Accreditation
SINTA 2Nationally Accredited Journal
Vol. 9 No. 9 (2025): Bioscientia Medicina: Journal of Biomedicine & Translational Research
Articles
-
Pancreas-Sparing Mucosectomy for a Complex Gastric Duplication Cyst: A Case Report
Views: 510Downloads: 240Background: Gastric duplication (GD) is a rare congenital anomaly, representing 2–9% of all gastrointestinal duplications. These embryologic abnormalities are typically managed by complete surgical resection due to the risk of complications, including malignancy. However, this standard approach becomes perilous when the duplication cyst is intimately adherent to vital organs. We present a case where a large gastric duplication cyst was inseparable from the pancreas, necessitating a deviation from standard management.
Case presentation: An 8-month-old female infant presented with a four-month history of non-bilious vomiting and progressive abdominal distension. A palpable, cystic, 8x5 cm mass was identified in the left upper abdomen. Abdominal ultrasound revealed a loculated, septated cystic lesion, and a barium study demonstrated a significant filling defect on the greater curvature of the stomach. Initial management was delayed as the family sought alternative medicine. Surgical exploration revealed a large gastric duplication cyst arising from the greater curvature, which was found to be densely adherent to the body and tail of the pancreas. To avoid catastrophic pancreatic injury, a complete resection was abandoned in favor of a pancreas-sparing mucosectomy. The entire mucosal lining of the duplication was excised, and the shared muscular wall was preserved and repaired. Postoperatively, the patient had a transient ileus but recovered well, with complete resolution of symptoms. At an 11-day follow-up, she was thriving, feeding well, and had gained significant weight. Histopathology confirmed a benign gastric duplication cyst.
Conclusion: This case highlights that for complex gastric duplication cysts where resection would endanger vital structures, complete mucosal excision is a safe, effective, and organ-preserving surgical alternative. This technique successfully mitigates the risks of both the untreated anomaly and iatrogenic surgical complications, underscoring the importance of surgical judgment and adaptability in managing rare congenital anomalies.
-
Navigating a Therapeutic Triad: A Case of Pulmonary Tuberculosis Complicated by Drug-Induced Liver Injury and Prediabetes
Views: 539Downloads: 168Background: The management of pulmonary tuberculosis (TB) is frequently complicated by adverse drug reactions, with drug-induced liver injury (DILI) being one of the most severe. The clinical challenge is significantly amplified in patients with underlying metabolic disorders such as prediabetes, which can impair immune responses and affect treatment outcomes. This report details the complex management of a geriatric patient presenting with this therapeutic triad.
Case presentation: A 67-year-old male with newly diagnosed, drug-sensitive pulmonary tuberculosis developed severe hepatotoxicity ten days after initiating standard first-line anti-tuberculosis therapy. Clinical presentation included jaundice, nausea, and vomiting, with laboratory findings showing a severe hepatocellular injury pattern (SGOT 204 U/L, SGPT 126 U/L) and hyperbilirubinemia (Total Bilirubin 2.6 mg/dL). Concurrently, he was diagnosed with prediabetes (HbA1c 5.9%) and was suffering from severe malnutrition (BMI 15.6 kg/m²). The offending drugs were immediately withdrawn, and supportive therapy was initiated. Following normalization of liver function, a modified anti-tuberculosis regimen was cautiously reintroduced using a stepwise re-challenge protocol that entirely omitted pyrazinamide.
Conclusion: The patient was successfully managed with a modified nine-month regimen of isoniazid, rifampicin, and ethambutol, achieving clinical and biochemical stability without recurrence of liver injury. This case highlights that a meticulous, stepwise approach—involving prompt drug withdrawal, supportive care, and a tailored re-challenge protocol—can lead to successful TB treatment outcomes without recurrence of DILI, even in a patient with multiple converging high-risk factors.
-
Head-to-Head Comparison of Urinary Hydroxyproline and Serum CTX-I in Monitoring Antiresorptive Therapy for Osteoporosis: A Network Meta-Analysis
Views: 491Downloads: 142Background: Bone turnover markers (BTMs) are essential for monitoring the efficacy of antiresorptive therapies in osteoporosis. While serum C-terminal telopeptide of type I collagen (s-CTX-I) is the recommended reference marker for bone resorption, the utility of the classic marker, urinary hydroxyproline (u-HYP), in the modern therapeutic era remains debated. This study aimed to provide the first network meta-analysis (NMA) to compare the responsiveness of u-HYP and s-CTX-I to antiresorptive treatments.
Methods: We conducted a systematic review and NMA of randomized controlled trials (RCTs) published between January 2015 and December 2024. We searched PubMed, Embase, and the Cochrane Central Register of Controlled Trials for RCTs of antiresorptive therapies (alendronate, denosumab, risedronate) in postmenopausal women with osteoporosis that reported changes in s-CTX-I or u-HYP at 3-6 months. A Bayesian random-effects NMA was performed to calculate the standardized mean difference (SMD) and rank the responsiveness of each marker.
Results: Seven RCTs involving 3,451 patients met the inclusion criteria. The evidence network was well-connected for both markers. Antiresorptive therapies induced a significantly greater reduction in s-CTX-I levels compared to u-HYP. For instance, the effect of denosumab versus placebo was substantially larger when measured by s-CTX-I (SMD: -1.88; 95% Credible Interval [CrI]: -2.25 to -1.51) than by u-HYP (SMD: -0.95; 95% CrI: -1.22 to -0.68). Surface Under the Cumulative Ranking (SUCRA) analysis confirmed that s-CTX-I had a 98.2% probability of being the more responsive marker, compared to 1.8% for u-HYP. Heterogeneity was manageable, and no significant inconsistency was detected between direct and indirect evidence.
Conclusion: This network meta-analysis provides robust, synthesized evidence that serum CTX-I demonstrates a markedly superior dynamic response to antiresorptive therapy compared to urinary hydroxyproline. These findings reinforce the position of s-CTX-I as the preferred biomarker for monitoring treatment efficacy in clinical practice.
-
Harnessing Nature's Adjuvant: A Systematic Review and Meta Analysis of Phyllanthus niruri's Immunomodulatory and Chemosensitizing Mechanisms in Colorectal Cancer
Views: 755Downloads: 168Background: Colorectal cancer (CRC) poses a significant global health burden, and the limitations of conventional therapies necessitate the exploration of effective adjuvants. Phyllanthus niruri (PNL), a medicinal herb, has demonstrated notable anticancer properties. This study aims to systematically review and quantitatively synthesize the evidence from preclinical and clinical studies on PNL's efficacy in CRC.
