Category: Nevin Manimala

Drugs R D. 2025 May 23. doi: 10.1007/s40268-025-00510-z. Online ahead of print.

ABSTRACT

BACKGROUND AND OBJECTIVES: During the coronavirus disease-2019 (COVID-19) pandemic there was the uncertainty that the long-term immune response generated upon natural infection or triggered by available severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) vaccines could impact the clinical endpoints of ongoing clinical trials, in particular, whether the immunogenicity of biotherapeutics could be affected.

METHODS: Here, we describe the different stages to build an adequate COVID-19 serology testing strategy to ultimately assess whether the presence of anti-SARS-CoV-2 antibodies could impact the immunogenicity data of a clinical trial supporting the approval of GP2411 (Jubbonti^®/Wyost^®; a denosumab biosimilar to Prolia/XGeva) conducted during the pandemic. We first assessed the sensitivity and specificity of US Food and Drug Administration Emergency Use Authorization (FDA EUA)-approved commercial SARS-CoV-2 anti-IgG enzyme-linked immunosorbent (ELISA) assay. Then, we validated the assay in accordance with bioanalytical guidelines and demonstrated that the analysis of validation parameters as singlicates met all bioanalytical acceptance criteria and showed comparable results to those of duplicate analyses. Lastly, we report data on anti-SARS-CoV-2 IgG antibody responses in healthy participants treated with a single dose of a biotherapeutic.

RESULTS: SARS-CoV-2 serology was assessed in 1970 serum samples collected from 499 healthy participants who were dosed throughout a clinical study that was conducted during the COVID-19 pandemic. Anti-SARS-CoV-2 IgG antibodies triggered by natural infection and/or vaccination were detected in 1165 serum samples from 82% of the study participants. Anti-SARS-COV-2 IgG responses were of comparable magnitude in study participants who were vaccinated during the course of the study or had a confirmed COVID-19 infection. A total of 6408 serum samples from the same study were evaluated for the presence of anti-drug antibodies (ADAs), with 64% of the participants being positive. Independent of the presence of anti-SARS-CoV-2 IgG antibodies, all ADA-positive study participants showed ADAs of very low magnitude. Neutralizing ADAs were detected in less than 1% of study participants without an association to anti-SARS-CoV-2 IgG responses.

CONCLUSIONS: The established bioanalytical strategy allowed the reliable detection of COVID-19 adaptive responses in study participants. The development of anti-SARS-CoV-2 IgG responses (triggered by either a natural infection or a vaccine) did not have any clinically meaningful impact on the immunogenicity of the biotherapeutic administered in the study.

PMID:40408051 | DOI:10.1007/s40268-025-00510-z

Discov Oncol. 2025 May 23;16(1):877. doi: 10.1007/s12672-025-02618-9.

ABSTRACT

BACKGROUND: Dysbiosis of the gut microbiota (GM) has been reported to be associated with cancers, including bladder cancer (BLCA). However, the specific causal relationship between GM and BLCA, as well as the mediating role of circulating metabolic biomarkers (CMBs), has remained unclear. Therefore, we aimed to elucidate the causal relationship among GM, CMBs, and BLCA, through a mendelian randomization (MR) approach.

METHOD: The summary statistics of 473 GM (n = 5959) and 233 CMBs (n = 136,016) from the NHGRI-EBI GWAS Catalog, and BLCA (cases n = 2053 and controls n = 287,137) from the FinnGen study were leveraged for our research. Bidirectional MR analysis was conducted to investigate the causal link between GM and BLCA, and two-step MR (TSMR) was employed to identified potential mediating CMBs. The inverse-variance weighted (IVW) was primarily utilized for effect estimation. Additionally, the Cochrane’s Q test was used to evaluate heterogeneity, and the MR-Egger method was employed to evaluate pleiotropy.

RESULT: The study revealed that 15 GM and 12 CMBs were causally associated with BLCA (p < 0.05). Specially, dorea was found to significantly increase the risk of developing BLCA (OR = 2.20, 95% CI: 1.29-3.75). Furthermore, TSMR analysis indicated that total cholesterol levels in small HDL and cholesterol esters in small HDL mediate the causal relationship between dorea and BLCA, with mediated proportions of 2.46% and 2.14%, respectively.

CONCLUSION: The findings of this study provide compelling evidence supporting the mediating role of CMBs in the causal relationship on GM and BLCA.

PMID:40408003 | DOI:10.1007/s12672-025-02618-9

Lifetime Data Anal. 2025 May 23. doi: 10.1007/s10985-025-09656-z. Online ahead of print.

