Bioscientia Medicina - Journal of Biomedicine and Translational Research
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The Complex Interplay of Prematurity, Respiratory Distress Syndrome, and Necrotizing Enterocolitis: Insights from a Case Study
Background: Necrotizing enterocolitis (NEC) remains a devastating inflammatory bowel disease predominantly affecting premature infants, carrying significant morbidity and mortality risks. Respiratory distress syndrome (RDS), common in this population, is increasingly recognized not just as a comorbidity but as a potential contributor to NEC pathogenesis, possibly through mechanisms involving gut hypoperfusion. Understanding the clinical progression and management challenges when these conditions coexist is crucial.
Case presentation: We present the case of a female infant born prematurely at 33-34 weeks gestation with a birth weight of 2280g. The infant developed early RDS, requiring Continuous Positive Airway Pressure (CPAP) support shortly after birth. On the second day of life, while RDS symptoms were improving, the infant developed signs suggestive of NEC, including abdominal distension, bilious gastric residuals, and subsequent irritability and feeding intolerance. The diagnosis of NEC (suspected Bell's stage II) was supported by clinical findings and radiological evidence of bowel wall thickening. Blood cultures identified Klebsiella pneumoniae. Initial antibiotic therapy proved insufficient, necessitating a change to meropenem and amikacin based on sensitivity testing. The infant was managed conservatively with bowel rest, parenteral nutrition, and targeted antibiotics, showing gradual clinical improvement. Enteral feeding with breast milk was successfully reintroduced, and the infant was discharged in good condition after 15 days of NICU care.
Conclusion: This case highlights the challenging clinical scenario where early-onset RDS in a premature, low-birth-weight infant precedes the development of NEC. It underscores the importance of high clinical suspicion for NEC even as respiratory status improves, the utility of microbial surveillance and sensitivity testing in guiding antibiotic therapy, and the potential for successful conservative management in NEC Bell's stage II. The interplay between RDS-induced physiological stress and intestinal vulnerability likely contributed to NEC development in this patient
Beyond Tumor Grade: Investigating the Heterogeneity of PD-L1 Expression in Soft Tissue Sarcomas and the Need for Subtype-Specific Analysis
Background: Soft tissue sarcomas (STS) represent a diverse group of malignant mesenchymal neoplasms with considerable histological variety and differing degrees of malignancy. Programmed Death-Ligand 1 (PD-L1) expression is a crucial immunotherapy target in various cancers, but its role and expression patterns in STS, particularly within the Indonesian population, remain inadequately defined. This study aimed to investigate the differences in PD-L1 expression between low-grade and high-grade STS and to determine the correlation between PD-L1 expression and histological grading in an Indonesian cohort.
Methods: This analytical observational study utilized a cross-sectional design, incorporating 29 archival paraffin-embedded tissue blocks from STS patients diagnosed at Dr. Saiful Anwar Regional General Hospital, Malang, Indonesia. PD-L1 expression was assessed immunohistochemically using the monoclonal antibody clone 22c3, and scoring was performed using the Combined Positive Score (CPS). Statistical analyses, including the Mann-Whitney U test and Spearman correlation, were employed to evaluate differences and correlations.
Results: The majority of STS cases (89.7%) exhibited negative PD-L1 expression. The mean PD-L1 CPS was 0.1429 in low-grade STS and 0.233 in high-grade STS. No statistically significant difference in PD-L1 expression was observed between the low-grade and high-grade groups (p=0.620). Furthermore, Spearman correlation analysis revealed no significant association between PD-L1 expression (numeric CPS and categorical positivity) and histological grade (r=0.094, p=0.629 for CPS; r=0.102, p=0.600 for interpretation).
Conclusion: This study found no significant difference in PD-L1 expression between low-grade and high-grade soft tissue sarcomas, nor a significant correlation with histological grade in the investigated Indonesian patient cohort. These findings suggest that PD-L1 expression, when assessed independently, may not be a reliable prognostic biomarker based solely on tumor grading in STS. Further research with larger sample sizes, encompassing diverse histological subtypes and incorporating additional immune biomarkers, is warranted
Ki-67 and HER2-Negative Status as Predictive Factors for Recurrence and Progression in Breast Cancer: Implications for Treatment Strategies
Background: Breast cancer remains a significant health challenge, with HER2-negative subtypes representing a majority of cases. Ki-67, a marker of cell proliferation, has emerged as a potential prognostic factor in various cancers, including breast cancer. This study aimed to evaluate the association of Ki-67 expression and HER2-negative status with tumor characteristics, treatment response, and disease progression in breast cancer patients.
