Category: Nevin Manimala

Genet Med Open. 2026 May 27;4:104406. doi: 10.1016/j.gimo.2026.104406. eCollection 2026.

ABSTRACT

PURPOSE: Genetic factors play a role in prostate cancer (PCa) development. This real-life, retrospective, multicenter study aimed to identify and characterize the germline genetic testing landscape in men with PCa and to assess the added benefit of next-generation sequencing (NGS) testing compared with testing for founder disease-causing variants.

METHODS: This study included all men who were referred for genetic counseling because of PCa. All patients were offered germline genetic testing. Demographic, clinical, and pathological information was retrieved from their medical records. Variant classification was determined using the American College of Medical Genetics and Genomics guidelines.

RESULTS: Of the 293 men with PCa tested, in 39 (13.3%), a positive genetic finding (pathogenic variant, likely pathogenic, or risk variant) was reported: 18 (6.1%) men had a positive test result for high-penetrance genes (BRCA1, BRCA2, ATM, NF1, and MSH6), and 21 (7.2%) had risk allele variants. One-third (33%) of the disease-causing or likely disease-causing variants identified through NGS in our PCa cohort were unique rather than founder variants. The only significant correlation between positive results and demographic or clinical factors was observed between a positive test result and a family history of cancer.

CONCLUSION: Our findings underscore the importance of NGS genetic investigations in patients with PCa, regardless of ethnicity or disease stage.

PMID:42502690 | PMC:PMC13400249 | DOI:10.1016/j.gimo.2026.104406

Arthroplast Today. 2026 Jul 18;40:102098. doi: 10.1016/j.artd.2026.102098. eCollection 2026 Aug.

ABSTRACT

BACKGROUND: Access to primary total knee arthroplasty (TKA) for morbidly obese (MO) patients is often restricted to reduce complications. We compared complication rates in patients who were MO or non-MO (NMO) at initial presentation based on whether their body mass index (BMI) had decreased by ≥5%, remained stable, or increased by ≥5% at the time of surgery, hypothesizing that preoperative weight loss does not reduce complication rates.

METHODS: Prospectively collected data for 2219 unilateral, primary TKAs were retrospectively reviewed. Cases were performed between 2012 and 2023 at the same academic center by 4 fellowship-trained surgeons using standardized protocols. Twenty-eight percent (n = 627) were MO and 72% (n = 1592) were NMO at initial presentation. Outcomes included intraoperative and 90-day complications and reoperations. Outcome covariates included patient demographics and comorbidities, as well as operative details. Independent samples t-tests and chi-squared tests were used for statistical analysis.

RESULTS: Intraoperative complications (P = .999), medical complications (P ≥ .398), death (P = .299), superficial or deep infection (P = .731), and reoperation on the index joint within 90 days of surgery (P = .801) did not differ in MO patients with a ≥5% decrease vs stable BMI before surgery. These outcomes also did not differ between NMO patients with a ≥5% decrease in BMI and those with stable BMI before surgery (P ≥ .250).

CONCLUSIONS: Findings suggest that withholding surgery from patients who are clinically indicated for TKA pending weight loss may not be necessary to reduce early postoperative complications.

PMID:42502678 | PMC:PMC13400762 | DOI:10.1016/j.artd.2026.102098

Nucl Med Mol Imaging. 2026 Aug;60(4):409-420. doi: 10.1007/s13139-026-01008-5. Epub 2026 Apr 8.

ABSTRACT

BACKGROUND: The reliability of PET radiomic features is fundamentally constrained by inherent stochastic noise originating from Poisson-distributed photon-counting statistics and additional fluctuations introduced by electronic signal processing. To assess its impact, we repeated PET scans under identical acquisition and reconstruction conditions to evaluate the consistency of radiomic feature measurements and quantify the noise-induced variability as a repeatability measure.