ABSTRACT

To investigate pairwise interactions arising from recurrent event processes in a longitudinal network, the framework of the stochastic block model is followed, where every node belongs to a latent group and interactions between node pairs from two specified groups follow a conditional nonhomogeneous Poisson process. Our focus lies on discrete observation times, which are commonly encountered in reality for cost-saving purposes. The variational EM algorithm and variational maximum likelihood estimation are applied for statistical inference. A specific method based on the defined distribution function F and self-consistency algorithm for recurrent events is used when estimating the intensity functions of edges. Numerical simulations illustrate the performance of our proposed estimation procedure in uncovering the underlying structure in the longitudinal networks with recurrent event processes. The dataset of interactions between French schoolchildren for influenza monitoring is analyzed.

PMID:40407998 | DOI:10.1007/s10985-025-09656-z

Obes Surg. 2025 May 23. doi: 10.1007/s11695-025-07917-2. Online ahead of print.

ABSTRACT

BACKGROUND: Laparoscopic surgery offers benefits like reduced bleeding, pain, and shorter hospital stays but poses port-site complications, especially in patients with obesity. Postoperative pain is less severe than in open surgery. Multimodal analgesia is promising, while the impact of fascial closure on complications remains debated. This study aims to compare the incidence of port-site complications in patients undergoing laparoscopic bariatric surgery, with or without fascial closure of the right working port.

METHODS: This randomized clinical trial was reported based on the CONSORT checklist. Seventy patients with severe obesity were compared in terms of fascial closure versus non-closure of the right working port during laparoscopic bariatric surgery. Thorough clinical, radiological, and nutritional assessment was done. Postoperative pain (using VAS) and port-site complications were assessed. Ethical approval was obtained, and informed consent was guaranteed.

RESULTS: Patients who underwent fascial closure of the right working port demonstrated significantly higher rates of moderate (85.7% vs. 5.7%) and severe pain (14.3% vs. 2.9%, p < 0.001) compared to the non-closure group. Port-site complications-bleeding (8.6% vs. 2.9%, p = 0.303), infection (11.4% vs. 14.3%, p = 0.721), and hernia (11.4% vs. 2.9%, p = 0.178)-were statistically comparable, suggesting that fascial closure may increase postoperative pain without significant impacts on other complications.

CONCLUSIONS: Fascial closure of the right working port after laparoscopic bariatric surgery in patients with obesity increases postoperative pain without reducing port-site complications like bleeding, infection, or herniation. Non-closure appears safer and effective in minimizing pain and adverse outcomes. Routine fascial closure may not be justified, warranting further research to optimize surgical techniques for patients with obesity.

PMID:40407981 | DOI:10.1007/s11695-025-07917-2

J Glob Health. 2025 May 23;15:04177. doi: 10.7189/jogh.15.04177.

ABSTRACT

BACKGROUND: Some surveillance systems for influenza, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and respiratory syncytial virus (RSV) utilise International Classification of Diseases (ICD)-coded data and are useful for analysing trends and enhancing quick, evidence-based decisions against the epidemic potential that threatens global health security. With variations in the design of systems globally, the World Health Organization requested a systematic review to identify key characteristics of influenza, SARS-CoV-2, and RSV surveillance systems that utilise ICD-coded data, and to assess their performance.

METHODS: We searched EMBASE, MEDLINE, and Global Health to identify relevant studies reporting on influenza, SARS-CoV-2, and RSV surveillance systems that use ICD-coded data. We independently assessed studies for the ICD codes used, their statistical estimates and limitations. We appraised included studies using Joana Briggs Institute’s critical appraisal tools and synthesised using narrative synthesis.

RESULTS: We identified 77 studies, reporting on 71 surveillance systems – 33 systems recorded surveillance data only, 15 systems recorded burden of disease data only, and 23 systems recorded both surveillance and burden of disease data. Surveillance systems utilised ICD-10 codes (75%), ICD-9 codes (22%), or both (3%). ICD-10 codes J09 and J10 were frequently used for influenza, U07.1 for COVID-19, and B97.4, J12.1, J20.5, and J21.0 for RSV. ICD-9 codes 487 and 488 were mostly used for influenza, and codes 466.11 and 480.1 for RSV. ICD-10 codes had low-to-moderate sensitivity (6.60-79.87%) and high specificity (97.40-99.72%) for influenza, low-to-high sensitivity (30.00-98.4%) and specificity (39.50-99.80%) for COVID-19, and low-to-high sensitivity (6.00-99.80%) and specificity (12.10-100.00%) for RSV. ICD-9 codes had low sensitivity (45.60%) and high specificity (97.90%) for influenza. Underestimation of infections or mortality attributable to influenza, SARS-CoV-2, or RSV is a major limitation to using ICD-coded data across surveillance systems.

CONCLUSIONS: The performance of ICD codes for syndromic- or disease-specific surveillance remains inconclusive, although using only ICD-coded data within these systems may underestimate influenza, SARS-CoV-2, or RSV-attributable morbidity and mortality. Future studies should assess the accuracy of ICD code combinations for surveillance of influenza, SARS-CoV-2, and RSV.

