Search Results (242)

Background: Cardiometabolic disorders and psychiatric conditions frequently coexist and may interact bidirectionally through shared metabolic, inflammatory, and neuroendocrine pathways. However, real-world clinical datasets often reveal substantial heterogeneity in multimorbidity patterns, and the extent to which psychiatric comorbidity clusters with metabolic dysfunction remains insufficiently characterized. This study aimed to evaluate the relationships between psychiatric diagnoses, metabolic biomarkers, hepatic and renal indicators, and polypharmacy within a clinically diverse cohort. Methods: We conducted a cross-sectional analysis of 47 patients from a cohort in a real-world clinical database. Psychiatric comorbidity was identified using diagnostic text-mining. Cardiometabolic markers included TyG index, FIB-4 score, serum creatinine, UACR, and total medication count. Group comparisons used Shapiro–Wilk testing for normality and either unpaired t-tests or Mann–Whitney tests as appropriate. Spearman correlations and a heatmap visualization were used to explore interactions among biomarkers. Results: Psychiatric comorbidity was present in 48.9% of patients and was associated with higher medication burden (6.0 ± 2.5 vs. 3.3 ± 2.1) and elevated TyG index (9.15 ± 0.80 vs. 6.19 ± 4.80), although differences did not reach statistical significance. Hepatic (FIB-4) and renal (creatinine) biomarkers exhibited wide variability, particularly among individuals without psychiatric diagnoses. Correlation analyses revealed weak-to-moderate associations among biomarkers, underscoring the heterogeneous nature of organ involvement in this cohort. Conclusions: Psychiatric comorbidity clustered with increased metabolic stress and polypharmacy, suggesting an integrated cardiometabolic–psychiatric vulnerability. The marked heterogeneity of hepatic and renal markers indicates that multimorbidity follows non-linear patterns not captured by single biomarkers. Integrated, multidisciplinary management strategies and larger longitudinal studies are needed to clarify causal pathways and optimize care for patients with combined cardiometabolic and psychiatric risk. Full article

Alcohol-associated liver disease (ALD) is the leading cause of liver-related mortality. In ALD, excessive inflammatory response may induce a massive loss of hepatocytes and lead to irreversible liver damage with progressive fibrosis. Chemokines stimulate the migration of immune cells to the site of inflammation and contribute to the inflammatory cascade that may result in organ failure. We aimed to investigate blood concentrations of CXCL9/MIG, CXCL10/IP-10, and CXCL16 chemokines and their diagnostic and prognostic significance in patients with ALD. In a prospective observational study, 88 individuals were recruited, including 63 patients with ALD (44 men and 19 women, aged 48.49 ± 10.88) and 25 healthy control volunteers matched for age, sex, and ethnicity. In blood samples, concentrations of CXCL9/MIG, CXCL10/IP-10, and CXCL16 were measured using immunoenzymatic ELISAs. Correlations were examined between CXCL levels and (a) traditional inflammatory markers (C-reactive protein, white blood cell count, neutrophil count, lymphocyte count, and neutrophil-to-lymphocyte ratio-NLR) and (b) liver dysfunction severity scores: Child–Turcotte–Pugh (CTP), MELD-NA, MELD 3.0, and modified Maddrey’s discriminant function (mDF). Patients’ survival within 30 days of hospital admission was recorded for analysis. CXCL capabilities in predicting the severity of liver dysfunction and ALD outcome were validated. ALD patients showed significant systemic upregulation of all studied chemokines compared to the control group. Patients with advanced liver disease, classified as MELD-Na ≥ 20, MELD3.0 > 19, and CTP class C, as well as poor short-term outcomes, presented with significantly higher CXCL9 and CXCL10 levels compared to their counterparts. ALD non-survivors had significantly higher concentrations of all studied CXCLs in comparison to controls. Positive correlations between CXCL16 and CRP, leukocytosis, neutrophils, and NLR were confirmed (0.67; 0.46; 0.48; 0.54, respectively). Although none of the chemokines correlated with ALT activity, CXCL9, CXCL10, and CXCL16 showed positive correlations with bilirubin and alkaline phosphatase and inverse correlations with albumin levels. Our findings revealed the diagnostic and prognostic value of the studied CXCLs in ALD. In particular, CXCL9 and CXCL10 may have potential for discrimination of severe liver dysfunction and poor short-term prognosis. Further multicenter studies are required to confirm our results. Full article

