Category: Nevin Manimala

Cancer Invest. 2025 Jan 24:1-11. doi: 10.1080/07357907.2025.2457144. Online ahead of print.

ABSTRACT

Accurate and timely diagnosis of t(9;22)-positive leukemias is vital to improving survival in pediatric patients. In low-resource settings, where healthcare disparities are exacerbated by limited resources, cost-effective and efficient diagnostic methods are essential for bridging these gaps and ensuring better outcomes. Among the diagnostic tools evaluated among 23 patients sample, RT-PCR demonstrated superior sensitivity (100%) and the shortest turnaround time (7 days), significantly outperforming FISH and karyotyping in both accuracy and timeliness. This capability of RT-PCR to provide reliable and rapid results enables earlier treatment initiation, which is critical in managing these aggressive leukemias. Simplified statistical reporting underscores RT-PCR’s unmatched sensitivity, while FISH and karyotyping, though useful, showed moderate performance with longer delays. By adopting RT-PCR as the primary diagnostic tool in LMICs, healthcare systems can make faster and more accurate treatment decisions, reduce overall treatment costs by avoiding diagnostic delays, and ultimately improve survival rates in pediatric leukemia patients.

PMID:39851090 | DOI:10.1080/07357907.2025.2457144

Palliat Support Care. 2025 Jan 24;23:e39. doi: 10.1017/S1478951524001640.

ABSTRACT

OBJECTIVES: To incorporate a longitudinal palliative care curriculum into obstetrics and gynecology (Ob-Gyn) residency that could become standardized to ensure competencies in providing end of life (EOL) care.

METHODS: This was a prospective cohort study conducted among 23 Ob-Gyn residents at a tertiary training hospital from 2021 to 2022. A curriculum intervention was provided via lecture and simulation. An inpatient palliative care rotation was also created for the intern class. Scores for knowledge and confidence were compared pre- and post-curriculum. Performance on patient simulations was compared for interns who had the inpatient palliative rotation versus those that had not in a crossover fashion. Number of palliative care consults was also compared before and during the curriculum. A pooled, weighted rank-based test was used for analysis of the data with a p-value < 0.05 considered significant.

RESULTS: One hundred percent of the 23 eligible participants participated in this study. A statistically significant increase in scores on all quizzes (p-values 0.047, <0.001, and <0.001) and confidence surveys (composite score p-value < 0.001) was seen after curriculum completion. No statistically significant difference was able to be identified in standardized patient simulation performance. Palliative care consultation increased by 55%.

SIGNIFICANCE OF RESULTS: EOL care is a critical component of any physician’s practice including obstetrician gynecologists. However, prior studies demonstrate a lack of standardized training. Our study demonstrates that a multimodal palliative care curriculum is an effective method to train Ob-Gyn residents and improve palliative care involvement in patient care.

PMID:39851085 | DOI:10.1017/S1478951524001640

Palliat Support Care. 2025 Jan 24;23:e36. doi: 10.1017/S1478951524001330.

ABSTRACT

Teaching death, spirituality, and palliative care equips students with critical skills and perspectives for holistic patient care. This interdisciplinary approach fosters empathy, resilience, and personal growth while enhancing competence in end-of-life care. Using experiential methods like simulations and real patient interactions, educators bridge theory and practice. Integrating theological insights and inclusive-pluralism encourages meaningful dialogue, preparing students to address patients’ physical, emotional, and spiritual needs. This holistic pedagogy not only improves patient outcomes but also promotes collaboration and compassion in healthcare.

PMID:39851082 | DOI:10.1017/S1478951524001330

Mol Cancer Ther. 2025 Jan 24. doi: 10.1158/1535-7163.MCT-23-0614. Online ahead of print.

