Nevin Manimala

PLoS One. 2025 Jun 20;20(6):e0326216. doi: 10.1371/journal.pone.0326216. eCollection 2025.

ABSTRACT

BACKGROUND: Toripalimab, a monoclonal antibody designed to target PD-1, has recently received approval from the U.S. Food and Drug Administration (FDA) for use as a first-line treatment in adults diagnosed with metastatic or recurrent locally advanced nasopharyngeal carcinoma (NPC). The purpose of this study is to utilize the FAERS database and bibliometric analysis to examine adverse events associated with toripalimab in real-world settings, thereby enhancing the safety management of clinical medications.

METHODS: This research implemented a disproportionality analysis to assess the safety of toripalimab by reviewing all adverse event reports from the FAERS database dating back to 2004, wherein toripalimab was recognized as the main suspected medication. Various statistical techniques were applied in the analysis, such as the reporting odds ratio (ROR), proportional reporting ratio (PRR), multi-item gamma Poisson shrinker (MGPS), and Bayesian confidence propagation neural network (BCPNN), to evaluate the adverse events linked to toripalimab. CiteSpace is utilized to search for authors, countries, keywords, and various indicators within research fields, facilitating the identification of research hotspots and future trends.

RESULTS: From 2004 to 2024, 441 AEs linked to toripalimab were recorded across 27 SOCs. The top five SOCs were procedural complications, investigations, blood/lymphatic disorders, gastrointestinal disorders, and skin/subcutaneous disorders. At the PT level, the top five AEs by ROR were myelosuppression (n = 192, ROR 687.41), decreased granulocyte count (n = 11, ROR 515.72), immune-mediated hepatic disorder (n = 7, ROR 343.20), immune-mediated myocarditis (n = 3, ROR 214.68), and bicytopenia (n = 3, ROR 117.49). Additionally, 91.62% of AEs occurred within the first 30 days, and immune-related AEs were highlighted in bibliometric analysis.

CONCLUSION: This research provides initial safety information regarding the real-world application of toripalimab, affirming previously acknowledged adverse effects and concurrently uncovering new possible risks. These results could act as important cautionary evidence for healthcare professionals and pharmacists engaged in administering toripalimab for NPC.

PMID:40540517 | DOI:10.1371/journal.pone.0326216

PLoS One. 2025 Jun 20;20(6):e0325206. doi: 10.1371/journal.pone.0325206. eCollection 2025.

ABSTRACT

BACKGROUND: The arterial switch operation (ASO) is the standard surgical treatment for transposition of the great arteries (TGA). Postoperative complications such as branch pulmonary artery (PA) stenosis are commonly observed. This study aimed to investigate the possible potential anatomical mechanisms contributing to isolated branch PA stenosis using cardiac computed tomography (CCT).

METHODS: A retrospective, single-center study was conducted on pediatric patients under 18 years of age diagnosed with TGA, with or without ventricular septal defect (VSD), who underwent ASO and cardiac CCT between January 2004 and October 2022. Baseline characteristics, echocardiographic data, and CCT findings were compared between patients with and without isolated branch PA stenosis. Special attention was given to the angle between the PA bifurcation and the ascending aorta (AAO).

RESULTS: Among 30 patients enrolled, 46.67% (14/30) had isolated branch PA stenosis, while 53.33% (16/30) had no stenosis. Baseline and echocardiographic variables showed no significant differences between groups, except for the PA bifurcation angle relative to the AAO. Patients with isolated right PA (RPA) stenosis demonstrated significantly greater leftward angulation (median angle: 25° [IQR: 24, 30]) compared to the no-stenosis group (median angle: -2° [IQR: -8, 6.5]). Similarly, isolated left PA (LPA) stenosis was associated with greater rightward angulation (median angle: -22° [IQR: -32, -20]) compared to the no-stenosis group (P = 0.042).

CONCLUSION: Alterations in the PA bifurcation angle relative to the AAO may contribute to the development of isolated branch PA stenosis following ASO. Preoperative planning to optimize the PA bifurcation angle to within ±20 degrees may help reduce the risk of postoperative stenosis. A larger study incorporating advanced cardiac imaging into routine ASO follow-up is warranted.

