• ARDS
• Anaphylaxis
• Anti-inflammatory
• CIRCI
• Glucocorticoids
• Infection
• Inflammation

• Animals
• Glucocorticoids/therapeutic use
• Glucocorticoids/adverse effects
• Glucocorticoids/pharmacology
• Dog Diseases/drug therapy
• Cat Diseases/drug therapy
• Cats
• Intensive Care Units
• Dogs

• CIRCI
• glucocorticoids
• sepsis
• vasopressor resistance

• Animals
• Dogs
• Retrospective Studies
• Dexamethasone/therapeutic use
• Dexamethasone/analogs & derivatives
• Dog Diseases/drug therapy
• Dog Diseases/mortality
• Female
• Male
• Shock, Septic/veterinary
• Shock, Septic/drug therapy
• Shock, Septic/mortality
• Critical Illness
• Hypotension/veterinary
• Hypotension/drug therapy
• Glucocorticoids/therapeutic use
• Vasoconstrictor Agents/therapeutic use
• Adrenal Cortex Hormones/deficiency

• Acute kidney failure
• Dialysis
• Electrolyte disorder
• Hyperhydration
• Metabolic acidosis

• Humans
• Acute Kidney Injury/therapy
• Acute Kidney Injury/diagnosis
• Renal Dialysis/methods
• Emergencies
• Kidney Transplantation
• Nephrology/methods

• ASIA syndrome
• EBV
• HLA-II
• SARS-CoV-2
• hypophysitis
• long COVID
• myalgic encephalomyelitis
• post-COVID-19 vaccine syndrome

• Humans
• COVID-19 Vaccines/adverse effects
• COVID-19 Vaccines/immunology
• Fatigue Syndrome, Chronic/immunology
• Fatigue Syndrome, Chronic/etiology
• Fatigue Syndrome, Chronic/virology
• HLA-DRB1 Chains/genetics
• HLA-DRB1 Chains/immunology
• Post-Acute COVID-19 Syndrome/immunology

• Adrenal cortex
• Areas of cortical zonations
• COVID-19
• Corticosteroid receptor
• Structural disorganization

• Humans
• Critical Illness
• Retrospective Studies
• COVID-19
• Adrenal Cortex
• Adrenal Glands
• Adrenal Cortex Hormones

• Adrenal insufficiency
• Critical illness related corticosteroid insufficiency
• Paediatric critical care

• Humans
• Child
• Adrenal Insufficiency/diagnosis
• Adrenal Insufficiency/drug therapy
• Critical Illness/therapy
• Adrenal Cortex Hormones/therapeutic use
• Hydrocortisone/therapeutic use
• Glucocorticoids/therapeutic use

• hyperglycemia
• intensive care unit
• mortality
• pulmonary hypertension
• stress

• Humans
• Male
• Female
• Cohort Studies
• Hypertension, Pulmonary/etiology
• Critical Illness
• Hyperglycemia/etiology
• Comorbidity

• acute gastrointestinal injury
• adrenocorticotropic hormone
• cortisol

• no funding to report

• corticosteroid
• diagnosis
• insufficiency
• saudi arabia
• survey

• binding proteins
• cortisol
• critical illness
• glucocorticoid receptor
• sepsis

• Humans
• Hydrocortisone/metabolism
• Critical Illness/therapy
• Pro-Opiomelanocortin/metabolism
• Pro-Opiomelanocortin/pharmacology
• Hypothalamo-Hypophyseal System
• Adrenal Insufficiency/drug therapy
• Adrenal Insufficiency/metabolism
• Hypothalamus
• Pituitary Diseases/metabolism
• Adrenocorticotropic Hormone/metabolism
• Pituitary-Adrenal System/metabolism

• Research Foundation-Flanders
• Methusalem Program of the Flemish Government
• European Research Council
• European Union’s
• Horizon 2020
• European Respiratory Society
• University Hospitals Leuven

• Equine neonates
• Hypothalamic-pituitary-adrenal axis
• Neurosteroids
• Relative adrenal insufficiency
• Sepsis

