Bioscientia Medicina - Journal of Biomedicine and Translational Research
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Differential Roles of CD117 and Ki67 in Gastrointestinal Stromal Tumors: Diagnostic Utility Versus Prognostic Power
Background: Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal neoplasms of the digestive tract, primarily driven by mutations in KIT or PDGFRA genes. CD117 (c-KIT) expression is a key diagnostic marker, while the Ki67 labeling index reflects cellular proliferation. Risk stratification, often using modified NIH criteria based on tumor size, mitotic rate, and location, guides prognosis and treatment. This study investigated the distinct roles of CD117 and Ki67 expression in relation to risk stratification in GIST patients.
Methods: This cross-sectional analytical study examined 27 GIST cases diagnosed between January 2021 and December 2024 from three Indonesian hospitals. Formalin-fixed paraffin-embedded tissues were analyzed using immunohistochemistry for CD117 (clone YR145) and Ki67 (clone K2). CD117 positivity was defined as ≥5% tumor cell staining, and high Ki67 expression as >10% nuclear staining. Risk stratification utilized the modified NIH criteria. The Chi-square test assessed correlations (p<0.05 significance).
Results: The cohort predominantly comprised patients >50 years (66.7%), males (59.3%), with gastric tumors (51.9%), large tumor size (>5cm in 96.3%), spindle cell morphology (77.8%), and high mitotic rates (74.1%). Most cases (85.2%) were classified as high-risk. CD117 was positive in 81.5% (22/27) of cases but showed no significant correlation with risk stratification (p=0.561). High Ki67 expression was found in 74.1% (20/27) of cases and demonstrated a significant positive correlation with high-risk stratification (p=0.002). The combination of CD117 and Ki67 status also showed a significant association with risk stratification (p=0.001).
Conclusion: While CD117 expression remains a cornerstone for GIST diagnosis and targeted therapy selection, it did not correlate significantly with risk stratification in this cohort. Conversely, a high Ki67 labeling index was significantly associated with high-risk GIST, underscoring its potential as a valuable prognostic marker alongside established risk stratification parameters.  
Non-Operative Management Accelerates Recovery: Reduced Length of Hospital Stay in Partial Small Bowel Obstruction with Virgin Abdomens
Background: Small bowel obstruction (SBO) represents a formidable challenge in surgical practice. Partial SBO (PSBO) in individuals without a history of abdominal surgery, termed "virgin abdomens," introduces distinct diagnostic and therapeutic considerations. While non-operative management (NOM) has become a cornerstone for adhesive SBO, comprehensive data elucidating its impact on PSBO in virgin abdomens, especially concerning the length of hospital stay (LOS), are not extensively available. This study was designed to meticulously compare the LOS between NOM and operative interventions in patients diagnosed with PSBO affecting virgin abdomens, specifically within a tertiary care setting in Indonesia.
Methods: A retrospective analytic observational methodology, utilizing a cross-sectional design, was implemented at Dr. Kariadi General Hospital, Semarang, covering patients admitted from January through December 2024. The study included patients over 18 years of age with a confirmed diagnosis of PSBO in a virgin abdomen. Exclusion criteria encompassed total SBO, obstructions located in the colon, or any record of prior abdominal surgical procedures. The principal outcome measure, LOS, was rigorously compared between the cohort managed non-operatively and the cohort that underwent surgical procedures. Statistical analysis was performed using appropriate tests, with a p-value below 0.05 established as the threshold for statistical significance.
Results: The study cohort comprised 167 eligible patients. For the 112 patients (67.1%) subjected to surgical intervention, the mean LOS was recorded at 13.2±8.72 days. Conversely, the 55 patients (32.9%) managed conservatively demonstrated a markedly shorter mean LOS of 7.74±6.12 days. This observed difference in LOS was statistically highly significant (p < 0.001). The mean age of the participants was 50.60±14.94 years, with females constituting 52.1% of the group.
