Bioscientia Medicina - Journal of Biomedicine and Translational Research
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Serum Nerve Growth Factor Levels in Painful Diabetic Neuropathy: A Systematic Review and Meta-Analysis
Background: Painful diabetic neuropathy (PDN) is a severe complication of type 2 diabetes mellitus (T2DM). Nerve Growth Factor (NGF) is vital for neuronal health, but its status as a systemic biomarker in PDN is contested due to conflicting reports on serum levels. This study aimed to quantitatively synthesize the literature on the association between serum NGF concentrations and the presence of PDN in patients with T2DM.
Methods: PubMed, Scopus, Web of Science, and Embase were searched for observational studies from January 2015 to August 2025 that measured serum NGF in T2DM patients with PDN versus control groups (T2DM without PDN or healthy individuals). Data were independently extracted by two reviewers. A random-effects model was used to calculate the pooled Standardized Mean Difference (SMD) and 95% confidence intervals (CIs) to account for assay variability. Heterogeneity was explored using the I² statistic and meta-regression.
Results: From 1,482 records, seven cross-sectional studies (485 PDN patients, 511 controls) were included. The meta-analysis revealed that patients with PDN had significantly lower serum NGF concentrations compared to controls, with a pooled SMD of -1.28 (95% CI: -1.79 to -0.77, p < 0.00001). Substantial heterogeneity was present (I² = 84%). Meta-regression showed that a longer duration of diabetes was significantly associated with a greater reduction in NGF levels (p = 0.02). No significant publication bias was detected.
Conclusion: This meta-analysis provides consolidated evidence that lower systemic NGF levels are a strong feature of established PDN. The findings support the neurotrophic deficit hypothesis in PDN pathophysiology and identify NGF as a candidate biomarker requiring rigorous validation in longitudinal studies that carefully differentiate painful from painless neuropathy phenotypes
Functional Limb Salvage Following a 24-Hour-Delayed Fasciotomy for Pediatric Hand Compartment Syndrome: A Case Report
Background: Acute compartment syndrome (ACS) in the pediatric hand is a formidable surgical emergency where delayed diagnosis can lead to devastating neuromuscular deficits and limb loss. The narrow therapeutic window, often termed the "golden hours," is considered critical for preventing irreversible ischemic necrosis. Presentations delayed beyond this period, especially in pre-verbal children, pose a significant clinical and ethical dilemma regarding the utility and risks of surgical intervention.
Case presentation: A 2-year-old female presented to our emergency department 24 hours after a severe crush injury to her right hand from a noodle-making machine. The hand was massively swollen, cyanotic, and insensate, with no detectable capillary refill or digital oximetry readings. A clinical diagnosis of advanced, multi-compartmental ACS was made. Emergency surgical decompression was performed via seven incisions, releasing all ten osteofascial compartments. Intraoperative assessment revealed dusky, non-contractile but bleeding muscle. Following staged debridements, the patient demonstrated remarkable recovery. At six months, she achieved full range of motion in all digits except the middle finger and demonstrated age-appropriate grip and pincer grasp, with the primary sequela being a fixed flexion contracture of the middle finger's proximal interphalangeal joint.
Conclusion: This report highlights a case of unexpected functional recovery following a significantly delayed fasciotomy. The outcome supports a nuanced approach to delayed pediatric ACS, suggesting that in select cases, aggressive surgical decompression should be considered as the potential for a positive outcome may exist. This case serves as a powerful, hypothesis-generating observation that raises critical questions about the absolute temporal limits for surgical intervention and underscores the importance of individualized surgical judgment
Anesthesia Management in a Neonate with Esophageal Atresia Undergoing Esophagotomy and Thoracotomy: A Case Report
Background: Esophageal atresia (EA) and tracheoesophageal fistula (TEF) are congenital anomalies requiring surgical repair in the neonatal period. Anesthetic management for these cases is complex, involving careful planning and execution to ensure a safe perioperative course. This case report details the anesthetic challenges and management of a neonate with EA undergoing thoracotomy and esophagotomy.
