Accreditation
SINTA 2Nationally Accredited Journal
Vol. 10 No. 1 (2026): Bioscientia Medicina: Journal of Biomedicine & Translational Research
Articles
-
Single-Dose Intralesional Bacillus Calmette-Guérin (BCG) Immunotherapy Induces Complete and Sustained Remission of Recalcitrant Anogenital Condylomata: A Mechanistic Case Series
Views: 511Downloads: 476Background: Anogenital condylomata acuminata caused by Human Papillomavirus (HPV) presents a significant therapeutic challenge due to high recurrence rates after conventional cytodestructive therapies. Intralesional immunotherapy aims to induce a host-mediated immune response, offering a promising alternative. This report investigates the efficacy, safety, and immunological rationale of a novel, single-dose Bacillus Calmette-Guérin (BCG) protocol in an immunologically primed population.
Methods: In this prospective case series, three immunocompetent patients with extensive, therapy-refractory anogenital condylomata were enrolled. Following a standardized protocol, each patient received a single, calculated intralesional injection of BCG vaccine into the largest index lesion. The primary outcome was complete clinical and dermoscopic clearance. Patients were evaluated at regular intervals for efficacy and safety over a 12-month follow-up period.
Result: All three patients achieved complete clinical and dermoscopic clearance of both the injected and distant, untreated lesions within a rapid timeframe of 6 to 10 weeks. The treatment was well-tolerated, with adverse events limited to anticipated and transient local inflammatory reactions. No recurrences were documented in any patient during the 12-month follow-up period.
Conclusion: Single-dose intralesional BCG immunotherapy appears to be a highly effective, durable, and safe therapeutic strategy for recalcitrant anogenital condylomata. The observed pan-lesional clearance strongly suggests the induction of a systemic, cell-mediated anti-HPV immune response. These compelling preliminary findings provide a strong rationale for validation through larger, randomized controlled trials.
-
The Eye as a Window to Systemic Hemodynamics: A Novel Approach to Estimating Central Venous Pressure via Tonometry in Sepsis
Views: 374Downloads: 236Background: Effective hemodynamic management in sepsis is critical, yet current practices are constrained by the risks and interpretive challenges of invasive central venous pressure (CVP) monitoring. The clinical utility of CVP is debated, fueling the search for safer alternatives. This study investigates a novel approach, exploring intraocular pressure (IOP) as a non-invasive surrogate for CVP, predicated on the direct anatomical link between the ocular venous drainage system and the central circulation.
Methods: We conducted a prospective, single-center observational study in a tertiary intensive care unit, enrolling 20 adult patients with sepsis and indwelling central venous catheters. High-fidelity measurements of CVP via a pressure transducer and IOP via Perkins applanation tonometry were performed simultaneously. Data were collected at a baseline steady-state and again 15 minutes after a standardized fluid challenge (median volume 300 mL) to assess the dynamic relationship. The association was quantified using Pearson correlation and modeled with simple linear regression.
Results: A strong, statistically significant positive correlation was observed between CVP and IOP at baseline (r=0.756, p=0.001). This physiological coherence was profoundly amplified following the fluid challenge, strengthening to a very strong correlation (r=0.947, p<0.001). The post-challenge data yielded a robust, preliminary predictive model, defined by the equation: CVP (mmHg) = -0.619 + (0.522 x IOP (mmHg)). The slope of this relationship was precisely estimated (95% CI: 0.435 to 0.609). The model demonstrated high predictive power, with post-challenge IOP accounting for 89% of the variance in CVP (R²=0.89).
Conclusion: This pilot investigation provides compelling evidence for a strong and dynamic correlation between IOP and CVP in critically ill patients with sepsis. The findings suggest that ocular tonometry shows significant promise as a non-invasive method for assessing right-sided filling pressures and, more importantly, for tracking the dynamic response to fluid therapy, thereby offering a potential window into venous congestion. While intriguing, these results are from a small cohort. The derived formula is strictly hypothesis-generating and requires extensive validation in larger, more diverse clinical trials before any potential for clinical application can be considered.
-
Spontaneous Respiration Intubation as a Cornerstone of Multidisciplinary Management for Delayed Tracheoesophageal Fistula Repair in a Critically Ill Neonate
Views: 381Downloads: 454Background: The perioperative management of neonates with esophageal atresia and Type C tracheoesophageal fistula (EA/TEF) is exceptionally challenging, particularly in cases of delayed diagnosis complicated by aspiration pneumonia and congenital heart disease. The primary anesthetic risk is catastrophic gastric insufflation and hemodynamic collapse from positive pressure ventilation (PPV) before fistula control. This report details a successful multidisciplinary strategy centered on an airway technique that preserves spontaneous ventilation.
Case presentation: A 16-day-old, 2.5 kg female neonate with Type C EA/TEF presented for surgical repair following a delayed referral. The case was critically complicated by severe aspiration pneumonia (cultures positive for Klebsiella pneumoniae), which was managed with targeted antibiotic therapy, and hemodynamically significant congenital heart defects (2.5 mm patent ductus arteriosus, 3 mm patent foramen ovale). After 48 hours of intensive cardiorespiratory and nutritional optimization in the neonatal intensive care unit (NICU), the patient underwent surgery. To circumvent the life-threatening risks of PPV, an inhalational induction with sevoflurane was performed, maintaining spontaneous ventilation. The airway was secured via direct laryngoscopy without neuromuscular blockade. A right extrapleural thoracotomy, fistula ligation, and primary esophageal anastomosis were successfully performed. Intraoperative lung retraction-induced desaturation was managed with coordinated surgeon-anesthetist maneuvers. The postoperative course was uneventful.
Conclusion: In a high-risk neonate with delayed TEF presentation and profound cardiorespiratory compromise, securing the airway while maintaining spontaneous ventilation is a cornerstone of safe anesthetic practice. This approach, integrated within a comprehensive, multidisciplinary management plan, directly mitigates the risk of gastric perforation and cardiovascular collapse, thereby enabling a successful surgical repair and favorable outcome.
-
A Neuroinflammatory Biomarker Profile Associated with Neuropathic Pain in Hansen's Disease: A Systematic Review and Meta-Analysis of S100B, TNF-α, and IL-6
Views: 445Downloads: 247Background: Neuropathic pain (NP) is a severe, chronic complication of Hansen's disease (HD), persisting after antimicrobial therapy and profoundly diminishing quality of life. Its pathophysiology is driven by persistent, complex neuroinflammatory processes within the peripheral nervous system. Circulating biomarkers, especially the glial-derived protein S100B, offer a potential objective window into this underlying pathology. This study aimed to meta-analyze the association between circulating S100B, TNF-α, and IL-6 and the presence of NP in patients with HD.
Methods: A systematic search of PubMed, Scopus, and Web of Science databases was conducted for observational studies published between January 2015 and December 2025 that compared biomarker levels in HD patients with and without NP, diagnosed using validated screening instruments. Data from eligible studies were extracted independently, and methodological quality was assessed using the Newcastle-Ottawa Scale. A random-effects meta-analysis was performed to compute the pooled standardized mean difference (SMD) with 95% confidence intervals (CIs) for each biomarker.
