoimmune diseases was observed in 36 % of patients, with thyroid disorders being the most prominent among them, and an 8 % indication for liver transplantation. In the evaluation of autoantibodies, ANA was detected in 52 %, followed by SMA at 20 %, and Anti-LKM-1 at 16 %. Liver biopsy findings were like the global literature, with interface hepatitis and lymphoplasmacytic infiltration observed. Immunohistochemical analysis showed immunostaining for NFκB, MAPK-p38, and TNF-α, corroborating the inflammatory and immunological characteristics of the disease. Immunoassay analysis in peripheral blood confirmed the activation of the MAPK-p38 signaling pathway, with a statistically significant difference between AIH patients and healthy controls. CONCLUSIONS The epidemiological and histological findings of AIH in this study in Northeast Brazil were like global population data. Immunohistochemical analysis of liver tissue and immunoassay analysis in peripheral blood confirmed the activation of TNF-α and the NFκB and MAPK-p38 signaling pathways in AIH patients.
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Affiliation(s)
| | | | | | | | | | | | | | | | - Sura Wanessa Santos Rocha
- Graduate Program in Applied Cellular and Molecular Biology (BCMA), Brazil; Institute of Biological Sciences, University of Pernambuco (ICB), Brazil.
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28
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Brito-Dellan N, Franco-Vega MC, Ruiz JI, Lu M, Sahar H, Rajapakse P, Lin HY, Peterson C, Alviarez DL, Altay H, Tomy S, Manzano JGM. Optimizing Inpatient Care for Lung Cancer Patients with Immune Checkpoint Inhibitor- Related Pneumonitis Using a Clinical Care Pathway Algorithm. RESEARCH SQUARE 2024:rs.3.rs-4209489. [PMID: 38659939 PMCID: PMC11042393 DOI: 10.21203/rs.3.rs-4209489/v1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 04/26/2024]
Abstract
Purpose Immune checkpoint inhibitor-related pneumonitis (ICI-P) is a condition associated with high mortality, necessitating prompt recognition and treatment initiation. This study aimed to assess the impact of implementing a clinical care pathway algorithm on reducing the time to treatment for ICI-P. Methods Patients with lung cancer and suspected ICI-P were enrolled, and a multi-modal intervention promoting algorithm use was implemented in two phases. Pre- and post-intervention analyses were conducted to evaluate the primary outcome of time from ICI-P diagnosis to treatment initiation. Results Of the 82 patients admitted with suspected ICI-P, 73.17% were confirmed to have ICI-P, predominantly associated with non-small cell lung cancer (91.67%) and stage IV disease (95%). Pembrolizumab was the most commonly used immune checkpoint inhibitor (55%). The mean times to treatment were 2.37 days in the pre-intervention phase and, 3.07 days (p=0.46), and 1.27 days (p=0.40) in the post-intervention phases 1 and 2, respectively. Utilization of the immunotoxicity order set significantly increased from 0% to 27.27% (p = 0.04) after phase 2. While there were no significant changes in ICU admissions or inpatient mortality, outpatient pulmonology follow-ups increased statistically significantly, demonstrating enhanced continuity of care. The overall mortality for patients with ICI-P was 22%, underscoring the urgency of optimizing management strategies. Notably, all patients discharged on high-dose corticosteroids received appropriate gastrointestinal prophylaxis and prophylaxis against Pneumocystis jirovecii pneumonia infections at the end of phase 2. Conclusion Implementing a clinical care pathway algorithm for ICI-P management standardizes care practices and enhances patient outcomes, underscoring the importance of structured approaches.
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Affiliation(s)
| | | | | | - Maggie Lu
- The University of Texas MD Anderson Cancer Center
| | - Hadeel Sahar
- The University of Texas MD Anderson Cancer Center
| | | | | | | | | | - Haider Altay
- The University of Texas MD Anderson Cancer Center
| | - Sophy Tomy
- The University of Texas MD Anderson Cancer Center
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Pan L, Hu J. Effect of prior anticoagulation therapy on outcomes of traumatic brain injury: A systematic review and meta‑analysis. Exp Ther Med 2024; 27:160. [PMID: 38476913 PMCID: PMC10928994 DOI: 10.3892/etm.2024.12448] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/01/2023] [Accepted: 02/02/2024] [Indexed: 03/14/2024] Open
Abstract
Anticoagulants are commonly prescribed for multiple conditions. However, their influence on traumatic brain injury (TBI) outcomes, especially mortality, is not clear. The present study aimed to explore the effect of prior anticoagulation treatment on the outcomes of TBI. PubMed, Embase, Cochrane Central Register of Controlled Trials, Scopus and CINAHL databases were systematically searched for studies on individuals diagnosed with TBI, with a subgroup on prior anticoagulation therapy. Outcomes of interest included overall mortality, in-hospital mortality, length of hospital and intensive care unit stay, need for neurosurgical intervention and discharge rate. Cohort and case-control studies, published up to September 2023, were examined. Analysis was performed using STATA version 14.2 software and the Newcastle Ottawa Scale was used for bias assessment. A total of 22 studies (102,036 participants) were included in the analysis. Patients with TBI with prior anticoagulation treatment showed a statistically higher overall mortality risk [odds ratio (OR): 1.967, 95% confidence interval (CI): 1.481-2.613]. Subgroup analyses revealed age-specific and TBI severity-specific variations. Prior anticoagulation treatment was associated with a 1.860-times higher rate of in-hospital mortality and a significantly increased likelihood of requiring neurosurgical intervention (OR: 1.351, 95%CI: 1.068-1.708). However, no significant difference was noted in lengths of hospital or ICU stays. Patients with TBI and prior anticoagulation therapy are at higher risk of overall and in-hospital mortality and have significantly higher likelihood of needing neurosurgical interventions. The results emphasized the need for tailored therapeutic approach and more comprehensive clinical guidelines. Future investigations on specific anticoagulant types and immediate post-TBI interventions could offer further insights.
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Affiliation(s)
- Linghong Pan
- Department of Emergency, Huzhou Central Hospital, Affiliated Central Hospital of Huzhou University, Huzhou, Zhejiang 313000, P.R. China
| | - Jiayao Hu
- Department of Emergency, Huzhou Central Hospital, Affiliated Central Hospital of Huzhou University, Huzhou, Zhejiang 313000, P.R. China
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Geraldes C, Roque A, Sarmento-Ribeiro AB, Neves M, Ionita A, Gerivaz R, Tomé A, Afonso S, Silveira MP, Sousa P, Bergantim R, João C. Practical management of disease-related manifestations and drug toxicities in patients with multiple myeloma. Front Oncol 2024; 14:1282300. [PMID: 38585008 PMCID: PMC10995327 DOI: 10.3389/fonc.2024.1282300] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/23/2023] [Accepted: 02/07/2024] [Indexed: 04/09/2024] Open
Abstract
Multiple myeloma (MM) is a very heterogeneous disease with multiple symptoms and clinical manifestations. MM affects mainly elderly patients and is difficult to manage in the presence of comorbidities, polypharmacy, frailty and adverse events of disease-targeted drugs. The rapid changes in MM treatment resulting from constant innovations in this area, together with the introduction of numerous new drugs with distinct mechanisms of action and toxicity profiles, have led to an increased complexity in the therapeutic decision-making and patient management processes. The prolonged exposure to novel agents, sometimes in combination with conventional therapies, makes this management even more challenging. A careful balance between treatment efficacy and its tolerability should be considered for every patient. During treatment, a close monitoring of comorbidities, disease-related manifestations and treatment side effects is recommended, as well as a proactive approach, with reinforcement of information and patient awareness for the early recognition of adverse events, allowing prompt therapeutic adjustments. In this review, we discuss various issues that must be considered in the treatment of MM patients, while giving practical guidance for monitoring, prevention and management of myeloma-related manifestations and treatment-related toxicities.
