Bioscientia Medicina - Journal of Biomedicine and Translational Research
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The Emerging Role of Integrins in Diabetic Kidney Disease: A Systematic Review and Meta-Analysis of Their Diagnostic and Prognostic Utility for Early Risk Stratification
Get PDFBackground: Current biomarkers for diabetic kidney disease (DKD), notably albuminuria and eGFR, are markers of established renal damage, limiting opportunities for early intervention. Integrins, cell-matrix adhesion receptors integral to podocyte health, are emerging as potential upstream indicators of the initial injury that drives DKD. This systematic review and meta-analysis provide the first quantitative synthesis of the evidence on the diagnostic and prognostic utility of integrins in DKD.
Methods: Following PRISMA guidelines, we systematically searched PubMed, Scopus, Embase, and Web of Science for studies published up to July 2025. We included studies that evaluated integrins in urine, serum, or tissue for the diagnosis of early DKD (microalbuminuria) or for predicting disease progression. Data were pooled using bivariate random-effects models for diagnosis and generic inverse variance models for prognosis.
Results: Eight studies involving 2,874 patients met the inclusion criteria. For diagnosing early DKD, five studies (n=1,880) yielded a pooled sensitivity of 0.88 (95% CI: 0.82-0.92) and specificity of 0.85 (95% CI: 0.79-0.90). The area under the summary receiver operating characteristic curve was 0.91 (95% CI: 0.88-0.94), indicating excellent accuracy. A subgroup analysis of non-invasive samples (urine/serum) demonstrated similarly high performance. For prognosis, three prospective studies (n=1,224) showed that elevated baseline integrins were associated with a significantly increased risk of disease progression (pooled Hazard Ratio: 2.15, 95% CI: 1.65-2.79) over a median 5-year follow-up.
Conclusion: Based on the current, albeit limited, evidence, integrins show significant promise as highly sensitive and specific biomarkers for the early detection and potent predictors for the progression of DKD. While these preliminary findings require validation in larger cohort studies, the measurement of non-invasive integrins may represent a valuable future tool for improving early DKD risk stratification
Beta-Blocker Therapy in Older (≥75 Years) and Frail Patients with Heart Failure: A Systematic Review and Meta-Analysis
Get PDFBackground: Beta-blockers are a cornerstone of therapy for heart failure with reduced ejection fraction (HFrEF), but their efficacy and safety in the burgeoning population of very elderly and frail patients, particularly those with preserved ejection fraction (HFpEF), remain uncertain. This population is characterized by unique pathophysiological features, including altered pharmacokinetics, heightened inflammation, and autonomic dysregulation, which may modulate the treatment effect.
Methods: We conducted a systematic review and meta-analysis following PRISMA guidelines. We searched MEDLINE, Embase, and CENTRAL for randomized controlled trials (RCTs) and observational studies published between 2015-2025 that evaluated beta-blockers versus placebo or standard care in patients aged ≥75 years or defined as frail with heart failure. The primary efficacy outcome was all-cause mortality. The primary safety outcome was treatment discontinuation due to adverse events.
Results: Eight studies (three RCTs, five observational) involving 8,512 patients were included. In the overall population, beta-blocker therapy was associated with a reduction in all-cause mortality (Hazard Ratio: 0.88; 95% CI: 0.79−0.98), but with significant heterogeneity (I2=68%). Subgroup analysis revealed this benefit was confined to patients with HFrEF (HR: 0.72; 95% CI: 0.63−0.83), with no benefit observed in HFpEF (HR: 1.09; 95% CI: 0.95−1.25). In frail patients with HFpEF, a trend towards harm was noted (HR: 1.21; 95% CI: 0.98−1.49). Beta-blockers significantly increased treatment discontinuation (Odds Ratio: 2.15; 95% CI: 1.55−2.98), driven primarily by bradycardia.