Conclusion: In clinically stable patients presenting with partial small bowel obstruction in virgin abdomens, non-operative management was associated with a significantly diminished length of hospital stay when compared to surgical intervention. This conservative strategy proves to be an effective and advantageous approach in appropriately selected patient populations, offering the potential to lessen hospital burden and enhance recovery timelines
Optimizing Sunburn Prevention in Children: A Meta-Analysis of the Efficacy of Sunscreen Application, Protective Apparel, and Shade-Seeking Behaviors
Background: Childhood sunburn significantly elevates lifelong skin cancer risk, underscoring the need for effective prevention. While sunscreen, protective apparel, and shade-seeking are advocated, a quantitative synthesis of their efficacy in children is crucial. This meta-analysis aimed to consolidate and quantify the evidence on the effectiveness of these core sun protection strategies in preventing pediatric sunburn.
Methods: A systematic search of PubMed/MEDLINE, Scopus, Cochrane CENTRAL, and Web of Science (January 2014 - December 2024) identified randomized controlled trials and cohort studies evaluating sunscreen, protective apparel, or shade-seeking behaviors for sunburn prevention in individuals aged 0-18 years. Data on sunburn incidence were extracted, study quality assessed, and pooled Risk Ratios (RR) with 95% confidence intervals (CI) calculated using a random-effects model.
Results: Six studies (two RCTs, four cohort studies) involving 8,500 children were included. Regular sunscreen use (SPF ≥30) significantly reduced sunburn incidence (RR 0.65, 95% CI 0.55-0.77). Protective apparel use also demonstrated substantial protection (RR 0.70, 95% CI 0.60-0.82). Enhanced shade provision and shade-seeking behaviors effectively lowered sunburn risk (RR 0.75, 95% CI 0.62-0.90). Multi-component strategies combining these approaches showed consistent protective benefits.
Conclusion: This meta-analysis provides robust quantitative evidence that diligent sunscreen application, consistent use of protective apparel, and active shade-seeking are all significantly effective in reducing sunburn incidence in children. These findings strongly support multifaceted public health initiatives emphasizing comprehensive sun protection to safeguard pediatric skin health
The Predictive Value of Sperm Mitochondrial DNA Copy Number on Male Infertility: A Systematic Review and Meta-Analysis
Background: The integrity and quantity of mitochondrial DNA (mtDNA) in spermatozoa are considered critical for male reproductive potential. While qualitative damage like deletions has been linked to infertility, the significance of quantitative changes, specifically mtDNA copy number (mtDNAcn), remains debated. This study aimed to systematically review and meta-analyze the existing evidence to determine the association between sperm mtDNAcn and male infertility.
Methods: We conducted a systematic search of PubMed, Science Direct, and Scopus databases for observational studies published between January 2014 and December 2024. The search included studies that compared sperm mtDNAcn between infertile men, who were diagnosed with conditions such as oligozoospermia, asthenozoospermia, and teratozoospermia, and normozoospermic fertile controls. Data were pooled using a random-effects model to calculate the standardized mean difference (SMD) with 95% confidence intervals (CIs). Heterogeneity was assessed using the I² statistic.
Results: Seven case-control studies comprising 658 infertile men and 612 normozoospermic controls met the inclusion criteria. The quality of the included studies was moderate to high. The pooled data revealed that sperm mtDNAcn was significantly higher in infertile men compared to fertile controls (SMD = 1.28, 95% CI: 0.81 to 1.75, p &lt; 0.00001). Significant heterogeneity was observed among the studies (I² = 88%, p<0.00001). Subgroup analysis based on infertility phenotype showed a consistently elevated mtDNAcn across oligozoospermia, asthenozoospermia, and oligoasthenoteratozoospermia (OATs). The funnel plot was largely symmetrical, and Egger’s test showed no significant evidence of publication bias (p = 0.12).
Conclusion: This meta-analysis provides strong evidence that an elevated sperm mtDNA copy number is significantly associated with male infertility. This quantitative alteration may serve as a crucial biomarker for assessing sperm quality and spermatogenic dysfunction. The findings suggest that increased mtDNAcn likely represents a compensatory response to underlying mitochondrial defects and oxidative stress, warranting further investigation into its clinical utility for diagnosing and managing male infertility
Diagnostic Accuracy of Pulmonary Function Tests in Identifying Shrinking Lung Syndrome: A Meta-Analysis
Background: Shrinking lung syndrome (SLS) is a rare but significant pleuropulmonary complication of systemic autoimmune diseases, primarily systemic lupus erythematosus (SLE). Early and accurate diagnosis is crucial for timely intervention, but often challenging due to the insidious onset and overlapping symptoms with other respiratory conditions. This meta-analysis aims to synthesize the existing evidence on the diagnostic performance of various PFT parameters in identifying SLS.