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Affiliation(s)
- Catarina Geraldes
- Serviço de Hematologia Clínica, Centro Hospitalar e Universitário de Coimbra, Coimbra, Portugal
- Faculty of Medicine, University of Coimbra, Coimbra, Portugal
- Coimbra Institute for Clinical and Biomedical Research, Faculty of Medicine, University of Coimbra, Coimbra, Portugal
- Center for Innovative Biomedicine and Biotechnology (CIBB), University of Coimbra, Coimbra, Portugal
- Clinical Academic Center of Coimbra (CACC), Coimbra, Portugal
| | - Adriana Roque
- Serviço de Hematologia Clínica, Centro Hospitalar e Universitário de Coimbra, Coimbra, Portugal
- Institute of Physiology, Faculty of Medicine, University of Coimbra, Coimbra, Portugal
| | - Ana Bela Sarmento-Ribeiro
- Serviço de Hematologia Clínica, Centro Hospitalar e Universitário de Coimbra, Coimbra, Portugal
- Faculty of Medicine, University of Coimbra, Coimbra, Portugal
- Coimbra Institute for Clinical and Biomedical Research, Faculty of Medicine, University of Coimbra, Coimbra, Portugal
- Center for Innovative Biomedicine and Biotechnology (CIBB), University of Coimbra, Coimbra, Portugal
- Clinical Academic Center of Coimbra (CACC), Coimbra, Portugal
| | - Manuel Neves
- Hemato-Oncology Unit, Champalimaud Foundation, Lisboa, Portugal
| | - Alina Ionita
- Hematology Department, Portuguese Institute of Oncology Francisco Gentil, Lisboa, Portugal
| | - Rita Gerivaz
- Serviço de Hemato-oncologia, Hospital Garcia de Orta, Lisboa, Portugal
| | - Ana Tomé
- Serviço de Hemato-oncologia, Hospital Garcia de Orta, Lisboa, Portugal
| | - Sofia Afonso
- Serviço de Hematologia Clínica, Centro Hospitalar Universitário Cova da Beira, Covilhã, Portugal
- Faculdade de Ciências da Saúde, Universidade da Beira Interior, Covilhã, Portugal
| | - Maria Pedro Silveira
- Serviço de Imuno-Hemoterapia, Hospital Prof. Doutor Fernando Fonseca, EPE, Amadora, Portugal
| | - Patrícia Sousa
- Serviço de Imuno-Hemoterapia, Hospital Prof. Doutor Fernando Fonseca, EPE, Amadora, Portugal
| | - Rui Bergantim
- Serviço de Hematologia Clínica, Centro Hospitalar Universitário de São João (CHUSJ), Porto, Portugal
- Instituto de Investigação e Inovaçáo em Saúde, Universidade do Porto, Porto, Portugal
- Institute of Pathology and Molecular Immunology, Abel Salazar Institute of Biomedical Sciences, University of Porto, Porto, Portugal
| | - Cristina João
- Hemato-Oncology Unit, Champalimaud Foundation, Lisboa, Portugal
- NOVA Medical School, Universidade Nova de Lisboa, Lisboa, Portugal
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Fischbach W, Bornschein J, Hoffmann JC, Koletzko S, Link A, Macke L, Malfertheiner P, Schütte K, Selgrad DM, Suerbaum S, Schulz C. Update S2k-Guideline Helicobacter pylori and gastroduodenal ulcer disease of the German Society of Gastroenterology, Digestive and Metabolic Diseases (DGVS). ZEITSCHRIFT FUR GASTROENTEROLOGIE 2024; 62:261-321. [PMID: 38364851 DOI: 10.1055/a-2181-2225] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 02/18/2024]
Affiliation(s)
| | - Jan Bornschein
- Translational Gastroenterology Unit John, John Radcliffe Hospital Oxford University Hospitals, Oxford, United Kingdom
| | - Jörg C Hoffmann
- Medizinische Klinik I, St. Marien- und St. Annastiftskrankenhaus, Ludwigshafen, Deutschland
| | - Sibylle Koletzko
- Kinderklinik und Kinderpoliklinik im Dr. von Haunerschen Kinderspital, LMU-Klinikum Munich, Munich, Deutschland
- Department of Paediatrics, Gastroenterology and Nutrition, School of Medicine Collegium Medicum University of Warmia and Mazury, 10-719 Olsztyn, Poland
| | - Alexander Link
- Klinik für Gastroenterologie, Hepatologie und Infektiologie, Universitätsklinikum Magdeburg, Magdeburg, Deutschland
| | - Lukas Macke
- Medizinische Klinik und Poliklinik II Campus Großhadern, Universitätsklinikum Munich, Munich, Deutschland
- Deutsches Zentrum für Infektionsforschung, Standort Munich, Munich, Deutschland
| | - Peter Malfertheiner
- Klinik für Gastroenterologie, Hepatologie und Infektiologie, Universitätsklinikum Magdeburg, Magdeburg, Deutschland
- Medizinische Klinik und Poliklinik II Campus Großhadern, Universitätsklinikum Munich, Munich, Deutschland
| | - Kerstin Schütte
- Klinik für Allgemeine Innere Medizin und Gastroenterologie, Niels-Stensen-Kliniken Marienhospital Osnabrück, Osnabrück, Deutschland
| | - Dieter-Michael Selgrad
- Medizinische Klinik Gastroenterologie und Onkologie, Klinikum Fürstenfeldbruck, Fürstenfeldbruck, Deutschland
- Klinik für Innere Medizin 1, Universitätsklinikum Regensburg, Regensburg, Deutschland
| | - Sebastian Suerbaum
- Universität Munich, Max von Pettenkofer-Institut für Hygiene und Medizinische Mikrobiologie, Munich, Deutschland
- Nationales Referenzzentrum Helicobacter pylori, Pettenkoferstr. 9a, 80336 Munich, Deutschland
- Deutsches Zentrum für Infektionsforschung, Standort Munich, Munich, Deutschland
| | - Christian Schulz
- Medizinische Klinik und Poliklinik II Campus Großhadern, Universitätsklinikum Munich, Munich, Deutschland
- Deutsches Zentrum für Infektionsforschung, Standort Munich, Munich, Deutschland
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Wang Y, Guo D, Winkler R, Lei X, Wang X, Messina J, Luo J, Lu H. Development of novel liver-targeting glucocorticoid prodrugs. MEDICINE IN DRUG DISCOVERY 2024; 21:100172. [PMID: 38390434 PMCID: PMC10883687 DOI: 10.1016/j.medidd.2023.100172] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/24/2024] Open
Abstract
Background Glucocorticoids (GCs) are widely used in the treatment of inflammatory liver diseases and sepsis, but GC's various side effects on extrahepatic tissues limit their clinical benefits. Liver-targeting GC therapy may have multiple advantages over systemic GC therapy. The purpose of this study was to develop novel liver-targeting GC prodrugs as improved treatment for inflammatory liver diseases and sepsis. Methods A hydrophilic linker or an ultra-hydrophilic zwitterionic linker carboxylic betaine (CB) was used to bridge cholic acid (CA) and dexamethasone (DEX) to generate transporter-dependent liver-targeting GC prodrugs CA-DEX and the highly hydrophilic CA-CB-DEX. The efficacy of liver-targeting DEX prodrugs and DEX were determined in primary human hepatocytes (PHH), macrophages, human whole blood, and/or mice with sepsis induced by cecal ligation and puncture. Results CA-DEX was moderately water soluble, whereas CA-CB-DEX was highly water soluble. CA-CB-DEX and CA-DEX displayed highly transporter-dependent activities in reporter assays. Data mining found marked dysregulation of many GR-target genes important for lipid catabolism, cytoprotection, and inflammation in patients with severe alcoholic hepatitis. These key GR-target genes were similarly and rapidly (within 6 h) induced or down-regulated by CA-CB-DEX and DEX in PHH. CA-CB-DEX had much weaker inhibitory effects than DEX on endotoxin-induced cytokines in mouse macrophages and human whole blood. In contrast, CA-CB-DEX exerted more potent anti-inflammatory effects than DEX in livers of septic mice. Conclusions CA-CB-DEX demonstrated good hepatocyte-selectivity in vitro and better anti-inflammatory effects in vivo. Further test of CA-CB-DEX as a novel liver-targeting GC prodrug for inflammatory liver diseases and sepsis is warranted.
