Medical sciences (Basel, Switzerland)最新文献

Influenza has long been a well-documented contributor to cardiovascular morbidity and mortality, particularly among high-risk groups. COVID-19 has notably altered the seasonality and natural history of pandemic influenza, with broad implications for related cardiac complications. This review examines the interaction between influenza and cardiovascular illness, especially myocardial infarction, congestive heart failure, stroke, and other acute cardiac events. We review the impact of the COVID-19 pandemic on influenza transmission dynamics, public health policy, and the evolving burden of cardiovascular complications. New evidence indicates that both diseases exacerbate endothelial dysfunction, systemic inflammation, and prothrombotic states, thereby increasing cardiovascular risk. A comparative analysis of pre- and post-COVID-19 influenza-related cardiac complications clarifies evolving trends and guides future preventive strategies. In light of the recent resurgence of influenza following the relaxation of COVID-19 mitigation measures, maximizing vaccine coverage and collaborating to manage viral infections in patients with cardiovascular disease are critical. This review focuses on key research needs to understand long-term cardiac consequences and the urgent requirement for targeted public health strategies to counter viral-mediated cardiovascular threats. In the post-COVID era, integrating influenza and COVID-19 vaccination strategies into cardiovascular risk management may represent a critical opportunity to reduce virus-triggered cardiovascular morbidity and mortality.

Cancer remains a significant global health burden despite advances in diagnosis and treatment. In recent years, drug repurposing has emerged as a promising strategy in oncology, offering reduced costs and shorter development timelines compared with de novo drug discovery. Among repurposed agents, the antifungal drug itraconazole has demonstrated anticancer activity across multiple tumor types, particularly when used in combination with other therapeutic modalities. In this review, we summarize current preclinical and clinical evidence supporting the use of itraconazole in cancer therapy, with a specific focus on its combination with chemotherapeutic agents and programmed cell death protein 1 (PD-1) immune checkpoint inhibitors. We highlight proposed mechanisms underlying this synergy, including modulation of tumor metabolism, angiogenesis, and immune signaling pathways. Additionally, we discuss key challenges and limitations, such as drug-drug interactions and toxicity considerations, that must be addressed to optimize clinical translation. Overall, the combination of itraconazole with chemotherapy or anti-PD-1 therapy represents a promising therapeutic strategy warranting further investigation in well-designed trials.

Background: Pain neuroscience education (PNE) can support understanding of low back pain and facilitate engagement with active care. Most PNE materials have been developed in English, and there is little culturally adapted content for Urdu-speaking populations. Locally relevant educational resources may help improve clarity, acceptability, and communication in clinical settings. Objective: To develop, culturally adapt, and content-validate Urdu PNE materials for individuals with LBP and for use by healthcare professionals in Pakistan. Methods: A four-stage adaptation process was used. Phase 1 involved drafting a ten-module English PNE booklet and clinician guide based on contemporary pain-science literature. Phase 2 included forward-backward translation into Urdu and cultural adaptation by translators and a bilingual pain researcher. In Phase 3, three focus-group sessions with clinicians and a person with LBP informed iterative revisions. In Phase 4, a multidisciplinary panel (clinicians and individuals with LBP, n = 32) assessed seven domains of the final Urdu materials for clarity, relevance, and cultural appropriateness using Lawshe's content validity ratio (CVR). Results: Focus-group feedback led to simplification of Urdu phrasing, refinement of metaphors, and adjustments to illustrations. All seven domains exceeded the minimum CVR threshold (0.30) for n = 32, with a mean overall CVR of 0.69 ± 0.12. Cultural appropriateness (CVR = 0.88) and content accuracy (CVR = 0.86) showed the highest agreement. Conclusions: The adapted Urdu PNE materials were judged to be clear, relevant, and culturally appropriate by clinicians and individuals with LBP. These materials may be useful for supporting pain-related education in clinical and community settings. These findings establish preliminary content validity; further studies are needed to evaluate feasibility, implementation, and clinical outcomes.