Methods: We conducted a systematic search of PubMed, Embase, Scopus, and Web of Science databases from January 2013 to May 2024. We included studies that reported the diagnostic accuracy of PFTs (specifically, total lung capacity [TLC], forced vital capacity [FVC], diffusing capacity for carbon monoxide [DLCO], and maximal inspiratory pressure [MIP]) in differentiating SLS from other respiratory conditions or healthy controls in patients with systemic autoimmune diseases. Heterogeneity was assessed using the I² statistic.
Results: Nine studies, comprising a total of 685 patients with systemic autoimmune diseases (215 with SLS and 470 without SLS), were included. The pooled sensitivity and specificity of TLC ≤ 80% predicted for diagnosing SLS were 0.85 (95% CI, 0.78-0.90) and 0.72 (95% CI, 0.63-0.80), respectively. For FVC ≤ 80% predicted, the pooled sensitivity and specificity were 0.78 (95% CI, 0.69-0.85) and 0.65 (95% CI, 0.55-0.74), respectively. DLCO showed lower sensitivity (0.68; 95% CI, 0.57-0.77) but higher specificity (0.80; 95% CI, 0.71-0.87). MIP demonstrated a sensitivity of 0.75 (95% CI: 0.61, 0.85) and a specificity of 0.60 (95% CI: 0.44, 0.74). Significant heterogeneity was observed across studies (I² > 50% for most analyses).
Conclusion: PFTs, particularly TLC, are valuable tools in the diagnostic workup of SLS. While TLC demonstrates good sensitivity, its moderate specificity necessitates a comprehensive evaluation, integrating clinical findings, imaging, and potentially other biomarkers
Temporal Dynamics of Postoperative Enterocolitis in Hirschsprung Disease: A Comparative Analysis of Earlier Onset After TAERPT versus the Duhamel Procedure
Background: Hirschsprung-associated enterocolitis (HAEC) remains the most formidable cause of morbidity in surgically corrected Hirschsprung disease (HD). While the transanal endorectal pull-through (TAERPT) and the Duhamel procedure are standard treatments, a critical knowledge gap exists regarding the timing of postoperative HAEC onset associated with each technique. This study aimed to investigate and compare the temporal dynamics of HAEC presentation following these distinct surgical reconstructions.
Methods: This single-center, retrospective cohort study reviewed 64 HD patients who underwent either TAERPT (n=32) or a modified Duhamel procedure (n=32) between January 2022 and January 2023 at a tertiary referral hospital. The primary outcome was the incidence of severe HAEC (HAEC score ≥10). The principal secondary outcome was the time to onset of the first episode of mild-to-moderate HAEC (score <10). Due to the non-normal distribution of onset data, the Mann-Whitney U test was used for statistical comparison.
Results: Baseline demographic and clinical characteristics were comparable between the two cohorts. The incidence of severe HAEC was 0% in both the TAERPT and Duhamel groups. All recorded complications were mild-to-moderate and managed non-surgically. A statistically significant and clinically profound difference in the timing of these complications was observed. The median onset of HAEC in the TAERPT group was 6.0 months (Interquartile Range [IQR], 3.0-6.0), which was significantly earlier than the median onset of 8.5 months (IQR, 3.0-24.0) in the Duhamel group (p < 0.001). The mean onset times were 5.50 ± 1.90 months and 16.09 ± 16.33 months, respectively.
