Bioscientia Medicina : Journal of Biomedicine and Translational Research
Bioscientia Medicina : Journal of Biomedicine and Translational Research is published by CMHC (Research & Sains Center) colaborated with HM Publisher. Bioscientia Medicina : Journal of Biomedicine and Translational Research is an open access international scholarly journal in the field of biomedicine, medicine and translational research aimed to publish a high-quality scientific paper including original research papers, case reports, reviews, short communication, and technical notes.
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Retinal Neural Layer Thickness and Contrast Sensitivity in Type 2 Diabetes Without Clinical Retinopathy: A Cross-Sectional Study
Background: Retinal neural dysfunction may occur in type 2 diabetes mellitus (T2DM) before clinically visible diabetic retinopathy. Objective: We evaluated whether retinal nerve fiber layer (RNFL) and ganglion cell-inner plexiform layer (GCL-IPL) thickness were associated with contrast sensitivity in adults with T2DM without clinical retinopathy. Methods: This cross-sectional study included 30 eyes from 16 participants examined from September 2024 to June 2025. Swept-source optical coherence tomography measured average and quadrant RNFL thickness and macular GCL-IPL thickness. Monocular contrast sensitivity was assessed with the Pelli-Robson chart. Source-reported analyses included exploratory Spearman correlations, generalized estimating equations (GEE) for inter-eye clustering, and exploratory receiver operating characteristic (ROC) analysis. Results: Mean RNFL thickness was 101.3 ± 12.55 µm, GCL-IPL thickness was 81.53 ± 7.34 µm, and contrast sensitivity was 1.773 ± 0.227 logCS. Eye-level correlations with contrast sensitivity were ρ=0.758 for GCL-IPL and ρ=0.640 for average RNFL (both source-reported p<0.001). In the exploratory GEE model, coefficients were 0.0104 logCS per µm for GCL-IPL (95% CI 0.001-0.019) and 0.0062 for RNFL (95% CI 0.001-0.011). Exploratory AUCs were 0.872 and 0.804, respectively. Conclusion: Thicker GCL-IPL and RNFL measurements were associated with better contrast sensitivity in this small cohort. The estimates are hypothesis-generating and require confirmation with participant-level data, larger samples, and external validation before clinical use.
Muhammad Aulia Molid Ogest Putra Calisanie
Copyright (c) 2026 Ramzi Amin, Ririn Rahayu, Petty Purwanita, Muhammad Aulia Molid Ogest Putra Calisanie https://creativecommons.org/licenses/by-nc-sa/4.0
Association of Foveal Avascular Zone Diameter with Best-Corrected Visual Acuity in Diabetic Retinopathy: A Cross-Sectional Optical Coherence Tomography Angiography Study
Background: Foveal avascular zone (FAZ) enlargement reflects capillary loss in diabetic retinopathy (DR), but its relationship with visual acuity varies across protocols and populations. Objective: We assessed the association between swept-source optical coherence tomography angiography (OCTA)-derived FAZ diameter and best-corrected visual acuity (BCVA). Methods: This cross-sectional study included 32 adults with DR examined from April to December 2024. One eye per participant underwent 3×3-mm swept-source OCTA. Superficial and deep FAZ diameter, superficial vessel density, central subfield thickness, and LogMAR BCVA were assessed using correlations, severity-group comparisons, multivariable regression, and exploratory secondary analyses. Results: Mean age was 57.8±8.4 years; 17 participants (53.1%) were men. Mean superficial FAZ diameter was 617.6±171.6 µm and BCVA was 0.539±0.341 LogMAR. FAZ diameter correlated with worse BCVA (r=0.582, 95% confidence interval [CI] 0.293–0.774; p<0.001) and increased from 458.3±82.1 µm in mild nonproliferative DR to 812.5±125.8 µm in proliferative DR (F(3,28)=16.35; p<0.001; η²=0.637). FAZ was the largest standardized correlate in the exploratory adjusted model (β=0.485; p<0.001; adjusted R²=0.412). An exploratory 580-µm cutoff yielded an area under the curve of 0.847 (95% CI 0.723–0.971). Conclusion: Larger superficial FAZ diameter was associated with worse BCVA and greater DR severity. The proposed cutoff and secondary models require independent validation.
Copyright (c) 2026 Ramzi Amin, Rezandi Pratama, Petty Purwanita, Muhammad Aulia Molid Ogest Putra Calisanie https://creativecommons.org/licenses/by-nc-sa/4.0
Global and Site-Specific Osteoarthritis Burden, 1990–2021, and Rehabilitation Capacity Modeling for Indonesia: A Spatiotemporal Analysis
Background: Osteoarthritis is a major and growing cause of disability, but prevalence does not directly measure clinically assessed rehabilitation need, demand, utilization, or unmet need. Objective: We quantified global, regional, national, and joint-site burden and linked rehabilitation-amenable prevalence to transparent capacity scenarios for Indonesia. Methods: We integrated annual WHO/IHME rehabilitation-amenable osteoarthritis estimates for 195 countries (1990–2021), published GBD 2019 site-specific prevalence, published GBD 2021 incidence and years lived with disability, and WHO rehabilitation specifications. EAPC was calculated from annual posterior-mean age-standardized rates using log-linear regression; published joinpoint AAPC retained its original name. Deterministic scenarios converted Indonesia’s 2021 prevalence into direct-contact hours and multidisciplinary FTE-year equivalents. Results: In 2021, 371.6 million people globally and 9.08 million in Indonesia had osteoarthritis-related functioning problems for which rehabilitation could be beneficial. From 1990 to 2021, prevalence increased by 137.7% globally and 199.8% in Indonesia. Prevalence EAPC was 0.34% annually globally and 0.55% in Indonesia. Knee osteoarthritis had the highest site-specific rate, whereas hand incidence and YLDs had the fastest published AAPCs in several middle-SDI settings. Indonesia’s foundational, scale-up, and comprehensive scenarios produced 5,673, 29,223, and 93,914 direct-contact FTE-year equivalents. Conclusion: Rehabilitation-amenable osteoarthritis burden increased faster in Indonesia than globally and varied by joint site and development level. Scenario outputs are model-based decision quantities, not national staffing requirements or workforce gaps, and require stakeholder validation with local severity, capacity, delivery, referral, adherence, and workforce data.
Copyright (c) 2026 Dina Wulandari https://creativecommons.org/licenses/by-nc-sa/4.0
Calcium Channel Blockers in Kidney Transplant Recipients: Cyclosporine-Era Kidney-Function Effects and Tacrolimus Pharmacokinetic Implications: A Meta-Analysis
Background: Post-transplant hypertension and calcineurin-inhibitor nephrotoxicity threaten cardiovascular and graft outcomes after kidney transplantation. Calcium channel blockers offer haemodynamic benefit and alter calcineurin-inhibitor exposure, but cyclosporine and tacrolimus studies assessed different evidence domains. Objective: To pool the comparative effect of calcium channel blockers on kidney-function outcomes in adult kidney transplant recipients, and to distinguish the cyclosporine-era kidney-function evidence from the tacrolimus-era pharmacokinetic implications. Methods: Comparative randomised trials and cohorts in adult kidney transplant recipients were identified through PubMed, the Cochrane Library, citation pathways, and reference checking. Kidney-function outcomes were directionally harmonised. Compatible standardised mean differences were pooled using a restricted maximum-likelihood random-effects model with Hartung–Knapp inference. Prediction intervals, subgroup analyses, influence diagnostics, sensitivity analyses, and Cochrane RoB 2 assessments were completed. Results: At least 22 reports represented at least 21 independent datasets; seven cyclosporine-treated trials with 639 participants supplied compatible kidney-function data. Calcium channel blockers were favoured (Hedges g 0.38, 95% CI 0.11 to 0.66; I²=45.2%; τ²=0.042), although the 95% prediction interval ranged from −0.19 to 0.96. Leave-one-out estimates ranged from 0.26 to 0.45. DerSimonian–Laird and critical-risk sensitivities yielded g 0.38 and 0.37. A tacrolimus clinical subgroup and primary Egger test were not estimable. Conclusion: Calcium channel blockers were associated with modestly better kidney-function measurements during cyclosporine treatment, but very-low-certainty evidence precluded a uniform benefit claim. Tacrolimus evidence instead concerned CYP3A5-dependent exposure and dose sparing; the two evidence streams remain clinically linked but quantitatively non-equivalent.