• Horses
• Animals
• Hydrocortisone
• Adrenocorticotropic Hormone
• Critical Illness
• Animals, Newborn
• Horse Diseases
• Progesterone
• Aldosterone
• Progestins
• Steroids
• Sepsis/veterinary
• Hospitalization

• immunomodulatory therapy
• immunosuppression
• inflammation
• innate immunity
• traumatic brain injury

• endoscopic retrograde cholangiopancreatography
• general medicine
• hypoglycemia
• illness-related corticosteroid insufficiency
• macrophage activation syndrome
• occult bacteremia
• rural hospital

SARS-CoV-2 infection may cause multiple organ failure. However, scarce information can be found on the impact on the endocrine system. This study was conducted to determine plasma Adrenocorticotropic hormone (ACTH) and plasma cortisol levels in a cohort of COVID-19 patients with Acute Respiratory Distress Syndrome (ARDS).

A prospective cohort study was conducted on COVID-19 patients who manifested ARDS and were admitted to the ICU of Dr. Soetomo Tertiary Hospital, Surabaya, Indonesia. Morning plasma ACTH and plasma total cortisol were measured on 45 recruited patients. The outcome of the patient was justified based on the survivance on days 7th and 30th during the follow-up with groupings of surviving for survived patients and nonsurvive for deceased patients.

The ACTH and cortisol median were 1.06 (0.5–64.57) pg/mL and 17.61 (0.78–75) μg/dL, respectively. Both parameters were assembled to allow the allocation of the 45 subjects into the survive and nonsurvive groups. There was a moderate correlation between ACTH and cortisol levels in all groups (r = 0.46, p < 0.002) and particularly ACTH and cortisol levels in COVID-19 patients who survived on the 7th-day and 30th-day follow-up (r = 0.518 and r = 0.568, respectively, with p < 0.05). It is important to note that there was no correlation for an individual parameter, either ACTH only or cortisol only, compared to the outcome among patients with various comorbid.

ACTH or cortisol alone has no correlation to the outcome of these patients. Therefore, further study of the potential use of corticosteroid treatments guided by ACTH and cortisol levels in reducing the risk of ARDS warrants further investigation.

Intraoperative hyperglycemia has been associated with multiple postoperative complications such as surgical site infection, myocardial infarction, stroke, and death. These complications are not confined to only diabetic patients. However, the incidence of intraoperative hyperglycemia in non-diabetic patients has not been fully elucidated. Additionally, these patients’ risk factors were not well established in previous studies.

Four hundred forty non-diabetic patients who underwent intermediate- to high-risk surgery were included in the study. We prospectively measured the capillary blood glucose level in all patients during surgery. The incidence of intraoperative hyperglycemia was defined as at least one episode of blood glucose level of more than 180 mg/dL. Risk factors for hyperglycemia were assessed using multivariable logistic regression analysis.

Sixty-five (14.7%) patients developed hyperglycemia during surgery. The independent risk factors for intraoperative hyperglycemia were an American Society of Anesthesiologists status ≥ 3 (odds ratio [OR] 6.09, 95% confidence interval [CI]: 2.67–13.89, p < 0.001), preoperative impaired fasting blood sugar (OR 2.28, 95%CI:1.13–4.61, p = 0.021), duration of anesthesia ≥ 3 h (OR 4.06, 95%CI: 1.23–13.45, p = 0.021), intraoperative hypotension (OR 5.37, 95%CI: 2.35–12.29, p < 0.001), intraoperative blood transfusion (OR 4.35, 95%CI: 2.15–8.79, p < 0.001), and steroid use (OR 2.39, 95%CI: 1.20–4.76, p = 0.013). Surgical site infection was higher in patients with intraoperative hyperglycemia compared with patients without intraoperative hyperglycemia (4 [6.1%] vs. 6 [1.6%], respectively, p = 0.035).

The incidence of intraoperative hyperglycemia was significant in non-diabetic patients during intermediate- to high-risk surgery. Risk factors should be identified to prevent intraoperative hyperglycemia.

