Antimicrobial resistance is strongly correlated with the volume of antibiotics used. Most antibiotics are prescribed in primary care, mostly for respiratory tract infections (RTIs), and are often unneeded.

The current knowledge regarding the use of C-reactive protein (CRP) rapid testing in primary care is outlined. A comprehensive literature search and narrative review of the evidence on CRP rapid testing for patients presenting with symptoms of RTIs was conducted to develop a holistic perspective on the subject. Relevant studies were identified through a PubMed search up to April 2025.

CRP testing is an effective, cost-efficient tool to reduce unnecessary antibiotic use for lower RTIs in primary care. This test should be included in guidelines and implemented when a clinician is uncertain about the prognosis of an infection. It should complement history taking and clinical examination before deciding to prescribe antibiotics, primarily to rule out serious infections, but should never be used as a standalone test. To tackle antimicrobial resistance, the reduction of unnecessary antibiotic use in acute RTIs is optimized with clear guidance, advanced communication training for clinicians, and delayed antibiotic prescribing strategies when applicable.

This study uses two-sample MR analysis with GWAS summary statistics to evaluate the causal relationship between metabolic syndrome and low back pain. A two-sample Mendelian randomization analysis used GWAS summary statistics for low back pain from the FinnGen database and metabolic syndrome data, including waist circumference, hypertension, fasting blood glucose, HDL cholesterol, and triglyceride levels. Various methods like inverse variance weighted, MR-Egger, weighted median, and mode assessed the causal relationship, with sensitivity analyses addressing heterogeneity and pleiotropy. Our analysis found a statistically significant causal association between essential hypertension (OR  2.38, 95% CI 1.42-3.96; Padj = 0.002), metabolic syndrome (OR  1.05, 95% CI 1.01-1.10; Padj = 0.023) and waist circumference (OR   49, 95% CI 1.32-1.68; Padj < 0.001) and low back pain (OR  1.41, 95% CI 1.30-1.53, Padj < 0.001). In contrast, fasting blood glucose (FBG), HDL cholesterol, and triglycerides showed no significant associations with low back pain across all MR methods. The results of sensitivity analyses indicated that the heterogeneity and pleiotropy were unlikely to disturb the causal estimate. Our study indicates that increased essential hypertension, metabolic syndrome and waist circumference is causally associated with a higher risk of low back pain. Interventions targeting metabolic syndrome components, particularly blood pressure control and weight management, could help reduce the risk of low back pain. Further research is needed to explore the underlying biological pathways linking these metabolic factors to low back pain.

Acmella paniculata has been traditionally used in folklore medicine to alleviate pain and manage articular rheumatism. This study explores its potential anti-inflammatory and antiarthritic effects through in silico and in vivo approaches. A. paniculata bioactives' antiarthritic mechanisms were elucidated using computational techniques, namely, gene set enrichment analysis, network pharmacology, molecular docking, and molecular dynamics (MD) simulations using KEGG pathway analysis, PyRx, Discovery Studio, and GROMACS tools. A. paniculata hydroalcoholic extract (APE) and the ethyl acetate fraction (APF) were analyzed via LC‒MS for phytochemical profiling. In vivo studies assessed anti-inflammatory and antiarthritic potential in carrageenan-induced paw edema and complete Freund's adjuvant (CFA)-induced arthritis models in Wistar rats. Ferulic acid, isoferulic acid, and acetyl aleuritolic acid were identified as bioactives that targeted RELA, a key NF-κB component. Stable interactions were confirmed through docking and MD simulations. LC‒MS verified these compounds in APE and APF. In vivo study revealed significant reductions in paw volume, arthritis scores, and inflammatory markers (CRP, RF, IL-6, and TNF-α) and improved histopathological outcomes in the APE and APF-treated groups compared to the CFA. These findings highlight the anti-inflammatory and antiarthritic potential of A. paniculata via multi-protein modulation, particularly NF-κB signaling, and it can be utilized as a promising therapeutic for rheumatoid arthritis.

Childhood obesity has been associated with high levels of systemic inflammation, increasing the risk of metabolic and cardiovascular diseases throughout life. Genetic and environmental factors, such as parental body mass index (BMI), can influence this relationship, impacting the inflammatory health of offspring from childhood. This study investigates the influence of parental BMI on the relationship between BMI and high-sensitivity C-reactive protein (hs-CRP) levels in offspring. A cross-sectional study was conducted with 423 children and adolescents from a municipality in southern Brazil. Offspring BMI was calculated using measured weight and height, while parental BMI was determined from self-reported measurements and classified based on World Health Organization cutoff points. hs-CRP levels were assessed using a high-sensitivity assay. The moderating effect of parental BMI on the relationship between offspring BMI and hs-CRP levels was analyzed through multiple linear regression models using the PROCESS macro extension for SPSS. Results indicated a direct association between offspring BMI and hs-CRP levels across all models, showing that hs-CRP levels increased linearly with BMI in offspring. A direct relationship between paternal obesity and offspring hs-CRP levels was observed, along with a significant inverse interaction between paternal BMI and offspring BMI with hs-CRP levels. Among schoolchildren with lower BMI, those with parents with obesity exhibited higher hs-CRP levels compared to peers with parents classified as eutrophic or overweight. These findings suggest that children of parents with obesity tend to have elevated levels of inflammation, regardless of their own BMI.

The blood test is one of the most performed investigations in clinical practice, with samples typically analysed in a centralised laboratory. Many of these tests monitor routine conditions that would benefit from a point-of-care approach, reducing the burden on practitioners, patients and healthcare systems. Such a decentralised model requires the development of sophisticated, yet easy-to-use technology; however, platforms that combine high-performance with low-cost and simplicity remain scarce. Moreover, most research papers only address a subset of requirements and study specific aspects in isolation. A systems approach that considers the interplay between each element of the technology is clearly required to develop a coherent solution. Here, we present such a systems approach in the context of testing for C-reactive protein (CRP), a commonly requested test in clinical practise that indicates inflammation and is particularly relevant for monitoring patients with chronic diseases, e.g. those with rheumatoid arthritis or who are undergoing cancer therapy. The approach we take here features an entirely passive microfluidic cartridge for blood separation, integrated with a high-performance sensing platform which we have tested in a real-world context. The device is compatible with a handheld detection unit and is simple to use yet can accurately detect CRP levels at clinically relevant levels.