Results: Seven studies, comprising 812 patients (405 with NP, 407 without NP), met the inclusion criteria. The meta-analysis revealed that serum S100B levels were significantly elevated in HD patients with NP compared to those without (SMD = 1.28, 95% CI [0.95, 1.61], p < 0.001). This finding was accompanied by very high statistical heterogeneity (I² = 78%). Concurrently, the analysis demonstrated significantly higher circulating levels of TNF-α (SMD = 0.89, 95% CI [0.62, 1.16]) and IL-6 (SMD = 0.75, 95% CI [0.48, 1.02]) in the NP group.
Conclusion: This meta-analysis establishes a strong statistical association between a distinct neuroinflammatory biomarker profile—characterized by elevated circulating S100B, TNF-α, and IL-6—and the presence of neuropathic pain in Hansen's disease. S100B, as a marker of Schwann cell distress, is a particularly relevant component of this profile. These findings underscore the pivotal role of neuroinflammation in HD-related NP, although the high heterogeneity and non-specific nature of these systemic markers necessitate a cautious interpretation regarding their immediate clinical applicability.
-
Dynamic Coupling of Systemic and Intratumoral Estradiol in HER2-Positive and Triple-Negative Breast Cancer: A Validation Study of a Non-Invasive Surrogate
Views: 342Downloads: 257Background: The role of estradiol in the tumor microenvironment (TME) of estrogen receptor (ER)-negative breast cancers is increasingly recognized. Direct measurement of intratumoral estradiol is invasive, creating a barrier to clinical research. This study aimed to determine if circulating plasma estradiol can serve as a high-fidelity, non-invasive surrogate for intratumoral concentrations in HER2-positive (HER2+) and triple-negative breast cancer (TNBC).
Methods: This retrospective, cross-sectional study included 60 women with primary operable HER2+ (n=21) and TNBC (n=39) who underwent mastectomy. Paired pre-operative plasma and post-operative tumor tissue samples were analyzed. Estradiol concentrations were quantified using a validated high-performance liquid chromatography-radioimmunoassay (HPLC-RIA) protocol. Clinicopathological data, including Body Mass Index (BMI), were collected. The primary outcome was the correlation between plasma and intratumoral estradiol, assessed by Spearman's rank correlation. Paired concentrations were compared using the Wilcoxon signed-rank test.
Results: Baseline clinicopathological characteristics, including BMI, were well-balanced between the HER2+ and TNBC cohorts. A highly significant, strong positive correlation was found between plasma and intratumoral estradiol concentrations across the entire cohort (Spearman's ρ = 0.78, p < 0.001). This correlation remained robust in subgroup analyses of menopausal status and tumor grade. Interestingly, median intratumoral estradiol levels (30.0 pg/mL; IQR: 10.0-65.0) were significantly lower than paired median plasma levels (132.0 pg/mL; IQR: 40.0-225.0) (p < 0.001).
Conclusion: Plasma estradiol demonstrates a strong and direct correlation with intratumoral estradiol in HER2+ and TNBC, validating its use as a reliable, non-invasive surrogate. This provides a crucial tool to explore the pathophysiology of the TME. The finding that intratumoral levels are lower than systemic circulation, yet tightly coupled, suggests a dynamic equilibrium that warrants further investigation into local estradiol metabolism and signaling in ER-negative disease.
-
Catastrophic Zone I Open Globe Injury: Pathophysiological Insights and Staged Surgical Triumphs in a Case of Corneal Rupture, Lens Extrusion, and "Blackball" Hyphema
Views: 407Downloads: 305Background: Complex open globe injuries (OGIs) involving the simultaneous destruction of multiple anterior segment structures represent a formidable challenge in ophthalmic traumatology. These injuries necessitate a staged surgical approach to restore ocular integrity and optimize the potential for visual rehabilitation.
Case presentation: A 44-year-old male presented with a severe Zone I OGI in the left eye from a high-velocity projectile stone. His initial best-corrected visual acuity was limited to light perception. Examination revealed an 8-mm corneal rupture with uveal prolapse, complete anterior extrusion of the crystalline lens, and a Grade IV "blackball" hyphema. The Ocular Trauma Score (OTS) was calculated as 1, predicting a very poor visual outcome. Immediate primary repair involved anterior vitrectomy, lensectomy, hyphema evacuation, and corneal suturing. After a six-month stabilization period, a secondary scleral-fixated intraocular lens (IOL) was implanted using a double-needle Yamane technique.
Conclusion: Despite the devastating nature of the initial injury and a grim prognosis as per the OTS, a principled, staged surgical strategy resulted in a final best-corrected visual acuity of 20/50. This case highlights that adherence to damage-control principles—prioritizing anatomical restoration in the primary surgery and deferring refractive correction—can lead to unexpectedly favorable functional outcomes in the most severe categories of ocular trauma.
-
Temporal Dynamics of Postoperative Enterocolitis in Hirschsprung Disease: A Comparative Analysis of Earlier Onset After TAERPT versus the Duhamel Procedure
Views: 359Downloads: 250Background: Hirschsprung-associated enterocolitis (HAEC) remains the most formidable cause of morbidity in surgically corrected Hirschsprung disease (HD). While the transanal endorectal pull-through (TAERPT) and the Duhamel procedure are standard treatments, a critical knowledge gap exists regarding the timing of postoperative HAEC onset associated with each technique. This study aimed to investigate and compare the temporal dynamics of HAEC presentation following these distinct surgical reconstructions.
Methods: This single-center, retrospective cohort study reviewed 64 HD patients who underwent either TAERPT (n=32) or a modified Duhamel procedure (n=32) between January 2022 and January 2023 at a tertiary referral hospital. The primary outcome was the incidence of severe HAEC (HAEC score ≥10). The principal secondary outcome was the time to onset of the first episode of mild-to-moderate HAEC (score <10). Due to the non-normal distribution of onset data, the Mann-Whitney U test was used for statistical comparison.
Results: Baseline demographic and clinical characteristics were comparable between the two cohorts. The incidence of severe HAEC was 0% in both the TAERPT and Duhamel groups. All recorded complications were mild-to-moderate and managed non-surgically. A statistically significant and clinically profound difference in the timing of these complications was observed. The median onset of HAEC in the TAERPT group was 6.0 months (Interquartile Range [IQR], 3.0-6.0), which was significantly earlier than the median onset of 8.5 months (IQR, 3.0-24.0) in the Duhamel group (p < 0.001). The mean onset times were 5.50 ± 1.90 months and 16.09 ± 16.33 months, respectively.
Conclusion: Although both TAERPT and the Duhamel procedure demonstrated excellent safety profiles regarding severe HAEC, their associated temporal patterns of mild-to-moderate enterocolitis are markedly different. The significantly earlier onset of complications following TAERPT suggests that postoperative surveillance strategies should be procedure-specific, with intensified clinical vigilance during the first postoperative year for TAERPT patients.