Background/Objectives: Emergency medical services (EMSs) are essential for reducing mortality among critically ill patients. This study aims to evaluate the influence of temporal factors, such as time of day, day of the week, month, and year, on mortality in EMS activations, comparing health systems in the U.S. and Spain. Methods: This multicenter observational study, which is based on two databases (Spain's Sacyl and the U.S.'s NEMSIS), analyzed EMS activation in high-priority adult patients (>18 years) between 2018 and 2023. Demographic variables, transport characteristics, and response times were included. Short-term mortality was the primary outcome. Results: A total of 54,981 EMS activations (11,713 from the Sacyl dataset and 43,268 from the NEMSIS dataset) were analyzed. Mortality was higher among older patients and males, with significant increases during shifts from 06:00 to 12:00 and from 18:00 to 24:00. Mortality also varied by year, with higher rates in 2022 and 2023 than in 2018. Notable differences were observed between the U.S. and Spain, especially in shifts and months, with higher mortality during the 12:00 to 18:00 shift and in October in the NEMSIS cohort. Conclusions: These findings have direct implications for emergency medical service operations, suggesting that resource allocation, staffing models, and clinical protocols should be strategically optimized based on temporal risk patterns to improve patient outcomes during identified high-risk periods.

Oxidative stress (OS) is a critical regulator of placental development; however, its specific effects on trophoblast biology remain incompletely elucidated. This narrative review synthesizes evidence derived from studies using human placental tissues and trophoblast cell models to delineate how excessive reactive oxygen species (ROS) disrupt molecular and cellular pathways essential for normal placentation. The literature search was restricted to human-based and in vitro investigations. Across these studies, OS was consistently shown to impair mitochondrial function in trophoblasts, resulting in increased mitochondrial ROS generation, loss of mitochondrial membrane potential, and activation of apoptotic signaling cascades. These mitochondrial disturbances were associated with reduced trophoblast proliferation, migration, and invasion, as well as dysregulation of angiogenic balance. Furthermore, several studies reported alterations in mitophagy, involvement of redox-sensitive pathways such as CYP1A1 and KLF9, and the extracellular release of mitochondrial DNA, which was linked to reduced cell viability and increased necrotic cell death. Collectively, the available evidence indicates that OS interferes with key trophoblast-dependent developmental processes, providing mechanistic insight into the pathogenesis of placental dysfunction observed in pregnancy complications such as preeclampsia (PE) and intrauterine growth restriction (IUGR). Elucidation of these pathways may inform the development of targeted therapeutic strategies aimed at preserving placental function and improving adverse pregnancy outcomes.

Background/Objectives: Type 2 diabetes mellitus (T2DM) significantly elevates the risk of coronary artery disease (CAD), particularly in Asian populations where both conditions are epidemic. While shared genetic factors contribute to this comorbidity, evidence from Asian cohorts remains fragmented, with limited focus on population-specific variants. This meta-analysis synthesizes evidence on genetic variants associated with CAD risk in Asian patients with T2DM. Methods: We systematically searched several databases according to the PRISMA statement and checklist. Pooled odds ratios (ORs) with corresponding 95% confidence intervals (CIs) were calculated using random-effects models, with heterogeneity assessed via I² and Cochran's Q, and publication bias via funnel plots and Egger's test. Results: In total, data on 11,268 subjects were reviewed, including 4668 cases and 6600 controls. Among 950 identified studies, 18 met eligibility criteria, and 14 studies provided sufficient data for the meta-analysis. The random-effects pooled estimate across all studied variants was not statistically significant (OR = 1.16 [95% CI: 0.68-2.00]; z = 0.56, p = 0.58). However, analysis of individual loci revealed gene-specific associations with CAD among this population: PCSK1 gene (OR = 2.12 [95% CI: 1.26-3.52]; p < 0.05; weight = 8.77%), GLP1R gene (OR = 2.25 [95% CI: 1.27-3.97]; p < 0.01; weight = 8.62%). ADIPOQ gene (OR = 8.00 [95% CI: 2.34-27.14]; p < 0.01; weight = 6.35%). Several genes were associated with an elevated risk of CAD: PCSK1 gene (OR = 2.12 [95% CI: 1.26-3.52]; p < 0.05; weight = 8.77%), GLP1R gene (OR = 2.25 [95% CI: 1.27-3.97]; p < 0.01; weight = 8.62%) and ADIPOQ gene (OR = 8.00 [95% CI: 2.34-27.14]; p < 0.01; weight = 6.35%). Several genes were associated with possible protective effects: ACE gene (OR = 0.41 [95% CI: 0.23-0.73]; p < 0.01; weight = 8.57%), Q192R gene (OR = 0.20 [95% CI: 0.08-0.52]; p < 0.001; weight = 7.41%). Heterogeneity was substantial (τ² = 0.78; I² = 81.95%; Q (13) = 64.67, p < 0.001). Conclusions: This first meta-analysis of genetic variants associated with CAD in Asian populations with T2DM identified specific locus-level associations implicating lipid metabolism, incretin signaling, and oxidative stress pathways. The lack of a significant pooled effect, alongside high heterogeneity, underscores the complexity and population-specific nature of this genetic architecture. These findings suggest that effective precision risk stratification may depend more on specific variants than on a broad polygenic signal, highlighting the need for further research in a larger, distinct sample size.