A 31-year-old Cameroonian man presented to the emergency department (ED) with a productive cough, exertional dyspnoea, and asthenia for a few days. The initial evaluation was limited due to cultural barriers, lack of known medical history, and the patient's migration journey through Libya, Tunisia, and Germany over the past 5 years before recently arriving in Switzerland. Clinical examination revealed no red flags. Blood counts were normal, C-reactive protein (CRP) was elevated at 91 mg/L, and a chest X-ray was unremarkable. A diagnosis of influenza-like syndrome was made. The patient returned the following day with increased fatigue and fever. A rapid malaria test was negative, a blood smear was ordered, and CRP levels rose to 148 mg/L. During an influenza epidemic, PCR confirmed Influenza A. The patient was reassured and prescribed ibuprofen and paracetamol. Subsequently, the laboratory detected not malaria but filariae, and a diagnosis of Loiasis (Loa loa) was established. The patient was referred for specialist consultation. Treatment with albendazole was initiated, leading to gradual improvement.

Paraffin section is an important technique in histology research, and transparency is the key step connecting the procedures of dehydration and wax immersion in paraffin sectioning technology. However, the commonly used transparent reagent xylene is toxic to the human body and the environment and included in the list of carcinogens. Few biosafe and environmentally friendly transparent reagents have been widely used to replace xylene. In this study, we found a green transparent reagent, dimethyl carbonate (DMC). Physical and chemical analysis showed that DMC was nontoxic and biodegradable. The feasibility analysis of DMC as a substitute for xylene showed that DMC improved the quality of wax band, staining quality, cell boundary, cell morphology, and section integrity in the sections of plant and animal tissues. The toxicological analysis showed that DMC had no significant effect on the key organs of mice, did not induce obvious inflammation in vivo, and showed higher biosafety than xylene. DMC can be used as a transparent reagent to replace xylene in paraffin section, based on its better physical properties, better paraffin sectioning effect, and higher biosafety. DMC is expected to be widely used in the technical fields of tissue section through further optimization and improvement of the method.

Acrolein, a polyamine produced from spermine during brain infarction, has recently been used in clinical settings for brain infarction risk assessment. However, few studies have investigated the diagnostic usefulness of acrolein measurement in postmortem specimens. In this study, we measured the acrolein concentration in postmortem specimens to assess its potential as a marker for stroke diagnosis. Acrolein concentrations in the serum and urine were measured using an enzyme-linked immunosorbent assay in 25, 19, 21, and 93 brain infarction, subarachnoid hemorrhage, cerebral hemorrhage, and control cases, respectively. No correlations or significant differences were observed between the acrolein concentrations in blood or urine, age, time since death, or sex. However, the serum acrolein concentrations increased significantly in cases of brain infarction, subarachnoid hemorrhage, and cerebral hemorrhage compared with non-stroke cases, with diagnostic cutoff values of 117.1, 119.9, and 130.3 nmol/mL, respectively. Conversely, the urinary acrolein concentrations decreased in specimens from subarachnoid hemorrhage and cerebral hemorrhage cases, suggesting dilution due to higher urine volumes. In conclusion, our findings suggest that serum acrolein concentration remains unaffected by the time elapsed after death. Moreover, the measurement of serum acrolein in postmortem specimens is effective in diagnosing stroke.

The study aimed to investigate the pharmacokinetic profile of voriconazole in patients with COVID-19-associated pulmonary aspergillosis (CAPA) to optimize dosing strategies.

Population pharmacokinetic modeling was conducted using clinical data from CAPA patients to analyze voriconazole's pharmacokinetic behavior. A one-compartment model with first-order elimination was employed to characterize voriconazole disposition. Covariate analysis was further utilized to evaluate the impact of continuous renal replacement therapy (CRRT) and select biochemical markers on voriconazole clearance.

The model estimated voriconazole's apparent clearance (CL/F) at 3.17 L/h and apparent volume of distribution (V/F) at 135 L for a standard patient with CAPA. Covariates such as CRRT, C-reactive protein, gamma-glutamyl transpeptidase, aspartate aminotransferase, and platelet count were found to significantly influence voriconazole clearance. Monte Carlo simulations indicated that patients on CRRT required both a higher loading dose and an increased maintenance dose compared to those not on CRRT.

This study provides an evidence-based guide for voriconazole dosing adjustments in CAPA patients, particularly for those undergoing CRRT. The findings emphasize the importance of individualized dosing to improve therapeutic outcomes in this high-risk population.

Stroke remains a leading cause of death and disability, underscoring the urgent need for treatments that enhance recovery. GDF11 (growth differentiation factor 11), a member of the TGF-β (transforming growth factor-β) superfamily, is a circulating protein involved in cellular development and tissue repair. GDF11 has gained attention for its potential regenerative properties in aging and disease contexts, making it a candidate for stroke recovery therapies.

The therapeutic benefits of rGDF11 (recombinant GDF11) were evaluated using a rat ischemic stroke model, in which focal cerebral infarcts were induced in 8- to 10-week-old young adult male Sprague-Dawley rats by permanently occluding the proximal right middle cerebral artery. Rats received single or multiple doses of rGDF11 (0.1-4 mg/kg) or vehicle from 24 to 72 hours post-injury. Sensorimotor functions were evaluated, and brain and serum samples were examined to determine the mechanisms of action and identify biomarkers, using immunofluorescence, target-specific ELISAs, and an aptamer-based proteomics platform.

We confirmed rGDF11 activity in vitro and in established in vivo mouse models of cardiac hypertrophy and glucose metabolism and assessed the efficacy of rGDF11 treatment in 6 preclinical stroke studies using independent Contract Research Organizations, with all study animals and treatment groups blinded. All 6 studies revealed consistent improvement in sensorimotor outcomes with rGDF11. rGDF11-treated rats showed increased cortical vascularization and radial glia in the ventricular zone. Serum analysis revealed that rGDF11 caused dose-dependent decreases in CRP (C-reactive protein) and identified novel pharmacodynamic biomarkers and pathways associated with potential mechanisms of action of rGDF11.

These results demonstrate that systemically delivered rGDF11 enhances neovascularization, reduces inflammation, promotes neurogenesis, and improves sensorimotor function post-injury in a rat model of ischemic stroke. More importantly, these data define an optimized and clinically feasible rGDF11 dosing regimen for therapeutic development in ischemic stroke and identify a panel of candidate pharmacodynamic and mechanistic biomarkers to support clinical translation.

