Abstract: Background and Objectives: Catheter-related bloodstream infections (CRBSI) and infective endocarditis (IE) lead to substantial morbidity, prolonged hospitalizations, and increased mortality. This study aimed to determine the incidence of IE among hospitalized HD patients with CRBSI and identify risk factors associated with 90-day all-cause mortality. Materials and Methods: We conducted a retrospective analysis of patients diagnosed with CRBSI. Clinical, microbiological, and echocardiographic data were evaluated. Risk factors for 90-day mortality were analyzed using univariate analysis and multivariable Cox proportional hazards regression models. Results: A total of 130 patients were included. Gram-positive organisms were the predominant pathogens (59.6%), with Staphylococcus aureus identified in 27.5% (n=30) of cases. Gram-negative bacteria accounted for 21.1% of infections. IE was diagnosed in 17 patients, representing an incidence of 13.1% within the CRBSI cohort. Significant differences were observed between the IE and non-IE groups regarding the need for surgery, hemoglobin levels, length of hospital stay, and microbial etiology (p < 0.05). The 90-day all-cause mortality rate was 10.8% (n=14). Univariate analysis identified older age, female gender, history of heart failure, and hypoalbuminemia as factors associated with increased mortality (p < 0.05). In the multivariable Cox regression, age remained the sole independent predictor of 90-day mortality (Hazard Ratio: 1.047; 95% CI: 1.0–1.096; p=0.048). Conclusions: Staphylococcus aureus is the leading pathogen in HD patients with CRBSI and IE. Given the 13.1% IE incidence, routine echocardiographic screening represents a clinically sound and justified strategy for patients with CRBSI, regardless of initial culture results, to ensure early diagnosis and intervention.

Abstract:

Background/Objectives: Non-invasive fibrosis scores are widely used for risk stratification in metabolic dysfunction–associated steatotic liver disease (MASLD); however, their performance in obese individuals remains controversial. The Fibrosis-4 index (FIB-4) is commonly recommended as a first-line tool, yet may underestimate fibrosis risk in severe obesity. The BAST score, which incorporates metabolic and anthropometric parameters, has been proposed as an alternative. This study aimed to characterize both the degree and direction of discordance between FIB-4 and BAST in obese patients with MASLD. Methods: This predefined secondary analysis included 2,950 adults with obesity (BMI ≥30 kg/m²) and MASLD from the multicenter OBREDI-TR cohort. Fibrosis risk categories were assigned using standard cut-offs for FIB-4 and BAST. Agreement was assessed using weighted Cohen’s kappa. Associations between discordance patterns, obesity class, and visceral adiposity index (VAI) were evaluated using chi-square tests and general linear models. Results: Overall agreement between FIB-4 and BAST was very poor (κ = 0.041, p < 0.001). Discordance was observed in 22.3% of patients and increased markedly with obesity severity. In class III obesity, discordance was predominantly driven by low-risk classification according to FIB-4 despite high-risk classification by BAST. Patients with this discordant pattern exhibited significantly higher VAI values compared with concordant cases (p < 0.001), independent of study center. Conclusions: In obese patients with MASLD, particularly those with morbid obesity, FIB-4 frequently classifies patients as low risk while BAST identifies elevated fibrosis risk. This systematic discordance suggests that FIB-4 may underestimate fibrosis burden in the context of severe obesity and visceral adiposity, supporting the need for a phenotype-oriented, multimodal approach to fibrosis risk assessment.

Abstract: Cadmium (Cd) is a ubiquitous environmental pollutant that enters the circulation from the lungs and gastrointestinal tract. For most people, staple foods form the main route of Cd exposure. Current evidence suggests that Cd may increase the prevalence of iron deficiency and anemia in environmentally exposed people. Concerningly, intravenous iron administration to treat iron deficiency anemia has resulted in adverse bone outcomes in a higher-than-expected frequency; for which reasons remain unclear. The bone-derived hormone, fibroblast growth factor 23 (FGF23), the regulator of vitamin D and phosphate homeostasis, has been speculatively implicated, given that anemia, iron deficiency and inflammatory conditions all are known to increase FGF23 expression levels in osteoblasts. Additionally, early studies demonstrated that Cd increased FGF23 expression by osteoblast-like cells and suppressed FGF23 cleavage leading to an abrupt rise in serum FGF23, which, in turn, mediated an effect of Cd on tubular phosphate reabsorption. In this review, experimental breakthrough studies showing Cd-induced iron deficiency, and a reduction in iron absorption by Cd are summarized together with intestinal absorption of Cd, and an increment of Cd uptake and Cd body burden in those with low body iron stores. Potential contributions of Cd, anemia and iron deficiency in the context of hypophosphatemic osteomalacia development after intravenous iron supplementation, are discussed. Mechanism of Cd-induced ferroptosis in pathogenesis of osteoporosis, emphasizing heme oxygenase-1 (HO-1)/bilirubin axis and zinc deficiency are presented.

