Search Results (2,696)

Objectives: The purpose of this study was to investigate the protective effects and underlying mechanisms of fucoidan on contrast-induced acute kidney injury (CI-AKI) in mice, focusing on the TLR4/NF-κB and Nrf2/GPX4 pathways. Methods: Five-week-old male ICR mice were randomly divided into normal control, contrast model, low-dose (100 mg/kg), and high-dose (300 mg/kg) fucoidan groups. Renal index, biochemical markers, histopathology, oxidative stress indicators, inflammatory cytokine levels, and the expression of TLR4/NF-κB, Nrf2/HO-1, and ferroptosis-related proteins were assessed. Untargeted metabolomics followed by KEGG pathway enrichment was also performed. Results: Our results showed that contrast successfully established the CI-AKI model, as evidenced by an increased kidney index, abnormal biochemical parameters, severe renal pathological damage, oxidative stress imbalance, inflammatory activation, ferroptosis, and metabolic disturbances. Fucoidan dose-dependently improved kidney index and biochemical markers, alleviated pathological injury, enhanced antioxidant capacity, suppressed inflammation and ferroptosis, and reversed metabolic pathway disorders (e.g., purine and glycerophospholipid metabolism), with the high dose showing more pronounced effects. Conclusions: Fucoidan could effectively ameliorate CI-AKI, and its effects are closely associated with the inhibition of the TLR4/NF-κB pathway, activation of the Nrf2/HO-1 pathway, regulation of ferroptosis-related proteins, and improvement of key metabolic disturbances, suggesting a new research direction for the prevention of CI-AKI. Full article

Background/Objectives: Nonselective beta blockers (NSBBs) are widely used in cirrhosis for portal hypertension, but their safety in older adults with decompensated cirrhosis remains uncertain. Methods: We conducted a retrospective multicenter cohort study using the TriNetX Research Network. Adults aged 30–90 years with decompensated cirrhosis were stratified into three groups: 30–60 years, 61–90 years, and a prespecified subgroup of 81–90 years. NSBB exposure (propranolol, nadolol, or carvedilol) within 30 days of decompensation was assessed, and 1:1 propensity score matching was performed within each age group. The primary outcome was 12-month all-cause mortality. Secondary outcomes included acute kidney injury (AKI), electrolyte abnormalities, and acute care utilization. Results: After matching, 40,074 pairs (30–60 years), 96,084 pairs (61–90 years), and 19,024 pairs (81–90 years) were analyzed. NSBB use was associated with lower 12-month mortality in ages 30–60 (4.0% vs. 4.6%; RR 0.86, 95% confidence interval [CI] 0.81–0.92). 61–90-year cohort, mortality was similar between groups (7.4% vs. 7.4%; RR 0.99, 95% CI 0.96–1.02). Patients aged 81–90 years, NSBB use was associated with higher mortality (10.9% vs. 10.0%; RR 1.08, 95% CI 1.02–1.16). Across age strata, NSBB was associated with increased AKI, hyperkalemia, and acute care visits. Conclusions: NSBB therapy was associated with reduced mortality in younger adults (30–60 years) but not in older patients (61–90 years) and was associated with increased mortality among those aged 81–90 years. These findings support individualized NSBB use and suggest that patient age should be considered when weighing potential benefits and risks. Full article

