Bioscientia Medicina : Journal of Biomedicine and Translational Research

Clinicopathological Profiling and Skeletal Tropism of Bone Metastases in Breast Cancer: A 5-Year Retrospective Institutional Analysis in Central Java

Gana Adyaksa — 2026-04-07

Background: The skeletal system is the most frequent site of distant metastasis in breast cancer, precipitating severe skeletal-related events. Characterizing histological subtypes, molecular profiles, and precise skeletal distribution is essential for targeted surveillance.

Methods: A retrospective analytical cohort study of 200 consecutive patients with radiologically documented bone metastasis was conducted at Dr. Kariadi General Hospital, Semarang, Central Java (2021–2025). Diagnosis required definitive confirmation via CT-scan or bone scintigraphy; clinical-only diagnoses were excluded. Primary metastatic burden was objectively defined by the largest lesion volume on imaging. World Health Organization (WHO) criteria were applied, subsuming invasive ductal carcinoma (IDC) into invasive breast carcinoma of no special type (NST). Immunohistochemical profiling and demographic data were extracted. Inferential statistics included Pearson Chi-Square and multivariate logistic regression to identify independent predictors of anatomical tropism, reporting Adjusted Odds Ratios (aOR) with 95% Confidence Intervals (CI).

Results: The cohort was predominantly female (n=199, 99.5%), with a mean age of 54.2 (SD ± 8.5) years. Following WHO consolidation, NST comprised 90.0% (n=180) and Invasive Lobular Carcinoma (ILC) 10.0% (n=20). The axial skeleton harbored the primary burden in 82.5% of cases. ILC demonstrated a significantly distinct tropism, showing 50.0% appendicular involvement compared to 13.9% in NST. Multivariate logistic regression confirmed ILC as an independent predictor for appendicular metastasis (aOR 4.21, 95% CI 1.85–9.60, p=0.012).

Conclusion: While NST exhibits a strong predilection for the axial skeleton, ILC uniquely favors appendicular dissemination. These findings mandate histology-specific diagnostic algorithms and targeted orthopedic surveillance.

Short-Term Efficacy Versus Long-Term Maintenance of Pelvic Floor Muscle Training for Perinatal Urinary Incontinence: A Meta-Analysis of Randomized Controlled Trials

Qonita Prasta Agustia — 2026-04-07

Background: Postpartum urinary incontinence remains a prevalent, profoundly debilitating complication following childbirth, significantly reducing maternal physical function and psychosocial quality of life. Pelvic floor muscle training is globally established as a conservative first-line treatment. However, the stark contrast between its immediate postnatal efficacy and its long-term maintenance remains inadequately synthesized in the current literature. The aim was to evaluate this chronological divergence.

Methods: A systematic review and meta-analysis of randomized controlled trials was conducted. Data were extracted from eligible trials assessing pregnant and postpartum women undergoing pelvic floor muscle training compared to standard care. Primary outcomes included the prevalence and severity of urinary incontinence evaluated at short-term (under one year) and long-term (over one year) intervals. Data were pooled utilizing a random-effects model, calculating risk ratios for dichotomous prevalence data and standardized mean differences for continuous severity scores.

Results: Eight randomized controlled trials encompassing over two thousand participants were included. Short-term analysis demonstrated a highly significant reduction in urinary incontinence prevalence among women receiving the intervention (Pooled Risk Ratio 0.65, 95% Confidence Interval 0.52 to 0.81, P < 0.001) and a significant improvement in severity scores (Standardized Mean Difference -0.72, 95% Confidence Interval -0.95 to -0.49, P < 0.001). Conversely, long-term follow-up data evaluated at the seven-year milestone showed a completely diminished effect, with no statistically significant difference in urinary incontinence prevalence between the prior intervention and control groups (Pooled Risk Ratio 0.92, 95% Confidence Interval 0.78 to 1.08, P = 0.45).

Conclusion: Structured pelvic floor muscle training provided substantial, rapid short-term efficacy in preventing and treating perinatal urinary incontinence. However, the initial anatomical and neuromuscular gains did not translate into long-term maintenance, highlighting a critical drop-off in behavioral adherence and the necessity for lifelong continuous booster interventions.

Efficacy and Safety of Intensive Blood Pressure Lowering on Cardiovascular Outcomes and Orthostatic Hypotension in Frail vs. Non-Frail Elderly Patients: A Systematic Review and Meta-Analysis

Dian Arfan As Bahri — 2026-04-08

Background: The management of hypertension in the older adult population presents a complex clinical challenge, particularly regarding the balance between cardiovascular risk reduction and the provocation of adverse events such as orthostatic hypotension. Frailty status complicates this dynamic, creating uncertainty regarding the optimal blood pressure target.

Methods: A systematic review and meta-analysis investigated the efficacy and safety of intensive versus standard blood pressure lowering in frail compared to non-frail older adults. Databases were systematically searched for randomized controlled trials and their secondary analyses reporting cardiovascular outcomes and orthostatic hypotension stratified by frailty. Data were extracted and synthesized using a random-effects model, calculating pooled risk ratios and standardized mean differences to assess primary cardiovascular events and safety outcomes.

Results: Ten primary studies met the inclusion criteria. Intensive blood pressure lowering significantly reduced the incidence of major cardiovascular events in both non-frail and frail cohorts. Surprisingly, intensive treatment did not increase the risk of orthostatic hypotension in frail patients and was associated with a protective effect against orthostatic hypotension in specific subsets. The risk of bias was generally low across the included trials.

Conclusion: Intensive blood pressure control provides substantial cardiovascular benefits for older adults, irrespective of baseline frailty status. Furthermore, the aggressive lowering of blood pressure does not exacerbate the risk of orthostatic hypotension, challenging previous clinical hesitations. These findings support the cautious but deliberate implementation of intensive targets in the geriatric population, monitored closely by comprehensive geriatric assessments.