PMID:40406976 | DOI:10.7189/jogh.15.04177

J Adv Nurs. 2025 May 23. doi: 10.1111/jan.17084. Online ahead of print.

ABSTRACT

AIMS: Nurse migration remains a significant issue in global healthcare, often driven by economic incentives, work environment factors, and professional development opportunities. Greece’s prolonged economic crisis and low nurse-to-population ratios have further intensified the outflow of skilled nursing personnel. We aimed to examine how demographic, educational, and professional factors, along with working conditions and perceived challenges, influence Greek nurses’ motivation to migrate after the COVID-19 pandemic.

DESIGN: This quantitative study surveyed 121 Greek nurses-both employed and unemployed, from various regions.

METHODS: Structured questionnaires featuring closed-ended, Likert-scale, and open-ended items were used. Questions covered demographics, working conditions, migration motives, and perceived challenges. Data were analysed using Pearson’s Chi-Square, Likelihood Ratio tests, and correlation coefficients, with statistical significance set at p < 0.05.

RESULTS: Economic prospects, quality of life, and access to language support emerged as key “pull” factors. Conversely, family obligations, emotional attachments to Greece, fear of discrimination, and inadequate language skills served as barriers to migration. Age and marital status both shaped participants’ attitudes; younger nurses were generally more optimistic about overseas opportunities, while those with multiple children expressed greater reluctance. Increased computer literacy and higher education correlated with reduced concerns, and leadership responsibilities were linked to heightened caution about relocating.

CONCLUSION: Findings underscore the complexity of nurse migration decisions. Policymakers and healthcare institutions should consider providing enhanced career development, language support, and better working conditions to retain Greek nurses and mitigate the impact of ongoing workforce shortages.

IMPACT: This study highlights critical factors influencing nurse migration, informing policies to improve retention and address workforce shortages in Greece.

PATIENT OR PUBLIC CONTRIBUTION: Participants provided insights on migration motives, enriching understanding of healthcare workforce dynamics and informing policy development for retention.

PMID:40406975 | DOI:10.1111/jan.17084

Adipocyte. 2025 Dec;14(1):2499500. doi: 10.1080/21623945.2025.2499500. Epub 2025 May 23.

ABSTRACT

Inflammatory changes in perivascular adipose tissue are associated with atherosclerotic lesions in the adjacent artery and can also be used as a marker in patient workup. While adipocyte size is known to be closely related to adipose tissue dysfunction and inflammation, it has not been widely studied in perivascular adipose tissue obtained from healthy human subjects without clinical atherosclerosis. In this cross-sectional study, we addressed this issue by measuring adipocyte size and defining its relationship to cardiovascular risk factors in a healthy cohort of living kidney donors. The presence of cardiovascular risk factors was established by a standardized questionnaire, clinical measurements and body composition analyses. Adipocyte size was measured in the perivascular depot. The proportions of various macrophage subtypes were determined by flow cytometry. To confirm the results, the proportion of CD68 + macrophages was additionally assessed by immunohistochemistry. A correlation and principal component analyses were performed to explore associations. Adipocyte size in perivascular adipose tissue correlated with markers of lipid metabolism, inflammation, and glucose metabolism. Further, the positive correlation with the pro-inflammatory subpopulation of macrophages suggests a strong local effect of perivascular adipose tissue. Perivascular adipocyte size was associated with cardiovascular risk factors and markers of inflammation in a healthy cohort of living kidney donors. This further supports the local role of adipose tissue dysfunction and inflammation in early atherosclerosis development and detection.

PMID:40406925 | DOI:10.1080/21623945.2025.2499500

JAMA Neurol. 2025 May 23. doi: 10.1001/jamaneurol.2025.1522. Online ahead of print.

ABSTRACT

IMPORTANCE: Nontraumatic subarachnoid hemorrhage (SAH) represents the third most common stroke type with unique etiologies, risk factors, diagnostics, and treatments. Nevertheless, epidemiological studies often cluster SAH with other stroke types leaving its distinct burden estimates obscure.

OBJECTIVE: To estimate the worldwide burden of SAH.

DESIGN, SETTING, AND PARTICIPANTS: Based on the repeated cross-sectional Global Burden of Disease (GBD) 2021 study, the global burden of SAH in 1990 to 2021 was estimated. Moreover, the SAH burden was compared with other diseases, and its associations with 14 individual risk factors were investigated with available data in the GBD 2021 study. The GBD study included the burden estimates of nontraumatic SAH among all ages in 204 countries and territories between 1990 and 2021.

EXPOSURES: SAH and 14 modifiable risk factors.

