Bioscientia Medicina : Journal of Biomedicine and Translational Research

Synergistic Effects of Stem Cell Integration on Cochlear Implant Performance in Sensorineural Hearing Loss: A Systematic Review and Meta-Analysis of Neural Preservation and Speech Perception

2026-03-04T02:09:05+00:00

Background: Cochlear implantation represents the paramount intervention for severe-to-profound sensorineural hearing loss. However, device efficacy is fundamentally constrained by retrograde degeneration of spiral ganglion neurons and post-insertional intracochlear fibrosis. This study aimed to quantitatively evaluate the synergistic efficacy of integrating stem cell therapies with cochlear implants to preserve neural architecture and enhance auditory functional outcomes.

Methods: A systematic review and meta-analysis were executed following PRISMA guidelines. Comprehensive searches of electronic databases utilized specific Medical Subject Headings targeting biohybrid electrodes, mesenchymal stem cells, and spiral ganglion survival. Inclusion criteria strictly selected controlled in vivo preclinical models and human clinical trials evaluating concurrent stem cell application with implantation. Risk of bias was assessed utilizing SYRCLE and ROBINS-I tools. Random-effects models synthesized Standardized Mean Differences for neural preservation, with subgroup analyses evaluating delivery modalities.

Results: Eight pivotal studies met stringent inclusion criteria. Meta-analysis demonstrated a highly significant preservation of spiral ganglion density in stem cell-integrated cohorts compared to implant-alone controls (Pooled Standardized Mean Difference = 2.45; 95% Confidence Interval: 1.54–3.36; p < 0.001). Subgroup analysis revealed that electrode coating yielded superior neuroprotection compared to bolus injections. Electrophysiological data demonstrated significantly lowered Electrically Evoked Auditory Brainstem Response thresholds. Clinical cohorts exhibited stable impedances and rapid improvements in speech perception.

Conclusion: Stem cell-integrated cochlear implants orchestrate a potent bio-electronic synergy, modulating neuroinflammation and mitigating neural degeneration primarily through paracrine neurotrophic signaling. This bio-electronic integration represents a transformative paradigm in auditory rehabilitation, maximizing the fidelity of neural stimulation and optimizing clinical outcomes.

Admission Serum Procalcitonin Thresholds and the PELOD-2 Score: A Prospective Analytical Study for Identifying Risk Ratios of Severe Organ Dysfunction in Pediatric Critical Care

2026-03-03T19:06:25+00:00

Background: Multiple organ dysfunction syndrome (MODS) remains a predominant cause of mortality in Pediatric Intensive Care Units (PICUs). While the Pediatric Logistic Organ Dysfunction-2 (PELOD-2) score is the established standard for assessing severity, it requires time-consuming serial calculations. There is an urgent need for a rapid, admission-based prognostic biomarker. This study evaluates the association between serum procalcitonin (PCT) and the severity of organ dysfunction in critically ill children.

Methods: A prospective cross-sectional study was conducted at Dr. Moewardi Regional General Hospital, Indonesia, involving 25 children aged 1 month to 18 years with suspected infection. Organ dysfunction was quantified using the PELOD-2 score, and serum PCT was measured via Enzyme-Linked Fluorescent Assay (ELFA) within 24 hours of admission. Statistical analysis utilized Spearman’s rank correlation, multivariate linear regression, and Receiver Operating Characteristic (ROC) curve analysis.

Results: The cohort had a median age of 12 months. The median PCT level was 0.88 ng/mL. A significant positive correlation was observed between serum PCT and PELOD-2 scores (r = 0.39, p = 0.051; multivariate beta = 0.42, p = 0.043). ROC analysis identified a PCT threshold of greater than 11 ng/mL as the optimal indicator for moderate-to-severe organ dysfunction (AUC 0.82). Patients exceeding this threshold had a significantly elevated risk (Risk Ratio = 2.20; 95 percent CI: 1.15–4.24; p = 0.035).

Conclusion: Early serum procalcitonin measurement serves as a powerful independent factor associated with organ dysfunction severity. A cutoff value of greater than 11 ng/mL significantly stratifies risk, allowing clinicians to anticipate the progression of organ failure.

Evaluating the Indigenous Probiotic Lactococcus lactis D4 as an Adjuvant to Capecitabine: Modulation of NF-κB in a Colorectal Carcinogenesis Model

2026-03-04T19:07:12+00:00

Background: Chronic inflammation driven by the nuclear factor kappa-B (NF-κB) signaling pathway is a fundamental driver of colorectal cancer (CRC) pathogenesis, promoting tumor survival, mucosal proliferation, and profound chemoresistance. Capecitabine is a standard first-line fluoropyrimidine chemotherapy; however, its clinical utility is frequently compromised by dose-limiting toxicities and the activation of inflammatory feedback loops. Lactococcus lactis D4, a novel probiotic strain isolated from traditional Indonesian fermented buffalo milk (dadih), possesses well-documented immunomodulatory properties.

Methods: A randomized controlled experimental study was conducted utilizing male Sprague-Dawley rats (n=37). Colorectal carcinogenesis was chemically induced via intraperitoneal administration of 1,2-dimethylhydrazine (DMH). Following strict histopathological confirmation of malignancy, the cohort was randomized into five distinct groups: Negative Control, Positive Control, L. lactis D4 monotherapy, Capecitabine monotherapy, and Combination therapy. Interventions were administered daily for 14 days. Outcomes included NF-κB protein expression assessed via immunohistochemistry (IHC) and targeted gene expression quantification via RT-qPCR.

Results: Immunohistochemical analysis demonstrated that the positive control group exhibited significantly elevated NF-κB protein expression (35.87 ± 13.53%). Capecitabine monotherapy significantly reduced this expression to 16.07 ± 3.79% (p=0.003). The Combination therapy achieved a profound reduction in NF-κB protein expression down to 12.99 ± 4.92%; however, this was not statistically superior to Capecitabine alone (p=1.000). Conversely, RT-qPCR analysis revealed no statistically significant difference in NF-κB mRNA levels among the experimental groups (p=0.094).

