Bioscientia Medicina - Journal of Biomedicine and Translational Research
Not a member yet
1245 research outputs found
Sort by
Efficacy of Hematopoietic Stem Cell Transplantation with CCR5Δ32 Homozygous Donors in Achieving Sustained HIV-1 Remission: A Systematic Literature Review
Get PDFBackground: The pursuit of a cure for Human Immunodeficiency Virus type 1 (HIV-1) infection has led to the exploration of innovative therapeutic strategies. Hematopoietic stem cell transplantation (HSCT) from donors homozygous for the CCR5Δ32 mutation, which confers resistance to HIV-1 infection, has emerged as a promising approach following the notable cases. This study aimed to evaluate the efficacy of HSCT with CCR5Δ32 homozygous donors in achieving sustained HIV-1 remission.
Methods: A systematic search of major electronic databases, including PubMed, Scopus, and Web of Science, was conducted for studies published between 2013 and 2024 that reported on the outcomes of HIV-1 positive individuals who underwent HSCT with CCR5Δ32 homozygous donors. The primary outcome of interest was sustained HIV-1 remission, defined as the absence of detectable viral load in the absence of antiretroviral therapy (ART) for a period of at least 12 months post-transplantation. Data on patient characteristics, transplantation procedures, conditioning regimens, graft-versus-host disease (GVHD), and duration of remission were extracted and synthesized.
Results: Five case studies met the inclusion criteria. These studies predominantly involved individuals with advanced HIV-1 infection who also had hematological malignancies necessitating HSCT. All patients received allogeneic HSCT from donors with the CCR5Δ32/Δ32 genotype. Conditioning regimens varied but generally included chemotherapy with or without total body irradiation. Graft-versus-host disease was a common complication, ranging from mild to severe. Sustained HIV-1 remission, defined by the interruption of ART with undetectable viral load, was achieved in most reported cases for varying durations. Data, based on the patterns observed in these five cases, suggested that approximately 60-80% of patients receiving HSCT from CCR5Δ32 homozygous donors might achieve at least 12 months of ART-free HIV-1 remission, with a smaller subset achieving long-term remission beyond 5 years.
Conclusion: HSCT with CCR5Δ32 homozygous donors demonstrated a significant potential for achieving sustained HIV-1 remission in a select group of individuals, primarily those with hematological malignancies
Is Serum Vitamin D a Determinant of Carpal Tunnel Syndrome Severity? A Cross-Sectional Observational Study
Get PDFBackground: Carpal tunnel syndrome (CTS) represents one of the most frequently encountered compressive neuropathies affecting the upper extremities. Emerging evidence suggests a potential link between vitamin D status and CTS incidence and severity, with vitamin D deficiency proposed as an independent risk factor influencing symptom severity. This study aimed to investigate the association between serum 25-hydroxyvitamin D levels and the electrophysiologically determined severity of CTS in a cohort of patients in Padang, Indonesia.
Methods: This cross-sectional observational study was conducted over eight months, from July 2024 to February 2025, at the Neurological Polyclinic of Dr. M. Djamil General Hospital Padang. Patients diagnosed with CTS based on clinical presentation and confirmed by nerve conduction studies (NCS) were consecutively enrolled. Exclusion criteria were applied to ensure a homogenous study population. Serum 25-hydroxyvitamin D levels were quantified using the Enzyme-Linked Immunosorbent Assay (ELISA) method. CTS severity was categorized as mild, moderate, or severe based on standardized NCS parameters. The association between serum 25-hydroxyvitamin D levels and CTS severity grades was analyzed using the Kruskal-Wallis test, with a p-value < 0.05 considered statistically significant.
Results: A total of 45 subjects meeting the inclusion criteria were included in the final analysis. The median age of the participants was 36 years (range 20-71), with a predominance of female patients (n=37, 82.2%). The mean Body Mass Index (BMI) was 24.1 ± 4.66 kg/m². Based on NCS findings, CTS severity was classified as mild in 20 patients (44.4%), moderate in 16 patients (35.6%), and severe in 9 patients (20%). The overall median serum 25-hydroxyvitamin D level across all CTS patients was 27.80 ng/mL (range 10.4 - 278.4 ng/mL). When stratified by severity, the median vitamin D levels were 23.75 ng/mL for mild CTS, 27.95 ng/mL for moderate CTS, and 37.50 ng/mL for severe CTS. Despite an apparent trend of increasing median vitamin D levels with increasing CTS severity, the Kruskal-Wallis test revealed no statistically significant association between serum 25-hydroxyvitamin D levels and the severity of CTS (p = 0.094).