MATERIALS AND METHODS: An American College of Radiology-accredited (ACR) phantom was utilized to evaluate measurement variability in PET radiomic features under two scenarios: uniform (Experiment 1) and non-uniform (Experiment 2) radiotracer distributions, employing ¹⁸F-FDG and ⁶⁸Ga-PSMA tracers. A total of 93 radiomic features across six categories were extracted using PyRadiomics. Each experiment was repeated ten times, and measurement variability was quantified using the coefficient of variation (CV). Features were benchmarked and classified into three quality grades of repeatability: Grade A (CV < 10%), Grade B (10% ≤ CV < 20%), and Grade C (CV ≥ 20%).

RESULTS: Experiment 1 identified 22 Grade A and 14 Grade C features, whereas Experiment 2 yielded 30 Grade A and 15 Grade C features. Notably, CV values exhibited substantial variability. In Experiment 1, CV ranged from 0.17% to 205% for ¹⁸F-FDG and from 0.14% to 140% for ⁶⁸Ga-PSMA. Similarly, in Experiment 2, CV spanned from 0.16% to 230% for ¹⁸F-FDG and from 0.23% to 79% for ⁶⁸Ga-PSMA.

CONCLUSION: By isolating inherent stochastic noise, this study applied the coefficient of variation to evaluate measurement variability across repeated PET scans and benchmarked radiomic features into three repeatability quality categories. While some features demonstrated high noise resilience, others showed poor repeatability across repeated scans. These findings highlight the need to establish repeatability standards to guide the development of noise-robust features that support trustworthy imaging biomarkers for clinical applications.

SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s13139-026-01008-5.

PMID:42502658 | PMC:PMC13400607 | DOI:10.1007/s13139-026-01008-5

Nucl Med Mol Imaging. 2026 Aug;60(4):363-370. doi: 10.1007/s13139-026-00992-y. Epub 2026 Feb 20.

ABSTRACT

PURPOSE: Targeted radionuclide therapy (TRT), specifically peptide receptor radionuclide therapy (PRRT) with [¹⁷⁷Lu]Lu-DOTA-TATE is an established treatment for somatostatin receptor-expressing neuroendocrine tumors across different grades; however, its efficacy in other tumors expressing somatostatin receptors remains less defined. This study aimed to evaluate the safety and efficacy of PRRT with [¹⁷⁷Lu]Lu-DOTA-TATE in patients with medullary thyroid cancer (MTC) who presented with progressive recurrence or metastases refractory to standard therapies.

METHODS: Ten patients with MTC (3 females, 7 males; mean age 45.0 ± 13.0 years) underwent slow intravenous injection of [¹⁷⁷Lu]Lu-DOTA-TATE combined with lysine-arginine co-infusion in 2000 mL normal saline. Each patient received a median of 4 cycles (IQR: 3.0-5.3) with a mean activity of 5.5 ± 1.5 GBq per cycle. Post-treatment imaging and serial measurements of calcitonin and carcinoembryonic antigen (CEA) were performed. Hematologic and biochemical toxicities were assessed according to CTCAE criteria.

RESULTS: Calcitonin levels showed a marked numerical decline from 6452.6 ± 8565.7(median:1897.5, interquartile range:127-12993.8) pg/mL to 540.9 ± 632.1 (390, IQR;141.8-723.3) pg/mL, although this change did not reach conventional statistical significance (P = 0.093), while CEA levels decreased significantly from 119.0 ± 186.2 (40, IQR:10.9-199) ng/ml ng/mL to 56.1 ± 67.9 (22, deIQR:5.7-112.3) ng/mL (P = 0.017). Based on calcitonin levels, biochemical response, stable disease, and progression were observed in 4, 4, and 2 patients, respectively; in contrast, CEA showed a biochemical response in 3 patients, with the remaining 7 demonstrating stable disease and no cases of biochemical progression. The median percentage reductions from baseline were clinically meaningful, reaching – 39.3% for calcitonin and – 25.8% for CEA. On imaging assessment, the best overall response comprised partial response in 4 patients, stable disease in 4 patients, and progressive disease in 2 patients. Only grade 1 hematologic toxicity was observed, with no hepatic or renal toxicity detected. White blood cell counts declined from 6144.4 ± 2362.3/µL to 4927.8 ± 1635.3/µL (P = 0.027), while other hematologic, renal, and hepatic parameters remained stable.