The study was prospectively registered at https://www.thaiclinicaltrials.org (TCTR20191114001).

Reduced glucocorticoid-receptor (GR) expression in blood suggested that critically ill patients become glucocorticoid-resistant necessitating stress-doses of glucocorticoids. We hypothesised that critical illness evokes a tissue-specific, time-dependent expression of regulators of GR-action which adaptively guides glucocorticoid action to sites of need.

We performed a prospective, observational, cross-sectional human study and two translational mouse studies. In freshly-isolated neutrophils and monocytes and in skeletal muscle and subcutaneous adipose tissue of 137 critically ill patients and 20 healthy controls and in skeletal muscle and adipose tissue as well as in vital tissues (heart, lung, diaphragm, liver, kidney) of 88 septic and 26 healthy mice, we quantified gene expression of cortisone-reductase 11β-HSD1, glucocorticoid-receptor-isoforms GRα and GRβ, GRα-sensitivity-regulating-co-chaperone FKBP51, and GR-action-marker GILZ. Expression profiles were compared in relation to illness-duration and systemic-glucocorticoid-availability.

In patients’ neutrophils, GRα and GILZ were substantially suppressed (p≤0·05) throughout intensive care unit (ICU)-stay, while in monocytes low/normal GRα coincided with increased GILZ (p≤0·05). FKBP51 was increased transiently (neutrophils) or always (monocytes,p≤0·05). In patients’ muscle, 11β-HSD1 and GRα were low-normal (p≤0·05) and substantially suppressed in adipose tissue (p≤0·05); FKBP51 and GILZ were increased in skeletal muscle (p≤0·05) but normal in adipose tissue. GRβ was undetectable. Increasing systemic glucocorticoid availability in patients independently associated with further suppressed muscle 11β-HSD1 and GRα, further increased FKBP51 and unaltered GILZ (p≤0·05). In septic mouse heart and lung, 11β-HSD1, FKBP51 and GILZ were always high (p≤0·01). In heart, GRα was suppressed (p≤0·05), while normal or high in lung (all p≤0·05). In diaphragm, 11β-HSD1 was high/normal, GRα low/normal and FKBP51 and GILZ high (p≤0·01). In kidney, 11β-HSD1 transiently increased but decreased thereafter, GRα was normal and FKBP51 and GILZ high (p≤0·01). In liver, 11β-HSD1 was suppressed (p≤0·01), GRα normal and FKBP51 high (p≤0·01) whereas GILZ was transiently decreased but elevated thereafter (p≤0·05). Only in lung and diaphragm, treatment with hydrocortisone further increased GILZ.

Tissue-specific, time-independent adaptations to critical illness guided GR-action predominantly to vital tissues such as lung, while (partially) protecting against collateral harm in other cells and tissues, such as neutrophils. These findings argue against maladaptive generalised glucocorticoid-resistance necessitating glucocorticoid-treatment.

Research-Foundation-Flanders, Methusalem-Program-Flemish-Government, European-Research-Council, European-Respiratory-Society.

• CIRCI
• Critical illness
• Glucocorticoid receptor
• Glucocorticoid resistance
• ICU
• Sepsis

• Animals
• Lipopolysaccharides/pharmacology
• Metformin/metabolism
• Metformin/pharmacology
• Metformin/therapeutic use
• Mice
• Microglia/metabolism
• NF-kappa B/metabolism
• Prognosis
• Sepsis/complications
• Sepsis/drug therapy
• Sepsis/metabolism
• Sepsis-Associated Encephalopathy/drug therapy
• Sepsis-Associated Encephalopathy/metabolism
• Sepsis-Associated Encephalopathy/pathology

• Drug Therapy, Combination
• Humans
• Hydrocortisone/therapeutic use
• Prospective Studies
• Shock, Septic/drug therapy
• Vitamins/therapeutic use

• Adult
• Diabetes Mellitus
• Humans
• Hyperglycemia/complications
• Injury Severity Score
• Prospective Studies
• Stress, Physiological
• Trauma Centers
• Wounds and Injuries/complications

• Hamad Medical Corporation

Intravenous leiomyomatosis (IVL) is a rare estrogen-dependent neoplasm. However, identifiable and reliable biomarkers are still not available for clinical application, especially for the diagnosis and prognosis of the disease.