Copyright (c) 2026 Harnavi Harun, Evelin Veronike, Garri Prima Decroli, Muhammad Ridhwan Fatharanifurqan https://creativecommons.org/licenses/by-nc-sa/4.0
Laser Haemorrhoidoplasty versus Stapled Haemorrhoidopexy for Grade II–III Haemorrhoidal Disease: A Systematic Review and Meta-Analysis of Postoperative Pain and Perioperative Outcomes
Background: Postoperative pain and delayed recovery are the principal drawbacks of excisional haemorrhoid surgery, and two minimally invasive alternatives — laser haemorrhoidoplasty (LH) and stapled haemorrhoidopexy (SH) — are increasingly used to overcome them. Although each has repeatedly been compared with conventional haemorrhoidectomy, the direct head-to-head evidence comparing LH with SH has never been pooled quantitatively. Objective: This systematic review and meta-analysis compared the perioperative, early postoperative pain and safety outcomes of LH and SH in adults with symptomatic haemorrhoidal disease. Methods: PubMed, Scopus-indexed journals, Crossref and Google Scholar were searched systematically for randomised and comparative studies directly comparing LH with SH. Ten studies were included and seven contributed poolable data. Random-effects models (DerSimonian–Laird, with Hartung–Knapp–Sidik–Jonkman intervals for inference on continuous outcomes) generated risk ratios (RR) for dichotomous outcomes and standardised mean differences (SMD, Hedges g) for continuous outcomes; raw mean differences were reported for interpretability. Risk of bias was appraised with RoB 2 and ROBINS-I, and the certainty of evidence was rated for each outcome. Results: Laser haemorrhoidoplasty was associated with a significantly shorter operative time (SMD −1.65, 95% CI −2.47 to −0.84; p<0.001; approximately 8 minutes shorter on average), a shorter hospital stay (SMD −3.07, 95% CI −5.58 to −0.55; p=0.017) and a non-significant trend toward less intraoperative blood loss (SMD −2.30, 95% CI −4.74 to 0.13; p=0.064). Early postoperative pain (≤24 h) did not differ significantly on pooling (SMD −0.66, 95% CI −1.95 to 0.63; p=0.32; I² 98%); this reflected a time-dependent crossover in which LH was less painful in the first hours but SH became less painful from 24 hours onward. Overall complications favoured LH numerically but not significantly (RR 0.58, 95% CI 0.25 to 1.30; p=0.18), an advantage confined to short-follow-up studies and reversed in the single 24-month trial. Recurrence, bleeding, anal stenosis and urinary retention were comparable. The certainty of evidence was low to very low for all outcomes. Conclusion: Laser haemorrhoidoplasty offered consistent intraoperative advantages over stapled haemorrhoidopexy, whereas early pain and safety were comparable and duration of follow-up was the dominant effect-modifier. Both are reasonable minimally invasive options; technique selection should be individualised pending adequately powered long-term trials.
Surgical Outcomes and Recurrence in Adult Abdominal Cocoon (Sclerosing Encapsulating Peritonitis): A Systematic Review and Meta-Analysis of Pooled Proportions
Background: Abdominal cocoon, also termed sclerosing encapsulating peritonitis (SEP) or encapsulating peritoneal sclerosis (EPS), is a rare cause of intestinal obstruction in which the small bowel is encased within a fibrocollagenous membrane, producing the prototypical frozen abdomen. Its surgical outcomes had never been pooled quantitatively. Objective: To quantitatively pool the surgical outcomes of adult abdominal cocoon — peri-operative mortality, morbidity, recurrence and pre-operative diagnostic yield — in patients undergoing operative management. Methods: PubMed, Scopus, the Cochrane Library and Google Scholar were searched for observational studies reporting the operative management and outcomes of adult abdominal cocoon. Ten case series (179 operated patients) were included. As all studies were single-arm, proportions were pooled with the Freeman–Tukey transformation under a DerSimonian–Laird random-effects model; robustness was tested with a logit-normal model, leave-one-out analysis and the Egger test, and quality with the Joanna Briggs Institute checklist. Results: Pooled peri-operative mortality was 4.5% (95% CI 0.2–12.1%; k=7); because zero-event studies influence the double-arcsine transformation, a logit-normal model gave 13.1% and the crude proportion 7.9%, so mortality is best summarised as low-to-moderate. Pooled morbidity was 19.5% (95% CI 5.9–36.9%; k=5), recurrence 3.3% (95% CI 0.0–21.8%; k=3) and pre-operative diagnostic yield 19.1% (95% CI 6.0–36.0%; k=4). Leave-one-out kept mortality between 3.0% and 8.5%. Conclusion: Surgery for adult abdominal cocoon achieved low-to-moderate mortality and acceptable morbidity with infrequent recurrence, supporting membrane excision and adhesiolysis in selected patients, while the low pre-operative diagnostic rate signals a need for greater awareness.
When Bleeding Stops but Organs Fail: Fatal Multiple Organ Dysfunction Syndrome Following Massive Atonic Postpartum Haemorrhage in a Young Primipara — A Case Report
Background: Postpartum haemorrhage from uterine atony can precipitate profound haemorrhagic shock within minutes, and in resource-constrained referral systems the interval between the onset of bleeding and definitive source control is frequently the decisive determinant of survival. Objective: To document, in granular day-by-day detail, the evolution of fatal multiple organ dysfunction syndrome following massive atonic postpartum haemorrhage in a young woman with no antecedent organ disease, and to translate that trajectory into transferable lessons for haemorrhage systems in resource-limited settings. Case presentation: We describe a 28-year-old primipara referred four hours after a vacuum-assisted vaginal delivery of twins complicated by severe pre-eclampsia. On arrival she was stuporous, hypotensive (70/68 mmHg), tachycardic (142 beats/min) and oliguric, with active vaginal bleeding and a haemoglobin of 2.4 g/dL. Resuscitation and haemorrhage control proceeded in parallel: high-flow oxygen, dual large-bore access, crystalloid and colloid loading, tranexamic acid, balanced blood-component transfusion, bimanual compression, intubation and emergency laparotomy. A flaccid, bluish, atonic uterus and a fourth-degree perineal tear were identified; subtotal hysterectomy with sphincteroplasty and perineorrhaphy achieved haemostasis. Despite massive transfusion and intensive care, prolonged hypoperfusion evolved into ischaemic hepatitis, severe coagulopathy, stage III acute kidney injury requiring haemodialysis, hospital-acquired pneumonia with drug-resistant sepsis, acute pulmonary oedema and upper gastrointestinal bleeding. Progressive multiple organ dysfunction syndrome culminated in asystolic cardiac arrest on postoperative day 15. Conclusion: This case illustrates a principle easily overlooked: definitive surgical haemostasis does not reverse organ injury already committed during the pre-operative shock interval. Objective cumulative blood-loss measurement, immediate haemorrhage-bundle and massive-transfusion protocol activation, explicitly documented uterotonic therapy, rapid balanced resuscitation and structured post-haemostasis organ surveillance are the interventions most likely to interrupt the lethal trajectory.
