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Allogeneic human umbilical cord blood for acute ischemic stroke: Phase I clinical trial

Tzu Chi Med J. 2025 May 9;37(3):321-327. doi: 10.4103/tcmj.tcmj_249_24. eCollection 2025 Jul-Sep.

ABSTRACT

OBJECTIVES: Transplantation of human umbilical cord blood cells (hUCB) may enhance neuroprotection, and thus, the intravenous (IV) infusion of hUCB in patients with acute ischemic stroke (AIS) is being tested for its safety and efficacy.

MATERIALS AND METHODS: We conducted a 12-month, open-label, and single-center, phase I trial of hUCB treatment in AIS patients at the age of 45-80 years, with magnetic resonance imaging evidence of acute infarction in the internal carotid artery supplied territory and the National Institute of Health Stroke Scale (NIHSS) score between 6 and 18. Eligible participants received a single-dose IV infusion of hUCB followed by the two doses of mannitol infusion within 9 days after the onset of stroke symptoms. The primary endpoint was the incidence of adverse events (AEs) and the secondary endpoints were the changes in NIHSS, Barthel index (BI), and Berg Balance Scale (BBS) scores.

RESULTS: Six patients (Male: Female = 3: 3) were enrolled with a mean age at 65.8 years. A total of 40 AEs occurred in six participants during this study, which included nine serious adverse events. Only transient erythema multiforme and hematuria were probably and possibly related to hUCB infusion, respectively. The mean NIHSS score was 11.5 at baseline and it significantly improved at 1, 3, 6, 9, and 12 months after treatment (mean change from baseline: -4.0, -5.3, -6.8, -7.0, and -7.3). The mean BI score was 22.5 at baseline and it significantly increased at 3 and 6 months after treatment (mean change from baseline: 26.7 and 42.5, respectively). The BBS score increased numerically but did not reach statistical significance. The changes in cytokine levels and spleen size were unremarkable.

CONCLUSION: The IV hUCB was safe and well tolerated in AIS patients, and the preliminary efficacy results demonstrated its therapeutic potential, supporting the conduct of a randomized, placebo controlled, phase II clinical trial in future.

PMID:40741608 | PMC:PMC12306862 | DOI:10.4103/tcmj.tcmj_249_24

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Clinical Profile and Outcomes of Patients With Necrotizing Soft Tissue Infections: A Prospective Observational Study

Cureus. 2025 Jun 30;17(6):e87035. doi: 10.7759/cureus.87035. eCollection 2025 Jun.

ABSTRACT

INTRODUCTION: Necrotising soft tissue infection (NSTI) is uncommon, and its management is complex due to its diverse clinical presentations, multiple associated comorbidities, and a wide range of potential microbial aetiologies. This study aims to illustrate the clinical profile, microbiological spectrum, and factors affecting mortality among patients with NSTI.

METHODS: This single-centre, hospital-based, prospective observational study included all patients with NSTI aged 18 years or older. The primary outcome was the impact of time to surgery on mortality. Secondary outcomes included identifying the aetiology, microbiological flora, major co-morbidities, and overall outcomes in these patients. Results: During the study period, 87 patients were enrolled. There were 65 (74.7%) male and 22(25.3%) female patients with an age range of 18 years to 88 years. Postoperatively, 18 patients succumbed to death, while 69 survived. Overall, the average timing of the first intervention after admission was six hours, with no significant statistical difference between the survivor and non-survivor group (p-value = 0.575). Our study found types I and II infections in 26 (34.5%) and 45 (65.4%) patients, respectively, and Escherichia coli (E. coli) was the most common isolate in both types. The antibiotic resistance pattern revealed increased resistance to third-generation cephalosporins and fluoroquinolones for the Enterobacteriaceae group and E. coli.

CONCLUSION: High APACHE II and LRINEC scores, anaemia, hypoalbuminemia, and high creatinine are associated with a higher risk of death. Prompt multidisciplinary management of these patients significantly improves outcomes and reduces mortality.

PMID:40741589 | PMC:PMC12309787 | DOI:10.7759/cureus.87035

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Cardiovascular Toxicity Associated With Immune Checkpoint Inhibitors: Interpreting the Discrepancy Between Clinical Trials and Real-World Data

Cureus. 2025 Jun 30;17(6):e87049. doi: 10.7759/cureus.87049. eCollection 2025 Jun.