PMID:40540492 | DOI:10.1371/journal.pone.0325206

Genetics. 2025 Jun 20:iyaf118. doi: 10.1093/genetics/iyaf118. Online ahead of print.

ABSTRACT

Epistasis can profoundly influence evolutionary dynamics. Temporal genetic data, consisting of sequences sampled repeatedly from a population over time, provides a unique resource to understand how epistasis shapes evolution. However, detecting epistatic interactions from sequence data is technically challenging. Existing methods for identifying epistasis are computationally demanding, limiting their applicability to real-world data. Here, we present a novel computational method for inferring epistasis that substantially reduces computational costs without sacrificing accuracy. We validated our approach in simulations and applied it to study HIV-1 evolution over multiple years in a data set of 16 individuals. There we observed a strong excess of negative epistatic interactions between beneficial mutations, especially mutations involved in immune escape. Our method is general and could be used to characterize epistasis in other large data sets.

PMID:40540490 | DOI:10.1093/genetics/iyaf118

PLoS One. 2025 Jun 20;20(6):e0322228. doi: 10.1371/journal.pone.0322228. eCollection 2025.

ABSTRACT

OBJECTIVE: Acute kidney injury (AKI) is one of the common complications after hip fracture in the elderly, and its hospitalization rate, mortality rate and medical expenses are high, resulting in serious social and economic burden. Therefore, we aim to systematically evaluate the incidence and risk factors of postoperative AKI in elderly patients with hip fracture, so as to identify the occurrence of postoperative AKI in elderly patients with hip fracture early, so as to prevent it in advance.

METHODS: This meta-analysis adhered to PRISMA guidelines and was registered in PROSPERO (CRD42024498009).We systematically searched Embase, Pubmed, web of science, the cochrane Library, CBM, VIP, CNKI, and Wanfang Data to collect studies on the incidence or influencing factors of postoperative acute kidney injury in elderly patients with hip fracture published up to 18 December 2023. All studies were screened, relevant data extracted, and quality assessed by two independent authors, and meta-analysis was performed using Stata 15.0 software.

RESULTS: A total of 22 articles were included, with a total sample size of 25195 cases and 16 influencing factors. The results of meta-analysis showed that the incidence of postoperative AKI in elderly patients with hip fracture was 17.2% [95%CI (14.3% ~ 20%), P < 0.0001], and there were 6 statistically significant influencing factors, which were baseline serum potassium [OR(95%CI)=2.23 (1.22, 4.05)], hypertension [OR(95%CI)=3.00 (1.75, 5.88)], and chronic kidney disease [OR(95%CI)=4.40 (1.10, 14.75)], diabetes mellitus [OR (95% CI) = 1.84 (1.19, 2.83)], intraoperative hypotension [OR (95% CI) = 5.61 (3.36, 9.35)], and operative time [OR (95% CI) = 1.01 (1.00, 1.02)].

CONCLUSIONS: Our study indicated that the incidence of postoperative AKI in elderly patients with hip fracture was 17.2%. Baseline serum potassium, hypertension, chronic kidney disease, diabetes, operative hypotension and operation time were the influencing factors of postoperative AKI in elderly patients with hip fracture. PROSPERO registration number for this study: CRD42024498009.

PMID:40540489 | DOI:10.1371/journal.pone.0322228

PLoS One. 2025 Jun 20;20(6):e0326040. doi: 10.1371/journal.pone.0326040. eCollection 2025.

ABSTRACT

BACKGROUND: Lymphedema is a chronic condition that significantly affects both physical function and quality of life of breast cancer patients. Although there is no definitive cure, various treatment options exist to alleviate its symptoms. Among these, Complex Decongestive Therapy (CDT) is widely regarded as a primary approach. This study seeks to evaluate the effectiveness of CDT for breast cancer patients with upper limb lymphedema and aims to assess the benefits of this treatment despite the challenges and constraints in resource-limited settings.

METHODS: This observational study was conducted among 42 female breast cancer patients with unilateral upper limb lymphedema attending the Lymphedema Clinic of the Department of Palliative Medicine at Bangladesh Medical University in Dhaka, Bangladesh. Limb volume, skin condition, and clinical signs and symptoms were assessed at baseline. All patients received the intensive phase of Complex Decongestive Therapy (CDT) for 6 weeks, with follow-up assessments conducted at the 3rd week and the 6th week.