Background: Quantitative flow ratio (QFR) is a novel technology to assess the functional significance of coronary stenoses based on standard coronary angiography, which can be alternatives to invasive fractional flow reserve (FFR) assessment. However, the evidence is limited to single-center studies and small sample sizes. This study systematically determined the diagnostic performance of QFR to diagnose functionally significant stenosis with FFR as the reference standard. Methods: A systematic review and meta-analysis of studies assessing the diagnostic performance of angiography-derived QFR systems were performed. All relevant studies from six literature databases were searched and screened according to the inclusion and exclusion criteria. The pooled sensitivity, specificity, positive likelihood ratio (LR+), negative likelihood ratio (LR-), and diagnostic odds ratio (DOR), along with their 95% confidence intervals (CIs), were calculated using DerSimonian-Laird methodology. The summary receiver operating characteristic (SROC) curve and area under the curve were estimated. Meta-regression analysis was performed to identify a potential source of heterogeneity. Results: Fifty-seven studies comprising 13,215 patients and 16,125 vessels were included in the final analysis. At the vessel level, the pooled sensitivity and specificity of QFR for detecting a significant coronary stenosis were 0.826 (95% CI: 0.798-0.851) and 0.919 (95% CI: 0.902-0.933). Pooled LR+ and LR- were 10.198 (95% CI: 8.469-12.281) and 0.189 (95% CI: 0.163-0.219), with a pooled DOR of 53.968 (95% CI: 42.888-67.910). The SROC revealed an area under the curve (AUC) of 0.94 (95% CI: 0.91-0.96). The summary AUCs were 0.90 (95% CI: 0.87-0.92) for fixed-flow QFR (fQFR), 0.95 (95% CI: 0.92-0.96) for contrast-flow QFR (cQFR), 0.97 (95% CI: 0.95-0.98) for Murray law-based QFR (μQFR), and 0.91 (95% CI: 0.89-0.94) for non-specified QFR. The adjusted pooled DORs were as follows: 126.25 for μQFR, 45.49 for cQFR, 26.12 for adenosine-flow QFR (aQFR), 25.88 for fQFR, and 36.54 for non-specified QFR. Conclusions: The accuracy of angiography-derived QFR was strong to assess the functional significance of coronary stenoses with FFR as a reference. μQFR demonstrated the highest diagnostic performance among the five evaluated modes.

Background: Rate-dependent depression of the Hoffmann reflex (RDD-HR) is a neurophysiological marker of spinal inhibition altered in several neurological conditions, yet no consensus exists on optimal stimulation frequency, number of stimuli, or the feasibility of upper limb recordings. This study aimed to define practical, standardized parameters for reliable RDD-HR assessment in upper and lower limbs of healthy adults, as a first step toward clinical application. Methods: In this observational study, bilateral Hoffmann reflexes were recorded from the flexor carpi radialis and soleus muscles in 21 healthy adults. Stimulation was delivered using three 10-pulse trains at seven frequencies (0.1-5 Hz). RDD-HR was quantified as the median H-reflex area, expressed as a percentage of the first response (lower values indicate greater depression). Optimal frequencies and minimal stimuli were identified by sigmoid fitting and confidence analyses, with train and stimulus effects tested by two-way ANOVA. Results: RDD-HR displayed a sigmoidal frequency-response across all limbs. Maximal depression occurred at 1-5 Hz, with no significant differences between these frequencies, supporting 1 Hz as optimal. Depression was greater in lower limbs (~30%) than upper limbs (~47%). Reliable estimates were obtained using a single train of seven stimuli, with no benefit from averaging across trains. Upper limb recordings required lower stimulation intensities. Conclusions: RDD-HR can be reliably assessed using a simplified protocol based on a single seven-pulse train at two key frequencies. This standardized approach provides a methodological foundation for future clinical validation of RDD-HR as a biomarker of spinal inhibitory dysfunction.