ABSTRACT

TIGIT and PVRIG are immune checkpoints co-expressed on activated T and NK cells, contributing to tumor immune evasion. Simultaneous blockade of these pathways may enhance therapeutic efficacy, positioning them as promising dual targets for cancer immunotherapy. This study aimed to develop a bispecific antibody (BsAb) to co-target TIGIT and PVRIG. Expression of TIGIT and PVRIG was assessed on tumor-infiltrating lymphocytes (TILs) from patients with various cancers, including non-small cell lung cancer (n=63) and colorectal cancer (n=26). The BsAb was engineered by fusing anti-PVRIG nanobodies to the N terminus of anti-TIGIT antibodies. Functional characterization of the BsAb was performed in vitro and in vivo, including assessments of T and NK cell activation and cytotoxicity. Pharmacokinetics and safety profiles were evaluated in cynomolgus monkeys. Statistical analyses were conducted using the Student’s t-test. The results showed that the BsAb effectively blocked TIGIT and PVRIG from binding their respective ligands, CD155 and CD112, leading to significant increases in T cell activation (2.8-fold, p<0.05) and NK cell cytotoxicity (1.8-fold, p<0.05). In vivo, the BsAb demonstrated potent anti-tumor activity, both as a monotherapy and in combination with anti-PD-1 or anti-PD-L1, in humanized PBMC and transgenic mouse models. Pharmacokinetic studies in cynomolgus monkeys revealed a favorable profile, with no dose-limiting toxicities observed after four repeated doses of 200 mg/kg. These findings provide compelling preclinical evidence for the therapeutic potential of targeting the TIGIT-PVRIG axis with a bispecific antibody. This approach shows promise for enhancing anti-tumor immunity and warrants further investigation in clinical trials.

PMID:39851063 | DOI:10.1158/1535-7163.MCT-23-0614

Circ Genom Precis Med. 2025 Jan 24:e004631. doi: 10.1161/CIRCGEN.124.004631. Online ahead of print.

ABSTRACT

BACKGROUND: Lp(a; Lipoprotein[a]) is a predictor of atherosclerotic cardiovascular disease (ASCVD); however, there are few algorithms incorporating Lp(a), especially from real-world settings. We developed an electronic health record (EHR)-based risk prediction algorithm including Lp(a).

METHODS: Utilizing a large EHR database, we categorized Lp(a) cut points at 25, 50, and 75 mg/dL and constructed 10-year ASCVD risk prediction models incorporating Lp(a), with external validation in a pooled cohort of 4 US prospective studies. Net reclassification improvement was determined among borderline-intermediate risk patients.

RESULTS: We included 5902 patients aged ≥18 years (mean age 48.7±16.7 years, 51.2% women, and 7.7% Black). Our EHR model included Lp(a), age, sex, Black race/ethnicity, systolic blood pressure, total and high-density lipoprotein cholesterol, diabetes, smoking, and hypertension medication. Over a mean follow-up of 6.8 years, ASCVD event rates (per 1000 people-years) ranged from 8.7 to 16.7 across Lp(a) groups. A 25 mg/dL increment in Lp(a) was associated with an adjusted hazard ratio of 1.23 (95% CI, 1.10-1.37) for composite ASCVD. Those with Lp(a) ≥75 mg/dL had an 88% higher risk of ASCVD (hazard ratio, 1.88 [95% CI, 1.30-2.70]) and more than double the risk of incident stroke (hazard ratio, 2.55 [95% CI, 1.54-4.23]). C-statistics for our EHR and EHR+Lp(a) models in our EHR training data set were 0.7475 and 0.7556, respectively, with external validation in our pooled cohort (n=21 864) of 0.7350 and 0.7368, respectively. Among those at borderline/intermediate risk, the net reclassification improvement was 21.3%.

CONCLUSIONS: We show the feasibility of developing an improved ASCVD risk prediction model incorporating Lp(a) based on a real-world adult clinic population. The inclusion of Lp(a) in ASCVD prediction models can reclassify risk in patients who may benefit from more intensified ASCVD prevention efforts.

PMID:39851061 | DOI:10.1161/CIRCGEN.124.004631

Arch Ital Urol Androl. 2025 Jan 23:12658. doi: 10.4081/aiua.2025.12658. Online ahead of print.

ABSTRACT

OBJECTIVES: This research aimed to compare the prostate cancer (PCa) features, survival rate, and functional outcomes after open suprapubic Radical Prostatectomy (RP) between younger men (≤ 55 years) and older men (> 55 years).