Conclusion: Beta-blocker therapy reduces mortality in elderly patients with HFrEF, consistent with findings in younger populations. However, in elderly and frail patients with HFpEF, beta-blockers offer no mortality benefit and may be associated with harm, likely due to a pathophysiological mismatch between the drug's mechanism and the disease state
Autologous Parietal Peritoneum as a Biliary Interposition Conduit for Complex Post-Cholecystectomy Bile Duct Injuries: A Feasibility Study and Report of Two Cases
Get PDFBackground: Complex iatrogenic bile duct injuries (BDIs) are formidable surgical challenges, with Roux-en-Y hepaticojejunostomy (RYHJ) being the standard reconstruction. However, RYHJ permanently alters gastrointestinal physiology and is associated with significant long-term morbidity. This has prompted a search for physiology-preserving alternatives. We describe a novel technique using a tubularized autologous parietal peritoneal graft for biliary reconstruction.
Case presentation: This report details the successful management of two patients with high-grade, post-cholecystectomy BDIs (Strasberg-Bismuth Type E1 and E3). Both patients presented with obstructive jaundice and controlled biliary fistulae. Definitive single-stage reconstruction was performed. A segment of parietal peritoneum was harvested, tubularized over a T-tube to create an interposition conduit, and anastomosed to bridge the biliary defect. The repair was reinforced with a pedicled omental flap. Both patients demonstrated complete resolution of jaundice and normalization of liver function tests, with radiological evidence of graft patency and no stricture at 12-month follow-up.
Conclusion: This preliminary experience in two patients suggests that the use of a tubularized autologous parietal peritoneal graft is a surgically feasible technique for the reconstruction of complex BDIs. This approach offers a potential physiology-preserving alternative to traditional bilioenteric anastomosis. Its safety, efficacy, and long-term durability remain unknown and require rigorous evaluation in larger prospective studies
Lower Body Negative Pressure for Spaceflight Associated Neuro-ocular Syndrome: A Systematic Review and Meta-Analysis
Get PDFBackground: Spaceflight associated neuro-ocular syndrome (SANS) is a critical health risk for astronauts on long-duration missions, characterized by potentially vision-altering ocular changes. Lower body negative pressure (LBNP) is a primary countermeasure designed to reverse the foundational cephalad fluid shifts. This study provides the first rigorous, quantitative synthesis of LBNP's efficacy on key SANS-related ocular parameters.
Methods: Following PRISMA guidelines, a systematic search of PubMed, ScienceDirect, and the Cochrane Library (2015–2025) was conducted. Studies quantifying the effect of LBNP on intraocular pressure (IOP), optic nerve sheath diameter (ONSD), or choroidal thickness (CT) in microgravity or its ground-based analogs were included. A random-effects meta-analysis calculated the pooled mean difference (MD). Leave-one-out sensitivity analysis and assessment of publication bias were performed to ensure robustness.
Results: Seven studies (N=89 subjects) met the criteria. The meta-analysis demonstrated that LBNP application resulted in statistically significant reductions in IOP (MD = -2.15 mmHg; 95% CI [-3.01, -1.29]; p < 0.001), ONSD (MD = -0.31 mm; 95% CI [-0.45, -0.17]; p < 0.001), and subfoveal Choroidal Thickness (MD = -18.50 µm; 95% CI [-25.65, -11.35]; p < 0.001). Subgroup analysis revealed a more pronounced effect in ground-based studies. The results were robust in sensitivity analyses, and funnel plots suggested a low risk of publication bias.
Conclusion: This meta-analysis provides robust, quantitative evidence supporting LBNP's efficacy in acutely mitigating the cardinal structural signs of SANS. By directly counteracting the underlying pathophysiology, LBNP is affirmed as a cornerstone countermeasure technology essential for preserving astronaut ocular health during the upcoming era of deep space exploration
The Impact of Intravascular Imaging (IVUS/OCT) Guidance on Preventing In-Stent Restenosis and Improving Long-Term Clinical Outcomes in Complex PCI: A Meta-Analysis
Get PDFBackground: Percutaneous coronary intervention (PCI) in patients with complex coronary artery disease is associated with a higher risk of adverse events, including in-stent restenosis (ISR). Intravascular imaging, using either intravascular ultrasound (IVUS) or optical coherence tomography (OCT), has been proposed to optimize stent implantation and improve outcomes, but its definitive role requires comprehensive evidence synthesis.
