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.
Copyright and licensing Copyright in each article remains with the author(s). Authors grant Bioscientia Medicina: Journal of Biomedicine and Translational Research a non-exclusive right of first publication and the right to identify itself as the original publisher. No exclusive transfer of copyright is required. All articles are published under the Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License (CC BY-NC-SA 4.0): https://creativecommons.org/licenses/by-nc-sa/4.0/. Users may copy, redistribute, remix, transform, and build upon the material for non-commercial purposes, provided appropriate attribution is given, a link to the license is supplied, changes are indicated, and adaptations are distributed under the same license. The license applies to the article's scholarly content unless a credit line states otherwise. Third-party material may be subject to separate rights. Authors retain patent, trademark, moral, and research-data rights. The copyright year follows the article's publication date.
Visual Recovery to 6/6 After Plasma Exchange Begun 29 Days Into a Corticosteroid-Refractory Aquaporin-4-IgG-Positive Optic Neuritis Attack: A Case Report
Background: Optic neuritis in aquaporin-4 immunoglobulin G (AQP4-IgG)-positive neuromyelitis optica spectrum disorder (NMOSD) is severe and frequently corticosteroid-refractory. Plasma exchange is recommended within days of onset, and the evidence that later treatment still helps is thin. Whether an attack first treated a month after onset can still recover fully is unresolved. Objective: To describe the visual and structural recovery that followed therapeutic plasma exchange begun 29 days after onset — far outside the recommended window — in a corticosteroid-refractory aquaporin-4-IgG-positive optic neuritis attack, and to audit the record against the quantified determinants of outcome. Case presentation: A 34-year-old woman with systemic lupus erythematosus, antiphospholipid syndrome and AQP4-IgG seropositivity documented one month earlier presented 24 days after the onset of painful visual loss in the right eye. Best-corrected visual acuity was 3/60 and the Ishihara score 0 of 25. No relative afferent pupillary defect was demonstrable in the affected eye, because the fellow eye, atrophic since an attack 11 years earlier, showed the defect instead. A full Optic Neuritis Treatment Trial course of intravenous methylprednisolone, from day 24 to day 27, produced no measurable change. Plasma exchange was started on day 29; acuity reached 6/60 on day 33 and 6/6 on day 35, and the Ishihara score rose to 5 of 25 by day 40 without any procedure-related adverse event. At day 53 the peripapillary retinal nerve fibre layer measured 91 micrometres in the treated eye against 41 in the fellow eye. Conclusion: Complete recovery of high-contrast acuity followed plasma exchange begun 29 days after onset, far outside the recommended window, while colour vision recovered only partially. A chronically damaged fellow eye can abolish the relative afferent pupillary defect in an acutely inflamed eye, and the attack occurred on azathioprine in a patient already known to be seropositive.
Copyright (c) 2026 Anak Agung Ayu Putri Oktiadewi, Anak Agung Mas Putrawati Triningrat, Gede Kambayana, Ni Kadek Mulyantari, I Gusti Ayu Made Juliari https://creativecommons.org/licenses/by-nc-sa/4.0
Excess Adiposity Predicts In-Hospital Mortality but Not SCORTEN in Stevens–Johnson Syndrome and Toxic Epidermal Necrolysis: A Three-Year Retrospective Cohort at Dr. Moewardi General Hospital, Surakarta