Higher Ictal EEG Amplitude Predicts Greater PANSS Improvement in Schizophrenia Patients Undergoing Electroconvulsive Therapy: A Two-Group Analytical Study in Surakarta, Indonesia
Background: Schizophrenia frequently responds incompletely to antipsychotics, and electroconvulsive therapy (ECT) remains an important somatic augmentation for severe or treatment-resistant disease; however, the neurophysiological determinants of ECT response are shifting from seizure duration toward ictal electroencephalographic (EEG) quality, of which peak ictal amplitude is a putative but under-tested marker. Objective: To determine whether peak ictal EEG amplitude predicts the magnitude of symptomatic improvement, measured by the Positive and Negative Syndrome Scale (PANSS), in schizophrenia patients undergoing electroconvulsive therapy. Methods: This analytical two-group study at RSJD dr. Arif Zainuddin, a tertiary psychiatric hospital in Surakarta, Central Java, Indonesia, enrolled 36 consecutively sampled inpatients (18 per group) with DSM-5-TR/ICD-11-confirmed schizophrenia undergoing ECT, reported per STROBE. Peak ictal EEG amplitude was dichotomised at 1000 µV; the Positive and Negative Syndrome Scale (PANSS), applied by trained raters using the validated Indonesian adaptation, was measured before and after the ECT course. Analyses included paired and independent t-tests, correlation, receiver-operating-characteristic (ROC) analysis, and multivariable linear and penalised logistic regression. Results: Both groups improved (both paired p<0.001), but the ≥1000 µV group achieved markedly greater total-PANSS reduction (34.7±9.2 vs 23.2±8.5 points; mean difference 11.5, 95% CI 5.5–17.5; t(34)=3.90; p=0.0004; Cohen d=1.30) and higher ≥30% response (72.2% vs 16.7%). Continuous amplitude correlated with PANSS reduction (r=0.73, p<0.001), the adjusted odds ratio for response was 4.85 (95% CI 1.56–15.06), and amplitude discriminated responders well (AUC 0.88; Youden cut-off ~1093 µV; sensitivity 81%, specificity 90%). Conclusion: Higher ictal EEG amplitude independently predicts greater symptomatic improvement in schizophrenia, supporting routine intra-procedural amplitude monitoring to optimise therapeutic seizure quality, particularly in resource-constrained psychiatric practice.
Admission Systemic Immune-Inflammation Index and Its Association with High Thrombus Burden and No-Reflow in ST-Segment Elevation Myocardial Infarction: A Retrospective Cohort Study
Background: ST-segment elevation myocardial infarction (STEMI) is a thrombo-inflammatory emergency, and successful epicardial recanalisation during primary percutaneous coronary intervention (PCI) does not always restore myocardial perfusion. The Systemic Immune-Inflammation Index (SII), derived from routine platelet, neutrophil and lymphocyte counts, may reflect thrombo-inflammatory risk. Objective: This study evaluated the association of admission SII with high thrombus burden and no-reflow in STEMI patients undergoing primary PCI. Methods: This STROBE-compliant retrospective cohort study consecutively sampled 118 STEMI patients at Prof. dr. I.G.N.G. Ngoerah General Hospital, Denpasar. High thrombus burden was defined as TIMI thrombus grade 4-5 and no-reflow as post-procedural TIMI flow grade =2. The optimal SII cut-off was derived by receiver operating characteristic analysis (Youden index); associations were assessed with chi-square/Fisher tests and modified Poisson regression with robust standard errors. Results: High thrombus burden occurred in 99 patients (83.9%) and no-reflow in 16 (13.6%). High SII was associated with high thrombus burden (90.8% vs 75.5%; relative risk 1.203, 95% CI 1.013-1.428; p=0.025) and no-reflow (20.0% vs 5.7%; relative risk 3.53, 95% CI 1.062-11.753; p=0.024), persisting after adjustment (adjusted relative risk 1.194 and 3.226, respectively). Discrimination was weak-to-modest (AUC 0.597 and 0.674). Conclusion: Admission SII was independently associated with high thrombus burden and no-reflow but had insufficient accuracy for standalone prediction, supporting its role as a simple adjunctive marker rather than a definitive predictor.
Synergistic Reduction of TNF-α by Combined Ursodeoxycholic Acid and Multi-Strain Probiotics in a Rat Model of Cholestasis
Background: Cholestasis is a complex hepatobiliary disorder in which impaired bile flow provokes a sustained inflammatory response, with tumor necrosis factor-alpha (TNF-α) acting as a central pro-inflammatory mediator. Ursodeoxycholic acid (UDCA) is the first-line therapy, but a substantial subset of patients responds incompletely, motivating adjunctive strategies that target extrahepatic, gut-derived drivers of inflammation through the gut–liver axis. Objective: To evaluate whether multi-strain probiotics potentiate the anti-inflammatory (TNF-α–lowering) effect of ursodeoxycholic acid (UDCA) in experimental cholestasis. Methods: This randomised, post-test-only controlled experimental study was reported in accordance with ARRIVE 2.0 guidelines. Thirty-five male Sprague-Dawley rats were randomised into seven groups (n=5): healthy control (K1), disease control (K2), UDCA monotherapy (K3), probiotic monotherapy (K4), and three UDCA plus dose-escalating probiotic combinations (K5–K7). Cholestasis was induced by common bile duct ligation; interventions ran for 21 days. Serum TNF-α was quantified by ELISA and analysed with one-way ANOVA, Tukey HSD and Games-Howell post hoc tests, effect sizes, and dose-response regression. Results: TNF-α differed markedly across groups (F(6,28)=783.5, p<0.001, η²=0.994). Ligation raised TNF-α from 5.69±0.25 pg/mL (K1) to 17.88±0.43 pg/mL (K2; p<0.001, Cohen's d=34.7). Both monotherapies reduced TNF-α (K3 14.91±0.49; K4 12.50±0.32; both p<0.001), but combination therapy achieved significantly greater suppression, lowest in K7 (7.91±0.18 pg/mL; 55.8% reduction; 81.8% normalisation toward healthy). A significant dose-dependent decline occurred across combination groups (slope=−0.113 pg/mL per mg, r=−0.94, R²=0.89, p<0.001). Conclusion: Combined UDCA and probiotics produce a synergistic, dose-dependent reduction of TNF-α in experimental cholestasis, supporting probiotics as a rational adjunct targeting the gut–liver axis and warranting translational evaluation in cholestatic patients.
Dietary Pattern and Psychological Stress Are Not Associated with Gastro-oesophageal Reflux Symptoms in Female Preclinical Medical Students: A Precision-Focused Cross-Sectional Study
Background: Gastro-oesophageal reflux disease is among the most prevalent chronic gastrointestinal disorders worldwide and its absolute burden continues to rise, yet studies of behavioural determinants in young adults report statistical significance without magnitude and almost never state the effect size their design could detect. Objective: To estimate the association of dietary pattern and psychological stress with symptom-defined gastro-oesophageal reflux, and the precision with which those associations could be detected, in a restriction-based sample of female preclinical medical students. Methods: This STROBE-compliant cross-sectional study used a restriction-based design to isolate behavioural exposures from adiposity and the other dominant reflux risk factors. Of 120 randomly selected female preclinical medical students at the Faculty of Medicine, Universitas Pembangunan Nasional "Veteran" Jakarta, 104 responded (86.7%) and 87 met eligibility criteria fixing female sex, body mass index 18.5-24.9 kg/m2, never-smoking, no alcohol intake and no gastro-active medication. Dietary pattern, stress and reflux symptoms were measured with validated Indonesian instruments and analysed with exact tests, Firth penalised logistic regression, Bayesian estimation, quantitative bias analysis and formal precision analysis. Results: GERD-Q positivity was 12.6% (95% CI 7.2-21.2); 8.0% had a poor dietary pattern and 43.7% reported stress. Adjusted odds ratios were 3.35 (95% CI 0.55-16.12; p = 0.208) for poor dietary pattern and 1.10 (95% CI 0.31-3.78; p = 0.339) for stress; Bayes factors favouring the null ranged from 0.99 to 2.05 and from 1.78 to 4.90 across four priors. Minimum detectable odds ratios were 12.23 and 4.32. Correcting for outcome misclassification raised the dietary odds ratio to 6.61. Conclusion: Neither exposure was associated with reflux symptoms; the study excludes only large effects, and about 459 participants would be needed to detect the observed dietary effect.