Conclusion: Serum 25-hydroxyvitamin D levels were not found to be significantly associated with the severity of carpal tunnel syndrome as determined by nerve conduction studies. Further research with larger sample sizes and diverse populations is warranted to clarify the potential role of vitamin D in the pathophysiology and clinical presentation of CTS
Nicotine Hypersensitivity in Inflammatory Dermatoses: A Systematic Review of Evidence for Nicotine as a Cutaneous Hapten
Get PDFBackground: Inflammatory dermatoses, such as seborrheic dermatitis (SD) and atopic dermatitis (AD), affect a significant portion of the population, yet their precise etiology often remains debated. Nicotine, a ubiquitous alkaloid primarily associated with tobacco but also present in certain plants and therapeutic products, has been proposed as a potential hapten capable of triggering hypersensitivity reactions manifesting as inflammatory skin conditions. This systematic review aimed to evaluate the existing evidence supporting the role of nicotine as a cutaneous hapten involved in the pathophysiology of inflammatory dermatoses.
Methods: A systematic literature search was conducted using PubMed, Embase, and Google Scholar databases for studies published between January 2014 and December 2024. Keywords included "nicotine," "hapten," "allergy," "hypersensitivity," "contact dermatitis," "seborrheic dermatitis," "atopic dermatitis," "urticaria," and "skin reaction." Inclusion criteria encompassed original research (in vivo human studies, case reports/series, in vitro mechanistic studies) investigating nicotine's potential to elicit immune-mediated skin reactions consistent with a hapten mechanism. Data extraction focused on study design, population, nicotine source/exposure, diagnostic methods (patch test, prick test), and key findings related to hypersensitivity. Quality assessment was performed using appropriate tools (CARE guidelines for case reports, Joanna Briggs Institute checklists for other study types).
Results: Following title/abstract screening and full-text review, six studies met the inclusion criteria. These included one cross-sectional prick-test study, two case reports detailing reactions to electronic cigarettes, one patch-test study, and two in vitro studies investigating mast cell responses. The prick-test study (N=30) reported positive reactions to nicotine in 20% of non-smokers and 7% of smokers, including one patient with SD. Case reports described eczematous reactions (perioral, hand dermatitis) associated with e-cigarette use. The patch test study indicated positive reactions in a subset of individuals exposed to nicotine patches. In vitro studies demonstrated nicotine-induced mast cell degranulation and mediator release (histamine), potentially inhibited by mast cell stabilizers.
Conclusion: Consistent evidence from the included studies published between 2014-2024 suggests nicotine possesses the potential to act as a cutaneous hapten, capable of eliciting hypersensitivity reactions in susceptible individuals. Findings include positive diagnostic tests (prick/patch), clinical correlations (e-cigarette dermatitis), and plausible biological mechanisms involving mast cell activation. These reactions may contribute to or mimic inflammatory dermatoses like SD or contact dermatitis. Further robust clinical and mechanistic research is warranted to confirm these findings and clarify the prevalence and clinical significance of nicotine hypersensitivity in various dermatological conditions
The Mosaic of Risk in Neonatal Asphyxia: A Systematic Review of Clinical, Placental, and Systemic Predictors
Get PDFBackground: Neonatal asphyxia, a critical failure of gas exchange during the perinatal period, remains a primary cause of neonatal mortality and long-term neurodevelopmental disability worldwide, including hypoxic-ischemic encephalopathy (HIE). Its etiology is a complex mosaic of interconnected factors. Understanding this intricate risk profile is essential for developing effective prevention and intervention strategies. The aim of this study is to systematically review and synthesize recent evidence (published 2019–2025) on the spectrum of maternal, fetal, intrapartum, placental, and systemic risk factors associated with neonatal asphyxia.
Methods: This systematic review was conducted following the PRISMA guidelines. A comprehensive literature search was performed in PubMed, ScienceDirect, and Google Scholar for observational studies published between January 1st, 2019, and April 1st, 2025. Dual reviewers independently conducted study selection, data extraction, and risk of bias assessment using the Newcastle-Ottawa Scale (NOS). Due to significant clinical and methodological heterogeneity, a narrative synthesis was performed.
Results: The search yielded 870 articles, from which 13 observational studies met the inclusion criteria. The synthesis of these studies revealed a consistent and powerful link between neonatal asphyxia and a wide array of predictors. Key factors included maternal comorbidities (hypertensive disorders), prenatal maternal psychological stress, intrapartum complications (prolonged labor, meconium-stained amniotic fluid), placental pathology (maternal vascular malperfusion, meconium-associated changes), fetal characteristics (low birth weight), and crucial systemic factors, such as maternal immigrant status and sociodemographic disparities. Predictive models developed in two of the included studies demonstrated good discriminative performance in identifying high-risk pregnancies, offering potential for clinical application.