ABSTRACT

Real-world data on cardiovascular immune-related adverse events (CV-irAEs) in cancer patients treated with immune checkpoint inhibitors (ICIs) present findings that differ from those reported in meta-analyses of clinical trials. This study aims to estimate the incidence of CV-irAEs from observational studies among patients undergoing ICI therapy for various malignancies and investigate the discrepancy between the results of meta-analyses and observational studies. A systematic literature review and meta-analysis were conducted according to the Preferred Reporting Items for Systematic reviews and Meta-analyses (PRISMA) guidelines. The PubMed database was searched for observational studies that included cancer patients treated with ICIs. Α single-arm meta-analysis using the metaprop command in Stata Statistical Software: Release 16 (StataCorp LLC, College Station, Texas, United States) was performed for the following outcomes: myocarditis, pericardial disease, arrhythmias, cardiac failure, Takotsubo cardiomyopathy, ischemic heart disease, heart valve disease, venous thromboembolism and artery disease. ICI treatment agents were classified into three major classes: PD-1 inhibitors, PD-L1 inhibitors, CTLA4 inhibitors, or their combinations. Heterogeneity was quantified using the I2 statistic and small study effect, and potential publication bias was assessed by inspecting funnel plots, as well as by Egger’s test. A total of 42 studies were included. The incidence of CV-irAEs within the entire population undergoing treatment with ICIs was assessed as follows: total CV-irAEs: 8% (95% confidence interval (CI): 6%, 10%), arrhythmias: 18% (95%CI: 10%, 27%), myocarditis: 11% (95%CI: 5%, 18%), cardiac failure: 8% (95%CI: 2%, 15%), ischemic heart disease: 6% (95%CI: 3%, 11%), pericardial disease: 5% (95%CI: 1%, 10%), artery disease 5% (95%CI: 1%, 12%), and venous thromboembolism: 3% (95%CI: 0%, 8%); cardiomyopathy and heart valve disease had minimal number of observed episodes, thus the pooled incidence results are referring as zero, 0% (95%CI: 0%, 0%) and total CV deaths: 1% (95%CI: 0%, 3%). Median time to CV-irAEs was estimated at 119 days (interquartile range (IQR) 53-180). The most common CV-irAEs were arrhythmias, myocarditis, and cardiac failure with life-threatening complications. Data derived from meta-analyses of clinical trials in most cases indicated that the total incidence of CV-irAEs varied between 0.05% and 1.30%, while in large pharmacovigilance databases, it ranged from 0.125% to 6.7%. In our meta-analysis of post-market surveillance studies, higher estimates were obtained, which offer an insight into the long-term prevalence and outcomes for patients experiencing CV complications associated with ICIs. Longer follow-up period and different definitions of cardiotoxicity may account for the higher cardiotoxicity rates that seem to reflect an emerging threat.

PMID:40741581 | PMC:PMC12310155 | DOI:10.7759/cureus.87049

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Combined Intramedullary Nailing and Interfragmentary Screws in Distal Tibial Fractures With Articular Extension

Cureus. 2025 Jun 30;17(6):e87033. doi: 10.7759/cureus.87033. eCollection 2025 Jun.

ABSTRACT

The treatment of distal tibial fractures with an articular fracture line remains controversial. Intramedullary nailing allows for the maintenance of good frontal and sagittal alignment, as well as rapid and satisfactory functional recovery. In this retrospective case series, we present our department’s experience with 20 patients presenting with AO 43C1 and 43C2 fractures, treated with intramedullary nailing combined with interfragmentary screw fixation over an eight-year period, with a follow-up of 18 months. Postoperative alignment was assessed using radiographic measurements of the anterior distal tibial angle (ADTA) and lateral distal tibial angle (LDTA), immediately and at follow-up. Functional outcomes were evaluated using the American Orthopaedic Foot and Ankle Society (AOFAS) score. Descriptive statistical analysis was used to report means, standard deviations, and proportions. Acceptable alignment was achieved in 95% of patients. The AOFAS score exceeded 86% in 88% of patients, indicating excellent outcomes. Interfragmentary screw fixation prior to nailing improved construct stability, minimized malalignment risk, and enhanced functional recovery.

PMID:40741563 | PMC:PMC12309624 | DOI:10.7759/cureus.87033

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Diagnostic Value of Exercise Stress Testing Combined With Beta-Blocker Therapy (Metoprolol) in Hypertensive Patients With Suspected Coronary Artery Disease

Cureus. 2025 Jun 30;17(6):e87041. doi: 10.7759/cureus.87041. eCollection 2025 Jun.