Abstract: BACKGROUND In Kenya, end-stage renal disease is a significant public health burden treated primarily with hemodialysis in county hospitals, yet comprehensive outcome data from these routine settings are scarce. AIM To evaluate one-year clinical outcomes and identify independent predictors of mortality among ESRD patients undergoing hemodialysis at a Kenyan county hospital. METHODS We conducted a retrospective cohort study of all patients who initiated hemodialysis for ESRD at Murang'a County Referral Hospital between January 2024 and January 2025. Data on demographics, clinical characteristics, comorbidities, and treatment parameters were extracted from hospital electronic medical records and dialysis unit records. Cox proportional hazards regression was used to identify factors associated with one-year mortality. RESULTS Of 79 patients analysed (median age 62.0 years, IQR 48.0-74.0; 65.8% male), the one-year all-cause mortality rate was 34.2% (27/79). The cohort demonstrated a heavy reliance on central venous catheters (89.9%, 71/79) rather than arteriovenous fistulas (10.1%, 8/79). 3 Non-survivors were significantly older (median 73.0 vs 58.0 years, p<0.001) and had lower baseline haemoglobin (7.1 vs 8.6 g/dL, p=0.008). In multivariable analysis, older age (aHR 1.05 per year, 95% CI 1.01-1.09, p=0.012) and central venous catheter use (aHR 3.12, 95% CI 1.08-9.01, p=0.036) remained independent predictors of mortality. Lower eGFR and hemoglobin were significant in univariate analysis but not in the adjusted model. Comorbidities, including HIV and diabetes, did not reach statistical significance. CONCLUSION This study found high one-year mortality in Kenyan hemodialysis patients, with older age and catheter use showing strong associations with death. The near-universal use of CVCs is a marker of systemic challenges in pre-dialysis care, underscoring the urgent need for vascular access programs and improved care strategies to improve survival.

Abstract: Background: The antimicrobial peptide LL-37 has emerged as a key mediator linking innate and adaptive immunity and has been implicated in the pathogenesis of immune-mediated inflammatory diseases. While circulating levels of LL-37 and anti-LL-37 antibodies have been investigated in several conditions, their presence and relevance within the local joint microenvironment remain insufficiently explored. This study aimed to evaluate anti-LL-37 antibodies in synovial fluid from patients with psoriatic arthritis (PsA), rheumatoid arthritis (RA), and knee osteoarthritis (GoA), and to analyze their associations with pro-inflammatory cytokines. Methods: Synovial fluid samples were obtained from patients with PsA, RA, GoA, and from healthy controls. Levels of anti-LL-37 antibodies, IL-1β, IL-6, and IL-23 were measured using enzyme-linked immunosorbent assay (ELISA). Correlation analyses were performed to assess relationships between anti-LL-37 antibodies and cytokine levels. Receiver operating characteristic (ROC) curve analysis was used to evaluate the diagnostic performance of anti-LL-37 antibodies. Results: Anti-LL-37 antibody levels were significantly elevated in synovial fluid from patients with PsA compared to RA, GoA, and healthy controls. Patients with RA exhibited lower anti-LL-37 levels despite pronounced elevations of IL-1β and IL-6. In GoA, anti-LL-37 concentrations were comparable to those of healthy controls. A strong positive correlation between anti-LL-37 antibodies and IL-23 was observed in PsA, whereas correlations with IL-1β and IL-6 were more prominent in RA. ROC analysis demonstrated moderate diagnostic accuracy of anti-LL-37 antibodies in distinguishing PsA from healthy controls, but limited utility in RA and GoA. Conclusions: The findings support a disease-specific role of anti-LL-37 antibodies in the immunopathogenesis of psoriatic arthritis and highlight their association with the IL-23/Th17 axis within the synovial microenvironment. Anti-LL-37 antibodies may serve as a complementary biomarker for PsA and provide further insight into the distinct immunological mechanisms underlying inflammatory versus degenerative joint diseases.