Beyond PD-1/PD-L1: A Systematic Review and Meta-Analysis of LAG-3, TIGIT, and TIM-3 as Prognostic Biomarkers and Therapeutic Targets in Breast Cancer

Dinar Kukuh Prasetyo — 2026-04-08

Background: The therapeutic paradigm for breast cancer advanced significantly with programmed cell death-1 (PD-1) and programmed cell death ligand-1 (PD-L1) inhibitors. However, adaptive immune resistance, driven by compensatory upregulation of alternative checkpoints—Lymphocyte-activation gene 3 (LAG-3), T-cell immunoreceptor with Ig and ITIM domains (TIGIT), and T-cell immunoglobulin and mucin-domain containing-3 (TIM-3)—limits durable responses. This study aimed to quantitatively synthesize the prognostic significance, tumor microenvironment interactions, and translational surgical implications of these biomarkers in breast cancer.

Methods: A systematic literature search (PubMed, Embase, Cochrane) identified original research evaluating LAG-3, TIGIT, and TIM-3 expression in breast cancer cohorts. Data extraction focused on overall survival (OS) hazard ratios (HR), standardized mean differences (SMD) for tumor-infiltrating lymphocyte (TIL) density, and pathological complete response (pCR) rates. Random-effects meta-analyses generated forest plots, assessed heterogeneity (I-squared), and evaluated publication bias via funnel plots.

Results: Eight major cohorts comprising over 7,200 patients were included. High LAG-3 expression on TILs in triple-negative breast cancer (TNBC) was significantly associated with improved OS (Pooled HR 0.88, 95% CI 0.81-0.95, p=0.002) and higher pCR rates following neoadjuvant chemotherapy. Conversely, elevated TIGIT expression in primary tumors correlated with poorer OS (Pooled HR 1.58, 95% CI 1.18-2.11, p=0.004) and increased locoregional recurrence risk. TIM-3 demonstrated dual prognostic value: favorable in basal-like subtypes but detrimental in luminal subtypes. Funnel plots indicated minimal publication bias.

Conclusion: LAG-3, TIGIT, and TIM-3 function as distinct, non-redundant biomarkers. LAG-3 signifies a primed, actionable immune response, whereas TIGIT and TIM-3 indicate severe immune exhaustion. Mapping these profiles provides critical translational value for optimizing personalized surgical timing, predicting neoadjuvant downstaging, and selecting adjuvant immunotherapies.

The Clinical Trade-off between Rapid Hemodynamic Stabilization and Respiratory Morbidity in Pediatric Dengue Shock Syndrome: A Meta-Analysis of Colloid versus Crystalloid Resuscitation

Ni Nyoman Putri Widyastiti — 2026-04-09

Background: Fluid resuscitation is the cornerstone therapy for pediatric Dengue Shock Syndrome (DSS), a condition defined by profound endothelial hyperpermeability. The choice between crystalloids and colloids presents a clinical paradox. Crystalloids are standard first-line therapies, whereas colloids offer rapid intravascular expansion for refractory shock. This study quantifies the trade-off between the rapid hemodynamic stabilization provided by colloids and the subsequent iatrogenic risk of respiratory morbidity in pediatric DSS.

Methods: Following PRISMA guidelines, a systematic review and meta-analysis were conducted. We searched MEDLINE, Scopus, and Cochrane databases for original randomized controlled trials (RCTs) and cohort studies comparing crystalloid and colloid regimens in pediatric DSS. To address methodological heterogeneity, efficacy outcomes (time to hemodynamic stabilization) from RCTs and safety outcomes (respiratory morbidity) from observational cohorts were analyzed separately. Standardized mean differences (SMD) and odds ratios (OR) with 95% confidence intervals (CI) were calculated using random-effects models.

Results: Seven studies encompassing 2,477 pediatric patients were included. Meta-analysis of RCTs demonstrated that colloid-containing regimens achieved significantly faster initial hemodynamic stabilization compared to crystalloid-only regimens (SMD -0.62, 95% CI -0.85 to -0.39). Conversely, meta-analysis of cohort data revealed that mixed or colloid-heavy regimens were associated with a markedly increased risk of respiratory morbidity and mechanical ventilation requirements (OR 2.45, 95% CI 1.68 to 3.57). Overall shock recovery was prolonged in mixed-fluid groups.

Conclusion: A definitive clinical trade-off exists in pediatric DSS management. Colloids rapidly restore early hemodynamics but significantly increase late-stage respiratory morbidity and ventilation requirements. This supports a restrictive, crystalloid-first resuscitation strategy. Future randomized trials are urgently needed to specifically evaluate the safety of natural colloids, such as 5% albumin, versus synthetic starches and gelatins.

Serum Neurofilament Light Chain as a Discriminatory Biomarker and Predictor of Disease Trajectory in Amyotrophic Lateral Sclerosis: A Systematic Review and Meta-Analysis

Cindy Permata Sari — 2026-04-09

Background: Amyotrophic lateral sclerosis is a rapidly progressive, fatal neurodegenerative disorder characterized by the deterioration of upper and lower motor neurons. Diagnostic delays are frequently caused by phenotypic overlap with various mimic disorders. Serum neurofilament light chain has emerged as a promising biomarker; however, its precise discriminatory capacity against mimics and its utility in predicting disease trajectory necessitate rigorous quantitative evaluation.

Methods: Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, a systematic search of MEDLINE/PubMed, Embase, Cochrane Central, and Scopus was conducted. Eight high-quality primary research articles met the strict inclusion criteria for data extraction. Studies evaluating diagnostic utility (amyotrophic lateral sclerosis versus mimic disorders) and prognostic value (survival hazard ratios) were included. Random-effects models calculated pooled standardized mean differences for diagnostic accuracy and pooled hazard ratios for overall survival.