-
Intraoperative Endoscopy as a Navigational Adjunct in Laparoscopic Heller Myotomy for Achalasia: A Consecutive Case Series
Views: 334Downloads: 381Background: Laparoscopic Heller myotomy (LHM) is a primary surgical treatment for esophageal achalasia. Achieving a complete myotomy while avoiding mucosal perforation is paramount for success, yet intraoperative challenges persist. Intraoperative endoscopy (IOE) is recommended by guidelines but remains underutilized. This study aims to illustrate the methodological application and clinical utility of a standardized IOE protocol in LHM.
Methods: This study was a retrospective analysis of a prospectively maintained database of a consecutive series of patients who underwent LHM with routine IOE for achalasia at our institution in 2023. We present three consecutive cases. Preoperative evaluation included esophagography, upper endoscopy, and high-resolution manometry (HRM). The primary outcomes were the adequacy of myotomy, incidence of mucosal perforation, and postoperative symptomatic relief measured by the Eckardt score at three months.
Results: Three female patients (aged 19, 30, and 65) with achalasia (Type I and II) underwent LHM with IOE. The mean preoperative Eckardt score was 9.3 ± 1.5. IOE was successfully used in all cases to: (1) precisely identify the gastroesophageal junction (GEJ) via transillumination, (2) facilitate submucosal dissection through controlled insufflation, (3) confirm mucosal integrity with an air leak test, and (4) verify a patulous GEJ post-myotomy. No mucosal perforations occurred. At three-month follow-up, the mean Eckardt score significantly improved to 0.3 ± 0.6 (p < 0.05). All patients reported resolution of dysphagia and significant improvement in nutritional status.
Conclusion: Our experience with this consecutive series supports the utility of systematic IOE during LHM. It appears to be a valuable tool for enhancing procedural safety, ensuring myotomy adequacy, and achieving optimal short-term functional outcomes. These findings reinforce existing guidelines and should encourage wider adoption of this critical surgical adjunct.
-
Ultrasound-Guided Neuraxial Precision in a High-Risk Adolescent Parturient: Navigating Anesthetic Management in the Confluence of Nephrotic Syndrome, Diastolic Heart Failure, and Anasarca
Views: 363Downloads: 244Background: Anesthetic management for cesarean delivery in parturients with concurrent nephrotic syndrome and decompensated heart failure presents a profound clinical challenge. Severe anasarca can obliterate anatomical landmarks, while complex cardiorenal pathophysiology creates a state of extreme hemodynamic fragility. This case report describes a systematic, ultrasound-guided approach to overcome these obstacles.
Case presentation: A 15-year-old primigravida at 33 weeks gestation, with new-onset nephrotic syndrome and decompensated heart failure (NYHA Class III), required an emergency cesarean section. Clinical examination revealed severe anasarca, rendering lumbar spinal landmarks impalpable. A systematic pre-procedural lumbar ultrasound examination was performed using a low-frequency curvilinear transducer. This allowed for precise identification of the L3-L4 interspace and an accurate skin-to-dura depth measurement of 4.6 cm. A single-attempt subarachnoid block was successfully performed with a reduced dose (10 mg) of hyperbaric bupivacaine. An adequate T4 sensory block was achieved for surgery. The patient remained remarkably hemodynamically stable throughout the procedure, with no episodes of hypotension requiring vasopressor support. A healthy infant was delivered, and both maternal and neonatal outcomes were excellent.
Conclusion: This case demonstrates that a systematic pre-procedural ultrasound protocol is an indispensable tool for enhancing the safety and success of neuraxial anesthesia in high-risk obstetric patients. By enabling precise anatomical localization and informed dose reduction, it mitigates procedural risk and supports hemodynamic stability in the face of distorted anatomy and severe cardiorenal comorbidities.
-
Dose- and Time-Dependent Efficacy of Topical Hydroquinone in Establishing a C57BL/6 Mouse Model of Vitiligo
Views: 457Downloads: 787Background: Vitiligo is a complex autoimmune depigmenting disorder driven by melanocyte-specific CD8+ T cells, oxidative stress, and genetic susceptibility. The lack of standardized, accessible animal models that recapitulate these pathways hinders therapeutic development. This study aimed to systematically optimize and validate a chemically-induced vitiligo model in C57BL/6 mice.
Methods: Eighty (80) male C57BL/6 mice were randomized into ten groups (n=8/group). Experimental groups received once-daily topical applications of hydroquinone (HQ) at 2.5%, 5%, or 10%, or monobenzone (MBZ) at 40% for 8 or 16 days. Vehicle-treated mice served as controls. Efficacy was assessed via quantitative histopathology (Masson-Fontana staining for melanin area), biomolecular assays for oxidative stress (Malondialdehyde [MDA] and Superoxide Dismutase [SOD]), and RT-qPCR for melanogenesis-related (Tyr) and inflammation-related (Tnf) gene expression.
Results: A clear dose- and time-dependent depigmentation was observed. The 10% HQ 16-day protocol was maximally effective, inducing a profound reduction in epidermal melanin area (0.06 ± 0.02) compared to 16-day controls (0.40 ± 0.04; p < 0.001). This histopathological finding was significantly correlated with severe cutaneous oxidative stress, evidenced by a 3.75-fold increase in MDA (p < 0.001) and a 50% reduction in SOD activity (p < 0.001) versus controls. Furthermore, this regimen caused a potent suppression of Tyr expression (0.15-fold change; p < 0.001) and a significant upregulation of the pro-inflammatory cytokine Tnf (3.8-fold change; p < 0.001).
Conclusion: The 16-day topical application of 10% hydroquinone is a reliable, rapid, and highly reproducible protocol for inducing vitiligo-like depigmentation in C57BL/6 mice. This model successfully recapitulates key pathophysiological pillars of human vitiligo, including melanocytotoxicity, profound oxidative stress, and a pro-inflammatory cutaneous environment, establishing it as a valuable platform for preclinical therapeutic screening.
-
The Clinical Spectrum and Management Patterns of Orbital Meningioma: A 6-Year Single-Institution Case Series from Indonesia
Views: 353Downloads: 193Background: Orbital meningiomas (OMs) are rare, complex tumors whose clinical course and management are debated. Data from Southeast Asian populations, particularly Indonesia, is scarce. This study aims to define the clinical spectrum, radiological features, and management trends of OMs at a single Indonesian tertiary referral center, with a focus on hormonal factors in a predominantly female cohort.
Methods: A retrospective, descriptive case series was conducted on all patients diagnosed with orbital meningioma at Dr. M. Djamil General Hospital, Padang, Indonesia, from January 2018 to December 2023. Data on demographics, detailed clinical presentation (visual acuity, proptosis, extraocular movement), radiological findings (location, size, hyperostosis), and hormonal risk factors were collected. Management strategies, histopathological results (WHO grade), and follow-up outcomes were analyzed.