Conclusion: The combination of L. lactis D4 and Capecitabine effectively reduces NF-κB protein expression in a preclinical CRC model, achieving suppression levels comparable to primary chemotherapy. The distinct discordance between the significant protein suppression and the sustained mRNA expression levels suggests potential post-transcriptional or post-translational regulatory mechanisms that warrant further targeted molecular investigation.

Severity Matters: The Differential Impact of Mild versus Severe Portal Hypertension on Post-Hepatectomy Liver Failure — A Systematic Review and Meta-Analysis

2026-03-04T19:06:55+00:00

Background: Post-hepatectomy liver failure (PHLF) remains the principal cause of mortality following liver resection for malignancies, particularly in the context of hepatocellular carcinoma (HCC) and cirrhosis. While portal hypertension (PH) has traditionally been viewed as a monolithic contraindication to surgery, emerging evidence suggests that the risk it confers is heterogeneous. This study investigates the hypothesis that the risk of PHLF is strictly severity-dependent.

Methods: A systematic review and meta-analysis were conducted on observational studies involving patients undergoing hepatectomy for liver malignancies. Search strategies targeted studies stratifying outcomes by PH severity (mild vs. severe). Primary outcomes were the incidence of PHLF defined by ISGLS criteria. Data were synthesized using random-effects models to calculate pooled odds ratios (OR).

Results: Ten studies comprising 4,978 patients were included. The overall presence of PH significantly increased PHLF risk (Pooled OR 3.12; 95% CI: 2.15–4.53; p<0.001). However, stratification revealed a profound divergence: Severe PH (defined as HVPG ≥10 mmHg or clinically significant varices) was associated with a drastic risk escalation (OR 5.86; 95% CI: 2.19–15.65), whereas Mild PH showed a significantly lower risk profile (OR 2.45; 95% CI: 1.10–5.40). Sensitivity analyses confirmed that non-invasive surrogates for PH performed comparably to invasive hemodynamic monitoring in predicting failure.

Conclusion: The risk of PHLF is not binary but graded. Severe portal hypertension represents a prohibitive risk state characterized by hemodynamic intolerance to parenchymal reduction. Conversely, mild portal hypertension constitutes a distinct, manageable clinical entity where liver resection remains safe under optimized conditions. Surgical candidacy should be determined by severity grading rather than the mere presence of portal hypertension.

Efficacy, Safety, and Long-Term Continuation of Vaginal Pessaries for Pelvic Organ Prolapse: A Systematic Review and Meta-Analysis

2026-03-05T02:49:13+00:00

Background: Pelvic organ prolapse (POP) represents a profound failure of pelvic floor anatomy, significantly impairing patient quality of life through complex functional and anatomical derangements. Vaginal pessaries stand as the primary conservative intervention. However, the contemporary literature remains fragmented regarding their long-term adherence kinetics and comparative pathophysiological efficacy against definitive surgical reconstruction.

Methods: A systematic review and meta-analysis were conducted, adhering strictly to PRISMA 2020 guidelines. Major scientific databases, including PubMed, Scopus, and Cochrane CENTRAL, were systematically searched for randomized controlled trials and prospective cohorts published between 2016 and 2026. Data synthesis employed a random-effects model, calculating Standardized Mean Differences (SMD) for validated symptom scores and pooled prevalence for longitudinal continuation and adverse events.

Results: Seven major studies comprising 2,772 participants were included. The pooled short-term continuation rate under twelve months was 76.6% (95% CI 68.2–85.0%), which demonstrated a predictable decline to 53.4% (95% CI 45.1–61.7%) beyond one year. Meta-analysis of validated symptom scores (PFDI-20) demonstrated a robust, transformative reduction in prolapse distress (SMD -1.24; 95% CI -1.56 to -0.92, p < 0.0001), showing statistical equivalence to surgical outcomes in advanced prolapse cohorts. Adverse events were uniformly mild, dominated by vaginal discharge (pooled prevalence 18.6%) and occult stress incontinence (11.4%).

Conclusion: Vaginal pessaries provide a high magnitude of pathophysiological symptom relief that parallels surgical correction in the short to medium term. By biomechanically restoring the pelvic axes, pessaries neutralize visceral nerve traction. While long-term continuation inevitably declines due to behavioral fatigue, the superior safety profile establishes pessaries as a definitive therapeutic modality.

Digital Panoramic Radiography for Forensic Dental Age Estimation: A Biostatistical Validation Demonstrating the Superiority of the Willems Method over the Cameriere Approach in a Pediatric Cohort (6–14 Years)

2026-03-05T02:50:14+00:00

Background: Accurate dental age (DA) estimation is critical in pediatric dentistry, orthodontics, and forensic identification. Radiomorphological and radiometric techniques are widely utilized, yet their accuracy varies across diverse ethnic populations. This study aims to evaluate and compare the accuracy of the Willems (radiomorphological) and Cameriere (radiometric) methods against chronological age (CA) in a pediatric population in Padang, Indonesia.

Methods: A retrospective cross-sectional study was conducted using 168 digital panoramic radiographs of children (96 males, 72 females) aged 6 to 14 years. Dental maturation was assessed digitally utilizing CorelDraw X7. The Willems method evaluated the developmental stages of seven left mandibular teeth, while the Cameriere method measured open apices. Statistical analysis included paired t-tests, Pearson correlation coefficients, Mean Absolute Error (MAE), and Root Mean Square Error (RMSE) to rigorously assess accuracy.

Results: The mean CA of the cohort was 9.91 ± 0.28 years. The Cameriere method consistently underestimated DA across all age cohorts, yielding a mean DA of 8.63 ± 0.93 years (p < 0.05). Conversely, the Willems method demonstrated a mean DA of 10.73 ± 1.06 years, showing higher overall concordance with CA without statistically significant broad-scale deviations in the overarching comparative model (p < 0.05), despite minor stage-specific variances. Both methods exhibited a near-perfect positive correlation with CA (r > 0.98).