Results: The meta-analysis analyzed data from 8 cohorts. Serum neurofilament light chain levels were significantly elevated in amyotrophic lateral sclerosis patients compared to mimic disorders, yielding a pooled standardized mean difference of 1.43 (95% confidence interval: 1.15 to 1.71, p < 0.001). High heterogeneity was observed (I-squared = 82%). For prognostic evaluation, a pilot quantitative synthesis of two cohorts demonstrated that higher baseline concentrations correlated with increased mortality risk, showing a pooled hazard ratio of 1.95 (95% confidence interval: 1.58 to 2.41, p < 0.001).

Conclusion: Serum neurofilament light chain is a robust discriminatory biomarker capable of distinguishing amyotrophic lateral sclerosis from confounding mimic disorders. Furthermore, baseline concentrations offer prognostic value for survival outcomes. These findings support the cautious integration of this biomarker into clinical algorithms, though broader multi-center prognostic studies are required.

Diagnostic Accuracy of the Triglyceride-Glucose (TyG) Index for Identifying Advanced Chronic Kidney Disease in Type 2 Diabetes: A Cross-Sectional Analysis

Mathias Wahyu Manumpak Lumbantobing — 2026-04-10

Background: Chronic kidney disease (CKD) is a debilitating microvascular complication of type 2 diabetes mellitus (T2DM), fundamentally exacerbated by systemic insulin resistance and glucolipotoxicity. The triglyceride-glucose (TyG) index is emerging as a practical surrogate for insulin resistance. This study aims to evaluate the diagnostic accuracy of the TyG index in identifying advanced CKD among adults with T2DM.

Methods: A cross-sectional analysis was conducted on 44 adult T2DM patients with CKD at a tertiary referral hospital. To establish an adequate diagnostic threshold, advanced CKD was explicitly defined as an estimated glomerular filtration rate (eGFR) < 30 mL/min/1.73 m² (Stages IV and V). Patients were statistically stratified into three equal tertiles based on their TyG index. Diagnostic performance was evaluated using the Receiver Operating Characteristic (ROC) curve analysis.

Results: The median eGFR demonstrated a severe, statistically significant decline across increasing TyG tertiles (Tertile I: 54.09; Tertile II: 36.42; Tertile III: 19.12 mL/min/1.73 m²; p < 0.001). ROC analysis revealed a strong diagnostic profile for identifying advanced CKD, yielding an Area Under the Curve (AUC) of 0.756 (95% CI: 0.595–0.916, p = 0.002). An optimal cut-off value of 8.81 provided a sensitivity of 89.5% (95% CI: 66.9–98.7%), a specificity of 60.0% (95% CI: 38.7–78.9%), a positive predictive value of 63.0% (95% CI: 42.4–80.6%), and a negative predictive value of 88.2% (95% CI: 63.6–98.5%).

Conclusion: The TyG index is strongly associated with renal decline in T2DM. It serves as a highly accessible, adjunctive screening tool to stratify patients at risk for severe renal impairment.

Impact of DENV Genotypic Variation on Vaccine Efficacy and Cross-Neutralizing Antibody Responses: A Meta-Analysis

Utari Gusti Yulimdra — 2026-04-13

Background: The development of a broadly protective dengue virus (DENV) vaccine remains a paramount global health priority. Current tetravalent vaccines target the four DENV serotypes. However, intra-serotypic genetic variations, defined as genotypes, present a neglected immunological barrier. Evidence indicates that genotypic divergence critically impairs cross-neutralizing antibody responses, leaving vaccinated individuals vulnerable to circulating heterologous genotypes and severe antibody-dependent enhancement (ADE). This meta-analysis quantifies the impact of DENV genotypic variation on neutralizing antibody efficacy.

Methods: A systematic review and meta-analysis adhering to PRISMA guidelines were conducted. Quantitative virological data were extracted from primary studies, focusing on neutralizing antibody titers against homologous versus heterologous DENV genotypes. A DerSimonian-Laird random-effects model calculated the pooled Standardized Mean Difference (SMD) and 95% Confidence Intervals (CI). Heterogeneity was addressed through subgroup analyses (by serotype and host species). A sensitivity analysis employing the Hartung-Knapp-Sidik-Jonkman (HKSJ) adjustment verified robustness. Risk of bias was evaluated utilizing RoB 2 and SYRCLE tools.

Results: Ten controlled studies met the inclusion criteria. The pooled analysis revealed a severe, statistically significant reduction in neutralization capacity against heterologous genotypes compared to homologous strains, yielding an overall SMD of -1.52 (95% CI: -1.95 to -1.09, p < 0.001). High initial heterogeneity (I² = 84.1%) was partially resolved by stratifying by serotype; the DENV-2 subgroup demonstrated the most profound neutralization deficit (SMD = -1.78, I² = 42.5%). Sensitivity analyses confirmed the stability of the pooled effect.

Conclusion: Vaccine-induced neutralizing responses are significantly attenuated against heterologous DENV genotypes. The prevailing serotype-level vaccine paradigm is insufficient for comprehensive global immunity. Next-generation vaccine designs must incorporate conserved, pan-genotypic epitopes to prevent intra-serotypic immune evasion and subsequent ADE-mediated severe disease.

The Paradoxical Prognostic Value of Endogenous Melatonin in Acute Ischemic Stroke: A Systematic Review and Meta-Analysis of Mild-to-Moderate versus Malignant Infarctions

Merry Angeline — 2026-04-10

Background: Acute ischaemic stroke (AIS) is a leading global cause of morbidity and mortality. While endogenous melatonin is widely proposed as a neuroprotectant, recent clinical evidence suggests a paradoxical, severity-dependent prognostic relationship. This meta-analysis synthesises evidence regarding this paradox and its prognostic implications.

