Bioscientia Medicina : Journal of Biomedicine and Translational Research

Stratifying Neurological Severity in Acute Ischemic Stroke: The Independent and Combined Prognostic Value of Admission D-Dimer and High-Sensitivity C-Reactive Protein

2025-10-20T04:45:42+00:00

Background: Early risk stratification in acute ischemic stroke (AIS) is critical for optimizing patient management. The roles of inflammation and thrombosis in stroke pathophysiology suggest that high-sensitivity C-reactive protein (hs-CRP) and D-Dimer may serve as valuable prognostic biomarkers. This study aimed to evaluate the independent and combined value of admission D-Dimer and hs-CRP levels for predicting neurological severity in AIS patients.

Methods: We conducted a prospective, cross-sectional study at Haji Adam Malik General Hospital, Medan, Indonesia, involving 60 consecutive AIS patients. Neurological severity was assessed upon admission using the National Institutes of Health Stroke Scale (NIHSS), with patients categorized into moderate (NIHSS 5-18) and severe (NIHSS >18) groups. Plasma D-Dimer and serum hs-CRP levels were quantified. Statistical analyses included the Mann-Whitney U test, Spearman's correlation, Receiver Operating Characteristic (ROC) curve analysis, and multivariate logistic regression to determine the independent predictive value of the biomarkers.

Results: Of the 60 patients, 31 (51.7%) were classified as having severe stroke. Both D-Dimer and hs-CRP levels were significantly higher in the severe group compared to the moderate group (D-Dimer: median 3220 ng/mL vs. 670 ng/mL, P<0.001; hs-CRP: median 5.6 mg/dL vs. 0.9 mg/dL, P<0.001). ROC analysis demonstrated strong predictive performance for severe stroke, with an Area Under the Curve (AUC) of 0.89 (95% CI: 0.81-0.97) for D-Dimer and 0.83 (95% CI: 0.72-0.94) for hs-CRP. A combined model incorporating both biomarkers yielded a superior AUC of 0.92 (95% CI: 0.85-0.99). In multivariate logistic regression, both elevated D-Dimer (Odds Ratio [OR]: 6.8, 95% CI: 2.1-22.5, P=0.001) and hs-CRP (OR: 4.5, 95% CI: 1.5-13.8, P=0.008) remained independent predictors of severe stroke after adjusting for age and gender.

Conclusion: Admission levels of D-Dimer and hs-CRP are powerful, independent prognostic markers for neurological severity in patients with acute ischemic stroke. Their use, particularly in combination, could enhance early risk stratification and guide clinical decision-making.

Histamine-2 Receptor Antagonist for Gastric Bleeding Prophylaxis in Low-Risk Critically Ill Children: A Randomized Trial of Ranitidine

2025-10-20T04:57:38+00:00

Background: The utility of stress ulcer prophylaxis (SUP) in critically ill children is a subject of ongoing debate, particularly in patients who do not present with classic high-risk features for stress-related mucosal disease (SRMD). This study aimed to evaluate the efficacy of ranitidine for preventing gastric bleeding in a heterogeneous cohort of critically ill children.

Methods: A single-center, prospective, open-label, randomized controlled trial was conducted in a tertiary Pediatric Intensive Care Unit (PICU) in Indonesia. Children aged 1 month to 18 years admitted to the PICU were randomized to receive either intravenous ranitidine (1 mg/kg/dose twice daily) or standard care without prophylaxis for five days. The primary outcome was the incidence of overt gastric bleeding. Post-hoc power analysis and multivariable logistic regression were performed to contextualize the findings.

Results: From 243 patients screened, 60 were randomized (30 per group). The cohort was predominantly composed of infants (60.0%) with respiratory distress. Overt gastric bleeding occurred in 1 of 30 patients (3.3%) in the ranitidine group versus 3 of 30 patients (10.0%) in the control group. This difference was not statistically significant (Relative Risk [RR] 0.33; 95% CI 0.04–3.11; p=0.612). After adjusting for a baseline imbalance in age, the odds of bleeding remained non-significantly lower in the ranitidine group (Adjusted Odds Ratio [aOR] 0.29; 95% CI 0.03–3.20). The study was found to be severely underpowered (16% power), and none of the bleeding events were clinically significant.

Conclusion: In this small, underpowered trial of predominantly low-risk critically ill children, ranitidine did not significantly reduce the incidence of overt gastric bleeding. These findings, while limited by significant methodological weaknesses, do not support the routine use of SUP in similar pediatric populations and underscore the critical need for larger, more definitive trials to inform evidence-based risk-stratification strategies.

Platelet-Rich Plasma for Burn Wound Healing in Preclinical Models: A Systematic Review of Efficacy and Biomolecular Mechanisms

2025-08-05T18:27:50+00:00

Background: Burn injuries represent a major global health issue, with complex pathophysiology that often leads to significant morbidity. Platelet-rich plasma (PRP) has been identified as a potential therapeutic agent due to its high concentration of growth factors that promote tissue renewal. This review synthesizes preclinical evidence on the efficacy of PRP for burn wounds.

Methods: This systematic review followed PRISMA guidelines, searching PubMed, Scopus, and ScienceDirect for animal studies on PRP for burn wounds. The primary outcomes were wound healing, fibroblast scores, and VEGF/EGF levels. The SYRCLE tool was used for risk of bias assessment.

Results: Eleven studies involving 526 animals were included. The risk of bias across studies was generally high or unclear, primarily due to poor reporting of randomization and blinding. Macroscopically, PRP was reported to accelerate wound closure in partial-thickness burns within 4-7 days and in full-thickness burns from day 8 onward. On a biomolecular level, PRP was associated with increased fibroblast scores and elevated tissue concentrations of VEGF and EGF from the first day post-treatment (P<0.05 in multiple studies).

Conclusion: While the included studies suggest PRP may enhance healing, definitive conclusions are precluded by the high risk of bias and methodological heterogeneity across the preclinical evidence base.

