Nevin Manimala

JCO Glob Oncol. 2025 Mar;11:e2400337. doi: 10.1200/GO-24-00337. Epub 2025 Mar 7.

ABSTRACT

PURPOSE: Low rates of germline genetic testing (GGT) for breast cancer (BC) have been reported globally, with limited data from low- and middle-income countries (LMICs). In this study, we used real-world data to assess the GGT rate for BC in an LMIC and identified barriers to its use.

METHODS: We analyzed 2,974 newly diagnosed patients with BC from the AMAZONA III study, the largest Brazilian multicenter, prospective BC cohort. GGT rates were determined for the entire cohort and the high-risk hereditary BC group (HR), defined by the National Comprehensive Cancer Network criteria, between 2019 and 2020. Barriers to GGT performance associated with patient characteristics and health care systems were identified using multivariable Poisson regression model. Values of P < .05 were considered significant.

RESULTS: In the AMAZONA III cohort, 1,476 (49%) were classified as HR. Genetic counseling was recommended for 521 patients (35% of HR), and 282 (19%) underwent GGT. Notably, 97% of patients with HR treated within the public health care systems and 56% in the private system did not undergo GGT. Age, education, occupation, monthly income, availability of onsite genetic counseling, and treatment at a teaching center were factors associated with GGT uptake (P < .05). Of those tested, 50 (17%) harbored a germline pathogenic or likely pathogenic variant.

CONCLUSION: Only 9% of this robust Brazilian BC cohort underwent GGT, highlighting a considerable gap from the current recommendation to test all patients with BC under age 65 years. GGT is underused by patients with HR in both public and private health care systems, with those in the public system being more affected. The disparities and barriers identified emphasize the need for educational interventions and enhanced access to GGT. Prioritizing GGT is critical to improving BC outcomes in LMICs.

PMID:40053901 | DOI:10.1200/GO-24-00337

JCO Glob Oncol. 2025 Mar;11:e2400277. doi: 10.1200/GO-24-00277. Epub 2025 Mar 7.

ABSTRACT

PURPOSE: To evaluate the toxicity profile and efficacy of postoperative ultra-hypofractionated radiation therapy in elderly patients with breast cancer.

MATERIALS AND METHODS: This is a nonrandomized, single-center, prospective Phase II trial. Patients with breast cancer older than 65 years were treated with ultra-hypofractionated radiation therapy in 5 fractions of 5.7 Gy on alternate days in the breast or chest wall, or regional lymph nodes. The primary end point was acute toxicity.

RESULTS: A total of 60 patients were analyzed, with a median follow-up of 42.5 months (range, 13.8-66.2). Most patients presented pathologic stage I (56.6%, n = 34) or stage II (33.3%, n = 20) disease. Regional lymph node irradiation was performed in 22% (n = 13) of patients. During treatment, 51% (n = 31) of patients experienced grade 1 or 2 acute toxicity, with no cases of grade 3 acute toxicity reported. Late toxicity included 1.7% (n = 1) of patients developing grade 3 fibrosis and 1.7% (n = 1) developing grade 3 pneumonitis. Regional lymph node irradiation was not associated with a statistically significant increase in toxicity risk (P = .194). Cosmesis evaluations revealed no significant changes when comparing pretreatment assessments with evaluations at 10 weeks (P = .223) and 26 weeks (P = .615) post-treatment. Quality of life was not adversely affected, regardless of whether regional lymph nodes were irradiated. Recurrence rates included two patients with both locoregional and distant recurrence and five patients with distant recurrence. The 3-year disease-free survival probability was 81.7%, and the 3-year overall survival probability was 86.7%.

CONCLUSION: This study demonstrates the safety of ultra-hypofractionated radiation therapy in terms of toxicity in patients with breast cancer. The findings for side effects, cosmesis, quality of life, and survival outcomes are consistent with those observed in moderately hypofractionated radiation therapy regimens, suggesting its use as a viable treatment option in this demographic.

PMID:40053900 | DOI:10.1200/GO-24-00277

J Clin Oncol. 2025 Mar 7:JCO2402850. doi: 10.1200/JCO-24-02850. Online ahead of print.