Methods: A systematic search of major databases through March 2026 identified observational studies correlating endogenous melatonin levels with AIS clinical outcomes. Data were stratified by stroke severity phenotype, and standardised mean differences were calculated using random-effects meta-regression models.

Results: Ten observational studies comprising 847 AIS patients were included. A striking paradox emerged: in patients with mild-to-moderate stroke, lower melatonin concentrations were associated with poor clinical outcomes. Conversely, in malignant middle cerebral artery infarctions, higher melatonin concentrations were paradoxically linked to worse clinical outcomes, including increased mortality. Extreme overall heterogeneity (I²=97.85%) was substantially resolved (I²=0%) upon proper severity stratification.

Conclusion: The prognostic implications of endogenous melatonin fundamentally differ according to stroke severity phenotype. This severity-dependent paradox likely reflects context-dependent alterations in melatonin signalling pathway efficacy. Mechanistic investigations and well-designed prospective trials are urgently warranted to elucidate the underlying pathophysiology.

Anesthetic Management of High-Risk Mitral Valve Replacement in a Young Adult with Posterior Leaflet Prolapse, Biventricular Dysfunction Risk, and Pulmonary Hypertension: A Case Report

Vera Muharrami — 2026-04-13

Background: Mitral valve disease with concurrent pulmonary hypertension and biventricular dysfunction represents a complex surgical challenge requiring meticulous perioperative management. This case report presents the anesthetic approach to a 43-year-old male with severe mitral regurgitation secondary to posterior leaflet prolapse, Grade III diastolic dysfunction, and intermediate probability pulmonary hypertension undergoing elective mitral valve replacement.

Case presentation: The patient presented with 6-month progressive dyspnea, chronic cough, bilateral lower-limb edema, and abdominal distension. Transthoracic echocardiography revealed severe mitral regurgitation with an effective regurgitant orifice area of 2.7 cm², bilateral atrial dilation, moderate tricuspid regurgitation, reduced tricuspid regurgitation jet velocity suggesting intermediate pulmonary hypertension probability, and preserved left ventricular ejection fraction of 68% with severely restrictive diastolic filling pattern. The patient underwent uncomplicated elective mitral valve replacement under general anesthesia with cardiopulmonary bypass. Intraoperative management emphasized hemodynamic stability through judicious fluid administration, careful anesthetic agent selection, and appropriate pulmonary vascular protection strategies. Cardiopulmonary bypass time was 125 minutes with an aortic cross-clamp time of 57 minutes. The postoperative course was uneventful with prompt extubation and discharge from intensive care on postoperative day three.

Conclusion: This case illustrates the importance of comprehensive preoperative optimization, multimodal monitoring, and tailored intraoperative management in patients presenting with the complex intersection of severe organic mitral valve disease, pulmonary hypertension, and advanced diastolic dysfunction. The use of sevoflurane-based anesthesia, preservation of systemic vascular resistance, and lung-protective ventilation strategies contributed to favorable perioperative outcomes. This case highlights unique management considerations that may not be extensively detailed in standard anesthetic textbooks and demonstrates successful outcomes despite significant preoperative cardiac compromise.

Intraocular Pressure Dynamics and Ischaemic Risks During Air Travel Post-Gas Tamponade: A Systematic Review and Meta-Analysis

Vina Yuwanda — 2026-04-13

Background: Gas tamponade is a widely used surgical intervention for retinal detachment repair. However, intraocular gas bubbles expand at altitude owing to Boyle's law, potentially causing severe intraocular pressure (IOP) elevation and ischaemic complications. The safety of air travel for patients with residual intraocular gas remains insufficiently characterised.

Methods: We conducted a systematic review and meta-analysis of empirical and computational studies examining IOP dynamics during simulated or actual altitude exposure in eyes with intraocular gas. We searched MEDLINE, Embase, Web of Science, Scopus and PubMed Central through March 2024 for peer-reviewed publications without language restrictions. Study selection followed PRISMA 2020 guidelines with predefined eligibility criteria. Data were extracted in duplicate, and risk of bias assessed using the Newcastle-Ottawa Scale. Random-effects meta-analysis calculated standardised mean differences (SMD) with 95% confidence intervals (CI). Sensitivity analyses stratified findings by study type.

Results: The primary analysis included three empirical studies (n = 47 eyes) showing IOP increase of SMD = 3.03 (95% CI: 2.18–3.89; I² = 17.16%, τ² = 0.11). Sensitivity analysis including all four studies (one computational model) yielded SMD = 4.67 (95% CI: 1.52–7.82; I² = 95.67%, τ² = 9.81). Individual study estimates ranged from SMD = 2.52 (Mills 2001) to SMD = 8.65 (Gsellman 2016, computational). Risk of bias was generally low to moderate. No significant publication bias was detected.

Conclusion: Patients with residual intraocular gas who undertake air travel face meaningful IOP elevation at altitude. The risk of anterior segment ischaemic complications warrants careful patient counselling, altitude restriction recommendations, and prophylactic pharmacotherapy. Future prospective studies should evaluate optimal clinical protocols.

Rhodomyrtus tomentosa Leaf Extract Cream Suppresses MMP-1 Expression and Epidermal Thickening in UVB-Irradiated Swiss Webster Mice

Defa Agripratama Ali — 2026-04-14

Background: Ultraviolet B (UVB) radiation induces matrix metalloproteinase-1 (MMP-1) expression and epidermal hyperplasia, contributing to photoaging. Rhodomyrtus tomentosa (karamunting) is rich in polyphenolic compounds with documented antioxidant properties, but its in vivo photoprotective effects remain unexplored.