Abstract:

Objectives: We investigated the effects of Continuous Positive Airway Pressure (CPAP) on blood pressure (BP) and vigilance in taxi drivers with obstructive sleep apnea (OSA). Methods: Taxi drivers aged ≥60 years were recruited for polysomnography. Those diagnosed with OSA underwent 6 months of CPAP therapy. Baseline and follow-up assessments included 24-hour ambulatory blood pressure monitoring (ABPM) and the psychomotor vigilance test (PVT). Results: Among the 32 participants, 22 (68.8%) were diagnosed with OSA (median age 63.0 [62.0–65.0] years; 21 males). The average CPAP adherence was 3.1±2.3 hours per night, with 23.5% using CPAP for more than 4 hours per night. There were no significant changes in 24-hour mean systolic ABPM (125.9 [116.8–134.9] mmHg to 126.0 [118.3–133.7] mmHg; p=0.93) or reaction times measured by PVT (2.0 [0.0–3.0] lapses to 2.0 [1.0–3.0] lapses; p=0.82) after CPAP therapy. Conclusion: A high prevalence of OSA was observed among taxi drivers. CPAP adherence was suboptimal and did not result in significant improvements in BP or vigilance.

Abstract: Durable left ventricular assist devices (LVADs) are an established and highly effective therapy for patients with advanced heart failure. Ongoing technological improvements and structured follow-up programs have significantly enhanced device durability, reduced complications, and improved long-term survival. Consequently, a growing number of pa-tients with LVAD support require long-term outpatient care and increasingly present to both specialized and non-specialized hospitals, including for admissions unrelated to he-art failure. In this context, echocardiography plays a central role. It is essential not only for routine follow-up in dedicated LVAD clinics but also for the assessment of cardiac status during inpatient admissions for extracardiac conditions. However, echocardiographic evaluation in LVAD patients is technically demanding and requires a solid understanding of LVAD physiology, device–heart interactions, and the specific hemodynamic conditions of conti-nuous-flow support. Without this knowledge, standard echocardiographic parameters may be misleading. This review provides sonographers and cardiologists with a practical, clinically oriented framework for routine transthoracic echocardiography in patients with durable LVAD support. We summarize key principles of LVAD hemodynamics, discuss interpretation of LVAD console parameters, propose a standardized imaging protocol, and outline a struc-tured approach to common echocardiographic findings in routine ambulatory and inpa-tient settings.

Abstract: Chronic diseases—including diabetes mellitus, cardiovascular disease, chronic kidney disease, and autoimmune disorders—remain the leading causes of global morbidity and mortality. While biomedical pathophysiology defines the etiology and progression of these conditions, cultural factors significantly modulate how patients perceive illness, engage in treatment, and adhere to medical recommendations. This review synthesizes evidence from cross-cultural studies, with a specific focus on medical manifestations and therapeutic challenges, to examine how sociocultural determinants intersect with biological disease processes. We highlight nuanced case comparisons between South Asian, East Asian, Middle Eastern, African, Latinx, and Indigenous populations, illustrating how cultural constructs such as collectivism, fatalism, stigma, traditional medicine reliance, and health literacy directly influence outcomes in chronic disease management. Importantly, we integrate evidence-based recommendations for healthcare professionals, emphasizing culturally tailored interventions, precision medicine approaches, and the role of interdisciplinary care teams.