Results: Twenty patients were included, with a significant female predominance (n=16, 80%; F:M ratio 4:1). The median age at diagnosis was 47 years (range 28-71). A strong association with hormonal factors was noted; 50% (8/16) of female patients had a history of exogenous hormonal contraceptive use. The most common presenting symptoms were progressive proptosis (n=15, 75%) and visual loss (n=12, 60%). The mean proptosis was 5.5 ± 2.1 mm. The most frequent tumor location was retrobulbar (intraconal) (n=11, 55%), followed by optic nerve sheath (n=5, 25%). A multidisciplinary, conservative-led approach was the primary management strategy, with 75% (n=15) of patients managed with active observation and neurosurgical consultation. Surgical intervention was performed in 25% (n=5) of cases, primarily for severe symptoms or aggressive radiological features. Histopathology (n=5) confirmed WHO Grade I in four cases (80%) and WHO Grade II (atypical) in one case (20%).
Conclusion: Orbital meningiomas in this Indonesian cohort demonstrate a striking female predominance and a strong association with hormonal contraceptive use, suggesting a significant role for hormonal pathways in their pathophysiology. The management paradigm has shifted towards a multidisciplinary, observation-first approach, reserving surgical intervention for cases with documented progression, severe vision loss, or high-grade pathological features.
-
Whey Protein as an Adjuvant Therapy for Wound Healing and Infection Control: A Systematic Review and Meta-Analysis of Clinical and Preclinical Evidence
Views: 1,864Downloads: 687Background: Impaired wound healing and subsequent infections represent a significant clinical and economic burden. Nutritional status, particularly high-quality protein provision, is a critical, modifiable determinant of healing outcomes. Whey protein (WP), a rich source of essential amino acids and unique bioactive components, has emerged as a promising adjuvant therapy.
Methods: We conducted a systematic review and meta-analysis adhering to PRISMA guidelines. We searched PubMed, Scopus, and Web of Science from January 2015 to December 2024 for clinical randomized controlled trials (RCTs) and preclinical controlled studies evaluating WP supplementation on wound healing and infection. Rigorous inclusion criteria led to the selection of seven studies (four clinical RCTs, three preclinical) for quantitative synthesis. Data were pooled using a random-effects model to calculate Standardized Mean Differences (SMD) for continuous outcomes and Odds Ratios (OR) for dichotomous outcomes.
Results: The meta-analysis of four clinical RCTs (n=340 patients) demonstrated that WP supplementation significantly accelerated wound healing (SMD = 0.78; 95% CI 0.45, 1.11; p < 0.0001) with moderate heterogeneity (I²=38%). Furthermore, WP significantly reduced the odds of wound infection by 48% (OR = 0.52; 95% CI 0.31, 0.87; p=0.01) with no heterogeneity (I²=0%). Preclinical synthesis (3 studies, n=62 animals) revealed a significant reduction in pro-inflammatory cytokines (TNF-α, IL-6) at the wound site (SMD = -1.15; 95% CI -1.67, -0.63; p < 0.0001).
Conclusion: This meta-analysis provides robust quantitative evidence that whey protein functions as an effective adjuvant therapy, significantly enhancing wound repair and providing clinically relevant infection control. These benefits appear to be mediated by a dual mechanism: providing essential anabolic substrates for tissue repair and exerting potent immunomodulatory and antioxidant effects via bioactive components like lactoferrin and cysteine.
-
Adjunctive Vaginal Probiotic Therapy for Preterm Premature Rupture of Membranes: A Systematic Review and Meta-Analysis of Latency Period, Maternal Infection, and Neonatal Morbidity
Views: 525Downloads: 290Background: Preterm premature rupture of membranes (PPROM) significantly drives preterm birth rates and consequent neonatal morbidity and mortality. While standard antibiotic therapy aims to prolong pregnancy latency, it concurrently disrupts the protective vaginal microbiota. Adjunctive vaginal probiotics have been investigated as a means to restore beneficial flora, potentially mitigating ascending infection and improving perinatal outcomes. This study systematically synthesized the current randomized trial evidence regarding this adjunctive therapeutic strategy.
Methods: We performed a systematic review and meta-analysis following PRISMA guidelines. PubMed, EMBASE, and CENTRAL databases were searched (2014–October 2025) for randomized controlled trials (RCTs) comparing adjunctive vaginal probiotics plus antibiotics versus antibiotics (alone or with placebo) in singleton pregnancies complicated by PPROM between 24+0 and 34+0 weeks’ gestation. Primary outcomes included the latency period (days) and maternal chorioamnionitis or infectious morbidity. Key secondary outcomes were neonatal intensive care unit (NICU) admission, neonatal sepsis, and neonatal mortality. Data were pooled using a random-effects model, calculating Mean Differences (MD) or Risk Ratios (RR) with 95% Confidence Intervals (CI). Risk of bias was assessed using the Cochrane RoB 2 tool.
Results: Three RCTs, encompassing 330 participants, met the inclusion criteria. Significant methodological limitations, including high risk of bias and critical baseline confounding by gestational age in the largest trial, were identified across the included studies. A sensitivity analysis addressing high heterogeneity (I²=98%) for latency (excluding one retrospective study; n=290) indicated a modest but statistically significant prolongation associated with probiotics (MD 2.98 days; 95% CI 1.80–4.16; p<0.0001; I²=0%). Probiotic use was linked to a significantly lower risk of maternal infection (RR 0.43; 95% CI 0.24–0.77; p=0.005; I²=0%; n=270). Statistically significant reductions were also observed for NICU admission (RR 0.59; 95% CI 0.46–0.75; p<0.0001; I²=55%; n=330) and neonatal mortality (RR 0.38; 95% CI 0.18–0.81; p=0.01; I²=0%; n=270), although these estimates are likely inflated due to baseline confounding.
Conclusion: This meta-analysis suggests adjunctive vaginal probiotics may offer benefits in PPROM management by modestly prolonging latency and significantly reducing maternal infectious morbidity. While substantial reductions in NICU admission and neonatal mortality were observed, these findings must be interpreted with extreme caution due to the limited quantity and low quality of the primary evidence, particularly the high risk of bias and confounding. Definitive conclusions cannot be drawn, and routine clinical adoption is not supported by current evidence. High-quality, large-scale RCTs are imperative.
-
Ecthyma Contagiosum (Orf Virus) Masquerading as Subcorneal Pustular Dermatosis: A Diagnostic Pitfall in an Adolescent
Views: 323Downloads: 232Background: Ecthyma contagiosum (Orf) is a zoonotic viral infection caused by a Parapoxvirus, typically presenting as a self-limiting, solitary cutaneous lesion on the hands of occupationally exposed individuals. Atypical, multifocal, or pustular presentations can pose a significant diagnostic challenge, mimicking various inflammatory dermatoses.
Case presentation: We present the case of a 17-year-old female with no direct animal contact who developed a progressive, widespread, and painful pustular eruption on her extremities over three weeks. The clinical presentation was highly suggestive of Subcorneal Pustular Dermatosis (SPD), prompting treatment with systemic corticosteroids, which led to clinical worsening. A delayed epidemiological history revealed an environmental link to a nearby goat farm and a family cluster of similar, milder lesions. A diagnostic punch biopsy was pivotal, revealing viral cytopathic effects, including extensive ballooning degeneration and epidermal necrosis, inconsistent with SPD. Subsequent bacterial culture confirmed superinfection with Enterobacter cloacae ssp. cloacae. The diagnosis was established by the pathognomonic histopathological findings.