Methods: A retrospective cross-sectional study was conducted at Dr. Kariadi General Hospital, Semarang, Indonesia. Data from 94 patients diagnosed with breast cancer were collected, including immunohistochemical profiles, HER2 status, Ki-67 index, treatment regimens, and tumor size. Statistical analysis was performed using SPSS version 25.0 for Windows.
Results: The majority of patients (50%) presented with Luminal B-type breast cancer, and 77.7% had a Ki-67 index >20%. HER2-negative status was observed in 78.7% of patients. No significant correlation was found between HER2-negative status and the type of therapy given (p=0.131) or tumor size (p=0.467). Similarly, Ki-67 expression >20% did not correlate significantly with the type of therapy (p=0.070) or tumor size (p=0.156).
Conclusion: While Ki-67 and HER2-negative status are recognized as important prognostic factors in breast cancer, this study did not find a significant association with treatment modalities or tumor size in the studied population. Further research with a larger sample size and longer follow-up is needed to validate these findings and explore the complex interplay of Ki-67, HER2 status, and other clinical variables in breast cancer progression
Continuous Positive Airway Pressure (CPAP) versus Non-Invasive Ventilation (NIV) in Obesity Hypoventilation Syndrome: A Meta-Analysis
Background: Obesity hypoventilation syndrome (OHS) is a serious respiratory condition characterized by obesity, sleep-disordered breathing, and daytime hypercapnia. Both continuous positive airway pressure (CPAP) and non-invasive ventilation (NIV) are commonly used to treat OHS, but their comparative effectiveness remains unclear. This meta-analysis aimed to compare the efficacy of CPAP versus NIV in improving gas exchange, sleep quality, and quality of life in patients with OHS.
Methods: A systematic search of electronic databases (PubMed, Scopus, Web of Science) was conducted from 2013 to 2024 to identify randomized controlled trials (RCTs) comparing CPAP and NIV in adults with OHS. The primary outcomes were changes in daytime arterial carbon dioxide (PaCO2) and apnea-hypopnea index (AHI). Secondary outcomes included changes in daytime arterial oxygen (PaO2), sleep efficiency, and quality of life measures. Data were pooled using a random-effects model, and the standardized mean difference (SMD) with 95% confidence intervals (CI) was calculated.
Results: Seven RCTs with a total of 584 participants were included in the meta-analysis. Compared to CPAP, NIV was associated with a significantly greater reduction in PaCO2 (SMD -0.45; 95% CI -0.88 to -0.02; p=0.04) and AHI (SMD -0.61; 95% CI -1.17 to -0.05; p=0.03). NIV also showed a trend towards greater improvement in PaO2, although this was not statistically significant (SMD 0.32; 95% CI -0.06 to 0.70; p=0.10). No significant differences were observed between CPAP and NIV in sleep efficiency or quality of life measures.
Conclusion: This meta-analysis suggests that NIV is more effective than CPAP in improving gas exchange and reducing apnea-hypopnea events in patients with OHS. While both treatments appear to be well-tolerated, NIV may be the preferred initial treatment option for OHS, especially in patients with significant hypercapnia
Pregnancy-Triggered Severe Lupus Nephritis with Pleural Effusion: A Case Report
Background: Lupus nephritis (LN) is a severe manifestation of systemic lupus erythematosus (SLE), characterized by kidney inflammation. Pregnancy can trigger or exacerbate LN due to hormonal shifts and altered immune responses. This case highlights the challenges in diagnosing and managing pregnancy-associated LN.
Case presentation: A 27-year-old woman presented with anasarca, malar rash, shortness of breath, and foamy urine during her first pregnancy. She had a history of SLE with previous symptoms limited to skin and joint involvement. Investigations revealed nephrotic-range proteinuria, hematuria, elevated creatinine, and positive anti-nuclear antibodies (ANA). Renal biopsy confirmed Class IV lupus nephritis. She was diagnosed with pregnancy-triggered severe LN with nephrotic syndrome, pleural effusion, and a hypercoagulable state. Treatment included high-dose corticosteroids and mycophenolate mofetil, with close monitoring of both maternal and fetal health.