Abstract:

Background: Apelin-36 may be used to identify patients with ST-segment elevation myocardial infarction (STEMI) who are at risk for the no-reflow phenomenon. Patients presenting with STEMI were evaluated and stratified according to their apelin-36 levels. Methods: In this study, 161 patients presenting with STEMI within 12 hours of symptom onset and undergoing primary percutaneous coronary intervention (pPCI) were enrolled. Biochemical parameters, including apelin-36, troponin T, creatine kinase (CK), the MB fraction of creatine kinase (CK-MB), total cholesterol, triglycerides, and other routine laboratory parameters, were measured. Blood samples for apelin-36 measurement were collected prior to PCI, centrifuged to obtain serum, and preserved at -80⁰C until being assayed. Two-dimensional echocardiography was performed in all patients. Thereafter, patients were divided into two groups according to their level of Apelin-36. Results: Among the 161 consecutive STEMI patients, 115 (71.42%) had Apelin-36 levels ≤0.58ng/mL (group 1), whereas 46 (28.57%) had Apelin-36 levels >0.58ng/mL (group 2). In total, 51 (31.67%) STEMI patients experienced no-reflow phenomenon after PCI: 29 (18.01%) patients with apelin-36 ≤ 0.58ng/mL and 22 (13.66%) with a value > 0.58ng/mL (p < 0.001). In terms of Gensini score, the mean value in group 1 was (70.29 (±28.76), while in group 2, it was 81.95 (±23.82) (p=0.004). Overall, a positive correlation between apelin-36 and Gensini score was observed in both groups using Kendall’s correlation analysis (group 1: Figure 2, p=0.05; group 2: Figure 2, p<0.0001). Binary logistic regression analysis identified apelin-36 and diabetes mellitus as significant predictors at the 5% level, with p-values of 0.045 and 0.036, respectively. Patients with apelin-36 levels ≤ 0.58ng/mL had troponin T levels of 290.0 (8.5-9510.0), while those with a value > 0.58ng/mL had troponin T levels of 132.15 (9.4-5190.0) (p < 0.012). The receiver operating characteristics (ROC) curve of apelin-36 was used to plot the true positive rate against the false positive rate at different cut-off points, with AUC=0.67 (95% CI, 0.57-0.76), and the cut-off value for apelin-36 was 0.58ng/mL, with p=0.001. Conclusions: Significant associations were observed between apelin-36 and no-reflow phenomenon in patients with STEMI. An apelin-36 cut-off value of 0.58ng/mL, measured at admission, could be used to identify patients who were at increased risk of no-reflow phenomenon/reperfusion injury.

Abstract: Abstract Introduction: We have followed the onset of the acquired immune deficiency disease (AIDS) pandemic and human immunodeficiency virus (HIV) infection from its recognition in the US since 1981 (1) describing the disease’s impact on T-lymphocytes (2), leading to pulmonary and renal diseases, cancer (3) and fibrosis (4). The development of an effective therapeutic combination anti-retroviral therapy (cART) has revolutionized HIV’s impact globally and HIV infection is now regarded as a chronic disease. A major inflammatory component for chronic HIV is the gastrointestinal tract (GIT) which is a major site for HIV replication and persistence (5). However, few tools are currently available to assess the innate immune system (InImS) in HIV patients. In this study, we present data on InImS biomarkers in patients on cART showing that inflammation predicts mortality (1). Patients and Methods: From patients enrolled in a colorectal neoplasia prediction study (6) we followed 34 adult HIV positive Veterans on cART comparing colon InImS expression of a Paneth cell product, p87; the denominator) and blood ferritin (the numerator) to derive the FERAD ratio, and p87 expression by immunohistochemistry available in some of our HIV patients, and compare expression to 2,252 without HIV. Stool and colonoscopically-obtained tissue specimens were run in a p87 ELISA and immunohistochemistry for both fixed and native antigens, using the Adnab-9 antibody. Results: There were no significant differences in demographics aside from lower BMI in HIV patients (24.93±6.30 versus 28.0±6.13 kg/m2) p< 0.0001. HIV patients also had lower serum creatinine (0.99±0.23 versus 1.28±1.89; p< 0.0001) and were heavier smokers 88.9% vs 43.7% (OR 10.29[CI1.28-82.77];p< 0.008) and more frequent alcohol drinkers 71.4% vs 25.1% (OR 6.0 [CI1.7-20.9]) than controls. Native p87 antigen was elevated in HIV patients compared to controls in the ascending, transverse and descending colon (0.794±0.890 versus 0.170±0.201 respectively; p< 0.000004; 1.062±0.730 versus 0.202±0.377 respectively; p< 0.000003; and 0.611±0.182 versus 0.174±0.251 respectively; p< 0.0009), respectively; and Helicobacter pylori (H. pylori) detection was higher in HIV patients (84.6% versus 36%;p< 0.0002). We also ran these assays in cancer patients, for comparison. Conclusions: Colonic inflammation as expressed by p87, a Paneth cell product is significantly elevated in HIV patients and likely represents continued HIV activity leading to inflammation. Increased rates of smoking and drinking alcohol further contribute to inflammation, but there may be an ability to reduce p87 expression by intervention with folates (7) and manipulation of the abnormal HIV patient microbiome (8) may be effective therapies that warrant further study.