High neighborhood deprivation is linked to increased cancer and overall mortality. Prior studies demonstrated higher inflammation in people from high deprivation areas. The area deprivation index (ADI) is a composite measure of income, education, employment, and housing, which quantifies neighborhood deprivation. We used the All of Us dataset to test whether inflammation, measured via c-reactive protein (CRP), albumin, and the neutrophil-to-lymphocyte ratio (NLR), differs by ADI in cancer survivors.

Our sample included individuals with a history of lung, breast, prostate, and colorectal cancer, filtered for the presence of the inflammatory biomarkers. We used quartiles of ADI based on 3-digit zip code and biomarkers from electronic health records. We estimated the association between ADI and inflammation using adjusted logistic regression (n = 690 for CRP; n = 4242 for albumin; n = 5183 for NLR).

The sample had a mean age of 66.2 ± 10.1 years, 63.0% were female, and 86.8% were White. Mean CRP (11.5 ± 17.5 mg/L) and NLR (3.6 ± 2.2) indicated moderate to high inflammation. In the fully adjusted model, there were 2.04 (95% CI:1.02, 4.11) and 2.17 higher odds (95% CI:1.16, 4.13) of elevated CRP when comparing quartile 4 and quartile 3, respectively, to the lowest ADI quartile. Regression models were not significant for albumin or NLR.

Area deprivation is associated with CRP, a marker of stress that may lead to a higher risk of chronic diseases among cancer survivors. Future studies using a sample of cancer survivors with a wider range of ADI may help to strengthen this association.

The clinical usefulness of serum leucine-rich alpha-2 glycoprotein (LRG) levels as a surrogate marker of endoscopic activity including postoperative recurrence in patients with Crohn's disease (CD) remains unclear, and LRG production in the small intestinal mucosa has not been explored. The present study investigated the usefulness of serum LRG to ascertain endoscopic activity, the secretion of LRG from the small intestinal mucosa, and the significance of LRG as a predictor of postoperative disease course. We included 364 patients who underwent transanal endoscopy at Osaka University Hospital. Serum LRG correlated highly with endoscopic severity (LRG, r = 0.65; CRP, r = 0.37) and reflected strictly moderate endoscopic activity better than serum CRP. Especially, serum LRG reflected mucosal healing even in patients whose inflammation was confined to the small intestine. In multivariate analyses, serum LRG was an independent factor influencing mucosal healing. LRG was more strongly expressed in the inflamed mucosa of the small intestine compared with that in uninflamed mucosa, and serum LRG was more strongly correlated with postoperative small intestinal recurrence severity than CRP (LRG, r = 0.62; CRP, r = 0.32). In conclusion, serum LRG is a useful surrogate marker of endoscopic CD severity and activity, with increased LRG expression in the small bowel predicting postoperative recurrence.

Major surgery triggers an innate immune response that can become excessive, leading to immune suppression and an increased risk of infection. Neutrophils are crucial in this response, and changes in their phenotype are associated with the severity of the innate immune response. This study examines the effect of major surgery on neutrophil phenotypes using fully automated flow cytometry.

In this prospective single-center cohort study, adult patients undergoing either pancreaticoduodenectomy or on-pump coronary artery bypass grafting (CABG) were enrolled in the (BIGPROMISE) study. Blood samples were collected preoperatively (after anesthesia induction) and postoperatively (immediately after surgery). Neutrophil phenotypes were assessed using automated flow cytometry, with a rapid analysis time of less than 30 min.

The study included 24 patients undergoing CABG and 12 patients undergoing pancreaticoduodenectomy. Preoperative neutrophil heterogeneity was minimal, but significant postoperative changes in neutrophil subsets were observed in all patients, indicating acute systemic inflammation. Patients who underwent pancreatic surgery showed a more extensive inflammatory response, with 83% in Category 5, compared with 29% in the CABG group.

This is the first study to use fully automated flow cytometry to monitor perioperative changes in neutrophil phenotypes following major surgery. Our findings provide an in-depth readout of the innate immune response and neutrophil activation, highlighting a more pronounced response to pancreatic surgery than to cardiac surgery. Neutrophil phenotyping could serve as a valuable biomarker for patient stratification and management, although larger cohort studies are needed to confirm its predictive value for postoperative complications.

Skipping breakfast is associated with an increased risk of chronic inflammatory diseases. This study aimed to examine the association between breakfast-eating habits and inflammation, using high-sensitivity C-reactive protein (hs-CRP) as a marker.

A total of 4,000 Korean adult males with no history of myocardial infarction, angina, stroke, diabetes, rheumatoid arthritis, cancer, or current smoking were included. Data from the 2016-2018 Korea National Health and Nutrition Examination Survey were used for analysis. The frequency of breakfast consumption was assessed through a questionnaire item in the dietary survey section asking participants about their weekly breakfast consumption routines over the past year. Participants were categorized into two groups, namely "0-2 breakfasts per week" and "3-7 breakfasts per week"; hs-CRP concentrations were measured through blood tests.

Comparing between the "infrequent breakfast consumption (0-2 breakfasts per week)" and "frequent breakfast consumption (3-7 breakfasts per week)" groups, the mean hs-CRP was found to be significantly higher in the "infrequent breakfast consumption" group, even after adjusting for age, body mass index, physical activity, alcohol consumption, systolic blood pressure, blood pressure medication, fasting blood glucose, and triglycerides (mean hs-CRP: frequent breakfast consumption, 1.36±0.09 mg/L; infrequent breakfast consumption, 1.17±0.05 mg/L; P-value=0.036).

Less frequent breakfast consumption was associated with elevated hs-CRP levels. Further large-scale studies incorporating adjusted measures of daily eating patterns as well as food quality and quantity are required for a deeper understanding of the role of breakfast in the primary prevention of chronic inflammatory diseases.

Extensive research over the years has revealed the remarkable potential of gold nanoparticles (AuNPs) for detecting biomarkers in osteoarthritis (OA). AuNPs are a promising class of nanomaterials offering a wide range of diagnostic and clinical applications. It provides an effective and robust framework for qualitative and quantitative analysis of biomarkers present in the biological fluids of OA patients. AuNPs as theranostics have gained significant attention due to their discrete physical and optical characteristics, including localized surface plasmon resonance (LSPR), fluorescence, surface-enhanced Raman scattering, and quantized charging effect. These unique properties provide AuNPs as an excellent scaffold for ligand multiplexing, allowing accrued sensitivity for biomarker detection. Several reports have delved into the LSPR properties of the kinetics of biological interactions between the ligand and analyte. Tuneable radiative properties of AuNPs coupled with surface engineering allow facile detection of biomarkers in biological fluids. Herein, we have presented a comprehensive summary of distinct biomarkers generated from different molecular pathological processes in OA. An armamentarium of diagnostic methodologies such as aptamer conjugation, antibody coupling, ligand anchoring, and peptide decoration on the surface of AuNPs facilitates the identification and quantification of biomarkers. Additionally, a diverse range of sensing strategies for biomarker spotting, along with current challenges and future perspectives, have also been well delineated in the present manuscript.