Methods: Following PRISMA guidelines, a systematic search was conducted in PubMed, Scopus, Web of Science, and Google Scholar for in vitro, in vivo, and clinical trials on PNL and CRC published up to December 2023. Primary outcomes included cell viability, tumor volume, and immunological biomarkers. Data were extracted for meta-analysis, calculating standardized mean differences (SMD) with 95% confidence intervals (CI) using a random-effects model to account for heterogeneity, which was assessed using the I² statistic.
Results: Twenty-one primary studies were included in the systematic review, with a subset eligible for meta-analysis. The qualitative synthesis confirmed PNL's multimodal action, including apoptosis induction, Wnt/β-catenin pathway inhibition, and immunomodulation. The meta-analysis revealed that PNL treatment resulted in a significant reduction in tumor volume in animal models (SMD: -2.54; 95% CI: -3.87 to -1.21; p < 0.001) and a favorable decrease in the Neutrophil-to-Lymphocyte Ratio (NLR) (SMD: -1.89; 95% CI: -2.78 to -1.01; p < 0.001). Significant heterogeneity was observed across studies.
Conclusion: This systematic review and meta-analysis provides robust, synthesized evidence for the therapeutic efficacy of Phyllanthus niruri in colorectal cancer. PNL significantly reduces tumor growth and modulates key prognostic biomarkers, underscoring its potential as a powerful adjuvant therapy. These findings strongly advocate for the initiation of large-scale, standardized clinical trials to translate this promising natural agent into clinical practice.
-
Opioid Rotation vs. Dose Titration in Refractory Cancer Pain: A Meta-Analysis of Efficacy and Adverse Events
Views: 517Downloads: 243Background: The management of refractory cancer pain represents a formidable clinical challenge at the intersection of oncology and palliative medicine. When patients with advanced malignancy fail to achieve adequate analgesia or develop intolerable adverse effects from their opioid regimen, clinicians are faced with a crucial decision: to escalate the dose of the current opioid (dose titration) or to switch to a different opioid agent (opioid rotation). The optimal strategy remains a subject of intense debate and variable practice. This meta-analysis was conducted to rigorously compare the efficacy and safety of these two common interventions.
Methods: A systematic and comprehensive search was performed in the PubMed, EMBASE, and Cochrane Central Register of Controlled Trials databases for randomized controlled trials (RCTs) published between January 2015 and December 2024. We included studies that directly compared opioid rotation with dose titration in adult palliative care patients diagnosed with refractory cancer pain. The primary efficacy outcome was the change in pain intensity, analyzed using the Standardized Mean Difference (SMD) to accommodate pain scales such as the Numerical Rating Scale (NRS) and Visual Analogue Scale (VAS). Primary safety outcomes were the incidence of severe neurotoxicity and severe constipation. Data were pooled using a random-effects model, and results were expressed as SMD for the continuous pain outcome and Risk Ratio (RR) for dichotomous adverse events, with corresponding 95% confidence intervals (CI).
Results: Seven RCTs, encompassing a total of 962 patients, met the stringent inclusion criteria. The pooled analysis revealed that the strategy of opioid rotation resulted in a statistically significant and clinically substantial greater reduction in pain intensity compared to continued dose titration (SMD -0.65, 95% CI [-0.88, -0.42], p<0.00001; I²=81%). Furthermore, the risk of developing severe neurotoxicity, including delirium and myoclonus, was significantly lower in the rotation group (RR 0.62, 95% CI [0.45, 0.85], p=0.003; I²=18%). There was no statistically significant difference in the incidence of severe constipation between the two intervention groups (RR 0.90, 95% CI [0.71, 1.14], p=0.38; I²=24%).
Conclusion: In patients with refractory cancer pain, the strategy of opioid rotation provided superior analgesia and was associated with a markedly lower risk of severe neurotoxicity when compared to the continued dose titration of the same opioid. These findings provide strong, high-level evidence to support the use of opioid rotation as a primary and proactive strategy for managing uncontrolled pain or dose-limiting side effects in the palliative care population.
-
Efficacy and Safety of Bullectomy versus Conservative Management in Patients with Symptomatic Vanishing Lung Syndrome: A Systematic Review and Meta-Analysis of Respiratory Outcomes
Views: 513Downloads: 453Background: Vanishing lung syndrome (VLS), a severe form of giant bullous emphysema, causes debilitating dyspnea by compressing functional lung. A critical evidence gap exists regarding the optimal management strategy, forcing a contentious choice between surgical bullectomy and conservative care. This study provides the first meta-analytic synthesis comparing these two approaches.
Methods: Following PRISMA guidelines, we systematically searched PubMed, Embase, Scopus, and Web of Science for comparative studies (2015-2024) evaluating bullectomy versus conservative management in symptomatic VLS. Primary outcomes were changes in Forced Expiratory Volume in one second (FEV1), St. George's Respiratory Questionnaire (SGRQ) scores, and major complications. Data were pooled using a random-effects model, and bias was assessed with the ROBINS-I tool.
Results: Six non-randomized studies involving 488 patients were included. The overall risk of bias was moderate to serious. Compared to conservative care, bullectomy was associated with a substantial improvement in FEV1 (Mean Difference: 0.48 L; 95% CI: 0.35 to 0.61) and a profound improvement in quality of life (SGRQ MD: -15.55; 95% CI: -20.21 to -10.89). However, this efficacy was counterbalanced by a nearly six-fold increase in the risk of major complications (Risk Ratio: 5.82; 95% CI: 2.98 to 11.37).
Conclusion: Our synthesis suggests that for carefully selected patients, bullectomy offers superior physiological and quality-of-life outcomes over conservative management, but at the cost of significantly higher perioperative risk. These findings, derived from low-quality evidence, underscore the critical need for a highly individualized, multidisciplinary approach to patient selection and a thorough shared decision-making process.
-
Post-Pandemic Prevalence and Distribution of Refractive Errors in Balinese Schoolchildren: A Cross-Sectional Analysis
Views: 492Downloads: 293Background: Uncorrected refractive errors are a leading cause of preventable visual impairment in children worldwide, impacting academic and social development. The COVID-19 pandemic disrupted routine pediatric eye health services and altered children's lifestyles, creating an urgent need to re-evaluate the burden of these conditions. This study aimed to determine the prevalence and geographical distribution of refractive errors among elementary school children across six districts in Bali, Indonesia, during the post-pandemic period (2022–2023).