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Affiliation(s)
- Yazheng Wang
- Department of Pharmacology, SUNY Upstate Medical University, Syracuse, NY 13210, United States
| | - Dandan Guo
- Department of Pharmacology, SUNY Upstate Medical University, Syracuse, NY 13210, United States
| | - Rebecca Winkler
- Department of Pharmacology, SUNY Upstate Medical University, Syracuse, NY 13210, United States
| | - Xiaohong Lei
- Department of Pharmacology, SUNY Upstate Medical University, Syracuse, NY 13210, United States
| | - Xiaojing Wang
- Department of Pharmacology, SUNY Upstate Medical University, Syracuse, NY 13210, United States
| | - Jennifer Messina
- Department of Pharmacology, SUNY Upstate Medical University, Syracuse, NY 13210, United States
| | - Juntao Luo
- Department of Pharmacology, SUNY Upstate Medical University, Syracuse, NY 13210, United States
| | - Hong Lu
- Department of Pharmacology, SUNY Upstate Medical University, Syracuse, NY 13210, United States
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Carvajal-Gutiérrez W, Cisneros-Cisneros MA, Calixto OJ, Meneses-Toro MA, Rueda AJP, Vega-Báez MA, Álvarez-Vargas DA, Uscátegui-Ruiz AC, Romero-Sanchez C, Bello-Gualtero JM. Low Frequency of Upper Gastrointestinal Bleeding Despite Non-Steroidal Anti-Inflammatory Drugs and Corticosteroids in Patients with Rheumatoid Arthritis. Curr Rheumatol Rev 2024; 20:555-562. [PMID: 38362696 DOI: 10.2174/0115733971290285240207080745] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/30/2023] [Revised: 01/19/2024] [Accepted: 01/25/2024] [Indexed: 02/17/2024]
Abstract
BACKGROUND Rheumatoid arthritis (RA) is a chronic inflammatory disease. It has been identified that non-steroidal anti-inflammatory drugs (NSAIDs) and corticosteroids can be essential risk factors for developing complications such as upper gastrointestinal bleeding (UGIB). OBJECTIVE This study aimed to describe the safety profile of drugs used to treat RA focused in UGIB. METHODS A cross-sectional study of patients with RA between 2015 and 2021, a description of the population, and an evaluation of the relationship with UGIB through bivariate analysis and logistic regression. RESULTS Of 405 individuals, 16 presented UGIB (93.8% women, mean age was 65±13.6 years). No statistically significant differences were found regarding UGIB and medication use, except for the mean dose of corticosteroids. In the multivariate analysis, it was found that the presence of anemia in the last three months had an adjusted OR (AOR) of 16.1 (95% CI 2.74- 24.23) and higher HAQ values during the previous three months had an AOR of 6.17 (95% CI 1.79- 21.24). CONCLUSION This study found a low frequency of UGIB in patients with RA. More significant disability and anemia in the previous months were independently associated with UGIB. The low frequency of NSAID use in this population is noteworthy. In general, reasonable medication use related to this complication is recommended.
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Affiliation(s)
| | | | - Omar-Javier Calixto
- Rheumatology and Immunology Department, Hospital Militar Central, Bogotá, Colombia
- Clinical Immunology Group-Hospital Militar, School of Medicine, Universidad Militar Nueva Granada, Bogotá, Colombia
- Cellular and Molecular Immunology Group / INMUBO, Universidad El Bosque, Bogotá, Colombia
| | - Maria-Alejandra Meneses-Toro
- Rheumatology and Immunology Department, Hospital Militar Central, Bogotá, Colombia
- Clinical Immunology Group-Hospital Militar, School of Medicine, Universidad Militar Nueva Granada, Bogotá, Colombia
| | | | | | | | | | - Consuelo Romero-Sanchez
- Clinical Immunology Group-Hospital Militar, School of Medicine, Universidad Militar Nueva Granada, Bogotá, Colombia
- Cellular and Molecular Immunology Group / INMUBO, Universidad El Bosque, Bogotá, Colombia
| | - Juan-Manuel Bello-Gualtero
- Rheumatology and Immunology Department, Hospital Militar Central, Bogotá, Colombia
- Clinical Immunology Group-Hospital Militar, School of Medicine, Universidad Militar Nueva Granada, Bogotá, Colombia
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An AW, Chen X, Urbauer DL, Bruera E, Hui D. Impact of Dosing and Duration of Dexamethasone on Serious Corticosteroid-Related Adverse Events. J Pain Symptom Manage 2024; 67:59-68. [PMID: 37769822 DOI: 10.1016/j.jpainsymman.2023.09.021] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/01/2023] [Revised: 09/07/2023] [Accepted: 09/14/2023] [Indexed: 10/03/2023]
Abstract
CONTEXT Corticosteroids are commonly prescribed in oncology, but few studies have examined its adverse events (AEs) compared to placebo control. OBJECTIVES Using data from a double-blind, placebo-controlled randomized trial, we evaluated the association between the dose and duration of dexamethasone and serious AEs. METHODS This is a pre-planned secondary analysis of the Alleviating Breathlessness in Cancer Patients with Dexamethasone (ABCD) trial in which patients were randomized to dexamethasone 8 mg BID x1 week, then 4 mg BID x1 week or placebo, followed by an optional open-label phase with 4 mg BID x1 week, then 2 mg BID x1 week. The primary outcome was Grade 3+ AEs (CTCAE v4.03). We evaluated the association between AEs and dexamethasone exposure using multivariable logistic regression. RESULTS Among 119 cancer patients, 32 received intervention followed by open label (mean exposure 243 mg over 27 days), 47 received intervention with no open label, 20 received placebo followed by open label, and 20 received no dexamethasone. The most common AEs included insomnia (31%), dyspepsia (21%), neuropsychiatric symptoms (18%), and infections (17%). Overall, 38 (32%) had Grade 3+ AEs and 27 (23%) were hospitalized. Patients with the greatest exposure to dexamethasone experienced more Grade 3+ AEs compared to those with no exposure (65% vs. 15%); odds ratio of 15.1 (95% CI 1.4-160.8, P = 0.01). CONCLUSION Greater dexamethasone exposure, even at moderate doses, was associated with more serious AEs. Prescribers should cautiously weigh the risks and benefits of dexamethasone use, especially when considering for palliation of symptoms.