Corticosteroids, Azole Antifungals, and Biologic Agents for the Management of Allergic Bronchopulmonary Aspergillosis: A Systematic Review and Network Meta-Analysis

2025-08-06T18:28:15+00:00

Background: The management of allergic bronchopulmonary aspergillosis (ABPA) requires control of complex type 2 inflammation and reduction of fungal burden. The comparative efficacy of the primary therapeutic classes—corticosteroids, azole antifungals, and biologics—is not well established through direct evidence. This network meta-analysis was conducted to determine the optimal hierarchical treatment strategy for ABPA.

Methods: A systematic review of PubMed, EMBASE, and the Cochrane Central Register of Controlled Trials was performed for randomized controlled trials (RCTs) published from January 2015 to July 2025. We included RCTs in patients with ABPA comparing oral corticosteroids (OCS) alone to OCS plus itraconazole or OCS plus a biologic agent (omalizumab, mepolizumab, benralizumab). The primary outcome was a composite therapeutic response (≥25% IgE reduction plus clinical stability). A Bayesian random-effects network meta-analysis was performed, with results presented as odds ratios (OR) and 95% credible intervals (CrI).

Results: Seven RCTs enrolling 988 patients were included, forming a star-shaped evidence network anchored by a common placebo comparator. All active add-on therapies were superior to OCS alone for the primary outcome. Based on probabilistic rankings (SUCRA), OCS plus mepolizumab was most likely to be the most effective treatment (OR vs. OCS alone: 5.12; 95% CrI, 2.89-9.15; SUCRA: 94.5%), followed by OCS plus benralizumab (OR: 4.65; 95% CrI, 2.15-8.98; SUCRA: 87.2%), OCS plus omalizumab (OR: 3.88; 95% CrI, 2.10-7.15; SUCRA: 75.1%), and OCS plus itraconazole (OR: 2.54; 95% CrI, 1.55-4.17; SUCRA: 43.2%). Biologic agents demonstrated the greatest reduction in exacerbation rates.

Conclusion: In patients with ABPA, combination therapy is superior to OCS monotherapy. This analysis provides compelling indirect evidence that biologic agents, particularly IL-5 inhibitors, represent the most effective therapeutic class for achieving disease control. These findings provide a strong evidence base to guide a hierarchical treatment approach and support the early integration of targeted therapies into the ABPA management algorithm.

Beyond the Species Barrier: A Systematic Review and Risk of Bias Assessment on the Efficacy, Safety, and Translational Potential of Xenogenic Platelet-Rich Plasma for Wound Healing

2025-08-06T18:27:59+00:00

Background: Chronic wounds represent a significant clinical burden. Autologous platelet-rich plasma (PRP) is an effective but patient-limited therapy. Xenogenic PRP (xPRP), derived from animal sources, offers a potential off-the-shelf, scalable alternative. This review synthesizes the current preclinical and early clinical evidence on the efficacy and safety of xPRP for wound healing.

Methods: A systematic search was conducted in PubMed, Scopus, ScienceDirect, and Google Scholar up to July 2025, with no publication date restrictions, following PRISMA guidelines. Studies evaluating xPRP on wound healing outcomes in in vivo, in vitro, or ex vivo models were included. Two independent reviewers performed study selection, data extraction, and risk of bias assessment using the SYRCLE tool for animal studies and a modified QUIN tool for in vitro studies. Data were synthesized narratively due to heterogeneity.

Results: Eleven studies met the inclusion criteria, comprising ten animal and three in vitro investigations (two studies reported both components). Evidence from porcine, bovine, and deer xPRP sources consistently demonstrated significant improvements in wound closure rates, re-epithelialization, angiogenesis, and collagen deposition compared to saline controls. Porcine xPRP, for instance, accelerated wound closure by up to 45% over controls in diabetic rodent models. However, when compared to autologous PRP, xPRP generally showed slightly inferior, though still positive, outcomes. Immunogenic responses were minimal and localized, with no systemic adverse events reported. Risk of bias assessment revealed that while most studies had clear objectives, many were at high risk of bias due to a lack of randomization, allocation concealment, and blinded outcome assessment.

Conclusion: Xenogenic PRP demonstrates considerable promise as a bioactive therapeutic for wound healing, promoting key regenerative processes with a reassuring preliminary safety profile. However, the current evidence base is limited by methodological inconsistencies and a high risk of bias. Future research must prioritize standardized preparation protocols and methodologically rigorous, large-animal and human clinical trials to validate its translational potential.

The Rhomboid Flap for Facial Reconstruction Following Basal Cell Carcinoma Excision: A Case Report on Achieving Optimal Aesthetic and Functional Outcomes

2025-08-12T18:29:57+00:00

Background: Reconstruction of the lower eyelid following oncologic surgery presents a formidable challenge due to the region's unique anatomy and functional importance. The primary goal is to restore the lamellar structure while avoiding ectropion, a complication with significant functional and aesthetic consequences. This report details the successful application of a rhomboid flap, a classic transposition flap, for a moderate-sized defect in this high-risk anatomical subunit.

Case presentation: A 75-year-old male farmer presented with a 2x1 cm nodular basal cell carcinoma on his left lower eyelid. After surgical excision with 4 mm margins, a superolaterally based rhomboid flap was designed to close the defect. The procedure was performed under local anesthesia. The postoperative course was uncomplicated. Objective functional assessment at 12 weeks confirmed a normal lower lid position with margin-to-reflex distance 2 (MRD2) symmetrical to the contralateral eye and no evidence of ectropion or lagophthalmos. The cosmetic outcome was assessed as favorable using the Patient and Observer Scar Assessment Scale (POSAS), and the patient reported high satisfaction (5/5 on a Likert scale).

Conclusion: This case report illustrates the successful use of a rhomboid flap for a moderate-sized lower eyelid defect, resulting in a favorable functional and aesthetic outcome without complications in the short-term follow-up period. The technique successfully restored tissue volume and preserved normal eyelid function, critically preventing ectropion. It supports the rhomboid flap as a robust and reliable option in the reconstructive surgeon's toolkit for this challenging anatomical area.