In the present study, 30 patients with IVL and 30 healthy controls were recruited. Serum samples were isolated from these participants for further high performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) analysis to study metabolomics alterations and identify differentially expressed metabolites based on orthogonal partial least-squares discriminant analysis (OPLS-DA). Subsequently, lasso regression analysis and a generalized linear regression model were applied to screen out hub metabolites associated with the progression of IVL.

First, 16 metabolites in the positive ion mode were determined from the 240 identifiable metabolites at the superclass level, with ten metabolites upregulated in the IVL group and the remaining six metabolites downregulated. Our data further proved that four metabolites [hypoxanthine, acetylcarnitine, glycerophosphocholine, and hydrocortisone (cortisol)] were closely related to the oncogenesis of IVL. Hypoxanthine and glycerophosphocholine might function as protective factors in the development of IVL (OR = 0.19 or 0.02, respectively). Nevertheless, acetylcarnitine and hydrocortisone (cortisol), especially the former, might serve as risk indicators for the disease to promote the development or recurrence of IVL (OR = 18.16 or 2.10, respectively). The predictive accuracy of these hub metabolites was further validated by the multi-class receiver operator characteristic curve analysis (ROC) with the Scikit-learn algorithms.

Four hub metabolites were finally determined via comprehensive bioinformatics analysis, and these substances could potentially serve as novel biomarkers in predicting the prognosis or progression of IVL.

• HPLC-MS/MS
• biomarkers
• intravenous leiomyomatosis
• metabolomics
• progression

• Canine
• Emergency
• Hypoadrenocorticism
• Hypotension
• Sepsis

• Dimer
• Dysfunction
• Glucocorticoid receptor
• Monomer
• Mouse models
• Organ function
• Systemic inflammation

Background: Synchronized circadian rhythms play a key role in coordinating physiologic health. Desynchronized circadian rhythms may predispose individuals to disease or be indicative of underlying disease. Intensive care unit (ICU) patients likely experience desynchronized circadian rhythms due to disruptive environmental conditions in the ICU and underlying pathophysiology. This observational pilot study was undertaken to determine if 24-h rhythms are altered in ICU patients relative to healthy controls by profiling 24-h rhythms in vital signs and plasma metabolites.

Methods: We monitored daily rhythms in 5 healthy controls and 5 ICU patients for 24 h. Heart rate and blood pressure were measured every 30 min, temperature was measured every hour, and blood was sampled for mass spectrometry-based plasma metabolomics every 4 h. Bedside sound levels were measured every minute. Twenty-four hours rhythms were evaluated in vitals and putatively identified plasma metabolites individually and in each group using the cosinor method.

Results: ICU patient rooms were significantly louder than healthy controls' rooms and average noise levels were above EPA recommendations. Healthy controls generally had significant 24-h rhythms individually and as a group. While a few ICU patients had significant 24-h rhythms in isolated variables, no significant rhythms were identified in ICU patients as a group, except in cortisol. This indicates a lack of coherence in phases and amplitudes among ICU patients. Finally, principal component analysis of metabolic profiles showed surprising patterns in plasma sample clustering. Each ICU patient's samples were clearly discernable in individual clusters, separate from a single cluster of healthy controls.

Conclusions: In this pilot study, ICU patients' 24-h rhythms show significant desynchronization compared to healthy controls. Clustering of plasma metabolic profiles suggests that metabolomics could be used to track individual patients' clinical courses longitudinally. Our results show global disordering of metabolism and the circadian system in ICU patients which should be characterized further in order to determine implications for patient care.