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Affiliation(s)
- Amy W An
- Department of Gastrointestinal Medical Oncology (A.W.A.), The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
| | - Xi Chen
- Department of Biostatistics (X.C., D.L.U.), The University of Texas MD Anderson Cancer Center, Houston, Texas, USA
| | - Diana L Urbauer
- Department of Biostatistics (X.C., D.L.U.), The University of Texas MD Anderson Cancer Center, Houston, Texas, USA
| | - Eduardo Bruera
- Department of Palliative Care (E.B., D.H.), Rehabilitation and Integrative Medicine, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA
| | - David Hui
- Department of Palliative Care (E.B., D.H.), Rehabilitation and Integrative Medicine, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA
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Howard E. Nonvariceal upper gastrointestinal bleeding, COVID and mortality: confounders or true correlation? Proc AMIA Symp 2023; 37:42. [PMID: 38174005 PMCID: PMC10761007 DOI: 10.1080/08998280.2023.2279880] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/01/2023] [Accepted: 11/01/2023] [Indexed: 01/05/2024] Open
Affiliation(s)
- Ericka Howard
- University of Texas Southwestern Medical Center, Dallas, Texas, USA
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36
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Kondo M, Torisu T, Ihara Y, Kawasaki K, Umeno J, Kawatoko S, Tsuchimoto A, Nakano T, Okabe Y, Kitazono T. Clinical Features of Gastroduodenal Ulcers in Kidney Transplant Patients. Intern Med 2023; 62:3437-3443. [PMID: 37062748 PMCID: PMC10749817 DOI: 10.2169/internalmedicine.1508-22] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/26/2022] [Accepted: 02/26/2023] [Indexed: 04/18/2023] Open
Abstract
Objective The risk of developing peptic ulcers and gastrointestinal bleeding is high in patients with chronic kidney disease (CKD). Whether or not kidney transplant patients, who are treated with multiple medications, including immunosuppressive drugs, are at an increased risk of developing peptic ulcers is unclear. Methods In this retrospective study, we compared the clinical and endoscopic features of gastroduodenal ulcers between kidney transplant patients and CKD patients. The subjects underwent upper gastrointestinal endoscopy between January 2015 and March 2021. Results Gastroduodenal ulcers were observed more frequently (6.5%) in kidney transplant patients than in CKD patients (2.1%) (p=0.026). Due in part to the lower median age in the kidney transplant ulcer group than in the CKD ulcer group (59 vs. 70 years old, p=0.016), the rates of atrophic gastritis and Helicobacter pylori infection were also lower in the kidney transplant ulcer group than in the CKD ulcer group. Significantly more kidney transplant patients were treated with acid secretion inhibitors than CKD ulcer patients (100% vs. 34.8%, p=0.0005). Peptic ulcers were observed frequently in kidney transplant patients, even though common risk factors for gastroduodenal ulcers other than immunosuppressive drugs were few. All kidney transplant patients were taking immunosuppressive medications, and tacrolimus, mycophenolate mofetil, and methylprednisolone were taken more frequently than others. Conclusion Kidney transplant patients have a high risk of developing gastroduodenal ulcers. All kidney transplant patients take immunosuppressive medications, so there may be an association between immunosuppressive medications and gastroduodenal ulcer development.
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Affiliation(s)
- Masahiro Kondo
- Department of Medicine and Clinical Science, Graduate School of Medical Sciences, Kyushu University, Japan
| | - Takehiro Torisu
- Department of Medicine and Clinical Science, Graduate School of Medical Sciences, Kyushu University, Japan
| | - Yutaro Ihara
- Department of Medicine and Clinical Science, Graduate School of Medical Sciences, Kyushu University, Japan
| | - Keisuke Kawasaki
- Department of Medicine and Clinical Science, Graduate School of Medical Sciences, Kyushu University, Japan
| | - Junji Umeno
- Department of Medicine and Clinical Science, Graduate School of Medical Sciences, Kyushu University, Japan
| | - Shinichiro Kawatoko
- Department of Medicine and Clinical Science, Graduate School of Medical Sciences, Kyushu University, Japan
- Department of Anatomic Pathology, Pathological Sciences, Graduate School of Medical Sciences, Kyushu University, Japan
| | - Akihiro Tsuchimoto
- Department of Medicine and Clinical Science, Graduate School of Medical Sciences, Kyushu University, Japan
| | - Toshiaki Nakano
- Department of Medicine and Clinical Science, Graduate School of Medical Sciences, Kyushu University, Japan
| | - Yasuhiro Okabe
- Department of Surgery and Oncology, Graduate School of Medical Sciences, Kyushu University, Japan
| | - Takanari Kitazono
- Department of Medicine and Clinical Science, Graduate School of Medical Sciences, Kyushu University, Japan
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Abstract
In sepsis, dysregulation of the hypothalamic-pituitary-adrenal axis, alterations in cortisol metabolism, and tissue resistance to glucocorticoids can all result in relative adrenal insufficiency or critical illness-related corticosteroid insufficiency (CIRCI). The symptoms and signs of CIRCI during sepsis are nonspecific, generally including decreased mental status, unexplained fever, or hypotension refractory to fluids, and the requirement of vasopressor therapy to maintain adequate blood pressure. While we have been aware of this syndrome for over a decade, it remains a poorly understood condition, challenging to diagnose, and associated with significantly diverging practices among clinicians, particularly regarding the optimal dosing and duration of corticosteroid therapy. The existing literature on corticosteroid use in patients with sepsis and septic shock is vast with dozens of randomized controlled trials conducted across the past 4 decades. These studies have universally demonstrated reduced duration of shock, though the effects of corticosteroids on mortality have been inconsistent, and their use has been associated with adverse effects including hyperglycemia, neuromuscular weakness, and an increased risk of infection. In this article, we aim to provide a thorough, evidence-based, and practical review of the current recommendations for the diagnosis and management of patients with sepsis who develop CIRCI, explore the controversies surrounding this topic, and highlight what lies on the horizon as new evidence continues to shape our practice.
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Affiliation(s)
- Cosmo Fowler
- Critical Care Center, Department of Anesthesiology and Critical Care Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA
| | - Nina Raoof
- Critical Care Center, Department of Anesthesiology and Critical Care Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA
| | - Stephen M Pastores
- Critical Care Center, Department of Anesthesiology and Critical Care Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA
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Dutta AK, Jain A, Jearth V, Mahajan R, Panigrahi MK, Sharma V, Goenka MK, Kochhar R, Makharia G, Reddy DN, Kirubakaran R, Ahuja V, Berry N, Bhat N, Dutta U, Ghoshal UC, Jain A, Jalihal U, Jayanthi V, Kumar A, Nijhawan S, Poddar U, Ramesh GN, Singh SP, Zargar S, Bhatia S. Guidelines on optimizing the use of proton pump inhibitors: PPI stewardship. Indian J Gastroenterol 2023; 42:601-628. [PMID: 37698821 DOI: 10.1007/s12664-023-01428-7] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/01/2023] [Accepted: 07/10/2023] [Indexed: 09/13/2023]
Abstract
Proton pump inhibitors (PPIs) have been available for over three decades and are among the most commonly prescribed medications. They are effective in treating a variety of gastric acid-related disorders. They are freely available and based on current evidence, use of PPIs for inappropriate indications and duration appears to be common. Over the years, concerns have been raised on the safety of PPIs as they have been associated with several adverse effects. Hence, there is a need for PPI stewardship to promote the use of PPIs for appropriate indication and duration. With this objective, the Indian Society of Gastroenterology has formulated guidelines on the rational use of PPIs. The guidelines were developed using a modified Delphi process. This paper presents these guidelines in detail, including the statements, review of literature, level of evidence and recommendations. This would help the clinicians in optimizing the use of PPIs in their practice and promote PPI stewardship.