Conclusion: Although both TAERPT and the Duhamel procedure demonstrated excellent safety profiles regarding severe HAEC, their associated temporal patterns of mild-to-moderate enterocolitis are markedly different. The significantly earlier onset of complications following TAERPT suggests that postoperative surveillance strategies should be procedure-specific, with intensified clinical vigilance during the first postoperative year for TAERPT patients
Ultrasound-Guided Neuraxial Precision in a High-Risk Adolescent Parturient: Navigating Anesthetic Management in the Confluence of Nephrotic Syndrome, Diastolic Heart Failure, and Anasarca
Background: Anesthetic management for cesarean delivery in parturients with concurrent nephrotic syndrome and decompensated heart failure presents a profound clinical challenge. Severe anasarca can obliterate anatomical landmarks, while complex cardiorenal pathophysiology creates a state of extreme hemodynamic fragility. This case report describes a systematic, ultrasound-guided approach to overcome these obstacles.
Case presentation: A 15-year-old primigravida at 33 weeks gestation, with new-onset nephrotic syndrome and decompensated heart failure (NYHA Class III), required an emergency cesarean section. Clinical examination revealed severe anasarca, rendering lumbar spinal landmarks impalpable. A systematic pre-procedural lumbar ultrasound examination was performed using a low-frequency curvilinear transducer. This allowed for precise identification of the L3-L4 interspace and an accurate skin-to-dura depth measurement of 4.6 cm. A single-attempt subarachnoid block was successfully performed with a reduced dose (10 mg) of hyperbaric bupivacaine. An adequate T4 sensory block was achieved for surgery. The patient remained remarkably hemodynamically stable throughout the procedure, with no episodes of hypotension requiring vasopressor support. A healthy infant was delivered, and both maternal and neonatal outcomes were excellent.
Conclusion: This case demonstrates that a systematic pre-procedural ultrasound protocol is an indispensable tool for enhancing the safety and success of neuraxial anesthesia in high-risk obstetric patients. By enabling precise anatomical localization and informed dose reduction, it mitigates procedural risk and supports hemodynamic stability in the face of distorted anatomy and severe cardiorenal comorbidities
Fatal Disseminated Tuberculosis in Vaccinated Children with Failed BCG Scar Formation: A Clinical-Pathological Correlation and Immunological Review
Background: The Bacillus Calmette-Guérin (BCG) vaccine remains the cornerstone of preventative strategies against severe pediatric tuberculosis (TB), specifically disseminated forms such as miliary TB and tuberculous meningitis (TBM). While the formation of a cutaneous scar is historically viewed as a surrogate marker for successful vaccine uptake and delayed-type hypersensitivity (DTH), its absence is often clinically overlooked. This study investigates the correlation between the lack of BCG scarring, immunological anergy, and fatal disseminated disease outcomes.
Case presentation: We report a clinical-pathological analysis of two pediatric patients admitted to a tertiary care center in Indonesia. Case 1, an 11-month-old male vaccinated at birth, presented with status epilepticus and was diagnosed with Probable TBM Stage III. Despite vaccination, he lacked a BCG scar and exhibited Tuberculin Skin Test (TST) anergy (0 mm). Case 2, a 2-year-8-month-old female vaccinated at birth, presented with Type 1 respiratory failure due to severe miliary TB. She demonstrated profound wasting and TST anergy (0 mm). Both patients succumbed to the disease (Day 9 and Day 14, respectively) despite aggressive management.
Conclusion: The absence of a BCG scar in vaccinated children serves as a critical clinical indicator of "immunological silence." It correlates with a failure to mount the Th1-mediated granulomatous response necessary for containing lymphohematogenous spread. We recommend that scar failure be treated as a risk factor requiring enhanced surveillance and a lower threshold for preventative therapy
Unmasking Organic Pathology in Pediatric Recurrent Abdominal Pain: Diagnostic Yield, Histopathological Discordance, and the Asian Enigma in a Tertiary Indonesian Setting
Background: Recurrent abdominal pain (RAP) in children presents a complex diagnostic dichotomy between functional disorders and organic pathology. In Southeast Asia, this challenge is compounded by the Asian Enigma of variable Helicobacter pylori prevalence. This study evaluated the diagnostic yield of Esophagogastroduodenoscopy (EGD) and the correlation between macroscopic and histopathological findings in an Indonesian tertiary pediatric cohort.