A Mechanistic Approach to Post-Operative Analgesia: Safe Use of Etoricoxib in a Patient with Confirmed NSAID-Induced Urticaria/Angioedema (NIUA)

2025-08-06T18:27:42+00:00

Background: The management of acute pain in patients with NSAID-induced urticaria/angioedema (NIUA) is a clinical challenge. These cross-reactive hypersensitivity reactions are driven by cyclooxygenase-1 (COX-1) inhibition, precluding the use of most conventional analgesics. This report presents the successful management of severe post-operative pain in a patient with a confirmed, long-standing NIUA phenotype.

Case presentation: A 56-year-old male with a 40-year history of angioedema induced by multiple COX-1-inhibiting NSAIDs, confirmed by a previous oral provocation test, required urgent herniotomy. Baseline serum tryptase was normal. Post-operatively, initial analgesia with tramadol proved ineffective and induced emesis. Consequently, the patient was administered etoricoxib 90 mg once daily, a highly selective COX-2 inhibitor. This resulted in excellent and sustained pain control, with the Numeric Rating Scale (NRS) score decreasing from 8/10 to ≤2/10 over a seven-day course, and importantly, without eliciting any hypersensitivity reaction.

Conclusion: This case supports the hypothesis that a highly selective COX-2 inhibitor can provide safe and effective analgesia in patients with severe, cross-reactive NIUA. The analgesic choice was directly informed by the underlying pathophysiology, which involves shunting of the arachidonic acid pathway towards pro-inflammatory leukotriene production following COX-1 blockade. This report reinforces that selective COX-2 inhibition is a rational, first-line strategy for managing pain in this high-risk patient population.

Laser Therapy for Genitourinary Syndrome of Menopause (GSM): A Stratified Meta-Analysis of Histological, Clinical, and Safety Outcomes

2025-08-09T18:29:30+00:00

Background: Genitourinary syndrome of menopause (GSM) is a prevalent and chronic condition that diminishes quality of life. Vaginal laser therapy is a non-hormonal treatment, but its efficacy and safety require rigorous synthesis. This study was conducted to systematically evaluate the efficacy of laser therapy for GSM by prioritizing high-quality evidence and separately analyzing findings from different study designs, while also providing the first meta-analytic overview of safety.

Methods: A systematic search of PubMed, Scopus, Embase, and the Cochrane Library was performed for studies published between January 2015 and December 2024. The primary analysis of efficacy was restricted to randomized controlled trials (RCTs). A separate, secondary analysis was performed on prospective cohort studies. Primary outcomes were changes in vaginal epithelial thickness and the Visual Analog Scale (VAS) for dryness. Secondary outcomes included VAS for dyspareunia, vaginal health index (VHI), female sexual function index (FSFI), and systematically extracted adverse events. Data were pooled using a random-effects model.

Results: Seven studies (2 RCTs, 5 cohort studies) involving 595 patients were included. In the primary analysis of RCTs, laser therapy resulted in a significant increase in epithelial thickness (Mean Difference [MD] 50.15 µm) and a significant reduction in VAS for dryness (MD -4.54) with low-to-moderate heterogeneity. The secondary analysis of cohort studies also showed significant improvements, but with extremely high and significant heterogeneity (I² > 80%). Across all studies, reported adverse events were consistently mild and transient, including temporary erythema, edema, and minor discharge. No serious adverse events were reported.

Conclusion: Based on high-quality evidence from RCTs, vaginal laser therapy produces statistically significant improvements in the histological and clinical parameters of GSM. Evidence from cohort studies supports this finding but demonstrates considerable variability in real-world settings. While short-term safety appears favorable, the inconsistent treatment effect and lack of long-term data necessitate a cautious approach to patient selection and counseling.

Dismantling Immunosuppression in Colorectal Cancer: A Systematic Review and Meta-Analysis on Phyllanthus niruri as a Potent Antagonist of the IL-10 Axis in the Tumor Microenvironment

2025-08-10T18:29:38+00:00

Background: The immunosuppressive tumor microenvironment (TME) of colorectal cancer (CRC), orchestrated largely by Interleukin-10 (IL-10), presents a formidable barrier to effective anti-tumor immunity. Phytochemicals from traditional medicines offer a promising avenue for immunomodulation. Phyllanthus niruri, a plant with a long history in herbal medicine, has demonstrated significant immunomodulatory potential. This systematic review aims to synthesize and critically evaluate the evidence regarding the efficacy of P. niruri and its bioactive compounds in modulating the IL-10-mediated immunosuppressive axis in CRC.

Methods: A systematic search was conducted in PubMed, Scopus, Web of Science, and Google Scholar for studies published between January 2015 and August 2025. The review included in vitro, in vivo, and clinical studies investigating the effect of P. niruri on IL-10 expression and associated immune responses in CRC models. The PRISMA guidelines were followed. Study quality was assessed using SYRCLE's risk of bias tool for animal studies and the RoB 2 tool for clinical trials. A meta-analysis of IL-10 concentration data from preclinical models was performed using a random-effects model.

Results: From an initial 874 records, seven studies met the inclusion criteria: three in vitro, three in vivo, and one early-phase clinical trial. The selected studies consistently demonstrated that P. niruri extracts and its lignan, phyllanthin, significantly reduced IL-10 production in CRC cell lines, tumor tissues, and patient serum. Based on three preclinical studies, a meta-analysis revealed a significant standardized mean difference (SMD) in IL-10 reduction (SMD = -2.45; 95% CI: -3.10, -1.80; p < 0.00001). This IL-10 downregulation was correlated with a significant increase in cytotoxic T lymphocyte (CD8+) infiltration, repolarization of M2 to M1 macrophages, and enhanced expression of pro-inflammatory cytokines such as IFN-γ and TNF-α. Mechanistically, P. niruri was shown to inhibit the STAT3 and NF-κB signaling pathways, key regulators of IL-10 transcription.