Background/Objectives: The acute kidney injury (AKI) to chronic kidney disease (CKD) transition has been associated with a failed-repair proximal tubule (FR-PT) cell state. Hyperuricemia is an established CKD risk factor, but whether FR-PT cells have a coordinated metabolic signature reproducibly detectable across mouse models and human kidney disease remains unresolved. Methods: We assembled a pre-registered meta-analysis of 16 public mouse-kidney metabolomic cohorts (383 samples; five model classes; three injury phases) through a three-path harmonization pipeline. Convergent validation drew on KPMP single-nucleus RNA-seq (78,480 proximal tubule cells), two-sample Mendelian randomization of serum urate (102 instruments) against AKI/CKD/eGFR GWAS, and cross-cohort human plasma metabolomics across 2058 CKD/DKD patients. Results: Mouse meta-analysis identified uric acid (g = +2.70) and AICAR (g = +1.50) as the only cross-class conserved metabolites, with uric acid peaking during the AKI-to-CKD transition and returning to baseline in mouse CKD due to uricase clearance. Cross-class overlap between model classes was low (mean pairwise Jaccard = 0.109, below the pre-registered 0.20 threshold), invoking the pre-registered M-S1 stop rule: model-specific metabolic responses dominate, and the conserved signal is a small two-metabolite core superimposed on these largely model-specific programs. KPMP failed-repair PT cells exhibited transcriptional patterns consistent with coordinated four-arm purine-pathway dysregulation (de novo synthesis ↑, AMPK ↑, MOCOS ↑, URAT1 ↓), with this transcriptional pattern observed in both AKI and CKD donors (Spearman ρ = +0.900). Mendelian randomization was consistent with a possible causal contribution of serum urate to AKI/CKD/eGFR risk, with colocalization evidence at GCKR (PP.H4 = 1.000). Cross-cohort human plasma profiling across 2058 patients confirmed the systemic detectability of 29 purine-pathway metabolites in uricase-deficient humans (a translational-plausibility check, not validation of cellular source). Conclusions: The integrated data support a model in which FR-PT-associated purine-pathway reprogramming may contribute to the elevated urate signal observed during AKI-to-CKD transition, with uric acid as the candidate metabolic readout. Differences in uricase activity between mice and humans may help explain why chronic-phase urate signals are attenuated in mice but persist in humans. This work nominates a candidate cell-state metabolic readout of the AKI-to-CKD transition as a hypothesis for prospective testing; it does not establish causation, and therapeutic translation would require dedicated interventional studies. Full article

Background/Objectives: Centralisation of open abdominal aortic aneurysm (AAA) repair is widely advocated, but supporting evidence often conflates institutional volume with individual surgeon expertise. We report outcomes of open AAA repair at a small- to medium-volume centre and assess the contributions of surgeon experience, multidisciplinary perioperative care, and supervised surgical teaching. Methods: Retrospective analysis of all consecutive patients undergoing open AAA repair between January 2017 and December 2023. Endovascular procedures were excluded. The primary endpoint was 30-day all-cause mortality. Secondary endpoints included perioperative morbidity, acute kidney injury (AKI), length of stay, and overall survival. Results: A total of 195 patients underwent open AAA repair (162 elective; 33 urgent/emergency), with a mean of 27.9 cases annually. Mean age was 70.2 years (SD 8.1), and 85.6% were male. Thirty-day mortality was 1.5% overall (3/195) and 1.2% (2/162) for elective cases, with no significant difference between elective and urgent/emergency cases (1.2% vs. 3.0%; p = 0.430). No perioperative strokes occurred; myocardial infarction occurred in three patients (1.5%). Median operative time was 261 min (IQR 210–320), reflecting systematic supervised teaching in approximately 95% of cases. AKI occurred in 10.3%; clinically significant renal insufficiency at 30 days occurred in 5.1%, and no patient required permanent renal replacement therapy. The perioperative reintervention rate was 9.2%, and median hospital stay was 8 days (IQR 7–12). At a mean follow-up of 62.3 months (SD 25.1), overall mortality was 7.7% and aneurysm-related mortality 1.0%. Kaplan–Meier estimated overall survival was 98.5%, 95.8%, and 89.0% at 1, 3, and 7 years, respectively. Conclusions: Favourable outcomes can be achieved at small- to medium-volume centres through concentrated surgeon expertise, structured teaching, and a high-functioning multidisciplinary team. These findings support a more nuanced assessment of open AAA repair that considers surgeon experience, team performance, and demonstrated outcomes rather than institutional volume alone. Full article

Both SARS-CoV-2 infection and COVID-19 vaccination have been associated with renal complications. In the context of SARS-CoV-2 infection, kidney injury is primarily attributed to a complex interplay of systemic immune dysregulation and vascular damage. Severe infection triggers a cytokine-mediated inflammatory response characterized by elevated levels of pro-inflammatory mediators, resulting in systemic hemodynamic instability, increased capillary permeability, and renal hypoperfusion, ultimately leading to acute tubular injury. In addition, virus-induced endothelial activation promotes a prothrombotic state, microvascular injury, and further impairment of renal perfusion. Collectively, these processes converge to produce acute kidney injury (AKI) and, in severe or prolonged cases, may contribute to chronic tubulointerstitial damage and progressive renal dysfunction. In contrast, renal manifestations following COVID-19 vaccination are relatively uncommon and are thought to arise primarily from immune-mediated dysregulation rather than direct cytopathic effects. Reported cases include minimal change disease, IgA nephropathy, focal segmental glomerulosclerosis (FSGS), acute interstitial nephritis and other glomerulopathies, which present as either new-onset disease or relapses. These lesions are thought to result from transient immune activation following vaccination, including T-cell stimulation and altered humoral responses, which may trigger or unmask an underlying susceptibility to renal injury. Careful post-vaccination monitoring in high-risk populations may be warranted, and further molecular and population-level studies are needed to elucidate the underlying mechanisms and refine risk assessment. Full article