ABSTRACT

BACKGROUND: Hypertension is a prevalent risk factor for coronary artery disease (CAD), and early diagnosis is critical for preventing adverse cardiovascular events. While exercise stress testing (EST) is a common non-invasive tool, its diagnostic performance in hypertensive individuals, especially when combined with beta-blocker therapy, remains under-evaluated. The beta-blocker metoprolol may enhance diagnostic accuracy in this population.

OBJECTIVE: This study aimed to evaluate the diagnostic value of EST combined with metoprolol therapy in hypertensive patients with suspected CAD.

METHODOLOGY: This prospective, hospital-based controlled diagnostic study was conducted at the Department of Cardiology, Abbas Institute of Medical Science (AIMS), Muzaffarabad, Azad Jammu and Kashmir (AJK), from January 2023 to December 2024. A total of 224 hypertensive patients aged between 30 and 70 years with clinical suspicion of CAD (based on anginal symptoms, ECG changes, or physician judgment) were enrolled. Patients with a known history of CAD, contraindications to exercise or beta-blockers, or current beta-blocker use were excluded. All participants received a single oral dose of 50 mg metoprolol tartrate one hour prior to EST, performed using the Bruce protocol. Adverse effects and hemodynamic responses were monitored. A positive EST was defined by ischemic ECG changes, anginal symptoms, or abnormal blood pressure response. All patients underwent confirmatory testing with either coronary angiography or myocardial perfusion imaging (MPI), depending on clinical indication. Diagnostic metrics, including sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV), were calculated using confirmed CAD status as the gold standard. Confidence intervals were calculated to assess the precision of diagnostic estimates. Data were analyzed using IBM SPSS Statistics software, version 25.0 (IBM Corp., Armonk, NY), with categorical variables reported as frequencies and percentages, continuous variables as mean ± SD, and diagnostic accuracy of EST with metoprolol evaluated against confirmed CAD using sensitivity, specificity, PPV, NPV, and chi-square test (p < 0.05).

RESULTS: Out of 224 patients, 138 (61.61%) had a negative EST and 86 (38.39%) had a positive result. CAD was confirmed in 94 patients (41.96%). Of the 86 patients with a positive EST, 68 (79.07%) had confirmed CAD. Among the 138 patients with a negative EST, 26 (18.84%) were found to have CAD. The combination of EST and metoprolol demonstrated a diagnostic sensitivity of 72.34%, specificity of 86.15%, PPV of 79.07%, NPV of 81.16%, and an overall diagnostic accuracy of 80.36%.

CONCLUSION: In hypertensive patients with suspected CAD, combining EST with metoprolol provides a viable and non-invasive diagnostic strategy, offering high specificity and PPV despite moderate sensitivity.

PMID:40741561 | PMC:PMC12309863 | DOI:10.7759/cureus.87041

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Prevalence of Mouse Mammary Tumor Virus-Like Virus in Breast Milk and Associated Factors of Exposure Among Healthy Nursing Women in Morocco

Cureus. 2025 Jun 30;17(6):e87047. doi: 10.7759/cureus.87047. eCollection 2025 Jun.

ABSTRACT

BACKGROUND: The mouse mammary tumor virus (MMTV) has been identified as potentially oncogenic, and its presence in milk was reported and discussed. However, with respect to breast cancer etiology, the transmission routes for these viruses are not known. In this context, the objective of this study is to assess the presence of MMTV-like virus in breast milk and to explore the associated factors of its presence among healthy lactating women in Morocco.

METHODS: In this prospective study, milk samples were collected from 44 lactating women recruited from the Souissi Maternity Hospital of Rabat in Morocco. MMTV-like DNA was identified by polymerase chain reaction amplification using specific primers targeting the env gene.

RESULTS: The prevalence of the MMTV-like virus was 45.5% (20/44). Statistical analysis revealed a significant association with the use of henna. It seems that it increases the risk of the presence of MMTV-like virus in breast milk. The hypothesis could be the possible contamination of henna sold in bulk in local markets by urine and feces of mice during storage.

CONCLUSION: Nevertheless, these results need to be confirmed by multicenter studies to thoroughly investigate the impact of other factors and the potential contamination of henna with the virus through urine and feces of mice during storage.