Methods: A descriptive cross-sectional study was conducted using secondary data from the John Fawcett Foundation (JFF) school eye health screening program. The final analysis included 2,145 elementary school children (47.5% male, 52.5% female) from 13 schools across six districts in Bali, screened between January 2022 and December 2023. Visual acuity was measured using a Snellen chart, followed by non-cycloplegic autorefraction for all children failing the initial screening. Ametropia was defined based on established spherical equivalent and cylindrical thresholds. Prevalence was calculated for each district, and a Chi-square test was used to analyze the association with gender.
Results: The overall prevalence of ametropia was 4.1% (88/2,145). Myopia was the most common refractive error, accounting for 58 cases (2.7% of all children), followed by astigmatism with 22 cases (1.0%) and hypermetropia with 8 cases (0.4%). Significant geographical disparities were observed, with prevalence rates ranging from a low of 1.8% in Tabanan district to a high of 6.9% in Denpasar district. The highest prevalence rates were found in the urban and semi-urban districts of Denpasar (6.9%) and Buleleng (6.3%). There was no statistically significant association between gender and the presence of refractive error (p=0.115).
Conclusion: The post-pandemic prevalence of refractive errors in this large cohort of Balinese schoolchildren reveals a significant public health challenge defined by a sharp urban-rural divide. The concentration of refractive errors, primarily myopia, in urban centers like Denpasar points to the profound impact of environmental and lifestyle factors on visual development. This evidence provides a clear mandate for the strategic deployment of targeted pediatric eye care resources to the island's most affected communities, ensuring the early detection and management necessary to prevent lifelong visual impairment and secure the future well-being of Bali's next generation.
-
The Dual Role of Hypoxia-Inducible Factor-1α in Sepsis-Induced Immunomodulation and Organ Dysfunction: A Systematic Review and Meta-Analysis
Views: 502Downloads: 156Background: Sepsis, a life-threatening organ dysfunction caused by a dysregulated host response to infection, remains a leading cause of global mortality. Hypoxia-inducible factor-1α (HIF-1α) is a master transcriptional regulator of the cellular adaptive response to hypoxia but plays a complex, paradoxical role in sepsis. While essential for innate immune function, its sustained activation may amplify inflammation and drive organ damage. This meta-analysis was conducted to synthesize the evidence on the association of HIF-1α with key markers of immunomodulation and organ dysfunction in sepsis.
Methods: We performed a systematic review and meta-analysis following PRISMA guidelines. A comprehensive search of PubMed, Scopus, and Web of Science was conducted for studies published between January 2014 and December 2024. We included observational studies that measured HIF-1α levels in adult sepsis patients and reported outcomes related to organ dysfunction (Sequential Organ Failure Assessment [SOFA] score) or mortality, and immunomodulation (Interleukin-6 [IL-6] levels). Seven studies meeting the inclusion criteria were included in the final analysis. Data were pooled using a random-effects model. Standardized Mean Difference (SMD) and Odds Ratios (OR) with 95% confidence intervals (CI) were calculated.
Results: The seven included studies comprised 1,288 patients. The overall quality of the included studies was moderate to high as per the Newcastle-Ottawa Scale. The pooled analysis revealed that HIF-1α levels were significantly elevated in sepsis patients who died compared to those who survived (OR = 2.68, 95% CI: 1.55–4.64, p < 0.001), with moderate heterogeneity (I² = 45%). Furthermore, HIF-1α levels were strongly associated with greater organ dysfunction, as measured by the SOFA score (5 studies; SMD = 0.92, 95% CI: 0.51–1.33, p < 0.0001), with substantial heterogeneity (I² = 78%). HIF-1α levels also showed a significant positive correlation with the pro-inflammatory cytokine IL-6 (4 studies; SMD = 1.15, 95% CI: 0.65–1.65, p < 0.00001), with high heterogeneity (I² = 82%).
Conclusion: This meta-analysis provides robust evidence that elevated HIF-1α levels are significantly associated with increased sepsis severity, characterized by greater organ dysfunction, a heightened pro-inflammatory state, and a higher risk of mortality. These findings underscore the maladaptive consequences of sustained HIF-1α activation in sepsis, positioning it as a critical prognostic biomarker and a complex, high-value target for future therapeutic modulation.
-
The Temporal Windows of Glycemic Injury: Association of Early and Late First-Week Hyperglycemia with Retinopathy of Prematurity in Low-Birth-Weight Infants
Views: 406Downloads: 106Background: Retinopathy of prematurity (ROP) is a leading cause of childhood blindness, driven by aberrant retinal vascular development in preterm infants. While hyperglycemia is a recognized risk factor, its impact may vary depending on its timing relative to the biphasic pathogenesis of ROP. This study aimed to generate a hypothesis regarding the differential association of hyperglycemia on postnatal day 1 versus day 7 with the incidence of ROP in a high-risk neonatal population.
Methods: We conducted a retrospective, cross-sectional, hypothesis-generating study at Prof. Dr. I.G.N.G. Ngoerah General Hospital. Medical records of 68 preterm (<37 weeks gestation) and low-birth-weight (<2500 grams) infants who underwent ROP screening were reviewed. The exposures of interest were hyperglycemia (blood glucose >125 mg/dL) on postnatal day 1 (D1) and day 7 (D7). The primary outcome was the diagnosis of any stage of ROP. Statistical analysis involved Chi-square tests and exploratory multivariate logistic regression to adjust for select confounders.
Results: Of the 68 infants included (mean gestational age 30.5 ± 2.2 weeks, mean birth weight 1447.5 ± 373.0 grams), 11 (16.2%) were diagnosed with ROP. Hyperglycemia was present in 29.4% of infants on D1 and 13.2% on D7. In logistic regression analysis, a strong statistical association was observed between hyperglycemia and ROP for both D1 (Adjusted Odds Ratio [AOR] = 55.7; 95% Confidence Interval [CI]: 5.1–611.0; p=0.001) and D7 (AOR = 74.5; 95% CI: 9.0–613.4; p<0.001). However, the profoundly wide confidence intervals indicate significant statistical instability and imprecision.
Conclusion: This study found a strong, albeit statistically imprecise, association between hyperglycemia on both the first and seventh day of life and the incidence of ROP. These findings support the hypothesis that the timing of glycemic dysregulation may be critical, potentially impacting different phases of ROP pathogenesis. The results, while preliminary, underscore the need for larger, prospective studies to confirm these associations and elucidate the role of glycemic control in ROP prevention.