ABSTRACT

The European Paediatric Soft Tissue Sarcoma Study Group (EpSSG) RMS 2005 trial evaluated maintenance chemotherapy in high-risk rhabdomyosarcoma (RMS). Patients were randomly assigned to either discontinue treatment (standard arm) or receive six 28-day cycles of vinorelbine (25 mg/m²) once per day on days 1, 8, and 15, plus once daily low-dose cyclophosphamide (25 mg/m²; experimental arm). Initial results showed improved overall survival (OS), but disease-free survival (DFS) improvement was not statistically significant. This report presents mature survival outcomes after extended follow-up. Between April 2006 and December 2016, 186 patients were enrolled in the standard arm and 185 in the experimental arm. After a median follow-up of 122.1 months from diagnosis and 114 months from random assignment, recurrence, progression, or death occurred in 103 patients (61 standard arm, 42 experimental arm). The 10-year DFS was 66.5% (95% CI, 59 to 74) in the standard arm versus 77.1% (95% CI, 70.3 to 82.5) in the experimental arm (P = .025). Corresponding 10-year OS rates were 70.8% (95% CI, 63.3 to 77.0) and 82.9% (95% CI, 76.6 to 87.7; P = .0099). Long-term results of the RMS2005 trial confirm the survival benefit of maintenance chemotherapy with vinorelbine and low-dose cyclophosphamide for patients with high-risk RMS.

PMID:40053891 | DOI:10.1200/JCO-24-02850

Am J Speech Lang Pathol. 2025 Mar 7:1-39. doi: 10.1044/2024_AJSLP-24-00350. Online ahead of print.

ABSTRACT

PURPOSE: The aim of this systematic review was to analyze the published research on training approaches for preparing current and future speech-language pathologists (SLPs) to work effectively with people with aphasia (PWA). The review addresses key questions regarding the described training approaches, their key features, research quality, and efficacy.

METHOD: The review was conducted in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines and registered with International Prospective Register of Systematic Reviews (CRD42024453742). The literature search spanned nine databases. Eligibility criteria included peer-reviewed publications in English that reported on training programs involving current or future SLPs working with PWA. Studies were assessed for research quality using the American Speech-Language-Hearing Association’s (ASHA’s) levels of evidence framework. Narrative synthesis was used to identify key features in the training programs.

RESULTS: A total of 920 citations were identified, with 50 studies meeting the inclusion criteria for analysis. Included studies represented a broad range of training approaches, research designs, and research quality. The 50 studies fell into ASHA levels of evidence Ib, IIa, IIb, III, and IV. Statistical meta-analysis was not possible because of variability in research design and outcome measures, but the studies revealed statistically significant findings relevant to the question of what makes training effective for preparing clinicians to work with people with aphasia.

CONCLUSIONS: The current literature related to training of clinicians to work with PWA is heterogeneous in approach, outcome metrics, and methodological quality. There is evidence supporting several recommendations for training clinicians including integrating direct interactions with PWA during training, combining didactic and experiential learning, and incorporating reflective practices. Overall, the review highlights the need for well-described evidence-based training standards for speech-language pathology students working with PWA. Future research should aim to develop and validate comprehensive training guidelines to improve care quality for individuals with aphasia.

PMID:40053876 | DOI:10.1044/2024_AJSLP-24-00350

Aging (Albany NY). 2025 Mar 6;17. doi: 10.18632/aging.206217. Online ahead of print.

ABSTRACT

Inflammation plays a pivotal role in the age-related decline of skeletal muscle mass, leading to sarcopenia in the elderly. The prevalence of sarcopenia notably increases among males aged ≥ 70. However, it remains unclear whether inflammatory indexes are associated with the reduction in skeletal muscle mass in the elderly population. Thirty-one males aged ≥ 70, without severe diseases or dementia, were enrolled in the study. They underwent muscle mass measurements, physical measurements, and hematological tests at the onset of the study and after a one-year follow-up. Twenty-eight participants were successfully followed for one year. Appendicular skeletal muscle mass index (ASMI) decreased by 3.30 ± 2.41% in 14 participants and increased by 2.66 ± 1.61% in the other 14 participants compared to baseline levels. The baseline neutrophil-to-lymphocyte ratio (NLR) was 2.14 ± 0.56 in the ASMI-decreased group and 1.66 ± 0.62 in the ASMI-increased group. A statistically significant negative correlation was found between baseline NLR and the change in ASMI in linear regression analyses. The area under the curve (AUC) of the baseline NLR for predicting ASMI decline was 0.724, with an optimal sensitivity of 64.3% and specificity of 78.6% at a cut-off value of 1.94. NLR emerged as a potential prognostic marker for ASMI reduction in elderly males. However, further studies are necessary to assess its clinical utility.