Conclusion: Neonatal asphyxia arises from a complex interplay of risk factors that span the entire perinatal continuum, from pre-conceptual maternal health and systemic inequities to acute intrapartum events. Effective mitigation requires a multi-pronged approach encompassing comprehensive antenatal care that addresses both physical and mental health, vigilant intrapartum monitoring, and systemic efforts to ensure equitable access to high-quality perinatal care. The integration of validated risk prediction tools into clinical practice holds significant promise for reducing the global burden of this devastating condition
Head-to-Head Comparison of Urinary Hydroxyproline and Serum CTX-I in Monitoring Antiresorptive Therapy for Osteoporosis: A Network Meta-Analysis
Get PDFBackground: 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
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
Get PDFBackground: 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
Navigating a Complex Extraction: A Case Report on the Colonoscopic Management of Dual Rectal Foreign Bodies and a Proposed Treatment Algorithm
Get PDFBackground: 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
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
Get PDFBackground: 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
A Mechanistic Approach to Post-Operative Analgesia: Safe Use of Etoricoxib in a Patient with Confirmed NSAID-Induced Urticaria/Angioedema (NIUA)
Get PDFBackground: The management of acute pain in patients with NSAID-induced urticaria/angioedema (NIUA) is a clinical challenge. These cross-reactive hypersensitivity reactions are driven by cyclooxygenase-1 (COX-1) inhibition, precluding the use of most conventional analgesics. This report presents the successful management of severe post-operative pain in a patient with a confirmed, long-standing NIUA phenotype.
Case presentation: A 56-year-old male with a 40-year history of angioedema induced by multiple COX-1-inhibiting NSAIDs, confirmed by a previous oral provocation test, required urgent herniotomy. Baseline serum tryptase was normal. Post-operatively, initial analgesia with tramadol proved ineffective and induced emesis. Consequently, the patient was administered etoricoxib 90 mg once daily, a highly selective COX-2 inhibitor. This resulted in excellent and sustained pain control, with the Numeric Rating Scale (NRS) score decreasing from 8/10 to ≤2/10 over a seven-day course, and importantly, without eliciting any hypersensitivity reaction.
Conclusion: This case supports the hypothesis that a highly selective COX-2 inhibitor can provide safe and effective analgesia in patients with severe, cross-reactive NIUA. The analgesic choice was directly informed by the underlying pathophysiology, which involves shunting of the arachidonic acid pathway towards pro-inflammatory leukotriene production following COX-1 blockade. This report reinforces that selective COX-2 inhibition is a rational, first-line strategy for managing pain in this high-risk patient population
Dismantling Immunosuppression in Colorectal Cancer: A Systematic Review and Meta-Analysis on Phyllanthus niruri as a Potent Antagonist of the IL-10 Axis in the Tumor Microenvironment
Get PDFBackground: The immunosuppressive tumor microenvironment (TME) of colorectal cancer (CRC), orchestrated largely by Interleukin-10 (IL-10), presents a formidable barrier to effective anti-tumor immunity. Phytochemicals from traditional medicines offer a promising avenue for immunomodulation. Phyllanthus niruri, a plant with a long history in herbal medicine, has demonstrated significant immunomodulatory potential. This systematic review aims to synthesize and critically evaluate the evidence regarding the efficacy of P. niruri and its bioactive compounds in modulating the IL-10-mediated immunosuppressive axis in CRC.
Methods: A systematic search was conducted in PubMed, Scopus, Web of Science, and Google Scholar for studies published between January 2015 and August 2025. The review included in vitro, in vivo, and clinical studies investigating the effect of P. niruri on IL-10 expression and associated immune responses in CRC models. The PRISMA guidelines were followed. Study quality was assessed using SYRCLE's risk of bias tool for animal studies and the RoB 2 tool for clinical trials. A meta-analysis of IL-10 concentration data from preclinical models was performed using a random-effects model.
Results: From an initial 874 records, seven studies met the inclusion criteria: three in vitro, three in vivo, and one early-phase clinical trial. The selected studies consistently demonstrated that P. niruri extracts and its lignan, phyllanthin, significantly reduced IL-10 production in CRC cell lines, tumor tissues, and patient serum. Based on three preclinical studies, a meta-analysis revealed a significant standardized mean difference (SMD) in IL-10 reduction (SMD = -2.45; 95% CI: -3.10, -1.80; p < 0.00001). This IL-10 downregulation was correlated with a significant increase in cytotoxic T lymphocyte (CD8+) infiltration, repolarization of M2 to M1 macrophages, and enhanced expression of pro-inflammatory cytokines such as IFN-γ and TNF-α. Mechanistically, P. niruri was shown to inhibit the STAT3 and NF-κB signaling pathways, key regulators of IL-10 transcription.
Conclusion: While based on a limited but consistent body of evidence, our findings strongly support the role of Phyllanthus niruri as a potent modulator of the CRC immunosuppressive microenvironment by specifically targeting the IL-10 signaling axis. By reducing IL-10 production, P. niruri unleashes anti-tumor immunity, suggesting its potential as an adjuvant therapy to enhance the efficacy of conventional treatments and immunotherapies in CRC. Rigorous, large-scale clinical trials are warranted to translate these preclinical findings into clinical practice