Bioscientia Medicina - Journal of Biomedicine and Translational Research
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Bridging the Therapeutic Gap: A Systematic Review and Meta-Analysis on the Efficacy, Safety, and Pathophysiological Impact of Sodium Zirconium Cyclosilicate in Enabling Guideline-Directed Medical Therapy
Get PDFBackground: Hyperkalemia is a life-threatening complication of chronic kidney disease (CKD) and heart failure (HF), primarily impeding the use of life-saving renin-angiotensin-aldosterone system inhibitors (RAASi). This systematic review and meta-analysis evaluate the evidence for sodium zirconium cyclosilicate (SZC) in managing hyperkalemia and enabling RAASi therapy.
Methods: This systematic review searched Medline, Embase, and Cochrane CENTRAL to September 2025. Dual reviewers independently screened, extracted data, and assessed bias (Cochrane RoB 2, Newcastle-Ottawa Scale). We included RCTs and observational studies of SZC in adults with hyperkalemia. A random-effects meta-analysis was performed on RCTs reporting maintenance-phase efficacy and safety.
Results: The search yielded 1,254 citations, with 6 pivotal studies included. The meta-analysis of 3 RCTs found that SZC (5-10g daily) was significantly more effective than placebo at maintaining normokalemia over 12-28 days. The pooled mean difference in serum K+ was -0.58 mEq/L (95% CI: -0.65 to -0.51; I2 = 0%). SZC did increase the risk of edema (pooled Risk Ratio: 2.95; 95% CI: 1.51 to 5.76; I2 = 0%). The narrative synthesis of observational data confirmed that SZC use was associated with a >2.5-fold increase in the likelihood of continuing RAASi therapy.
Conclusion: Sodium zirconium cyclosilicate is a highly effective and rapidly acting agent for both acute correction and chronic management of hyperkalemia. Our meta-analysis provides a precise estimate of its high maintenance-phase efficacy. Its primary clinical benefit lies in providing a renal-independent pathway for potassium excretion, thereby "uncoupling" potassium levels from RAASi use and bridging a critical treatment gap
Beyond Phosphate Binding: A Systematic Review and Meta-Analysis on the Efficacy and Safety of the Novel Paracellular Phosphate Inhibitor, Tenapanor, for Hyperphosphatemia in Dialysis Patients
Get PDFBackground: Hyperphosphatemia is a critical driver of cardiovascular morbidity and mortality in patients with chronic kidney disease (CKD) undergoing dialysis. Current management, reliant on phosphate binders, is hampered by high pill burden and poor adherence. Tenapanor, a first-in-class, minimally-absorbed sodium/hydrogen exchanger 3 (NHE3) inhibitor, reduces paracellular phosphate absorption. We performed a systematic review and meta-analysis of all available Phase 3 trials to quantify its efficacy and safety.
Methods: We searched PubMed, Embase, and Cochrane CENTRAL through October 2025 for Phase 3 clinical trials evaluating tenapanor for hyperphosphatemia in dialysis patients. Data were extracted from 6 eligible studies (N=1573). We conducted separate random-effects meta-analyses for different study designs: 1) parallel-group monotherapy vs. placebo, 2) withdrawal-design monotherapy vs. placebo, 3) parallel-group add-on therapy vs. placebo, and 4) safety (diarrhea incidence) vs. placebo. Efficacy was measured by Mean Difference (MD) in serum phosphate change; safety by Risk Ratio (RR).
Results: Tenapanor demonstrated significant efficacy across all study designs. In parallel-group monotherapy (1 study, N=167), tenapanor was superior to placebo (MD: -1.89 mg/dL; 95% CI: -2.36 to -1.42). In withdrawal-design studies (2 RCTs, N=373), tenapanor maintained serum phosphate levels significantly better than placebo (Pooled MD: -0.75 mg/dL; 95% CI: -1.05 to -0.45; I2=0%). As an add-on therapy (1 RCT, N=235), tenapanor provided additional phosphate reduction versus binders alone (MD: -0.65 mg/dL; 95% CI: -0.96 to -0.35). Tenapanor significantly increased the risk of diarrhea versus placebo (3 RCTs, N=521; Pooled RR: 4.10; 95% CI: 2.50 to 6.72; I2=30%), which was the primary adverse event leading to discontinuation.