PMID:40741558 | PMC:PMC12310077 | DOI:10.7759/cureus.87047

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Impact of Simulation-Based Medical Education on Pre-clerkship Medical Students’ Confidence in Key Areas of Clinical Competence: An Exploratory Pre- and Post-survey Study

Cureus. 2025 Jun 30;17(6):e87059. doi: 10.7759/cureus.87059. eCollection 2025 Jun.

ABSTRACT

Background Medical education is adapting to meet the growing demands of healthcare and patient care complexities. Traditional clinical training often relies on limited patient encounters, which may not fully develop clinical competence. Simulation-based medical education (SBME) offers controlled, immersive environments for practicing clinical skills and decision-making without risking patient safety. While SBME has been well-studied in advanced training, its effectiveness in first- and second-year medical students remains underexplored. This study aims to explore and quantify pre-clerkship medical students’ perspectives on how SBME impacts confidence in clinical decision-making, communication, and clinical skills, compared to traditional learning methods alone. Methods This pre- and post-survey-based study assessed the impact of simulation (SIM) on students’ self-reported confidence in clinical decision-making, communication, and clinical skills. Six simulation scenarios that aligned with the undergraduate medical curriculum of one Canadian institution were conducted from October 2023 to March 2024. Participants completed pre- and post-simulation surveys using 5-point Likert scales. A total of 67 surveys were analyzed. Results All 67 surveys were analyzed (35 pre-, 32 post-simulation) using one-sided Wilcoxon Signed Rank Tests. Pre-simulation responses indicated low baseline confidence, with only one item rated above neutrality. Post-simulation ratings showed statistically significant improvements across all domains (p < 0.01). Students also reported that they perceived simulation as more effective than traditional didactic learning in preparing them for clinical practice. Conclusions This exploratory study suggests that simulation-based education can enhance pre-clerkship students’ confidence in clinical decision-making, communication, and procedural skills, domains often underdeveloped at this stage of training. These findings offer early evidence that high-fidelity simulation may accelerate perceived clinical readiness. However, due to the small, self-selected sample, non-parallel survey design, and reliance on subjective outcomes, results should be treated as exploratory. Further multi-site studies using objective measures are needed to assess long-term impact on knowledge and skill retention as well as clinical performance.

PMID:40741557 | PMC:PMC12310303 | DOI:10.7759/cureus.87059

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The Impact of Biological Sex, Medical School Background, and Geographic Location on Diversity in U.S. Neurosurgery Residency Programs

Cureus. 2025 Jun 30;17(6):e87051. doi: 10.7759/cureus.87051. eCollection 2025 Jun.

ABSTRACT

Background Following an analysis of the National Residency Matching Program statistics, it was found that there is a ratio of 1:1.75 of candidates matching into a neurosurgical residency. The population of students accepted into neurosurgery residency programs appears less diverse compared to other surgical specialties. The objective of this descriptive, observational study is to examine the current trends among students accepted into neurosurgical residency programs and increase exposure to a more diverse demographic within the field of neurosurgery. Methodology A bibliometric analysis of neurosurgical residents across U.S. neurosurgical programs was conducted from 2017 to 2024. Data were collected from the Fellowship and Residency Electronic Interactive Database and residency websites between January and March 2024. Data were further divided into postgraduate years, biological sex, and medical degree. Results A total of 1,608 neurosurgical residents from 116 residency programs were identified. A decreasing trend in osteopathic residents was found from 4.29% of residents graduating in 2025 to 2.12% graduating in 2031. A steady trend was discovered in the percentage of women residents, increasing from 23.33% for residents graduating in 2025 to 30.51% for those graduating in 2031. The highest percentage of osteopathic residents in neurosurgery programs was found in the West Pacific area (8.3%, n = 17), the second highest in the Middle Atlantic (7.8%, n = 26), and the third highest in the West South Central (6.7%, n = 13). The highest percentage of female residents was found in the New England area (37.1%, n = 47), the second highest in the Pacific region (34.1%, n = 68), and the third highest in the South Atlantic (24.7%, n = 80). Conclusions The number of osteopathic residents in neurosurgery programs suggests a potential decline, which could be attributed to geographical, academic, and other factors. The number of female residents suggests a gradual increase; however, future steps toward addressing the gender disparities should be taken.