Methicillin-sensitive Staphylococcus aureus (MSSA) bacteremia is a serious infection that requires timely diagnosis and treatment to prevent complications. Persistent fever after clearing bacteremia is uncommon, especially with normal inflammatory markers and no clear source of infection. This presents a significant diagnostic and management challenge.

A 36-year-old man presented with a three-day history of intermittent fever and was diagnosed with MSSA bacteremia. Initial investigations revealed mild splenomegaly. Despite treatment with intravenous flucloxacillin and negative repeat blood cultures, the fever persisted, prompting further evaluation. Advanced imaging did not reveal the source of infection. After completing a 14-day course of flucloxacillin, the fever resolved, and the patient recovered completely.

This case highlights the challenges in managing MSSA with persistent fever and no clear source of infection. This emphasizes the importance of adhering to evidence-based therapy and thorough evaluations, even when clinical presentations deviate from the typical course.

There is limited and conflicting data on the reduction of circulatory inflammatory mediators in patients with apical periodontitis (AP) following endodontic treatment.

To answer the following research question: in adult healthy patients with AP [Population (P)], is there a difference before [Comparator (C)] and after various endodontic treatments (nonsurgical, surgical or retreatment) [Intervention (I)] on systemic levels of inflammatory biomarkers [Outcome (O)] in the follow-up period [Time (T)]?

An electronic literature search was conducted in the databases Scopus, PubMed, Clarivate Analytics' Web of Science, Cochrane Database of Systematic Reviews and Grey literature from inception to July 2024 with no language restrictions. Observational studies examining changes in serum levels of inflammatory mediators were included. Two independent reviewers selected studies, extracted data and critically appraised the included studies. Qualitative and quantitative (meta-analysis) data synthesis methods were employed. The Newcastle-Ottawa Scale was used to assess the quality of the included studies.

Sixteen studies met the inclusion criteria, of which six were included in the meta-analysis. These studies were published between 1992 and 2024, involving a total of 596 patients (54% females) aged between 16 and 75 years. The meta-analysis of pooled data showed a significant decrease in high-sensitive C-reactive protein (hs-CRP) levels in the serum of patients with AP 6 months after treatment [2.26 ± 1.76 versus 1.28 ± 1.06 mg/L, (Z = 2.03, p = .04)] and a decrease in interleukin-1β (IL-1β) levels 12 months after treatment [13.01 ± 5.95 versus 10.86 ± 3.52 pg/mL, (Z = 3.72, p < .01)]. One study was assessed as poor quality, while all others were considered high quality.

Despite the differences in methodologies across the included studies, it has been established that effective endodontic treatment leads to a reduction in systemic inflammatory biomarkers in the body.

Following effective endodontic treatment in patients with AP, the systemic levels of hs-CRP and IL-1β exhibit a significant reduction at 6 and 12 months, respectively. Further clinical studies should investigate whether effective endodontic treatment and reduced levels of investigated biomarkers may change the clinical presentation of systemic diseases.

PROSPERO database (CRD42024559271).

Telomere length has been related to human health and ageing in multiple studies. However, these studies have analyzed a small set of variables, according to pre-formulated hypotheses. We used data from NHANES 1999-2002 to perform a preregistered cross-sectional analysis. From these four years we selected the participants with available leukocyte telomere length measure and with plausible daily energy intake, leading to a total study population of 7096 participants. Then, we divided the participants in three groups according to age: Young 20-39 (n = 2623), Middle 40-59 (n = 2210), Old 60-84 (n = 2263). On each group we performed Copula Graphical Modelling (CGM) to capture the links between the variables of interest, and we conducted certainty and sensitivity analyses to understand the robustness of the results. Blood levels of C-reactive protein and γ-tocopherol, and intake of caffeine and fibers are inversely related to telomere length across the age strata. Sex, race, smoking, physical activity and indicators of socioeconomic status have almost no direct connection with telomeres; however, they are directly linked to C-reactive protein, which in turn is connected to leukocyte telomere length. C-reactive protein is therefore a possible central mediator of the effect of these factors on telomeres.

Metabolic dysfunction-associated steatotic liver disease (MASLD) is a primary cause of chronic liver disease, with potential progression to cirrhosis and hepatocellular carcinoma (HCC). Although systemic inflammatory biomarkers are associated with liver diseases, their specific role in MASLD remains unclear. This study examines the association between systemic inflammatory biomarkers and MASLD.

This cross-sectional study enrolled 6613 adults aged 20 years or older from the National Health and Nutrition Examination Survey (NHANES) spanning from 2017 to March 2020. Among these participants,, 34.67% were aged 40-59 years, 50.85% were female, and 63.26% were Non-Hispanic White. We investigated 10 inflammatory biomarkers: ALI, SIRI, SII, SIPS, IBI, NLR, PLR, CAR, LMR, and PNI. Logistic regression models were performed to assess the linear association between systemic inflammatory biomarkers and MASLD. Restricted cubic spline (RCS) regression was employed to explore potential nonlinear relationships between biomarkers and MASLD risk. Additionally, subgroup analyses were conducted to examine the influence of various demographic and clinical characteristics on the observed associations.

After adjusting for key confounders, NLR and PLR exhibited negative association with MASLD risk, while ALI, CAR, and PNI exhibited the opposite association (P < 0.05). Most biomarkers, including ALI, SIRI, IBI, CAR, LMR, and PNI, exhibited significant non-linear correlations with MASLD (P < 0.05). Subgroup analyses revealed substantial age-related differences in the association between ALI and MASLD risk, as well as varying relationships between PNI and MASLD risk across various cardiovascular outcomes (P < 0.05).

Systemic inflammatory biomarkers are significantly associated with MASLD risk. Large-scale prospective studies are warranted to confirm these findings and elucidate the underlying mechanisms.