Copyright (c) 2026 Najwa Faradila Yuvitri, Sri Wahyuningsih, Wilfadri Putra Jonesti, Aulia Chairani https://creativecommons.org/licenses/by-nc-sa/4.0
Mycological Culture Profile and Clinical Predictors of Culture Positivity in Dermatophytosis: A Four-Year Retrospective Study at a Tertiary Referral Hospital in Bali, Indonesia
Background: Dermatophytosis is the commonest superficial mycosis, yet the aetiological spectrum in eastern Indonesia and the determinants of a positive fungal culture remain poorly characterised. We aimed to describe the mycological culture profile and identify predictors of culture positivity at a tertiary referral centre in Bali. Methods: This STROBE-compliant retrospective cross-sectional study analysed 214 consecutively sampled patients with dermatophytosis at the Dermatology and Venereology clinic of Ngoerah Hospital, Denpasar, between January 2020 and December 2023. Potassium-hydroxide (KOH) microscopy and Sabouraud culture data were extracted from records. Proportions carried 95% Wilson confidence intervals (CI); associations were assessed by chi-square/Fisher tests with odds ratios and Cramér's V, followed by multivariable logistic regression (adjusted odds ratio [aOR], Nagelkerke R²) and receiver-operating-characteristic analysis. Results: Mean age was 42.7 years and the male-to-female ratio 1.68:1; Fitzpatrick phototype IV predominated (51.9%). Culture was positive in 138 patients (64.5%; 95% CI 57.9–70.6). Trichophyton rubrum was the leading isolate (50.0%; 95% CI 41.8–58.2), followed by the T. mentagrophytes complex (15.9%) and Microsporum canis (10.1%); anthropophilic species comprised 81.2%. KOH positivity (aOR 5.20; 95% CI 2.27–11.87; p<0.001) independently predicted culture positivity, whereas prior antifungal use was protective (aOR 0.30; 95% CI 0.13–0.65; p=0.002); the model discriminated well (AUC 0.785; 95% CI 0.715–0.855). Conclusion: Dermatophytosis in Bali is dominated by anthropophilic T. rubrum, and culture yield is governed chiefly by prior antifungal exposure and KOH status, supporting a stewardship-oriented diagnostic pathway in which culture is prioritised for KOH-positive, treatment-naive and recalcitrant presentations.
Comparative Effectiveness of Channa micropeltes Albumin Extract Versus Human Albumin on Lactate and Central Venous Oxygen Saturation as Predictors of Mortality in Critically Ill Patients with Hypoalbuminemia: A Double-Blind Randomized Controlled Trial
Background: Hypoalbuminemia is highly prevalent in critically ill patients and is linked to impaired tissue perfusion and increased mortality. Human albumin is the gold-standard replacement but is costly and largely imported. Channa micropeltes (giant snakehead) albumin extract is a potential economical local alternative, yet comparative evidence on tissue-perfusion biomarkers—lactate and central venous oxygen saturation (ScvO2)—as predictors of mortality is scarce. Methods: A double-blind randomized controlled trial in the intensive care unit of Dr. Moewardi Regional General Hospital, Surakarta, enrolled 32 adults with serum albumin <2.8 g/dL randomized to oral Channa micropeltes extract 5 g every 12 h (n=16) or intravenous 20% human albumin (n=16) for three days. Lactate and ScvO2 were sampled via central venous catheter on day 0 and day 3; mortality was followed to day 4. Analyses included repeated-measures ANOVA, Cohen's d, ROC curves and multivariable logistic regression. Results: Lactate fell in both arms (Channa 5.29±1.32 to 3.52±1.00; human 5.31±0.94 to 3.63±1.09 mmol/L; both p<0.001; d≥1.5) and ScvO2 rose (Channa +10.53%; human +9.54%; both p<0.001), with no between-group difference (Δ lactate p=0.812; Δ ScvO2 p=0.620). Day-3 biomarker AUCs for mortality were 0.572 and 0.498. Albumin type was not associated with mortality (adjusted OR 0.354; 95% CI 0.067–1.862; p=0.220; NNT 16). No serious adverse events occurred. Conclusion: Channa micropeltes albumin extract was non-inferior to human albumin for restoring tissue-perfusion biomarkers, supporting its potential as an economical, locally available alternative in critically ill patients with hypoalbuminemia.
Early Individualized Medical Nutrition Therapy in Recurrent Luminal B Breast Cancer Complicated by Post-Chemotherapy Febrile Neutropenia and Pancytopenia with Moderate Malnutrition: A Case Report
Background: Breast cancer is the most common malignancy among women, and malnutrition affects approximately 30–50% of hospitalized patients with cancer, independently increasing treatment-related toxicity, prolonging hospitalization, and worsening survival. When cytotoxic chemotherapy precipitates febrile neutropenia and pancytopenia, reduced intake, systemic inflammation, and bone-marrow suppression converge, yet nutritional care is frequently deprioritized during the neutropenic nadir. Case presentation: A 58-year-old woman with recurrent left breast cancer (luminal B subtype), previously treated with mastectomy and three chemotherapy cycles, presented with two weeks of anorexia, fever (40.6 °C), vomiting, diarrhea, and 3 kg weight loss. Anthropometry showed a body mass index of 17.6 kg/m2 and a mid-upper-arm circumference of 23 cm; laboratory testing confirmed febrile neutropenia (absolute neutrophil count 0.05 ×103/µL) with pancytopenia and hypoalbuminemia (2.7 g/dL). She met three phenotypic and two etiologic Global Leadership Initiative on Malnutrition (GLIM) criteria, establishing moderate malnutrition. Alongside supportive care and granulocyte colony-stimulating factor, individualized medical nutrition therapy targeting 2,100 kcal/day and 90 g protein/day was delivered as a soft oral diet with a peptide-based oral nutritional supplement and vitamin B12. Oral intake rose from 50% or less to 86% by day three and 93% by day four; over six days, weight, appetite, physical function, and all hematologic indices recovered, and she was discharged stable. Conclusion: Early, individualized medical nutrition therapy initiated before severe malnutrition develops can support concurrent nutritional, immune, and hematologic recovery in breast cancer patients with post-chemotherapy hematologic toxicity. Routine nutritional screening and prompt, protein-focused intervention should be integrated into oncology care.
Risk of Amiodarone-Induced Pulmonary Toxicity Versus Placebo in Patients with Cardiac Arrhythmias and Heart Failure: A Meta-Analysis of Randomised Controlled Trials
Background: Amiodarone is the most effective antiarrhythmic agent for maintaining sinus rhythm, yet its long-term use is constrained by extracardiac toxicity, of which pulmonary toxicity is the most feared because it carries appreciable mortality and is frequently misdiagnosed. No contemporary meta-analysis has isolated amiodarone-induced pulmonary toxicity as the single primary endpoint across cardiac arrhythmia and heart-failure populations; this study quantified that risk. Methods: PubMed/MEDLINE, Scopus and Web of Science were searched for placebo- or usual-care-controlled randomised controlled trials (RCTs) of oral amiodarone in adults with cardiac arrhythmia or heart-failure indications reporting pulmonary toxicity. Two reviewers extracted 2×2 data and assessed risk of bias with Cochrane RoB 2.0. Because the outcome was dichotomous, the risk ratio (RR) was pooled using a DerSimonian–Laird random-effects model, with the odds ratio (OR) and Peto OR as corroborative measures. Results: Nine RCTs comprising 6,209 patients (3,175 amiodarone; 3,034 control) were included. Pulmonary toxicity occurred in 77 of 3,175 amiodarone-treated patients (2.43%) versus 42 of 3,034 controls (1.38%). Amiodarone significantly increased pulmonary-toxicity risk (RR 1.70, 95% CI 1.17–2.45, p = 0.005), with no detectable heterogeneity (I² = 0%). The OR (1.74) and Peto OR (1.81) were concordant, and the estimate remained harmful under every single-study deletion (RR 1.46–2.64). Higher-dose strata showed a numerically larger effect (RR 2.50) than lower-dose strata (RR 1.69; subgroup p = 0.48). Conclusion: Amiodarone was associated with an approximately 70% relative increase in pulmonary-toxicity risk versus placebo, a robust and homogeneous finding. The absolute excess was modest (about one additional case per 95 patients treated), supporting continued use with structured baseline and periodic pulmonary surveillance, particularly at higher maintenance doses and longer durations.