RESULT: A significant reduction in the volume of the affected limbs was observed from baseline to the 6th week, as well as from the 3rd week to the 6th week. Although no statistically significant improvement in skin edema was recorded during this period, visible clinical improvement in skin texture was noted. After receiving CDT and proper skin care, 59.5% of patients regained normal skin on the affected limb. Additionally, there was a significant reduction in self-reported symptoms such as tightness, heaviness, and pain in the affected limb from baseline to the 6th week.

CONCLUSION: Lymphedema management using all components of Complex Decongestive Therapy (CDT) was found to be effective in reducing limb volume and alleviating the distressing symptoms of patients. Timely referral of lymphedema patients to specialized clinics and initiation of CDT can significantly reduce their ongoing suffering in Bangladesh.

PMID:40540462 | DOI:10.1371/journal.pone.0326040

Int J Surg. 2025 Jun 20. doi: 10.1097/JS9.0000000000002790. Online ahead of print.

ABSTRACT

BACKGROUND: In-situ, ante-situm, ex-situ liver resections under hypothermic perfusion (HP) are expanding tumor resectability as they could allow extensive hepatectomies and intricate vascular reconstructions. Meanwhile, hypothermic oxygenated machine perfusion (HOPE) has been well-established in liver transplantation, showing improved graft and patient outcomes. However, the quality of surgical treatment using HOPE in these non-transplant liver surgeries remains unproven.

MATERIALS AND METHODS: An exhaustive literature research and polled analysis to study the efficacy of HOPE for in-situ, ante-situm, ex-situ liver resections for hepatic malignancies were performed. Considering the sufficiency of reported data, the ante-situm liver resection under HOPE for intrahepatic cholangiocarcinoma was selected to make comparisons focusing on perioperative surgical outcome and long-term oncological outcomes. Control groups were ante-situm liver resection under conventional HP and ante-situm liver resection without conventional HP (relying on total vascular exclusion, TVE).

RESULTS: Three publications, reporting two case reports and one case series report, were identified with seven cases altogether. Generally, median hospital stay was 17 (12-30) days, 90-day severe complications occurred 14.3% (1/7) patients, no 90-day mortality was observed, median survival was 14.5 (6-34) months. Median hospital stay, 90-day severe complication and mortality rates of ante-situm approach under HOPE (n = 5) were better than conventional HP (n = 6) or TVE approaches (n = 6) [17 (12-30) vs. 26.5 (16-70) vs. 28 (20-54), 20% vs. 50% vs. 33.3%, 0% vs. 16.7% vs. 16.7%; no statistical significance]; however, 6-month recurrence rate was higher (60% vs. 0% vs. 20%), restricted mean recurrence-free survival was shorter [6.6 (95%CI: 3.6-9.2) vs. 9.1 (95%CI: 5.5-11) vs. 8.7 (95%CI: 4.8-12.7)], and restricted mean overall survival showed insignificance.

CONCLUSIONS: Although HOPE may improve perioperative outcomes of in-situ, ante-situm, ex-situ liver resections, current evidence suggests suboptimal oncological results of ante-situm approach under HOPE, highlighting the need for further refinement.

PMID:40540312 | DOI:10.1097/JS9.0000000000002790

Musculoskeletal Care. 2025 Jun;23(2):e70137. doi: 10.1002/msc.70137.

ABSTRACT

BACKGROUND: The rise of telehealth has transformed healthcare delivery, but its impact on treatment adherence compared with traditional outpatient departments (OPD) remains underexplored.

OBJECTIVE: This study aimed to assess and compare patient adherence to treatment protocols in telehealth with regular OPD settings among patients with neck pain.

METHODS: A cross-sectional study was conducted at SGT University with neck pain patients in telehealth and traditional OPD settings. Adherence was measured using a validated adherence scale and electronic health records. Data were analysed using statistical methods to identify significant differences between the two groups.

RESULTS: A total of 300 patients participated, with 150 in the telehealth group and 150 in the regular OPD group. Preliminary findings indicated adherence rates. Factors influencing adherence, such as convenience and accessibility, were also analysed.

CONCLUSION: Telehealth appears to enhance treatment adherence compared with traditional outpatient care. These findings suggest that integrating telehealth into healthcare delivery may improve patient outcomes. Future research should explore long-term adherence trends and the underlying mechanisms that drive these differences.