Background: Obesity represents a multisystemic disorder that extends beyond metabolic dysfunction, involving hepatic, renal, and cardiovascular axes. This study introduces the Cardio–Reno–Metabolic–Liver–Obesity (CaRaMeL-O) framework as an integrated tool to assess multi-organ metabolic stress in adults with obesity. Methods: In this cross-sectional study, 287 adults with obesity (mean BMI 35.1 ± 4.6 kg/m²) were evaluated. The CaRaMeL-O score (0–13 points) incorporated metabolic (TyG index), hepatic (FIB-4, transaminases), and renal (eGFR, UACR) parameters, as well as classical and lifestyle risk factors. Participants were stratified into low, moderate, and high risk categories. Group comparisons were conducted using ANOVA and Kruskal–Wallis tests, while multivariate regressions identified independent predictors of FIB-4 and eGFR. Distributional characteristics were further analyzed using Weibull modeling. Results: Higher CaRaMeL-O scores were associated with a progressive increase in TyG (p < 0.001) and FIB-4 (p < 0.001), while eGFR showed a mild, nonsignificant downward trend. In multivariate models, age was the strongest predictor of FIB-4 (β_std = 0.33), whereas age, FIB-4, BMI, blood pressure, and UACR independently predicted eGFR. TyG did not remain significant after full adjustment. Weibull analysis revealed distinct distributional profiles, with TyG showing a narrow, homogeneous curve and FIB-4 and eGFR broader, right-skewed patterns. Conclusions: The CaRaMeL-O framework effectively captures inter-organ metabolic stress, demonstrating that hepatic and metabolic alterations precede overt renal decline. This integrated score may support early stratification and targeted prevention in obesity-related cardio-metabolic risk. Full article

Background/Objectives: Sepsis-associated liver injury (SALI) is a critical and often early complication of sepsis, defined by distinct hyper-inflammatory and immunosuppressive phases that shape patient phenotypes. Methods: Characterizing these phases establishes a foundation for immunomodulation strategies tailored to individual immune responses, as discussed subsequently. Results: The initial inflammatory response activates pathways such as NF-κB and the NLRP3 inflammasome, leading to a cytokine storm that damages hepatocytes and is frequently associated with higher SOFA scores and a higher risk of 28-day mortality. Kupffer cells and infiltrating neutrophils exacerbate hepatic injury by releasing proinflammatory cytokines and reactive oxygen species, thereby causing cellular damage and prolonging ICU stays. During the subsequent immunosuppressive phase, impaired infection control and tissue repair can result in recurrent hospital-acquired infections and a poorer prognosis. Concurrently, hepatocytes undergo significant metabolic disturbances, notably impaired fatty acid oxidation due to downregulation of transcription factors such as PPARα and HNF4α. This metabolic alteration corresponds with worsening liver function tests, which may reflect the severity of liver failure in clinical practice. Mitochondrial dysfunction, driven by oxidative stress and defective autophagic quality control, impairs cellular energy production and induces hepatocyte death, which is closely linked to declining liver function and increased mortality. The gut-liver axis plays a central role in SALI pathogenesis, as sepsis-induced gut dysbiosis and increased intestinal permeability allow bacterial products, including lipopolysaccharides, to enter the portal circulation and further inflame the liver. This process is associated with sepsis-related liver failure and greater reliance on vasopressor support. Protective microbial metabolites, such as indole-3-propionic acid (IPA), decrease significantly during sepsis, removing key anti-inflammatory signals and potentially prolonging recovery. Clinically, SALI most commonly presents as septic cholestasis with elevated bilirubin and mild transaminase changes, although conventional liver function tests are insufficiently sensitive for early detection. Novel biomarkers, including protein panels and non-coding RNAs, as well as dynamic liver function tests such as LiMAx (currently in phase II diagnostics) and ICG-PDR, offer promise for improved diagnosis and prognostication. Specifying the developmental stage of these biomarkers, such as identifying LiMAx as phase II, informs investment priorities and translational readiness. Current management is primarily supportive, emphasizing infection control and organ support. Investigational therapies include immunomodulation tailored to immune phenotypes, metabolic and mitochondrial-targeted agents such as pemafibrate and dichloroacetate, and interventions to restore gut microbiota balance, including probiotics and fecal microbiota transplantation. However, translational challenges remain due to limitations of animal models and patient heterogeneity. Conclusion: Future research should focus on developing representative models, validating biomarkers, and conducting clinical trials to enable personalized therapies that modulate inflammation, restore metabolism, and repair the gut-liver axis, with the goal of improving outcomes in SALI. Full article