Conclusion: The Willems radiomorphological method significantly outperforms the radiometric Cameriere approach in this specific Southeast Asian pediatric demographic. The Cameriere method requires population-specific formulaic adaptation due to consistent physiological underestimation.

General Anesthesia and Modified Rapid Sequence Induction for Emergency Cesarean Delivery in an Eclamptic Adolescent with Severe Thrombocytopenia

2026-03-05T02:49:40+00:00

Background: Eclampsia complicated by severe thrombocytopenia presents a critical anesthetic challenge, often representing an absolute contraindication to neuraxial anesthesia. When alternative approaches are mandated, General Anesthesia with Rapid Sequence Induction or a modified rapid sequence approach is crucial for high-risk obstetric emergencies.

Case presentation: A 16-year-old primigravida at 35 weeks gestation presented with eclampsia, acute fetal distress, and severe thrombocytopenia. Initial vitals showed a blood pressure of 150/98 mmHg. Laboratory findings confirmed severe preeclampsia with a critical platelet count of 42,000/µL. An airway assessment revealed a Mallampati class II airway with mild pharyngolaryngeal edema. Due to the high risk of spinal epidural hematoma, neuraxial anesthesia was contraindicated. An emergency cesarean section was performed using a modified rapid sequence induction. Following preoxygenation, induction was achieved with fentanyl 100 µg, midazolam 3 mg, and propofol 100 mg. Due to institutional unavailability of rocuronium, atracurium 30 mg was utilized. After a 2.5-minute onset interval utilizing apneic oxygenation and continuous cricoid pressure, the patient was successfully intubated on the first attempt with a Macintosh size 3 blade. The intraoperative course was hemodynamically stable.

Conclusion: A modified rapid sequence induction utilizing atracurium provides an effective alternative for airway control and physiological stability in eclamptic adolescents with coagulopathy, particularly in resource-limited settings where standard rapid-acting non-depolarizing agents are unavailable.

Comparative Prognostic Value of Podocyturia Versus Microalbuminuria in Predicting Diabetic Nephropathy Progression: A Meta-Analysis

2026-03-07T19:07:39+00:00

Background: Diabetic nephropathy represents the primary etiology of end-stage renal disease globally. Historically, clinical practice relied upon microalbuminuria as the definitive non-invasive biomarker for early detection. However, advanced histopathological evidence establishes that severe structural degradation of the glomerular filtration barrier, specifically the visceral epithelial cells known as podocytes, occurs significantly earlier than the clinical manifestation of microalbuminuria. Podocyturia, defined as the urinary excretion of intact podocytes and podocyte-specific proteins or messenger RNA, emerged as a direct indicator of active glomerular injury. This meta-analysis investigated the comparative prognostic value of podocyturia versus microalbuminuria in predicting the longitudinal progression of diabetic nephropathy.

Methods: A systematic literature search was executed to identify comparative clinical studies evaluating both podocyturia and microalbuminuria in diabetic cohorts. Seven essential manuscripts met rigorous inclusion criteria. Following peer-review recommendations, statistical pooling was strictly stratified by study design. Data extraction focused on prognostic effect sizes in longitudinal cohorts and diagnostic effect sizes in cross-sectional cohorts. Statistical synthesis utilized DerSimonian-Laird random-effects models to calculate pooled Standardized Mean Differences and 95% confidence intervals.

Results: Synthesized data demonstrated podocyturia possessed a significantly superior prognostic value compared to microalbuminuria. In longitudinal cohorts, the pooled Standardized Mean Difference for podocyturia predicting progression was 1.95 (95% CI: 1.50 to 2.40, p < 0.001), whereas microalbuminuria was 0.58 (95% CI: 0.25 to 0.91, p = 0.04). Cross-sectional data similarly demonstrated massive podocyte biomarker elevation in strictly normoalbuminuric patients.

Conclusion: Podocyturia represents a substantially more accurate, sensitive, and temporally earlier prognostic biomarker for diabetic nephropathy progression than microalbuminuria. Incorporating podocyte-specific urinary quantification into routine clinical practice could fundamentally alter early therapeutic intervention strategies, shifting the focus toward arresting primary podocyte detachment.

Pulse Corticosteroid Therapy for the Complete Reversal of Severe Bilateral Sudden Sensorineural Hearing Loss in High-Activity Systemic Lupus Erythematosus: A Comprehensive Case Report

2026-03-07T19:07:20+00:00

Background: Sudden sensorineural hearing loss (SSNHL) is an alarming otologic emergency. While predominantly idiopathic, it can manifest as a rare, severe complication of autoimmune disorders, including systemic lupus erythematosus (SLE). The underlying pathophysiology in SLE-induced SSNHL often involves aggressive microvascular compromise and immune complex deposition.

Case presentation: We present the case of a 21-year-old female with a history of SLE, congestive heart failure, and previous non-hemorrhagic stroke, who presented with acute-onset bilateral hearing loss of one day's duration. She exhibited high SLE disease activity with a MEX-SLEDAI score of 12. Initial pure-tone audiometry revealed very severe SSNHL in the right ear (Air Conduction [AC] 98.75 dB) and severe SSNHL in the left ear (AC 87.5 dB). Due to resource constraints, advanced immunological testing was unavailable; however, a severe lupus flare was confirmed clinically. The patient was immediately treated with intravenous methylprednisolone pulse therapy (500 mg/day) followed by an oral tapering regimen. Subsequent audiometric evaluations demonstrated rapid, complete audiological recovery to normal thresholds bilaterally.

Conclusion: High-dose systemic corticosteroid pulse therapy, when initiated within 24 hours of symptom onset, can achieve complete reversal of severe bilateral SSNHL in patients with high-activity SLE. Rapid recognition and aggressive immunosuppression are vital to rescuing cochlear function, even in resource-limited clinical environments.

Acute Urinary Retention and Obstructive Uropathy Secondary to Imperforate Hymen in a Premenarchal Adolescent: A Comprehensive Case Report

2026-03-10T19:07:57+00:00

Background: Imperforate hymen, occurring in approximately 1 in 1,000 to 1 in 10,000 female births, is a rare congenital anomaly of the female reproductive tract that frequently remains undiagnosed until menarche. It can present atypically as acute urinary retention due to mechanical pelvic compression.