-
Enhancing the Early Inflammatory Response: The Role of Ozonated Aloe Vera Oil on IL-6 and TNF-α in Cutaneous Wound Repair
Views: 613Downloads: 127Background: Dysregulation of the initial inflammatory phase is a primary driver of impaired healing and the formation of chronic wounds, creating a critical need for therapies that can optimize this early response. This study tested the hypothesis that a novel formulation of ozonated aloe vera oil functions as a sophisticated bioregulator, promoting a beneficial, pro-regenerative inflammatory phenotype by transiently enhancing the host's innate repair signals.
Methods: This was a preclinical, randomized, controlled study using fifty male Sprague-Dawley rats with 1 cm full-thickness excisional wounds. The therapeutic agent, ozonated aloe vera oil, was chemically characterized by its peroxide value (PV). Animals were randomized to receive topical treatment with either a positive control (aloe vera oil), a negative control (gentamicin ointment), or one of three graded doses of ozonated oil (Low PV, Medium PV, High PV). The primary outcomes, systemic (serum) and local (wound tissue homogenate) concentrations of Interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α), were quantified by ELISA on days 3 and 7.
Results: On day 3, all ozonated oil formulations induced a profound and significant upregulation of both local and systemic TNF-α and IL-6 compared to controls (p < 0.001). The topical treatment increased systemic TNF-α levels by over 40% and local tissue concentrations by over 60%. Critically, this pro-inflammatory surge was transient; by day 7, both local and systemic cytokine levels in all groups had returned to statistically indistinguishable baseline levels.
Conclusion: Ozonated aloe vera oil acts as a potent, transient modulator of the wound microenvironment, enhancing the expression of key initiatory cytokines. This mechanism, likely mediated by the activation of redox-sensitive transcription factors, optimizes the crucial first phase of healing without inducing pathological chronic inflammation. This study supports a novel therapeutic paradigm aimed at enhancing, rather than suppressing, the body's innate capacity for repair.
-
Redefining the Therapeutic Ladder in Refractory Chronic Constipation: A Systematic Review and Meta-Analysis of the Role of Ileal Bile Acid Transporter (IBAT) Inhibitors
Views: 665Downloads: 118Background: Chronic constipation (CC) refractory to conventional laxatives is a prevalent clinical challenge that significantly impairs quality of life. Ileal bile acid transporter (IBAT) inhibitors, a novel class of drugs, modulate colonic function by increasing the delivery of bile acids to the colon. This study aimed to quantitatively synthesize the evidence for the efficacy and safety of IBAT inhibitors in this difficult-to-treat population to clarify their position in the therapeutic algorithm.
Methods: Following PRISMA guidelines, we systematically searched PubMed, Scopus, Embase, and Cochrane CENTRAL, along with clinical trial registries, from inception to June 1st, 2025. We included parallel-group, randomized controlled trials (RCTs) comparing the IBAT inhibitor elobixibat with placebo in adults with CC refractory to at least two prior laxative classes. The primary efficacy outcome was the overall responder rate. Key secondary outcomes included change in spontaneous bowel movements (SBMs) per week, quality of life (QoL) scores, and incidence of adverse events. Data were pooled using a random-effects model. Number needed to treat (NNT) and to harm (NNH) were calculated.
Results: Our search identified six eligible RCTs enrolling 2,155 patients. Patients treated with elobixibat were significantly more likely to be responders compared to placebo (Risk Ratio [RR] = 2.58; 95% CI: 1.87–3.56; p < 0.00001), with moderate heterogeneity (I² = 59%). The NNT to achieve one additional responder was 5 (95% CI: 4–7). Elobixibat significantly increased the mean number of SBMs per week (Mean Difference [MD] = 1.65; 95% CI: 1.19–2.11; p < 0.00001; I² = 64%). The most common adverse events were gastrointestinal; elobixibat significantly increased the risk of diarrhea (RR = 4.21; 95% CI: 3.01–5.89; NNH = 6) and abdominal pain (RR = 2.35; 95% CI: 1.63–3.38; NNH = 11). Most events were mild to moderate.
Conclusion: This meta-analysis provides robust evidence that the IBAT inhibitor elobixibat is a highly effective therapy for refractory CC, offering a significant improvement in symptoms for a substantial portion of patients. This benefit must be carefully balanced against the high incidence of mechanism-based gastrointestinal side effects. These findings establish elobixibat as a potent, mechanistically distinct option, thereby informing its strategic placement on the therapeutic ladder for patients failed by conventional laxatives.
-
Re-evaluating WHO Warning Signs in Pediatric Dengue: Abdominal Pain, Not Vomiting, is Associated with Plasma Leakage
Views: 1,086Downloads: 203Background: Dengue virus infection represents a significant cause of morbidity and mortality in pediatric populations across endemic regions. The progression to severe disease is characterized by a critical phase of plasma leakage. The World Health Organization (WHO) has established warning signs to aid in clinical triage, yet the independent clinical significance of these signs, particularly abdominal pain and vomiting, requires more precise clarification to optimize patient management.
Methods: This study was a retrospective, cross-sectional analysis conducted at Wangaya General Hospital in Denpasar, Indonesia. Electronic medical records of 172 pediatric patients hospitalized with a diagnosis of dengue between January and May 2024 were reviewed. The primary outcome was significant plasma leakage, defined as a hematocrit increase of 20% or more from the admission baseline. Bivariate and multivariate logistic regression analyses were performed to determine the association of abdominal pain and vomiting with plasma leakage, controlling for the confounding effects of age, gender, and the day of fever at assessment.
Results: In the multivariate logistic regression model, the presence of abdominal pain was independently and significantly associated with an increased likelihood of plasma leakage (Adjusted Odds Ratio [aOR]: 2.15, 95% Confidence Interval [CI]: 1.05–4.41; p=0.036). Conversely, the association for vomiting was not statistically significant after adjustment for confounders (aOR: 1.25, 95% CI: 0.65–2.42; p=0.508). The co-occurrence of both symptoms was also identified as a significant indicator of plasma leakage in the adjusted model (aOR: 2.09, 95% CI: 1.01–4.34; p=0.047).
Conclusion: In this retrospective analysis of a hospitalized pediatric study, abdominal pain emerged as a robust independent correlate of significant plasma leakage, whereas vomiting did not. This differential association suggests that abdominal pain should be weighted more heavily in the clinical assessment of children with dengue as a key indicator of ongoing or impending hemoconcentration. These findings, while limited by their retrospective nature, can help refine clinical risk assessment in resource-constrained settings.