Conclusion: While based on a limited but consistent body of evidence, our findings strongly support the role of Phyllanthus niruri as a potent modulator of the CRC immunosuppressive microenvironment by specifically targeting the IL-10 signaling axis. By reducing IL-10 production, P. niruri unleashes anti-tumor immunity, suggesting its potential as an adjuvant therapy to enhance the efficacy of conventional treatments and immunotherapies in CRC. Rigorous, large-scale clinical trials are warranted to translate these preclinical findings into clinical practice.

The 15-Year Shadow: Borderline Lepromatous Leprosy with Erythema Nodosum Leprosum Following Prolonged Treatment Default

2025-08-11T18:30:03+00:00

Background: Leprosy, caused by Mycobacterium leprae, persists as a global health issue where the primary challenges are not merely microbial but are deeply rooted in delayed diagnosis and poor treatment adherence. These delays, often driven by profound social stigma, lead to progressive, irreversible disability and sustain community transmission. Erythema Nodosum Leprosum (ENL), an acute immunological complication, further devastates patients' quality of life and complicates management.

Case presentation: A 53-year-old Indonesian farmer presented with a 15-year history of untreated leprosy, a journey of neglect initiated by fear of treatment side effects and community ostracism. Clinical examination revealed advanced borderline lepromatous (BL) leprosy with diffuse skin infiltration, multiple anesthetic plaques, and thickened, tender peripheral nerves. He had established WHO Grade 1 disability, characterized by significant sensory loss in his hands and feet and early intrinsic muscle atrophy. A slit-skin smear confirmed a bacteriological index of +3 with a morphological index of 5%, indicating a high load of viable bacilli. Histopathology confirmed BL leprosy with a concurrent mild ENL reaction. A comprehensive, patient-centered management plan was initiated, including a 12-month course of multidrug therapy (MDT-MB), adjunctive care, and intensive counseling.

Conclusion: This case powerfully illustrates the "shadow effect" of leprosy—how years of untreated disease, fueled by psychosocial barriers, culminate in a complex nexus of advanced infection, immunological reaction, and permanent neurological impairment. The patient's successful re-engagement with the health system underscores that eradicating the burden of leprosy requires a paradigm shift from a purely pharmacological approach to a deeply humanistic one. Effective control hinges on building compassionate health systems that actively dismantle stigma, empower patients with knowledge, and deliver holistic, multidisciplinary care to prevent the profound human cost of neglect.

Nummular Dermatitis Masquerading as Recalcitrant Tinea Corporis: A Diagnostic Pitfall Resolved by Dermoscopy and Histopathology

2025-08-11T18:29:47+00:00

Background: The morphological mimicry between nummular dermatitis (ND) and tinea corporis represents a significant source of diagnostic error in clinical practice. This convergence on a similar clinical phenotype—the annular plaque—often leads to inappropriate antifungal therapy and a protracted, debilitating course for the patient, as powerfully illustrated in this case.

Case presentation: We present the case of a 22-year-old female with a five-year history of chronic, recalcitrant, and intensely pruritic annular plaques on her lower legs, with a baseline pruritus score of 8/10 on a Visual Analog Scale (VAS). Previous treatments based on presumptive diagnoses, including potent topical corticosteroids and systemic antifungals, had failed. This report demonstrates a pivot from a morphology-based assessment to a multimodal diagnostic algorithm. The cornerstone of this shift was dermoscopy, which revealed patchy, irregularly distributed red dotted vessels—a classic signature of an eczematous process—and a notable absence of features suggestive of a dermatophyte infection. The diagnosis was confirmed by histopathology. A strong correlation between disease flares and psychosocial stressors was identified, and a holistic management plan targeting the cutaneous inflammation, the compromised skin barrier, and the neurogenic triggers led to a rapid and substantial improvement in her clinical status and quality of life, with the Dermatology Life Quality Index (DLQI) score decreasing from 9 to 3 and the pruritus VAS score dropping to 1/10.

Conclusion: This case argues for a revised diagnostic paradigm for chronic annular lesions, one that de-emphasizes ambiguous morphology and prioritizes the integration of a detailed psychodermatological history with in-vivo microscopic analysis via dermoscopy. This approach not only prevents therapeutic futility but also underscores that successful, long-term management of ND is contingent upon a patient-centered strategy that addresses the interconnectedness of the skin barrier, the immune system, and the psycho-neuro-cutaneous axis.

Rigid Esophagoscopy for an Impacted Kaffir Lime in the Proximal Esophagus: A Case Report and Discussion of a Unique Mechanical-Chemical Injury

2025-08-12T18:29:40+00:00

Background: Esophageal food bolus impaction is a common otolaryngological emergency. However, impaction by a large, whole citrus fruit is exceedingly rare and presents unique diagnostic and therapeutic challenges, particularly concerning the object's size, radiolucency, and potential for causing both mechanical and chemical mucosal injury.

Case presentation: We present the case of a 42-year-old male with acute-onset dysphagia and hypersalivation after ingesting a whole kaffir lime. Laryngoscopy revealed pooled secretions in the pyriform sinus, a key indicator of high esophageal obstruction, despite non-contributory plain radiography. The patient underwent emergent rigid esophagoscopy under general anesthesia. A 36 mm kaffir lime was identified at 15 cm from the incisors and successfully extracted en bloc using alligator grasping forceps. Post-extraction evaluation revealed localized mucosal excoriation without evidence of deep laceration or perforation. The patient recovered fully with no long-term sequelae.

Conclusion: This case highlights the successful management of a rare and challenging esophageal foreign body. It underscores the diagnostic primacy of clinical findings over negative radiography for radiolucent objects and demonstrates the distinct advantages of rigid esophagoscopy—superior airway control, a wider operating channel, and use of robust instrumentation—for large, solid foreign bodies lodged in the proximal esophagus. In this instance, the impaction did not lead to severe complications within 24 hours, but prompt removal is essential to mitigate the risks of pressure necrosis and chemical esophagitis.