Case presentation: A 12-year-old premenarchal girl presented to the emergency department with an 8-hour history of acute urinary retention, cyclic lower abdominal pain, and nausea. Her history revealed a 4-month progression of dysuria and painful defecation. Physical examination demonstrated a bulging, bluish vaginal membrane. Transabdominal ultrasonography revealed a 520 mL hematocolpos severely compressing the bladder neck, resulting in bilateral mild hydroureteronephrosis. The variance between the imaging estimate (520 mL) and the actual surgical yield (480 mL) reflects standard clinical overestimation in ultrasonographic volume calculations. The patient underwent an emergency cruciate hymenotomy with mucosal marsupialization. Postoperative recovery was uneventful. A 3-month follow-up confirmed the complete resolution of the hydroureteronephrosis and the establishment of normal, unobstructed menses.

Conclusion: Delayed diagnosis of imperforate hymen can precipitate severe obstructive uropathy. Integrating routine external genitalia examinations in premenarchal adolescents presenting with lower urinary tract symptoms is imperative to prevent irreversible urological sequelae.

Cell-Free Regenerative Therapy for Pulmonary Hypertension: Human Breastmilk Stem Cell Secretome Restores Endothelial Barrier Integrity and BMPR2 Signaling Under Hypoxic Stress

2026-03-10T19:07:42+00:00

Background: Pulmonary hypertension (PH) is a severe vascular disorder characterized by chronic hypoxia-induced endothelial dysfunction, leading to aberrant remodeling and right ventricular failure. The human breastmilk-derived stem cell (hBSC) secretome contains bioactive factors that may promote endothelial regeneration. However, the temporal dynamics of secretome-mediated repair on critical structural and signaling molecules remain poorly understood.

Methods: An in vitro experimental study was conducted using human umbilical vein endothelial cells (HUVECs) exposed to severe hypoxia (1% O₂, 10% CO₂, 37°C) to replicate PH-associated endothelial dysfunction. Cells were divided into four groups: normoxia control, hypoxia control, and hypoxia treated with hBSC secretome for 24 and 72 hours. Expression of bone morphogenetic protein receptor type 2 (BMPR2) and vascular endothelial cadherin (VE-cadherin) was quantified via ELISA. CCK-8 assays evaluated cellular viability. Data were analyzed using one-way ANOVA and least significant difference (LSD) post-hoc tests.

Results: Hypoxia significantly diminished cell viability and reduced BMPR2 and VE-cadherin expression compared to normoxia (p<0.001). Administration of hBSC secretome significantly restored BMPR2 and VE-cadherin levels at both 24 and 72 hours (p<0.001), surpassing normoxic baselines. BMPR2 expression plateaued between 24 and 72 hours, while VE-cadherin expression demonstrated sustained functional recovery.

Conclusion: The hBSC secretome actively reverses hypoxia-induced endothelial injury through rapid, time-dependent modulation of BMPR2 signaling and VE-cadherin junctional integrity, presenting a viable cell-free therapeutic target for PH.

Delayed Right-Sided Traumatic Diaphragmatic Rupture Complicated by Hepatothorax and Visceral Herniation a Decade Post-Trauma: A Case Report

2026-03-11T01:24:28+00:00

Background: Traumatic diaphragmatic rupture (TDR) is a rare consequence of high-energy blunt trauma, accounting for less than 1% of all traumatic injuries. Right-sided ruptures are particularly uncommon, representing only 5% to 20% of cases, largely due to the protective anatomical positioning of the liver. Consequently, right-sided injuries are notoriously difficult to detect, often leading to a delayed diagnosis.

Case presentation: We present the case of a 29-year-old female who presented with progressive dyspnea ten years after sustaining a motor vehicle collision. Her initial injury was managed as a right-sided hemothorax, with the diaphragmatic defect remaining undetected. A decade later, imaging revealed an elevated right hemidiaphragm with massive herniation of the liver, gallbladder, transverse colon, and omentum into the right thoracic cavity. The patient underwent a successful abdomino-thoracotomy with primary repair of a 10 cm x 4 cm defect, reinforced with a prosthetic mesh. She was discharged on postoperative day seven with an uneventful recovery.

Conclusion: This case emphatically highlights the persistent, lifelong risk of delayed visceral herniation following thoracoabdominal trauma. A high index of suspicion must be maintained for patients presenting with delayed respiratory symptoms, as prompt surgical intervention yields excellent outcomes.

Therapeutic Efficacy of Thymoquinone in Attenuating Obstructive Renal Fibrosis: A Dose-Response Analysis of Tumor Necrosis Factor-Alpha Suppression and Histopathological Remodeling

2026-03-12T19:08:16+00:00

Background: Chronic kidney disease is characterized by progressive renal fibrosis, a maladaptive process driven by chronic inflammation and extracellular matrix accumulation. Tumor necrosis factor-alpha (TNF-α) plays a central role in this fibrogenic cascade. Thymoquinone (TQ), the primary bioactive compound of Nigella sativa, exhibits potent anti-inflammatory properties.

Methods: In this therapeutic intervention model, 107 male Wistar rats were subjected to Unilateral Ureteral Obstruction (UUO). To test TQ's ability to halt established fibrogenesis, treatment was delayed until day 7 post-obstruction. Rats were randomized to receive TQ intraperitoneally at 5, 10, or 20 mg/kg body weight for 14 days. Outcomes included renal function (urea/creatinine), tubulointerstitial injury (PAS staining), fibrosis area (Sirius Red staining), and localized TNF-α mRNA expression (reverse transcriptase PCR normalized to GAPDH). Data were analyzed using ANOVA followed by Tukey’s Honestly Significant Difference (HSD) test.