Case presentation: A five-day-old male infant presented with EA, pneumonia, and sepsis. After preoperative optimization, the neonate underwent thoracotomy and esophagotomy under general anesthesia with invasive monitoring. The perioperative course was complicated by the patient's comorbidities, requiring meticulous airway management, hemodynamic monitoring, and temperature regulation.
Conclusion: Successful anesthetic management of neonates with EA undergoing thoracotomy necessitates a multidisciplinary approach, addressing the unique challenges posed by the condition and associated comorbidities. This case highlights the importance of preoperative optimization, careful intraoperative management, and vigilant postoperative care in achieving a positive outcome
Beetroot (Beta vulgaris) Extract: A Potential Therapeutic Agent for Modulating Post-Cholecystectomy Colonic Inflammation? An In Vivo Evidence Review
Background: Cholecystectomy, while a common and effective treatment for symptomatic gallstones, can induce alterations in bile flow and gut microbiota composition, potentially leading to colonic inflammation. Beetroot (Beta vulgaris) extract, rich in betalains, nitrates, and other bioactive compounds, has demonstrated anti-inflammatory and antioxidant properties in various models. This systematic review evaluates the in vivo evidence for the efficacy of beetroot extract in modulating colonic inflammation following cholecystectomy.
Methods: A systematic search of PubMed, Scopus, Web of Science, and Embase databases was conducted from January 2013 to May 2024, using keywords related to "beetroot," "Beta vulgaris," "cholecystectomy," "colon," "inflammation," and "in vivo." Studies investigating the effects of beetroot extract on colonic inflammation in animal models post-cholecystectomy were included. Data on inflammatory markers, histological changes, oxidative stress markers, and gut microbiota alterations were extracted.
Results: Seven in vivo studies met the inclusion criteria. Beetroot extract administration was associated with significant reductions in colonic levels of pro-inflammatory cytokines (TNF-α, IL-6, IL-1β) in five studies. Data showed an average reduction of TNF-α by 35% (p < 0.01), IL-6 by 28% (p < 0.05), and IL-1β by 42% (p < 0.001) across these five studies. Four studies reported improvements in histological scores of colonic inflammation, indicating reduced tissue damage. Three studies demonstrated a decrease in MPO activity, a marker of neutrophil infiltration, with data showing an average reduction of 25% (p < 0.05).
Conclusion: The available in vivo evidence, albeit limited, suggests that beetroot extract possesses significant potential for mitigating colonic inflammation following cholecystectomy. The observed anti-inflammatory effects are likely mediated by a combination of betalain-induced antioxidant and anti-inflammatory actions, nitrate-derived nitric oxide signaling, and modulation of the gut microbiota
Perioperative Blood Glucose Levels as a Predictor of Hospital Length of Stay in Complicated Appendicitis: A Prospective Cohort Study
Background: Complicated appendicitis presents significant management challenges. Perioperative blood glucose levels are emerging as potential prognostic indicators in surgery. This study aimed to evaluate the correlation between perioperative blood glucose levels and hospital length of stay in patients with complicated appendicitis.
Methods: This prospective cohort study was conducted at Dr. Moewardi General Hospital, Indonesia, from October 2020 to October 2021. We enrolled 49 adult patients with complicated appendicitis. Preoperative and postoperative blood glucose levels were measured. The primary outcome was hospital length of stay. Spearman’s correlation and ROC curve analyses were performed.
Results: Significant positive correlations were found between hospital length of stay and preoperative blood glucose (r=0.324, p=0.023), postoperative blood glucose (r=0.484, p=0.000), age (r=0.324, p=0.023), and surgical site infection (r=0.360, p=0.011). Postoperative blood glucose showed the strongest correlation. ROC analysis identified a postoperative blood glucose level >123 mg/dL as a cut-off for prolonged hospitalization (>3 days), with 65.2% sensitivity and 65.4% specificity (AUC=0.71).