Methods: A retrospective, analytical cross-sectional study was conducted on 108 pediatric patients aged 1 to 18 years fulfilling Rome IV criteria for RAP between January 2022 and July 2025. EGD was performed, with biopsies taken based on macroscopic abnormalities or clinical suspicion (n=65). Diagnostic yield was calculated, and H. pylori prevalence was subjected to sensitivity analysis to account for non-biopsied patients. Multivariate logistic regression identified predictors of organic findings.
Results: The cohort was predominantly female (65.7%) and adolescent (48.1%). The overall diagnostic yield for macroscopic abnormalities was 77.8%, dominated by macroscopic gastritis (39.8%). H. pylori infection was confirmed in 26.9% of the total cohort, rising to 44.6% (95% Confidence Interval: 32.5%–57.3%) among biopsied patients. Sensitivity analysis estimated the true prevalence range between 26.9% and 48.0%. Notably, in a subset of patients with normal macroscopic mucosa (n=10), 30% exhibited microscopic inflammation, indicating endoscopic-histologic discordance. Independent predictors of organic pathology included age over 10 years (adjusted Odds Ratio 2.41) and vomiting (adjusted Odds Ratio 3.12).
Conclusion: EGD reveals a high burden of organic disease in Indonesian children with RAP, challenging the functional paradigm in this setting. The significant rate of H. pylori and potential microscopic inflammation in normal-appearing mucosa suggest that biopsy should be considered routine rather than targeted to avoid verification bias
Predictive Value of Circulating Pro-Fibrotic Cytokines for Progression in Idiopathic Pulmonary Fibrosis and Progressive Pulmonary Fibrosis (PPF): A Systematic Review and Meta-Analysis
Background: The clinical trajectory of patients with idiopathic pulmonary fibrosis (IPF) and the broader phenotype of progressive pulmonary fibrosis (PPF) is highly variable. Current prognostic models lack precision, highlighting an urgent need for reliable biomarkers. Circulating pro-fibrotic cytokines are implicated in fibrogenesis, but their individual predictive utility for disease progression remains debated. This systematic review and meta-analysis were conducted to synthesize the available evidence and quantify the predictive value of key circulating pro-fibrotic cytokines for disease progression in patients with IPF and PPF.
Methods: A systematic literature search was performed in PubMed, Embase, and Scopus databases for studies published between January 1st, 2014, and December 31st, 2024. We included longitudinal cohort studies that evaluated the association between baseline circulating levels of Transforming Growth Factor-beta 1 (TGF-β1), Chemokine Ligand 18 (CCL18), or Interleukin-6 (IL-6) and a composite endpoint of disease progression (all-cause mortality, lung transplantation, or a significant decline in Forced Vital Capacity [FVC]). Hazard Ratios (HRs) and their 95% Confidence Intervals (CIs) were extracted. A random-effects model was used to pool the data. Heterogeneity was assessed using the I² statistic, and publication bias was evaluated with funnel plots and Egger’s test.
Results: The search yielded 1,842 citations, from which seven studies comprising a total of 1,158 patients met the inclusion criteria. Elevated baseline levels of all three cytokines were significantly associated with an increased risk of disease progression. The pooled HR for TGF-β1 (4 studies, 650 patients) was 2.15 (95% CI: 1.55-2.98, p < 0.001), with moderate heterogeneity (I² = 55%). For CCL18 (5 studies, 812 patients), the pooled HR was 1.98 (95% CI: 1.41-2.78, p < 0.001), with substantial heterogeneity (I² = 68%). For IL-6 (3 studies, 515 patients), the pooled HR was 2.41 (95% CI: 1.78-3.26, p < 0.001), with low heterogeneity (I² = 21%). Subgroup analysis suggested a consistent predictive effect across both IPF and non-IPF PPF cohorts.
Conclusion: This meta-analysis provides robust evidence that elevated circulating levels of TGF-β1, CCL18, and IL-6 are potent and independent predictors of disease progression in patients with IPF and PPF. These biomarkers hold significant promise for enhancing patient risk stratification, improving prognostic accuracy, and guiding personalized therapeutic decisions in clinical practice