Results: UUO induced significant structural injury and upregulated TNF-α expression compared to sham controls (p < 0.001). TQ intervention significantly reduced the tubulointerstitial injury score, with the greatest reduction at 20 mg/kg (p < 0.01). The positively stained fibrotic area exhibited a U-shaped response, maximally decreased at the 10 mg/kg dose (p < 0.01). Similarly, TNF-α mRNA relative expression was significantly suppressed by TQ, exhibiting a pharmacological ceiling effect at 10 mg/kg (p < 0.01).

Conclusion: Thymoquinone administered therapeutically mitigates established structural renal fibrosis and tubulointerstitial injury by downregulating TNF-α-mediated inflammation. A 10 mg/kg dose represents the optimal therapeutic threshold for anti-fibrotic efficacy in obstructive nephropathy.

Dose-Dependent Amelioration of Ureteral Obstruction-Induced Kidney Fibrosis by Thymoquinone via GPx-Mediated Antioxidant Defense

2026-03-15T19:08:32+00:00

Background: Chronic kidney disease inevitably progresses to renal fibrosis, driven heavily by oxidative stress and the depletion of endogenous antioxidants including Glutathione Peroxidase (GPx). Thymoquinone (TQ), a bioactive compound from Nigella sativa, exhibits potent antioxidant properties. This study investigates the dose-dependent efficacy of TQ in mitigating renal fibrosis via GPx modulation in a Unilateral Ureteral Obstruction (UUO) model.

Methods: Thirty male Rattus norvegicus were randomly assigned to six groups (n=5): Sham, UUO + olive oil (Negative Control), UUO without oil, and UUO treated with TQ at 5, 10, and 20 mg/kg body weight for 14 days. Renal function (ureum, creatinine) and oxidative stress (Malondialdehyde) were measured. GPx mRNA expression was quantified using Reverse Transcription-Polymerase Chain Reaction. Tubulointerstitial injury (TII) and Positively Stained Area (PSA) for fibrosis were assessed histopathologically.

Results: UUO induction significantly downregulated GPx expression (median 0.52 versus 1.40 in Sham, p=0.001) and exacerbated TII (score 3.58) and PSA (11.42%). TQ administration dose-dependently upregulated GPx expression, peaking at 20 mg/kg (median 0.62, p=0.009 versus Negative Control). Furthermore, TQ 20 mg/kg significantly reduced the TII score to 2.26 and decreased fibrotic PSA, ameliorating morphological damage.

Conclusion: Thymoquinone exerts potent, dose-dependent antifibrotic and renoprotective effects in obstructive nephropathy by restoring GPx-mediated antioxidant defenses and preventing tubulointerstitial remodeling.

The Ocular Toll of Drug Tourism: A Systematic Review and Meta-Analysis of Cannabis and Methamphetamine Impact on Retinal Architecture and Pupillary Dynamics

2026-03-16T01:50:53+00:00

Background: Drug tourism involves individuals traveling across international borders to access recreational illicit substances. While psychiatric and cardiovascular toxicities of substances like cannabis and methamphetamine are established, quantitative data regarding their impact on ocular microstructures and functional dynamics remain scarce. This study aims to systematically review and meta-analyze the structural and functional ocular alterations induced by these substances.

Methods: A systematic review and meta-analysis complying with Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines were conducted. Electronic databases (PubMed, Scopus, Web of Science, Cochrane Library) were searched from inception to January 2026. Data extraction targeted pupillary dynamics and structural optical coherence tomography measurements. Methodological quality was assessed using the Newcastle-Ottawa Scale and Cochrane Risk of Bias tools. A DerSimonian-Laird random-effects model was utilized in Review Manager 5.4 to pool continuous data, calculating Standardized Mean Differences and 95% Confidence Intervals. Heterogeneity was evaluated via the I-squared statistic.

Results: Nine primary research articles were included. The mean Newcastle-Ottawa Scale score was 8.1, indicating a low risk of bias. Chronic cannabis users exhibited significantly reduced pupillary constriction velocity (Standardized Mean Difference -0.85, 95% Confidence Interval -1.20 to -0.50, p < 0.001), prolonged reaction latency (Standardized Mean Difference 0.65, 95% Confidence Interval 0.30 to 1.00, p < 0.01), and decreased corneal endothelial cell density (Standardized Mean Difference -0.78, 95% Confidence Interval -1.15 to -0.41, p < 0.001). Methamphetamine abuse was associated with profound global retinal nerve fiber layer thinning (Standardized Mean Difference -1.12, 95% Confidence Interval -1.55 to -0.69, p < 0.001) and reduced minimum rim width (Standardized Mean Difference -0.95, p < 0.001).

Conclusion: Recreational cannabis and methamphetamine abuse cause significant, quantifiable ocular morbidity. Methamphetamine induces ischemic neurodegenerative retinal loss, while cannabis disrupts autonomic pupillary pathways and corneal integrity. Comprehensive ophthalmological screening is critical for individuals with substance abuse histories.

Navigating Diagnostic Constraints in Pediatric Herpes Simplex Encephalitis: Successful Empirical Acyclovir Therapy without PCR Confirmation

2026-03-16T01:36:04+00:00

Background: Herpes simplex encephalitis is an acute or subacute disease associated with focal or global cerebral dysfunction caused by herpes simplex virus type 1 or type 2. Without adequate antiviral administration, the mortality rate reaches 70 percent, with only 9 percent of survivors returning to normal function. While cerebrospinal fluid polymerase chain reaction testing is the gold standard for diagnosis, its availability is severely restricted in resource-limited clinical environments.

Case presentation: We report the case of a 4-year-old girl who presented with a profoundly decreased level of consciousness following a five-day history of fluctuating fever. Physical examination revealed a soporific state with a Glasgow Coma Scale of E4V1M1. Initial non-contrast computed tomography of the head was unremarkable. Cerebrospinal fluid analysis demonstrated a mononuclear pleocytosis. Despite the lack of polymerase chain reaction confirmation and the absence of advanced electrophysiological monitoring, the patient was empirically diagnosed with herpes simplex encephalitis based on clinical deterioration and cerebrospinal fluid findings. Immediate management included intravenous acyclovir, dexamethasone, phenobarbital, and supportive care. The patient demonstrated significant clinical improvement and was discharged on day 24 without severe immediate neurological deficits.