METHODS: In this retrospective cohort study, we studied 134 patients with clinically localized PCa who underwent RP at our centers between 2011 and 2019, with 26 (19.40%) patients aged ≤ 55. Pathological parameters, survival rate (at 5 and 10 years), and functional outcomes such as erectile function and continence rate (at two years from RP) were evaluated retrospectively, and the two groups were compared. The Chi-square test, Kaplan-Meier, and Cox proportional hazards method were used for statistical analysis.

RESULTS: Men aged ≤ 55 had greater rates of organ-confined tumors, lower D’Amico risk grouping, and pathologic Gleason grade than their older counterparts (all p<0.05). The median follow-up was 81 months. The overall survival rate at five and ten years in younger men vs older counterparts was 96.15% vs. 93.47% and 92.15% v. 82.13% but was not statistically significant (p=0.1539). Five-year biochemical recurrence-free and metastasis-free survival rates in younger men vs older counterparts were 96.2% vs 81.5% and 75.7% vs 51.5%. Men > 55 years were associated with worse BCR-free and metastasis-free survival in univariate analysis and worsening BCR in multivariate analysis. The continence rate was significantly improved in men aged ≤ 55 years compared to older counterparts (OR: 5.08; 95% CI: 1.61-22.61; p=0.013). However, erectile function was not statistically significant between groups [for moderate ED: (OR:1.08; 95% CI: 0.43-2.79, p=0.865), for severe ED (OR: 1.60; 95% CI: 0.35-11.50, p=0.579=)].

CONCLUSIONS: Our study showed that survival rates were similar in younger men (≤ 55 years) and their older counterparts. However, older patients who underwent RP had more advanced disease, worse BCR-free survival, and worse continence rate. For localized prostate cancer patients under 55 years of age, radical prostatectomy is an excellent treatment option with excellent long-term survival results. Given the relatively small number of patients younger than 55, a large cohort study with long-term postprocedural follow-up is needed to validate this observation.

PMID:39851058 | DOI:10.4081/aiua.2025.12658

Circ Cardiovasc Interv. 2025 Jan 24:e014528. doi: 10.1161/CIRCINTERVENTIONS.124.014528. Online ahead of print.

ABSTRACT

BACKGROUND: Intravascular imaging (IVI) is widely recognized to improve outcomes after percutaneous coronary intervention (PCI). However, IVI is underutilized and is not yet established as a performance measure for quality PCI.

METHODS: We examined temporal trends of IVI use for all PCIs performed at Veterans Affairs hospitals in the United States from 2010 to 2022 using retrospective observational cohorts. IVI was defined as intravascular ultrasound or optical coherence tomography. A contemporary subset of PCIs from 2020 to 2022 was used to examine clinical characteristics associated with IVI use and test the reliability of IVI as a pass/fail performance measure. We then used a generalized linear mixed model to estimate the proportion of IVI use variability attributable to the hospital, physician, and patient level. Cox proportional hazard models were used to assess the association of IVI with clinical outcomes at 1 year.

RESULTS: IVI use increased from 12.3% in 2010 to 43.1% in 2022 in 136 071 PCIs included in the study. Among 22 918 PCIs in the contemporary cohort, IVI was more frequent with nonemergent presentations, chronic total occlusions, and left main lesions but usage variability was primarily attributable to hospital (54%) and physician (33%) levels. As a pass/fail performance measure, reliability was high (>0.96) at hospital and physician levels. However, IVI use was not associated with statistically significant differences in mortality or major adverse cardiovascular events in this cohort.

CONCLUSIONS: IVI use for PCI is increasing rapidly at Veterans Affairs hospitals in the United States but with marked variation at the hospital and physician levels. IVI meets established criteria for an effective performance measure and should be measured and reported by local and national organizations to encourage further uptake. Ongoing training and quality improvement may be required to maximize the benefit of IVI as it is more widely utilized.