CONCLUSION: [¹⁷⁷Lu]Lu -DOTA-TATE PRRT was safe and effective in controlling disease progression and reducing tumor markers in MTC patients unresponsive to conventional therapy, supporting further evaluation in larger studies.

PMID:42502651 | PMC:PMC13400521 | DOI:10.1007/s13139-026-00992-y

Nucl Med Mol Imaging. 2026 Aug;60(4):353-362. doi: 10.1007/s13139-025-00981-7. Epub 2026 Feb 11.

ABSTRACT

OBJECTIVE: Optimized reconstruction algorithms can enhance the image quality and signal-to-noise ratio (SNR) of positron emission tomography (PET) images. This study aimed to compare the impacts of the ordered subset expectation maximization (OSEM) and regularized expectation maximization image reconstruction (HYPER Iterative) algorithms on the image quality and epileptogenic zone (EZ) detection sensitivity in fluorine-18-DPA-714 (¹⁸F-DPA-714) images of drug-resistant focal epilepsy patients.

METHODS: Drug-resistant focal epilepsy patients who underwent presurgical brain ¹⁸F-DPA-714 PET imaging between May 2023 and July 2024 were retrospectively included. PET images were reconstructed using the OSEM (number of iterations ranging from 2 to 6) and HYPER Iterative algorithms [penalization factors (β) of 0.3, 0.5, and 0.8]. Image quality was evaluated by subjective (overall image quality, image noise, and EZ conspicuity) and quantitative assessment [mean standardized uptake value (SUVmean), SUVmax, contrast-to-noise ratio (CNR), SNR, and standardized uptake value ratio (SUVr)]. The sensitivity of detecting EZs in optimal PET images reconstructed by the OSEM and HYPER Iterative algorithms was compared, with histopathology as the gold standard.

RESULTS: Thirty patients were included. The subjective assessment revealed that the HYPER Iterative algorithms outperformed OSEM in overall image quality, with HY0.8 achieving the highest score. Among OSEM algorithms, O5 had the top score and outperformed O6 significantly. Image noises scores were higher in HY0.5 and HY0.8 than in HY0.3 and OSEM algorithms. EZ conspicuity scores were better for HYPER Iteratives, O5, and O6 than for O2 – O4. Quantitative assessment revealed that the SNR was higher in O2, HY0.5, and HY0.8 than in O6, with HY0.8 significantly higher SNR than O5. The SUVr was higher in O6 and HY0.3 compared with O2. No significant differences were observed in SUVmean, SUVmax, mean standardized uptake value of cerebellar gray matter (SUVb) or CNR across all groups. For EZ detection, O5 and HY0.8 were optimal for the OSEM and HYPER Iterative algorithms, respectively. HY0.8 achieved a numerically 13.3% higher sensitivity for EZ detection than O5(80.0% vs. 66.7%), though this difference did not reach statistical significance (p = 0.125).

CONCLUSIONS: The HYPER Iterative algorithm is capable of reducing image noise, enhancing EZ conspicuity, and improving the overall image quality in ¹⁸F-DPA-714 PET for patients with drug-resistant focal epilepsy, further increasing visual interpretability. A penalization factor of 0.8 results in a numerical improvement in the detection sensitivity of EZ, thus facilitating readers’ confidence in detecting EZs.

SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s13139-025-00981-7.

PMID:42502649 | PMC:PMC13400539 | DOI:10.1007/s13139-025-00981-7

Int J Cardiol Heart Vasc. 2026 Jul 17;65:101976. doi: 10.1016/j.ijcha.2026.101976. eCollection 2026 Aug.

ABSTRACT

AIMS: Compared with intravenous iron, oral iron is less expensive, avoids healthcare complexities, and reduces the risk of iron overload. However, conventional oral formulations have not improved clinical outcomes in heart failure (HF) and iron deficiency (ID), largely due to poor absorption. Sucrosomial iron (SI) partially bypasses hepcidin-controlled absorption and showed favorable effects in a small case-control study, warranting further evaluation in a randomized trial.