Conclusion: The patient’s steroid therapy was immediately ceased, and targeted antibiotic therapy was initiated, leading to complete resolution. This case highlights the Orf virus as a critical clinical chameleon and a diagnostic pitfall for generalized pustular eruptions. It underscores the necessity of a high index of suspicion for zoonoses, even in non-occupational settings, and confirms the indispensable role of histopathology in differentiating viral cytopathy from sterile neutrophilic dermatoses to prevent iatrogenic harm from inappropriate immunosuppression.
-
Vitamin D in the Breast Cancer Continuum: A Systematic Review and Meta-Analysis of Primary Prevention, Patient Prognosis, and Adjunctive Treatment Response
Views: 929Downloads: 430Background: The role of vitamin D across the breast cancer spectrum remains complex and contested. Compelling preclinical antineoplastic mechanisms contrast with inconsistent clinical findings. Large randomized controlled trials (RCTs) show null effects for primary prevention, while observational studies often link higher vitamin D status at diagnosis with better prognosis. Key conflicts include this prevention-prognosis disconnect, debates over linear versus J-shaped prognostic dose-responses, and a "receptor-status paradox" where estrogen receptor-positive (ER-positive) disease shows prognostic links, but hormone receptor-negative (HR-negative)/triple-negative (TNBC) subtypes derive greater benefit (improved pathological complete response, pCR) from vitamin D intervention during neoadjuvant chemotherapy (NACT). This study systematically synthesizes evidence across these distinct clinical contexts.
Methods: Following PRISMA guidelines, we systematically reviewed PubMed, EMBASE, and CENTRAL (January 1st, 2014–September 2nd, 2025) for high-impact RCTs and large prospective cohort studies evaluating vitamin D supplementation or serum 25-hydroxyvitamin D (25(OH)D) levels regarding breast cancer incidence, prognosis (survival/recurrence), or pCR after NACT. Quality was assessed (Cochrane RoB 2; Newcastle-Ottawa Scale). Data were extracted dually. Findings were synthesized stratigraphically (prevention, prognosis, treatment). A random-effects meta-analysis pooled pCR data from NACT RCTs.
Results: Six high-quality studies (3 RCTs, 3 cohorts; N=31,026) were included. (1) Prevention: The VITAL RCT (N=25,871; mean baseline 25(OH)D 30.8 ng/mL) found no reduction in incident invasive breast cancer with 2000 IU/day vitamin D3 (HR 1.02, 95% CI 0.79–1.31). (2) Prognosis: Cohort studies (N=4,835) showed higher 25(OH)D linked to better OS (Adj HR T3 vs T1: 0.72). Complexity emerged: one study linked benefit specifically to ER-positive recurrence (Adj HR 0.87), while another reported a J-shaped curve for EFS, with worse outcomes at both low (≤52 nmol/L; Adj HR 1.63) and high (≥99 nmol/L; Adj HR 1.37) levels versus intermediate. (3) Treatment: Meta-analysis of two NACT RCTs (N=310) showed vitamin D supplementation significantly increased pCR rates (38.1% vs 22.6%; Pooled RR 1.69, 95% CI 1.21–2.36; P=0.002; I²=0%). Subgroup data strongly suggested greater benefit in HR-negative/TNBC and baseline-deficient patients.
Conclusion: Vitamin D supplementation appears ineffective for primary breast cancer prevention in replete populations. Its prognostic role is complex, suggesting an optimal 25(OH)D range (potentially ~30-40 ng/mL) and possible ER-specific hormonal modulation effects, though causality from observational data remains uncertain. Critically, vitamin D intervention during NACT significantly improves pCR, particularly in HR-negative/TNBC, likely via distinct chemosensitization/immunomodulatory mechanisms. This synthesis provides a framework for understanding these context-dependent roles, supporting vitamin D assessment and potentially adjunctive NACT supplementation, especially in deficient patients with aggressive subtypes, pending necessary validation in larger trials.
-
Fatal Lung-Kidney Crosstalk in Bronchopulmonary Dysplasia: A Case of Refractory Weaning Unmasking Confirmed Williams Syndrome and Severe Obstructive Nephrolithiasis
Views: 279Downloads: 274Background: Bronchopulmonary dysplasia (BPD) is the most common, serious morbidity of prematurity, frequently complicated by a protracted and difficult weaning process from respiratory support. Refractory weaning failure, defined as a lack of response to conventional BPD therapies, should trigger a broad investigation for non-pulmonary, systemic confounders.
Case presentation: We present the case of a 1,480-gram, 35+4 weeks' gestation female infant with severe hyaline membrane disease who subsequently developed moderate-to-severe BPD. The infant exhibited refractory respiratory failure, failing multiple extubation attempts, and showing no clinical improvement despite standard BPD management, including a 15-day course of furosemide. On day 58, investigation for worsening cholestasis incidentally revealed a 1.3 cm obstructive right renal calculus with severe hydronephrosis and acute pyelonephritis. This finding, coupled with evolving "elfin" facies, prompted a systemic workup. Key confirmatory data included severe hypercalcemia (13.4 mg/dL) and an echocardiogram revealing supravalvular aortic stenosis (SVAS). These findings, along with a characteristic phenotype, established a clinical diagnosis of Williams Syndrome. The infant rapidly developed urosepsis and anuric acute kidney injury (AKI), culminating in irreversible respiratory failure.
Conclusion: This case provides a definitive clinico-pathological correlation for a rare and fatal triad. The severe nephrolithiasis is explained by a "two-hit" mechanism: baseline idiopathic hypercalcemia from Williams Syndrome, massively amplified by iatrogenic hypercalciuria from furosemide therapy. The patient's demise was a direct consequence of lung-kidney crosstalk, wherein the obstructive urosepsis and AKI induced a fatal inflammatory and hydrostatic pulmonary edema that overwhelmed the infant's BPD-compromised lungs.
-
Adaptive Radiotherapy (ART) versus Non-Adaptive IMRT for Locoregionally Advanced Nasopharyngeal Carcinoma: A Meta-Analysis of Dosimetric Advantages, Clinical Outcomes, and Organ-at-Risk Sparing
Views: 340Downloads: 224Background: Intensity-modulated radiotherapy (IMRT) is the cornerstone of treatment for nasopharyngeal carcinoma (NPC), offering high dose conformity. However, anatomical variations during the multi-week therapy course can compromise dosimetric accuracy. Adaptive radiotherapy (ART), which adjusts the treatment plan based on intra-treatment imaging, aims to mitigate these effects. This meta-analysis synthesized contemporary comparative evidence (2014–2025) on the efficacy and safety of ART versus non-adaptive IMRT in locoregionally advanced NPC.