Background and Objectives: Metabolic dysfunction-associated steatotic liver disease (MASLD) is highly prevalent and may influence the outcome of critical illness. Although abnormal liver function tests (LFTs) are frequent in the intensive care unit (ICU), the contribution of MASLD to organ-specific hepatic vulnerability and mortality remains unclear. This study aimed to evaluate whether pre-existing metabolic dysfunction-associated steatotic liver disease (MASLD) is associated with baseline and new-onset liver function test (LFT) abnormalities and with intensive care unit (ICU) outcomes in non-cirrhotic medical ICU patients. Materials and Methods: We conducted a retrospective cohort study of adult non-cirrhotic patients admitted to a tertiary medical ICU between December 2020 and December 2023, who underwent hepatobiliary ultrasonography within six months before admission. MASLD was defined as hepatic steatosis with ≥1 cardiometabolic risk factor. The baseline and 72 h LFTs, injury patterns, and ICU outcomes were compared between MASLD and non-MASLD patients. Logistic regression was used to identify the independent predictors of new-onset LFT elevation and ICU mortality. Results: Among 609 patients, MASLD was diagnosed in 240 (39.4%). LFT elevation at admission was more frequent in patients with MASLD (52% vs. 39%, p = 0.03), driven mainly by higher alkaline phosphatase (ALP). At 72 h, ALP (96 [67–146] vs. 85 [60–137]) and gamma-glutamyl transferase (GGT) (50 [27–123] vs. 42 [20–100]) levels remained higher in patients with MASLD (p < 0.01), although rates of new-onset LFT elevation were similar (p > 0.05). Compared to non-MASLD patients, those with MASLD more often required invasive mechanical ventilation (IMV) (64% vs. 33%), central venous catheterization (70% vs. 44%), CRRT (28% vs. 10%), blood product replacement (50% vs. 28%), and developed nosocomial infections (44% vs. 29%) (p < 0.05 for all); however, MASLD was not an independent predictor of mortality. The independent risk factors for mortality were IMV, shock, and higher APACHE II scores. Conclusions: common among medical ICU patients and is associated with a cholestatic biochemical profile and poor ICU outcomes. However, early hepatic injury and ICU mortality are primarily determined by systemic severity and organ support requirements, not the MASLD itself. Full article

Background and Objectives: Pelvic floor disorders are highly prevalent among women globally and can severely compromise daily functioning and well-being. Emerging energy-based modalities have reshaped conservative management strategies, by allowing individualized therapeutic approaches. The aim of this study was to evaluate the utility of customized energy-based applications, via an innovative multimodal EVA/DAFNE device that incorporates multimodal energy-based synergistic technologies for the treatment of pelvic floor dysfunction. Materials and Methods: Patients with PFDs (pelvic organ prolapse, all types of urinary incontinence, bladder voiding dysfunction, and dyspareunia) who selected conservative treatments were prospectively enrolled. Baseline and after-treatment quality of life was assessed using the following validated tools: Urinary Distress Inventory-6 (UDI-6), Pelvic Organ Prolapse Distress Inventory-6 (POPDI-6), Female Sexual Function Index-6 (FSFI-6), Marinoff Scale, 0-100 VAS, and Vaginal Health Index. Overall improvement was measured through the Patient Global Impression of Improvement (PGI-I). Three to five sessions of treatment tailored according to the patient’s symptoms and clinical findings were delivered. Data were analyzed using standard statistical methods. Results: Twenty-six women with PFD who desired energy-based conservative treatment were recruited. Mean age was 48.6 ± 16.7 years. Indications for treatment were dyspareunia (n = 10; 38.5%), stress urinary incontinence (n = 9; 34.6%), mild pelvic organ prolapse (n = 6; 23.1%), genitourinary syndrome of menopause (n = 5; 19.2%), voiding dysfunction (n = 4; 15.4%), and overactive bladder syndrome (n = 2; 7.7%). Mean number of treatments was four. Baseline and after-treatment quality-of-life scores differed significantly. According to PGI-I scores 88.5% of patients considered themselves improved. Conclusions: Our study provides pilot estimates as to the safety and efficacy of a multimodal integrated treatment protocol for the treatment of PFD. Integrating multimodal energy-based conservative therapy into tailored treatment protocols can prove efficient and useful. Full article