Abstract: Nontuberculous mycobacteria (NTM) is a general term for mycobacteria other than the Mycobacterium tuberculosis complex and Mycobacterium leprae. There are over 150 species of NTM, which are widely distributed not only in natural environments such as water systems and soil, but also in residential environments such as bathrooms. Inhalation exposure from these environments can lead to pulmonary NTM disease, a respiratory infection. In Japan, 90% of pulmonary NTM disease cases are caused by two species, Mycobacterium avium and M. intracellulare. Because the two species are biochemically similar, they are collectively referred to as Mycobacterium avium complex (MAC). Pulmonary MAC disease is broadly divided into two types: the fibrocavitary type and the nodular/bronchectamic type, each with its own characteristics. The two cases reported here were both elderly women with refractory MAC pulmonary disease, with different phenotypes: a fibrocavitary type and a long-standing, progressive nodular and bronchiectatic type. Treatment was performed with a regimen using liposomal amikacin (ALIS). ALIS is an aminoglycoside antibiotic that works by binding to bacterial liposomes and inhibiting protein synthesis. Using amikacin liposomal technology and a specialized inhaler, ALIS efficiently reaches alveolar macrophages, directly killing MAC bacteria within. However, the unique administration method, which requires inhaler cleaning, makes continued use difficult given the characteristics of patients with refractory MAC pulmonary disease. Even when treatment is possible, frequent side effects, such as hoarseness and dysphonia, while not severe, further contribute to the difficulty of initiating treatment. In both of these cases, treatment was made possible with the cooperation of the patient's family, and no adverse effects were observed. This is the first report in the world to show that the therapeutic effect was confirmed even when the number of treatments was less than half the standard number, and that thanks to the new drug delivery method of inhalation, it can become a new treatment option when existing drugs cannot be used or are ineffective for some reason, and that it may be safe to use even in elderly patients.

Abstract:

Background: Robotic-assisted surgery (RAS) is increasingly used for colorectal cancer (CRC), but its clinical and oncologic advantages over conventional laparoscopy (LS) remain uncertain. Prior meta-analyses have included overlapping RCTs but vary in methodology, scope, and analytical transparency. This review aims to provide an updated, independently re-analyzed synthesis of RCTs published from 2015–2025, with full PRISMA compliance, explicit analytic reproducibility, and expanded evaluation of bias and evidence certainty. Methods: A systematic review and meta-analysis was conducted according to PRISMA guidelines. The protocol was retrospectively registered in PROSPERO (Registration ID: CRD420251237158). PubMed, Embase, and Cochrane CENTRAL were searched (January 1, 2015–January 31, 2025). Full reproducible search strings, PICOS criteria, and inclusion/exclusion rules were predefined. Only RCTs comparing RAS vs LS for malignant colorectal disease were included. Data extraction was performed independently by two reviewers. Meta-analyses used DerSimonian–Laird random-effects models; standardized procedures were applied for converting medians/IQRs into means/SDs and for continuity corrections in zero-event trials. Risk of bias was assessed using Cochrane RoB 2.0, and evidence certainty was graded using GRADE. Results: A total of 12 RCTs encompassing 3,107 patients met the inclusion criteria. RAS resulted in significantly lower conversion-to-open rates (OR 0.42; 95% CI 0.28–0.63; I²=18%) compared with LS. Operative time was consistently longer with RAS (MD +23.8 minutes; 95% CI 14.2–33.4; I²=67%). Overall postoperative complications (Clavien–Dindo ≥II) were comparable (OR 0.91; 95% CI 0.76–1.13; I²=22%). Length of stay showed a small but significant reduction with RAS (MD −0.8 days; 95% CI −1.3 to −0.2; I²=49%). Pathologic outcomes showed lower circumferential resection margin (CRM) positivity with RAS (OR 0.59; 95% CI 0.41–0.85). Lymph node retrieval was slightly higher with RAS (MD +0.71 nodes; 95% CI 0.25–1.18). Distal margins and TME completeness were equivalent. No RCT reported mature long-term oncologic outcomes; evidence remains limited to short-term surrogates. Conclusions: In contemporary RCTs, RAS provides fewer conversions and slightly better pathologic surrogates, while maintaining similar morbidity compared to LS. The main trade-off remains longer operative time and higher resource use. True oncologic equivalence cannot be confirmed until long-term RCT data mature. Advanced imaging (e.g., SOMATOM Force CT), age-specific MIS evidence, and the emergence of endoluminal robotic systems are likely to shape future refinements in technique and patient selection.