Introduction: Nosocomial lower respiratory tract infections (nLRTIs), including hospital-acquired pneumonia (HAP) and ventilator-associated pneumonia (VAP), remain significant challenges due to high mortality, morbidity, and healthcare costs. Implementing accurate and timely diagnostic strategies is pivotal for guiding optimized antimicrobial therapy and addressing the growing threat of antimicrobial resistance. Areas Covered: This review examines emerging microbiological diagnostic methods for nLRTIs. Although widely utilized, traditional culture-based techniques are hindered by prolonged processing times, limiting their clinical utility in timely decision-making. Advanced molecular tools, such as real-time PCR and multiplex PCR, allow rapid pathogen identification but are constrained by predefined panels. Metagenomic next-generation sequencing (mNGS) provides comprehensive pathogen detection and resistance profiling yet faces cost, complexity, and interpretation challenges. Non-invasive methods, including exhaled breath analysis using electronic nose (e-nose) technology, gene expression profiling, and biomarker detection, hold promise for rapid and bedside diagnostics but require further validation to establish clinical applicability. Expert Opinion: Integrating molecular, metagenomic, biomarker-associated, and traditional diagnostics is essential for overcoming limitations. Continued technological refinements and cost reductions will enable broader clinical implementation. These innovations promise to enhance diagnostic accuracy, facilitate targeted therapy, and improve patient outcomes while contributing to global efforts to mitigate antimicrobial resistance.

To outline the latest discoveries regarding the utility and reliability of serum biomarkers in idiopathic recurrent acute pericarditis (IRAP), considering recent findings on its pathogenesis. The study highlights the predictive role of these biomarkers in potential short- (cardiac tamponade, recurrences) and long-term complications (constrictive pericarditis, death).

The pathogenesis of pericarditis has been better defined in recent years, focusing on the autoinflammatory pathway. New studies have demonstrated the pivotal role of the classical inflammatory biomarkers in distinguishing pericarditis phenotypes (high-grade vs. low-grade inflammation) and in defining outcomes of this condition. Pericarditis involves intense inflammatory activity, which causes elevation of different markers, such as C-reactive protein, erythrocyte sedimentation rate, neutrophils and platelets, serum amyloid A and D-Dimer. Conversely, lymphocytes are often reduced, as well as hemoglobin during the acute phase. Cardiac troponins T and I are elevated in up to 30% of cases. A Biomarker for CRP-negative cases is needed. Other markers have been proposed for diagnosis and prognosis in IRAP, such as anti-heart antibodies and anti-intercalated disk antibodies, but we need further studies to validate them.

We need to better understand how the menstrual cycle interacts with other biological systems, such the inflammation and immune response. One way to study this interaction is through C-reactive protein (CRP). Studies of CRP concentrations across the menstrual cycle have been inconsistent. This study explores menstrual cycle CRP variation in two geographically different samples of Polish and Polish American individuals.

Analyses were conducted on 76 Polish and 22 Polish American daily urine samples collected on the first day of menstruation until the start of their next period. CRP, estrone-3-glucuronide, and pregnanediol-3-glucuronide were assayed. Sample-specific linear mixed models were used to examine cycle effects and median CRP concentrations across cycle phases and between the start of menses and remainder of the cycle were compared using Kruskal-Wallace and Dunn tests.

Polish and Polish American samples had distinct menstrual cycle CRP phenotypes. The Polish sample did not show cycle effects. The Polish American LMM demonstrated that CRP decreases after the first 3 days of menses (estimate -0.17, t-value -5.2). The KW and Dunn tests supported this. CRP concentrations were higher during the early follicular (median 0.406, p < 0.05), specifically the first 3 days of menstruation (median 0.466, p < 0.01), and lower in the luteal (median 0.277, p < 0.05).

Results suggest that changes in CRP during menstrual cycle are not universal across populations. In the Polish American sample, CRP was highest during the early follicular, specifically the first 3 days of menstruation, suggesting a potential relationship between the menstrual cycle and inflammation.

White matter damage is closely associated with cognitive and psychiatric symptoms and is prevalent in cerebral small vessel disease (CSVD); although the pathophysiological mechanisms involved in CSVD remain elusive, inflammation plays a crucial role. We sought to investigate the relationship between systemic inflammation markers and imaging markers of CVSD, namely white matter hyperintensity (WMH) and microstructural injury.

We conducted a study involving both cross-sectional and longitudinal data from the UK Biobank Cohort. We performed multiple linear regression analyses, adjusted for potential confounders, to explore the associations between systemic inflammation markers (e.g., systemic immune-inflammation index [SII], neutrophil-to-lymphocyte ratio [NLR], C-reactive protein [CRP] levels, monocyte count, neutrophil count) and macro- and microstructural white matter injury, as markers of CSVD. We performed Mendelian randomization analysis to investigate the genetically predictive effect of monocytes on WMH, as well as mediation analysis to clarify whether inflammatory markers affected cognitive function via white matter injury.

We included 36 411 participants (mean age 54.8 ± 7.5 yr, 51.9% female) from the UK Biobank Cohort. We found that SII was significantly associated with both WMH and microstructural injury markers (fractional anisotropy, mean diffusivity, intracellular volume fraction, and isotropic compartment volume fraction [ISOVF]), and the neutrophil-to-lymphocyte ratio was significantly associated with WMH and some markers of microstructural injury (mean diffusivity and ISOVF). Our analysis revealed that the CRP level was significantly associated with WMH and WMH progression but not with microstructural injury. We also demonstrated that monocyte count was significantly associated with WMH and ISOVF, and that neutrophil count was significantly associated with WMH, mean diffusivity, and ISOVF. In 2-sample Mendelian randomization analyses, we found positive associations between genetic determinants of monocytes and WMH. The mediating role of WMH suggested that a higher SII value and monocyte count could contribute to cognitive impairment through white matter injury.

Although the study includes both cross-sectional and longitudinal components, the sample size for the longitudinal aspect is limited, and the use of blood biomarkers from a single timepoint is also a limitation of this research.

The SII and neutrophil-to-lymphocyte ratio may be early detection markers for white matter damage in patients with CSVD, whereas the CRP level is more closely associated with disease severity and progression. Our findings highlight the clinical relevance of systemic inflammation markers with white matter macro- and microstructural injuries, revealing that systemic inflammation is likely involved in the mechanism of early white matter injury among patients with CSVD.