• ICU—intensive care unit
• circadian rhythms
• cortisol (Cor)
• critical illness
• metabolomics
• precision medicine

• AdaBoost
• Addison's
• Artificial intelligence
• Boosted tree
• Canine

• Addison Disease/diagnosis
• Addison Disease/veterinary
• Algorithms
• Animals
• Dog Diseases/diagnosis
• Dogs
• Female
• Machine Learning
• Male

• ascorbic acid
• corticosteroids
• esophagectomy
• lung injury

• Adrenal Cortex Hormones/administration & dosage
• Adrenal Cortex Hormones/adverse effects
• Aged
• Ascorbic Acid/administration & dosage
• Ascorbic Acid/adverse effects
• Biomarkers/blood
• Esophagectomy/adverse effects
• Esophagectomy/methods
• Female
• Humans
• Intensive Care Units
• Length of Stay
• Lung/drug effects
• Lung/physiopathology
• Lung Injury/diagnosis
• Lung Injury/etiology
• Lung Injury/physiopathology
• Lung Injury/prevention & control
• Male
• Oxygen/blood
• Pilot Projects
• Respiration, Artificial
• Retrospective Studies
• Thiamine/administration & dosage
• Thiamine/adverse effects
• Thoracoscopy/adverse effects
• Time Factors
• Treatment Outcome

• Adrenal Cortex Hormones/administration & dosage
• Adrenal Cortex Hormones/adverse effects
• Adrenal Cortex Hormones/therapeutic use
• Cross Infection/epidemiology
• Dose-Response Relationship, Drug
• Humans
• Influenza, Human/drug therapy
• Influenza, Human/mortality
• Influenza, Human/therapy
• Length of Stay
• Observational Studies as Topic
• Respiration, Artificial
• Severity of Illness Index

• Community-acquired pneumonia
• mortality
• outcomes
• steroids

• Adrenal Cortex Hormones/administration & dosage
• Adrenal Cortex Hormones/adverse effects
• Adrenal Cortex Hormones/therapeutic use
• Anti-Bacterial Agents/therapeutic use
• Biomarkers
• Community-Acquired Infections
• Humans
• Inflammation Mediators/metabolism
• Length of Stay
• Pneumonia/drug therapy
• Pneumonia/epidemiology
• Pneumonia/microbiology
• Practice Guidelines as Topic
• Severity of Illness Index
• Time Factors

Hypothalamic-pituitary-adrenal axis dysfunction may lead to the occurrence of critical illness-related corticosteroid insufficiency. Critical illness-related corticosteroid insufficiency can easily occur after traumatic brain injury, but few studies have examined this occurrence. A multicenter, prospective, cohort study was performed to evaluate the function of the hypothalamic-pituitary-adrenal axis and the incidence of critical illness-related corticosteroid insufficiency during the sub-acute phase of traumatic brain injury. One hundred and forty patients with acute traumatic brain injury were enrolled from the neurosurgical departments of three tertiary-level hospitals in China, and the critical illness-related corticosteroid insufficiency incidence, critical-illness-related corticosteroid insufficiency-related risk factors, complications, and 28-day mortality among these patients was recorded. Critical illness-related corticosteroid insufficiency was diagnosed in patients with plasma total cortisol levels less than 10 μg/dL (275.9 nM) on post-injury day 4 or when serum cortisol was insufficiently suppressed (less than 50%) during a dexamethasone suppression test on post-injury day 5. The results demonstrated that critical illness-related corticosteroid insufficiency occurred during the sub-acute phase of traumatic brain injury in 5.6% of patients with mild injury, 22.5% of patients with moderate injury, and 52.2% of patients with severe injury. Traumatic brain injury-induced critical illness-related corticosteroid insufficiency was strongly correlated to injury severity during the sub-acute stage of traumatic brain injury. Traumatic brain injury patients with critical illness-related corticosteroid insufficiency frequently presented with hemorrhagic cerebral contusions, diffuse axonal injury, brain herniation, and hypotension. Differences in the incidence of hospital-acquired pneumonia, gastrointestinal bleeding, and 28-day mortality were observed between patients with and without critical illness-related corticosteroid insufficiency during the sub-acute phase of traumatic brain injury. Hypotension, brain-injury severity, and the types of traumatic brain injury were independent risk factors for traumatic brain injury-induced critical illness-related corticosteroid insufficiency. These findings indicate that critical illness-related corticosteroid insufficiency is common during the sub-acute phase of traumatic brain injury and is strongly associated with poor prognosis. The dexamethasone suppression test is a practical assay for the evaluation of hypothalamic-pituitary-adrenal axis function and for the diagnosis of critical illness-related corticosteroid insufficiency in patients with traumatic brain injury, especially those with hypotension, hemorrhagic cerebral contusions, diffuse axonal injury, and brain herniation. Sub-acute infection of acute traumatic brain injury may be an important factor associated with the occurrence and development of critical illness-related corticosteroid insufficiency. This study protocol was approved by the Ethics Committee of General Hospital of Tianjin Medical University, China in December 2011 (approval No. 201189).