Introduction: Gastrointestinal bleeding (GIB) is a potentially life-threatening condition associated with significant morbidity, mortality, and healthcare burden. While endoscopy remains the first-line method of management, transarterial embolization (TAE) plays an important role where endoscopic therapy fails or is not feasible. Aim: The aim of this study was to evaluate the demographics, etiologies, management patterns, and reintervention rates of patients with GIB undergoing angiography and TAE. Methods: This retrospective study included 43 patients who underwent angiography for GIB. Patients were stratified as upper (UGIB) or lower GIB (LGIB). Descriptive statistics were used to summarize demographics, clinical characteristics, pre-procedural investigations, interventions, and outcomes. Results: Of the 43 patients (mean age 58.9 ± 17.9 years), 62.8% had UGIB and 37.2% had LGIB. Pre-procedural evaluation was performed in 97.7% of patients, including CT scans (88.4%) and endoscopy (67.4%). Embolization was performed in 76.7% of cases, including prophylactic (39.5%) and therapeutic (32.6%) approaches. Of the patients with contrast extravasation on CT, 66.7% underwent embolization, with 64.3% of these patients requiring no further intervention. Within 30 days, 18.6% of all patients who underwent angiography required endoscopic reintervention, 16.3% required surgery, and 7.0% died due to ongoing/recurrent bleeding. Complications were infrequent, including acute kidney injury (2.3%) and access site hematoma (4.7%). Conclusions: Angiography with TAE is a valuable and broadly safe intervention for GIB refractory to endoscopic management. Despite a moderate rate of reintervention, it provides effective hemorrhage control in a substantial proportion of patients. Further studies are required to identify predictors of clinical success and optimize patient selection. Full article

Rhabdomyolysis-associated acute kidney injury is driven by myoglobin-mediated oxidative stress, inflammation, mitochondrial impairment, and tubular cell death. This study evaluated the nephroprotective activity of green-synthesized Withania somnifera-functionalized selenium nanoparticles (Ws-SeNPs) in glycerol-induced renal injury and compared their efficacy with native W. somnifera extract and sodium selenite. The chemical profile of the plant extract was characterized by LC–MS/MS, and Ws-SeNPs were evaluated using dynamic light scattering, zeta potential analysis, transmission electron microscopy, and FTIR spectroscopy. Thirty-five male rats were assigned to Control, ARF, ARF & Ws, ARF & selenium, and ARF & Ws-SeNPs. ARF was induced by intramuscular injection of 50% glycerol. Glycerol administration induced marked skeletal muscle injury, renal dysfunction, tubular damage, oxidative stress, inflammation, mitochondrial dysregulation, pyroptosis, apoptosis, and histopathological alterations. Both Ws and sodium selenite provided partial protection, whereas Ws-SeNPs produced the greatest improvement in renal function and tissue architecture. Their protective effect was associated with restoration of Nrf2-dependent antioxidant defenses, suppression of NF-κB/NLRP3/GSDMD-associated inflammatory and pyroptotic signaling, preservation of mitochondrial regulatory pathways, and attenuation of apoptosis. These findings indicate that Ws-SeNPs provide multi-target protection against glycerol-induced rhabdomyolysis-associated renal injury and may represent a promising phytochemical-based selenium nanoformulation for further preclinical investigation. Full article