MAIN OUTCOMES AND MEASURES: Absolute numbers and age-standardized rates with 95% uncertainty intervals (UIs) of SAH incidence, prevalence, mortality, and disability-adjusted life-years (DALYs) as well as risk factor-specific population attributable fractions (PAFs).

RESULTS: In 2021, the global age-standardized SAH incidence was 8.3 (95% UI, 7.3-9.5), prevalence was 92.2 (95% UI, 84.1-100.6), mortality was 4.2 (95% UI, 3.7-4.8), and DALY rate was 125.2 (95% UI, 110.5-142.6) per 100 000 people. The highest burden estimates were found in Latin America, the Caribbean, Oceania, and high-income Asia Pacific. Although the absolute number of SAH cases increased, especially in regions with a low sociodemographic index, all age-standardized burden rates decreased between 1990 and 2021: the incidence by 28.8% (95% UI, 25.7%-31.6%), prevalence by 16.1% (95% UI, 14.8%-17.7%), mortality by 56.1% (95% UI, 40.7%-64.3%), and DALY rate by 54.6% (95% UI, 42.8%-61.9%). Of 300 diseases, SAH ranked as the 36th most common cause of death and 59th most common cause of DALY in the world. Of all worldwide SAH-related DALYs, 71.6% (95% UI, 63.8%-78.6%) were associated with the 14 modeled risk factors of which high systolic blood pressure (population attributable fraction [PAF] = 51.6%; 95% UI, 38.0%-62.6%) and smoking (PAF = 14.4%; 95% UI, 12.4%-16.5%) had the highest attribution.

CONCLUSIONS AND RELEVANCE: Although the global age-standardized burden rates of SAH more than halved over the last 3 decades, SAH remained one of the most common cardiovascular and neurological causes of death and disabilities in the world, with increasing absolute case numbers. These findings suggest evidence for the potential health benefits of proactive public health planning and resource allocation toward the prevention of SAH.

PMID:40406922 | DOI:10.1001/jamaneurol.2025.1522

J Int Med Res. 2025 May;53(5):3000605251340304. doi: 10.1177/03000605251340304. Epub 2025 May 23.

ABSTRACT

ObjectiveThis retrospective cohort study aimed to develop and validate a nomogram for predicting in-hospital mortality among patients with community-acquired pneumonia admitted to the intensive care unit.MethodsData of patients meeting the inclusion criteria were extracted from the Medical Information Mart for Intensive Care-IV database, and the patients were randomly allocated into training (n = 3798, 70%) and validation (n = 1629, 30%) cohorts. First-day intensive care unit admission parameters were averaged. Least Absolute Shrinkage and Selection Operator regression and multivariate logistic regression analyses were used to identify mortality risk factors in the training cohort, followed by nomogram construction. Model performance was evaluated based on discrimination (area under the curve), calibration (Hosmer-Lemeshow test and bootstrap resampling), and clinical utility (decision curve analysis). Data from emergency intensive care unit were used to perform external validation of the value of the model.ResultsIn total, 5427 patients were included. Age, red cell distribution width, Sequential Organ Failure Assessment, Acute Physiology Score-III, blood urea nitrogen-to-serum creatinine ratio, anion gap, osmolarity, and sepsis were identified as independent risk factors for hospital mortality. The nomogram demonstrated superior discrimination compared with Sequential Organ Failure Assessment and Acute Physiology Score-III in the validation (area under the curve: 0.772 vs. 0.685-0.724) and training (area under the curve: 0.787 vs. 0.708-0.740; p < 0.05) sets. Calibration and decision curve analyses confirmed robust performance (Hosmer-Lemeshow p = 0.11; net benefit threshold: 20%-80%). In both cohorts, calibration and decision curve analyses showed that the nomogram had good calibration degree, discriminative ability, and clinical benefits. Data from emergency intensive care unit showed that the area under the curve of the model was 0.7864 (95% confidence interval, 0.76-0.81), area under the curve of Sequential Organ Failure Assessment was 0.7217 (95% confidence interval, 0.69-0.75), and area under the curve of Acute Physiology Score-III was 0.7055 (95% confidence interval, 0.68-0.73).ConclusionsThis nomogram provides moderate predictive accuracy for hospital mortality in critically ill patients with community-acquired pneumonia and may aid prognosis assessment.

PMID:40406909 | DOI:10.1177/03000605251340304

Chem Commun (Camb). 2025 May 23. doi: 10.1039/d5cc00856e. Online ahead of print.

ABSTRACT

Herein, we investigate a two-point crosslinked amyloid-β (Aβ) dimer, which forms an intermolecular β-sheet. The atomic force microscopy statistical results indicate that the heights of these dimers are approximately 0.37 nm, providing a baseline for the Aβ peptide sizes and improving our understanding of Aβ oligomers in Alzheimer’s disease.

PMID:40406894 | DOI:10.1039/d5cc00856e