Methods: Following PRISMA guidelines, PubMed, Embase, Scopus, and Cochrane Library were searched for studies comparing ART with non-adaptive IMRT (cohorts or hybrid/phantom plan comparisons) in locoregionally advanced NPC. Primary outcomes were locoregional recurrence-free survival (LRFS) and overall survival (OS); secondary outcomes included progression-free survival (PFS), distant metastasis-free survival (DMFS), and dosimetric metrics for targets (D98, Conformity Index [CI]) and organs-at-risk (OARs: parotid Dmean, spinal cord Dmax, brainstem Dmax). Hazard Ratios (HR) and Mean Differences (MD) were pooled using random-effects models. Data estimation methods (Tierney, Wan, Cochrane) were employed where necessary. Heterogeneity was assessed using I².
Results: Nine studies (2 cohort, 7 dosimetric/anatomical) involving 362 patients (clinical) and 215 datasets (dosimetric) were included. ART significantly improved LRFS compared to non-adaptive IMRT (pooled HR = 0.53, 95% CI 0.32–0.88; I²=0%). No significant differences were found for OS (HR=0.98, 95% CI 0.64–1.50), PFS (HR=0.70, 95% CI 0.45–1.07), or DMFS (HR=0.88, 95% CI 0.48–1.62). Compared to hybrid/phantom plans, ART significantly enhanced target coverage (pooled PTV D98 MD = 2.15 Gy, 95% CI 1.10–3.20 Gy; I²=78%) and conformity (pooled CI MD = 0.05, 95% CI 0.02–0.08; I²=85%). ART significantly reduced OAR doses: parotid Dmean (pooled MD = -3.50 Gy, 95% CI -4.95 to -2.05 Gy; I²=90%), spinal cord Dmax (pooled MD = -3.95 Gy, 95% CI -5.80 to -2.10 Gy; I²=93%), and brainstem Dmax (pooled MD = -2.75 Gy, 95% CI -4.40 to -1.10 Gy; I²=91%). Dosimetric analyses exhibited high heterogeneity.
Conclusion: ART significantly improves LRFS in locoregionally advanced NPC compared to non-adaptive IMRT. It provides substantial dosimetric advantages, enhancing target coverage and conformity while critically reducing doses to parotid glands, spinal cord, and brainstem. Despite high dosimetric heterogeneity and no demonstrated OS benefit, the improvements in LRFS and dose delivery support the thoughtful implementation of ART.
-
Bridging the Therapeutic Gap: A Systematic Review and Meta-Analysis on the Efficacy, Safety, and Pathophysiological Impact of Sodium Zirconium Cyclosilicate in Enabling Guideline-Directed Medical Therapy
Views: 400Downloads: 275Background: Hyperkalemia is a life-threatening complication of chronic kidney disease (CKD) and heart failure (HF), primarily impeding the use of life-saving renin-angiotensin-aldosterone system inhibitors (RAASi). This systematic review and meta-analysis evaluate the evidence for sodium zirconium cyclosilicate (SZC) in managing hyperkalemia and enabling RAASi therapy.
Methods: This systematic review searched Medline, Embase, and Cochrane CENTRAL to September 2025. Dual reviewers independently screened, extracted data, and assessed bias (Cochrane RoB 2, Newcastle-Ottawa Scale). We included RCTs and observational studies of SZC in adults with hyperkalemia. A random-effects meta-analysis was performed on RCTs reporting maintenance-phase efficacy and safety.
Results: The search yielded 1,254 citations, with 6 pivotal studies included. The meta-analysis of 3 RCTs found that SZC (5-10g daily) was significantly more effective than placebo at maintaining normokalemia over 12-28 days. The pooled mean difference in serum K+ was -0.58 mEq/L (95% CI: -0.65 to -0.51; I2 = 0%). SZC did increase the risk of edema (pooled Risk Ratio: 2.95; 95% CI: 1.51 to 5.76; I2 = 0%). The narrative synthesis of observational data confirmed that SZC use was associated with a >2.5-fold increase in the likelihood of continuing RAASi therapy.
Conclusion: Sodium zirconium cyclosilicate is a highly effective and rapidly acting agent for both acute correction and chronic management of hyperkalemia. Our meta-analysis provides a precise estimate of its high maintenance-phase efficacy. Its primary clinical benefit lies in providing a renal-independent pathway for potassium excretion, thereby "uncoupling" potassium levels from RAASi use and bridging a critical treatment gap.
-
Beyond Glycemia: Independent Hemodynamic and Metabolic Drivers of Incident Diabetic Kidney Disease in a 5-Year Prospective Indonesian Primary Care Cohort
Views: 361Downloads: 226Background: The relative contributions of hyperglycemia, hypertension, and metabolic adiposity to the progression of diabetic kidney disease (DKD) are debated, particularly in Southeast Asian populations and in the context of modern polypharmacy. We aimed to prospectively quantify the independent impact of glycemic burden, hemodynamic stress, and central adiposity on the 5-year incidence of DKD in an Indonesian primary care cohort.
Methods: We conducted a 5-year, multi-center, prospective cohort study at 25 primary care clinics in Indonesia. We randomly sampled and enrolled 1,250 T2DM patients without pre-existing DKD (eGFR > 60 mL/min/1.73m² and normoalbuminuria). The primary composite outcome was incident DKD, defined as persistent albuminuria (ACR ≥ 30 mg/g on 2 of 3 occasions) or a sustained eGFR decline of ≥ 30%. Baseline predictors included HbA1c, Systolic Blood Pressure (SBP), and Waist-to-Height Ratio (WHtR). Multivariable Cox proportional-hazards models were used to estimate Hazard Ratios (HRs), adjusting for demographics, baseline eGFR, and baseline use of RAAS inhibitors (RAASi) and SGLT2 inhibitors.
Results: Of 1,250 participants, 980 (78.4%) completed the 5-year follow-up. Over a median 4.9 years, 215 participants (21.9%) developed the composite DKD outcome. In the fully-adjusted multivariable Cox model, all three pathways were strong, independent predictors of incident DKD. The standardized HR for SBP (per 1-SD increase) was 1.68 (95% CI: 1.40–2.01; p<0.001), for HbA1c (per 1-SD increase) was 1.45 (95% CI: 1.22–1.73; p<0.001), and for WHtR (per 1-SD increase) was 1.39 (95% CI: 1.18–1.65; p<0.001).
Conclusion: In this prospective primary care cohort, hemodynamic stress (SBP), glycemic burden (HbA1c), and metabolic adiposity (WHtR) were all independent, potent drivers of incident DKD, even after controlling for the use of protective cardio-renal medications. These findings confirm that a multi-pillar strategy, aggressively targeting blood pressure, glucose, and weight/metabolic health simultaneously, is essential for DKD prevention.
-
Modulation of TGF-β/Smad and Nrf2 Signaling Pathways by Thymoquinone in the Attenuation of Renal Fibrosis: A Systematic Review and Meta-Analysis of Pre-clinical Models
Views: 399Downloads: 366Background: Renal fibrosis is the irreversible, final common pathway for all progressive forms of chronic kidney disease (CKD), leading to end-stage renal disease. Its pathogenesis is characterized by the over-activation of pro-fibrotic signaling, chiefly the Transforming Growth Factor-beta (TGF-β)/Smad pathway, and the failure of endogenous cytoprotective mechanisms like the nuclear factor erythroid 2-related factor 2 (Nrf2) antioxidant response. Thymoquinone (TQ), the primary bioactive constituent of Nigella sativa, is a pleiotropic compound with known anti-inflammatory and antioxidant properties. This study was designed to systematically quantify its mechanistic efficacy in modulating the core Nrf2 and TGF-β pathways in established pre-clinical models of renal fibrosis and injury.