METHODS: The Effect of Oral sucRosomIal Iron on exerciSE Capacity and Quality of Life in Patients With Heart Failure (RISE-HF; NCT06270498) is a randomized, placebo-controlled, double-blind study enrolling 60 patients with HF with left ventricular ejection fraction <50%, ID (transferrin saturation (TSAT) < 20%), ferritin <400 μg/L and hemoglobin (Hb) 10-16 g/dL. Participants are randomized 1:1 to receive SI (Sideral Forte®: sucrosomial iron 30 mg + 70 mg vitamin C) or placebo for 24 weeks, with daily dose tailored to Hb (2 capsules for Hb 10-13.9 g/dL; 1 capsule for Hb 14-16 g/dL). Co-primary endpoints are changes from baseline to week 12 in exercise capacity, assessed by the 6-min walk test (6MWT) distance, and in quality of life, assessed by the Kansas City Cardiomyopathy Questionnaire-12. Secondary endpoints include changes in individual co-primary endpoints at week 24, effects on iron status and oxidative stress biomarkers, N-terminal pro type-B natriuretic peptide and echocardiographic indices of cardiac function, and gastrointestinal tolerability.

CONCLUSIONS: RISE-HF will determine whether SI can safely improve exercise capacity, quality of life, and iron status in patients with HF and TSAT-defined ID, justifying a larger multicenter trial.

PMID:42502637 | PMC:PMC13400243 | DOI:10.1016/j.ijcha.2026.101976

Rural Remote Health. 2026 Jul;26(3):10953. doi: 10.22605/RRH10953. Epub 2026 Jul 24.

ABSTRACT

INTRODUCTION: Efficient use of health worker time is critical for improving service delivery in low resource and rural settings, where persistent workforce shortages limit progress toward universal health coverage. Ethiopia faces a severe health workforce deficit, yet empirical evidence on how hospital-based professionals utilize their working hours, particularly in rural and remote hospitals, remains limited. This study assessed productive time use among health professionals and examined factors associated with achieving an 8-hour productive workday.

METHODS: A cross sectional time-motion study was conducted in 18 public and private hospitals, including rural facilities across Ethiopia. A total of 180 health professionals representing five cadres were observed over two full working days using a standardized time-motion protocol. Productive activities included direct and indirect patient care and essential administrative functions. Structured interviews assessed workload, workplace conditions, and performance management practices. Descriptive statistics and multivariable logistic regression identified predictors of high productivity.

RESULTS: Health professionals spent a total of 5.55 hours per day on productive activities (69.4% of official working hours). Nearly one-third of time was lost to non-productive activities, primarily waiting for patients and having extended breaks. Productivity was positively associated with postgraduate training, greater experience, higher daily patient load, and receipt of performance appraisal. Patterns were consistent across rural and urban hospitals, though rural facilities reported longer waiting times and greater supply constraints.

CONCLUSION: Despite systemic constraints, health professionals dedicate a substantial share of their time to productive tasks. A portion of non-productive time reflects system-level factors such as patient flow disruptions and supply constraints rather than individual inefficiency, particularly in rural hospitals. Addressing these bottlenecks – alongside strengthening workforce capacity through training, supervision, and performance systems – could improve efficiency within existing resources and support equitable, high-quality care.

PMID:42502183 | DOI:10.22605/RRH10953

BMC Pediatr. 2026 Jul 24;26(1):683. doi: 10.1186/s12887-026-07239-x.

ABSTRACT

OBJECTIVES: Ventilator-associated pneumonia (VAP) is a frequent and serious infection among mechanically ventilated children in pediatric intensive care units (PICUs), with oral colonization playing a key role in its pathogenesis. Effective oral hygiene measures are therefore crucial to reduce VAP incidence and improve clinical outcomes. This study aimed to compare the incidence of VAP in PICU patients receiving routine oral care versus toothbrushing with chlorhexidine, and to evaluate the impact on mechanical ventilation duration, PICU stay, and mortality with secondary outcomes including microbiological colonization, inflammatory markers, and inotropic support requirements.