Enzyme-Inducing Antiseizure Medications and Hypovitaminosis D in Children with Epilepsy: A Cross-Sectional Study in West Sumatera, Indonesia
Background. Long-term antiseizure-medication (ASM) therapy can accelerate vitamin D catabolism via hepatic cytochrome P450 induction, predisposing children with epilepsy to hypovitaminosis D and its skeletal consequences; Indonesian tertiary-centre data remain scarce. Methods. This cross-sectional study examined the association between ASM class, number and duration and serum 25-hydroxyvitamin D [25(OH)D] in children aged 1–18 years at Dr. M. Djamil General Hospital, Padang, West Sumatera, between April and October 2025. Of 82 records screened, 77 were eligible; 25(OH)D was measured by enzyme-linked fluorescent assay, with hypovitaminosis D defined as <30 ng/mL. Associations were tested with Fisher–Freeman–Halton exact and chi-square tests, odds ratios, ANOVA, multivariable logistic regression and ROC analysis. Results. Hypovitaminosis D affected 48 children (62.3%; 95% CI 51.2–72.3), with mean 25(OH)D of 18.3±6.7 versus 41.6±11.2 ng/mL in deficient versus replete children. ASM class was significantly associated with vitamin D status (exact p=0.037; Cramér's V=0.283): all nine enzyme-inducing users were deficient, versus 56.0% non-enzyme-inducing and 58.1% combination (ANOVA p=0.045, η²=0.080). Neither ASM number (p=0.642) nor duration (p=0.348) was associated. Enzyme-inducing exposure carried the largest adjusted odds (adjusted OR 5.66, 95% CI 0.62–52.06), and the model discriminated moderately (AUC 0.685). Conclusion. Hypovitaminosis D is prevalent in Indonesian children with epilepsy and is most strongly linked to enzyme-inducing ASMs, supporting early routine 25(OH)D monitoring and supplementation from treatment initiation.
Discordance Between Plasma and Intratumoral Estradiol in Treatment-Naïve Luminal Breast Cancer: A Cross-Sectional Study
Background: Estradiol drives luminal breast cancer, and plasma estradiol is widely used as a systemic marker; whether it reflects the intratumoral hormonal milieu is uncertain. This study evaluated the relationship between plasma and intratumoral estradiol and their demographic determinants in treatment-naive luminal breast cancer. Methods: An observational analytical cross-sectional study was conducted at Dr. Moewardi Regional General Hospital and the Anatomical Pathology Laboratory, Universitas Sebelas Maret, Surakarta, Indonesia (2019-2024). Fifty-six treatment-naive patients with Luminal A or Luminal B breast cancer were enrolled by total sampling. Plasma estradiol was measured by enzyme-linked immunosorbent assay and intratumoral estradiol by immunohistochemistry; data were analysed with Spearman correlation, chi-square/Fisher tests, logistic regression and ROC analysis, with effect sizes and 95% confidence intervals. Results: Plasma estradiol did not correlate with intratumoral estradiol (Spearman rho = 0.136; 95% CI -0.13 to 0.39; p = 0.319) and discriminated tissue positivity at chance level (AUC = 0.42; 95% CI 0.25-0.59). Age >=50 years (OR 7.27; 95% CI 2.01-26.29; p = 0.001) and postmenopausal status (OR 11.61; 95% CI 2.85-47.38; p < 0.001) were associated with high plasma estradiol, and postmenopausal status remained independent after adjustment (adjusted OR 11.16; 95% CI 2.68-46.54). Neither variable was associated with intratumoral estradiol (p = 0.863 and p = 0.665). Conclusion: Systemic estradiol does not represent the tumour hormonal state in luminal breast cancer; intratumoral estrogen appears governed by local intracrine mechanisms. Tumour-specific assessment may guide endocrine therapy more accurately than plasma measurement alone.
Progressive Fahr's Syndrome with Severe Hypocalcemia in a Woman with Uncontrolled Type 2 Diabetes Mellitus and Coronary Artery Disease: A Case Report
Background: Fahr's syndrome denotes bilateral, symmetric calcification of the basal ganglia and other deep cerebral structures arising from an identifiable secondary cause, most commonly a disorder of calcium–phosphate metabolism. Its association with diabetes mellitus and systemic vascular calcification is increasingly recognized but seldom documented in a single patient. Case presentation: A 58-year-old woman presented with one month of intermittent confusion, bilateral resting hand tremor, intermittent muscle cramps, and gait imbalance. Three months earlier she had a first-ever generalized tonic–clonic seizure coinciding with a new diagnosis of type 2 diabetes mellitus, after which she was non-adherent to insulin therapy. Examination revealed a fine resting tremor, a positive Trousseau sign, and impaired finger-to-nose testing. Investigations showed severe hypocalcemia (4.4 mg/dL), HbA1c 9.7%, and electrocardiographic anterior ischemia with cardiomegaly on chest radiography. Non-contrast cranial computed tomography demonstrated extensive bilateral symmetric calcification of the basal ganglia, cerebellum, thalami, and corona radiata–centrum semiovale. She was diagnosed with Fahr's syndrome with hypocalcemia, type 2 diabetes mellitus, and coronary artery disease, and managed with insulin, calcium lactate, vitamin D3, aspirin, simvastatin, and bisoprolol, with symptomatic improvement by the third hospital day. Conclusion: Bilateral intracranial calcification warrants a structured search for secondary causes, particularly calcium–phosphate disturbance. The coexistence of uncontrolled diabetes, coronary artery disease, and progressive brain calcification supports a panvascular contribution and underscores the need for sustained metabolic control and longitudinal neurological follow-up, given that no curative therapy currently exists.
Optimal Timing of Tracheostomy in Critically Ill Adults Requiring Prolonged Mechanical Ventilation: An Updated Meta-Analysis of Randomized Controlled Trials
Background: Tracheostomy is among the most frequently performed procedures in the intensive care unit (ICU), yet the optimal timing relative to the onset of invasive mechanical ventilation remains contested. This study aimed to provide an updated quantitative synthesis of randomized controlled trials (RCTs) comparing early versus late tracheostomy in critically ill adults, incorporating the two most recent landmark trials. Methods: PubMed was systematically searched, supplemented by reference-list screening, for RCTs comparing early with late tracheostomy in mechanically ventilated adults. Study selection and data extraction were performed independently and in duplicate. Risk of bias was appraised with the Cochrane RoB 2 tool and the certainty of evidence with the GRADE framework. Dichotomous outcomes (all-cause mortality, ventilator-associated pneumonia [VAP]) were pooled as risk ratios (RR); continuous outcomes (duration of mechanical ventilation, ventilator-free days) as standardized mean differences (SMD, Hedges’ g), using a DerSimonian–Laird random-effects model. Results: Nine RCTs enrolling 2,500 critically ill adults were included. Early tracheostomy was not associated with reduced all-cause mortality (RR 0.88, 95% CI 0.70–1.09; p=0.24; I²=58.9%; prediction interval 0.48–1.59; seven trials; moderate certainty). A non-significant trend towards fewer VAP episodes was observed (RR 0.67, 95% CI 0.42–1.05; p=0.08; I²=71.0%; four trials; low certainty). Early tracheostomy showed non-significant tendencies towards a shorter duration of mechanical ventilation (SMD −1.38, 95% CI −3.44 to 0.68; I²=97.2%) and more ventilator-free days (SMD 0.20, 95% CI −0.07 to 0.47). Leave-one-out and Hartung–Knapp–Sidik–Jonkman analyses confirmed the robustness of the neutral mortality finding. Conclusion: In critically ill adults requiring prolonged mechanical ventilation, early tracheostomy did not significantly reduce mortality and conferred, at most, modest and uncertain benefits on VAP and ventilation-related resource use. Timing should remain an individualized clinical decision rather than a uniform protocol.