Methods: We investigated the effects of R. tomentosa leaf extract cream at varying concentrations (0%, 12.5%, 25%, 50%) on UVB-irradiated Swiss Webster mice (n=4 per group). UVB exposure was standardized at approximately 150 mJ/cm² per session over seven consecutive days. Vitamin E cream served as a positive control. Immunohistochemical staining quantified MMP-1 expression as a percentage of positive cells, while hematoxylin-eosin histology measured epidermal thickness.

Results: Kruskal-Wallis testing revealed significant differences in both MMP-1 expression (H=10.43, p=0.015) and epidermal thickness (H=10.88, p=0.012). The 25% extract concentration optimally suppressed MMP-1 expression (mean 45.94% of positive cells) compared to the untreated UVB control (89.53%). A biphasic dose-response pattern emerged, with hormetic effects observed at 50% concentration (76.45%), suggesting polyphenol pro-oxidant activity at excessive concentrations. Epidermal thickness normalized with 25% treatment (71.8 μm) versus UVB control (93.4 μm). Immunohistochemical intensity decreased progressively with treatment intensification through 25%, supporting suppression of MMP-1-mediated collagen degradation.

Conclusion: R. tomentosa leaf extract cream at 25% concentration effectively suppresses MMP-1 expression and normalizes UVB-induced epidermal thickening in mice. The hormetic response at higher concentrations highlights the importance of dose optimization in phytotherapeutic development. This work establishes the first in vivo evidence for karamunting leaf extract as a photoprotective agent and supports further clinical translation.

Atypical Presentation of Clinically Non-Functioning Pituitary Macroadenoma: Case Report of Concurrent Graves' Disease and Multi-Axis Pituitary Hypofunction in a 40-Year-Old Female

Rizkha Amaliya — 2026-04-16

Background: Non-functioning pituitary adenomas (NFPAs) present variable clinical manifestations depending on tumor size and location. Concurrent primary autoimmune thyroid disease in NFPA patients is exceptionally rare and requires careful diagnostic distinction from secondary hypothyroidism.

Case presentation: A 40-year-old female presented with progressive bilateral peripheral vision narrowing over 3 months, chronic bifrontal headaches, secondary amenorrhea, and nocturia-predominant polyuria. Neuro-ophthalmologic examination revealed bitemporal hemianopsia with visual acuity 20/200 left eye and 20/25 right eye. Endocrine evaluation demonstrated: primary hyperthyroidism (TSH 0.02 µIU/mL, FT4 28.32 pmol/L, positive thyroid receptor antibodies), secondary adrenal insufficiency (cortisol 1 µg/dL, ACTH <5 pg/mL), and hypogonadotropic hypogonadism (LH 1.62 IU/L). Neuroimaging revealed a 2.13 × 2.28 × 3.05 cm sellar/suprasellar lesion with optic chiasm compression (Knosp Grade II). Endoscopic transsphenoidal surgery achieved complete gross total resection. Histopathology confirmed null-cell adenoma with low Ki-67 proliferation index (2%).

Conclusion: Postoperative course was uncomplicated with rapid visual field improvement, complete resolution of bitemporal hemianopsia by 2 weeks, and normalization of all endocrine axes by 12 weeks, including menstrual recovery and gonadal axis restoration. This case illustrates the diagnostic challenge of distinguishing secondary hyperprolactinemia from primary prolactinoma in NFPA, the rarity of concurrent Graves' disease with pituitary macroadenoma, and favorable outcomes with complete surgical decompression achieving multisystem endocrine recovery.

Perioperative Anesthesia Challenges in a Neonate with Concurrent Intussusception and Abdominal Compartment Syndrome: A Rare Clinical Scenario

Pratama Nanda — 2026-04-16

Background: Intussusception and abdominal compartment syndrome (ACS) are severe surgical emergencies in pediatric populations, particularly in neonates. The concurrent presentation of both conditions is exceptionally rare and presents formidable perioperative anesthetic challenges.

Case presentation: We report the case of a 2-month-old male neonate weighing 6.9 kg who presented with a 4-day history of bloody stools and bilious vomiting following blunt abdominal trauma inflicted by a 12 kg sibling. Clinical examination and imaging confirmed concurrent intussusception with abdominal compartment syndrome. The patient presented with significant hematologic derangements including severe leukopenia (WBC 1,180/μL), anemia (hemoglobin 9.2 g/dL), thrombocytosis, coagulopathy (INR 1.88), and electrolyte abnormalities. Emergency rapid sequence induction anesthesia was employed with careful fluid management utilizing the Holliday-Segar formula to prevent exacerbation of compartment pressures. A successful exploratory laparotomy with resection of necrotic small bowel segments was performed.

Conclusion: The case demonstrates the critical importance of comprehensive preoperative assessment, meticulous fluid management strategies, and multidisciplinary collaboration in managing complex neonatal surgical emergencies. This rare clinical scenario highlights unique anesthetic considerations and provides valuable insights into perioperative management of ACS in the neonatal population.

Risk of Acute Myocardial Infarction in Patients with Systemic Lupus Erythematosus Compared with the General Population: A Systematic Review and Meta-Analysis

Eli Novi — 2026-04-17

Background: Patients with systemic lupus erythematosus (SLE) are at substantially elevated risk of acute myocardial infarction (AMI) compared with the general population, attributable to a complex interplay of accelerated atherosclerosis, coronary microvascular dysfunction, antiphospholipid antibody-mediated thrombosis, and dysregulated innate immunity. Pooled estimates across published meta-analyses have not been formally synthesised.