Background/Objectives: Whether a remote history of SARS-CoV-2 infection independently affects early haemodynamic stability after elective cardiopulmonary bypass (CPB) remains uncertain. We evaluated whether prior COVID-19 (>7 weeks before surgery) was associated with postoperative vasopressor requirements or early complications in adults undergoing elective CPB. Methods: We conducted a single-centre prospective cohort study including adults (≥18 years) scheduled for elective on-pump coronary, valve, or combined cardiac surgery between 1 August 2022 and 30 October 2023. Patients undergoing emergency procedures or surgery < 7 weeks after infection were excluded. The exposure was a documented history of COVID-19 for >7 weeks preoperatively. The primary outcome was postoperative vasopressor use within 24 h of ICU admission; secondary outcomes included inotrope use, arrhythmias, acute cardiac or respiratory failure, pneumonia, acute kidney injury (KDIGO), delirium, stroke, length of stay, and mortality. Multivariable logistic regression adjusted for age, CPB duration, obesity, anaemia, chronic kidney disease, sex, EuroSCORE I, left ventricular ejection fraction, and procedure type. Results: Of 351 screened patients, 280 elective CPB cases were analyzed; 101 (36.1%) had prior COVID-19. Vasopressor use occurred in 151/280 (53.9%) patients, with no difference between COVID and non-COVID groups (53.5% vs. 54.2%; p = 1.00). Prior COVID-19 was not associated with vasopressor requirement (adjusted OR 0.94, 95% CI 0.56–1.59). Independent predictors were longer CPB duration (aOR 2.80 per hour; p < 0.001) and older age (aOR 1.028 per year; p = 0.02). Secondary outcomes, including organ dysfunction and mortality, did not differ between groups. Conclusions: In adults undergoing elective CPB ≥ 7 weeks after SARS-CoV-2 infection, prior COVID-19 did not increase early vasopressor needs or short-term postoperative complications. Haemodynamic requirements were primarily driven by CPB duration and age. Further research using dose-standardized vasoactive metrics and formal COVID-19 severity stratification is warranted. Full article

Trauma is a major cause of morbidity and mortality in dogs and cats. While prognostic tools are well-established in human medicine, few guidelines exist in veterinary trauma care. The Animal Trauma Triage (ATT) score and modified Glasgow Coma Scale (mGCS) are used to assess illness severity, but their clinical utility in veterinary patients remains undervalued. This study aimed to evaluate the prognostic value of ATT and mGCS scores and their association with organ dysfunction and survival in polytraumatized veterinary patients. We hypothesized that multi-organ failure (MOF) is more prevalent in non-survivors and correlates with higher ATT and lower mGCS scores. A prospective observational study was conducted for 30 patients (20 dogs and 10 cats) admitted to two veterinary hospitals. Clinical data, trauma scores, and outcomes were collected and analyzed. The overall survival rate was 83.3%; blunt trauma accounted for 80% of cases. Non-survivors (n = 5) had higher respiratory rates at admission (p = 0.01). The ATT score accurately predicted all fatalities, while the mGCS score showed limited prognostic value. MOF was the leading cause of death in 60% of non-survivors. ATT appears to be a more reliable tool for outcome prediction, enabling improved triage, resource allocation, and early intervention in veterinary trauma cases. Full article

Background: Diabetes often causes microvascular complications such as neuropathy. Autonomic neuropathy remains under-recognized, and its impact on quality of life (QoL) is unclear. This study investigated associations between symptoms of autonomic dysfunction, including organ-specific subdomains, and QoL in individuals with type 1 (T1D) and type 2 diabetes (T2D). Methods: A cross-sectional population-based survey was conducted in the North Denmark Region among individuals with T1D and T2D, assessing autonomic symptom burden with the Composite Autonomic Symptom Score-31 (COMPASS-31), general well-being with the Short Form Health Survey (SF-36), and psychological well-being with the Hospital Anxiety and Depression Scale. Multivariate linear regression assessed associations between autonomic symptom scores and QoL outcomes. Results: The COMPASS-31 scores were 8.9 (2.9; 22.8) in T1D and 12.4 (5.3; 26.1) in T2D. SF-36 physical composite scores were 52.1 (43.2; 56.4) in T1D and 49.3 (40.3; 54.8) in T2D, with similar mental composite scores (50.7 (40.3; 56.9) vs. 51.4 (41.2; 57.2)). Signs of moderate to severe anxiety were observed in 9.9% (95% confidence interval (CI): 8.1–11.9) of T1D and 8.9% (95% CI: 8.1–9.6) of T2D, while depression was present in 5.9% (95% CI: 4.5–7.6) and 5.1% (95% CI: 4.5–5.7). Higher autonomic symptom burden, especially pupillary, vasomotor, and bladder domains, was associated with lower SF-36 score and higher anxiety and depression scores. Conclusions: the Autonomic symptom burden is associated with reduced QoL and increased psychological distress in individuals with diabetes. These findings emphasize the importance of assessing and managing autonomic symptoms in diabetes care to support overall well-being. Full article