Background/Objectives: Acute ischemic stroke (AIS) associated with cervical carotid artery pathology remains a therapeutic challenge due to uncertainty regarding emergent carotid artery stenting (eCAS) and the need for intensified antithrombotic therapy, which may increase the risk of hemorrhagic transformation (HT). This retrospective cohort study evaluated the functional and safety outcomes of eCAS within an extended treatment time window. Methods: We analyzed 139 consecutive patients with anterior circulation AIS and large vessel occlusion treated with mechanical thrombectomy between 2019 and 2024. Patients were eligible for MT within 24 h based on clinical-core mismatch (DAWN) or perfusion-core mismatch (DEFUSE 3) criteria. Outcomes were compared between patients treated with eCAS and those undergoing MT without stenting. Results: Twenty-five patients underwent eCAS, predominantly for tandem lesions (80%). Median age was 66 years, median baseline NIHSS was 14, and median infarct core volume on DWI/CTP was 15 mL. Baseline characteristics were comparable between groups, except for the site of occlusion (p < 0.001). A good functional outcome (modified Rankin Scale, mRS 0-2 at 90 days) was observed in 60% of patients in the eCAS group versus 43% in the non-stenting group, without statistical significance (p = 0.067). Rates of parenchymal hematoma (12% vs. 18.4%) and symptomatic intracerebral hemorrhage (8% vs. 3.5%) were similar between groups. Conclusions: In this single-center cohort, eCAS performed in an extended time window did not demonstrate a clear signal of increased hemorrhagic risk. However, residual confounding and imbalance between treatment groups persisted despite the application of inverse probability weighting (IPW), and the findings should be interpreted cautiously.

Background/objective: The rising prevalence of Type 2 Diabetes Mellitus (T2DM), coupled with sedentary behavior and an increase in obesity rates in South Asian countries, calls for effective management strategies. We aimed to assess the efficacy of lifestyle interventions on glycemic control among adults with T2DM in South Asian countries.

Methods: A systematic review and meta-analysis of randomized controlled trials (RCTs) were conducted to assess the effectiveness of lifestyle interventions on glycemic control in adults diagnosed with T2DM in South Asia. We conducted a comprehensive search in CINAHL, Embase, PubMed, Cochrane Library, Web of Science (WoS), and Scopus to identify related studies published from 2000 to 13 June 2024. We assessed the risk of bias using the ROB 2.0 tool and calculated the pooled mean differences in HbA1c and FBG levels under a random-effects model. We conducted subgroup and leave-one-out sensitivity analyses to assess and explore sources of heterogeneity. PROSPERO Registration: CRD42024552286.

Results: We included 16 RCTs with a total of 1499 participants. Lifestyle interventions reduced HbA1c levels by 0.86% (95% CI: -1.30 to -0.42, p < 0.01) and FBG levels by 22.49 mg/dL (95% CI: -32.88 to -12.10, p < 0.01). We observed substantial heterogeneity (I² = 98% for HbA1c and I² = 87% for FBG). Subgroup analyses indicated larger HbA1c reductions in long-term (-1.44%) than short-term trials (-0.62%), and greater FBG decreases in long-term (-23.7 mg/dL) versus short-term studies (-22.5 mg/dL). Physical activity interventions had the largest improvements (HbA1c -0.99%; FBG -26.1 mg/dL), followed by dietary (HbA1c -0.59%; FBG -15.8 mg/dL) and combined programs (HbA1c -0.55%). Participants aged >50 years achieved greater glycemic improvements (HbA1c -0.92%; FBG -24.0 mg/dL) compared to younger adults (HbA1c -0.60%; FBG -21.3 mg/dL). Despite high heterogeneity, sensitivity analyses confirmed the robustness of the overall findings.

Conclusions: Lifestyle modifications yielded a clinically significant reduction in HbA1c and FBG in adults with T2DM in South Asia. Although heterogeneity of the included studies was substantial, the direction of the effects was uniformly consistent across subgroups. To further validate these findings and assess their long-term effects, large-scale and standardized RCTs conducted for longer durations are necessary.