Background: Stevens–Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are rare drug-induced reactions in which in-hospital death occurs in 12–49% of cases, yet the reference prognostic instrument, SCORTEN, contains no anthropometric variable. Whether body mass index (BMI) carries independent prognostic information is unknown. Objective: To determine whether body mass index carries independent prognostic information — for in-hospital mortality and for the SCORTEN severity score — in adults admitted with Stevens–Johnson syndrome and toxic epidermal necrolysis. Methods: This retrospective observational analytic study used total sampling of the ICD-10 L51.1/L51.2 admission register at Dr. Moewardi General Hospital, Surakarta, from January 2022 to December 2024. Forty-three adults were classified by Asia-Pacific BMI thresholds and analysed against SCORTEN, diagnostic class and in-hospital mortality using exact, Firth-penalised and interval-valued methods, with STROBE reporting. Results: Eight patients died (18.6%; 95% CI 9.7–32.6). BMI was not associated with SCORTEN (Spearman ρ = 0.163; 95% CI −0.14 to 0.44; p = 0.296), and all 3,280 exhaustively enumerated reconstructions of the incompletely reported score distribution reproduced a non-significant coefficient (ρ 0.061–0.287); the minimum detectable |ρ| was 0.42, so this null is uninformative rather than negative (BF01 = 3.10). Mortality rose across the ordered BMI strata from 0% to 36.4% (Cochran–Armitage z = 2.053; p = 0.040, exact permutation p = 0.056), and at the Asia-Pacific overweight threshold reached 35.3% versus 7.7% (odds ratio 6.55; 95% CI 1.14–37.75; Fisher exact p = 0.042; Firth-penalised odds ratio 5.54, 95% CI 1.20–34.09; number needed to harm 3.6; E-value 8.65; fragility index 1). Conclusion: Excess adiposity is associated with in-hospital death in Indonesian patients with epidermal necrolysis through a channel SCORTEN does not capture. The estimate is imprecise and requires prospective multicentre confirmation.
Copyright (c) 2026 Nugrohoaji Dharmawan, Aulia Yasmin https://creativecommons.org/licenses/by-nc-sa/4.0
Segmental Open Mandibular Fracture with Type 2 Diabetes Mellitus Managed by Intraoral Open Reduction, Internal Fixation and 101 Days of Arch Bar Retention: A Case Report with a Structured Care-Gap Analysis
Background: Mandibular fracture is the maxillofacial injury most often treated operatively, and road traffic collision is its dominant cause. Published series report fixation technique and union; far fewer report the perioperative variables that govern outcome when a metabolic comorbidity is present. Objective: To present the staged intraoral repair of a segmental open mandibular fracture in an adult with type 2 diabetes mellitus and, through a structured audit of the record, to identify the measurable perioperative determinants of outcome that were not documented during care. Case presentation: A 51-year-old man was struck by a car while riding a motorcycle and sustained a multiple open mandibular fracture of the symphysis, right parasymphysis and a segmental right body, with an anterior open bite, an interincisal opening of 24 mm, right mandibular crepitus and an avulsed right mandibular canine. He had treated hypertension and type 2 diabetes mellitus. Computed tomography with three-dimensional reconstruction defined the pattern and excluded condylar and intracranial injury. On the eighth day after injury, intraoral open reduction with four plates was combined with Erich arch bar maxillomandibular fixation. Rigid intermaxillary fixation was released at 21 days and the mandibular arch bar retained for 101 days. At day 116 mouth opening was unrestricted and mastication pain-free, with no infection, dehiscence, malunion or plate exposure. Structured review of the record showed that four determinants of outcome were never documented: any glycaemic measurement, inferior alveolar nerve sensation, the disposition of the avulsed canine and the retained dental roots, and a closing interincisal measurement. Conclusion: A staged intraoral repair restored occlusion and function in a diabetic adult with a segmental open mandibular fracture. The favourable result was achieved despite four recording gaps, each fixable at no cost, that would have converted a good outcome into a demonstrated one.