Methods: We conducted a systematic review and meta-analysis of randomized controlled trials (RCTs). Major electronic databases (PubMed, EMBASE, Cochrane CENTRAL) were searched from January 2014 to May 2025 for RCTs comparing intravascular imaging-guided PCI with angiography-guided PCI in patients undergoing complex procedures. The primary efficacy endpoint was Major Adverse Cardiovascular Events (MACE), a composite of cardiac death, target-vessel myocardial infarction, and clinically-driven target lesion revascularization. The key secondary endpoint was angiographic ISR. A random-effects model was used to calculate pooled Risk Ratios (RRs) and 95% Confidence Intervals (CIs).
Results: Seven RCTs, enrolling a total of 9,150 patients, met the inclusion criteria. The median follow-up was 24 months. Intravascular imaging guidance was associated with a significant reduction in the risk of MACE (RR: 0.66; 95% CI: 0.55-0.79; p<0.0001) compared to angiography guidance, with moderate heterogeneity (I²=52%). The risk of angiographic ISR was also significantly lower in the imaging-guided group (RR: 0.49; 95% CI: 0.38-0.63; p<0.0001). Furthermore, imaging guidance led to a significant reduction in cardiac death (RR: 0.55; 95% CI: 0.38-0.80) and clinically-driven target lesion revascularization (RR: 0.54; 95% CI: 0.42-0.69).
Conclusion: This meta-analysis provides definitive evidence that the use of intravascular imaging (IVUS or OCT) to guide complex PCI significantly reduces the incidence of long-term major adverse cardiovascular events and in-stent restenosis. These findings support the routine adoption of intravascular imaging as the standard of care to optimize outcomes in this high-risk patient population
Opioid Rotation vs. Dose Titration in Refractory Cancer Pain: A Meta-Analysis of Efficacy and Adverse Events
Get PDFBackground: The management of refractory cancer pain represents a formidable clinical challenge at the intersection of oncology and palliative medicine. When patients with advanced malignancy fail to achieve adequate analgesia or develop intolerable adverse effects from their opioid regimen, clinicians are faced with a crucial decision: to escalate the dose of the current opioid (dose titration) or to switch to a different opioid agent (opioid rotation). The optimal strategy remains a subject of intense debate and variable practice. This meta-analysis was conducted to rigorously compare the efficacy and safety of these two common interventions.
Methods: A systematic and comprehensive search was performed in the PubMed, EMBASE, and Cochrane Central Register of Controlled Trials databases for randomized controlled trials (RCTs) published between January 2015 and December 2024. We included studies that directly compared opioid rotation with dose titration in adult palliative care patients diagnosed with refractory cancer pain. The primary efficacy outcome was the change in pain intensity, analyzed using the Standardized Mean Difference (SMD) to accommodate pain scales such as the Numerical Rating Scale (NRS) and Visual Analogue Scale (VAS). Primary safety outcomes were the incidence of severe neurotoxicity and severe constipation. Data were pooled using a random-effects model, and results were expressed as SMD for the continuous pain outcome and Risk Ratio (RR) for dichotomous adverse events, with corresponding 95% confidence intervals (CI).
Results: Seven RCTs, encompassing a total of 962 patients, met the stringent inclusion criteria. The pooled analysis revealed that the strategy of opioid rotation resulted in a statistically significant and clinically substantial greater reduction in pain intensity compared to continued dose titration (SMD -0.65, 95% CI [-0.88, -0.42], p<0.00001; I²=81%). Furthermore, the risk of developing severe neurotoxicity, including delirium and myoclonus, was significantly lower in the rotation group (RR 0.62, 95% CI [0.45, 0.85], p=0.003; I²=18%). There was no statistically significant difference in the incidence of severe constipation between the two intervention groups (RR 0.90, 95% CI [0.71, 1.14], p=0.38; I²=24%).