Conclusion: The absence of molecular diagnostics and advanced neuro-monitoring must not delay the administration of intravenous acyclovir in pediatric patients exhibiting fever and altered mental status. Empirical antiviral intervention remains the most critical determinant of survival and neurological recovery.

Unveiling Peutz-Jeghers Syndrome in the Fourth Decade: A Rare Case of Colorectal-Predominant Polyposis and High-Grade Dysplasia without Pathognomonic Pigmentation

2026-03-16T08:28:21+00:00

Background: Peutz-Jeghers syndrome (PJS) is a rare autosomal dominant condition characterized by gastrointestinal hamartomatous polyposis and mucocutaneous pigmentation. While typically presenting in childhood with small bowel predominance, adult-onset cases lacking classical phenotypic markers present severe diagnostic challenges.

Case presentation: A 41-year-old male with no significant family history presented with a six-month history of progressive constipation, altered stool caliber, and hematochezia. Clinical examination revealed an absolute absence of pathognomonic mucocutaneous pigmentation. Abdominal imaging and full colonoscopy demonstrated an extensive colorectal polyposis burden extending from the rectosigmoid junction to the caecum. Histopathology of the resected tissue confirmed hamartomatous polyps featuring arborizing smooth muscle cores alongside focal high-grade dysplasia. The patient successfully underwent an elective total proctocolectomy with an ileal J-pouch anal anastomosis and a diverting loop ileostomy. Postoperative recovery was completely unremarkable.

Conclusion: This case underscores the profound phenotypic heterogeneity of PJS. The presence of an extensive colorectal burden and high-grade dysplasia in an adult lacking mucocutaneous pigmentation highlights the definitive malignant potential of hamartomatous polyps and the critical necessity for prompt surgical intervention and tailored surveillance in atypical clinical presentations.

Modulating Patellofemoral Joint Stress Through Targeted Neuromuscular Training in Runners: A Systematic Review and Meta-Analysis

2026-03-23T19:09:08+00:00

Background: Patellofemoral pain syndrome remains a highly prevalent running-related injury, characterized by retropatellar pain exacerbated by knee flexion. While multifactorial, biomechanical imbalances and proximal neuromuscular deficits are primary contributors. This systematic review and meta-analysis evaluated the efficacy of targeted neuromuscular training and gait retraining on pain, functional capacity, and biomechanical parameters in runners with patellofemoral pain syndrome.

Methods: A systematic search and analysis were conducted, incorporating nine randomized controlled trials. Inclusion criteria focused on adult runners diagnosed with patellofemoral pain syndrome undergoing neuromuscular exercise or gait retraining compared to control or standard care. Primary outcomes included self-reported pain and functional status. Standardized Mean Differences with 95 percent confidence intervals were calculated using an inverse-variance random-effects model.

Results: Nine randomized controlled trials involving robust sample sizes were analyzed. The pooled meta-analysis for pain reduction demonstrated a statistically significant large effect size favoring targeted neuromuscular and gait retraining interventions (Standardized Mean Difference = -1.38, 95 percent confidence interval [-1.85, -0.91], p less than 0.001). Functional outcomes also showed significant improvement in the intervention groups (Standardized Mean Difference = 1.51, 95 percent confidence interval [1.02, 2.00], p less than 0.001). Biomechanical analyses indicated significant modulations in hip kinematics, notably reduced peak hip adduction.

Conclusion: Targeted neuromuscular training and gait retraining significantly reduced pain and improved lower extremity function in runners. These interventions successfully modulated patellofemoral joint stress through enhanced proximal control and altered strike mechanics.

Concomitant Erythema Nodosum Leprosum and Bullous Dapsone Hypersensitivity Syndrome in Relapsed Multibacillary Leprosy: Pathophysiological Insights and Therapeutic Strategy

2026-03-27T01:22:25+00:00

Background: Multibacillary leprosy management is frequently complicated by severe immunological reactions and adverse drug events. Erythema nodosum leprosum is an immune-complex-mediated complication, while dapsone hypersensitivity syndrome is an idiosyncratic, potentially life-threatening drug reaction. The concomitant presentation of these distinct entities, especially with bullous eruptions, creates a profound diagnostic and therapeutic dilemma.

Case presentation: A 42-year-old male with a history of relapsed borderline lepromatous leprosy and rheumatoid arthritis presented with exquisitely painful erythematous nodules, high-grade fever, and bullous eruptions exactly 72 hours after the re-initiation of multidrug therapy. Physical examination recorded a Visual Analog Scale pain score of 9. Expanded histopathological evaluation confirmed a dual pathology: extensive dermal neutrophilic infiltration characteristic of Erythema Nodosum Leprosum, occurring alongside pronounced subepidermal blistering and marked eosinophilic exocytosis indicative of a dapsone-induced bullous eruption. Standard multidrug therapy was immediately discontinued. A modified regimen comprising rifampicin, clarithromycin, and carefully titrated immunosuppressants (methylprednisolone and azathioprine) was initiated.

Conclusion: The substitution of dapsone with clarithromycin facilitated rapid clinical resolution of both the bullous eruptions and recurrent immune reactions. This case underscores the critical need for precise temporal tracking, individualized therapeutic modifications, and comprehensive histopathological evaluation in leprosy patients demonstrating complex, overlapping hypersensitivity syndromes.

Renal and Cardiovascular Outcomes of SGLT2 Inhibitors versus ARNI in Cardiorenal Syndrome: A Network Meta-Analysis of Randomized Controlled Trials

2026-03-27T04:23:50+00:00

Background: Cardiorenal syndrome involves complex pathophysiological cross-talk between the heart and kidneys, frequently culminating in refractory pulmonary congestion. Two primary pharmacological pillars, Sodium-Glucose Cotransporter-2 inhibitors and Angiotensin Receptor-Neprilysin Inhibitors, independently provide profound cardiovascular and renal benefits. However, direct comparative efficacy remains unquantified, creating clinical dilemmas in therapeutic sequencing.