Copyright (c) 2026 Deasy Nurwianti, Al Hafiz, Tuti Handayani https://creativecommons.org/licenses/by-nc-sa/4.0
Feasibility, Visual Outcomes and Severity-Stratified Response to Pre-operative Intravitreal Bevacizumab Before Vitrectomy in Proliferative Diabetic Retinopathy
Background: Proliferative diabetic retinopathy is a leading cause of vision loss in working-age Indonesians, and pre-operative anti-vascular endothelial growth factor therapy has been proposed to make vitrectomy safer, yet Southeast Asian trial evidence is almost absent. Objective: To assess the feasibility, visual outcomes, and severity-stratified response to pre-operative intravitreal bevacizumab before 23-gauge pars plana vitrectomy in patients with proliferative diabetic retinopathy. Methods: In a single-centre, single-blind pilot randomised controlled trial at the Department of Ophthalmology, Faculty of Medicine, Universitas Sriwijaya/ Dr. Mohammad Hoesin Central General Hospital, Palembang (July–November 2025), 21 adults with proliferative diabetic retinopathy and non-clearing vitreous haemorrhage were allocated 1:1, stratified by haemorrhage severity, to intravitreal bevacizumab 1.25 mg/0.05 mL given 3–7 days before 23-gauge pars plana vitrectomy (n = 11) or to vitrectomy alone (n = 10). Progression criteria were pre-specified; the clinical outcome was best-corrected visual acuity change in LogMAR at one week. Results: All progression criteria fell in the green zone (recruitment 95.5%, 95% CI 78.2–99.2; retention and adherence 100%). Bevacizumab-treated eyes gained more vision, but imprecisely (Hodges–Lehmann shift 0.35 LogMAR, envelope 0.10 to 0.50; Hedges' g 0.65), the trial retaining only 14.8% power for the observed difference. Baseline vitreous haemorrhage severity dominated visual gain (adjusted B -0.397 LogMAR per grade, 95% CI -0.639 to -0.155; Cochran–Armitage trend p = 0.015). Conclusion: Pre-operative bevacizumab is feasible in an Indonesian tertiary centre and warrants a severity-stratified multicentre trial.
Copyright (c) 2026 Ramzi Amin, Fajar Prasetya, Abdul Karim Ansyori https://creativecommons.org/licenses/by-nc-sa/4.0
Diagnostic Accuracy and Optimal CD4 Threshold for Detecting Cytomegalovirus Retinitis in Advanced HIV Disease: A Prospective Indonesian Study
Background: Cytomegalovirus retinitis (CMVR) is a leading preventable cause of AIDS-related blindness where systematic screening is absent, and World Health Organization guidance triggers ophthalmic assessment below a CD4 count of 50–100 cells/µL, a range not previously calibrated in an Indonesian population. Objective: To determine the diagnostic accuracy of the CD4 count against adjudicated cytomegalovirus retinitis, and to derive an optimal CD4 threshold for triggering ophthalmic screening, in Indonesian adults with advanced HIV disease. Methods: This prospective single-gate diagnostic accuracy study, reported to STARD 2015, enrolled 51 consecutive adults with HIV-1 infection and a CD4 count below 100 cells/µL at Dr. Mohammad Hoesin Central General Hospital, Palembang, from January 2024 to January 2025. The index test was the CD4 count by flow cytometry; the reference standard was masked adjudication by two retina specialists using dilated ophthalmoscopy, fundus photography and optical coherence tomography (Cohen's κ = 0.91). Because only aggregated summaries were released, estimands the data do not identify are reported as sharp bounds. Results: CMVR was present in 17 of 51 participants (33.3%, 95% CI 22.0–47.0); the median CD4 count was 17.0 cells/µL (IQR 11.0–27.0) versus 48.0 (30.0–72.0). The area under the ROC curve was 0.863 (95% CI 0.741–0.985). At the Youden-derived threshold of 32.5 cells/µL apparent sensitivity was 88.2% (95% CI 65.7–96.7) and specificity 91.2% (77.0–97.0); after correction for in-sample threshold selection these became 80.5% and 93.8%, and across two admissible reconstructions sensitivity ranged from 76.5% to 88.2%. CD4 rose monotonically across fulminant, indolent and frosted-branch phenotypes (bounded Kruskal–Wallis p = 0.001–0.013). Conclusion: A CD4 count of approximately 30–35 cells/µL, with an unconditional visual-symptom over-ride, prioritises dilated retinal examination within the World Health Organization stratum in Indonesian HIV services.
