Nevin Manimala

Gigascience. 2025 Oct 30:giaf139. doi: 10.1093/gigascience/giaf139. Online ahead of print.

ABSTRACT

BACKGROUND: While cell-free DNA (cfDNA) is a promising biomarker for cancer diagnosis and monitoring, there is limited agreement on optimal cfDNA collection and extraction protocols as well as analysis pipelines of the corresponding cfDNA sequencing data. In this paper, we address the latter by studying the effect of various bioinformatics preprocessing choices on derived genetic and epigenetic cfDNA features and study how observed feature differences influence the downstream task of separating between healthy and cancer cfDNA samples.

RESULTS: Using low-pass whole-genome cfDNA sequencing data from 20 lung cancer and 20 healthy samples, we assessed the influence of various preprocessing settings such a read trimming, filtering of secondary alignments and choice of genome build as well as practices such as downsampling or selecting for short fragment on derived cfDNA features including cfDNA fragment size, fragment end motifs, copy number alterations, and nucleosome footprints. Our results demonstrate that the analyzed features are robust to common preprocessing choices, but exhibit variable sensitivity to sequencing coverage. Fragment length statistics and end motifs are the least affected by low coverages, whereas nucleosome footprint analysis is very sensitive to it. Our findings confirm that selecting for shorter fragments, enhances cancer-specific signals, however, by removing data, also reduces signals in general. Interestingly, we find that fragment end motif analysis benefits the most from in silico size selection. We also observe that the filtering of low-quality and secondary alignments and choice of genome build result in slight improvements in cancer classification performance based on nucleosome coverage and copy number features.

CONCLUSIONS: Altogether, we conclude that cfDNA analysis is minimally affected by different bioinformatics preprocessing settings, however we describe some synergistic effects between analytical approaches, which can be leveraged to improve cancer detection.

PMID:41165721 | DOI:10.1093/gigascience/giaf139

JAMA. 2025 Oct 30. doi: 10.1001/jama.2025.18109. Online ahead of print.

NO ABSTRACT

PMID:41165718 | DOI:10.1001/jama.2025.18109

JAMA Netw Open. 2025 Oct 1;8(10):e2540065. doi: 10.1001/jamanetworkopen.2025.40065.

ABSTRACT

IMPORTANCE: There is a need to determine the relative effect of message-based psychotherapy (MBP), an asynchronous approach that uses emails, texts, or voice or video messages to permit therapeutic exchanges, compared with video-based psychotherapy (VBP) and whether a combination of modalities would result in better outcomes for those who do not respond to either treatment alone.

OBJECTIVES: To compare MBP with VBP on a commercial digital mental health platform and test combinations of modalities for participants who did not respond to single-modality treatment.

DESIGN, SETTING, AND PARTICIPANTS: In this sequential multiple assignment randomized clinical trial, psychotherapy was delivered by therapists on a commercial digital mental health platform from January 10, 2022, to January 14, 2024, among 850 participants who were 18 years of age or older, English or Spanish speaking, living in the US in a state where the digital mental health platform had available therapists, scored 10 or more on the 9-item Patient Health Questionnaire (PHQ-9), and received a diagnosis of depression during intake assessment.

INTERVENTIONS: At baseline, participants were randomized to MBP or weekly VBP. At week 6, nonresponders were rerandomized to MBP with weekly or monthly VBP. Participants received treatment for 12 weeks.

MAIN OUTCOMES AND MEASURES: Primary outcomes included depression severity (measured by the PHQ-9), social functioning, response to treatment, and remission. Secondary outcomes included treatment engagement, therapeutic alliance, and indicators of treatment quality and satisfaction. Analysis was performed on an intention-to-treat basis.