Methods: We conducted a systematic review and meta-analysis following PRISMA guidelines. We performed a comprehensive search of major databases (including PubMed and Scopus) for pre-clinical in vivo studies published between 2014 and 2025 that investigated TQ monotherapy or TQ-dominant combination therapy in rodent models of renal injury. The eight studies that met the inclusion criteria utilized diverse models: Unilateral Ureteral Obstruction (UUO), cisplatin-induced nephrotoxicity, gentamicin-induced nephrotoxicity, 5-fluorouracil (5-FU)-induced acute kidney injury (AKI), lipopolysaccharide (LPS)-induced inflammation, carfilzomib (CFZ)-induced renal impairment, and ischemia-reperfusion (IRI). Primary outcomes were the expression of renal Nrf2 and TGF-β1. Secondary outcomes included markers of fibrosis (collagen deposition, histology scores), renal function (BUN, creatinine), oxidative stress (MDA, SOD, GSH, CAT), and inflammation (TNF-α, NF-κB, IL-6, IL-1β). Data were pooled using a random-effects model, and primary analyses were stratified by injury model subgroup.
Results: Thymoquinone treatment resulted in a profound and significant upregulation of the protective Nrf2 pathway (SMD: 2.38; 95% CI [1.05, 3.71]; p < 0.001; 3 studies) and its downstream target Heme Oxygenase-1 (HO-1). Concurrently, TQ treatment markedly suppressed the primary pro-fibrotic driver, TGF-β1 (SMD: -2.09; 95% CI [-2.99, -1.19]; p < 0.001; 2 studies). This pivotal dual modulation translated into significant functional and structural improvements. TQ robustly attenuated renal fibrosis scores (SMD: -1.89; 95% CI [-2.55, -1.23]; p < 0.001; 2 studies). Stratified subgroup analysis showed TQ significantly improved renal function in both chemotoxic AKI models (BUN SMD: -2.31; 95% CI [-3.22, -1.40]) and chronic obstructive/fibrosis models (BUN SMD: -1.17; 95% CI [-1.75, -0.59]). This functional protection was underpinned by potent, broad-spectrum reversal of oxidative stress and inflammation across all subgroups.
Conclusion: Thymoquinone consistently ameliorates renal injury and fibrosis across a wide spectrum of pre-clinical models. Its mechanism of action is multifaceted, critically involving the dual modulation of opposing pro-fibrotic and protective pathways: it suppresses the TGF-β1 cascade while simultaneously activating and restoring the Nrf2 antioxidant response. This body of evidence strongly supports Thymoquinone as a high-potential candidate for translational research and development as a novel, network-targeting therapy for human renal fibrosis.
-
Beyond Phosphate Binding: A Systematic Review and Meta-Analysis on the Efficacy and Safety of the Novel Paracellular Phosphate Inhibitor, Tenapanor, for Hyperphosphatemia in Dialysis Patients
Views: 594Downloads: 594Background: Hyperphosphatemia is a critical driver of cardiovascular morbidity and mortality in patients with chronic kidney disease (CKD) undergoing dialysis. Current management, reliant on phosphate binders, is hampered by high pill burden and poor adherence. Tenapanor, a first-in-class, minimally-absorbed sodium/hydrogen exchanger 3 (NHE3) inhibitor, reduces paracellular phosphate absorption. We performed a systematic review and meta-analysis of all available Phase 3 trials to quantify its efficacy and safety.
Methods: We searched PubMed, Embase, and Cochrane CENTRAL through October 2025 for Phase 3 clinical trials evaluating tenapanor for hyperphosphatemia in dialysis patients. Data were extracted from 6 eligible studies (N=1573). We conducted separate random-effects meta-analyses for different study designs: 1) parallel-group monotherapy vs. placebo, 2) withdrawal-design monotherapy vs. placebo, 3) parallel-group add-on therapy vs. placebo, and 4) safety (diarrhea incidence) vs. placebo. Efficacy was measured by Mean Difference (MD) in serum phosphate change; safety by Risk Ratio (RR).
Results: Tenapanor demonstrated significant efficacy across all study designs. In parallel-group monotherapy (1 study, N=167), tenapanor was superior to placebo (MD: -1.89 mg/dL; 95% CI: -2.36 to -1.42). In withdrawal-design studies (2 RCTs, N=373), tenapanor maintained serum phosphate levels significantly better than placebo (Pooled MD: -0.75 mg/dL; 95% CI: -1.05 to -0.45; I2=0%). As an add-on therapy (1 RCT, N=235), tenapanor provided additional phosphate reduction versus binders alone (MD: -0.65 mg/dL; 95% CI: -0.96 to -0.35). Tenapanor significantly increased the risk of diarrhea versus placebo (3 RCTs, N=521; Pooled RR: 4.10; 95% CI: 2.50 to 6.72; I2=30%), which was the primary adverse event leading to discontinuation.
Conclusion: Tenapanor represents a new mechanistic paradigm for hyperphosphatemia management. It is a highly effective phosphate-lowering agent, both as monotherapy and add-on therapy, but is associated with a significant, mechanism-based risk of gastrointestinal side effects.
-
Complete Clinical and Trichoscopic Remission of Refractory Patch Alopecia Areata with a Multi-Modal Microneedling and Vitamin D3 Protocol: A Case Report
Views: 535Downloads: 428Background: Refractory patch alopecia areata (AA) presents a significant therapeutic challenge, as many patients fail first-line treatments. This gap necessitates the exploration of novel, mechanistically-targeted therapeutic strategies.
Case presentation: We present the case of a 44-year-old female with a 2.5 × 3.0 cm patch of AA, refractory to a 3-month compliant trial of topical 0.25% desoximetasone and 5% minoxidil. Baseline diagnostics included histopathology (peribulbar lymphocytic infiltrate), quantitative trichoscopy (yellow dots, black dots, exclamation mark hairs), and laboratory workup, which revealed a serum 25-hydroxyvitamin D [25(OH)D] insufficiency (18.2 ng/mL). A multi-modal protocol was initiated: (1) systemic 5,000 IU/day oral cholecalciferol, (2) 10 sessions of 1.5 mm microneedling at two-week intervals, and (3) immediate post-procedure application of topical 100,000 IU cholecalciferol. Significant regrowth of pigmented terminal hairs was observed by week 12. After 20 weeks (10 sessions), complete clinical regrowth was achieved. Final quantitative trichoscopy confirmed the full resolution of all pathological markers, with a healthy density of terminal hairs. The patient’s systemic 25(OH)D level was corrected to 41.5 ng/mL. The treatment was well-tolerated.