Copyright (c) 2026 Ramzi Amin, Fadillah Amrina, Petty Purwanita, Nuzulul Aini https://creativecommons.org/licenses/by-nc-sa/4.0
Mechanism-Specific Tear Film Instability Across Diabetic Retinopathy Severity: Fluorescein Break-Up Pattern Classification in Type 2 Diabetes Mellitus
Background: Diabetic retinopathy and dry eye disease coexist in type 2 diabetes mellitus, yet conventional metrics treat tear film instability as one entity and cannot identify which layer has failed. Objective: This pilot study asked whether the Asia Dry Eye Society fluorescein break-up pattern classification tracks Early Treatment Diabetic Retinopathy Study (ETDRS) severity. Methods: Fifteen patients (30 eyes) with type 2 diabetes and any retinopathy grade were enrolled under a quota framework at RSUP Dr. Mohammad Hoesin Palembang, Indonesia, from November 2024 to July 2025. Break-up patterns were classified into five categories under cobalt-blue slit-lamp biomicroscopy on three consecutive observations; Ocular Surface Disease Index (OSDI) and tear break-up time (TBUT) were recorded. Analysis used rank correlation with exact permutation testing, proportional-odds regression and receiver operating characteristic analysis. Results: Pattern distribution differed across grades (Fisher–Freeman–Halton p = 0.007; Cramér's V = 0.536). Within the aqueous-deficiency pathway, line break progressed to area break (rho = 0.905, 95% CI 0.666–0.975, exact p = 0.002); within the decreased-wettability pathway, dimple break progressed to spot break (rho = 0.824, 95% CI 0.445–0.953, exact p = 0.009). Each one-grade increase multiplied the odds of a more severe pattern 7.442-fold (95% CI 2.555–21.673), and grade discriminated severe-mechanism patterns with an area under the curve of 0.87 (95% CI 0.681–0.955). OSDI and TBUT deteriorated monotonically (both p < 0.001), whereas random break showed no gradient (rho = 0.095, p = 0.618). Conclusion: Mechanism-specific tear film failure scales with retinopathy severity, supporting fluorescein-based tear film oriented diagnosis in Indonesian practice.
Copyright (c) 2026 Ramzi Amin, Siti Shalihah Ramadhani Novizar, Petty Purwanita https://creativecommons.org/licenses/by-nc-sa/4.0
Adjunctive Diquafosol Sodium 3% and Tear-Ferning Recovery After Pars Plana Vitrectomy: An Exploratory Randomized Trial
Background: Ocular-surface disturbance after pars plana vitrectomy (PPV) may impair tear-film stability and mucin-related function. Diquafosol sodium stimulates aqueous and mucin secretion through P2Y₂-receptor signaling, but evidence after PPV remains limited. Objective: This study evaluated adjunctive diquafosol sodium 3% using tear-ferning grade as an exploratory outcome. Methods: This single-center randomized trial enrolled 36 adults after PPV. Participants received diquafosol sodium 3% six times daily for eight weeks plus standard postoperative care (n=18) or standard care alone (n=18). Treatment was open label; tear-ferning assessment was performed by a masked assessor. Ferning grade was measured at postoperative weeks 1, 2, 4, and 8. Between-group comparisons used the Mann–Whitney U test with multiplicity adjustment, and standardized effect magnitudes were summarized using Hedges g with 95% confidence intervals. Results: Mean ferning grades were similar at week 1 (3.94±0.236 vs 3.72±0.461; p=0.203), week 2 (3.67±0.594 vs 3.72±0.461; p=0.938), and week 4 (2.89±0.323 vs 3.00±0.000; p=0.584). At week 8, the diquafosol group had a lower mean grade than the control group (2.11±0.471 vs 2.72±0.461; p=0.003), with a standardized effect magnitude of 1.28 (95% CI 0.57–1.99). No adverse events were reported. Conclusion: Adjunctive diquafosol was associated with better tear-ferning grade at eight weeks after PPV. The finding is exploratory and requires confirmation using larger, multicenter, placebo-controlled trials with multidimensional ocular-surface outcomes.