RESULTS: The analytic sample included 850 participants (mean [SD] age, 33.8 [10.5] years; 562 women [66.1%]; mean [SD] PHQ-9 score, 15.0 [4.8]), with 423 randomized to MBP and 427 to VBP. Treatment disengagement by week 5 was more likely for VBP than MBP (VBP, 91 [21.3%]; MBP, 56 [13.2%]; Cramér V = 0.10; 95% CI, 0.03-0.13; P = .003). There were no significant differences on depression or social functioning score changes between MBP and VBP or on depression score changes for nonresponders randomized to MBP with weekly vs monthly VBP. At week 12, MBP and VBP did not differ in the proportion of participants who responded to treatment (MBP, 144 of 303 [47.5%]; VBP, 134 of 284 [47.2%]; Cramér V < .001; 95% CI, -0.08 to 0.09; P = .99) or who experienced remission (MBP, 95 of 303 [31.4%]; VBP, 86 of 284 [30.3%]; Cramér V = 0.01; 95% CI, -0.07 to 0.09; P = .85). Among nonresponders, VBP had a stronger initial therapeutic alliance than MBP at week 4 (P < .001; d = 0.48-0.57). Among participants assessed for rerandomization, there were no statistically significant differences among those who responded to treatment by week 5 (MBP, 105 of 363 [28.9%]; VBP, 93 of 336 [27.7%]; Cramér V = 0.01; 95% CI, -0.06 to 0.08; P = .78). Therapeutic alliance ratings increased across all conditions by week 10; however, these changes were not statistically significant. Video-based psychotherapy was more frequently recommended than MBP (VBP, 69 of 71 [97.2%]; MBP, 70 of 80 [87.5%]; odds ratio, 0.18; 95% CI, 0.04-0.88; P = .03). There were no significant differences in clinical outcomes between nonresponders randomized to weekly vs monthly VBP.

CONCLUSIONS AND RELEVANCE: In this sequential multiple assignment randomized clinical trial comparing MBP with VBP, there were no differences between groups on improvement in depression or social functioning. More participants in the VBP group disengaged from treatment, while VBP also had greater therapeutic alliance early in treatment among nonresponders. There were no differential effects from rerandomizing nonresponders. Findings reinforced MBP as a viable alternative to VBP. Broader insurance reimbursement for MBP could improve access to evidence-based care. Future research should explore optimizing early alliance-building in MBP.

TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04513080.

PMID:41165707 | DOI:10.1001/jamanetworkopen.2025.40065

JAMA Netw Open. 2025 Oct 1;8(10):e2540453. doi: 10.1001/jamanetworkopen.2025.40453.

ABSTRACT

IMPORTANCE: Replantation and revascularization are among the most technically challenging surgical procedures and have varying success rates. Methods to assess surgeon skill for this complex undertaking are lacking.

OBJECTIVE: To examine whether a surgeon proficiency score is associated with clinical outcomes across multiple institutions.

DESIGN, SETTING, AND PARTICIPANTS: This multicenter retrospective cohort study analyzed all digit replantation and revascularization after traumatic amputations for adult patients from January 1, 2000, to August 31, 2022, at 8 medical institutions in the United States, India, and Singapore. Data were collected and analyzed from February to October 2024.

EXPOSURE: Surgeon proficiency (range, 1.0 to 7.5; higher score indicates greater proficiency) and procedure difficulty (range, -1.0 to 7.5; higher score indicates greater difficulty) scores. Each surgeon’s procedures were sorted chronologically, then divided in half. Proficiency scores were calculated for each surgeon based on the difficulty and outcomes of their early procedures and validated using outcomes from their later procedures. Difficulty scores were calculated based on patient and injury characteristics.

MAIN OUTCOMES AND MEASURES: The outcome of interest was procedure success, defined as digit survival at 1 month after the operation.

RESULTS: Of 653 digits that were replanted or revascularized by 65 surgeons, 458 (70.1%) were successful. Mean (SD) patient age was 41.0 (15.7) years, and 571 patients (87%) were male. Difficulty scores ranged from 1.0 to 7.5, with a mean of 2.7, and were significantly higher in failed procedures than in successful procedures (mean [SD], 3.2 [1.4] vs 2.5 [1.2]; P < .001). Proficiency scores ranged from -0.37 to 4.14, with a mean of 1.40. For each 1-point increase in proficiency score, a surgeon’s future success rate increased by 7.5% (95% CI, 5.5%-8.1%; P < .001). After adjusting for surgeon experience, difficulty score, and additional patient- and injury-level characteristics using mixed-effects logistic regression, greater surgeon proficiency score and lower difficulty score were associated with greater likelihood of individual procedure success (surgeon proficiency: odds ratio [OR], 1.46; 95% CI, 1.02 to 2.10; P = .04; difficulty: OR, 0.70; 95% CI, 0.57 to 0.86; P = .001).