Methods: A systematic review and network meta-analysis were conducted utilizing nine pivotal randomized controlled trials. A frequentist network meta-analysis approach utilizing random-effects models was employed. Time-to-event and continuous outcomes were harmonized and pooled utilizing Standardized Mean Differences to allow for indirect head-to-head comparisons between the two drug classes.

Results: The network comprised 43,450 patients. Both therapies significantly reduced cardiovascular events compared to standard care. In indirect comparisons, Angiotensin Receptor-Neprilysin Inhibitors demonstrated a superior reduction in the risk of urgent heart failure hospitalizations (Standardized Mean Difference -0.14; 95 percent Confidence Interval, -0.27 to -0.01) compared to Sodium-Glucose Cotransporter-2 inhibitors. Conversely, regarding the primary composite renal outcome (estimated glomerular filtration rate decline, end-stage renal disease, or renal death), Sodium-Glucose Cotransporter-2 inhibitors exhibited overwhelming statistical superiority over Angiotensin Receptor-Neprilysin Inhibitors (Indirect Standardized Mean Difference -0.35; 95 percent Confidence Interval, -0.50 to -0.20; p<0.001).

Conclusion: Both drug classes are indispensable for managing cardiorenal syndrome. Angiotensin Receptor-Neprilysin Inhibitors provide superior acute cardiovascular hemodynamic relief, whereas Sodium-Glucose Cotransporter-2 inhibitors offer unparalleled long-term structural protection of renal function. Tailored therapeutic sequencing must leverage these distinct physiological advantages.

Metabolic and Hematologic Synergism in Idiopathic Intracranial Hypertension: Reversal of Bilateral Papilledema via Multidisciplinary Gynecological and Systemic Interventions

2026-04-02T19:11:46+00:00

Background: Idiopathic Intracranial Hypertension (IIH) conventionally presents with elevated intracranial pressure without structural etiologies, heavily associating with central adiposity. Emerging clinical frameworks recognize the intersecting roles of hematologic and metabolic abnormalities, notably iron deficiency anemia and hypovitaminosis D.

Case presentation: A 41-year-old obese female (Body Mass Index 30.04 kg/m²) presented with progressive, painless bilateral visual blurring. Initial evaluation revealed a right eye visual acuity of 6/7.5 and a severely reduced left eye visual acuity of 1/60, alongside prominent bilateral papilledema and flame-shaped hemorrhages. The patient was incorrectly diagnosed with optic neuritis externally. Upon referral, rigorous evaluation successfully dismantled the misdiagnosis; intact pupillary reflexes, absence of a relative afferent pupillary defect, and an enlarged blind spot pointed definitively to papilledema. A lumbar puncture confirmed an elevated opening pressure of 340 mmH₂O with normal cerebrospinal fluid composition. Targeted systemic profiling uncovered severe iron deficiency anemia (Hemoglobin 7.90 g/dL) driven by chronic menorrhagia from a uterine myoma, compounded by marked hypovitaminosis D. A tailored multidisciplinary intervention was initiated. A conservative acetazolamide dosage (500 mg/day) was utilized to minimize systemic stress, combined with cholecalciferol supplementation, ferrous sulfate, and a laparotomic myomectomy. One month post-operatively, hemoglobin normalized to 11.70 g/dL, visual acuity was fully restored to 6/6 bilaterally, and papilledema completely resolved.

Conclusion: IIH is a multifactorial systemic syndrome. Prompt identification and aggressive correction of hematologic and metabolic drivers, including surgical eradication of hemorrhagic etiologies, are imperative for reversing intracranial hypertension and preventing permanent optic neuropathy.

The Double Inflammatory Burden: Red Cell Distribution Width as an Exploratory Biomarker for Functional Outcome in Ischemic Stroke with Comorbid Systemic Lupus Erythematosus

2026-04-02T19:11:30+00:00

Background: Ischemic stroke in patients with systemic lupus erythematosus (SLE) presents a highly unique clinical phenotype characterized by amplified systemic inflammation, profound endothelial dysfunction, and a pervasive prothrombotic state. The combined, synergistic effect of this double inflammatory burden exacerbates acute neuronal injury and leads to significantly poorer clinical recovery. This study evaluated Red Cell Distribution Width (RDW), a widely available surrogate marker of systemic inflammation, oxidative stress, and impaired erythrocyte deformability, as a prognostic biomarker for functional outcomes in this specific, high-risk inflammatory phenotype.

Methods: In this retrospective analytical pilot study, 34 adult patients diagnosed with acute ischemic stroke and comorbid SLE were analyzed. Admission RDW values, National Institutes of Health Stroke Scale (NIHSS) scores, and 90-day Modified Rankin Scale (mRS) scores were collected. A poor functional outcome was rigorously defined as an mRS score of 3–6. Statistical evaluation included Mann-Whitney U tests, Spearman rank correlation, receiver operating characteristic (ROC) curve analysis, and multivariable logistic regression to adjust for baseline neurological severity.

Results: RDW demonstrated a statistically significant positive correlation with initial stroke severity (NIHSS; r = 0.397; p = 0.020) and 90-day functional disability (mRS; r = 0.711; p < 0.001). The median RDW was significantly higher in patients with poor outcomes compared to those with good outcomes (15.6% versus 13.4%, p < 0.001). ROC analysis yielded an excellent Area Under the Curve of 0.89 (p < 0.001) with an optimal predictive cut-off established at 13.75%. In multivariable analysis adjusting for baseline stroke severity, an admission RDW of 13.75% or higher remained a strongly associated factor for severe long-term disability (adjusted Odds Ratio: 14.82, 95% Confidence Interval: 1.95–112.45, p = 0.009).

Conclusion: RDW is a promising, inexpensive, and universally available prognostic biomarker that demonstrates a strong association with severe functional disability in ischemic stroke patients with comorbid SLE, accurately reflecting the profound neurotoxic impact of the double inflammatory burden.