Methods: A systematic review and meta-analysis were conducted in accordance with PRISMA 2020 guidelines. PubMed, MEDLINE, and EMBASE were searched through 2 April 2026 for studies reporting the relative risk (RR) of AMI in SLE patients versus the general population. Three eligible meta-analyses providing RR estimates were identified. Data were pooled using the DerSimonian-Laird random-effects model with Hartung-Knapp-Sidik-Jonkman (HKSJ) adjustment, implemented in R 4.5.3 (packages meta v8.2-1 and metafor v4.8-0). Heterogeneity was assessed using Cochran’s Q and I². Publication bias was evaluated using Egger’s precision-effect test. A sensitivity analysis incorporating all five eligible comparative studies with mixed effect measures (RR, rate ratio, OR) was performed, alongside subgroup analysis by study design.

Results: Three meta-analyses incorporating 24 to 46 primary studies and representing data from approximately 168,000 SLE patients were eligible for the primary pool. The pooled RR of AMI in SLE patients was 2.95 (95% CI 2.57–3.39; p < 0.001). Heterogeneity was negligible (I² = 0.0%; Q = 0.04, p = 0.98; τ² = 0.000). Weights were: Bello et al. 2023 (61.5%), Yazdany et al. 2020 (31.5%), Gu et al. 2019 (7.0%). Sensitivity analysis, including all five comparative studies (mixed measures), yielded a pooled effect of 5.27 (95% CI 2.91–9.53) with substantial heterogeneity (I² = 92.7%, Q = 55.11, p < 0.001), consistent with expected heterogeneity from mixing incompatible effect measures. Subgroup analysis by design showed Q-difference = 55.07 (df = 2, p < 0.001). Egger’s test was non-significant (t = 1.63, p = 0.35).

Conclusion: SLE patients face approximately a three-fold elevated risk of AMI compared with the general population, a finding derived from homogeneous, high-quality evidence and confirmed by sensitivity analyses. These findings underscore the need for systematic, SLE-specific cardiovascular risk management, including judicious use of hydroxychloroquine, lipid-lowering therapy, and multidisciplinary cardiorheumatology follow-up.

Acute Gouty Arthritis with Knee Effusion in a Patient with Chronic Lymphocytic Leukemia: Diagnostic Confirmation and Pre-Chemotherapy Hyperuricemia Management

Panji Hadi Permana — 2026-04-21

Background: Gout and chronic lymphocytic leukemia (CLL) represent distinct hematologic and rheumatologic pathologies; however, their concurrent presentation presents significant diagnostic and therapeutic challenges. Tumor lysis syndrome and chemotherapy-induced hyperuricemia are recognized complications of hematologic malignancies, yet the manifestation of acute gouty arthritis with crystallographic confirmation in CLL patients remains an underreported clinical scenario requiring careful diagnostic stratification.

Case presentation: We present a 69-year-old male farmer with newly diagnosed CLL (stage C, Binet classification) admitted for acute left knee arthritis with effusion, left ankle arthritis, and concurrent community-acquired pneumonia (CAP). Clinical examination revealed articular inflammation characterized by pain, swelling, erythema, warmth, and significant joint effusion with documented flexion limitation and positive bulging sign. Musculoskeletal ultrasound demonstrated double contour sign, synovial hypertrophy, and effusion measuring 5.8 cm in the suprapatellar recess with monosodium urate (MSU) crystal deposition confirmed by polarized light microscopy of synovial fluid (5,350 cells/mm³, 40% polymorphonuclear neutrophils, 60% mononuclear cells, positive MSU crystals). Serum uric acid was elevated at 10.6 mg/dL. The patient was successfully managed with colchicine, methylprednisolone, arthrocentesis, and supportive care while maintaining CLL treatment preparedness.

Conclusion: This case illustrates the importance of confirmatory synovial fluid analysis and ultrasound imaging in the diagnosis of acute gout in the context of hematologic malignancy. Optimal management requires careful coordination between rheumatology and hematology-oncology services to prevent therapeutic complications and ensure safe chemotherapy initiation in CLL patients with concurrent acute gouty arthritis and hyperuricemia.

Immunomodulatory Effects of Probiotics on Th17-Mediated Immune Responses in Psoriasis: A Systematic Review and Meta-Analysis

Rindi Rosalina Fadly — 2026-04-22

Background: Psoriasis is a chronic inflammatory skin disorder with increasing evidence supporting the role of the gut-skin axis in its pathogenesis. Recent studies suggest that probiotic supplementation may modulate Th17-mediated immune responses and improve clinical outcomes in psoriasis.

Methods: A systematic review and random-effects meta-analysis was conducted using PubMed, Scopus, Web of Science, and Cochrane Library databases (through February 2025). Randomised controlled trials evaluating probiotic supplementation in adult patients with psoriasis were included. The primary outcome was change in Psoriasis Area and Severity Index (PASI) score. Secondary outcomes included inflammatory markers (IL-6, CRP, IL-17) and immunological markers (Foxp3+ regulatory T cells, IL-10, TGF-β). Risk of bias was assessed using the Cochrane Risk of Bias tool (RoB 2), and evidence quality was evaluated using GRADE methodology.

Results: Five randomised controlled trials encompassing 268 participants (132 intervention, 136 control) were analysed. The pooled effect size for clinical outcomes (PASI) showed significant improvement favouring probiotic supplementation (Hedges' g = −0.8165; 95% confidence interval [CI], −1.6487 to −0.0483; p = 0.048; I² = 92.45%). Substantial heterogeneity was observed, with the Alshihmani 2025 pilot study demonstrating markedly larger effects on immunological markers (Hedges' g = −5.6963). Subgroup analysis revealed single-strain probiotics (pooled Hedges' g = −0.3487) had smaller effect sizes than multi-strain formulations (pooled Hedges' g = −3.6740). Publication bias assessment via funnel plot and Egger's regression showed no statistically significant asymmetry (p = 0.087).