Conclusion: Tenapanor represents a new mechanistic paradigm for hyperphosphatemia management. It is a highly effective phosphate-lowering agent, both as monotherapy and add-on therapy, but is associated with a significant, mechanism-based risk of gastrointestinal side effects
Divergent Inflammatory Trajectories: Independent Predictive Value of Admission Neutrophil-to-Lymphocyte and Lymphocyte-to-Monocyte Ratios for Acute Ischemic Stroke Severity in a Southeast Asian Cohort
Get PDFBackground: Systemic sterile inflammation acts as a critical pathophysiological driver in the acute phase of ischemic stroke, mediating secondary brain injury through blood-brain barrier disruption and microvascular thrombosis. While the Neutrophil-to-Lymphocyte Ratio (NLR) and Lymphocyte-to-Monocyte Ratio (LMR) have emerged as potential biomarkers in Western populations, their independent prognostic utility and specific diagnostic thresholds within Southeast Asian populations remain under-explored. This region presents unique challenges due to potential variations in baseline hematological profiles driven by genetic polymorphisms and environmental factors. This study aims to elucidate the association between admission NLR and LMR levels and the severity of Acute Ischemic Stroke (AIS) and to determine optimal population-specific prognostic cut-offs.
Methods: We conducted a retrospective cross-sectional comparative study involving 128 patients with confirmed AIS admitted to Wangaya Regional General Hospital, Indonesia, between January 2025 and August 2025. Patients were stratified based on admission National Institutes of Health Stroke Scale (NIHSS) scores into a Mild Group (NIHSS ≤ 6, n=64) and a Moderate-Severe Group (NIHSS > 6, n=64). Infection was strictly excluded using clinical and radiological criteria independent of admission leukograms to prevent circular bias. Receiver Operating Characteristic (ROC) curve analysis was performed to determine diagnostic accuracy and identify optimal cut-offs. To address potential multicollinearity between NLR and LMR, two separate multivariate binary logistic regression models were constructed to determine independent predictors of severity.
Results: The study population had a mean age of 60.5 years. The Moderate-Severe Group exhibited significantly higher NLR (6.12 ± 3.41 vs. 2.85 ± 1.20; p < 0.001) and lower LMR (2.15 ± 0.92 vs. 4.22 ± 1.50; p < 0.001) compared to the Mild Group. ROC analysis identified optimal cut-offs of ≥ 4.82 for NLR (AUC: 0.782; Sensitivity: 76.6%) and ≤ 2.89 for LMR (AUC: 0.724; Sensitivity: 71.9%). In the multivariate analysis Model 1, NLR ≥ 4.82 remained an independent predictor of severity (Adjusted Odds Ratio [aOR]: 4.12; 95% CI: 1.78–9.54; p = 0.001). In the separate Model 2, LMR ≤ 2.89 was also confirmed as an independent predictor (aOR: 2.85; 95% CI: 1.24–6.55; p = 0.014).
Conclusion: Elevated NLR and reduced LMR at admission are robust, independent indicators of stroke severity in this Indonesian cohort. These accessible hematological biomarkers reflect the divergent trajectories of post-ischemic neuroinflammation—innate immune hyperactivity and adaptive immune exhaustion. They provide a cost-effective method for risk stratification in resource-limited settings, warranting their integration into routine initial assessment protocols
Efficacy and Safety of Adjunctive Corticosteroids in Non-HIV Pneumocystis jirovecii Pneumonia with Respiratory Failure: A Systematic Review and Meta-Analysis of Randomized and Observational Studies
Get PDFBackground: Pneumocystis jirovecii pneumonia in HIV-negative immunocompromised patients carries a mortality rate significantly higher than in the HIV-positive population. While adjunctive corticosteroids are the standard of care for HIV-associated pneumonia to prevent Immune Reconstitution Inflammatory Syndrome, their efficacy in non-HIV patients remains controversial due to differing immunopathogenesis. This study evaluated the efficacy and safety of adjunctive corticosteroids in non-HIV patients with respiratory failure, specifically addressing the discordance between historical observational data and recent randomized evidence.
Methods: We conducted a systematic review and meta-analysis in accordance with PRISMA guidelines, searching databases from January 2014 to July 2025. We included randomized controlled trials and observational studies of non-HIV adults with pneumonia receiving adjunctive corticosteroids. To address methodological heterogeneity, we performed stratified analyses separating randomized trial data from observational cohorts and conducted sensitivity analyses to account for outliers. Risk of bias was assessed using Cochrane RoB-2 and the Newcastle-Ottawa Scale.