Conclusion: This case underscores the importance of recognizing and promptly managing LN in pregnancy. Early diagnosis, multidisciplinary care, and individualized treatment are crucial to optimize maternal and fetal outcomes
Impact of Acupoint Specificity on Cardiovascular Outcomes: A Systematic Review and Meta-Analysis
Background: Acupuncture, a cornerstone of Traditional Chinese Medicine (TCM), is increasingly utilized for cardiovascular diseases (CVDs). A central tenet is acupoint specificity – the hypothesis that stimulating specific acupoints yields distinct therapeutic effects compared to non-specific points or sham interventions. However, the empirical evidence supporting acupoint specificity for cardiovascular outcomes remains debated. This systematic review aimed to evaluate the current evidence regarding the impact of acupoint specificity on clinically relevant cardiovascular outcomes.
Methods: A systematic search was conducted in major biomedical databases (PubMed, Embase, Cochrane Library, Scopus) for randomized controlled trials (RCTs) published between January 2014 and December 2024. Studies were included if they compared acupuncture at specific, predefined acupoints relevant to cardiovascular conditions against a control group involving sham acupuncture (non-penetrating, superficial needling at non-acupoints, or needling at irrelevant acupoints) or minimal acupuncture. The primary outcomes included changes in blood pressure (systolic and diastolic), heart rate variability (HRV) parameters, angina frequency/severity, and major adverse cardiovascular events (MACE). Study quality was assessed using the Cochrane Risk of Bias tool.
Results: Seven RCTs involving 850 participants met the inclusion criteria, addressing hypertension (n=3), stable angina (n=2), heart failure support (n=1), and HRV modulation in healthy subjects (n=1). Three studies (one hypertension, one angina, one HRV) suggested statistically significant benefits of specific acupoint stimulation (such as PC6, ST36, LR3) over sham controls for primary outcomes (such as greater reduction in systolic blood pressure, reduced angina frequency, specific HRV modulation). Heterogeneity was substantial across studies, even within the same condition, particularly concerning acupoint selection, stimulation parameters, and control group design.
Conclusion: The evidence supporting clinically significant acupoint specificity for cardiovascular outcomes remains inconclusive and inconsistent. While some studies suggest potential benefits of stimulating specific points like PC6 or ST36 compared to sham interventions, others fail to demonstrate superiority. High-quality, rigorously designed RCTs with standardized protocols, appropriate sham controls, and adequate sample sizes are imperative to clarify the role of acupoint specificity in acupuncture's cardiovascular effects
Metoclopramide-Induced Extrapyramidal Syndrome in a Child: Diagnostic Challenges and Management
Background: Metoclopramide, a dopamine D2 receptor antagonist, is used for its antiemetic and prokinetic properties. However, its use in pediatric populations is restricted due to a significant risk of neurological adverse effects, particularly acute extrapyramidal symptoms (EPS). These reactions, including acute dystonia, are more frequent in children compared to adults, posing diagnostic and management challenges.
Case presentation: We report the case of a 10-year-old girl who presented with acute torticollis and oculogyric crisis following the administration of metoclopramide syrup for fever and vomiting. The symptoms developed approximately one day after initiating the medication. Physical examination and basic laboratory results were otherwise largely unremarkable, apart from elevated white blood cells suggestive of an underlying infection. A diagnosis of metoclopramide-induced acute extrapyramidal syndrome was made.
Conclusion: The patient experienced rapid resolution of symptoms within 30 minutes following the administration of intravenous diphenhydramine. Metoclopramide was discontinued, and she was discharged without symptom recurrence. This case underscores the importance of recognizing metoclopramide-induced EPS in children, the diagnostic difficulties posed by its varied presentation potentially mimicking other serious neurological conditions, and the effectiveness of prompt management with anticholinergic agents like diphenhydramine. Clinicians must maintain a high index of suspicion, adhere to restrictive prescribing guidelines for metoclopramide in pediatrics, and consider safer antiemetic alternatives
Nebulized Heparin for Inhalation Injury in Burn Patients: An Updated Systematic Review and Meta-Analysis of Efficacy and Safety Outcomes
Background: Inhalation injury significantly increases morbidity and mortality in burn patients, primarily through airway obstruction, inflammation, and impaired gas exchange. Nebulized heparin has been investigated as a potential therapy to counteract local pulmonary coagulopathy and fibrin cast formation. However, evidence regarding its clinical efficacy and safety remains conflicting. This systematic review and meta-analysis aimed to synthesize updated evidence on the efficacy and safety outcomes of nebulized heparin in burn patients with inhalation injury.