Conclusion: Perioperative blood glucose levels significantly correlate with hospital length of stay in complicated appendicitis, with postoperative levels showing the strongest association. Monitoring postoperative blood glucose may help predict and potentially reduce the duration of hospitalization
The Efficacy of NeuroAid™ (MLC601) in Modulating NF-κB Expression and Improving Outcomes in Traumatic Brain Injury: A Preclinical Study
Background: Traumatic brain injury (TBI) represents a significant global health concern, leading to substantial mortality and long-term disability. The intricate pathophysiology of TBI involves primary mechanical damage followed by a cascade of secondary injury events, including neuroinflammation, apoptosis, and oxidative stress. The nuclear factor kappa B (NF-κB) signaling pathway plays a pivotal role in orchestrating the inflammatory response post-TBI and has emerged as a potential therapeutic target. This preclinical study aimed to investigate the efficacy of NeuroAid™ (MLC601), a traditional herbal medicine, in modulating NF-κB expression and improving outcomes in a rat model of TBI.
Methods: This study employed a true experimental in vivo design with a post-test only control group. Male Wistar rats (n=18) were randomly divided into two groups: a control group (n=9) subjected to TBI via a weight-drop method, and an experimental group (n=9) subjected to the same TBI procedure followed by intraperitoneal administration of NeuroAid™ (MLC601) at a dose of 2.5 mg/kg body weight at 5 minutes, 8 hours, and 16 hours post-injury. NF-κB expression in brain tissue samples collected 1 hour after the final dose was assessed using immunohistochemistry and quantified by an immunoreactivity score considering both the intensity and percentage of NF-κB expression.
Results: Immunohistochemical analysis revealed the presence of NF-κB expression in both the nucleus and cytoplasm of neurons in both the control and experimental groups. While the experimental group treated with NeuroAid™ (MLC601) exhibited a lower average immunoreactivity score (0.93) compared to the control group (1.29), the difference in NF-κB expression between the two groups was not statistically significant (p = 0.122).
Conclusion: In this preclinical study using a Wistar rat model of TBI, the administration of NeuroAid™ (MLC601) did not result in a statistically significant reduction in NF-κB expression compared to the untreated control group. Although a trend towards lower NF-κB expression was observed in the NeuroAid™-treated group, further research with larger sample sizes, different dosages, and extended treatment durations is warranted to fully elucidate the potential therapeutic effects of NeuroAid™ (MLC601) in the management of traumatic brain injury
Determinants of Recurrence in Intracranial Meningioma: A Decade of Experience with Surgical and Pathological Correlations in Bandung, Indonesia
Background: Intracranial meningiomas are common primary central nervous system tumors, mostly benign, yet recurrence remains a significant clinical challenge influencing patient prognosis. Understanding the characteristics and determinants of recurrence, particularly in specific populations, is crucial. Data on recurrent meningioma from developing countries like Indonesia are limited. This study aimed to describe the clinicopathological features and surgical management experience of recurrent intracranial meningiomas over a 10-year period at a tertiary referral hospital in Bandung, Indonesia.
Methods: A retrospective analysis was conducted on all adult patients (≥18 years) surgically treated for recurrent intracranial meningioma at the Department of Neurosurgery, Dr. Hasan Sadikin General Hospital, Bandung, between January 2012 and December 2022. Patients with incomplete records were excluded. Data collected included demographics, clinical presentation, radiological findings (tumor location, bone infiltration, tumor invasion), surgical history (number of resections, time to recurrence), and histopathological results. Descriptive statistics were used for analysis.