Intravenous Iron Therapy Reverses Myocardial Iron Deficiency and Improves Functional Capacity in Non-Anemic Heart Failure: A Meta-Analysis of Randomized Controlled Trials

2026-04-02T19:11:15+00:00

Background: Iron deficiency is a profound metabolic comorbidity in chronic heart failure, driving deleterious consequences on patient prognosis and functional independence. Crucially, these detriments manifest entirely independently of circulating hemoglobin. While guidelines advocate for intravenous iron in symptomatic heart failure patients, the isolated efficacy and underlying mechanisms in the strictly non-anemic demographic remain subjects of clinical scrutiny.

Methods: A systematic review and meta-analysis of randomized controlled trials was executed, adhering to PRISMA guidelines. We aggregated data from 10 trials (such as FAIR-HF, CONFIRM-HF, HEART-FID, FAIR-HF2). The primary endpoint was functional capacity improvement, evaluated via the Standardized Mean Difference of the Six-Minute Walk Test distance and Peak Oxygen Consumption. Secondary endpoints incorporated skeletal/myocardial energetics and heart failure hospitalizations. Data from non-anemic subgroups were extracted. Pooled effects were derived using a DerSimonian and Laird random-effects model, accompanied by sensitivity and safety analyses.

Results: Ten trials encompassing 7,545 patients were included, isolating approximately 4,120 individuals within the non-anemic, iron-deficient sub-stratum. Intravenous iron significantly improved functional capacity in non-anemic patients compared to placebo (Standardized Mean Difference: 0.42, 95% Confidence Interval: 0.28 to 0.56, p < 0.001). Mechanistic data revealed significant reductions in phosphocreatine recovery half-times, objectively signifying restored mitochondrial oxidative phosphorylation. Furthermore, intravenous iron yielded a significant reduction in cumulative heart failure hospitalizations within this subgroup (Risk Ratio: 0.81, 95% Confidence Interval: 0.72 to 0.91, p = 0.003). Safety profiles indicated a slightly elevated risk of transient hypophosphatemia with specific formulations, though severe adverse events were comparable to placebo.

Conclusion: Intravenous iron therapy successfully reverses the metabolic detriments of myocardial iron deficiency in heart failure patients devoid of anemia, translating into substantial enhancements in exercise capacity and attenuation of morbidity. Routine biochemical screening for iron deficiency should be universally prioritized regardless of baseline hemoglobin.

Efficacy of Anti-IgE Therapy on Concurrent Upper and Lower Airway Outcomes in United Airway Disease: A Systematic Review and Meta-Analysis

2026-04-06T19:11:15+00:00

Background: United Airway Disease represents a paradigm wherein the upper and lower respiratory tracts function as a continuous immunological unit. Inflammatory conditions like allergic rhinitis, chronic rhinosinusitis with nasal polyps, and allergic asthma frequently co-occur, driven systemically by Type 2 inflammation and Immunoglobulin E. This study aimed to evaluate the concurrent efficacy of systemic anti-IgE therapy (omalizumab) on upper and lower airway outcomes in patients with United Airway Disease, addressing varying phenotypes and study designs.

Methods: A systematic review and meta-analysis were conducted according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. The protocol was prospectively registered in PROSPERO. Data were extracted from nine primary studies. Standardized mean differences and risk ratios were pooled using a DerSimonian-Laird random-effects model with inverse variance weighting. To address methodological heterogeneity, a priori subgroup analyses stratified the data by study design (randomized controlled trials versus observational cohorts) and upper airway phenotype (allergic rhinitis versus chronic rhinosinusitis with nasal polyps). Publication bias was assessed via Egger’s regression test.

Results: Nine studies comprising 1900 patients were included. Omalizumab significantly improved lower airway outcomes, with a pooled standardized mean difference of 1.45 (95% Confidence Interval: 1.12 to 1.78). Subgroup analysis revealed robust effects in both randomized trials and observational cohorts. Upper airway outcomes demonstrated profound symptom resolution (Standardized Mean Difference 1.32). Phenotypic stratification showed significant improvements in both allergic rhinitis and chronic rhinosinusitis with nasal polyps subgroups, though effect sizes varied slightly by local tissue remodeling profiles. The annualized rate of severe asthma exacerbations was reduced by a risk ratio of 0.48. Egger’s test indicated no significant publication bias (P = 0.15).

Conclusion: Systemic anti-IgE therapy concurrently ameliorates upper and lower respiratory tract pathologies in United Airway Disease. These findings support the systemic use of biologics in patients who remain refractory to optimized standard-of-care topical therapies, aligning with stepwise clinical guidelines for severe disease management.

VAT Dyes as Primary Sensitizers in Occupational Contact Dermatitis: Clinical and Patch Test Profiles in the Traditional Sasirangan Textile Industry

2026-04-07T02:40:22+00:00

Background: Occupational contact dermatitis (OCD) significantly impacts workers in the informal textile sector. While disperse dyes are well-documented sensitizers, the allergenic potential of VAT dyes in traditional manufacturing, such as the Indonesian Sasirangan batik industry, remains under-evaluated.

Methods: An analytical observational cross-sectional study was conducted on 40 Sasirangan artisans (20 wet workers, 20 dry workers). Clinical diagnoses were established using the Mathias criteria and NOSQ-2002. Epicutaneous patch testing was performed using a baseline series and specific synthetic dyes (1% in petrolatum), read at 48, 72, and 96 hours per ICDRG criteria. Multivariable logistic regression complemented the primary statistical analysis to assess predictive risk factors.

Results: The prevalence of positive patch tests was 62.5% (25/40). The primary sensitizers were VAT dye willanthrene brill rose 4R (42.5%) and VAT dye willanthrene green B (37.5%). A significant correlation was found between a clinical history of OCD and positive patch test outcomes (p=0.014, OR=5.6). Surprisingly, job type (wet vs. dry), handwashing frequency, and PPE use did not significantly correlate with patch test positivity (p>0.05), highlighting the pervasive nature of dye allergens across the workspace.

Conclusion: VAT dyes are potent primary sensitizers in the traditional Sasirangan textile industry. A clinical history of OCD is a strong predictor of patch test positivity, emphasizing the need for targeted allergen identification and barrier protection.