Results: Ten studies comprising 2,900 patients were analyzed. The randomized trial demonstrated no statistically significant reduction in 28-day mortality with corticosteroids (21.5% vs 32.4%, p=0.069). In the observational arm, initial pooled analysis suggested benefit, but sensitivity analysis removing a large administrative database study shifted the result to null. Crucially, higher cumulative steroid doses were associated with increased 90-day mortality (Hazard Ratio 1.01 per 100mg equivalent; p<0.05) and a significantly increased risk of secondary infections and hyperglycemia. Subgroup analysis revealed no benefit for pulse-dose regimens over standard dosing.
Conclusion: Unlike in HIV, adjunctive corticosteroids do not confer a consistent survival benefit in non-HIV Pneumocystis pneumonia and are associated with dose-dependent toxicity. The routine use of corticosteroids should be abandoned in favor of a cautious approach restricted to severe, early hypoxemia using standard rather than pulse doses
Precipitation of Occult Lymphomatous Hemorrhage by Early Initiation of Factor Xa Inhibitors: A Pharmacovigilance Case Study and Critical Reappraisal of DOAC Safety
Get PDFBackground: The concurrent management of cancer-associated thrombosis (CAT) and active malignancy represents a precarious clinical equilibrium, particularly when the neoplasm involves occult extranodal gastrointestinal (GI) sites. While direct oral anticoagulants (DOACs) have largely supplanted low-molecular-weight heparin (LMWH) as the standard of care for CAT, emerging pharmacovigilance data suggest a specific vulnerability in patients with luminal GI malignancies.
Case presentation: We report the case of a 76-year-old frail female presenting with extensive left iliofemoral deep vein thrombosis (DVT). Diagnostic evaluation identified a perfect storm of pathology: Stage IV diffuse large B-cell lymphoma (DLBCL) with bulky retroperitoneal lymphadenopathy encasing the inferior vena cava (IVC) and a suspicious infiltrative mass in the proximal jejunum. Following standard guidelines, the patient was initiated on rivaroxaban. However, this intervention precipitated a catastrophic upper GI hemorrhage (hemoglobin drop to 6.5 g/dL) within 96 hours. A retrospective pharmacokinetic audit revealed critical predisposing factors: severe hypoalbuminemia (1.6 g/dL) increasing the free drug fraction, and an estimated glomerular filtration rate (eGFR) <30 mL/min, suggesting the patient was effectively overdosed relative to her physiological clearance.
Conclusion: The empiric use of rivaroxaban in elderly patients with uncharacterized abdominal masses, renal impairment, and cachexia carries unacceptable hemorrhagic risks. We advocate for a systematic bleed-risk stratification protocol, prioritizing LMWH or Apixaban, and the judicious use of IVC filters as bridging therapies in high-risk phenotypes
Psoriasiform Digital Bowen’s Disease: A Diagnostic Challenge and Short-Term Response to Liquid Nitrogen Cryotherapy
Get PDFBackground: Bowen’s disease (BD), or squamous cell carcinoma in situ, classically presents as a slowly enlarging erythematous plaque on sun-exposed skin. However, digital Bowen’s disease represents a distinct and rare clinical subset that frequently poses a significant diagnostic dilemma. Due to its unique anatomical location and morphological variability, digital BD often masquerades as benign inflammatory dermatoses, particularly psoriasis or chronic eczema, leading to dangerous therapeutic delays.
Case presentation: We report the case of a 46-year-old male presenting with a solitary, rough, erythematous plaque on the dorsal aspect of the left index finger that had persisted for one year. The lesion was initially misdiagnosed and treated as an inflammatory condition without success. Detailed dermoscopic evaluation revealed a specific "psoriasiform" vascular pattern characterized by clustered glomerular vessels and surface scaling, raising suspicion for malignancy. Histopathological analysis confirmed the diagnosis of Bowen’s disease, demonstrating full-thickness epidermal atypia with psoriasiform hyperplasia. Notably, the presence of histological koilocytic atypia suggested a potential synergistic etiology involving Human Papillomavirus (HPV) infection alongside chronic ultraviolet exposure. The patient was treated with a tissue-sparing protocol of liquid nitrogen cryotherapy to preserve digital function.