Deciphering Activity in Early Facial Vitiligo: A Case Report Integrating Clinical, Wood's Lamp, and Dermoscopic Findings

2025-08-13T18:30:06+00:00

Background: The management of non-segmental vitiligo hinges on accurately assessing disease activity to guide appropriate therapy. A clinical challenge arises in patients presenting with a low vitiligo area scoring index (VASI), suggesting limited disease, which may be discordant with underlying inflammatory activity, potentially leading to therapeutic inertia.

Case presentation: A 34-year-old woman with Fitzpatrick skin type III presented with a two-month history of rapidly progressing facial vitiligo, preceded by an erythematous phase. Despite a low VASI score of 1, the patient-reported vitiligo disease activity (VIDA) score was +4. Dermoscopy was instrumental, revealing definitive in-vivo evidence of inflammation and instability, including a pinkish background, telangiectasias, and a reversed pigment network. Based on this discordance between disease extent and activity, a multi-modal therapeutic regimen was initiated. A six-month follow-up demonstrated disease stabilization and significant perifollicular repigmentation, with resolution of the inflammatory dermoscopic signs.

Conclusion: This case report illustrates the critical importance of an integrated diagnostic approach that moves beyond area-based assessment. It highlights how dermoscopy, when used to resolve the clinical paradox of low-extent but high-activity disease, can serve as an objective biomarker to justify timely and robust immunomodulatory intervention. This approach is crucial for altering the disease trajectory and optimizing patient outcomes.

The Unseen Danger: A Meta-Analysis of Bystander Injuries in Firework-Related Ocular Trauma

2025-08-18T06:01:34+00:00

Background: Firework-related ocular trauma represents a significant, preventable cause of severe vision loss, with incidence rates peaking during global cultural and national festivals. While the risks to active firework users are well-established, the burden of injury sustained by passive spectators, or bystanders, remains poorly quantified. This study aimed to synthesize global data to define the magnitude of this unseen danger.

Methods: A systematic review and meta-analysis were conducted following PRISMA guidelines. PubMed, Scopus, EMBASE, and Web of Science were searched for studies published between January 2015 and December 2025 that reported separable data on firework-related ocular injuries in bystanders and operators. A random-effects model calculated the pooled proportion of bystander injuries. Secondary outcomes included pooled odds ratios (ORs) for open globe injury (OGI) and severe vision loss (SVL; Visual Acuity <3/60).

Results: Eleven studies, encompassing 2,440 patients, met the inclusion criteria. This meta-analysis, despite significant heterogeneity in the source data (I² = 89%), suggests that nearly half of all victims were bystanders, with a pooled proportion of 47.5% (95% CI: 41.8%–53.2%). Bystanders had significantly lower odds of sustaining an OGI compared to operators (pooled OR: 0.72, 95% CI: 0.58–0.90). However, the odds of suffering permanent SVL were not statistically different between the two groups (pooled OR: 0.91, 95% CI: 0.73–1.14), indicating a comparable risk of blinding injury.

Conclusion: These findings must be interpreted with caution due to high inter-study heterogeneity and unmeasured clinical confounders. Nonetheless, the analysis strongly suggests that the risk to bystanders is unacceptably high and that public health paradigms focused solely on operator safety are insufficient. This study underscores the urgent need for prospective, standardized data collection and a shift in prevention strategies toward protecting passive spectators.

Impaired Stimulated Pancreatic β-Cell Responsiveness is a Dominant Feature of Bisphenol A-Associated Metabolic Dysfunction in Type 2 Diabetes: A Cross-Sectional Analysis of Adjusted Associations in an Indonesian Cohort

2025-08-14T18:30:06+00:00

Background: Exposure to the endocrine-disrupting chemical bisphenol A (BPA) is a suspected contributor to the type 2 diabetes mellitus (T2DM) pandemic. This study aimed to move beyond simple correlation and investigate the adjusted association between urinary BPA and the dual pathophysiological defects of T2DM—insulin resistance and pancreatic β-cell failure—with a novel emphasis on contrasting basal versus stimulated β-cell function in an understudied Indonesian cohort.

Methods: In a cross-sectional study, 40 patients with T2DM were recruited from a tertiary hospital in Palembang, Indonesia. Urinary BPA was quantified by liquid chromatography–mass spectrometry (LCMS). Insulin resistance was assessed by the homeostasis model assessment of insulin resistance (HOMA-IR). β-cell function was evaluated using the C-peptide index (CPI) at fasting and 1-hour post-75g oral glucose tolerance test (OGTT). Multivariable linear regression models were constructed to determine the association between urinary BPA (log-transformed) and metabolic indices, adjusting for age, gender, and body mass index (BMI).

Results: After adjusting for confounders, higher log-urinary BPA remained a significant independent predictor of higher log-HOMA-IR (β = 0.58, 95% CI: 0.31-0.85, p < 0.001). BPA was also independently associated with poorer β-cell function, showing a significant inverse association with the fasting CPI (β = -0.45, 95% CI: -0.73 to -0.17, p = 0.003). Critically, this association was markedly stronger and more profound with the 1-hour stimulated CPI (β = -0.79, 95% CI: -0.99 to -0.59, p < 0.001). The variance in stimulated CPI explained by the model (R2) was substantially higher than for other indices.

Conclusion: Higher environmental BPA exposure is independently associated with both heightened insulin resistance and compromised β-cell function in T2DM. The distinctly stronger association with impaired stimulated β-cell secretion, even after adjusting for key confounders, identifies a critical mechanism by which BPA may accelerate functional β-cell exhaustion, the pivotal event in T2DM progression.

Ocular Parasitoses in the Globally Mobile Population: A Systematic Review of Etiology, Pathophysiology, and Clinical Management

2025-08-17T18:31:08+00:00

Background: 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.