-
Pharmacological and Non-Pharmacological Strategies for Sedation and Analgesia in Critically Ill Children: A Systematic Review and Narrative Synthesis
Views: 503Downloads: 169Background: The management of pain and agitation in the Pediatric Intensive Care Unit (PICU) is critical for patient comfort and preventing adverse outcomes. A wide array of sedation and analgesia strategies exists, but a synthesized appraisal of contemporary evidence is needed to guide clinical practice. This systematic review evaluates the efficacy and safety of various pharmacological and non-pharmacological interventions for sedation and analgesia in critically ill children.
Methods: A systematic search was conducted in PubMed, Embase, Cochrane CENTRAL, and CINAHL for studies published between January 2020 and December 2024. Following the PRISMA 2020 guidelines, two independent reviewers screened studies, extracted data, and assessed the risk of bias using the Cochrane RoB 2 tool for Randomized Controlled Trials (RCTs) and the Newcastle-Ottawa Scale (NOS) for observational studies.
Results: From 4,366 identified records, five studies (two RCTs, three observational) involving 875 patients met the inclusion criteria. Study 1, an RCT (n=120), found that adjunctive ketamine significantly reduced mechanical ventilation duration by a mean of 2.1 days (95% CI: 1.2-3.0, p=0.001) compared to standard care. Study 3, a prospective cohort study (n=350), linked continuous sedation to longer PICU stays (median 9 vs. 6 days, p<0.001) and a higher incidence of iatrogenic withdrawal syndrome (45% vs. 18%, p<0.001) compared to intermittent sedation. Study 4, an RCT on music therapy (n=85), demonstrated a significant reduction in postoperative pain scores. Observational studies supported the opioid-sparing effects of multimodal analgesia (Study 5) and noted differences in recovery profiles between midazolam and propofol (Study 2).
Conclusion: This review highlights the benefits of a multimodal, goal-directed approach to pediatric sedation and analgesia. Adjunctive ketamine and non-pharmacological interventions show promise in reducing opioid reliance and improving clinical outcomes. Protocols favoring intermittent sedation may reduce length of stay and withdrawal incidence. These findings support a paradigm shift away from deep, continuous sedation towards more nuanced, patient-centered strategies.
-
The Gut-Muscle Axis in Sarcopenia: A Meta-Analysis of Gut Microbiome Compositional Features and Their Correlation with Muscle Mass, Strength, and Physical Performance in Older Adults
Views: 839Downloads: 307Background: Sarcopenia, the age-related decline in muscle mass and function, is a major geriatric syndrome. The gut-muscle axis has emerged as a key area of investigation, yet the association between gut microbiome composition and sarcopenic parameters in humans remains quantified by a collection of studies with varied methodologies. This meta-analysis aimed to synthesize the existing correlational evidence linking gut microbiome features to the core components of sarcopenia in older adults.
Methods: We performed a systematic search of PubMed, Scopus, Web of Science, and Embase for observational studies published between January 2015 and July 2025 that assessed gut microbiome composition and sarcopenia metrics in adults aged ≥60. Correlation coefficients (r) were pooled using a random-effects model. We assessed heterogeneity using the I² statistic, conducted pre-specified subgroup and sensitivity analyses, and evaluated study quality with the Newcastle-Ottawa Scale (NOS).
Results: Six cross-sectional studies (N=1,189) met the inclusion criteria. The methodological quality was high (median NOS score = 8). The pooled analysis revealed a significant, small positive correlation between gut microbial alpha diversity and muscle strength (handgrip strength) (pooled r = 0.19, 95% CI: 0.11-0.27; I² = 41%). The relative abundance of the genus Faecalibacterium, known for its potential to produce butyrate, was significantly correlated with physical performance (pooled r = 0.24, 95% CI: 0.16-0.32; I² = 28%). A non-significant negative correlation was found between the family Enterobacteriaceae and muscle mass (pooled r = -0.14, 95% CI: -0.29-0.01; I² = 62%). Subgroup analysis suggested this heterogeneity was partly explained by the diagnostic criteria used for sarcopenia.
Conclusion: This meta-analysis provides quantitative evidence of a modest but significant association between gut microbiome composition and muscle health in older adults. A microbial profile with higher diversity and greater abundance of putative beneficial taxa is correlated with better muscle function. These associative findings, while limited by the cross-sectional nature of the data and the potential for reverse causality, reinforce the clinical relevance of the gut-muscle axis and underscore the need for longitudinal, multi-omic studies to elucidate mechanisms and test microbiome-targeted therapies.
-
Orthoplastic Limb Salvage of a Gustilo-Anderson Grade IIIB Open Trans-Articular Knee Fracture: A Case Report on Staged Reconstruction with a Rotational Fasciocutaneous Flap
Views: 347Downloads: 214Background: High-energy, open trans-articular knee fractures with extensive soft-tissue loss represent a formidable challenge, carrying a high risk of deep infection, nonunion, and amputation. Successful limb salvage necessitates a collaborative orthoplastic approach, combining aggressive surgical debridement and skeletal stabilization with timely, vascularized soft-tissue coverage.
Case presentation: A 16-year-old male was admitted after a severe traffic accident, sustaining a Gustilo-Anderson Grade IIIB open fracture of the right knee. The injury comprised a comminuted distal femur fracture, a comminuted tibial plateau fracture (Schatzker VI), a comminuted patellar fracture, and a proximal fibula fracture. A 12x15 cm soft-tissue defect with a depth of 6 cm exposed the joint capsule and all fracture sites. The patient underwent a staged management protocol. The initial surgery involved extensive debridement of non-viable tissue and stabilization with a spanning multi-planar external fixator, followed by a second-look debridement. Definitive coverage was achieved on day five with a large, medially-based rotational fasciocutaneous flap and a split-thickness skin graft over the donor site. At the 1-year follow-up, all fractures had united, and the soft-tissue envelope was stable and sensate. The patient achieved a functional knee range of motion of 0-100 degrees and could ambulate without aids. The Lysholm knee score was 85, and the Knee Society Score (KSS) was 88.
Conclusion: This case report demonstrates that a meticulously planned, staged orthoplastic strategy can achieve successful limb salvage even in devastating open knee injuries. A large, local rotational fasciocutaneous flap can serve as a reliable and less complex alternative to free tissue transfer for covering massive defects in this region, particularly in young patients with favorable tissue characteristics.