• brain herniation
• corticosteroid
• critical illness-related corticosteroid
• dexamethasone suppression test
• diffuse axonal injury
• gastrointestinal bleeding
• hemorrhagic cerebral contusions
• hospital-acquired pneumonia
• insufficiency
• prognosis
• traumatic brain injury

• Arrest
• Cholesterol
• Critical illness
• Heart
• Lipoproteins

• Biomarkers/blood
• Cardiopulmonary Resuscitation/adverse effects
• Cardiopulmonary Resuscitation/methods
• Cardiopulmonary Resuscitation/statistics & numerical data
• Cholesterol/blood
• Critical Illness/epidemiology
• Diagnostic Tests, Routine/methods
• Female
• Humans
• Male
• Middle Aged
• Nervous System Diseases/blood
• Nervous System Diseases/diagnosis
• Nervous System Diseases/epidemiology
• Nervous System Diseases/etiology
• Out-of-Hospital Cardiac Arrest/blood
• Out-of-Hospital Cardiac Arrest/complications
• Out-of-Hospital Cardiac Arrest/epidemiology
• Out-of-Hospital Cardiac Arrest/therapy
• Outcome Assessment, Health Care/methods
• Predictive Value of Tests
• Prognosis
• Republic of Korea/epidemiology
• Retrospective Studies
• Time Factors

• Adrenal Cortex Hormones/adverse effects
• Adrenal Cortex Hormones/therapeutic use
• Chemotherapy, Adjuvant/adverse effects
• Cross Infection/etiology
• Cross Infection/mortality
• Hospital Mortality
• Humans
• Influenza A Virus, H1N1 Subtype
• Influenza, Human/drug therapy
• Influenza, Human/mortality
• Intensive Care Units/statistics & numerical data
• Observational Studies as Topic
• Randomized Controlled Trials as Topic
• Respiration, Artificial/statistics & numerical data

• Corticosteroids
• Septic shock
• Vasodilatory shock

• Adult
• Aged
• Aged, 80 and over
• Anti-Inflammatory Agents/therapeutic use
• Female
• Hemodynamics/drug effects
• Humans
• Hydrocortisone/therapeutic use
• Male
• Middle Aged
• Shock, Septic/diagnosis
• Shock, Septic/drug therapy

• Corticosteroids
• Critical illness
• Erythropoietin
• Low-dose hydrocortisone
• Progesterone
• Trauma patients
• Traumatic brain injury

• angiotensin II
• corticosteroids
• methylene blue
• midodrine
• sepsis
• septic shock
• vasopressin

• Adrenal Insufficiency
• Critical Illness
• Humans
• Intensive Care Units
• Prospective Studies
• Observational Studies as Topic