Copyright (c) 2026 Ramzi Amin, Petty Purwanita, Rizka Yunanda https://creativecommons.org/licenses/by-nc-sa/4.0
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
Does Germline BRCA1/2 Status Modify the Effect of Neoadjuvant Pembrolizumab on Pathological Complete Response in Early-Stage Triple-Negative Breast Cancer? A Systematic Review and Meta-analysis of Treatment-Biomarker Interactions
Background: Germline BRCA1/2 pathogenic variants are associated with chemotherapy response, but higher response among pembrolizumab-treated carriers does not establish a treatment-predictive interaction. Objective: To determine whether germline BRCA1/2 status modifies the effect of neoadjuvant pembrolizumab on pathological complete response in early-stage triple-negative breast cancer, estimated as a within-study treatment-by-biomarker interaction on the ratio-of-odds-ratios scale. Methods: Accessible bibliographic, registry, and citation sources were searched from inception through the final accessible-source update for comparative cohorts of neoadjuvant pembrolizumab plus chemotherapy versus chemotherapy alone reporting pathological complete response (pCR) by germline BRCA1/2 status. One author approved screening, extraction, ROBINS-I, and ICEMAN judgements. Treatment-by-biomarker interactions were expressed as ratios of odds ratios (RORs) and pooled by restricted-maximum-likelihood random effects with Hartung-Knapp inference. Results: Three retrospective cohorts (655 participants) were included; two (415 participants) provided complete interaction cells. Study RORs were 3.65 (95% CI 0.52-25.62) and 2.76 (0.39-19.39). The pooled ROR was 3.17 (0.54-18.51; p=0.076), with tau-squared=0 and I-squared=0%. The third cohort remained qualitative because noncarrier cells were irreconcilable. Risk of bias was serious, interaction credibility was low, and certainty was very low. Conclusion: The direction of effect is compatible with greater relative pembrolizumab-associated pCR improvement among carriers, but the evidence does not establish a predictive interaction. Prospective adjusted interaction analyses are required.
Copyright (c) 2026 I Made Aridana Sandika, Made Oka Sastrawan, Ngurah Gede Boyke Arsa Wibawa https://creativecommons.org/licenses/by-nc-sa/4.0
Neglected Total Rhegmatogenous Retinal Detachment with Proliferative Vitreoretinopathy Coexisting with Bilateral Grade IV Hypertensive Retinopathy in Severe Pre-eclampsia: A Case Report from an Indonesian Archipelagic Province
Background: Pre-eclampsia injures the eye through the same endothelial mechanism that injures the kidney and brain, and its retinal signs track systemic severity. Rhegmatogenous retinal detachment arises by an entirely different mechanism, yet where vitreoretinal care is distant the two may present together in one patient, a coexistence not previously described. Objective: To describe a previously unreported coexistence of chronic rhegmatogenous retinal detachment and grade IV hypertensive retinopathy of severe pre-eclampsia in one patient, and to set out the structural features that distinguish the two mechanisms at the bedside — the distinction that determines whether treatment is medical or surgical. Case presentation: A 36-year-old woman was examined three weeks after a term vaginal delivery, four months after sudden visual loss in the left eye that began in the fifth month of a pregnancy complicated by pre-eclampsia. She also reported 19 years of unassessed visual loss in the right eye. Blood pressure was 154/114 mmHg. Acuity was hand movement right and 0.1 decimal left. The right eye showed total retinal detachment with a break at 9 o'clock, fixed folds, pigment clumping, grade C posterior proliferative vitreoretinopathy, posterior subcapsular cataract and a 7-degree sensory exotropia; the left eye showed optic disc swelling, peripapillary haemorrhage and a macular star. Both eyes met Scheie grade IV. Left macular tomography gave a central subfield of 182 micrometres and a minimum foveal thickness of 98, with five of nine sectors below the first percentile. No relative afferent pupillary defect was detectable. Conclusion: Chronic rhegmatogenous and hypertensive retinal disease can coexist in one patient and must be separated structurally, because only one responds to blood pressure control. Sub-percentile macular thinning tempers the expectation of full recovery, and bilateral disease can abolish the relative afferent pupillary defect that would otherwise flag a blind eye.
Copyright (c) 2026 Willy Yahya, Daniel Johosua Siegers, Ari Andayani, I Wayan Ardy Paribrajaka 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.