Menopausal Status as the Strongest Independent Predictor of Neoadjuvant Chemotherapy Response in Locally Advanced Breast Cancer
Background: Neoadjuvant chemotherapy (NAC) is the standard treatment for locally advanced breast cancer (LABC), yet predicting individual patient response remains challenging. This study investigates menopausal status and other clinicopathological factors as predictors of NAC response in a Southeast Asian population. Methods: This retrospective cohort study analyzed 247 LABC patients treated with NAC between 2022–2023 at the Oncology Surgery Division, Prof. Dr. I.G.N.G. Ngoerah General Hospital, Denpasar, Bali. Variables included menopausal status (premenopausal vs. postmenopausal), histological type, histological grading, molecular subtype, lymphovascular invasion (LVI), tumor-infiltrating lymphocytes (TIL), and age. Bivariate analysis used chi-square tests; multivariate logistic regression identified independent predictors. Results: Among 247 patients (mean age 51.7 ± 9.1 years), 130 (52.6%) achieved positive response. Postmenopausal patients demonstrated significantly higher response rates (79.7% vs. 12.1%, p<0.001). Multivariate analysis revealed menopausal status as the strongest predictor (OR=14.999, 95%CI: 6.045–37.213, p<0.001), followed by molecular subtype (OR=4.182, p=0.006), histological grading (OR=3.596, p=0.010), and histological type (OR=0.367, p=0.017). Age, LVI, and TIL lost statistical significance in the multivariate model. Conclusion: Menopausal status emerged as the strongest independent predictor of NAC response in LABC, suggesting that hormonal factors play a pivotal role in chemotherapy sensitivity. These findings support more aggressive NAC regimens or combined endocrine-cytotoxic strategies for postmenopausal patients and warrant validation in prospective Southeast Asian cohorts.
Ni Gusti Ayu Agung Manik Yuniawaty Wetan
Efficacy and Safety of Adding Antiangiogenic Therapy to EGFR-Tyrosine Kinase Inhibitors versus EGFR-Tyrosine Kinase Inhibitor Monotherapy in EGFR-Mutant Non-Small Cell Lung Cancer: A Systematic Review and Meta-Analysis of Randomised Controlled Trials
Background. Resistance to epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) limits the durability of targeted therapy in EGFR-mutant non-small cell lung cancer (NSCLC). Inhibiting the vascular endothelial growth factor (VEGF) axis has been proposed to delay this resistance, but individual trials diverge and the antiangiogenic class has not been synthesised together across treatment settings. This study quantified the effect of adding antiangiogenic therapy to an EGFR-TKI on progression-free survival (PFS) and toxicity. Methods. Four databases were searched for randomised controlled trials (RCTs) comparing an EGFR-TKI plus an antiangiogenic agent (bevacizumab or ramucirumab) with the same EGFR-TKI alone in EGFR-mutant NSCLC. The pre-specified primary analysis was PFS in the first-line setting, expressed as the hazard ratio (HR) and pooled with an inverse-variance random-effects (DerSimonian-Laird) model; a restricted maximum-likelihood model confirmed it. Heterogeneity used I², τ² and a 95% prediction interval; risk of bias used Cochrane RoB 2.0. Results. Seven RCTs (eight reports; 1,512 patients; six first-line, one second-line) were included. In the six first-line trials the combination prolonged PFS (pooled HR 0.61, 95% CI 0.53-0.70; p<0.0001) with no heterogeneity (I²=0%; prediction interval 0.50-0.74); the restricted maximum-likelihood estimate was identical. The benefit was consistent for bevacizumab (HR 0.62, 0.52-0.73) and ramucirumab (HR 0.59, 0.46-0.76), a mean prolongation of median PFS of about 5.5 months. Adding the second-line osimertinib/T790M trial attenuated the effect (HR 0.66, 0.56-0.77; I²=32%), driven by absence of benefit in that setting (HR 0.96). Leave-one-out estimates were stable (0.59-0.63); the Egger test was non-significant. Grade ≥3 adverse events were increased (risk ratio 1.95, 1.47-2.57; absolute increase about 29 percentage points; number needed to harm about 4). Conclusion. Adding antiangiogenic therapy to a first-line EGFR-TKI consistently prolongs PFS in EGFR-mutant NSCLC as a VEGF-pathway class effect, at the cost of roughly doubled severe toxicity and without a demonstrated overall-survival gain. The benefit was not evident in the second-line osimertinib/T790M setting, suggesting the strategy delays rather than overcomes resistance.
Anesthetic Management of a Young Adult with Severe Rheumatic Mitral and Aortic Stenosis Undergoing Double Valve Replacement: A Case Report
Background. Rheumatic heart disease remains a leading cause of valvular pathology in young adults of low- and middle-income countries. The coexistence of severe mitral stenosis (MS) and severe aortic stenosis (AS) confronts the anesthesiologist with directly opposed hemodynamic imperatives and a markedly narrowed margin of safety, particularly during separation from cardiopulmonary bypass (CPB). Case presentation. A 41-year-old man presented with a 14-year history of exertional syncope, progressive dyspnea, orthopnea, and paroxysmal nocturnal dyspnea. Transthoracic echocardiography demonstrated severe rheumatic MS (mitral valve area 0.8 cm²) and severe rheumatic AS (aortic valve area 0.8 cm², mean gradient 56 mmHg) with preserved left ventricular ejection fraction (67%), reduced right ventricular contractility (TAPSE 17 mm), and atrial fibrillation. He underwent double valve replacement under general anesthesia using an opioid-based, hemodynamically stable induction with full invasive monitoring. Separation from CPB was complicated by two episodes of ventricular tachycardia requiring synchronized cardioversion (30 J and 20 J) and was managed with a milrinone–dobutamine–norepinephrine strategy. The patient was transferred ventilated to intensive care on inotropic and antiarrhythmic support and stabilized. Conclusion. Combined severe MS and AS demands an individualized plan reconciling contradictory goals: adequate preload and a controlled, unhurried heart rate for MS, against maintained afterload and coronary perfusion for AS. Meticulous invasive monitoring, a stable induction, anticipation of right ventricular dysfunction, and readiness for perioperative arrhythmia are decisive for a safe outcome.