Background: This study was designed to measure the effect of stress-induced hyperglycemia (SIH) and diabetic hyperglycemia (DH) versus non-diabetic normoglycemia (NDN) on the outcomes of trauma patients in the intensive care unit (ICU). Methods: Diabetes mellitus (DM) was determined based on patient history and/or a hemoglobin A1c (HbA1c) level of ≥6.5% at admission. The patients who had serum glucose levels of ≥200 mg/dL in the absence or presence of DM were assigned into the groups SIH and DH, respectively. Diabetic normoglycemia (DN) and NDN were determined based on serum glucose levels of <200 mg/dL in patients with and without DM, respectively. Patients with burn injury or incomplete data were excluded. Detailed data of trauma patients in the ICU of a Level-I trauma center from 1 January 2009 to 31 December 2016 were retrieved from the database of the Trauma Registry System. These patients were classified into four exclusive groups, including NDN (n = 1745), DN (n = 306), SIH (n = 225) and DH (n = 206). The Pearson chi-square test was used to compare categorical data between groups. Continuous variables were compared using one-way analysis of variance along with the Games–Howell post hoc test. To decrease the confounding effect of the differences in sex and age, preexisting comorbidities and injury severity score (ISS) among different groups of patients, 1:1 ratio propensity score-matched cohorts were assigned using the NCSS software. The effect of hyperglycemia on the outcomes of patients with and without DM was assessed with a logistic regression analysis. Results: Among those selected propensity score-matched patient cohorts, the patients with SIH and DH had a 3.88-fold (95% CI, 2.13–7.06; p < 0.001) and 1.83-fold (95% CI, 1.00–3.34; p = 0.048) higher mortality, respectively, than those with NDN. Moreover, the patients in the SIH group (10.0 vs. 7.4 days; p = 0.005) and those in the DH group (10.1 vs. 7.4 days; p = 0.006) who were admitted to the ICU had a significantly longer length of stay than those in the NDN group. In addition, the SIH group had a 2.13-fold (95% CI, 1.04–4.36; p = 0.038) higher adjusted odds ratio for mortality than the DH group. Conclusions: This study revealed significantly worse outcomes in terms of mortality among patients with SIH and DH who were admitted to the ICU after controlling for sex and age, preexisting comorbidities and ISS. In addition, patients who had SIH presented significantly higher adjusted odds for mortality than those DH patients. These results suggest that hyperglycemia is detrimental in patients with or without DM who were admitted to the ICU, and there is a different pathophysiological mechanisms behind the SIH and DH.

• diabetes mellitus
• diabetic hyperglycemia
• intensive care unit
• mortality
• stress-induced hyperglycemia

Microvascular endothelial cells play a pivotal role in the pathogenesis of sepsis-induced inflammatory responses and multiple organ failure. Therefore, they represent an important target for pharmacological intervention in the treatment of sepsis. Glucocorticosteroids were widely used in the treatment of sepsis but vast evidence to support their systemic use is lacking. The limited effects of glucocorticoids in the treatment of sepsis may be explained by differential effects of drug initiated NF-κB inhibition in different cell types and insufficient drug delivery in target cells. The current study aimed therefore to investigate the effects of an endothelial targeted delivery of dexamethasone in a mouse model of endotoxemia induced by two consecutive i.p. injections of lipopolysaccharide (LPS). To achieve endothelial cell specific delivery of dexamethasone, we modified SAINT-O-Somes, a new generation of liposomes that contain the cationic amphiphile SAINT-C18 (1-methyl-4-(cis-9-dioleyl) methyl-pyridinium chloride, with antibodies against vascular cell adhesion molecule-1 (VCAM-1). In LPS challenged mice, the systemic administration of free dexamethasone had negligible effects on the microvascular inflammatory endothelial responses. Dexamethasone-loaded anti-VCAM-1 SAINT-O-Somes specifically localized at VCAM-1 expressing endothelial cells in the microvasculature of inflamed organs. This was associated with a marginal attenuation of the expression of a few pro-inflammatory genes in kidney and liver, while no effects in the lung were observed. This study reveals that, although local accumulation of the targeted drug was achieved, endothelial targeted dexamethasone containing anti-VCAM-1 SAINT-O-Somes exhibited marginal effects on inflammatory endothelial cell activation in a model of endotoxemia. Studies with more potent drugs encapsulated into anti-VCAM-1 SAINT-O-Somes will in the future reveal whether this delivery system can be further developed for efficacious endothelial directed delivery of drugs in the treatment of sepsis.

• Drug-resistant tuberculosis
• Infection control
• Intensive care
• Latent tuberculosis
• Multi-drug resistant tuberculosis
• Tuberculosis