Conclusion: Complete clinical resolution of the lesion was observed at the three-week follow-up interval, resulting in a hypopigmented macule with full preservation of joint mobility. This case highlights the critical necessity of distinguishing "psoriasiform" malignancies from true inflammatory diseases through the recognition of specific vascular arrangements in dermoscopy. Furthermore, it suggests that cryotherapy is a pragmatic, function-sparing alternative to surgical excision for digital malignancies, provided that rigorous long-term surveillance is maintained to monitor for recurrence
Pharmacological and Non-Pharmacological Strategies for Sedation and Analgesia in Critically Ill Children: A Systematic Review and Narrative Synthesis
Get PDFBackground: The management of pain and agitation in the Pediatric Intensive Care Unit (PICU) is critical for patient comfort and preventing adverse outcomes. A wide array of sedation and analgesia strategies exists, but a synthesized appraisal of contemporary evidence is needed to guide clinical practice. This systematic review evaluates the efficacy and safety of various pharmacological and non-pharmacological interventions for sedation and analgesia in critically ill children.
Methods: A systematic search was conducted in PubMed, Embase, Cochrane CENTRAL, and CINAHL for studies published between January 2020 and December 2024. Following the PRISMA 2020 guidelines, two independent reviewers screened studies, extracted data, and assessed the risk of bias using the Cochrane RoB 2 tool for Randomized Controlled Trials (RCTs) and the Newcastle-Ottawa Scale (NOS) for observational studies.
Results: From 4,366 identified records, five studies (two RCTs, three observational) involving 875 patients met the inclusion criteria. Study 1, an RCT (n=120), found that adjunctive ketamine significantly reduced mechanical ventilation duration by a mean of 2.1 days (95% CI: 1.2-3.0, p=0.001) compared to standard care. Study 3, a prospective cohort study (n=350), linked continuous sedation to longer PICU stays (median 9 vs. 6 days, p<0.001) and a higher incidence of iatrogenic withdrawal syndrome (45% vs. 18%, p<0.001) compared to intermittent sedation. Study 4, an RCT on music therapy (n=85), demonstrated a significant reduction in postoperative pain scores. Observational studies supported the opioid-sparing effects of multimodal analgesia (Study 5) and noted differences in recovery profiles between midazolam and propofol (Study 2).
Conclusion: This review highlights the benefits of a multimodal, goal-directed approach to pediatric sedation and analgesia. Adjunctive ketamine and non-pharmacological interventions show promise in reducing opioid reliance and improving clinical outcomes. Protocols favoring intermittent sedation may reduce length of stay and withdrawal incidence. These findings support a paradigm shift away from deep, continuous sedation towards more nuanced, patient-centered strategies
Ocular Parasitoses in the Globally Mobile Population: A Systematic Review of Etiology, Pathophysiology, and Clinical Management
Get PDFBackground: The unprecedented scale of global travel has amplified the diagnostic challenge of ocular parasitoses in non-endemic regions. These infections, while rare, can cause severe visual morbidity and are often misdiagnosed. This systematic review synthesizes the current evidence on parasitic eye infections in international travelers to create a comprehensive, state-of-the-art resource for clinicians.
Methods: A systematic literature search was conducted in PubMed, Scopus, ProQuest, and the Cochrane Library in accordance with the PRISMA 2020 guidelines. The search included terms for parasitic eye diseases and international travelers. All case reports, case series, and observational studies published in English detailing confirmed ocular parasitic infections in patients with a history of international travel were eligible. Data on demographics, travel, clinical presentation, diagnosis, and management were extracted from all eligible studies, and their methodological quality was assessed using the Joanna Briggs Institute (JBI) checklist. A qualitative narrative synthesis of the findings was performed.
Results: From an initial 1,408 records, 19 studies met the full inclusion criteria and were included in the final synthesis. These studies detailed infections from a wide range of helminthic and protozoan pathogens, including Loa loa, Dirofilaria spp., Thelazia callipaeda, Gnathostoma spp., Onchocerca volvulus, Toxoplasma gondii, Trypanosoma cruzi, Acanthamoeba spp., and Taenia solium (cysticercosis). Infections were acquired across Africa, Asia, and the Americas. Clinical presentations were highly diverse, ranging from migrating subconjunctival worms to sight-threatening chorioretinitis, keratitis, and intraocular cysts. Diagnosis consistently relied on a combination of high-magnification biomicroscopy, advanced serological and molecular assays like PCR, and targeted imaging. Management was pathogen-specific, involving microsurgical extraction for accessible helminths and tailored antimicrobial therapy for protozoan and systemic infections.