CONCLUSIONS AND RELEVANCE: This multi-institutional cohort study of patients who underwent digit replantation or revascularization found that surgeon proficiency score was associated with 1-month success. These findings suggest that national trauma referral networks should incorporate difficulty and proficiency scoring tools when coordinating patient transfers after traumatic digit amputation. Centers with high replant volume or those who are geographically well-positioned to become replant centers should aim to recruit and improve reimbursement for surgeons with high proficiency scores. Meanwhile, surgeons with low proficiency scores should seek out additional training to improve their skills.

PMID:41165706 | DOI:10.1001/jamanetworkopen.2025.40453

JAMA Netw Open. 2025 Oct 1;8(10):e2540559. doi: 10.1001/jamanetworkopen.2025.40559.

ABSTRACT

IMPORTANCE: The routine use of intraoperative transesophageal echocardiography (TEE) during coronary artery bypass graft (CABG) surgery remains controversial. Its benefit across different patient populations is unclear.

OBJECTIVES: To identify patient subgroups with the greatest or least likelihood to benefit from intraoperative TEE during CABG, stratified by hospital surgical volume.

DESIGN, SETTING, AND PARTICIPANTS: This 2-stage, matched retrospective cohort study applied target trial emulation methodologies to the Society of Thoracic Surgeons (STS) Adult Cardiac Surgery Database (ACSD) to quantify the conditional treatment effect of intraoperative TEE among subpopulations undergoing isolated CABG at low, medium, and high surgical volume hospitals. The study cohort consisted of patients aged 18 years or older who underwent isolated CABG surgery between July 1, 2014, and June 30, 2022. Data analysis was conducted from August 8, 2023, to December 15, 2024.

EXPOSURE: Receipt of an intraoperative TEE during CABG surgery.

MAIN OUTCOMES AND MEASURES: The primary outcome was mortality within 30 days of surgery. Statistical analyses included multivariable logistic regression and multiple TEE vs without TEE matched comparisons stratified by surgical volume and patient subpopulations.

RESULTS: Of 1 266 055 patients who underwent isolated CABG, 963 976 (76.1%) were male, and the mean (SD) age was 65.7 (10.0) years. Among these patients, 61.8% received TEE and 39.0% did not receive TEE. Intraoperative TEE use (vs without TEE) was associated with a significant survival benefit among patients treated at hospitals with low surgical volume (2.47% vs 2.94%; odds ratio [OR], 0.83 [95% CI, 0.78-0.89], P < .001) and medium surgical volume (2.09% vs 2.34%; OR, 0.89 [95% CI, 0.85-0.93], P < .001) but not high surgical volume (1.72% vs 1.77%; OR, 0.97 [95% CI, 0.91-1.03], P = .48). Among patients who underwent isolated CABG at low and medium surgical volume hospitals, TEE provided the greatest survival benefit to subpopulations with greater than 50% (vs ≤50%) left-main coronary stenosis, 3 or more (vs <3) diseased coronaries, and (3) a preoperative inotropic requirement.

CONCLUSIONS AND RELEVANCE: In isolated CABG, intraoperative TEE was associated with survival benefit at low- and medium-volume hospitals, particularly in patients with complex coronary disease or hemodynamic instability, but not at high-volume hospitals. These results highlight persistent equipoise and the need for randomized evaluation.

PMID:41165705 | DOI:10.1001/jamanetworkopen.2025.40559

JAMA Netw Open. 2025 Oct 1;8(10):e2540720. doi: 10.1001/jamanetworkopen.2025.40720.

ABSTRACT

IMPORTANCE: New resistant mutations of respiratory syncytial virus type B (RSV-B) have been observed during the first year of implementation nirsevimab treatment. During the second season of implementation of nirsevimab treatment in France, RSV-B was predominant.

OBJECTIVES: To assess and compare the effectiveness of nirsevimab treatment in preventing RSV bronchiolitis in pediatric emergency departments during the first and second seasons of implementation of treatment in France.

DESIGN, SETTING, AND PARTICIPANTS: This a multicenter test-negative case-control study included 636 infants younger than 1 year who received a diagnosis of a first bronchiolitis episode in 5 pediatric emergency departments in France during the 2 first seasons of implementation of nirsevimab treatment (from October 5, 2023, to February 29, 2024, and from October 15, 2024, to January 31, 2025) and underwent a nasopharyngeal test for RSV.