Repeated Optical Biometry Failure as an Underrecognized Marker of Late In-the-Bag Intraocular Lens Decentration in Axial Myopia: A Case Report
Background: Late in-the-bag intraocular lens (IOL) dislocation is a delayed complication of cataract surgery driven by progressive zonular weakness, with axial myopia recognized as an independent risk factor. Its role as a hidden cause of optical biometry failure, however, has received little emphasis in the literature. Case presentation: A 58-year-old woman with longstanding axial myopia presented seven years after uneventful right-eye phacoemulsification with progressively blurred vision, monocular diplopia, and ghost images. Best-corrected visual acuity (BCVA) was 6/38 in the right eye improving to 6/15 with pinhole; refractometry revealed a new −4.00 D cylinder at axis 90° with persistent visual distortion consistent with irregular astigmatism. Slit-lamp examination showed inferior decentration of an in-the-bag posterior chamber IOL with a visible inferior haptic. Posterior segment evaluation through the displaced optic was hazy. Repeated optical biometry of the affected eye failed to acquire a valid axial-length signal across three sessions, whereas the fellow eye yielded reliable measurements. The patient was referred to a tertiary vitreoretinal center for IOL repositioning or exchange with possible pars plana vitrectomy and scleral fixation. Conclusion: In a myopic pseudophakic eye presenting with new-onset monocular diplopia and an astigmatic shift, repeated failure of optical biometry should be recognized as a critical diagnostic clue to underlying IOL instability, prompting timely tertiary referral and individualized surgical planning.
Intraoperative Incisional Wound Irrigation with 0.05% Chlorhexidine versus 0.9% Saline to Prevent Surgical Site Infection after Laparotomy for Hollow-Viscus Perforation Peritonitis: A Double-Blind Randomized Controlled Trial
Background: Surgical site infection (SSI) is the most frequent complication of abdominal surgery and a major source of morbidity, prolonged hospitalization and cost, particularly in dirty (class IV) wounds created by gastrointestinal perforation; intraoperative incisional irrigation may lower wound bioburden, yet the optimal irrigant is undefined. Methods: We conducted a double-blind randomized controlled trial at a tertiary referral center in Bandung, Indonesia (November 2019–August 2020) comparing incisional irrigation with 0.05% chlorhexidine versus 0.9% saline in adults undergoing emergency laparotomy for hollow-viscus perforation peritonitis. After fascial closure, incisions were irrigated by allocation and patients were followed for 30 days, with superficial SSI (ASEPSIS score) as the primary outcome. Results: Of 141 patients screened, 96 were analyzed (49 chlorhexidine, 47 saline). Superficial SSI occurred in 5/49 (10.2%) chlorhexidine versus 14/47 (29.8%) saline patients (χ²=5.795, p=0.016; Fisher exact p=0.021; OR 0.268, 95% CI 0.088–0.818; relative risk 0.343; absolute risk reduction 19.6%; number-needed-to-treat 5.1). In multivariable logistic regression, chlorhexidine remained independently protective (adjusted OR 0.228, 95% CI 0.062–0.836, p=0.026), while intra-abdominal contamination (aOR 1.377 per 100 mL, p=0.008) and operative time (aOR 1.645 per 30 min, p=0.027) increased risk; the model discriminated well (AUC 0.835). No irrigation-related adverse events occurred. Conclusion: Incisional irrigation with 0.05% chlorhexidine markedly reduced superficial SSI after laparotomy for perforation peritonitis and offers a low-cost strategy for dirty abdominal wounds.
Efficacy and Safety of Travoprost Intraocular Implants in Open-Angle Glaucoma and Ocular Hypertension: A Systematic Review and Meta-Analysis
Background: Open-angle glaucoma (OAG) and ocular hypertension (OHT) are leading causes of irreversible visual impairment and require lifelong reduction of intraocular pressure (IOP). Topical prostaglandin analogues are the standard first-line therapy, yet their effectiveness is constrained by poor adherence. The travoprost 75 µg intracameral implant has emerged as a sustained-release alternative designed to bypass these adherence barriers. The present systematic review and meta-analysis quantitatively synthesised the efficacy and safety of this device in adults with OAG or OHT. Methods: PubMed was searched in accordance with the PRISMA 2020 statement. Original research articles evaluating the travoprost 75 µg intracameral implant in adults with OAG or OHT were eligible. Two reviewers screened, extracted data, and independently appraised risk of bias using Cochrane RoB 2.0 (RCTs) or the Newcastle–Ottawa Scale (non-randomised). Standardised mean changes in IOP were synthesised as Hedges' g under a DerSimonian–Laird random-effects model with Knapp–Hartung adjustment. Pre-specified sensitivity, leave-one-out, alternative-pool, and design sub-group analyses were performed. The funnel plot was inspected; Egger's test was deferred because k < 10. Results: Of 30 PubMed records, 10 original research studies were eligible and 6 contributed to the primary quantitative synthesis (2,152 total enrolled participants; 1,525 implant-arm participants pooled in the within-group synthesis). The pooled within-group Hedges' g for IOP reduction was 4.35 (95% CI 3.14 to 5.56; p = 0.0002). Heterogeneity was very high (I² = 96.1%, τ² = 1.121, Q = 53.64, p < 0.0001). The 95% prediction interval, derived from the same model, spanned approximately 1.13 to 7.56. The randomised-controlled-trial-only pool (k = 4) yielded a more conservative pooled estimate of g = 3.76 (95% CI 2.94 to 4.58; I² = 88.6%). Leave-one-out analyses confirmed robustness (g range 3.98–4.56). Serious ocular adverse events were rare (one endophthalmitis in the slow-eluting arm of the GC-010 phase 3 trial, with no further cases in the remaining cohorts); transient ocular hyperemia, iritis, and elevated IOP were the most common, broadly consistent with the topical-travoprost class profile. Conclusion: The travoprost 75 µg intracameral implant produced a large and consistent reduction in IOP across designs and follow-up windows, with a safety profile non-inferior to topical timolol 0.5%. The substantial heterogeneity, near-uniform sponsor footprint, and limited head-to-head comparisons against topical prostaglandin monotherapy temper the certainty of the evidence and warrant pragmatic, independent, multi-ethnic trials. Within these limits, the implant is a clinically meaningful addition to interventional glaucoma therapy, particularly for patients in whom topical adherence is the dominant driver of disease progression.
Prophylactic Statin Therapy for the Prevention of Anthracycline-Induced Cardiotoxicity in Patients with Breast Cancer: A Systematic Review and Meta-Analysis of Randomized Controlled Trials and Cohort Studies
Background. Anthracycline-based chemotherapy remains a cornerstone of curative-intent breast-cancer treatment but carries a dose-dependent risk of cancer therapy-related cardiac dysfunction (CTRCD). Statins exert pleiotropic anti-inflammatory, antioxidative, and endothelial-stabilizing effects that may attenuate myocardial injury; however, prior meta-analyses pooled breast-cancer and lymphoma populations, obscuring breast-cancer-specific signals. Methods. A systematic review and random-effects meta-analysis was conducted per PRISMA 2020. PubMed, Cochrane, Scopus, and Web of Science were searched for randomized controlled trials (RCTs) and propensity-matched cohort studies enrolling adult breast-cancer patients receiving anthracycline-based chemotherapy with or without trastuzumab. Co-primary outcomes were CTRCD incidence and standardized change in left-ventricular ejection fraction (LVEF, Hedges' g). Risk of bias was assessed using RoB 2.0 and ROBINS-I. Sensitivity analyses included leave-one-out exclusion and restriction to breast-cancer-only RCTs. Results. Ten studies (1,239 patients; six RCTs, four cohort studies) were included. The pooled risk ratio for CTRCD was 0.49 (95% CI 0.28–0.85; p = 0.011; I² = 0%). The pooled standardized mean difference for LVEF change was 0.38 (95% CI −0.06 to 0.81; I² = 81%), corresponding to approximately +2.1 LVEF percentage points. Sensitivity analyses restricted to breast-cancer-only RCTs strengthened the CTRCD effect (RR 0.36, 95% CI 0.16–0.82). HER2-positive subgroup analyses yielded a pooled RR of 0.28 (95% CI 0.10–0.80). Conclusion. Prophylactic statin therapy is associated with a clinically meaningful and statistically significant reduction in CTRCD in breast-cancer patients receiving anthracyclines. The protective effect is particularly pronounced in HER2-positive patients. A cautious, risk-stratified use of statins as a cardioprotective adjunct is supported pending adequately powered, breast-cancer-specific randomized trials.