Optic Neuritis After Viral Vector versus mRNA COVID-19 Vaccines: A Systematic Review and Comparative Meta-Analysis

2025-08-18T05:02:24+00:00

Background: The global deployment of COVID-19 vaccines, utilizing distinct viral vector and mRNA technologies, has been followed by reports of rare neuro-ophthalmic adverse events, including optic neuritis (ON). This study aimed to systematically compare the clinical phenotypes, autoimmune serological profiles, and visual outcomes of ON cases with onset in temporal association with viral vector versus mRNA COVID-19 vaccination.

Methods: A systematic review was conducted across PubMed, Scopus, and EMBASE databases for case reports and case series published up to August 2025 detailing ON after COVID-19 vaccination. Data were extracted on clinical presentation, MRI findings, serostatus for aquaporin-4 (AQP4-IgG) and myelin oligodendrocyte glycoprotein (MOG-IgG) antibodies, treatments, and visual outcomes. Separate meta-analyses of proportions and comparative odds ratios (OR) were calculated for key outcomes, including distinct analyses for NMOSD and MOGAD.

Results: Our analysis of published reports included 20 studies, comprising 90 patients (40 viral vector, 50 mRNA). Cases associated with viral vector vaccines had significantly higher odds of presenting with bilateral disease (OR 4.31, 95% CI [1.67, 11.11]). This platform was also associated with markedly increased odds of AQP4-IgG positivity (NMOSD) (OR 5.15, 95% CI [1.35, 19.61]) and MOG-IgG positivity (MOGAD) (OR 4.58, 95% CI [1.09, 19.21]). Consequently, these patients had higher odds of requiring aggressive immunotherapy and of suffering incomplete visual recovery (OR 3.41, 95% CI [1.14, 10.21]).

Conclusion: Our analysis of published case reports suggests that while ON following COVID-19 vaccination is a very rare event, its clinical phenotype may differ based on the vaccine platform. Cases associated with viral vector vaccines appear more likely to manifest as a severe, bilateral, antibody-mediated condition characteristic of NMOSD or MOGAD. These findings, which do not establish causality, underscore the critical importance of prompt autoantibody testing to guide appropriate management. The established benefits of vaccination continue to overwhelmingly outweigh the exceptionally low absolute risk of such adverse events.

Navigating Surgical Strategies for Symptomatic Tarlov Cysts: A Case Report of Successful Microsurgical Excision and Imbrication

2025-08-18T18:31:13+00:00

Background: Symptomatic Tarlov (perineural) cysts are a rare but debilitating cause of chronic radicular pain, arising from cerebrospinal fluid (CSF) accumulation within the nerve root sheath. The diagnostic journey is often complex, requiring a definitive link between the lesion and the patient's symptoms, and the optimal surgical strategy remains a subject of considerable debate.

Case presentation: A 56-year-old male presented with a six-month history of intractable right S2 radiculopathy (VAS 8/10) and severe functional impairment (Oswestry Disability Index 78%), which had failed a comprehensive trial of conservative management. Magnetic resonance imaging revealed a large cystic lesion at the right S2 level, with features characteristic of a Tarlov cyst, causing severe nerve root compression. Following a thorough discussion of the risks and benefits, the patient underwent an S2 laminectomy with microsurgical partial cyst excision and wall imbrication. Postoperative histopathology confirmed the diagnosis of a perineural cyst, identifying nerve fibers within the fibroconnective tissue of the cyst wall.

Conclusion: The patient experienced immediate and sustained resolution of his radicular pain (VAS 0/10) and a profound improvement in functional status (ODI 12%) at one-year follow-up, with radiological confirmation of successful cyst obliteration. This case highlights the potential of a direct microsurgical approach, guided by a strong clinical-radiological correlation and confirmed by histopathology, to provide a durable and life-altering cure for patients disabled by symptomatic Tarlov cysts.

The Efficacy of Phyllanthus niruri Linn in Modulating Inflammatory and Cancer Stem Cell Markers in Colorectal Cancer: A Stratified Systematic Review and Meta-Analysis

2025-08-19T18:31:22+00:00

Background: The progression of colorectal cancer (CRC) is driven by a complex interplay between chronic inflammation and a resilient population of cancer stem cells (CSCs). Phyllanthus niruri Linn (PNL), a medicinal plant with established immunomodulatory effects, presents a promising adjuvant therapeutic strategy. This study aimed to move beyond qualitative summaries to quantitatively assess PNL's efficacy by synthesizing evidence on its modulation of key inflammatory and CSC biomarkers.

Methods: Following PRISMA guidelines, a systematic search of PubMed, ScienceDirect, Google Scholar, and Scopus (2015–2025) was conducted. Studies quantifying the effects of PNL on Interleukin-8 (IL-8), Cyclooxygenase-2 (COX-2), or CD133 in CRC models were included. Recognizing the profound biological differences between experimental systems, a stratified meta-analysis was performed. Data were pooled using a random-effects model, stratified by study type (in vitro vs. in vivo) and intervention (monotherapy vs. combination therapy). The Standardized Mean Difference (SMD) was the primary effect measure.

Results: Seven studies met the inclusion criteria. In a stratified analysis of in vivo models, PNL monotherapy significantly reduced COX-2 (SMD -2.11; 95% CI [-3.10, -1.12]) and IL-8 (SMD -1.95; 95% CI [-3.01, -0.89]). The effect on the CSC marker CD133 was most pronounced in vitro (SMD -2.98; 95% CI [-4.87, -1.09]), while still significant in in vivo models (SMD -2.15; 95% CI [-3.45, -0.85]). The analysis revealed that the biological context (in vitro vs. in vivo) is a significant determinant of the observed effect size.

Conclusion: This stratified meta-analysis provides robust, context-specific evidence of PNL's ability to suppress key inflammatory and CSC markers in CRC. The findings reveal that PNL's potent anti-CSC activity observed in vitro is translated into a significant, though attenuated, effect in vivo, highlighting the critical influence of the tumor microenvironment and pharmacokinetics. This work substantiates the dual-pronged therapeutic potential of PNL as a promising bioactive adjuvant in CRC therapy.