PMID:39851056 | DOI:10.1161/CIRCINTERVENTIONS.124.014528

Arch Ital Urol Androl. 2025 Jan 23:13268. doi: 10.4081/aiua.2025.13268. Online ahead of print.

ABSTRACT

INTRODUCTION: Excision and primary anastomosis (EPA) urethroplasty is the standard treatment for traumatic urethral strictures, but managing them remains challenging for urologists. Identifying factors leading to EPA urethroplasty failure benefits both patients and surgeons. This study aims to analyze risk factors for urethral stricture recurrence after one-year follow-up of EPA urethroplasty.

MATERIALS AND METHODS: Data on male patients undergoing EPA urethroplasty at the Urology Department of Saiful Anwar General Hospital from January 2013 until December 2023 were prospectively recorded. Successful urethroplasty, defined as the absence of additional treatment necessity, was assessed until 12 months follow-up. Demographic data, time to surgery, stricture etiology, comorbidities, prior urethral interventions, and operation steps were recorded. Univariate and multivariate Cox regression analyses were performed using IBM SPSS Statistics version 21.

RESULT: Total 95 patients were observed, and 89 patients were included, averaging 41.2 ± 15.59 years old. EPA urethroplasty succeeded in 91% of cases over a median follow-up of 16.3 months. Pelvic fracture urethral injury (PFUI) was the predominant etiology in 74% of cases, with an average stricture length of 25.4 ± 16.3 mm. The average time to surgery was performed on average 6.67 ± 4.07 months after diagnosis. In univariate analysis, body mass index (BMI), time to surgery, and stricture length were associated with urethral stricture recurrence. However, only time to surgery showed a significant association in multivariate analysis.

CONCLUSIONS: Obesity, the length of the stricture, and delayed surgical intervention are associated with an increased risk of urethral stricture recurrence in patients following EPA. EPA urethroplasty demonstrates a high success rate in managing traumatic urethral strictures.

PMID:39851052 | DOI:10.4081/aiua.2025.13268

J Atten Disord. 2025 Jan 24:10870547251313879. doi: 10.1177/10870547251313879. Online ahead of print.

ABSTRACT

OBJECTIVE: This study investigated the psychometric properties of the Arabic version of the Adult Self-Report Scale-5 (the ASRS-5-AR) within a large sample of adults residing in Saudi Arabia.

METHODS: This cross-sectional study applied the ASRS-5-AR to a random sample of 4,299 Saudi and non-Saudi adults, aged 19 to 66 years (31.16 ± 9.26 years), living in the regions of Riyadh, Makkah, and the Eastern Province in Saudi Arabia. Collected data were analyzed using IBM SPSS Statistics 26, JASP 0.18.3.0 software, and MedCalc 22.030 statistical software.

RESULTS: The ASRS-5-AR demonstrated strong internal consistency, with all six items showing significant positive correlation with the total score (.675-.735). Results of confirmatory factor analysis revealed a goodness-of-fit coefficient of 0.983 for the one-factor model and McDonald’s omega, Cronbach’s α, and Spearman-Brown coefficients of 0.786, 0.788, and 0.724, respectively. In addition, the findings revealed statistically significant differences in self-reported ADHD symptoms based on age (F = 18.68; p < .001), level of education (F = 2.61; p < .05), and marital status (F = 22.30; p < .001). However, there were no significant differences in self-reported ADHD symptoms between males and females (t = 0.625; p > .05) or Saudi and non-Saudi participants (t = 0.409; p > .05) or based on region of residence (t = 2.19; p > .05).

CONCLUSIONS: This study provides valuable insights into the psychometric properties of the ASRS-5-AR within a large sample of adults in Saudi Arabia. The findings demonstrate acceptable reliability of the ASRS-5-AR within this population. While these findings suggest the ASRS-5-AR may be a useful tool for initial assessment, further research is crucial. Future studies should focus on establishing accurate cutoff scores by comparing a general population sample with a clinically diagnosed sample of adults with ADHD in Saudi Arabia. This will allow for a more accurate evaluation of the scale’s utility in identifying individuals who may require further clinical assessment.

PMID:39851051 | DOI:10.1177/10870547251313879