Plasma secretory proteins are associated with various diseases, including aortic dissection (AD). However, current research on the correlation between AD and plasma protein levels is scarce or lacks specificity. This study aimed to explore plasma secretory proteins as potential biomarkers for AD. Through genome-wide association studies, expression quantitative trait locus (eQTL) analysis, and human plasma protein profiling, we identified DBNL, NPC2, SUMF2, and TFPI as high-risk genes and CCN3, PRKCSH, TEX264, and TGFBR3 as low-risk genes for AD. Further cell localization and differential expression analysis of these eight genes were conducted using single-cell data. We also examined their expression in three Gene Expression Omnibus datasets, measured their mRNA levels in AD versus normal tissues using qPCR, and assessed their protein levels in patients' blood versus healthy individuals using enzyme-linked immunosorbent assay. Our findings suggest that CCN3, consistently downregulated in both mRNA and plasma levels during AD, may have a protective role. Initial enrichment analyses of differentially expressed CCN3 cells suggested their involvement in focal adhesion, actin cytoskeleton regulation, and the PI3K-Akt signaling pathway.

The rising global incidence of atherosclerosis highlights the inadequacies in our understanding of the pathophysiology and treatment of the disease. Increasing evidence outlines the importance of the intestinal microbiome in atherosclerosis, wherein gut-derived uremic toxins (GDUTs) may be of concern. Plasma levels of the GDUTs trimethylamine n-oxide (TMAO), p-cresyl sulfate, and indoxyl sulfate are associated with accelerated renal function decline and increased cardiovascular risk. Thus, reducing the amount of GDUTs in circulation is expected to benefit patients with atherosclerosis. Because some beneficial bacteria can clear GDUTs in vitro and in vivo, orally administered probiotics targeting the intestinal tract represent a promising way to bring about these changes. Atherosclerosis such, this perspective reviews the potential use of probiotics to treat atherosclerosis, particularly in patients with non-traditional risk factors and/or impaired renal function.

The CALLY index, which is derived from C-reactive protein (CRP) content, serum albumin level, and total lymphocyte count, reflects the immune, nutritional, and inflammatory status of the body. Lack of sufficient evidence on the correlation between the CALLY index and the prognosis of cancer patients with various cancer forms. This study seeks to elucidate the association between the CALLY index and mortality from all causes as well as specific causes in cancer patients within a U.S.

This investigation encompassed 3511 cancer-afflicted adults from the National Health and Nutritional Examination Surveys (NHANES) spanning 1999 to 2018. The CALLY index was measured at baseline only. The relationship between the CALLY index and mortality from both all causes and cancer specifically was examined using Cox proportional hazards models. Additionally, restricted cubic spline, piecewise linear regression, and various subgroup and sensitivity analyses were employed.

Over a median follow-up of 103 months, 1,355 deaths occurred, and the incidence of all-cause mortality for these participants was 38.34%. Our findings indicate that an elevated CALLY index correlates with a diminished risk of all-cause mortality. Upon applying a natural logarithmic transformation to the CALLY index, the comprehensively adjusted model revealed that each one-unit increment in ln CALLY corresponded to a 18% decrease in all-cause mortality risk among cancer patients (HR = 0.82, 95% CI:0.79-0.86). Analyses of mortality due to cardiac and cancer-related causes yielded consistent results, which were robust across various subgroup and sensitivity analyses.

The CALLY index demonstrated a linear and negative association with all-cause mortality, as well as mortality caused by cancer and cardiac conditions, highlighting its significant prognostic value in patients with oncological conditions.

Para-pneumonic effusion in children is often associated with bacterial infections; however, dual viral infections, including respiratory syncytial virus (RSV) and COVID-19, can also lead to severe respiratory complications, as demonstrated in this case. This case report presents the clinical course of a pediatric patient with both RSV and COVID-19 infections, leading to para-pneumonic effusion.  A three-year-old girl with a history of asthma and prior febrile convulsions presented to the Emergency Department with fever, cough, vomiting, and fatigue. Chest X-ray revealed left-sided pleural effusion. Initial laboratory results showed elevated inflammatory markers, including a white blood cell count of 22 x 109/L, C-reactive protein (CRP) of 319 mg/L, and procalcitonin of 3.9 ng/mL. Nasal swab polymerase chain reaction confirmed RSV and COVID-19 co-infection. The patient was treated with intravenous ceftriaxone, azithromycin (to cover atypical pathogens), vancomycin (to address possible MRSA [methicillin-resistant Staphylococcus aureus]), and corticosteroids to manage severe inflammation with COVID-19. Following a six-day stay in the Pediatric Intensive Care Unit (PICU) for respiratory support and intravenous therapy, the patient showed significant clinical improvement. Serial imaging demonstrated a reduction in pleural effusion, and inflammatory markers decreased markedly. The patient was discharged after 29 days of hospitalization on oral antibiotics, in stable condition, with a follow-up scheduled. This case underscores the potential severity of dual viral infections in pediatric patients and the importance of prompt diagnosis and comprehensive management to prevent complications such as para-pneumonic effusion.

We investigated associations between bioaerosol exposures and work-shift changes in lung function and inflammatory markers among recycling workers.

Inhalable dust was measured with personal samplers and analyzed for endotoxin, bacteria, and fungi (incubated at 25 °C and 37 °C) levels. Lung function (FEV1, FVC) was measured before and after work-shifts and serum concentrations of inflammatory markers (CRP, SAA, CC16, IL1B, IL2, IL4, IL5, IL6, IL8, IL10, IL13, and TNF) after the shift. Associations were explored by linear mixed-effects models.

We included 170 measurements from 88 production workers exposed to inhalable dust, endotoxin, bacteria, and fungi (25 °C and 37 °C) at geometric mean levels of 0.6 mg/m3, 10.7 EU/m3, 1.6×104 CFU/m3, 4.4×104 CFU/m3, and 103 CFU/m3, respectively, and 14 administrative workers exposed at 7-fold lower levels. No associations were observed between bioaerosol exposures and work-shift change in lung function. IL2, IL6, IL10, and TNF concentrations were positively associated with inhalable dust levels, SAA and IL6 with bacteria, CRP, SAA, IL8, and TNF with fungi (25 °C or 37 °C), with the latter being the only statistically significant finding (exp(β) 1.40, 95% confidence interval 1.01-1.96).

This study of recycling workers exposed to bioaerosol levels generally below those of farmers and compost workers and above background levels did not indicate any acute effect on lung function. Several inflammatory markers tended to increase with exposure, suggesting a systemic effect. Future research should combine data from bioaerosol-exposed workers to uncover health risks that may form the basis for health-based occupational exposure limits.