Abstract: Anderson–Fabry disease (FD) is an X-linked lysosomal storage disorder caused by pathogenic variants in the GLA gene, resulting in deficient α-galactosidase A activity and progressive accu-mulation of globotriaosylceramide (Gb3) and its derivative lyso-Gb3 within lysosomes. Beyond substrate storage, FD involves a complex interplay of molecular, metabolic, and inflammatory disturbances that collectively drive multisystemic damage. It seems that Gb3 accumulation im-pairs autophagic flux, promotes mitochondrial dysfunction, and triggers endoplasmic reticulum stress, leading to oxidative imbalance and bioenergetic failure. Concurrently, activation of innate immune pathways, particularly the TLR4/NF-κB axis, induces pro-inflammatory cytokine release and endothelial dysfunction, while complement activation and adaptive immune responses con-tribute to chronic inflammation and fibrosis. These mechanisms define a sustained state of “met-aflammation,” linking lysosomal dysfunction to systemic inflammation. Understanding this molecular cross-talk provides a rationale for identifying novel biomarkers and designing thera-pies that go beyond enzymatic correction, including chaperone therapy, substrate reduction, and gene-based or anti-inflammatory approaches. A deeper comprehension of these interconnected patterns may guide the development of precision medicine strategies aimed at improving long-term outcomes in Fabry disease.

Abstract: Silent gastroesophageal reflux disease (GERD) may present without classic symptoms and instead manifest through respiratory and laryngeal signs. We report the case of a 27-year-old Middle Eastern Arab male with acute dry cough and hoarseness, unresponsive to antitussive therapy, ultimately diagnosed with silent GERD after significant improvement with proton pump inhibitor (PPI) therapy.

Abstract: Background: The comparative effects of pharmacological treatment, bariatric surgery, and diet on insulin resistance (IR) remain unclear. Aim: To study the comparative effects of the methods on IR: pharmacologic, bariatric surgery, and very-low-calorie diet (VLCD) in patients with type 2 diabetes mellitus (T2DM) and hypertension. Methods. Design: a 90-day prospective, multicenter, comparative clinical trial including 130 adult patients divided in three groups: Drug, Surgical, and VLCD groups. Endpoints: HOMA-IR; weight loss; HbA1c, systolic/diastolic blood pressure (SBP/DBP). Results. At 90 days, weight lost in Surgery (-19.8%) and VLCD groups (-17.4%) (P< 0.0001), while in Drug group the loss was unsignificant (-6.5%; P=0.06). SBP/DBP in Drug group decreased by -9.5% (P=0.0002) and -4.1% (P=0.09), respectively. SBP/DBP in: Surgical group decreased by -13.6% and -10.6%, respectively (P< 0.001); VLCD group -23.3% and 21.3%, respectively (P< 0.0001). HOMA-IR in Drug, Surgery and VLCD groups decreased by -42.2% (P=0.004), -87.6% (P< 0.0001), and -88.7% (P< 0.0001), respectively. In Drug group HOMA-IR did not reach normal level. Correlation-regression-analysis revealed a direct correlation between weight-loss and a decrease in HOMA-IR (r=0.526; F=33.2, P< 0.0001). HOMA-IR decreases by 65% if weight decreases by 10%; if weight decreases by 25%, then HOMA-IR decreases by 83%. Conclusions. HOMA-IR was associated with weight loss: the greater the weight loss, the lower HOMA-IR. Weight loss leads to reduce the need for antidiabetic/antihypertensive drugs in the patients.