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Affiliation(s)
- Amit Kumar Dutta
- Department of Gastroenterology, Christian Medical College and Hospital, Vellore, 632 004, India.
| | | | - Vaneet Jearth
- Postgraduate Institute of Medical Education and Research, Chandigarh, 160 012, India
| | - Ramit Mahajan
- Dayanand Medical College and Hospital, Ludhiana, 141 001, India
| | | | - Vishal Sharma
- Postgraduate Institute of Medical Education and Research, Chandigarh, 160 012, India
| | | | | | - Govind Makharia
- All India Institute of Medical Sciences, New Delhi, 110 029, India
| | | | - Richard Kirubakaran
- Center of Biostatistics and Evidence Based Medicine, Vellore, 632 004, India
| | - Vineet Ahuja
- All India Institute of Medical Sciences, New Delhi, 110 029, India
| | - Neha Berry
- BLK Institute of Digestive and Liver Disease, New Delhi, 201 012, India
| | - Naresh Bhat
- Aster CMI Hospital, Bengaluru, 560 092, India
| | - Usha Dutta
- Postgraduate Institute of Medical Education and Research, Chandigarh, 160 012, India
| | - Uday Chand Ghoshal
- Sanjay Gandhi Post Graduate Institute of Medical Sciences, Lucknow, 226 014, India
| | - Ajay Jain
- Choithram Hospital and Research Center, Indore, 452 014, India
| | | | - V Jayanthi
- Sri Ramachandra Medical College, Chennai, 600 116, India
| | - Ajay Kumar
- Institute of Digestive and Liver Diseases, BLK - Max Superspeciality Hospital, New Delhi, 201 012, India
| | | | - Ujjal Poddar
- Sanjay Gandhi Post Graduate Institute of Medical Sciences, Lucknow, 226 014, India
| | | | - Shivram P Singh
- Kalinga Gastroenterology Foundation, Cuttack, 753 001, India
| | - Showkat Zargar
- Department of Gastroenterology, Sher-i-Kashmir Institute of Medical Sciences, Kashmir, 190 011, India
| | - Shobna Bhatia
- Sir H N Reliance Foundation Hospital, Mumbai, 400 004, India
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Beaty W, Elnadoury O, Fridman D, Louie E, Lubinsky AS. Effects of corticosteroids in hospitalized patients with Legionella pneumonia: A retrospective cohort study. J Infect Chemother 2023; 29:849-854. [PMID: 37164062 DOI: 10.1016/j.jiac.2023.05.002] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/25/2023] [Revised: 04/03/2023] [Accepted: 05/06/2023] [Indexed: 05/12/2023]
Abstract
INTRODUCTION Legionella pneumophila is an important cause of pneumonia, however there is scant literature assessing the therapeutic benefit of corticosteroids in treatment. We sought to investigate the association between corticosteroid use and in-hospital mortality for patients hospitalized with Legionella pneumonia. METHODS Data was collected retrospectively from January 2012 to July 2019 at a 705 bed hospital in New York City. Patients were included if they received a positive Legionella test. Exclusion criteria included age <18, concurrent immunosuppression, and HIV diagnosis. We assessed the relationship between corticosteroid use and in-hospital mortality. Statistical analyses were performed in RStudio. RESULTS The study included 160 patients, among which 32 (20%) received steroids. Overall mortality was 7.5% (12.5% among steroid recipients, 6.2% among controls). 25% of patients were admitted to the ICU (37.5% among steroid recipients, 21.9% among controls). Adjusted analysis showed steroid recipients did not have significantly different mortality (aOR = 2.56, p = 0.436). Steroid use was not significantly associated with longer LOS (p = 0.22). Steroid use was significantly associated with hyperglycemia (aOR = 2.91, p = 0.018) and GI bleed (OR = 9.0, p = 0.014). CONCLUSIONS We found that in patients hospitalized with Legionella pneumonia, corticosteroid administration was not significantly associated with longer hospitalization or mortality. All findings held true when adjusting for known predictors of pneumonia severity. Corticosteroid use was associated with increased rates of hyperglycemia and GIB requiring blood transfusion. The results of this study are consistent with guidelines recommending against routine use of corticosteroids in CAP.
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Affiliation(s)
- William Beaty
- New York University Grossman School of Medicine, 550 1st Ave, New York, NY, 10016, USA.
| | - Ola Elnadoury
- Regeneron Pharmaceuticals Inc, 777 Old Saw Mill River Rd, Tarrytown, NY, 10591, USA.
| | - David Fridman
- New York University Langone Health, 550 1st Ave, New York, NY, 10016, USA.
| | - Eddie Louie
- New York University Langone Health, 550 1st Ave, New York, NY, 10016, USA.
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Sims C, Golenbiewski J, Eudy AM, Allen NB, Clowse MEB. Hospital Admissions and Mortality in Patients With Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis. J Clin Rheumatol 2023; 29:e124-e129. [PMID: 36730961 DOI: 10.1097/rhu.0000000000001917] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/04/2023]
Abstract
BACKGROUND/OBJECTIVES Anti-neutrophil cytoplasmic antibody-associated vasculitis has reported hospital mortality rates ranging between 10% and 20% with inadequate information regarding causes and outcomes of these hospitalizations. Characterization of outcomes in anti-neutrophil cytoplasmic antibody-associated vasculitis can improve patient care and prognostication following hospitalization. METHODS A medical records review of all hospitalizations between October 1, 2015, and December 31, 2018, of adults with granulomatosis with polyangiitis or microscopic polyangiitis at a single academic medical center was performed. Chart review confirmed diagnoses in patients identified by International Classification of Diseases, Tenth Revision code. Vasculitis activity was determined based on clinical data and treatment during the hospitalization. Differences in outcome measures were analyzed using Fisher exact test, t test, and Wilcoxon signed-rank test. RESULTS Of the 127 hospitalizations among 54 patients, active vasculitis was identified in 43 hospitalizations (33.9%). A total of 15 patients with active disease, including 10 patients with a new diagnosis, required intensive care unit (ICU)-level care. Of 84 hospitalizations when vasculitis was inactive, infection was diagnosed in 31 admissions (36.9%), with inactive disease representing 44% of all ICU admissions. Overall mortality was 7% for hospitalized patients and 15% for those admitted to the ICU. An additional 5 patients died within 28 days of discharge, for an overall mortality rate of 17%. All 4 hospital deaths and 3 of 5 postdischarge deaths were in the setting of known infection. CONCLUSION Most hospitalizations and patient deaths were in the context of inactive vasculitis, with infection being the most common cause. Infection and ICU admission were associated with patient death.
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Hysa E, Vojinovic T, Gotelli E, Alessandri E, Pizzorni C, Paolino S, Sulli A, Smith V, Cutolo M. The dichotomy of glucocorticosteroid treatment in immune-inflammatory rheumatic diseases: an evidence-based perspective and insights from clinical practice. Reumatologia 2023; 61:283-293. [PMID: 37745141 PMCID: PMC10515127 DOI: 10.5114/reum/170845] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/16/2023] [Accepted: 08/08/2023] [Indexed: 09/26/2023] Open
Abstract
Objectives Glucocorticosteroids (GCs) are the most used anti-inflammatory and immunosuppressive drugs due to their effectiveness in managing pain and disease modification in many immune-inflammatory rheumatic diseases (IRDs). However, their use is limited because of adverse effects (AEs). Material and methods The authors analyzed recent studies, including randomized controlled trials (RCTs), observational, translational studies and systematic reviews, providing an in-depth viewpoint on the benefits and drawbacks of GC use in rheumatology. Results Glucocorticosteroids are essential in managing life-threatening autoimmune diseases and a cornerstone in many IRDs given their swift onset of action, necessary in flares. Several RCTs and meta-analyses have demonstrated that when administered over a long time and on a low-dose basis, GC can slow the radiographic progression in early rheumatoid arthritis (RA) patients by at least 50%, satisfying the conventional definition of a disease-modifying anti-rheumatic drug (DMARD). In the context of RA treatment, the use of modified-release prednisone formulations at night may offer the option of respecting circadian rhythms of both inflammatory response and HPA activation, thereby enabling low-dose GC administration to mitigate nocturnal inflammation and prolonged morning fatigue and joint stiffness. Long-term GC use should be individualized based on patient characteristics and minimized due to their potential AEs. Their chronic use, especially at medium/high dosages, might cause irreversible organ damage due to the burden of metabolic systemic effects and increased risk of infections. Many international guidelines recommend tapering/withdrawal of GCs in sustained remission. Treat-to-target (T2T) strategies are critical in setting targets for disease activity and reducing/discontinuing GCs once control is achieved. Conclusions Glucocorticosteroids' use in treating IRDs should be judicious, focused on minimizing use, tapering and discontinuing treatment, when possible, to improve long-term safety. Glucocorticosteroids remain part of many therapeutic regimens, particularly at low doses, and elderly RA patients, especially with associated chronic comorbidities, may benefit from long-term low-dose GC treatment. A personalized GC therapy is essential for optimal long-term outcomes.