Background and Objectives: Patients with cirrhosis and acute kidney injury (AKI) frequently receive albumin, although plasma volume expansion may contribute to pulmonary or venous congestion. Point-of-care ultrasound (POCUS) may complement bedside assessment when formal echocardiography or advanced hemodynamic monitoring is not immediately available. This study evaluated baseline pulmonary and venous congestion using POCUS in patients with cirrhosis and AKI receiving albumin therapy. Materials and Methods: This exploratory prospective cohort included adults with cirrhosis, ascites, and ICA-AKI stage 1B or higher who were managed under an institutional protocol prescribing intravenous 20% or 25% albumin at 1 g/kg/day for two consecutive days, capped at 100 g/day. Before albumin administration, B-line-defined pulmonary congestion was assessed using a 28-site lung protocol, and IVC-defined venous congestion was assessed using inferior vena cava (IVC) diameter and collapsibility. Serum creatinine was recorded within 12 h before treatment and 48 h after initiation. Complete renal response was defined as serum creatinine within 0.3 mg/dL of the pre-AKI baseline; partial response was defined as regression by at least one ICA-AKI stage without complete response. Results: Twenty-two patients were included. B-line-defined pulmonary congestion was present in 18/22 (81.8%). IVC assessment was technically evaluable in 20 patients, of whom 6/20 (30.0%) met the criteria for IVC-defined venous congestion. The Hodges–Lehmann estimate of the median paired creatinine difference was +0.03 mg/dL (95% CI, −0.52 to 1.31) without pulmonary congestion and −0.33 mg/dL (95% CI, −0.67 to −0.20) with pulmonary congestion. Renal response occurred in 1/4 (25.0%) and 12/18 (66.7%), respectively (two-sided Fisher exact p = 0.264). Among patients with evaluable IVC examinations, renal response occurred in 8/14 (57.1%) without and 3/6 (50.0%) with IVC-defined venous congestion (p = 1.000). Conclusions: Baseline POCUS frequently identified ultrasound-defined congestion, but congestion status did not clearly distinguish short-term renal response. These exploratory findings support the feasibility of bedside POCUS phenotyping but do not establish that congestion modifies albumin response or clinical outcomes. Full article

Lithium remains a cornerstone mood stabilizer for bipolar disorder, with strong evidence for relapse prevention and a unique association with reduced suicide risk. Its benefit is counterbalanced by renal adverse effects, ranging from impaired urinary concentrating capacity and nephrogenic diabetes insipidus (NDI) to chronic tubulointerstitial nephropathy with progressive loss of glomerular filtration rate in a minority of long-term users. Mechanistically, lithium enters collecting duct principal cells via the epithelial sodium channel, disrupts vasopressin-regulated water handling by downregulating aquaporin-2, and can drive chronic interstitial injury. Risk is amplified by episodes of lithium intoxication, dehydration, interacting medications that reduce renal lithium clearance, longer treatment duration, and comorbid kidney disease. This review integrates psychiatric and nephrologic perspectives on lithium’s indications, mechanisms, renal phenotypes, and prevention strategies, and proposes a practical shared-care pathway for patients with bipolar disorder who develop polyuria, NDI, acute kidney injury, or chronic kidney disease during lithium therapy, emphasizing monitoring, targeted treatment of polyuria, mitigation of toxicity, and structured shared decision-making when renal function declines. Full article

Background/Objectives: Acute interstitial nephritis (AIN) is a cause of acute kidney injury (AKI) during immune checkpoint inhibitor (ICI) therapy, but biopsy-confirmed data are limited. We estimated institutional proportions of biopsy-confirmed AIN clinically attributed to ICI exposure (ICI-AIN) and characterized its presentation, pathology, treatment, and renal outcomes. Methods: We retrospectively reviewed native renal biopsies performed at Attikon University Hospital from February 2021 through December 2025. Cases were included when ICI exposure preceded AKI and the treating nephrology team documented clinicopathologic attribution to ICI exposure. Results: AIN was identified in 15 of 339 native renal biopsies; 12 cases were attributed to ICI exposure, representing 3.5% of native renal biopsies and 0.8% of 1472 unique ICI-treated patients. Median serum creatinine increased from 1.05 mg/dL at baseline to 3.50 mg/dL at biopsy assessment. During the AKI episode, 10 patients (83.3%) met Kidney Disease: Improving Global Outcomes (KDIGO) criteria for stage 3 AKI. All patients had pyuria, negative urine cultures, and subnephrotic proteinuria. Hematuria and peripheral eosinophilia occurred in four and two patients, respectively. All patients received corticosteroids, and none required kidney replacement therapy. Complete, partial, and absent recovery occurred in eight, two, and two patients, respectively; under the stricter baseline-relative definition, the corresponding numbers were five, five, and two. Conclusions: Biopsy-confirmed ICI-AIN was infrequently detected. Severe AKI was common, urinary findings were nonspecific, and residual renal dysfunction frequently persisted after corticosteroid treatment. Full article