PMID:40540309 | DOI:10.1002/msc.70137

JAMA Health Forum. 2025 Jun 7;6(6):e251381. doi: 10.1001/jamahealthforum.2025.1381.

ABSTRACT

IMPORTANCE: Food insecurity, which is characterized by limited or uncertain access to adequate food, affects approximately 40 million individuals in the US, including many patients with cancer. Understanding the association between food insecurity and cancer mortality is crucial for improving patient outcomes and addressing health disparities.

OBJECTIVE: To investigate the association of food insecurity with cancer-specific and all-cause mortality among US adults with a diagnosis of cancer.

DESIGN, SETTING, AND PARTICIPANTS: This cohort study used nationally representative data from the 2011 to 2012 National Health Interview Survey that were linked to the National Death Index, with mortality follow-up through December 31, 2019. It included 5603 respondents to the National Health Interview Survey 40 years and older who reported receiving a diagnosis of cancer and responded to food security questions.

EXPOSURE: Food insecurity was measured using a validated 10-item National Center for Health Statistics food insecurity scale, categorized as food secure (0-2) or food insecure (3-10) based on US Department of Agriculture guidelines.

MAIN OUTCOMES AND MEASURES: The primary outcomes were cancer-specific mortality (International Statistical Classification of Diseases and Related Health Problems, Tenth Revision codes: C00-C97) and all-cause mortality. Cox proportional hazards models were used to estimate hazard ratios (HRs) for these outcomes, adjusting for age, sex, race and ethnicity, household income, US region, body mass index, smoking, alcohol use, comorbidities, and survey year.

RESULTS: Among the 5603 participants (mean [SD] age, 67.03 [12.03] years; 3298 female individuals [59%]; 320 Hispanic individuals [6%], 22 Native American individuals [0.4%], 136 non-Hispanic Asian individuals [2%], 529 non-Hispanic Black individuals [9%], 4519 non-Hispanic White individuals [81%], and 75 multiracial or multiethnic individuals [1%]), the prevalence of food insecurity was 10.3% among survivors of cancer. Food insecurity was associated with higher all-cause mortality (HR, 1.28; 95% CI, 1.07-1.53) but not cancer-specific mortality after full adjustment. Subgroup analyses indicated that food insecurity was associated with cancer and all-cause mortality for those individuals with household incomes 200% or greater than the federal poverty level (cancer-specific mortality: HR, 1.93; 95% CI, 1.18-3.15; all-cause mortality: HR, 1.89; 95% CI, 1.34-2.68) and those not receiving food assistance (cancer-specific mortality: HR, 1.42; 95% CI, 1.00-2.01; all-cause mortality: HR, 1.42; 95% CI, 1.14-1.76). However, there was no significant association between food insecurity and cancer-specific or all-cause mortality for people with incomes less than 100% of the federal poverty level and households participating in food assistance programs.

CONCLUSIONS AND RELEVANCE: The results of this cohort study suggest that food insecurity is a substantial factor associated with increased mortality among survivors of cancer. Addressing food insecurity through routine screenings and connecting patients with food assistance programs may improve survival outcomes, and further research should examine the longitudinal effects of integrating routine food insecurity screenings within cancer care settings and expanding food assistance program eligibility.

PMID:40540285 | DOI:10.1001/jamahealthforum.2025.1381

JAMA Health Forum. 2025 Jun 7;6(6):e251476. doi: 10.1001/jamahealthforum.2025.1476.

ABSTRACT

IMPORTANCE: Private equity (PE) has rapidly been acquiring physician practices in the US, but a full understanding of its association with health care prices, spending, utilization, and quality is still unknown.

OBJECTIVE: To examine changes in colonoscopy prices, spending, utilization, and quality associated with PE acquisition of gastroenterology practices.

DESIGN, SETTING, AND PARTICIPANTS: This difference-in-differences event study and economic evaluation analyzed data from US gastroenterology practices that were acquired by PE firms between 2015 and 2021. Commercial claims covering more than 50 million enrollees were used to calculate price, spending, utilization, and quality measures from 2012 to 2021. The data were analyzed between April 2024 and September 2024.

EXPOSURES: PE acquisition of gastroenterology practices.