Conclusion: In patients with refractory cancer pain, the strategy of opioid rotation provided superior analgesia and was associated with a markedly lower risk of severe neurotoxicity when compared to the continued dose titration of the same opioid. These findings provide strong, high-level evidence to support the use of opioid rotation as a primary and proactive strategy for managing uncontrolled pain or dose-limiting side effects in the palliative care population
Orthoplastic Limb Salvage of a Gustilo-Anderson Grade IIIB Open Trans-Articular Knee Fracture: A Case Report on Staged Reconstruction with a Rotational Fasciocutaneous Flap
Get PDFBackground: High-energy, open trans-articular knee fractures with extensive soft-tissue loss represent a formidable challenge, carrying a high risk of deep infection, nonunion, and amputation. Successful limb salvage necessitates a collaborative orthoplastic approach, combining aggressive surgical debridement and skeletal stabilization with timely, vascularized soft-tissue coverage.
Case presentation: A 16-year-old male was admitted after a severe traffic accident, sustaining a Gustilo-Anderson Grade IIIB open fracture of the right knee. The injury comprised a comminuted distal femur fracture, a comminuted tibial plateau fracture (Schatzker VI), a comminuted patellar fracture, and a proximal fibula fracture. A 12x15 cm soft-tissue defect with a depth of 6 cm exposed the joint capsule and all fracture sites. The patient underwent a staged management protocol. The initial surgery involved extensive debridement of non-viable tissue and stabilization with a spanning multi-planar external fixator, followed by a second-look debridement. Definitive coverage was achieved on day five with a large, medially-based rotational fasciocutaneous flap and a split-thickness skin graft over the donor site. At the 1-year follow-up, all fractures had united, and the soft-tissue envelope was stable and sensate. The patient achieved a functional knee range of motion of 0-100 degrees and could ambulate without aids. The Lysholm knee score was 85, and the Knee Society Score (KSS) was 88.
Conclusion: This case report demonstrates that a meticulously planned, staged orthoplastic strategy can achieve successful limb salvage even in devastating open knee injuries. A large, local rotational fasciocutaneous flap can serve as a reliable and less complex alternative to free tissue transfer for covering massive defects in this region, particularly in young patients with favorable tissue characteristics
Beyond the Species Barrier: A Systematic Review and Risk of Bias Assessment on the Efficacy, Safety, and Translational Potential of Xenogenic Platelet-Rich Plasma for Wound Healing
Get PDFBackground: Chronic wounds represent a significant clinical burden. Autologous platelet-rich plasma (PRP) is an effective but patient-limited therapy. Xenogenic PRP (xPRP), derived from animal sources, offers a potential off-the-shelf, scalable alternative. This review synthesizes the current preclinical and early clinical evidence on the efficacy and safety of xPRP for wound healing.
Methods: A systematic search was conducted in PubMed, Scopus, ScienceDirect, and Google Scholar up to July 2025, with no publication date restrictions, following PRISMA guidelines. Studies evaluating xPRP on wound healing outcomes in in vivo, in vitro, or ex vivo models were included. Two independent reviewers performed study selection, data extraction, and risk of bias assessment using the SYRCLE tool for animal studies and a modified QUIN tool for in vitro studies. Data were synthesized narratively due to heterogeneity.
Results: Eleven studies met the inclusion criteria, comprising ten animal and three in vitro investigations (two studies reported both components). Evidence from porcine, bovine, and deer xPRP sources consistently demonstrated significant improvements in wound closure rates, re-epithelialization, angiogenesis, and collagen deposition compared to saline controls. Porcine xPRP, for instance, accelerated wound closure by up to 45% over controls in diabetic rodent models. However, when compared to autologous PRP, xPRP generally showed slightly inferior, though still positive, outcomes. Immunogenic responses were minimal and localized, with no systemic adverse events reported. Risk of bias assessment revealed that while most studies had clear objectives, many were at high risk of bias due to a lack of randomization, allocation concealment, and blinded outcome assessment.