-
Beyond Cholesterol: The Independent Roles of Inflammation and Renal Dysfunction in Carotid Atherosclerosis Among Indonesian Elders
Views: 421Downloads: 185Background: Atherosclerosis remains a leading cause of mortality in aging populations, driven by a complex interplay of metabolic and inflammatory factors. While dyslipidemia is a cornerstone of risk, the contributions of systemic inflammation, marked by high-sensitivity C-reactive protein (hsCRP), and declining renal function are increasingly recognized. This study aimed to elucidate the independent associations of hsCRP, dyslipidemia, and renal function with the presence of carotid atherosclerosis in an understudied elderly Indonesian population.
Methods: We conducted a single-center, case-control study at a tertiary hospital in Palembang, Indonesia, from January to June 2024. One hundred participants aged ≥60 years were enrolled from the geriatric outpatient clinic. Cases were defined by the presence of carotid plaque, identified via B-mode Doppler ultrasound, and defined according to international consensus criteria. Controls had no evidence of plaque. We performed multivariate logistic regression to identify independent predictors of atherosclerosis, including hsCRP, lipid parameters, and estimated glomerular filtration rate (eGFR).
Results: After multivariable adjustment, three factors emerged as significant, independent predictors of carotid atherosclerosis. High total cholesterol (≥200 mg/dL) was the most powerful predictor, associated with a more than seven-fold increased odds of plaque (Adjusted Odds Ratio [aOR]: 7.38; 95% Confidence Interval [CI]: 2.87–18.94; p<0.001). Elevated hsCRP (≥2 mg/L) (aOR: 3.38; 95% CI: 1.33–8.59; p=0.005) and abnormal eGFR (≤90 mL/min/1.73m²) (aOR: 3.36; 95% CI: 1.10–10.22; p<0.001) were also robustly associated with atherosclerosis, each conferring over a three-fold increase in odds.
Conclusion: In this elderly Indonesian study, dyslipidemia remains a dominant risk factor for carotid atherosclerosis. However, systemic inflammation (high hsCRP) and mild renal dysfunction (abnormal eGFR) are also powerful, independent contributors. These findings highlight the multifactorial nature of atherosclerosis and underscore the importance of a comprehensive risk assessment that extends beyond traditional lipid profiling to include markers of inflammation and renal health.
-
Point-of-Care Ultrasound in the Sequential Diagnosis of Postoperative Cardiac, Pulmonary, and Vascular Complications Following Thoracoabdominal Aortic Aneurysm Repair: A Case Report and Pathophysiological Review
Views: 365Downloads: 107Background: Open repair of a thoracoabdominal aortic aneurysm (TAAA) is a formidable surgical undertaking associated with profound physiological stress and a high risk of life-threatening postoperative complications. We present a case where a sequential, multi-system point-of-care ultrasound (POCUS) protocol was instrumental in unraveling a cascade of distinct but interconnected postoperative complications.
Case presentation: A 67-year-old male with a Crawford Type II TAA underwent an elective open repair. His postoperative course in the Intensive Care Unit (ICU) was complicated by a cascade of events. On postoperative day one, he developed hypotensive shock. Bedside cardiac ultrasound revealed new-onset, severe left ventricular systolic dysfunction (ejection fraction ~20-25%), indicative of profound myocardial stunning. By day three, this was followed by progressive hypoxemic respiratory failure. Lung ultrasound identified a large, compressive left-sided pleural effusion, which was contributing to his respiratory decline. On day four, the patient developed signs of acute left lower limb ischemia. Vascular ultrasound confirmed a complete occlusive thrombus in the popliteal artery. This rapid series of diagnoses, all made at the bedside with POCUS, facilitated targeted interventions including the initiation of inotropic support, goal-directed diuretic therapy, and emergency surgical thrombectomy, leading to a successful patient outcome.
Conclusion: This case highlights the unique diagnostic power of a structured, serial POCUS examination in the complex post-TAAA patient. It demonstrates how this non-invasive modality can effectively diagnose a "triple threat" of interconnected cardiac, pulmonary, and vascular complications, guiding real-time clinical decision-making and facilitating timely, life-saving interventions in the critical care setting.
-
A Retrospective Three-Year Analysis of Adult Scabies at a Tertiary Referral Center in Bali, Indonesia
Views: 407Downloads: 196Background: Scabies, a parasitic infestation by Sarcoptes scabiei var. hominis, is a global health challenge with significant morbidity, particularly in tropical climates. While often studied in community settings, the profile of adult patients presenting to tertiary care facilities remains under-documented. This study aimed to delineate the clinical-demographic characteristics of adult scabies patients at a major referral hospital in Bali, Indonesia, to better understand this specific patient study.
Methods: A retrospective, descriptive study was conducted utilizing electronic medical records from the Dermatology and Venereology outpatient clinic at Prof. Dr. I.G.N.G. Ngoerah General Hospital from January 2021 to December 2023. Following a total sampling method based on strict inclusion and exclusion criteria, data from 38 adult patients with a clinical diagnosis of scabies were extracted. The analysis focused on descriptive statistics to summarize patient demographics, contact history, and prescribed therapeutic regimens.
Results: The study of 38 patients had a mean age of 34.1 ± 2.5 years. A male predominance was noted (n=22, 57.9%). The highest frequency of cases was in the 40-49 year age bracket (n=9, 23.7%). Most patients had completed senior high school (n=17, 44.7%) and were employed in the private sector (n=20, 52.6%). A family history of scabies was prevalent (n=18, 47.4%). While indirect transmission via shared clothing was rare (reported by only 7.9%), direct contact through bed sharing with at least one other person was common (n=24, 63.2%). The standard therapeutic protocol was combination therapy, with topical 5% Permethrin and oral antihistamines being the most frequent regimen (n=24, 63.2%).
Conclusion: Adult scabies patients at this tertiary center are typically middle-aged, educated, working males. Transmission is overwhelmingly linked to intimate household contact, highlighting the inefficiency of fomite-based spread compared to direct skin-to-skin contact. The standard use of combination therapy reflects a proactive clinical approach to managing both the parasitic infestation and the complex immunologic cascade of pruritus. These findings provide a crucial clinical baseline for this specific patient population.
-
Navigating a Life-Threatening Airway Emergency: Clinical Diagnosis and Surgical Management of Ludwig's Angina in a Resource-Limited Setting
Views: 719Downloads: 201Background: Odontogenic abscesses, common in clinical practice, possess the potential to escalate into life-threatening emergencies. The contiguous spread of polymicrobial infections into the deep fascial spaces of the neck can precipitate Ludwig's angina, a rapidly progressive cellulitis of the floor of the mouth characterized by acute airway compromise. This report details the diagnosis and management of such a case, emphasizing the critical role of clinical acumen when gold-standard diagnostic modalities are unavailable.