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Affiliation(s)
- Elvis Hysa
- Laboratory of Experimental Rheumatology and Academic Division of Clinical Rheumatology, Department of Internal Medicine, University of Genova, Italy
- IRCCS – San Martino Polyclinic Hospital, Genova, Italy
| | - Tamara Vojinovic
- Laboratory of Experimental Rheumatology and Academic Division of Clinical Rheumatology, Department of Internal Medicine, University of Genova, Italy
- IRCCS – San Martino Polyclinic Hospital, Genova, Italy
| | - Emanuele Gotelli
- Laboratory of Experimental Rheumatology and Academic Division of Clinical Rheumatology, Department of Internal Medicine, University of Genova, Italy
- IRCCS – San Martino Polyclinic Hospital, Genova, Italy
| | - Elisa Alessandri
- Laboratory of Experimental Rheumatology and Academic Division of Clinical Rheumatology, Department of Internal Medicine, University of Genova, Italy
- IRCCS – San Martino Polyclinic Hospital, Genova, Italy
| | - Carmen Pizzorni
- Laboratory of Experimental Rheumatology and Academic Division of Clinical Rheumatology, Department of Internal Medicine, University of Genova, Italy
- IRCCS – San Martino Polyclinic Hospital, Genova, Italy
| | - Sabrina Paolino
- Laboratory of Experimental Rheumatology and Academic Division of Clinical Rheumatology, Department of Internal Medicine, University of Genova, Italy
- IRCCS – San Martino Polyclinic Hospital, Genova, Italy
| | - Alberto Sulli
- Laboratory of Experimental Rheumatology and Academic Division of Clinical Rheumatology, Department of Internal Medicine, University of Genova, Italy
- IRCCS – San Martino Polyclinic Hospital, Genova, Italy
| | - Vanessa Smith
- Department of Internal Medicine, Department of Rheumatology, University Hospital Ghent, Belgium
- Unit for Molecular Immunology and Inflammation, VIB Inflammation Research Center (IRC), Ghent, Belgium
| | - Maurizio Cutolo
- Laboratory of Experimental Rheumatology and Academic Division of Clinical Rheumatology, Department of Internal Medicine, University of Genova, Italy
- IRCCS – San Martino Polyclinic Hospital, Genova, Italy
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Zhang J, Ge P, Liu J, Luo Y, Guo H, Zhang G, Xu C, Chen H. Glucocorticoid Treatment in Acute Respiratory Distress Syndrome: An Overview on Mechanistic Insights and Clinical Benefit. Int J Mol Sci 2023; 24:12138. [PMID: 37569514 PMCID: PMC10418884 DOI: 10.3390/ijms241512138] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/21/2023] [Revised: 07/20/2023] [Accepted: 07/25/2023] [Indexed: 08/13/2023] Open
Abstract
Acute lung injury/acute respiratory distress syndrome (ALI/ARDS), triggered by various pathogenic factors inside and outside the lungs, leads to diffuse lung injury and can result in respiratory failure and death, which are typical clinical critical emergencies. Severe acute pancreatitis (SAP), which has a poor clinical prognosis, is one of the most common diseases that induces ARDS. When SAP causes the body to produce a storm of inflammatory factors and even causes sepsis, clinicians will face a two-way choice between anti-inflammatory and anti-infection objectives while considering the damaged intestinal barrier and respiratory failure, which undoubtedly increases the difficulty of the diagnosis and treatment of SAP-ALI/ARDS. For a long time, many studies have been devoted to applying glucocorticoids (GCs) to control the inflammatory response and prevent and treat sepsis and ALI/ARDS. However, the specific mechanism is not precise, the clinical efficacy is uneven, and the corresponding side effects are endless. This review discusses the mechanism of action, current clinical application status, effectiveness assessment, and side effects of GCs in the treatment of ALI/ARDS (especially the subtype caused by SAP).
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Affiliation(s)
- Jinquan Zhang
- Department of General Surgery, The First Affiliated Hospital of Dalian Medical University, Dalian 116011, China
- Institute (College) of Integrative Medicine, Dalian Medical University, Dalian 116044, China
| | - Peng Ge
- Department of General Surgery, The First Affiliated Hospital of Dalian Medical University, Dalian 116011, China
- Institute (College) of Integrative Medicine, Dalian Medical University, Dalian 116044, China
- Laboratory of Integrative Medicine, The First Affiliated Hospital of Dalian Medical University, Dalian 116011, China
| | - Jie Liu
- Department of General Surgery, The First Affiliated Hospital of Dalian Medical University, Dalian 116011, China
- Institute (College) of Integrative Medicine, Dalian Medical University, Dalian 116044, China
- Laboratory of Integrative Medicine, The First Affiliated Hospital of Dalian Medical University, Dalian 116011, China
| | - Yalan Luo
- Department of General Surgery, The First Affiliated Hospital of Dalian Medical University, Dalian 116011, China
- Institute (College) of Integrative Medicine, Dalian Medical University, Dalian 116044, China
- Laboratory of Integrative Medicine, The First Affiliated Hospital of Dalian Medical University, Dalian 116011, China
| | - Haoya Guo
- Department of General Surgery, The First Affiliated Hospital of Dalian Medical University, Dalian 116011, China
- Institute (College) of Integrative Medicine, Dalian Medical University, Dalian 116044, China
- Laboratory of Integrative Medicine, The First Affiliated Hospital of Dalian Medical University, Dalian 116011, China
| | - Guixin Zhang
- Department of General Surgery, The First Affiliated Hospital of Dalian Medical University, Dalian 116011, China
- Institute (College) of Integrative Medicine, Dalian Medical University, Dalian 116044, China
- Laboratory of Integrative Medicine, The First Affiliated Hospital of Dalian Medical University, Dalian 116011, China
| | - Caiming Xu
- Department of General Surgery, The First Affiliated Hospital of Dalian Medical University, Dalian 116011, China
- Institute (College) of Integrative Medicine, Dalian Medical University, Dalian 116044, China
- Laboratory of Integrative Medicine, The First Affiliated Hospital of Dalian Medical University, Dalian 116011, China
- Department of Molecular Diagnostics and Experimental Therapeutics, Beckman Research Institute of City of Hope, Biomedical Research Center, Comprehensive Cancer Center, Monrovia, CA 91016, USA
| | - Hailong Chen
- Department of General Surgery, The First Affiliated Hospital of Dalian Medical University, Dalian 116011, China
- Institute (College) of Integrative Medicine, Dalian Medical University, Dalian 116044, China
- Laboratory of Integrative Medicine, The First Affiliated Hospital of Dalian Medical University, Dalian 116011, China
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KASL clinical practice guidelines for management of autoimmune hepatitis 2022. Clin Mol Hepatol 2023; 29:542-592. [PMID: 37137334 PMCID: PMC10366804 DOI: 10.3350/cmh.2023.0087] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/01/2023] [Revised: 03/27/2023] [Accepted: 04/03/2023] [Indexed: 05/05/2023] Open
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Bordin DS, Livzan MA, Gaus OV, Mozgovoi SI, Lanas A. Drug-Associated Gastropathy: Diagnostic Criteria. Diagnostics (Basel) 2023; 13:2220. [PMID: 37443618 DOI: 10.3390/diagnostics13132220] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/28/2023] [Revised: 05/30/2023] [Accepted: 06/27/2023] [Indexed: 07/15/2023] Open
Abstract
Drugs are widely used to treat different diseases in modern medicine, but they are often associated with adverse events. Those located in the gastrointestinal tract are common and often mild, but they can be serious or life-threatening and determine the continuation of treatment. The stomach is often affected not only by drugs taken orally but also by those administered parenterally. Here, we review the mechanisms of damage, risk factors and specific endoscopic, histopathological and clinical features of those drugs more often involved in gastric damage, namely NSAIDs, aspirin, anticoagulants, glucocorticosteroids, anticancer drugs, oral iron preparations and proton pump inhibitors. NSAID- and aspirin-associated forms of gastric damage are widely studied and have specific features, although they are often hidden by the coexistence of Helicobacter pylori infection. However, the damaging effect of anticoagulants and corticosteroids or oral iron therapy on the gastric mucosa is controversial. At the same time, the increased use of new antineoplastic drugs, such as checkpoint inhibitors, has opened up a new area of gastrointestinal damage that will be seen more frequently in the near future. We conclude that there is a need to expand and understand drug-induced gastrointestinal damage to prevent and recognize drug-associated gastropathy in a timely manner.