Fibromyalgia syndrome (FMS) is a widespread musculoskeletal pain, often accompanied by fatigue and sleep disturbances. Poor sleep exacerbates inflammation and pain, potentially increasing levels of inflammatory markers. This study explored the effect of FMS severity on CRP levels, sleep quality and pain intensity. 89 FMS individuals were explored for FMS severity, pain and sleep quality. CRP levels in blood and erythrocyte sedimentation rate (ESR) were measured to assess inflammation. An increase in FMS severity was associated with an increase in CRP and ESR levels, pain intensity and sleep disturbances. However, a positive correlation between CRP levels and sleep quality indicates that Poor sleep quality in FMS may contribute to elevated CRP levels. Addressing sleep quality may mitigate the severity of FMS and its associated symptoms.

Inflammation plays a key role in chronic kidney disease (CKD). Monocyte-to-lymphocyte ratio (MLR) is a novel inflammatory marker. The purpose of this study was to evaluate the relationship between MLR and inflammation in CKD patients.

In total, 1,809 subjects were recruited from Wanzhai Town, Zhuhai City, between December 2017 and March 2018 for a cross-sectional survey. Patients were categorized based on the absence (hypersensitive C-reactive protein [hsCRP] level ≦3 mg/L) or presence (hsCRP level >3 mg/L) of inflammation. Logistic regression models and MLR quartiles were used to explore the relationship between MLR and inflammation in CKD patients.

Among 1,809 subjects, 403 (22.2%) had CKD. Significant differences in systolic blood pressure, estimated glomerular filtration rate, white blood cell (WBC), neutrophil, monocyte, MLR, and interleukin-6 (IL-6) levels were observed between noninflammatory group and inflammatory group. The highest MLR quartile had higher Scr, WBC, neutrophil, monocyte, IL-6, and hsCRP values and lower eGFR and lymphocyte values. Comparing the lowest quartile of MLR, the OR (95% CI) of inflammation risk in the highest quartile was 2.30 (1.24-4.27) after adjustment for confounding factors. The area under the curve of MLR for predicting inflammation was 0.631. The cutoff point for the MLR was 0.153.

A high MLR was significantly and independently associated with inflammation in patients with CKD, making MLR a potential marker for inflammation in this demographic. MLR may also predict the severity of CKD.

Coleoptera is the second-most significant insect group associated with decomposing carcasses, yet its role in the decomposition process and postmortem colonization following envenomation is poorly understood.

This study aimed to investigate the effects of the venoms from Cerastes cerastes and Naja haje on the decomposition of rabbit carcasses while evaluating the main beetle taxa attracted to these decaying remains.

Three groups of rabbits, each with five individuals, were utilized. The first group was injected with the venom of Cerastes cerastes, the second with Naja haje venom, and the control group received 0.85% physiological saline before euthanasia with CO2.

Four decomposition stages (fresh, bloating, decay, and dry) with durations varying based on venom type and carcass condition were observed. A total of 647 individual beetles of six species (Necrobia rufipes, Attagenus sp., Dermestes frischii, D. maculatus, Bledius sp., and Apentanodes sp.) belonging to four families (Cleridae, Dermestidae, Staphylinidae, and Tenebrionidae) were collected and identified. D. maculatus was the most abundant species. Fewer beetles were attracted to carcasses envenomed with N. haje compared to the other groups.

Envenomation by snake venom influences the attraction and succession rate of necrophilous coleopterans to carcasses, which is important for forensic investigations.

Despite being a less-invasive procedure, esophagectomy can cause severe infectious complications, such as pneumonia and anastomotic leakage. Herein, we aimed to clarify the inflammatory characteristics of pneumonia/anastomotic leakage after esophagectomy by assessing the difference between the postoperative trends of serum C-reactive protein (CRP) and procalcitonin (PCT) levels in patients with pneumonia/anastomotic leakage using the values on the consecutive postoperative day (POD).

This study included 439 patients who underwent minimally invasive esophagectomy. Serum CRP and PCT levels were measured on PODs 1-7, 10, and 14. Pneumonia and anastomotic leakage were defined as Clavien-Dindo grades ≥ 2.

Pneumonia and anastomotic leakage occurred in 96 and 51 patients, respectively. The CRP and PCT levels peaked on POD 3 (11.6 ± 6.8 mg/dL) and POD 2 (0.69 ± 2.9 ng/mL), respectively. Between PODs 3 and 14, CRP levels were significantly higher in patients with pneumonia and anastomotic leakage than in those without complications (P < 0.001). Between PODs 3 and 14, PCT levels were significantly higher in patients with pneumonia; however, on most PODs, there were no significant differences in PCT levels between patients with and without anastomotic leakage.

Inflammatory reactions caused by pneumonia may be more intense than those caused by anastomotic leakage after esophagectomy. Postoperative trends in serum CRP and PCT levels may vary depending on the complication type. Pneumonia and anastomotic leakage after esophagectomy can be potentially distinguished by the postoperative trend of PCT values before detailed examinations, such as computed tomography and endoscopy.

Infection after cesarean section is a major contributor to maternal morbidity. Measurement of C-reactive protein (CRP) is a laboratory test frequently conducted to rule out or confirm postoperative infection. The present study aimed to evaluate whether CRP is a suitable tool for ruling out infection after cesarean section and whether there are any reliable cut-off values.

2056 patients with cesarean section (CS) over a 3-year period were included in a retrospective analysis. Outcome parameters and risk factors for postoperative infection were collected. CRP values from preoperative and postoperative tests were compared. Cut-offs for ruling out infection were assessed.

Among 2056 CSs, postoperative infection occurred in 78 cases (3.8%). The prevalence of infection in emergency CS was lowest, at four out of 134 (2.9%), and the highest prevalence was seen in secondary CS, at 42 of 903 (4.6%; p = 0.35). CRP values in the infection group were significantly higher (preoperative, 1.01 mg/dl vs. 0.62 mg/dl; day 1 postoperative, 7.91 mg/dl vs. 6.44 mg/dl; day 4 postoperative, 8.44 mg/dl vs. 4.09 mg/dl; p = 0.01). A suitable cut-off value for ruling out infection was not identified.

Although CRP values were significantly higher in the infection group, the clinical relevance of this appears to be negligible. CRP testing does not appear to be a reliable tool for diagnosing or ruling out postoperative infection.