Incidence of Intraocular Inflammation, Retinal Vasculitis, and Retinal Vascular Occlusion Following Intravitreal Brolucizumab in Neovascular Age-Related Macular Degeneration: A Systematic Review and Meta-Analysis
Background. Brolucizumab is a humanized single-chain anti-VEGF antibody fragment licensed for neovascular age-related macular degeneration (nAMD). Post-marketing surveillance identified intraocular inflammation (IOI), retinal vasculitis (RV), and retinal vascular occlusion (RVO) as adverse events of special interest, sometimes causing irreversible visual loss. Published incidence estimates range from below 1% to above 10%. We aimed to estimate the pooled cumulative incidence of these events and characterize heterogeneity drivers. Methods. PubMed/MEDLINE, Cochrane CENTRAL, and Google Scholar were searched for phase 3 randomized controlled trials (RCTs), phase IIIb prospective studies, and retrospective/registry studies (≥30 eyes) reporting IOI, RV, or RVO incidence after intravitreal brolucizumab 6 mg in nAMD. A DerSimonian–Laird random-effects model with Freeman–Tukey arcsine transformation was applied; REML, Paule–Mandel, and GLMM (logit link) estimators were used in sensitivity analyses. Results. Ten independent datasets (33,280 brolucizumab-treated eyes; 1,130 events) were included. Pooled cumulative incidence of any IOI/RV/RVO was 5.54% (95% CI 4.23–7.02%; I² = 94.0%; Q = 150.48). Prospective studies yielded higher pooled incidence (8.42%, 95% CI 4.12–14.04%) than retrospective/registry studies (4.35%, 95% CI 3.28–5.56%). Leave-one-out sensitivity ranged 4.98–6.19%. Funnel-plot asymmetry was detected (Egger t = 3.27; p = 0.011). More than 75% of events occurred within six months of the first injection. Conclusion. Cumulative incidence of IOI/RV/RVO after brolucizumab 6 mg in nAMD approached 5.5%, with markedly higher rates under independent adjudication. These findings support careful patient selection, baseline screening for prior IOI history, and intensified monitoring after brolucizumab initiation.
Occupational and Environmental Ultraviolet–Sunlight Exposure, Including Outdoor Agricultural Work, and the Risk of Cataract: A Systematic Review and Meta-Analysis of Observational Studies
Background.Cataract remains the leading cause of avoidable blindness worldwide, and occupational sunlight exposure is suspected as a modifiable risk factor among outdoor workers, including agricultural workers in tropical low- and middle-income countries (LMICs) such as Indonesia. Previous quantitative syntheses pooled mixed exposure-contrast metrics into a single estimate and obtained heterogeneity in excess of I2 = 95%, providing limited interpretable guidance for clinicians and policy makers. Methods.A systematic search of PubMed/MEDLINE was conducted and supplemented by citation tracing and translated search strings for Scopus, Embase, Web of Science and Cochrane CENTRAL. Eligible studies were observational analyses of adults reporting an OR, HR or relative risk with a 95% CI for occupational or environmental UV-sunlight exposure and cataract. Risk of bias was assessed using the Newcastle-Ottawa Scale. Effect estimates were pooled using DerSimonian-Laird random-effects models with REML and Hartung-Knapp-Sidik-Jonkman sensitivity estimators. Results.Seven observational studies (combined n approximately 60,000) met the inclusion criteria. Pooled OR from four extreme high-vs-low contrast studies: 6.52 (95% CI 4.12-10.33; I2 = 67%). Three modest per-unit/ever-vs-never studies pooled at OR/HR 1.09 (95% CI 1.04-1.14; I2 = 0%). The contrast-type moderator explained approximately 45% of between-study heterogeneity (p < 0.001). Conclusion.Occupational and environmental UV-sunlight exposure is associated with a clinically significant increase in cataract risk. The magnitude depended on the exposure contrast. The findings support targeted ocular-protection programmes for outdoor agricultural workers in high-insolation LMICs such as Indonesia.
Determinants of In-hospital Mortality in Preterm Neonates Admitted to a Tertiary Indonesian NICU: A One-Year Retrospective Cohort of 209 Infants
Background. Preterm birth is the largest single contributor to global neonatal mortality, and Southeast Asia carries a disproportionate burden, yet contemporary multivariable data from Indonesian tertiary neonatal intensive care units (NICUs) remain limited. We aimed to identify maternal, perinatal and neonatal determinants of in-hospital mortality among preterm neonates at the NICU of Prof. I.G.N.G Ngoerah Hospital, Denpasar, Bali. Methods. In a single-centre retrospective cohort, 209 preterm neonates (gestational age <37 weeks and birth weight <2500 g) admitted between September 2024 and September 2025 were enrolled by total sampling. Bivariate logistic regression with p<0.25 inclusion threshold was followed by multivariable binary logistic regression; intermediate-outcome variables (RDS and surfactant therapy) were excluded a priori to avoid over-adjustment bias. Results. In-hospital mortality was 42.1% (88/209) and decreased monotonically across birth-weight strata, from 75.0% in infants <1000 g to 41.9% in 1000–1499 g and 22.9% in ≥1500 g (Cochran–Armitage trend p<0.001). Sepsis (56.8%) and respiratory distress syndrome (30.7%) accounted for 87.5% of deaths. In the multivariable model, birth weight 1000–1499 g (adjusted odds ratio [aOR] 0.36, 95% CI 0.15–0.90; p=0.029) and ≥1500 g (aOR 0.17, 95% CI 0.06–0.51; p=0.001) and each 1-point increment in 5-minute Apgar score (aOR 0.81, 95% CI 0.67–0.98; p=0.031) were independently associated with lower mortality. Maternal urinary tract infection trended toward higher mortality (aOR 2.85, 95% CI 0.97–8.35; p=0.057). Conclusion. Birth weight and 5-minute Apgar score are independent, immediately measurable predictors of in-hospital preterm mortality in this Indonesian tertiary NICU. Combining bedside risk stratification with antenatal corticosteroid coverage audit and universal antenatal urine-culture screening offers a translational pathway to reduce neonatal mortality in resource-constrained Southeast Asian settings.
Emergency Bedside Transvenous Pacing Without Fluoroscopic Guidance for Refractory Symptomatic Bradycardia Following Cardiac Arrest in Acute Inferior ST-Elevation Myocardial Infarction: A Case Report
Background: Symptomatic bradycardia is a recognized complication of acute inferior myocardial infarction due to atrioventricular node ischemia. Temporary transvenous pacemaker insertion traditionally requires fluoroscopic guidance, which may be unavailable in emergency departments. Alternative non-fluoroscopic approaches are essential in time-critical, resource-limited settings. Case presentation: A 62-year-old male with uncontrolled diabetes mellitus presented to the emergency department with respiratory and cardiac arrest. Following cardiopulmonary resuscitation, return of spontaneous circulation was achieved. Electrocardiography revealed inferior ST-elevation myocardial infarction with second-degree atrioventricular block type II. Despite administration of atropine sulfate (cumulative dose 1.25 mg intravenously) and vasopressor support, the patient developed refractory symptomatic bradycardia with heart rate declining to 25-30 beats per minute, culminating in a second cardiac arrest. After achieving return of spontaneous circulation for the second time, a temporary transvenous pacemaker was inserted at the bedside in the emergency department via the femoral vein using a blind technique with electrocardiographic monitoring as the sole guide for successful placement. The pacemaker was set to VVI mode at 70 beats per minute. Subsequent fluoroscopic confirmation in the catheterization laboratory revealed the catheter tip in the right ventricular outflow tract, which was repositioned to the right ventricular apex. Percutaneous coronary intervention was subsequently performed. Conclusion: Bedside blind temporary transvenous pacemaker insertion using electrocardiographic monitoring is a feasible and effective approach in emergency settings where fluoroscopic guidance is unavailable.