Cardiopulmonary bypass (CPB) during heart surgery provokes an inflammatory response that can cause post-operative organ injury, yet how CPB shapes key neutrophil effector programs is unclear. We investigated whether CPB differentially regulates neutrophil degranulation versus neutrophil extracellular trap (NET) formation and whether pre-operative neutrophil phenotypes associate with organ dysfunction. In a prospective cohort (n = 39) of children (1 day–4 years) undergoing CPB, blood samples were obtained before CPB and 24 h post-operatively. Purified neutrophils were analyzed for elastase activity and NET formation, alongside phenotypic markers of activation and neutrophil–platelet aggregation. Findings were correlated with acute kidney injury, respiratory failure, and cardiovascular dysfunction. CPB induced marked neutrophilia (4.5-fold rise; p < 0.0001). Elastase release was robustly enhanced after CPB and showed limited augmentation with secondary stimulation but did not predict organ dysfunction. In contrast, NET formation was significantly reduced after CPB. Importantly, diminished pre-operative responsiveness to low-dose NET priming was observed in patients who developed organ injury. Pediatric CPB uncouples neutrophil effector programs, priming degranulation while suppressing NETosis. Pre-operative NET “reserve” may define a clinically relevant innate immune endotype at risk for post-operative organ dysfunction and supports development of biomarker-driven treatment strategies in patients undergoing CPB. Full article

Background/Objectives: Computed tomography (CT) is the gold-standard diagnostic modality for acute diverticulitis, yet the association between early CT imaging and short-term clinical outcomes among hospitalized older adults has not been evaluated in a large multicenter propensity-matched cohort. We assessed whether early CT abdomen/pelvis (within 24 h of admission) was associated with improved short-term outcomes compared with delayed or absent CT among adults aged ≥65 years hospitalized with acute diverticulitis. Methods: We conducted a retrospective cohort study using the TriNetX US Collaborative Research Network through February 2026. Early CT was defined as CT abdomen/pelvis performed within 24 h of the index hospitalization. Patients underwent 1:1 propensity score matching using demographic, comorbidity, diverticulitis-related, medication, and laboratory variables. The primary outcome was 30-day all-cause mortality. Results: Among 86,214 eligible patients, 62,478 received early CT and 23,736 did not. After matching, 22,840 patients remained in each cohort. Early CT was associated with lower 30-day mortality (RR 0.72, 95% CI 0.62–0.84), 90-day mortality (RR 0.78, 95% CI 0.70–0.87), bowel surgery within 30 days (RR 0.81, 95% CI 0.73–0.90), sepsis (RR 0.76, 95% CI 0.69–0.84), acute kidney injury (RR 0.85, 95% CI 0.78–0.92), ICU admission (RR 0.79, 95% CI 0.72–0.87), and 30-day readmission (RR 0.86, 95% CI 0.80–0.93). Early CT was also associated with higher rates of percutaneous abscess drainage (RR 1.37, 95% CI 1.21–1.55) and shorter hospital length of stay (5.4 vs. 6.8 days; mean difference −1.4 days, 95% CI −1.6 to −1.2). Conclusions: Early CT imaging within 24 h of admission was associated with improved short-term outcomes among older adults hospitalized with acute diverticulitis, including lower mortality, reduced need for bowel surgery, lower rates of sepsis and acute kidney injury, shorter hospital stay, and higher utilization of percutaneous abscess drainage. These findings support guideline recommendations for prompt diagnostic CT imaging in this population and suggest that early CT may facilitate timely risk stratification, source control, and management optimization. Full article

Background: Chronic kidney disease (CKD) is a major global health burden, affecting more than 850 million people worldwide. Increasing evidence implicates engulfment and cell motility 1 (ELMO1), a cytoplasmic adaptor protein that regulates cytoskeletal remodeling, phagocytosis, and immune responses through the ELMO1–DOCK1–Rac1 signaling axis, in renal injury and disease progression. Methods: This narrative review identified relevant publications through searches of PubMed, Web of Science, and Google Scholar using combinations of the terms “ELMO1,” “kidney disease,” “diabetic kidney disease,” “IgA nephropathy,” “focal segmental glomerulosclerosis,” “acute kidney injury,” and “renal fibrosis.” English-language original research articles, genetic association studies, mechanistic investigations, and selected review articles were preferentially included according to their relevance to ELMO1 in kidney diseases. Results: Genetic association studies have implicated the ELMO1 locus in susceptibility to diabetic kidney disease (DKD), although associated variants and effect sizes differ across populations. Experimental studies suggest that ELMO1 regulates cytoskeletal remodeling, inflammatory responses, oxidative stress, and extracellular matrix deposition through the canonical ELMO1–DOCK1–Rac1 signaling pathway as well as Rac1-independent mechanisms. Available evidence supports a role for ELMO1 in DKD and renal fibrotic remodeling. In focal segmental glomerulosclerosis, the relevance of ELMO1 is primarily inferred from Rac1-associated podocyte injury pathways, whereas evidence in acute kidney injury remains limited and context-dependent. ELMO1 may contribute to inflammatory injury in ischemia–reperfusion settings but may also support efferocytosis and tissue repair in nephrotoxic injury models. In IgA nephropathy, evidence for a direct role of ELMO1 remains limited and is currently based largely on indirect mechanistic observations involving mucosal immunity and glomerular injury responses. Conclusions: ELMO1 is a context-dependent regulator of cytoskeletal, inflammatory, oxidative, and matrix-remodeling processes relevant to kidney disease. The strongest evidence currently supports its involvement in DKD, whereas its roles in other kidney diseases remain to be further defined in disease-specific, cell-type-specific, and stage-specific experimental models. Further studies are required to clarify its potential as a biomarker or therapeutic target in CKD. Full article