Abstract: Accumulating evidence suggests that exposure to pollution from environmental cadmium (Cd) contributes to diabetic kidney disease as indicated by albuminuria and a progressive decrease in the estimated glomerular filtration rate (eGFR). This study examined the effects of Cd exposure on eGFR and the excretion rates of albumin (Ealb) and β2-microglobulin (Eβ2M) in 65 diabetics and 72 controls. Excretion of Cd (ECd) was a measure of exposure, while excretion of N-acetylglucosaminidase (ENAG) reflected the extent of kidney tubular cell injury. In participants with an elevated excretion of Eβ2M, the prevalence odds ratios (POR) for a reduced eGFR rose 6.4-fold, whereas the POR for albuminuria rose 4.3-fold, 4.1-fold, and 2.8-fold in those with a reduced eGFR, diabetes, and hypertension, respectively. By using covariance analysis, which adjusted for the interactions, 43% of the variation in Ealb among diabetics could be explained by female gender (η2 = 0.176), ENAG (η2 = 0.162), hypertension (η2 = 0.146), smoking (η2 = 0.107) and body mass index (η2 = 0.097), while the direct contribution of ECd to Ealb variability was minimal (η2 = 0.005). Results from a mediation analysis inferred that Cd could indirectly contribute to albuminuria and a falling eGFR through inducing additional tubular cell injury, leading to reduced reabsorption of filtered protein, albumin and β2M included.

Abstract:

Background: Fluid resuscitation is a cornerstone in the management of sepsis and septic shock, yet the optimal strategy remains controversial. Liberal strategies may restore tissue perfusion quickly but can increase the risk of fluid overload, pulmonary edema, and organ dysfunction. Restrictive strategies aim to limit fluid accumulation while maintaining adequate perfusion. Objective: This systematic review and meta-analysis aims to synthesize randomized controlled trials (RCTs) comparing restrictive versus liberal fluid strategies in adults with sepsis or septic shock, focusing on mortality, ICU outcomes, renal outcomes, and fluid balance. Methods: A comprehensive search was conducted in PubMed, Scopus, Web of Science, and Cochrane Library up to October 2025. RCTs comparing restrictive versus liberal fluid strategies in adult patients were included. Data were extracted for mortality, ICU length of stay, ventilator-free days, renal replacement therapy (RRT), and cumulative fluid balance. Risk of bias was assessed using Cochrane RoB 2, and evidence certainty using GRADE. Meta-analysis was performed using random-effects models. Results: Twelve RCTs comprising 8,743 patients were included. Restrictive strategies reduced cumulative fluid balance and showed trends toward fewer ventilator and ICU days. Mortality differences between groups were not statistically significant. Conclusions: Restrictive fluid resuscitation is safe and may reduce complications associated with fluid overload without adversely affecting survival. Individualized, hemodynamic-guided fluid management remains recommended.

Abstract:

Background/Objectives: Metabolic dysfunction–associated steatotic liver disease (MASLD) is now the leading cause of chronic liver disease globally, mirroring the increasing prevalence of obesity, insulin resistance, and type 2 diabetes. Early detection of hepatic steatosis is vital for cardiometabolic risk assessment; however, conventional imaging is costly and impractical for population screening. This study aimed to develop interpretable machine-learning models to predict ultrasound-detected MASLD using routinely available clinical and biochemical data. Methods: We analyzed data from 644 adults (50% with MASLD on ultrasonography). Preprocessing, imputation, and feature selection were implemented within a single scikit-learn pipeline to avoid information leakage. An Elastic Net–regularized logistic regression identified the top 20 predictors, which were subsequently used across nine supervised machine learning (ML) classifiers. Model performance was evaluated via repeated stratified 5-fold cross-validation (25 resamples) using accuracy, F1 score, sensitivity, specificity, Youden’s J, balanced accuracy, and Area Under the Receiver Operating Characteristic Curve (AUROC). Interpretability was assessed using SHapley Additive exPlanations (SHAP). Results: Participants with MASLD exhibited greater adiposity, insulin resistance, and dyslipidemia compared with controls [p < 0.05 for body mass index (BMI), waist circumference, glucose, HbA1c, triglycerides). Elastic Net selection highlighted Weight, Ponderal Index, Fibrosis-4 Index (FIB-4), blood urea nitrogen (BUN)/Creatinine ratio, Aspartate Aminotransferase to Platelet Ratio Index (APRI), and Visceral Adiposity Index as the strongest predictors. Logistic Regression and Gradient Boosting achieved the best performance (accuracy = 0.65 ± 0.03; AUROC = 0.71 ± 0.04; balanced accuracy = 0.66 ± 0.06), outperforming rule-based indices such as Fatty Liver Index (FLI) and Hepatic Steatosis Index (HSI) reported in the literature. SHAP analysis confirmed clinically coherent feature effects, with higher anthropometric and hepatic injury indices increasing predicted MASLD probability. Conclusions: Routinely available clinical and biochemical parameters can predict hepatic steatosis with moderate accuracy using transparent, interpretable ML models. Logistic Regression and Gradient Boosting provided the best discrimination and generalizability, offering a pragmatic, low-cost approach for early MASLD screening in primary and metabolic care settings.