Case presentation: A 43-year-old male presented with a one-week history of progressive, painful swelling of his right mandible, accompanied by fever and trismus. The working diagnosis was Ludwig's angina secondary to an odontogenic abscess originating from the mandibular right second molar (tooth #47). Despite an initial radiological report erroneously noting an issue with tooth #37, all clinical evidence pointed to a right-sided pathology. Diagnosis was established through physical examination and basic radiography, which confirmed significant soft tissue swelling. Management involved immediate surgical incision and drainage under general anesthesia, aggressive intravenous antibiotic therapy, and meticulous postoperative care. The causative tooth was subsequently extracted. The patient experienced a complete resolution of symptoms and a full functional recovery.
Conclusion: Ludwig's angina remains a formidable surgical emergency. This case underscores that even with limited diagnostic resources, a decisive diagnosis based on strong clinical findings, followed by prompt and aggressive surgical decompression, is paramount to preventing mortality and ensuring a favorable patient outcome.
-
Unmasking the Culprit: Successful Restoration of Menstrual Function in a Case of Secondary Amenorrhea Due to Tuberculous Endometritis Mimicking Polycystic Ovary Syndrome
Views: 379Downloads: 188Background: Secondary amenorrhea presents a significant diagnostic challenge in gynecology. While Polycystic Ovary Syndrome (PCOS) is a common cause, rare etiologies like tuberculous endometritis can be overlooked, especially in patients with features suggestive of PCOS. This phenomenon, known as diagnostic overshadowing, can lead to delayed diagnosis and irreversible reproductive consequences.
Case presentation: A 35-year-old nulligravid woman with a diagnosis of Class I Obesity presented with a five-year history of secondary amenorrhea and a desire for fertility. Her clinical and initial ultrasonographic findings were suggestive of PCOS. However, persistent amenorrhea despite hormonal therapy prompted further investigation. Hysteroscopy revealed a fibrotic uterine cavity with micropolyps, and subsequent endometrial biopsy with histopathology, polymerase chain reaction (PCR), and culture confirmed a diagnosis of tuberculous endometritis. The patient was successfully treated with a six-month anti-tuberculosis regimen, cyclical progestin therapy, and a structured lifestyle modification program. Following treatment, she experienced a significant weight loss, resumption of regular menstrual cycles, and marked improvement in endometrial and ovarian ultrasound parameters.
Conclusion: This case underscores the critical importance of a comprehensive diagnostic evaluation for secondary amenorrhea, including endometrial sampling, even when a common diagnosis like PCOS is suspected. It highlights the potential for tuberculous endometritis to mimic PCOS and demonstrates the efficacy of a multidisciplinary approach in restoring menstrual and potentially reproductive function. Clinicians in tuberculosis-endemic regions must maintain a high index of suspicion for this insidious pathology to prevent long-term morbidity.
-
The Bidirectional Relationship Between Obstructive Sleep Apnea and Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD): A Systematic Review and Meta-Analysis of Longitudinal Studies
Views: 440Downloads: 217Background: Obstructive sleep apnea (OSA) and metabolic dysfunction-associated steatotic liver disease (MASLD) are highly prevalent, interconnected metabolic disorders. While their cross-sectional association is established, the temporal and potentially causal relationship remains unclear. This study aimed to quantitatively synthesize longitudinal evidence on the bidirectional risk between OSA and MASLD.
Methods: We systematically searched PubMed, Scopus, and Web of Science (January 1st, 2015 - July 1st, 2025) for longitudinal cohort studies in adults assessing the OSA-MASLD relationship. Two reviewers independently selected studies, extracted data, and assessed quality using the Newcastle-Ottawa Scale (NOS). The primary analysis, pre-specified for studies using objective diagnostics (Polysomnography/Imaging), utilized a random-effects model to pool hazard ratios (HR). Heterogeneity was quantified with the I2 statistic.
Results: The search identified 2,148 articles, with six longitudinal studies (185,432 participants) meeting eligibility criteria. Four studies (116,298 participants) assessed incident MASLD, while two (69,134 participants) assessed incident OSA. The primary meta-analysis of two studies using objective diagnostics found that baseline OSA was associated with a significantly increased risk of incident MASLD (pooled HR: 2.29; 95% CI: 1.93-2.71; I2=35%). A secondary analysis including two studies using administrative codes yielded a pooled HR of 1.87 (95% CI: 1.51-2.32), though with substantial heterogeneity (I2=78%). For the reverse direction, a narrative synthesis of two studies suggests MASLD increases the risk of incident OSA; an exploratory pooled analysis yielded an HR of 1.65 (95% CI: 1.39-1.96; I2=45%), a finding to be interpreted with caution due to the small study number.
Conclusion: This systematic review of longitudinal data provides the strongest evidence to date supporting a significant, bidirectional relationship between OSA and MASLD. The presence of objectively-diagnosed OSA more than doubles the risk of developing future MASLD. These findings provide a strong rationale for implementing mutual, risk-stratified screening and developing integrated management strategies to disrupt the vicious cycle linking these two common and morbid conditions.
-
Navigating a Complex Extraction: A Case Report on the Colonoscopic Management of Dual Rectal Foreign Bodies and a Proposed Treatment Algorithm
Views: 1,376Downloads: 1,109Background: The management of retained rectal foreign bodies (RFBs) constitutes a significant and escalating challenge in clinical practice. While general management principles exist, there is a paucity of literature detailing the specific biomechanical and pathophysiological complexities of cases involving dual, large-bodied foreign bodies of differing materials. The optimal instrumentation and the role of adjuvant maneuvers in these specific scenarios remain under-reported.
Case presentation: A 60-year-old male presented with a three-day history of rectal pain and acute urinary retention after inserting a plastic bottle (18 cm x 7 cm) and a silicone dildo (20 cm x 6 cm) into his rectum. An initial attempt at manual extraction under sedation failed. The patient was subsequently managed under general anesthesia with a successful colonoscopic extraction. A 10-mm toothed alligator jaw grasper, used in conjunction with synchronized external abdominal compression, proved critical for retrieving both objects sequentially. The total procedural time was 60 minutes, and the patient was discharged after a 3-day hospital stay without complications.