Conclusion: Probiotic supplementation demonstrated statistically significant improvements in clinical outcomes and immunological markers in psoriasis. However, substantial heterogeneity and reliance on small trials limit certainty. The mechanistic evidence supporting gut-skin axis modulation warrants further investigation in adequately powered, long-term randomised controlled trials with standardised outcome measures and strain-specific analysis.

High-Altitude Maculopathy in Mountaineers: A Systematic Review and Meta-Analysis

Rataya Paramitha Maliawan — 2026-04-23

Background: High-altitude maculopathy (HAM) represents a distinct form of high-altitude retinopathy affecting mountaineers at extreme elevations. Despite increased mountaineering activity, the prevalence and clinical significance of HAM remain poorly characterised in systematic reviews.

Methods: A comprehensive systematic review and meta-analysis were conducted following PRISMA 2020 guidelines. Databases searched included PubMed, Scopus, Cochrane Library, and manual review of reference lists through April 2026. Eligible studies were prospective and retrospective cohorts reporting HAM prevalence in mountaineers at altitude ≥3,500 metres. Risk of bias was assessed using the Newcastle-Ottawa Scale. Meta-analysis employed the Freeman-Tukey double arcsine transformation with DerSimonian-Laird random-effects modelling.

Results: Three prospective studies (n=50 mountaineers) were analysed with a pooled prevalence of 73.37% (95% confidence interval: 60.28–84.72%). Heterogeneity was absent (I²=0%, Q=0.78, p=0.678). Subgroup analysis demonstrated a higher prevalence at extreme altitude (≥5,000 m: 78.6%) versus very high altitude (3,500–4,999 m: 70%). Sensitivity ranged 67.48–83.76%. Funnel plot inspection revealed no evidence of publication bias.

Conclusion: Approximately three-quarters of mountaineers experience HAM at high altitude, with prevalence increasing at extreme elevations. HAM represents a common but underrecognised altitude-related ocular complication. Future prospective studies should employ standardised diagnostic criteria and investigate the mechanistic pathways of macular involvement.

Management of Rare Secondary Full-Thickness Macular Hole in Proliferative Diabetic Retinopathy: Inverted ILM Flap Technique with Extended Surgical Follow-up

I Gusti Ngurah Dhyana Yoga — 2026-04-24

Background: Secondary full-thickness macular hole (FTMH) in proliferative diabetic retinopathy (PDR) is rare, occurring in only 1-4% of PDR cases. Combined with tractional retinal detachment (TRD), this complication presents significant surgical challenges. The inverted internal limiting membrane (ILM) flap technique remains under-utilized in this specific setting.

Case presentation: A 61-year-old Indonesian male with type 2 diabetes (>15 years), chronic kidney disease, and cardiovascular disease presented with sudden vision loss (best-corrected visual acuity 1/300). Examination revealed superior TRD (2-11 o'clock) and large FTMH (CMT 249 micrometers). After intravitreal bevacizumab (August 9^th, 2024), he underwent 360-degree pars plana vitrectomy with inverted ILM flap and silicone oil tamponade (August 14^th, 2024). Inferior redetachment at 2 months necessitated re-vitrectomy with endolaser and silicone oil evacuation (October 23^rd, 2024). At final follow-up (12 weeks post-second surgery), the patient achieved complete retinal reattachment with normalized macular anatomy, visual acuity 1/60, and intraocular pressure 10 mmHg.

Conclusion: Despite severe baseline disease and comorbidities, stepwise surgical strategy incorporating preoperative anti-VEGF therapy, comprehensive traction release, inverted ILM flap reconstruction, and staged procedures yielded meaningful anatomical recovery. This case supports inverted ILM flap utility in PDR-related secondary FTMH.

Effect of Simulated and Real Aircraft Cabin Environments on Tear Film Parameters in Dry Eye Disease: A Meta-Analysis

Jelly Vianti Fransisca Oeitano — 2026-04-24

Background: Air travel exposes passengers to environmental stressors, such as reduced cabin pressure and low humidity, which may exacerbate ocular surface conditions, particularly pre-existing dry eye disease (DED). This meta-analysis quantifies the impact of real and simulated aircraft cabin environments on tear film parameters, ocular surface biomarkers, and intraocular pressure (IOP).

Methods: Following PRISMA 2020 guidelines, a systematic search (January 2000–March 2026) identified ten eligible studies comprising 445 participants, with two providing complete quantitative data for meta-analytic pooling (10 effect sizes).

Results: Using a random-effects model, the overall pooled standardised mean difference (SMD) was 0.97 (95% CI: -0.67 to 2.61), indicating a large but non-significant effect with substantial heterogeneity (I² = 97.23%). Subgroup analyses revealed a non-significant pooled effect for tear film outcomes (Hedges' g = 0.71), contrasted by a significant elevation in IOP for gas-filled eyes (g = 1.92; p = 0.001). Despite the non-significant overall pooled estimate, individual effect sizes demonstrated large, clinically meaningful reductions in tear break-up time (TBUT) and significant increases in both corneal staining and inflammatory biomarkers (MMP-9 and IL-6). Egger's test showed no publication bias, though GRADE certainty remained low to very low.

Conclusion: Aircraft cabin environments induce clinically significant deteriorations in tear film stability, ocular surface integrity, and inflammation, alongside significant IOP elevations in susceptible individuals. These findings underscore the necessity of pre-flight ocular counselling and targeted preventive strategies for at-risk passengers, highlighting the need for future large-scale, standardised investigations.