PMID:40053874 | DOI:10.18632/aging.206217

J Proteome Res. 2025 Mar 7. doi: 10.1021/acs.jproteome.4c01068. Online ahead of print.

ABSTRACT

Computational toolkits for data exploration and visualization from widely used omics platforms often lack flexibility and customization. While many tools generate standardized output, advanced programming skills are necessary to create high-quality visualizations. Therefore, user-friendly tools that simplify this crucial, yet time-consuming, step are essential. We developed EasyPubPlot (Easy Publishable Plotting), a straightforward, easy-to-use, no-coding, user experience-oriented, open-source, and shiny web application along with its associated R package to streamline data exploration and visualization for functional omics-empowered research. EasyPubPlot generates publishable scores plots, volcano plots, heatmaps, box plots, dot plots, and bubble plots with minimal necessary steps. The tool was designed to guide new users to accurate and efficient navigation. Step-by-step tutorials for each type of plot are also provided. Herein, we demonstrated EasyPubPlot’s competent functionality and versatility by showcasing metabolomics, proteomics, and transcriptomics data. Collectively, EasyPubPlot reduces the gap between data analysis and stunning visualization, thereby diminishing friction and focusing on science. The app can be downloaded and installed locally (https://github.com/Pharmaco-OmicsLab/EasyPubPlot) or used through a web application (https://pharmaco-omicslab.shinyapps.io/EasyPubPlot).

PMID:40053871 | DOI:10.1021/acs.jproteome.4c01068

Adv Neonatal Care. 2025 Mar 7. doi: 10.1097/ANC.0000000000001233. Online ahead of print.

ABSTRACT

BACKGROUND: Sex-specific differences exist in morbidity and growth yet little is known about other nutritional outcomes in preterm very low birth-weight (VLBW) infants. This is important because providing optimal nutrition is essential to promote growth and reduce neurodevelopmental impairment.

PURPOSE: To determine the effect of sex on days to full enteral feedings and other nutritional outcomes.

METHODS: This was a longitudinal 2-group cohort study using secondary analysis of existing data of 313 infants born ≤32 weeks gestation and weighing ≤1500 g. Information regarding nutritional outcomes was obtained from the infant’s electronic medical records.

RESULTS: While not statistically significant, male infants reached full feeds nearly 3 days later (18.1 vs 15.2; P = .89), required parenteral nutrition for nearly an additional 4 days (18.3 vs 14.1; P = .37), and had a central line for 3 days longer (19.6 vs 15.7; P = .65) than female infants. Males had higher direct bilirubin levels (P = .02), more emesis (P = .003), and more late-onset sepsis (P = .03). Birth weight for males was higher at birth but not at 6 weeks and while the slope of weight increase over the 6 weeks was higher in males (P = .04), growth velocity was similar between sexes yet tended to be higher in females.

IMPLICATIONS FOR PRACTICE AND RESEARCH: Nurses are essential in ensuring preterm infants in the neonatal intensive care unit receive optimal nutrition. This study supports nurses should consider sex-specific differences in nutritional outcomes among VLBW infants in precision based nutritional support.

PMID:40053867 | DOI:10.1097/ANC.0000000000001233

J Extra Corpor Technol. 2025 Mar;57(1):14-17. doi: 10.1051/ject/2024041. Epub 2025 Mar 7.

ABSTRACT

BACKGROUND: Patients receiving mechanical circulatory support (MCS) frequently require renal replacement therapy (RRT). Examining risk factors for requiring RRT in patients receiving MCS may allow improved understanding of these comorbidities and enhance patient outcomes.

METHODS: Following IRB approval, patient characteristics, comorbidities, and the need for RRT were studied in 129 patients who received MCS from January 2017 to October 2023. The clinical variables underwent machine learning to examine their relationships to the outcome of interest, the need for RRT.

RESULTS: In this study, the incidence of RRT was 36% with a 95% confidence interval ranging from 29% to 44%. Following machine learning, patients with a history of immunologic therapy or having a pacemaker or internal cardiac defibrillator (ICD) were associated with the need for RRT (χ² = 44, P = 0.0003). The c-index statistic for this model was 0.81. The anticoagulation therapy administered in these two groups was also analyzed. Patients in these two groups receiving unfractionated heparin were observed to have a higher incidence (44%) in the need for RRT.