MAIN OUTCOMES AND MEASURES: The main outcomes were price, spending per physician, number of colonoscopies per physician, number of unique patients per physician, and quality (polypectomy detection, incomplete colonoscopies, and 4 adverse event measures: cardiovascular, serious gastroenterology, nonserious gastroenterology, and any adverse event).

RESULTS: Data from more than 1.1 million patients (mean [SD] age, 47.1 [8.4] years; 47.8% male patients) undergoing 1.3 million colonoscopies were analyzed. The sample included 718 851 treated colonoscopies conducted by 1494 physicians among 590 900 patients across 1240 PE-acquired practice sites and 637 990 control colonoscopies conducted by 2550 physicians among 527 380 patients across 2657 independent practice sites. Colonoscopy prices at PE-acquired gastroenterology practices increased by 4.5% (95% CI, 2.5%-6.6%; P < .001) relative to independent gastroenterology practices. The estimated price effect increased to 6.7% (95% CI, 4.2%-9.3%; P < .001) when considering only colonoscopies performed by gastroenterologists in PE-acquired practices with market shares above the 75th percentile (24.4%) in 2021 as treated. Colonoscopy spending per physician increased by 16.0% (95% CI, 8.4%-24.0%; P < .001), while the number of colonoscopies and the number of unique patients per physician increased by 12.1% (95% CI, 5.3%-19.4%; P < .001) and 11.3% (95% CI, 4.4%-18.5%; P < .001), respectively; however, these spending and utilization measures were already increasing prior to PE acquisition. No statistically significant associations were detected for the 6 quality measures analyzed.

CONCLUSIONS AND RELEVANCE: In this economic evaluation, PE acquisition of gastroenterology practices led to higher prices and spending but had no discernible effect on quality. Policymakers may be well advised to monitor PE investment in physician practices given the increase in prices and spending without a commensurate increase in quality.

PMID:40540284 | DOI:10.1001/jamahealthforum.2025.1476

JAMA Netw Open. 2025 Jun 2;8(6):e2516468. doi: 10.1001/jamanetworkopen.2025.16468.

ABSTRACT

IMPORTANCE: Cancer-related cognitive impairment is a common concern after breast cancer treatment. However, the association between breast cancer survivorship and the risk of Alzheimer dementia (AD) remains unclear.

OBJECTIVE: To evaluate the risk of AD among breast cancer survivors compared with cancer-free controls and examine the potential association of cancer treatments with AD risk.

DESIGN, SETTING, AND PARTICIPANTS: This retrospective cohort study used data from the Korean National Health Insurance Service. A total of 70 701 patients who underwent breast cancer surgery between January 1, 2010, and December 31, 2016, were included and matched with cancer-free controls (1:3). Participants were followed up for a median (IQR) of 7.3 (5.7-9.0) years. Data analysis was performed from January 2024 to June 2024.

EXPOSURES: Breast cancer diagnosis, surgery, and subsequent treatments, including anthracycline chemotherapy and radiation therapy.

MAIN OUTCOMES AND MEASURES: The primary outcome was the incidence of AD. Subdistribution hazard ratios (SHRs) and 95% CIs were calculated using competing risk regression models, adjusting for sociodemographic factors and comorbidities.

RESULTS: Among 70 701 breast cancer survivors (mean [SD] age, 53.1 [8.5] years), 1229 cases of AD were detected, with an incidence rate of 2.45 per 1000 person-years. Survivors exhibited a slightly lower risk of AD compared with cancer-free controls (SHR, 0.92; 95% CI, 0.86-0.98), especially among individuals 65 years or older (SHR, 0.92; 95% CI, 0.85-0.99). However, landmark analyses found that this lower risk did not persist beyond 5 years of survival. Cancer treatment with radiation therapy (adjusted HR, 0.77; 95% CI, 0.68-0.87) was associated with reduced risk of AD among survivors.

CONCLUSIONS AND RELEVANCE: This cohort study of breast cancer survivors found a lower risk of AD compared with cancer-free controls, despite common concerns about cognitive decline after treatment. The findings suggest certain cancer treatments potentially have benefits for lower AD risk. Further research is needed to assess the long-term risk of AD in this population.

PMID:40540273 | DOI:10.1001/jamanetworkopen.2025.16468