DESIGN: A parallel-group superiority randomized controlled trial.

METHODS: A randomized controlled trial was conducted on 118 children aged 18 months to 16 years, including PICU patients requiring invasive mechanical ventilation for ≥ 48 h. On admission, patients were randomly allocated into two groups: the intervention group received oral care with toothbrushing plus 0.12% chlorhexidine mouth rinse, while the control group received routine care with 0.12% chlorhexidine rinse only. Both procedures were performed three times daily. VAP was diagnosed according to CDC criteria. Quantitative and qualitative analyses assessed variables distinguishing VAP cases from controls, and multivariate logistic regression identified independent predictors of disease severity.

RESULTS: The results of our study revealed that VAP occurred in 31 patients (52.5%) in the control group and 25 patients (42.3%) in the intervention group, indicating a lower incidence with toothbrushing plus chlorhexidine, although this difference was not statistically significant (p = 0.36). Among all participants, 45.8% died and 54.2% were discharged. Mortality was higher in the control group (53.7%) compared with the intervention group (46.3%), while discharge rates favored the intervention group (53.1% vs. 46.9%); however, these differences did not reach statistical significance (p = 0.46). Positive sputum cultures were more frequent in the control group (55.6%) than in the intervention group (44.4%), whereas negative cultures were more common among intervention patients (54.7% vs. 45.3%), with no significant difference between groups (p = 0.268).

CONCLUSION: Although adding toothbrushing to routine chlorhexidine oral care did not produce a statistically significant reduction in VAP incidence or mortality, a consistent trend toward clinical benefit was observed across multiple outcome measures, including lower rates of positive sputum cultures, reduced inotropic support requirements, and fewer new pulmonary infiltrates. These findings highlight the potential value of enhanced oral hygiene in the PICU and support the need for larger multicenter studies to confirm its effect.

TRIAL REGISTRATION: ClinicalTrials.gov, NCT07287566. Registered on November 20, 2025. Retrospectively registered at https://clinicaltrials.gov/ct2/show/NCT07287566 .

PROTOCOL AND STATISTICAL ANALYSIS PLAN ACCESS: The full study protocol and the statistical analysis plan are included in this document and are available from the corresponding author upon reasonable request.

PMID:42502162 | DOI:10.1186/s12887-026-07239-x

Infect Dis Ther. 2026 Jul 26. doi: 10.1007/s40121-026-01394-5. Online ahead of print.

ABSTRACT

INTRODUCTION: Human Immunodeficiency Virus (HIV) infection has currently become a manageable chronic disease with the prevalence of antiretroviral therapy (ART). The increase in life expectancy and the rising number of people aged more than 50 years among people living with HIV (PLWH) both indicate an increasing risk of chronic non-communicable diseases, especially cardiovascular disease (CVD). Moreover, the contribution of traditional risk factors to CVD far outweighs that of HIV-related factors, which indicates that interventions for reducing CVD risk factors in PLWH are urgent.

METHODS: We designed a multicentre non-randomized controlled trial (nRCT), which incorporated six acquired immunodeficiency syndrome (AIDS)-designated hospitals in Zhejiang Province, and three rounds of surveys were conducted from January 2023 to January 2024. Assessments were performed at baseline, 3 months and 6 months post-intervention, respectively. For the intervention group, PLWH were informed of their 5/10-year CVD risk, on the basis of the assessment in baseline, verbally or online to warn them of the risk of having CVD; at the same time, personalized risky behaviour reinforcement intervention was implemented face-to-face or online for about 15 min. For the control group, PLWH were not informed of the 5/10-year CVD risk and only received routine health education in the clinic without additional intervention. Intervention effects were assessed using 5/10-year CVD risk, health-related behaviours (e.g., smoking, alcohol consumption, physical activities and dietary nutrition), as well as CVD cognitive level. To minimize baseline differences and reduce confounding due to non-treatment factors (e.g., socio-demographic characteristics), propensity score matching (PSM) was applied to construct comparable intervention and control groups, and a generalized estimating equation (GEE) was used to estimate the effect of the intervention. This trial was retrospectively registered with the Chinese Clinical Trial Registry (ChiCTR2500112178) on 11 November 2025.