Results: Twenty-eight patients met the inclusion criteria. The cohort was predominantly female (n=24, 85.7%) with a median age of 46 years (range 26-67). The most common presenting symptoms were protrusion (n=11, 39.3%) and headache (n=7, 25.0%). Tumors were most frequently located in the parietal (n=10, 35.7%) and sphenoorbital (n=9, 32.1%) regions. Significant bone infiltration was observed in 75.0% (n=21) of cases. Tumor invasion into adjacent structures occurred in 21.4% (n=6), most commonly involving the cavernous sinus (n=2, 7.1% of total / 33.3% of invaded). The median time to recurrence detection was 36 months (range 6-144). Most patients (n=22, 78.6%) underwent two tumor removal surgeries during the study period. Based on available histopathology (n=17), meningothelial (n=10, 35.7% of total / 58.8% of available) and transitional (n=3, 10.7% of total / 17.6% of available) subtypes were the most common WHO Grade 1 diagnoses. One case each of atypical (Grade 2) and malignant (Grade 3) meningioma were identified.
Conclusion: Recurrent intracranial meningiomas predominantly affected middle-aged females, often presenting with symptoms related to mass effect in parietal and sphenoorbital locations. High rates of bone infiltration and significant tumor invasion, particularly involving the cavernous sinus, were characteristic features. Recurrence was typically diagnosed within 3 years, with meningothelial and transitional subtypes being the most frequent histologies observed in this recurrent group. These findings underscore the complex nature of meningioma recurrence and highlight the need for tailored management strategies and long-term surveillance, particularly in cases with high-risk features like bone and sinus invasion
Impact of Glycemic Control on Amsler Grid Findings in Patients with Diabetic Retinopathy in Palembang, Indonesia
Background: Diabetic retinopathy (DR) remains a principal cause of vision impairment globally, frequently affecting the macula and central vision. This study aimed to investigate the association between glycemic control status and the presence of Amsler grid abnormalities in patients diagnosed with diabetic retinopathy in Palembang.
Methods: This cross-sectional study was conducted at the outpatient ophthalmology and internal medicine clinics of a tertiary referral hospital in Palembang between January 2023 and December 2024. Patients aged 18 years or older with a confirmed diagnosis of type 1 or type 2 diabetes mellitus and any stage of diabetic retinopathy, capable of performing Amsler grid testing, were included after providing informed consent. Patients with other significant ocular pathologies affecting the macula or media opacities precluding fundus examination were excluded. Data collected included demographics, diabetes history, comprehensive ophthalmic examination findings, standardized Amsler grid testing results, and recent HbA1c levels. Glycemic control was categorized as good (<7.0%), fair (7.0-9.0%), and poor (>9.0%). Statistical analysis involved descriptive statistics, chi-square tests, t-tests/Mann-Whitney U tests, and multivariable logistic regression to assess the association between HbA1c levels and abnormal Amsler grid findings, adjusting for potential confounders.
Results: A total of 385 patients with DR (mean age 58.2 ± 9.5 years; 53.8% female) were included. The mean duration of diabetes was 12.4 ± 6.8 years, and the mean HbA1c was 8.9% ± 2.1%. Abnormal Amsler grid findings were reported by 161 participants (41.8%). Patients with abnormal Amsler grid findings had significantly higher mean HbA1c levels compared to those with normal findings (9.8% ± 1.9% vs. 8.3% ± 1.8%, p < 0.001). In the multivariable logistic regression analysis, after adjusting for age, diabetes duration, DR severity, and hypertension, poor glycemic control (HbA1c >9.0%) was independently associated with significantly higher odds of having abnormal Amsler grid findings compared to good glycemic control (HbA1c <7.0%) (Adjusted Odds Ratio [aOR] = 3.45, 95% CI: 1.98-6.01, p < 0.001). Fair glycemic control (HbA1c 7.0-9.0%) also showed increased odds, although to a lesser extent (aOR = 1.82, 95% CI: 1.05-3.15, p = 0.032). Each 1% increase in HbA1c was associated with a 35% increased odds of abnormal Amsler findings.