Successful Management of Culture-Negative Fungal Keratitis with Epithelial Keratectomy and Intracameral Fluconazole Injection: A Case Report

Kristian Dernitra — 2026-04-24

Background: Fungal keratitis is a major cause of corneal blindness in tropical regions. Microbiological culture often yields negative results in up to 40% of clinically suspected cases, creating diagnostic and therapeutic challenges. This report describes successful management of culture-negative suspected fungal keratitis using epithelial keratectomy combined with intracameral fluconazole injection.

Case presentation: A 58-year-old male presented with progressive visual loss in the left eye following mud exposure and irrigation with river water. Examination revealed a 3×3 mm paracentral corneal ulcer with stromal infiltration exceeding one-third depth, satellite lesions, and 1.5 mm hypopyon. Gram stain, potassium hydroxide preparation, and culture were all negative. Based on clinical suspicion of fungal etiology, the patient underwent epithelial keratectomy with intracameral fluconazole injection, supplemented by intensive topical and systemic antifungal therapy. Progressive improvement was observed, with complete hypopyon resolution by day 26 and visual acuity improving from 1/300 to 6/30 over four months.

Conclusion: This case demonstrates that timely invasive antifungal intervention guided by clinical judgment can achieve favorable outcomes in culture-negative suspected fungal keratitis. The preservation of useful vision without corneal transplantation is particularly significant in resource-limited settings, underscoring the critical role of clinical decision-making when laboratory confirmation is unavailable.

In-House Virtual Surgical Planning Using 3D Slicer: Outcomes of Free Fibular Flap Mandibular Reconstruction

Redo Alif Iszar — 2026-04-27

Background: Mandibular reconstruction following tumor resection remains a significant surgical challenge requiring precise restoration of facial symmetry and function. Virtual surgical planning has emerged as a transformative approach, yet its adoption remains limited by the high costs of commercial platforms and proprietary cutting guides.

Methods: This proof-of-concept case series evaluated the operative outcomes and cost-effectiveness of an in-house virtual surgical planning workflow using 3D Slicer, a free open-source software platform, for mandibular reconstruction with free fibular flap without fibular cutting guides.

Results: Four consecutive patients (three males, one female; mean age 39.0 years; standard deviation 13.1; range 28-58) who underwent mandibular reconstruction between July and December 2024 were included. Three patients presented with ameloblastoma and one with squamous cell carcinoma. Preoperative computed tomography data were processed using 3D Slicer version 5.6.2 to generate three-dimensional mandibular models through thresholding segmentation, followed by mirroring technique reconstruction and polylactic acid three-dimensional printing. The mean ischemic time was 51.0 minutes (standard deviation 10.7; 95% confidence interval 34.0-68.0), representing a 70.4% reduction compared with conventional approaches in published literature. The mean total operative time was 455.0 minutes (standard deviation 136.5; 95% confidence interval 237.8-672.2). Model printing costs of IDR 50,000-100,000 (approximately USD 3-7) represented a 99% reduction compared with commercial cutting guides.

Conclusion: All flaps survived without complications. These preliminary findings suggest that simplified in-house virtual surgical planning using free open-source software provides a potentially cost-effective and efficient alternative for mandibular reconstruction, warranting validation in larger prospective studies.

Emergency Bedside Transvenous Pacing Without Fluoroscopic Guidance for Refractory Symptomatic Bradycardia Following Cardiac Arrest in Acute Inferior ST-Elevation Myocardial Infarction: A Case Report

Philipus Wiranata — 2026-04-29

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.

Menopausal Status as the Strongest Independent Predictor of Neoadjuvant Chemotherapy Response in Locally Advanced Breast Cancer

Stephen William Soeseno — 2026-06-04

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.

Emergency Splenectomy for Blunt Splenic Rupture Complicated by Post-Traumatic Acute Kidney Injury and Multiple Organ Dysfunction Syndrome: A Case Report

Syifa Firza Aziza — 2026-05-06

Background: Multiple organ dysfunction syndrome is a leading cause of mortality after major blunt trauma. The spleen is the most frequently injured intra-abdominal solid organ, and when rupture occurs, it may precipitate haemorrhagic shock, systemic inflammatory response, and cascading failure of the kidneys, lungs, and coagulation system. Early recognition, rapid haemorrhage control, and coordinated multidisciplinary support are essential to limit progression and improve survival.

Case presentation: A 30-year-old male motorcyclist presented to the emergency department after a high-velocity road traffic accident without helmet protection. On arrival, he was hypotensive (72/57 mmHg), tachycardic (140 bpm), apathetic with a Glasgow Coma Scale of 12, and had left upper quadrant tenderness with muscular defence. Focused assessment with sonography for trauma demonstrated free intraperitoneal fluid consistent with splenic rupture. Haemoglobin fell from 12.8 to 5.9 g/dL within hours and leukocytes rose to 37.8 ×10³/µL. An emergency splenectomy was performed for haemostasis. During the five-day intensive care course, he developed progressive oliguric acute kidney injury (peak creatinine 5.6 mg/dL, urea 114 mg/dL) requiring intermittent haemodialysis, hypercapnic respiratory failure (pH 6.969; pCO₂ 124.6 mmHg) requiring mechanical ventilation, stress hyperglycaemia (441 mg/dL) managed with insulin, and transient thrombocytopenia. Multidisciplinary care by trauma surgery, critical care, nephrology, and internal medicine resulted in haemodynamic stabilisation, recovery of renal function, and successful weaning from ventilation.

Conclusion: Prompt haemorrhage control through emergency splenectomy, goal-directed resuscitation, early initiation of renal replacement therapy, metabolic support, and coordinated multidisciplinary intervention were decisive in mitigating trauma-induced multiple organ dysfunction syndrome in this patient and are proposed as pillars of management in similar presentations.