High-Dose Sucralfate as a Mucosal-Protective Cornerstone in the Organ-Sparing Management of Pediatric Grade 2A Corrosive Gastroduodenitis: A Case Report and Pathophysiological Review

2025-08-19T18:31:06+00:00

Background: Accidental corrosive ingestion is a formidable pediatric emergency that can lead to severe gastrointestinal injury and long-term sequelae. Sulfuric acid, a common agent, induces coagulative necrosis, primarily affecting the stomach. The optimal management for moderate-grade injuries (Zargar Grade 2A) is debated, with a focus on preventing stricture formation. This report details a case managed with an aggressive pharmacotherapeutic protocol centered on high-dose sucralfate.

Case presentation: A 2-year-10-month-old boy was admitted following accidental ingestion of battery acid. His presentation was atypical, with vomiting but no oropharyngeal lesions. Initial investigations revealed a significant systemic inflammatory response (leukocytosis: 19,220/mm³; thrombocytosis: 581,000/mm³) and aspiration pneumonitis. Despite a 12-day delay in endoscopy due to parental refusal, an aggressive conservative regimen was initiated upon admission. This protocol included high-dose, frequent-interval sucralfate (80 mg/kg every 2 hours), intensive intravenous acid suppression (omeprazole and ranitidine), and prophylactic antibiotics. The endoscopy on day 12 confirmed Zargar Grade 2A burns in the gastric fundus, pylorus, and proximal duodenum, with the esophagus spared. The patient improved rapidly, tolerated an oral diet by day 11, and was discharged on day 14.

Conclusion: Follow-up endoscopy at 6 weeks and 6 months confirmed complete mucosal healing without any evidence of stricture or gastric outlet obstruction. This case suggests that an immediate, aggressive, non-surgical protocol featuring high-dose sucralfate can be effective in managing pediatric Grade 2A corrosive gastroduodenal burns, promoting complete healing and preventing long-term complications. The findings underscore the potential of this pharmacotherapeutic strategy and warrant further investigation.

The Hidden Hazard of Celebration: A Meta-Analysis of Ocular Morbidity from Colored Powder Festivals and Implications for Global Travel Medicine

2025-08-20T18:31:25+00:00

Background: The globalization of colored powder festivals, such as Holi, has exposed millions, including international tourists, to significant ocular health risks from synthetic industrial dyes that have replaced traditional organic powders. This study was conducted to quantify the prevalence of acute ocular morbidities from these festivals, providing an evidence base to inform clinical practice and public health policy, particularly within travel medicine.

Methods: Following PRISMA guidelines, a systematic search was conducted in PubMed, Google Scholar, ScienceDirect, and ProQuest for observational studies published up to July 2024. Studies reporting ocular complications from colored powder exposure were included. Data were extracted by two independent reviewers, and methodological quality was assessed using JBI checklists. A random-effects model was used to calculate pooled prevalence for key ocular injuries. Heterogeneity was investigated using sensitivity analyses, and publication bias was assessed with funnel plots.

Results: Six studies from India, encompassing 189 patients, met the inclusion criteria for quantitative analysis. The patient population was predominantly young males (mean age 20-30 years). The meta-analysis revealed a high pooled prevalence of key ocular morbidities. The prevalence for chemical conjunctivitis was 95% (95% CI: 87%-100%), though with substantial but anticipated heterogeneity (I²=82%). The prevalence for corneal epithelial defects was 37% (95% CI: 23%-53%; I²=45%), and for superficial punctate keratopathy was 75% (95% CI: 57%-90%; I²=0%). Most injuries were bilateral.

Conclusion: Participation in colored powder festivals, based on extensive evidence from Holi in India, presents a quantifiable and significant risk of acute ocular morbidity. The high prevalence of chemical-induced ocular surface disease necessitates urgent recognition of this "hidden hazard." Proactive, evidence-based preventive strategies, including tiered recommendations for protective eyewear and updated pre-travel health advisories, are imperative to safeguard the vision of millions of celebrants worldwide.

Weber Syndrome Revisited: A Classic Midbrain Stroke Presentation Secondary to Severe Dyslipidemia

2025-08-20T18:31:10+00:00

Background: Weber syndrome is a classic brainstem stroke syndrome resulting from an ischemic lesion in the ventral midbrain. While historically defined by its striking clinical features—ipsilateral oculomotor nerve palsy and contralateral hemiparesis—its modern relevance lies in its direct causation by common, modifiable vascular risk factors. This report uses a quintessential case of Weber syndrome as a didactic tool to illustrate the profound microvascular consequences of a specific, severe metabolic phenotype.

Case presentation: A 60-year-old female with a history of medication non-adherence for hypertension and hypercholesterolemia presented with acute left hemiparesis, right ptosis, and diplopia. Examination confirmed a right oculomotor palsy and left hemiparesis. Her Body Mass Index was 28.5 kg/m². Laboratory workup revealed a severe mixed dyslipidemia (LDL-C 168 mg/dL, Triglycerides 218 mg/dL). Brain MRI confirmed an acute infarct in the right ventral mesencephalon. Vascular imaging was unremarkable, pointing towards intrinsic small vessel disease. A comprehensive, multidisciplinary management plan was initiated, focusing on aggressive medical therapy, intensive rehabilitation, and strategies to overcome barriers to medication adherence.

Conclusion: This case highlights the elegant yet unforgiving precision of neuroanatomy and the powerful diagnostic utility of modern neuroimaging. More profoundly, it demonstrates the direct pathophysiological link between severe atherogenic dyslipidemia and the occlusion of a single, critical perforating brainstem artery. The patient’s significant functional recovery underscores that a holistic approach—combining evidence-based pharmacotherapy with a robust, patient-centered rehabilitation program and a dedicated strategy to ensure long-term adherence—is paramount to optimizing outcomes after a debilitating stroke.