PMID:40741555 | PMC:PMC12310153 | DOI:10.7759/cureus.87051

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Clinico-Epidemiological Profile of Dengue in Children of Age Group 0-14 Years Admitted in a Tertiary Care Hospital

Cureus. 2025 Jun 30;17(6):e87027. doi: 10.7759/cureus.87027. eCollection 2025 Jun.

ABSTRACT

Background Dengue has emerged as the most common arboviral infection in India and worldwide. Dengue presents with a varied clinical spectrum in different age groups. The changing epidemiology and presentation are a challenge for early diagnosis and management. This prospective observational study aimed to determine the epidemiological profile of hospitalized dengue-positive children aged 0-14 years and correlate their clinical and hematological profiles. Methodology One hundred and five children with laboratory-confirmed dengue were enrolled in this study over a six-month study period. They were categorized into severe and non-severe dengue according to the World Health Organization (WHO) classification. Detailed clinical examination and laboratory investigations, including complete blood count, liver enzymes, coagulation profile, and imaging (chest X-ray and abdominal ultrasound), were performed. Data were analyzed using descriptive statistics, chi-square test, and logistic regression analysis. Results Out of the total 105 cases, 90 children (85.7%) had non-severe dengue and only 15 (14.3%) had severe dengue. The mean age of children was 92.02 months, with a male predominance (72, 68.6%). The most commonly identified symptoms were fever (105, 100%), vomiting (47, 44.76%), and abdominal pain (46, 43.81%). It was found that although thrombocytopenia was seen in 79 children (75.2%), it was not significantly associated with the severity of the disease (P = 0.2364). The study found a high recovery rate (101, 96.3%) with a mortality of 3 patients (2.8%) in severe cases. Elevated serum glutamate pyruvate transaminase (SGPT) levels (P = 0.0025), pleural effusion on chest X-ray (P = 0.000452), abdominal pain (P = 0.0041), and a positive tourniquet test (P < 0.0001) were found to be significantly associated with severe dengue. Non-structural protein 1 (NS1) antigen and immunoglobulin M (IgM) antibodies were both found to be positive more frequently in severe cases compared to non-severe cases (P = 0.0361). Conclusions This study observed a high rate of recovery and low mortality, owing to the timely management. A possible shift in the seasonal distribution of dengue was observed, with many cases occurring in the winter season. While thrombocytopenia was prevalent, it was not found to be significantly associated with disease severity or bleeding. On the other hand, elevated liver enzymes, pleural effusion, abdominal pain, and a positive tourniquet test were found to be more strongly associated with severe dengue. They may serve as valuable early clinical indicators for the severity of the disease.

PMID:40741554 | PMC:PMC12309428 | DOI:10.7759/cureus.87027

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Application of spectral characteristics of electrocardiogram signals in sleep apnea

Front Bioeng Biotechnol. 2025 Jul 16;13:1636011. doi: 10.3389/fbioe.2025.1636011. eCollection 2025.

ABSTRACT

BACKGROUND: Electrocardiogram (ECG) signals contain cardiopulmonary information that can facilitate sleep apnea detection. Traditional methods rely on extracting numerous ECG features, which is labor-intensive and computationally cumbersome.

METHODS: To reduce feature complexity and enhance detection accuracy, we propose a spectral feature-based approach using single-lead ECG signals. First, the ECG signal is preprocessed via ensemble empirical mode decomposition combined with independent component analysis (EEMD-ICA) to identify the most representative intrinsic mode function (IMF) based on the maximum instantaneous frequency in the frequency domain. Next, Hilbert transform-based time-frequency analysis is applied to derive the component’s 2D time-frequency spectrum. Finally, three spectral features-maximum instantaneous frequency (femax), instantaneous frequency amplitude (V), and marginal spectrum energy (S)-are quantitatively compared between normal and sleep apnea populations using an independent-sample t-test. These features are classified via a random forest machine learning model.

RESULTS: The femax and IMF7 components of the reconstructed signal exhibited statistically significant differences (p < 0.001) between normal and sleep apnea subjects. The random forest classifier achieved optimal performance, with 92.9% accuracy, 86.6% specificity, and 100% sensitivity.

CONCLUSION: This study demonstrates that spectral features derived from single-lead ECG signals, combined with EEMD-ICA and time-frequency analysis, offer an efficient and accurate method for sleep apnea detection.

PMID:40741538 | PMC:PMC12307459 | DOI:10.3389/fbioe.2025.1636011