Conclusion: This case report documents a complete remission associated with a multi-modal protocol. The contribution of the systemic vitamin D repletion is a major, unresolvable confounder, making attribution impossible. However, this hypothesis-generating case suggests a combined (systemic, physical, and topical) approach may represent a potential rescue strategy for refractory patch AA, warranting further controlled investigation.
-
Efficacy, Safety, and Metabolic Effects of Low-Molecular-Weight Heparin versus Unfractionated Heparin in Chronic Hemodialysis: A Systematic Review and Meta-Analysis of Clinical Studies
Views: 713Downloads: 254Background: The optimal anticoagulation for chronic hemodialysis (HD) remains debated. Unfractionated heparin (UFH) is the historical standard but carries risks of metabolic complications and requires intensive monitoring. Low-Molecular-Weight Heparin (LMWH) offers pharmacological advantages, but concerns over bleeding risk in end-stage renal disease (ESRD) have limited its use. This study aimed to provide a holistic comparison by synthesizing recent evidence on the efficacy, safety, and, uniquely, the key metabolic consequences of LMWH versus UFH.
Methods: This systematic review followed PRISMA 2020 guidelines. We searched PubMed, EMBASE, and CENTRAL from January 2014 to March 2025 for clinical studies comparing LMWH and UFH in chronic HD patients. We included 6 studies (3 prospective trials, 3 retrospective cohorts) totaling 7,890 patients. The primary efficacy outcome was circuit thrombosis; the primary safety outcome was major bleeding. Secondary outcomes focused on key metabolic markers (pre-dialysis potassium, lipid profile). Data from prospective trials and observational studies were analyzed separately using subgroup analysis and tested for interaction. Metabolic data were pooled using a random-effects model.
Results: The analysis of key metabolic outcomes, derived from homogenous prospective trials (I2=0%), was the most robust finding. LMWH use was associated with a clinically significant reduction in pre-dialysis serum potassium (Mean Difference [MD]: -0.30 mEq/L; 95% CI: -0.50 to -0.10) and a superior atherogenic profile, including lower triglycerides (MD: -20.10 mg/dL) and higher HDL (MD: +4.50 mg/dL). For safety, no difference in major bleeding was found, a finding that was consistent across prospective trials (OR: 0.78; 95% CI: 0.33-1.85) and large retrospective cohorts (OR: 0.87; 95% CI: 0.69-1.09), with no subgroup interaction (p=0.75). Efficacy for preventing circuit thrombosis was also similar.
Conclusion: This meta-analysis provides strong, high-quality evidence that LMWH confers significant and clinically relevant metabolic advantages over UFH, particularly in mitigating hyperkalemia and atherogenic dyslipidemia. Furthermore, our stratified analysis provides high confidence from real-world data that LMWH, when dosed appropriately, is as safe and effective as UFH.
-
Metastatic Medullary Thyroid Carcinoma Mimicking a Primary Soft Tissue Sarcoma of the Shoulder: A Case Report
Views: 307Downloads: 383Background: Medullary thyroid carcinoma (MTC) is a rare neuroendocrine malignancy accounting for 1-5% of thyroid cancers. While often presenting with cervical lymphadenopathy, distant metastasis to bone and soft tissue mimicking a primary sarcoma is exceptionally rare. This report details a case of MTC where the primary diagnostic challenge was a massive, destructive shoulder mass.
Case presentation: A 58-year-old woman presented with a disabling, 20 cm mass in her left shoulder, progressively enlarging over two years. The patient also noted a 30-year history of a stable, asymptomatic neck lump. Magnetic Resonance Imaging (MRI) revealed a large, hypervascular, destructive mass obliterating the scapula and invading surrounding musculature, with a radiological differential diagnosis of a primary soft tissue sarcoma. Laboratory investigation, however, revealed a massively elevated serum calcitonin (>2000 pg/mL) and carcinoembryonic antigen (CEA) (180 ng/mL). A CT-guided core biopsy of the shoulder mass, initially suspected to be a sarcoma, was negative for all sarcoma markers. Instead, it was strongly positive for neuroendocrine (Synaptophysin, Chromogranin A) and thyroid-specific (TTF-1, PAX-8) markers, as well as definitive MTC markers (Calcitonin, CEA). This confirmed the diagnosis of metastatic MTC. Staging was completed as pT3a pN1b M1. The patient underwent total thyroidectomy with bilateral central and left modified radical neck dissection, followed by planned palliative resection of the shoulder metastasis and systemic therapy with a selective RET inhibitor.
Conclusion: This case highlights a critical diagnostic pitfall. Metastatic MTC can present as a massive soft tissue neoplasm mimicking a primary sarcoma. In such cases, a systematic diagnostic approach combining serum biomarkers (Calcitonin, CEA) with a comprehensive immunohistochemical panel is essential to establish the correct diagnosis and initiate appropriate, life-extending targeted therapy.
-
Efficacy of the Full Mesenchymal Stromal Cell Secretome versus Purified Small Extracellular Vesicles in Preclinical Models of Erectile Dysfunction: A Systematic Review and Parallel Meta-Analysis
Views: 314Downloads: 206Background: Acellular therapies from Mesenchymal Stromal Cells (MSCs), including the full secretome (conditioned medium, CM) and purified small extracellular vesicles (sEVs), are promising restorative treatments for erectile dysfunction (ED). It remains unknown if the therapeutic benefit is driven by the complete secretome or if purified sEVs are the primary, sufficient component. This study aimed to systematically review and meta-analyze the preclinical evidence.
Methods: We conducted a systematic review and parallel meta-analysis adhering to PRISMA guidelines. PubMed, Scopus, and Web of Science were searched from January 1st, 2014, to July 31st, 2025. Studies were eligible if they were preclinical ED models evaluating MSC-CM or purified sEVs against a control. Two parallel meta-analyses were performed using a random-effects model. Primary outcomes were erectile function (Intracavernous Pressure / Mean Arterial Pressure ratio; ICP/MAP) and histopathology (Smooth Muscle / Collagen ratio; SM/Col).
Results: Our search yielded 1,942 records, with 87 full-text articles assessed. After applying strict PICO criteria, 7 primary studies were eligible for the meta-analysis (3 secretome, 4 sEVs). The overall risk of bias was moderate to high (0% allocation concealment). No studies directly compared secretome versus sEVs. The first meta-analysis (Secretome vs. Control, 3 studies, 4 data points, n=70) demonstrated a large, significant improvement in ICP/MAP (Standardized Mean Difference [SMD]: 2.40; 95% CI [1.65, 3.15]; p-value < 0.001), with extreme heterogeneity (I-squared=85%). The second meta-analysis (sEVs vs. Control, 4 studies, n=68) also showed a large, significant improvement (SMD: 2.75; 95% CI [1.90, 3.60]; p-value < 0.001), also with extreme heterogeneity (I-squared=88%).
Conclusion: Both the full MSC secretome and purified sEVs demonstrate large, significant therapeutic effects. However, this quantitative conclusion is severely limited by the exceptionally small number of studies and the profound biomolecular heterogeneity (in cell source and purification) that invalidates direct comparison. The primary finding remains the total lack of comparative data.