Methods: A systematic literature search was conducted in PubMed, EMBASE, Cochrane Library, and Web of Science for studies published between January 2014 and December 2024. We included randomized controlled trials (RCTs) and comparative cohort studies evaluating nebulized heparin versus placebo or standard care in adult and pediatric burn patients with inhalation injury. Primary efficacy outcomes included mortality and ventilator-free days (VFDs) at 28 days. Secondary outcomes included duration of mechanical ventilation (DoMV), hospital length of stay (LOS), changes in PaO2/FiO2 ratio, incidence of pneumonia, and safety outcomes (bleeding events). Data were synthesized, and a random-effects meta-analysis was planned to estimate pooled effect sizes (Risk Ratios [RR] or Standardized Mean Differences [SMD]). Study quality was assessed using appropriate tools.
Results: The search strategy yielded seven studies (3 RCTs, 4 cohort studies) meeting the inclusion criteria, encompassing a total of 950 patients. Study quality varied. The meta-analysis suggested a potential reduction in mortality associated with nebulized heparin compared to control groups (Risk Ratio [RR]: 0.79; 95% CI: 0.64-0.97, P=0.02; I²=45%). A trend towards increased VFDs (Standardized Mean Difference [SMD]: 0.35; 95% CI: -0.05 to 0.75, P=0.08; I²=60%) and reduced DoMV (SMD: -0.50; 95% CI: -0.85 to -0.15, P=0.005; I²=55%) was observed. Effects on hospital LOS and PaO2/FiO2 ratio were less consistent across studies. There was no significant difference in the incidence of pneumonia (RR: 0.95; 95% CI: 0.80-1.13, P=0.55; I²=20%). Safety analysis indicated no significant increase in major bleeding events (RR: 1.15; 95% CI: 0.88-1.50, P=0.30; I²=10%), although minor bleeding, like blood-stained sputum, was noted in some studies. Substantial heterogeneity was present for some outcomes.
Conclusion: Based on this updated systematic review and meta-analysis, nebulized heparin may be associated with reduced mortality and duration of mechanical ventilation in burn patients with inhalation injury, without a significantly increased risk of major bleeding. However, considerable uncertainty remains due to study heterogeneity and methodological limitations in the available literature. Its effect on pneumonia incidence appears negligible. Large-scale, high-quality RCTs are still needed to confirm these findings and establish optimal treatment protocols
Re-evaluating WHO Warning Signs in Pediatric Dengue: Abdominal Pain, Not Vomiting, is Associated with Plasma Leakage
Background: 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
Navigating Surgical Strategies for Symptomatic Tarlov Cysts: A Case Report of Successful Microsurgical Excision and Imbrication
Background: Symptomatic Tarlov (perineural) cysts are a rare but debilitating cause of chronic radicular pain, arising from cerebrospinal fluid (CSF) accumulation within the nerve root sheath. The diagnostic journey is often complex, requiring a definitive link between the lesion and the patient's symptoms, and the optimal surgical strategy remains a subject of considerable debate.
Case presentation: A 56-year-old male presented with a six-month history of intractable right S2 radiculopathy (VAS 8/10) and severe functional impairment (Oswestry Disability Index 78%), which had failed a comprehensive trial of conservative management. Magnetic resonance imaging revealed a large cystic lesion at the right S2 level, with features characteristic of a Tarlov cyst, causing severe nerve root compression. Following a thorough discussion of the risks and benefits, the patient underwent an S2 laminectomy with microsurgical partial cyst excision and wall imbrication. Postoperative histopathology confirmed the diagnosis of a perineural cyst, identifying nerve fibers within the fibroconnective tissue of the cyst wall.
Conclusion: The patient experienced immediate and sustained resolution of his radicular pain (VAS 0/10) and a profound improvement in functional status (ODI 12%) at one-year follow-up, with radiological confirmation of successful cyst obliteration. This case highlights the potential of a direct microsurgical approach, guided by a strong clinical-radiological correlation and confirmed by histopathology, to provide a durable and life-altering cure for patients disabled by symptomatic Tarlov cysts