RESULTS: A total of 948 PLWH were incorporated at baseline, after excluding ineligible participants, including 494 in the intervention group and 454 in the control group. The average age was 42.08 ( ± 11.94) years, with 826 male patients (87.13%). A total of 362 pairs were successfully matched after PSM. After matching, no statistical differences remained between the two groups. After 6 months’ intervention, the intervention group showed significant improvements in CVD cognitive level, with a total increase of 2.30 points compared with 0.41 points in the control group (P = 0.028). Additionally, PLWH who almost never drink and have > 8 h of sedentary time per day, increased and decreased 4.54% and 1.46% respectively, compared with the control group (P < 0.05). The 10-year CVD risk decreased by 0.63% in the intervention group and 0.18% in the control group. Moreover, the smoking rate and drinking rate decreased more in the intervention group compared with the control group, and the physical exercise compliance rate increased more as well, though there was no statistical difference compared with the control group (P > 0.05).

CONCLUSIONS: Risk warning and behavioural intervention effectively improved CVD cognitive level. Although the risk warning and behavioural intervention could not make PLWH completely quit smoking or using alcohol, the intervention led to notable improvements in reducing the frequency of some health risk behaviours.

PMID:42502148 | DOI:10.1007/s40121-026-01394-5

J Thromb Thrombolysis. 2026 Jul 25. doi: 10.1007/s11239-026-03368-3. Online ahead of print.

ABSTRACT

Transcatheter aortic valve replacement (TAVR) has extended its use to low-surgical-risk populations, yet long-term comparative data against surgical aortic valve replacement (SAVR) are still limited, particularly concerning durability and the need for reintervention. We conducted a search of PubMed/MEDLINE, Embase, CENTRAL, and ClinicalTrials.gov through March 2026 for randomized trials comparing TAVR with SAVR in patients with low surgical risk and severe aortic stenosis, specifically those with at least three years of follow-up. Outcomes were pooled as risk ratios (RR) using Mantel-Haenszel random-effects models, and durability and mortality outcomes were analyzed as time-to-event hazard ratios (HR) to accommodate different follow-up durations. Prespecified subgroup analyses by valve platform were performed. Four trials involving 3,014 patients (follow-up ranging from 3 to 10 years) were included. Cardiovascular mortality (HR 1.11, 95% CI 0.86-1.42; P = 0.43) and all-cause stroke (HR 1.09, 95% CI 0.73-1.64; P = 0.67) did not differ significantly between TAVR and SAVR. Aortic valve reintervention was higher with TAVR in risk-ratio analysis (RR 1.58, 95% CI 1.16-2.16) but did not reach statistical significance in the prespecified time-to-event analysis (HR 1.29, 95% CI 0.81-2.05). The excess reintervention risk was confined to the self-expanding valve platform. Permanent pacemaker implantation was significantly more frequent after TAVR (RR 2.08, 95% CI 1.48-2.93; P < 0.0001), with a significant interaction by valve platform (self-expanding RR 2.57 vs balloon-expandable RR 1.40; P = 0.02 for interaction). Bioprosthetic valve failure showed a nonsignificant trend favoring TAVR (HR 0.80, 95% CI 0.54-1.17). The only available 10-year randomized data (NOTION trial) showed significantly less severe structural valve deterioration with TAVR than with SAVR. The results suggest that TAVR and SAVR are equivalent in terms of cardiovascular mortality and stroke outcomes. However, pacemaker implantation rates were higher with TAVR and were strongly dependent on the valve platform used. The observed excess in reinterventions was confined to self-expanding valves and did not show robust support in the time-to-event analysis. The unique 10-year data from the self-expanding platform indicate less severe structural valve deterioration compared to SAVR, suggesting that durability should not be generalized across different device families. These findings advocate for individualized, platform-aware decision-making in clinical practice.

PMID:42502145 | DOI:10.1007/s11239-026-03368-3