Acute kidney injury (AKI) is a major global health challenge associated with substantial morbidity, mortality, and progression to chronic kidney disease. Increasing evidence indicates that oxidative stress, mitochondrial dysfunction, inflammatory signaling, regulated cell death, and maladaptive tissue repair play central roles in AKI pathogenesis, yet effective disease-modifying pharmacological therapies remain unavailable. This narrative review critically evaluated current evidence regarding the pharmacological characteristics, molecular mechanisms, and translational potential of alpha-mangostin (AM), the principal prenylated xanthone isolated from the pericarp of Garcinia mangostana L., through a comprehensive synthesis of experimental and mechanistic studies. Available preclinical evidence consistently demonstrates that AM improves renal function and attenuates histopathological injury, particularly in cisplatin-induced nephrotoxicity and glycerol-induced rhabdomyolysis models. These renoprotective effects are primarily associated with suppression of oxidative stress, activation of the Nrf2/HO-1 antioxidant pathway, inhibition of NF-κB-mediated inflammatory signaling, preservation of mitochondrial function, and attenuation of apoptosis. Several emerging pathways may also contribute to AM-mediated renoprotective effects; however, current evidence remains indirect, and their roles require validation in kidney-specific models. Clinical translation remains limited by poor oral bioavailability, insufficient pharmacokinetic data, lack of standardized formulations, and the absence of human clinical trials. Overall, current evidence suggests that AM has preliminary renoprotective potential in experimental AKI models. However, the limited number of available studies, predominance of cisplatin-induced nephrotoxicity models, insufficient pharmacokinetic and safety data, and absence of human clinical studies preclude conclusions regarding its clinical efficacy or translational readiness. Further validation in diverse and clinically relevant AKI models is required before clinical investigation can be considered. Full article

Background/Objectives: This study aimed to evaluate and compare the clinical characteristics and outcomes of patients with methicillin-susceptible Staphylococcus aureus (MSSA) and streptococcal native joint septic arthritis (NJSA). Methods: This retrospective multicenter study included adult patients with NJSA from three tertiary care hospitals between 2004 and 2023. Patients were categorized into three groups based on bacterial virulence and differences among streptococcal species: MSSA, non-viridans streptococci, and viridans streptococci. Results: A total of 213 NJSA cases were identified, comprising 164 MSSA, 35 non-viridans streptococcal, and 14 viridans streptococcal cases. Non-viridans streptococcal NJSA exhibited significantly more acute clinical features associated with systemic inflammation, including frequent fever, leukocytosis, thrombocytopenia, elevated C-reactive protein levels, higher total bilirubin levels, and acute kidney injury, compared to MSSA and viridans streptococcal NJSA. The clinical presentations were similar between the MSSA and viridans streptococcal groups. The non-viridans streptococcal group showed a higher incidence of concomitant bacteremia, but a lower proportion of positive joint culture results. Treatment approaches were consistent across the groups, except for a shorter duration of antibiotic therapy in the viridans group. Treatment failure rates were comparable: 9.8% for MSSA, 14.3% for non-viridans streptococci, and 21.4% for viridans streptococci. Conclusions: This study highlights the heterogeneous nature of streptococcal NJSA, with non-viridans streptococci presenting more aggressive clinical manifestations despite similar treatment responses across groups. These findings challenge conventional views on streptococci as a less virulent pathogen than MSSA and emphasize the need for diagnostic and management strategies tailored to the unique pathogenic traits of these bacteria. Full article