Abstract: Background The relative merits of the Henderson–Hasselbalch (HH) versus Stewart frameworks for interpreting dialysis-associated acid–base shifts remain debated. Dialysis alters systemic pH through exogenous bicarbonate delivery, chloride displacement, and removal of organic anions. We compared these approaches across hemodialysis (HD) and peritoneal dialysis (PD). Methods We studied 53 HD patients with paired pre/post HD blood gas and chemistry (106 observations) and 41 PD patients cross-sectionally, totaling 147 datasets. Derived variables followed the Figge/Stewart implementation [apparent SID (SIDa), effective SID (SIDe), strong ion gap (SIG), albumin-corrected anion gap (AGc)]. For HD, changes in pH (ΔpH) were modeled using HH predictors (ΔHCO₃⁻, ΔPCO₂) and Stewart predictors (ΔSIDa, ΔATOT, ΔPCO₂). For cross-sectional data (HD-pre, HD-post, and PD), HH- and Stewart-based level-models were fitted. Stewart-predicted pH was also computed using the Figge and the simplified Constable electroneutrality equation. Results HD increased pH by 0.11, driven by ΔHCO₃⁻ = +5.7 mΕq/L, ΔCl⁻ = −2.3 mEq/L, and declines in unmeasured anions (ΔSIG = −3.9; ΔAGc = −3.3). SIDa increased only marginally (+1.3 mEq/L), whereas SIDe rose by +5.3 mEq/L and fully tracked the alkalinization. In Δ-models, HH explained 90% of variance in ΔpH (R² = 0.903) compared with 51% for Stewart (R² = 0.514). In level-models, HH explained 96% of pH variance versus 36% for Stewart. Bland–Altman analysis showed systematic overestimation of pH by the Figge and Constable approach (bias +0.111), most pronounced pre-HD. PD patients had consistently higher AGc and SIG values than HD patients, indicating a greater burden of unmeasured anions. Conclusions Alkalinization during HD is primarily attributable to bicarbonate gain, chloride displacement, and organic-anion clearance. The HH framework provides superior predictive performance for ΔpH, while closed-system Stewart formulations based on SIDa underestimate alkalinization. However, a broader physicochemical interpretation using SIDe and SIG, which incorporate bicarbonate and unmeasured anions, coherently describes the observed physiology. Future applications of the Stewart approach in dialysis should emphasize SIDe and SIG to better reflect the open-system physiology of both HD and PD.

Abstract: The 2024 Japanese diagnostic criteria for primary sclerosing cholangitis (PSC) introduce a paradigm shift in recognizing small-duct PSC (sdPSC), particularly within ulcerative colitis (UC) cohorts. By integrating high-resolution magnetic resonance cholangiopancreatography (MRCP) and mandatory histopathology for normal cholangiograms, these updates address prior underdiagnosis and variability in sdPSC detection. Japanese cohort studies reveal sdPSC prevalence between 5–15%, with up to 55% progressing to large-duct disease. Earlier detection, facilitated by the 2024 criteria’s 86% MRCP sensitivity and clarified histologic thresholds, may halve diagnostic delays, curbing cirrhosis and malignancy risks. In UC patients, these refinements enhance colorectal neoplasia surveillance and enable preemptive management through unified gut–liver assessment. Yet, challenges persist, including biopsy hesitancy, donor shortages, and evolving genetic insights. Overall, the updated criteria mark a decisive move toward precision hepatology, aligning Japan’s PSC-UC strategy with proactive, spectrum-based detection and management for improved long-term outcomes.