Conclusion: This case provides powerful validation for colonoscopic extraction as a safe, effective, and definitive minimally invasive technique for complex, high-lying RFBs when manual methods fail. It highlights the indispensable role of general anesthesia for achieving complete pelvic floor relaxation and the biomechanical superiority of specific retrieval tools. The successful outcome underscores the value of a systematic, stepwise management algorithm that prioritizes patient safety and minimizes the need for surgical intervention.
-
Laparoscopic Primary Crural Repair for Acute-on-Chronic Organoaxial Gastric Volvulus Secondary to a Type II Paraesophageal Hernia: A Case Report and Review of Surgical Strategy
Views: 354Downloads: 136Background: Gastric volvulus, an abnormal rotation of the stomach, is a rare surgical emergency that can lead to life-threatening gastric ischemia and perforation, particularly when associated with a large paraesophageal hernia (PEH). While paraesophageal hernias are the most common predisposing factor in adults, the optimal surgical management, especially regarding the use of fundoplication and gastropexy, remains a subject of debate.
Case presentation: We present the case of a 46-year-old male with a six-month history of intermittent epigastric pain and early satiety, who presented with a three-week history of acute-on-chronic gastric outlet obstruction. His symptoms included intractable postprandial vomiting. Laboratory findings were significant for hemoconcentration and a hypochloremic, hypokalemic metabolic state, indicative of severe dehydration. A contrast-enhanced computed tomography scan confirmed a Type II PEH with an organoaxial gastric volvulus, causing complete obstruction. Following aggressive resuscitation, the patient underwent successful laparoscopic surgery. The procedure involved reduction of the herniated and volvulized stomach, complete excision of the hernia sac, and a primary posterior crural repair with pledgeted, non-absorbable sutures. A fundoplication or gastropexy was not performed. Intraoperative endoscopy confirmed successful de-rotation, a patent pylorus, and viable gastric mucosa. The patient had an uneventful recovery and remained asymptomatic with no evidence of reflux at a six-month follow-up.
Conclusion: This case highlights the classic "acute-on-chronic" presentation of gastric volvulus secondary to a PEH. It underscores the efficacy and safety of a laparoscopic approach, which facilitates rapid recovery. Furthermore, it suggests that in carefully selected cases with a moderate-sized hiatal defect and preserved anatomy post-reduction, a meticulous primary crural repair without routine fundoplication or gastropexy can be a sufficient and durable treatment, avoiding the potential morbidity of these additional procedures.
-
Modernizing a Classic Test: Validation and Clinical Utility of Infrared-Barrier and Near-Infrared Photometry for Erythrocyte Sedimentation Rate Determination
Views: 379Downloads: 169Background: The erythrocyte sedimentation rate (ESR) is a cornerstone laboratory test for monitoring inflammation. The manual Westergren method, while the established gold standard, is slow and hazardous, prompting a shift towards automation. This study provides a rigorous, head-to-head validation of two mechanistically distinct automated technologies—infrared-barrier photometry (IBP) and near-infrared photometry (NIP)—to assess their analytical performance and operational utility in a tertiary care setting.
Methods: A cross-sectional method comparison study was conducted on 59 outpatient samples at Adam Malik General Hospital, Indonesia. Each sample was analyzed for ESR using the manual Westergren method, the Caretium XC-A30 analyzer (IBP), and the Mindray BC-760 hematology analyzer (NIP). Method agreement was assessed using Passing-Bablok regression and Bland-Altman analysis. Clinical concordance was evaluated using categorized results.
Results: Both automated methods demonstrated excellent agreement with the Westergren reference. Passing-Bablok regression showed no significant proportional or constant bias for either method. The NIP method exhibited a near-perfect regression equation (y = 1.01x - 0.58), while the IBP method also performed well (y = 0.98x + 1.25). Bland-Altman analysis revealed a clinically insignificant mean bias of +0.44 mm/hr for NIP and -4.47 mm/hr for IBP. Clinical concordance was high, with 96.6% of NIP results and 91.5% of IBP results falling within the same clinical category as the Westergren method.
Conclusion: Both automated methods are valid and reliable alternatives to the Westergren method. The NIP technology, in particular, offers a substantial leap in laboratory efficiency by providing results in under two minutes from a standard EDTA sample. Its superior workflow integration and strong analytical performance support its adoption to drastically reduce turnaround times and enhance modern patient care pathways.
-
Targeting the TGF-β Pathway to Overcome Resistance to Immune Checkpoint Inhibitors in Microsatellite Stable Metastatic Colorectal Cancer: A Systematic Review and Pooled Analysis of Efficacy and Tumor Microenvironment Modulation
Views: 462Downloads: 222Background: The clinical utility of immune checkpoint inhibitors (ICIs) in metastatic colorectal cancer (mCRC) is restricted to a minority of tumors with mismatch repair deficiency. The vast majority, classified as microsatellite stable (MSS), display profound resistance driven by an immunosuppressive tumor microenvironment (TME) orchestrated by transforming growth factor-β (TGF-β). This study aimed to synthesize the evidence for combining TGF-β pathway inhibitors with ICIs to reverse this resistance.
Methods: A systematic search of PubMed, Embase, Cochrane Library, and major oncology conference abstracts was conducted through December 2024 for preclinical and clinical studies evaluating TGF-β inhibition combined with ICIs in CRC. Due to the non-randomized nature of the clinical evidence, a pooled analysis of the single-arm objective response rate (ORR) was performed using a random-effects model. Progression-free survival (PFS), duration of response (DoR), and TME modulation were synthesized narratively.
Results: Seven studies (four preclinical, three early-phase clinical) met the inclusion criteria. In the pooled analysis of 218 patients with predominantly MSS-mCRC from three clinical trials, the combination therapy yielded a pooled ORR of 14.2% (95% Confidence Interval [CI]: 9.1% – 20.2%), with moderate heterogeneity (I² = 38%). This represents a clinically meaningful improvement over the expected <1% response rate to ICI monotherapy in this population. Narrative synthesis of survival data indicated a median PFS ranging from 2.5 to 3.7 months and a promising median DoR exceeding 10 months in responders. Preclinical data consistently demonstrated that combination therapy synergistically inhibited tumor growth by remodeling the TME, marked by increased CD8+ T-cell infiltration and reduced stromal fibrosis.
Conclusion: This systematic review and pooled analysis provide the most current synthesis of evidence for targeting the TGF-β pathway in MSS-mCRC. While preliminary and based on early-phase trials, the data show that this combination strategy can induce durable responses in a subset of patients by promoting an inflamed TME. These findings strongly support the continued investigation of this approach in biomarker-driven, randomized controlled trials.