Conclusion: This study demonstrated a significant association between poorer glycemic control, as indicated by higher HbA1c levels, and the presence of abnormal Amsler grid findings among diabetic retinopathy patients in Palembang. These findings underscore the critical role of meticulous glycemic management in preserving not only retinal structure but also central visual function detectable through simple psychophysical tests. The Amsler grid serves as a valuable, accessible tool for functional monitoring in this patient population
Novel Enhalus acoroides Phytosomes: Formulation, Characterization, and Bioavailability Enhancement
Background: Enhalus acoroides (seagrass) possesses valuable bioactive compounds, including quercetin, with potential therapeutic applications, notably antidiabetic effects. However, the poor solubility and low bioavailability of compounds like quercetin limit their clinical efficacy. Phytosomes, phospholipid-based nanocarriers, represent a promising strategy to overcome these limitations. This study aimed to develop and characterize E. acoroides extract-loaded phytosomes to enhance its potential bioavailability.
Methods: E. acoroides was collected, processed, and extracted using ultrasound-assisted extraction (UAE). Total phenolic (TPC) and flavonoid content (TFC) were determined. Phytosomes were prepared using the thin-layer hydration method with varying extract-to-soya lecithin ratios (F1=1:1, F2=1:2, F3=1:3). Characterization involved particle size analysis, zeta potential measurement, Fourier Transform Infrared Spectroscopy (FTIR), Transmission Electron Microscopy (TEM), entrapment efficiency (EE%) determination via HPLC, and in vitro dissolution studies.
Results: The UAE extract yielded TPC of 0.318 ± 0.036 mg GAE/g and TFC of 1.023 ± 0.022 mg QE/g. Phytosome formulation F1 (1:1 ratio) exhibited optimal characteristics: particle size of 276.4 nm, PDI of 0.591, zeta potential of -18.0 mV, EE% of 80.47 ± 2.62%, and a spherical morphology. FTIR confirmed complexation. F1 phytosomes demonstrated significantly enhanced dissolution, releasing 87.13% of the entrapped compound over 12 hours compared to the crude extract.
Conclusion: E. acoroides extract was successfully encapsulated into phytosomes using a thin-layer method. The F1 formulation (1:1 extract:phospholipid ratio) demonstrated favorable physicochemical properties (nanoparticle size, moderate stability, high EE%) and markedly improved in vitro dissolution, suggesting enhanced bioavailability potential for E. acoroides phytoconstituents
Fatal Feline Rabies: A Case Report of Encephalitis Following a Cat Scratch in an Endemic Indonesian Region
Background: Rabies, a viral zoonosis caused by Lyssavirus, remains a significant public health threat, particularly in Asia and Africa, with an almost invariably fatal outcome once clinical symptoms manifest. While dogs are the primary vector, transmission via cats, especially through scratches, is an under-recognized risk in endemic areas like Indonesia. Delayed post-exposure prophylaxis (PEP) and gaps in surveillance contribute to ongoing fatalities.
Case presentation: We report the case of a 45-year-old Indonesian male from a rural, rabies-endemic area in Jembrana Regency, Bali, who developed fatal encephalitis. Approximately one month prior to symptom onset, he sustained a superficial scratch on his right hand from a free-roaming domestic cat. He did not seek immediate medical attention or PEP. His illness commenced with prodromal symptoms of fever and headache, rapidly progressing to agitation, dysphagia, severe hydrophobia, and aerophobia. Neurological examination revealed fluctuating consciousness, hyperactive reflexes, and marked autonomic dysfunction. Despite intensive supportive care in an isolation unit, his condition deteriorated, leading to death two days after admission. A clinical diagnosis of rabies encephalitis was made based on the characteristic symptoms, a clear history of exposure to a potential vector, and the epidemiological context.
Conclusion: This case underscores the critical importance of recognizing cats as significant vectors for rabies transmission, even via non-bite exposures like scratches, particularly in endemic settings. It highlights the urgent need for increased public awareness regarding prompt wound management and PEP for all potential rabies exposures, including those from felines. Furthermore, comprehensive rabies control strategies must incorporate feline vaccination and improved surveillance to effectively mitigate this fatal disease in regions like Indonesia