CONCLUSION: The incidence of RRT was high in this patient population. The novel associations in patients requiring MCS who have received prior immunologic therapy or have pre-existing pacemaker/ICDs suggest that an increased systemic inflammatory state exists that escalates the need for RRT. Unfractionated heparin appears to provide minimal protection from the need for RRT in patients requiring MCS. These findings suggest that other options for systemic anticoagulation in patients requiring MCS should be considered. Further investigation into how these background inflammatory conditions contribute to the need for RRT in patients requiring MCS is warranted.

PMID:40053853 | DOI:10.1051/ject/2024041

Proc Natl Acad Sci U S A. 2025 Mar 11;122(10):e2413443122. doi: 10.1073/pnas.2413443122. Epub 2025 Mar 7.

ABSTRACT

Large language models can now generate political messages as persuasive as those written by humans, raising concerns about how far this persuasiveness may continue to increase with model size. Here, we generate 720 persuasive messages on 10 US political issues from 24 language models spanning several orders of magnitude in size. We then deploy these messages in a large-scale randomized survey experiment (N = 25,982) to estimate the persuasive capability of each model. Our findings are twofold. First, we find evidence that model persuasiveness is characterized by sharply diminishing returns, such that current frontier models are only slightly more persuasive than models smaller in size by an order of magnitude or more. Second, we find that the association between language model size and persuasiveness shrinks toward zero and is no longer statistically significant once we adjust for mere task completion (coherence, staying on topic), a pattern that highlights task completion as a potential mediator of larger models’ persuasive advantage. Given that current frontier models are already at ceiling on this task completion metric in our setting, taken together, our results suggest that further scaling model size may not much increase the persuasiveness of static LLM-generated political messages.

PMID:40053360 | DOI:10.1073/pnas.2413443122

JAMA Netw Open. 2025 Mar 3;8(3):e250185. doi: 10.1001/jamanetworkopen.2025.0185.

ABSTRACT

IMPORTANCE: Best practices for improving access to assessment of hereditary cancer risk in primary care are lacking.

OBJECTIVE: To compare 2 population-based engagement strategies for identifying primary care patients with a family or personal history of cancer and offering eligible individuals genetic testing for cancer susceptibility.

DESIGN, SETTING, AND PARTICIPANTS: The EDGE (Early Detection of Genetic Risk) clinical trial cluster-randomized 12 clinics from 2 health care systems in Montana, Wyoming, and Washington state to 1 of 2 engagement approaches for assessment of hereditary cancer risk in primary care. The study population included 95 623 English-speaking patients at least 25 years old with a primary care visit during the recruitment window between April 1, 2021, and March 31, 2022.

INTERVENTION: The intervention comprised 2 risk assessment engagement approaches: (1) point of care (POC), conducted by staff immediately preceding clinical appointments, and (2) direct patient engagement (DPE), where letter and email outreach facilitated at-home completion. Patients who completed risk assessment and met prespecified criteria were offered genetic testing via a home-delivered saliva testing kit at no cost.

MAIN OUTCOMES AND MEASURES: Primary outcomes were the proportion of patients with a visit who (1) completed the risk assessment and (2) completed genetic testing. Logistic regression models were used to compare the POC and DPE approaches, allowing for overdispersion and including clinic as a design factor. An intention-to-treat analysis was used to evaluate primary outcomes.

RESULTS: Over a 12-month window, 95 623 patients had a primary care visit across the 12 clinics. Those who completed the risk assessment (n = 13 705) were predominately female (64.7%) and aged between 65 and 84 years (39.6%). The POC approach resulted in a higher proportion of patients completing risk assessment than the DPE approach (19.1% vs 8.7%; adjusted odds ratio [AOR], 2.68; 95% CI, 1.72-4.17; P < .001) but a similar proportion completing testing (1.5% vs 1.6%; AOR, 0.96; 95% CI, 0.64-1.46; P = .86). Among those eligible for testing, POC test completion was approximately half of that for the DPE approach (24.7% vs 44.7%; AOR, 0.49; 95% CI, 0.37-0.64; P < .001). The proportion of tested patients identified with an actionable pathogenic variant was significantly lower for the POC approach than the DPE approach (3.8% vs 6.6%; AOR, 0.61; 95% CI, 0.44-0.85; P = .003).

CONCLUSIONS AND RELEVANCE: In this cluster randomized clinical trial of risk assessment delivery, POC engagement resulted in a higher rate of assessment of hereditary cancer risk than the DPE approach but a similar rate of genetic testing completion. Using a combination of engagement strategies may be the optimal approach for greater reach and impact.

TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04746794.

PMID:40053353 | DOI:10.1001/jamanetworkopen.2025.0185