Conclusion: Xenogenic PRP demonstrates considerable promise as a bioactive therapeutic for wound healing, promoting key regenerative processes with a reassuring preliminary safety profile. However, the current evidence base is limited by methodological inconsistencies and a high risk of bias. Future research must prioritize standardized preparation protocols and methodologically rigorous, large-animal and human clinical trials to validate its translational potential
Nummular Dermatitis Masquerading as Recalcitrant Tinea Corporis: A Diagnostic Pitfall Resolved by Dermoscopy and Histopathology
Get PDFBackground: The morphological mimicry between nummular dermatitis (ND) and tinea corporis represents a significant source of diagnostic error in clinical practice. This convergence on a similar clinical phenotype—the annular plaque—often leads to inappropriate antifungal therapy and a protracted, debilitating course for the patient, as powerfully illustrated in this case.
Case presentation: We present the case of a 22-year-old female with a five-year history of chronic, recalcitrant, and intensely pruritic annular plaques on her lower legs, with a baseline pruritus score of 8/10 on a Visual Analog Scale (VAS). Previous treatments based on presumptive diagnoses, including potent topical corticosteroids and systemic antifungals, had failed. This report demonstrates a pivot from a morphology-based assessment to a multimodal diagnostic algorithm. The cornerstone of this shift was dermoscopy, which revealed patchy, irregularly distributed red dotted vessels—a classic signature of an eczematous process—and a notable absence of features suggestive of a dermatophyte infection. The diagnosis was confirmed by histopathology. A strong correlation between disease flares and psychosocial stressors was identified, and a holistic management plan targeting the cutaneous inflammation, the compromised skin barrier, and the neurogenic triggers led to a rapid and substantial improvement in her clinical status and quality of life, with the Dermatology Life Quality Index (DLQI) score decreasing from 9 to 3 and the pruritus VAS score dropping to 1/10.
Conclusion: This case argues for a revised diagnostic paradigm for chronic annular lesions, one that de-emphasizes ambiguous morphology and prioritizes the integration of a detailed psychodermatological history with in-vivo microscopic analysis via dermoscopy. This approach not only prevents therapeutic futility but also underscores that successful, long-term management of ND is contingent upon a patient-centered strategy that addresses the interconnectedness of the skin barrier, the immune system, and the psycho-neuro-cutaneous axis
The Hidden Hazard of Celebration: A Meta-Analysis of Ocular Morbidity from Colored Powder Festivals and Implications for Global Travel Medicine
Get PDFBackground: The globalization of colored powder festivals, such as Holi, has exposed millions, including international tourists, to significant ocular health risks from synthetic industrial dyes that have replaced traditional organic powders. This study was conducted to quantify the prevalence of acute ocular morbidities from these festivals, providing an evidence base to inform clinical practice and public health policy, particularly within travel medicine.
Methods: Following PRISMA guidelines, a systematic search was conducted in PubMed, Google Scholar, ScienceDirect, and ProQuest for observational studies published up to July 2024. Studies reporting ocular complications from colored powder exposure were included. Data were extracted by two independent reviewers, and methodological quality was assessed using JBI checklists. A random-effects model was used to calculate pooled prevalence for key ocular injuries. Heterogeneity was investigated using sensitivity analyses, and publication bias was assessed with funnel plots.
Results: Six studies from India, encompassing 189 patients, met the inclusion criteria for quantitative analysis. The patient population was predominantly young males (mean age 20-30 years). The meta-analysis revealed a high pooled prevalence of key ocular morbidities. The prevalence for chemical conjunctivitis was 95% (95% CI: 87%-100%), though with substantial but anticipated heterogeneity (I²=82%). The prevalence for corneal epithelial defects was 37% (95% CI: 23%-53%; I²=45%), and for superficial punctate keratopathy was 75% (95% CI: 57%-90%; I²=0%). Most injuries were bilateral.
Conclusion: Participation in colored powder festivals, based on extensive evidence from Holi in India, presents a quantifiable and significant risk of acute ocular morbidity. The high prevalence of chemical-induced ocular surface disease necessitates urgent recognition of this "hidden hazard." Proactive, evidence-based preventive strategies, including tiered recommendations for protective eyewear and updated pre-travel health advisories, are imperative to safeguard the vision of millions of celebrants worldwide