Background/Objectives: Sepsis is characterized by a dysregulated host response to infection, where immune-inflammatory and thrombo-inflammation drive organ dysfunction. Early recognition of high-risk patients is essential. In addition, the increasing prevalence of multidrug-resistant (MDR) pathogens complicates therapeutic strategies, as delays in appropriate antimicrobial therapy are strongly associated with poor outcomes. Methods: We conducted a retrospective, single-center cohort study including 120 critically ill patients fulfilling Sepsis-3 criteria. Demographic, clinical, and laboratory data were collected at intensive care unit (ICU) admission, 48 h, and 72 h. The neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) were calculated from complete blood counts. At the same time, the Carmeli score was used as a surrogate for MDR infection risk. Prognostic accuracy was assessed using ROC curve analysis and multivariable logistic regression. Results: Persistently elevated NLR at 72 h and a delayed decline in platelet counts were associated with higher mortality. NLR at 72 h showed good predictive accuracy (AUC = 0.765; 95% CI 0.668–0.863), and the combination of APACHE II and NLR improved prognostic performance (AUC = 0.827). Importantly, the Carmeli score, reflecting MDR infection risk, was an independent predictor of outcome, linking antimicrobial resistance risk with sepsis prognosis. Conclusions: Dynamic immune-inflammatory biomarkers (NLR, platelets), when integrated with MDR risk assessment through the Carmeli score, provide a simple and cost-effective strategy for early prognostic stratification in sepsis. This combined approach may help facilitate early therapeutic decisions and patient care triage. Full article

Secondary peritonitis (SP) remains a major clinical challenge due to its high complication rates and it often results in sepsis and multi-organ dysfunction. This study investigated the association between four nitric oxide synthase (NOS) single-nucleotide polymorphisms (SNPs)—NOS3 c.-786T>C (rs2070744), NOS3 c.894G>T (rs1799983), NOS3 27 bp variable number tandem repeat (VNTR) (rs61722009), and NOS2 (rs2297518)—and sepsis-related complications in 202 patients with SP. Demographic and baseline clinical characteristics, Acute Physiology and Chronic Health Evaluation (APACHE) II scores, Mannheim Peritonitis Index, and complications (multiple organ dysfunction syndrome (MODS), multiple organ failure (MOF), acute respiratory distress syndrome (ARDS), and sepsis) were analyzed for associations with the NOS gene variants. Haplotype analysis was also performed. No SNP showed an association with in-hospital mortality. However, the NOS3 c.-786T>C TT genotype was significantly associated with an increased risk of MOF (p = 0.008), and remained independently associated after multivariate adjustment (p_MOF = 0.006). The T4bG haplotype was significantly more frequent among patients with MODS (p = 0.026), MOF (p = 0.048), and sepsis (p = 0.018). These findings suggest that NOS gene variants, particularly NOS3 c.-786T>C and the T4bG haplotype, may potentially serve as biomarkers for risk stratification in critically ill patients. Full article

Per- and polyfluoroalkyl substances (PFAS) are environmentally persistent organofluorines linked to cancer, organ dysfunction, and other health problems. This study used quantitative structure–property relationship (QSPR) and quantitative structure–activity relationship (QSAR) modeling to examine the binding of PFAS to estrogen receptor alpha (ERα) and beta (ERβ). Molecular docking of 14,591 PFAS compounds was performed, and docking scores were used as a measure of receptor affinity. QSPR models were built for two datasets: the ERα and ERβ top binders (TBs), and a set of commonly exposed (CE) PFAS. These models quantified how chemical descriptors influence binding affinity. Across the models, higher density and electrophilicity indicated positive correlations with affinity, while surface tension indicated negative correlations. Electrostatic descriptors, including HOMO energy and positive Fukui index (F⁺ max), were part of the models but showed inconsistent trends. The CE QSPR models displayed correlations that conflicted with those of the TB models. Following QSPR analysis, 66 QSAR models were developed using a mix of top binders and experimental data. These models achieved strong performance, with R² values averaging 0.95 for training sets and 0.78 for test sets, that indicated reliable predictive ability. To improve generalizability, large-set QSAR models were created for each receptor. After outlier removal, these models reached R² values of 0.68–0.71, which supports their use in screening structurally diverse PFAS. Overall, QSPR and QSAR analyses reveal key chemical features that influence PFAS–ER binding. This predictive approach provides a scalable framework to assess the binding interactions of structurally diverse PFAS to ERs and other nuclear receptors. All the codes, data, and the GUI visualization of the results are freely available at sivaGU/QSPR-QSAR-Molecular-Visualization-Tool. Full article