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Affiliation(s)
- Dmitry S Bordin
- A.S. Loginov Moscow Clinical Scientific Center, Department of Pancreatic, Biliary and Upper Digestive Tract Disorders, 111123 Moscow, Russia
- Department of Propaedeutic of Internal Diseases and Gastroenterology, A.I. Yevdokimov Moscow State University of Medicine and Dentistry, 127473 Moscow, Russia
- Department of Outpatient Therapy and Family Medicine, Tver State Medical University, 170100 Tver, Russia
| | - Maria A Livzan
- Department of Faculty Therapy and Gastroenterology, Omsk Sate Medical University, 644099 Omsk, Russia
| | - Olga V Gaus
- Department of Faculty Therapy and Gastroenterology, Omsk Sate Medical University, 644099 Omsk, Russia
| | - Sergei I Mozgovoi
- Department of Pathological Anatomy, Omsk Sate Medical University, 644099 Omsk, Russia
| | - Angel Lanas
- Digestive Diseases Service, Aragón Health Research Institute (IIS Aragón), University Clinic Hospital, University of Zaragoza, 50009 Zaragoza, Spain
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Arjomandnejad M, Dasgupta I, Flotte TR, Keeler AM. Immunogenicity of Recombinant Adeno-Associated Virus (AAV) Vectors for Gene Transfer. BioDrugs 2023; 37:311-329. [PMID: 36862289 PMCID: PMC9979149 DOI: 10.1007/s40259-023-00585-7] [Citation(s) in RCA: 48] [Impact Index Per Article: 24.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 02/07/2023] [Indexed: 03/03/2023]
Abstract
Recombinant adeno-associated viruses (AAVs) have emerged as promising gene delivery vehicles resulting in three US Food and Drug Administration (FDA) and one European Medicines Agency (EMA)-approved AAV-based gene therapies. Despite being a leading platform for therapeutic gene transfer in several clinical trials, host immune responses against the AAV vector and transgene have hampered their widespread application. Multiple factors, including vector design, dose, and route of administration, contribute to the overall immunogenicity of AAVs. The immune responses against the AAV capsid and transgene involve an initial innate sensing. The innate immune response subsequently triggers an adaptive immune response to elicit a robust and specific response against the AAV vector. AAV gene therapy clinical trials and preclinical studies provide important information about the immune-mediated toxicities associated with AAV, yet studies suggest preclinical models fail to precisely predict the outcome of gene delivery in humans. This review discusses the contribution of the innate and adaptive immune response against AAVs, highlighting the challenges and potential strategies to mitigate these responses, thereby enhancing the therapeutic potential of AAV gene therapy.
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Affiliation(s)
- Motahareh Arjomandnejad
- Horae Gene Therapy Center, University of Massachusetts Chan Medical School, 386 Plantation Street, Worcester, MA, 01605, USA
| | - Ishani Dasgupta
- Horae Gene Therapy Center, University of Massachusetts Chan Medical School, 386 Plantation Street, Worcester, MA, 01605, USA
| | - Terence R Flotte
- Horae Gene Therapy Center, University of Massachusetts Chan Medical School, 386 Plantation Street, Worcester, MA, 01605, USA
- Department of Pediatrics, University of Massachusetts Chan Medical School, Worcester, MA, USA
| | - Allison M Keeler
- Horae Gene Therapy Center, University of Massachusetts Chan Medical School, 386 Plantation Street, Worcester, MA, 01605, USA.
- Department of Pediatrics, University of Massachusetts Chan Medical School, Worcester, MA, USA.
- NeuroNexus Institute, University of Massachusetts Chan Medical School, Worcester, MA, USA.
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Aktualisierte S2k-Leitlinie Helicobacter
pylori und gastroduodenale Ulkuskrankheit der Deutschen Gesellschaft für Gastroenterologie, Verdauungs- und Stoffwechselkrankheiten (DGVS) – Juli 2022 – AWMF-Registernummer: 021–001. ZEITSCHRIFT FUR GASTROENTEROLOGIE 2023; 61:544-606. [PMID: 37146633 DOI: 10.1055/a-1975-0414] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 05/07/2023]
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González-Ramos L, Mora-Cuesta VM, Iturbe-Fernández D, Tello-Mena S, Sánchez-Moreno L, Andia-Torrico D, Alonso-Lecue P, Ballesteros-Sanz MDLÁ, Naranjo-Gozalo S, Cifrián-Martínez JM. Early Postoperative Outcomes of Lung Transplant Recipients With Abdominal Adverse Events. Transplant Proc 2023; 55:459-465. [PMID: 37059668 DOI: 10.1016/j.transproceed.2023.02.012] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/15/2022] [Accepted: 02/03/2023] [Indexed: 04/16/2023]
Abstract
INTRODUCTION Patients undergoing lung transplantation (LT) are at high risk of developing serious abdominal complications, which can lead to higher rates of morbidity and mortality. The aim of this study was to investigate the incidence and spectrum of these complications when they develop during the first 30 days after LT, as well as their possible association with possible risk factors. METHODS A retrospective study of 552 patients undergoing LT between 01/02/2006 and 06/03/2021 was carried out. A descriptive and analytical evaluation of the patients who experienced complications and those who did not was performed comparatively. Data related to patient characteristics and the lung transplantation procedure were collected. RESULTS Overall, 8.2% of patients developed severe abdominal complications during the first 30 days; paralytic ileus was the most frequent (31.1%), closely followed by visceral perforation (26.7%). The percentage of patients who required an invasive procedure to manage post-transplant complications was 57.8%. Surgical intervention was required in 39.8%. The variables that showed a significant relationship with the development of severe short-term abdominal complications in the univariate analysis were the time of surgery, the use of ECMO/ ECC and red blood cell transfusion during or after surgery. In the multivariate study, however, only duration of surgery remained significant (p=0.03). CONCLUSION The incidence of severe short-term abdominal complications after LT period was 8%. The commonest complications were paralytic ileus and intestinal perforation. Most patients did not require surgery. The only risk factor found associated with these complications was the duration of the surgical intervention.