The Prognostic Utility of Immature Platelet Fraction (IPF) in Adult Sepsis: A Correlation Analysis with SOFA Score and Conventional Platelet Indices

2025-08-20T18:30:54+00:00

Background: Sepsis is a leading cause of mortality, driving the search for biomarkers that can accurately reflect its severity. The immature platelet fraction (IPF) measures real-time thrombopoiesis, which is profoundly stressed during sepsis. Its clinical utility relative to conventional platelet indices (MPV, PDW) in predicting organ dysfunction remains to be fully elucidated. This study aimed to explore the relationship between these platelet parameters and the Sequential Organ Failure Assessment (SOFA) score in adult sepsis patients.

Methods: An observational, cross-sectional study was conducted on 32 adult patients diagnosed with sepsis at a tertiary hospital in Medan, Indonesia. Upon admission, platelet indices and IPF were measured using a Sysmex XN-1000 hematology analyzer. The SOFA score was calculated to quantify organ dysfunction. The relationships between variables were assessed using Pearson or Spearman correlation analysis.

Results: The analysis revealed a statistically significant but weak positive correlation between IPF and the SOFA score (r=0.354, p=0.047). In contrast, conventional indices like MPV (r=0.219, p=0.228) and PDW (r=0.190, p=0.297) showed no significant association with the SOFA score. Mechanistically, strong positive correlations were confirmed between IPF and both MPV (r=0.768, p<0.001) and PDW (r=0.775, p<0.001), reflecting a coordinated bone marrow response.

Conclusion: This study reveals a critical paradox in sepsis: while the bone marrow mounts a robust thrombopoietic response, evidenced by the tight correlation between markers of platelet production, this response is poorly coupled with clinical outcomes. The weak association between IPF and organ dysfunction severity suggests that IPF's primary utility may not be as a standalone prognostic tool, but rather as a biomarker of a high-turnover, "futile thrombopoiesis." This highlights the complexity of platelet kinetics in sepsis and warrants further investigation into its role within a multi-marker prognostic strategy.

Ocular Vascular Occlusion Following COVID-19 and Travel Vaccinations: A Systematic Review and Exploration of Immuno-Thrombotic Mechanisms

2025-08-21T18:31:31+00:00

Background: Ocular vascular occlusion is a rare, vision-threatening emergency. While typically associated with systemic vascular comorbidities, reports have emerged suggesting a temporal link to various vaccinations. This review aims to synthesize the evidence on ocular vascular occlusion following both COVID-19 and non-COVID travel vaccinations to characterize its clinical spectrum and explore shared pathophysiological underpinnings.

Methods: A systematic search adhering to PRISMA 2020 guidelines was conducted in PubMed, Scopus, Cochrane Library, and ProQuest for studies published from January 1^st, 2013, to August 1^st, 2024. All study designs reporting ocular vascular occlusion temporally associated with COVID-19 or travel immunizations were included. Data on demographics, vaccine type, clinical presentation, and outcomes were extracted. Methodological quality was assessed using the Newcastle-Ottawa Scale (NOS) for observational studies and the Joanna Briggs Institute (JBI) checklist for case reports.

Results: From an initial 1,348 records, 12 studies met the inclusion criteria, encompassing case reports, series, and large database analyses. These studies described ocular vascular occlusion in individuals aged 15 to 86 years. A significant temporal clustering was observed, with the majority of individual cases occurring within seven days post-vaccination. Central retinal vein occlusion (CRVO) was the most reported subtype. A large retrospective cohort study reported a more than two-fold increased hazard for retinal occlusion post-vaccination compared to unvaccinated cohorts (HR 2.19, 95% CI 1.85-2.59, p<0.001). Both mRNA and adenoviral vector COVID-19 vaccines, as well as various travel vaccines including Zostavax, Yellow Fever, and Meningococcal B, were implicated.

Conclusion: This review characterizes a consistent temporal association between a diverse range of vaccines and subsequent ocular vascular occlusion, suggesting it is a rare but potential adverse event. The clustering of onset times and involvement of different vaccine platforms point towards a common underlying immuno-thrombotic mechanism. These findings highlight the need for clinical vigilance for acute visual changes post-vaccination, while underscoring that the absolute risk remains exceedingly low compared to the clear benefits of vaccination.

From Handlebar to Enucleation: Management and Prosthetic Outcome of a Severe Traumatic Globe Luxation

2025-08-24T18:31:59+00:00

Background: Traumatic globe luxation (TGL) is a rare, severe ocular emergency involving the complete displacement of the eyeball from the orbit. It presents a profound clinical challenge, demanding a rapid and accurate assessment of complex prognostic factors to guide the difficult decision between globe salvage and primary enucleation.

Case presentation: A 33-year-old male presented 18 hours after a motorcycle handlebar strike to his left orbit. The examination revealed a left globe luxation with No Light Perception (NLP) vision, a total afferent pupillary defect, and complete ophthalmoplegia. Computed tomography confirmed a closed-globe injury with a superior orbital rim fracture and a large retrobulbar hematoma, but could not delineate soft tissue integrity. Surgical exploration revealed two critical, paradoxical findings: an anatomically intact optic nerve despite its functional death, and a catastrophic avulsion of five of the six extraocular muscles. The medial, lateral, and inferior recti, along with both oblique muscles, were detached, while the superior rectus muscle was uniquely spared.

Conclusion: Based on the catastrophic loss of vascular supply from the avulsed muscles, which rendered the globe biologically non-viable, a primary enucleation was performed. This case suggests that in TGL, the integrity of the extraocular musculature is a paramount prognostic indicator, potentially superseding the anatomical status of the optic nerve in determining globe viability. It highlights the necessity of intraoperative exploration to definitively assess the extent of injury and illustrates a scenario where primary enucleation is not a treatment failure, but a definitive, rehabilitation-focused therapeutic strategy.