This study examined the relationships between anxiety and executive functioning in Arab Israeli female adolescents diagnosed with Attention-Deficit/Hyperactivity Disorder (ADHD), compared to their typically developing peers. The aim was to explore differences in emotional and metacognitive executive functions, as well as how anxiety correlates with these cognitive domains within a culturally specific and gender-sensitive population. Eighty adolescent girls aged 15–18 (40 with ADHD and 40 controls) completed self-report measures assessing anxiety and executive functions using the BRIEF-SR and State-Trait Anxiety Inventory. No significant group differences were found in behavioral aspects of executive functions (inhibition, shifting, emotional control, and monitoring) or in overall anxiety levels. However, the ADHD group demonstrated significantly greater difficulties in all metacognitive executive function domains—including working memory, planning, organization, and task completion—as well as higher scores on the Metacognitive Index and Global Executive Composite. Correlational analyses revealed that anxiety was significantly associated with both behavioral and metacognitive executive dysfunction in the control group. In the ADHD group, however, anxiety was only significantly related to behavioral regulation, not metacognitive functioning. These findings underscore the importance of metacognitive support in interventions for adolescent girls with ADHD. Culturally tailored educational strategies that target working memory, planning, and organizational skills may help improve academic performance and overall adaptive functioning in this underserved population. Full article

Background: Although tryptophanyl-tRNA synthetase (WRS) is a novel biomarker released during bacterial and viral infections, its prognostic value in sepsis has rarely been reported. This study aimed to evaluate the prognostic performance of WRS in patients with sepsis in the emergency department (ED). Methods: This prospective, observational study included 243 patients with sepsis. Blood samples were collected to measure full-length WRS levels. The prognostic value of WRS was evaluated using the area under the receiver operating characteristic curve, Kaplan–Meier survival curve analysis, and the Cox proportional hazards model. Results: The WRS levels were higher in patients with septic shock than in those without shock (p = 0.018). WRS could predict 30-day mortality (area under the curve, 0.648; 95% confidence interval [CI], 0.569–0.726; sensitivity, 56.7%; specificity, 73.3%; cut-off value, 84.15 µg/L; p < 0.001). Patients with WRS levels of ≥84.15 µg/L showed higher 30-day mortality than those with WRS levels of <84.15 µg/L. Among patients with WRS levels of ≥84.15 µg/L, those with positive urine culture results had higher 30-day mortality than those with negative urine culture. Patients with renal Sequential Organ Failure Assessment (SOFA) score of ≥1 had higher 30-day mortality than those with renal SOFA score of 0. WRS was an independent risk factor of 30-day mortality (hazard ratio = 1.003; 95% CI, 1.001–1.005; p = 0.014). Conclusions: WRS effectively predicted clinical outcome in patients with sepsis and could be more useful in those with kidney dysfunction or urinary tract infection. Full article

Sepsis and septic shock remain leading global causes of mortality, with endotoxin from Gram-negative bacteria playing a central role in their pathophysiology. Polymyxin B hemoperfusion (PMX-HP) was developed as an adjunctive therapy to directly remove circulating endotoxin in patients with sepsis and septic shock. Early clinical trials yielded conflicting results, largely due to challenges in patient selection. The endotoxin activity assay (EAA) has been investigated as a biomarker to identify patients most likely to benefit, but its limitations include indirect measurement, variability, and poor specificity. The recently completed TIGRIS trial, which enrolled septic shock patients with intermediate EAA values (0.60–0.89) and high organ dysfunction, demonstrated a significant survival benefit, thereby validating a targeted, precision medicine approach. This review critically appraises the role of EAA in guiding PMX-HP, highlights the lessons learned from the TIGRIS trial, and discusses complementary strategies such as integrating additional biomarkers, organ dysfunction scoring, and clinical phenotyping. Future research should embed EAA within multi-dimensional frameworks to optimize patient selection and establish PMX-HP as a precision therapy for endotoxemic sepsis and septic shock. Full article