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Affiliation(s)
- Laura González-Ramos
- Marqués de Valdecilla University Hospital, Respiratory Department, Santander, Spain
| | | | | | - Sandra Tello-Mena
- Marqués de Valdecilla University Hospital, Respiratory Department, Santander, Spain
| | | | | | | | | | - Sara Naranjo-Gozalo
- Marqués de Valdecilla University Hospital, Thoracic Surgery, Santander, Spain
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Kim S, Chaudhary PK, Kim S. Role of Prednisolone in Platelet Activation by Inhibiting TxA 2 Generation through the Regulation of cPLA 2 Phosphorylation. Animals (Basel) 2023; 13:ani13081299. [PMID: 37106862 PMCID: PMC10135208 DOI: 10.3390/ani13081299] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/27/2023] [Revised: 04/03/2023] [Accepted: 04/03/2023] [Indexed: 04/29/2023] Open
Abstract
Glucocorticoids have been commonly used in the treatment of inflammation and immune-mediated diseases in human beings and small animals such as cats and dogs. However, excessive use can lead to Cushing's syndrome along with several thrombotic and cardiovascular diseases. Although it is well-known that glucocorticoids exert a significant effect on coagulation, the effect of cortisol on platelet function is much less clear. Thus, we aimed to study the effects of prednisolone, one of the commonly used glucocorticoids, on the regulation of platelet function using murine platelets. We first evaluated the concentration-dependent effect of prednisolone on 2-MeSADP-induced platelet function and found that the 2-MeSADP-induced secondary wave of aggregation and dense granule secretion were completely inhibited from 500 nM prednisolone. Since 2-MeSADP-induced secretion and the resultant secondary wave of aggregation are mediated by TxA2 generation, this result suggested a role of prednisolone in platelet TxA2 generation. Consistently, prednisolone did not affect the 2-MeSADP-induced aggregation in aspirinated platelets, where the secondary wave of aggregation and secretion were blocked by eliminating the contribution of TxA2 generation by aspirin. In addition, thrombin-induced platelet aggregation and secretion were inhibited in the presence of prednisolone by inhibiting the positive-feedback effect of TxA2 generation on platelet function. Furthermore, prednisolone completely inhibited 2-MeSADP-induced TxA2 generation, confirming the role of prednisolone in TxA2 generation. Finally, Western blot analysis revealed that prednisolone significantly inhibited 2-MeSADP-induced cytosolic phospholipase A2 (cPLA2) and ERK phosphorylation in non-aspirinated platelets, while only cPLA2 phosphorylation, but not ERK phosphorylation, was significantly inhibited by prednisolone in aspirinated platelets. In conclusion, prednisolone affects platelet function by the inhibition of TxA2 generation through the regulation of cPLA2 phosphorylation, thereby shedding light on its clinical characterization and treatment efficacy in dogs with hypercortisolism in the future.
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Affiliation(s)
- Sanggu Kim
- Laboratory of Veterinary Pathology and Platelet Signaling, College of Veterinary Medicine, Chungbuk National University, Cheongju 28644, Republic of Korea
| | - Preeti Kumari Chaudhary
- Laboratory of Veterinary Pathology and Platelet Signaling, College of Veterinary Medicine, Chungbuk National University, Cheongju 28644, Republic of Korea
| | - Soochong Kim
- Laboratory of Veterinary Pathology and Platelet Signaling, College of Veterinary Medicine, Chungbuk National University, Cheongju 28644, Republic of Korea
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Iwano H, Sato T, Ishii Y, Niki S, Sawaya R, Tamakawa S, Yamada M. Delayed perforation after cold snare polypectomy for small colonic polyps in a patient receiving oral corticosteroids. DEN OPEN 2023; 3:e157. [PMID: 35898834 PMCID: PMC9307717 DOI: 10.1002/deo2.157] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 04/04/2022] [Revised: 06/28/2022] [Accepted: 07/04/2022] [Indexed: 11/12/2022]
Abstract
This case report describes a fatal outcome due to delayed perforation after cold snare polypectomy in a patient with bullous pemphigoid receiving oral corticosteroids. Cold snare polypectomy has become the standard treatment for small colorectal polyps because of the procedure's safety and simplicity. In this case, however, corticosteroid therapy and vasculitis may have caused local necrosis and tearing of the intestinal wall. Corticosteroids are widely used, and perforation after cold snare polypectomy is extremely rare. However, some patients on corticosteroid therapy may have special pathologies, such as in this case, and we advise physicians to use appropriate judgment and extreme caution in determining the indication for endoscopic therapy.
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Affiliation(s)
- Hirotoshi Iwano
- Department of Gastroenterology and Endoscopy Center Shibetsu City Hospital Hokkaido Japan
| | - Takayuki Sato
- Endoscopy Center Shibetsu City Hospital Hokkaido Japan
| | - Yoshifumi Ishii
- Department of Gastroenterology and Endoscopy Center Shibetsu City Hospital Hokkaido Japan
| | - Suguru Niki
- Department of Gastroenterology and Endoscopy Center Shibetsu City Hospital Hokkaido Japan
| | - Reiji Sawaya
- Department of Surgery Shibetsu City Hospital Hokkaido Japan
- Asahi Medical Clinic Hokkaido Japan
| | - Susumu Tamakawa
- Department of Pathology Asahikawa Medical Center Hokkaido Japan
| | - Masataka Yamada
- Department of Gastroenterology and Endoscopy Center Shibetsu City Hospital Hokkaido Japan
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McFarland D, Merchant D, Khandai A, Mojtahedzadeh M, Ghosn O, Hirst J, Amonoo H, Chopra D, Niazi S, Brandstetter J, Gleason A, Key G, di Ciccone BL. Selective Serotonin Reuptake Inhibitor (SSRI) Bleeding Risk: Considerations for the Consult-Liaison Psychiatrist. Curr Psychiatry Rep 2023; 25:113-124. [PMID: 36708455 DOI: 10.1007/s11920-023-01411-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 12/30/2022] [Indexed: 01/29/2023]
Abstract
PURPOSE OF REVIEW To present a clinically oriented review of selective serotonin reuptake inhibitor (SSRI)-related bleeding issues commonly addressed by consult-liaison psychiatrists. RECENT FINDINGS Concomitant medical, surgical, or hospital-based conditions exacerbate the risk of SSRI-related bleeding even though a review of the literature suggests it is only marginally elevated. Psychiatrists and other clinicians need to consider these conditions along with antidepressant benefits when answering the question: to start, hold, continue, or change the antidepressant? Where an evidence base is limited, mechanistic understanding may help consult-liaison psychiatrists navigate this terrain and collaborate with other medical specialties on responsible antidepressant management. Most often, the risk is cumulative; data are not directly applicable to complex clinical situations. This review incorporates a hematologic perspective and approach to bleeding risk assessment along with extant data on SSRI-induced bleeding risk ad specific medical conditions.
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Affiliation(s)
- Daniel McFarland
- Department of Psychiatry, University of Rochester Medical Center, Rochester, NY, USA. .,Wilmot Cancer Center, University of Rochester Medical Center, Rochester, NY, USA.
| | - Dale Merchant
- Department of Psychiatry, Westmead Hospital, Westmead, NSW, Australia.,Department of Consultation-Liaison Psychiatry, Concord Repatriation General Hospital, Sydney, NSW, Australia
| | - Abhisek Khandai
- Department of Psychiatry, University of Texas Southwestern Medical Center, Dallas, TX, USA
| | - Mona Mojtahedzadeh
- Department of Psychiatry, University of California Los Angeles, Los Angeles, CA, USA.,Simms-Mann Center for Integrative Oncology, University of California Los Angeles, Los Angeles, CA, USA
| | - Omar Ghosn
- Department of Psychiatry, University of California San Diego, La Jolla, San Diego, CA, USA
| | - Jeremy Hirst
- Department of Psychiatry, University of California San Diego, La Jolla, San Diego, CA, USA
| | - Hermioni Amonoo
- Department of Psychiatry, Brigham and Women's Hospital, Boston, MA, USA.,Department of Psychosocial Oncology, Dana-Farber Cancer Center, Boston, MA, USA
| | - Depti Chopra
- Department of Psychiatry, The University of Texas, MD Anderson Cancer Center, Houston, TX, USA
| | - Shehzad Niazi
- Department of Psychiatry, Mayo Clinic, Jacksonville, FL, USA
| | - Jennifer Brandstetter
- Department of Psychiatry, University Hospitals Cleveland Medical Center, Cleveland, OH, USA
| | - Andrew Gleason
- Department of Consultation-Liaison Psychiatry, Concord Repatriation General Hospital, Sydney, NSW, Australia.,Florey Institute of Neuroscience and Mental Health, The University of Melbourne, Melbourne, Australia
| | - Garrett Key
- Department of Psychiatry, Ascension Seton Medical Center, Austin, TX, USA
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