Recurrent pericarditis, an inflammatory syndrome with a pathogenesis not fully elucidated, often presents diagnostic challenges. This study aims to assess the correlation of D-Dimer (D-D) and procalcitonin (PCT) levels with clinical, laboratory and imaging features in recurrent idiopathic pericarditis. We analyzed 412 patients with idiopathic recurrent pericarditis from 2019 to 2023 in our referral center. D-D and PCT values were obtained from emergency room in other Italian facilities. Among the cohort, PCT levels were assessed in 50 of 412 patients (12.1%), with only 4 showing marginal elevation. D-D levels were measured in 48 of 412 patients (11.6%), with 33 of them exhibiting elevated values. None of these patients had venous thromboembolism, and elevated D-D levels were significantly associated with pleural effusion, fever, higher CRP, increased white blood cell counts, higher neutrophil counts, reduced relative lymphocyte counts. Multivariate analysis revealed fever as the sole correlate of elevated D-D. PCT elevation was infrequent and unrelated to any variables. In idiopathic recurrent pericarditis unrelated to specific conditions, we observed a close association between elevated D-D levels and non-specific inflammation markers, including fever, increased CRP, and neutrophil leukocytosis. PCT levels were typically normal or mildly elevated.

The purpose of this study was to examine the periodontal state and oral health-related quality of life (OHRQoL) of patients with end-stage renal disease (ESRD) and the effect of ESRD on OHRQoL by comparison with age- and sex-matched systemic healthy controls with similar periodontal status levels.

Fifty patients with ESRD and 150 healthy individuals without ESRD were recruited. Medical characteristics were recorded for the test group and periodontal examination was performed in both groups. A structured Korean version of the Oral Health Impact Profile (OHIP-14K) questionnaire for subjective evaluation of OHRQoL was administered. To evaluate the effect of ESRD on OHRQoL, 50 healthy controls who had been matched for age, sex, and periodontal status were selected and compared with ESRD patients by using propensity score-matched analysis.

ESRD patients had significantly higher mean score of Community Periodontal Index and mean numbers of missing teeth compared with the controls (P < 0.05). Mean OHIP-14K total score and mean scores of all subdomains were significantly higher in the test group than in the controls (P < 0.05). Even after matching analysis, mean OHIP-14K total score and mean scores of subdomains were significantly higher in the test group than in the control group (P < 0.05), except in one subdomain (physical pain).

Within the limitations of this investigation, the present study showed worse periodontal state and lower level of OHRQoL in ESRD patients compared with those in healthy subjects. Through comparison with matched healthy controls, ESRD was found to have a negative effect on OHRQoL.

In many diseases, sex differences in diagnostics and therapy play role that is increasingly becoming recognized as important. C-reactive protein (CRP) and white blood cell (WBC) levels are determined as inflammatory markers to detect inflammation and even infection after total shoulder arthroplasty (TSA). The general course of white blood cell, CRP, and hemoglobin (Hb) levels after TSA is well known, but there is insufficient evidence of a possible association with sex. Therefore, we aimed to investigate whether there is an influence of sex on CRP, WBCs, and Hb after TSA in the first 10 days after surgery in a complication-free course in male and female patients and to re-evaluate the specific postoperative CRP, WBC, and Hb course with their maximums (minimum for Hb) and further course until the end of the inpatient period.

We retrospectively studied patients treated with TSA, reverse shoulder arthroplasty (RSA), and prosthesis replacement between 2015 and 2021. Patients with active inflammation, rheumatoid arthritis, secondary osteoarthritis, active cancer, and documented postoperative complications were not included. CRP, WBC, and Hb levels before shoulder arthroplasty (SA) and up to 10 days after SA were recorded and analyzed for sex differences.

Data from a total of 316 patients (209 women and 107 men) were finally analyzed. There were no sex differences in the CRP and WBC values, but women had significantly lower preoperative Hb values, postoperative Hb values, and minimum Hb values. There were no significant differences in Hb, CRP, or WBC levels in the prosthesis exchange group.

The progression of CRP and WBC levels showed no sex-specific significant differences after TSA within the first 7 postoperative days. The study confirmed a decreased Hb value for women at all stages of SA. Blood loss was significantly higher for RSA than for TSA for both men and women.

The aim of this study is to examine the potential correlation between periodontitis and the risk of cardiovascular mortality and all-cause mortality in individuals diagnosed with hypertension, despite the established association between periodontitis and hypertension.

The study utilized data from the National Health and Nutrition Examination Survey (NHANES) conducted in 1999-2014 involving hypertensive individuals. Following the criteria proposed by Eke et al., periodontitis was classified. Survival estimates were calculated using Kaplan Meier analyses and a Kaplan Meier curve was generated. Weighted multivariate cox regression were employed to assess the association between periodontitis and all-cause mortality, as well as cardiovascular mortality.

Of the 21,645 individuals, 6,904 individuals were diagnosed with periodontitis. The Kaplan-Meier survival analysis revealed significantly higher rates of all-cause mortality (34.766% vs. 14.739%) and cardiovascular mortality (12.469% vs. 3.736%) in the periodontitis group compared to the non-periodontitis group. Hazard ratios (HRs) for all-cause mortality were 3.19 (95% CI 2.88-3.53) and for cardiovascular mortality were 3.80 (95% CI 3.13-4.61) in individuals with periodontitis compared to those without periodontitis.

Periodontitis is a risk factor for mortality in patient with hypertension, especially if it is moderate to severe. Improving periodontal health could lead to better outcomes for these patients.

We investigate the histopathology of the portal vein branches and lymphatic vessels to elucidate the mechanism of atrophy of the left lateral segment (LLS) of the liver in biliary atresia (BA).

LLS and right anterior segment (RAS) liver biopsy samples obtained during Kasai portoenterostomy (KPE) from ten consecutive patients with BA underwent histopathological investigation of the portal vein and lymphatic vessels using double chromogenic immunostaining for CD31/D2-40 and the hepatitis-like findings (HLF) score. Each parameter and clinical data were compared between prognostic groups.

HLF scores in the LLS were always higher than those in the RAS. There was no difference in portal vein and lymphatic vascular morphology, whereas the number of lymphatic vessels was correlated with the fibrotic area of all specimen areas. Left-to-right ratio of the number of lymphatic vessels was correlated with the age at KPE (r = 0.784, p = 0.007) and the pre-KPE CRP value (r = 0.723, p = 0.018).

Lymphangiogenesis on the LLS compared to the RAS was significantly correlated with the degree of fibrosis and the age at KPE. Further investigation is warranted to clarify the causes of LLS atrophy and lymphangiogenesis relevant to immune dysregulation.