Conclusion: Ocular parasitoses represent a critical diagnostic challenge in returning travelers. A detailed travel and exposure history is the single most important tool to guide the differential diagnosis. Effective management requires a high index of suspicion and a collaborative, interdisciplinary approach to prevent irreversible vision loss
Diagnostic Laparoscopy Versus Routine Exploratory Laparotomy in Hemodynamically Stable Abdominal Trauma: A Systematic Review and Meta-Analysis of Non-Therapeutic Intervention Rates and Clinical Outcomes
Get PDFBackground: Exploratory laparotomy (EL) has traditionally been the standard for evaluating significant abdominal trauma, but it carries a high rate of non-therapeutic procedures and associated morbidity. Diagnostic laparoscopy (DL) has emerged as a minimally invasive alternative, though its precise benefits remain to be quantified by a comprehensive meta-analysis of recent evidence. This study aims to compare the rates of non-therapeutic laparotomy and key clinical outcomes between DL and EL in the management of hemodynamically stable patients with abdominal trauma.
Methods: Following PRISMA guidelines, a systematic search of PubMed, Scopus, Web of Science, and the Cochrane Library was conducted for studies published between January 2015 and February 2025. We included comparative studies (randomized controlled trials and observational studies) evaluating DL versus EL in adult, hemodynamically stable patients with blunt or penetrating abdominal trauma. The primary outcome was the rate of non-therapeutic laparotomy. Secondary outcomes included overall postoperative morbidity, surgical site infection (SSI) rates, length of hospital stay (LOS), and mortality. A random-effects model was used for meta-analysis to calculate pooled Odds Ratios (OR) and Mean Differences (MD) with 95% Confidence Intervals (CI).
Results: Eight studies involving 1,550 patients (775 in the DL group, 775 in the EL group) were included. The DL group had a significantly lower rate of non-therapeutic laparotomy compared to the EL group (11.5% vs. 38.8%; pooled OR 0.18, 95% CI [0.10, 0.31], p<0.00001; I2=45%). Furthermore, DL was associated with a significant reduction in overall morbidity (OR 0.45, 95% CI [0.34, 0.60], p<0.00001; I2=22%) and SSI rates (OR 0.38, 95% CI [0.24, 0.61], p<0.0001; I2=0%). The mean LOS was shorter in the DL group by 3.15 days (MD -3.15, 95% CI [-3.88, -2.42], p<0.00001; I2=78%). There was no significant difference in mortality rates between the two groups (OR 0.85, 95% CI [0.45, 1.62], p=0.62; I2=0%).
Conclusion: In hemodynamically stable patients with abdominal trauma, a selective strategy involving diagnostic laparoscopy drastically reduces the likelihood of non-therapeutic surgical intervention. This approach is also associated with significantly lower postoperative morbidity, fewer surgical site infections, and a shorter hospital stay without compromising patient survival. These findings strongly support the integration of diagnostic laparoscopy as a primary diagnostic and therapeutic tool in modern trauma management algorithms
Presumed Polymyositis in Chronic Hepatitis C: Navigating Diagnostic Uncertainty and Therapeutic Imperatives in Recurrent Myopathy
Get PDFBackground: Polymyositis (PM) is a cell-mediated inflammatory myopathy for which viral triggers, particularly the Hepatitis C virus (HCV), are increasingly recognized. The convergence of these conditions creates a formidable clinical scenario, often compelling urgent therapeutic intervention despite incomplete diagnostic data. This report explores the management of such a case, highlighting the pragmatic decision-making required when definitive investigations are deferred.
Case presentation: A 48-year-old male with untreated chronic HCV infection (Genotype 1b, viral load 2.8 x 10⁶ IU/mL) presented with a debilitating relapse of severe, symmetric proximal muscle weakness, three years after a similar episode. He exhibited profound weakness (Medical Research Council grade 2/5 in hip flexors) and marked myonecrosis (Creatine Kinase 8,572 U/L). Although comprehensive myositis-specific autoantibodies were negative, a strong clinical and biochemical profile led to a presumptive diagnosis of an acute PM exacerbation. Definitive diagnostics, including muscle biopsy, were deferred by the patient. Empirical treatment with high-dose corticosteroids and azathioprine was initiated, predicated on a careful risk-benefit analysis concerning immunosuppression in active viral infection. This strategy resulted in rapid and significant clinical and biochemical improvement. The patient was subsequently scheduled for direct-acting antiviral therapy to address the underlying viral trigger.
Conclusion: This case underscores the critical challenge of managing severe, presumed autoimmune disease in the face of diagnostic ambiguity. It demonstrates that a therapeutic strategy guided by strong clinical evidence can be effective for controlling acute, disabling flares. Furthermore, it champions a necessary dual-paradigm approach: acute immunomodulation to preserve function, followed by targeted antiviral therapy to eradicate the probable etiological trigger, thereby aiming to prevent future recurrence and achieve durable remission