MAIN OUTCOMES AND MEASURES: The main outcome of the study was the RSV status of the bronchiolitis cases. Multivariable logistic regression was performed with nirsevimab as the explanatory variable, adjusted on age, sex, risk factors of bronchiolitis, type of childcare, month, and center of inclusion. Effectiveness was calculated for each season and compared using the likelihood ratio test. Subgroup analysis by age and severity as well as sensitivity analyses were performed.

RESULTS: The study included 636 patients with bronchiolitis (median age, 3.0 months [IQR, 1.4-5.0 months]; 333 boys [52.4%]). In both seasons, 162 of 636 patients (25.5%) were immunized with nirsevimab. During the first season of implementation, 273 of 384 patients (71.1%) tested positive for RSV; during the second season, 181 of 252 patients (71.8%) tested positive for RSV. The effectiveness of nirsevimab treatment against RSV bronchiolitis was estimated to be 83.2% (95% CI, 68.0%-91.4%) during the first season and 89.3% (95% CI, 77.8%-95.1%) during the second season; no statistically significant difference in effectiveness was found between the 2 seasons (P = .97). Subgroup and sensitivity analyses provided similar results.

CONCLUSIONS AND RELEVANCE: In this test-negative case-control study of nirsevimab treatment, its effectiveness in reducing pediatric emergency department visits for RSV bronchiolitis during the second season of national immunization was high and comparable with that observed in the first season. Although RSV-B resistant strains had been recently identified, it did not appear to have important clinical consequences to date. Continued close monitoring of RSV epidemiology in the context of the widespread nirsevimab use remains essential.

PMID:41165704 | DOI:10.1001/jamanetworkopen.2025.40720

JAMA Oncol. 2025 Oct 30. doi: 10.1001/jamaoncol.2025.4480. Online ahead of print.

ABSTRACT

IMPORTANCE: Hormonal contraceptives are widely used but how breast cancer risk differs by hormonal content remains unclear.

OBJECTIVE: To estimate the difference in breast cancer risk associated with different hormonal contraceptive formulations.

DESIGN, SETTING, AND PARTICIPANTS: This Swedish nationwide, population-based cohort study was conducted using linked national registers. All adolescent girls and women aged 13 to 49 years residing in Sweden as of January 1, 2006, with no history of breast cancer, ovarian cancer, cervical cancer, uterine cancer, bilateral oophorectomy, or infertility treatment were included and followed up from 2006 to 2019. Individuals were censored on meeting an exclusion criterion, reaching age 50 years, or study end, whichever occurred first. Data were analyzed from November 2023 to August 2025.

EXPOSURE: Ever use and duration of use of hormonal contraceptives, categorized by hormone formulations and route of administration.

MAIN OUTCOMES AND MEASURES: Time-dependent Cox regression was used to estimate hazard ratios (HRs) with 95% CIs for incident cases of in situ and invasive breast cancer.

RESULTS: Among 2 095 130 adolescent girls and women (median [IQR] age at diagnosis, 45 [41-48] years) who were followed up for 21 020 846 person-years, 16 385 breast cancer cases occurred. Ever use of any hormonal contraceptive was associated with increased breast cancer risk (HR, 1.24; 95% CI, 1.20-1.28), corresponding to 1 additional case per 7752 (95% CI, 5350-14 070) users, with both combined (HR, 1.12; 95% CI, 1.07-1.17) and progestin-only formulations (HR, 1.21; 95% CI, 1.17-1.25) being associated. Higher risk was associated with oral desogestrel-only formulations (HR, 1.18; 95% CI, 1.13-1.23) and oral desogestrel-combined formulations (HR, 1.19; 95% CI, 1.08-1.31), as well as implants containing etonogestrel, desogestrel’s active metabolite (HR, 1.22; 95% CI, 1.11-1.35), compared to levonorgestrel-containing combined pills (HR, 1.09; 95% CI, 1.03-1.15) and levonorgestrel, 52 mg, intrauterine system (HR, 1.13; 95% CI, 1.09-1.18). No statistically significant increased risk was observed for medroxyprogesterone acetate injection, etonogestrel vaginal ring, or combined oral drospirenone, despite having many users.

CONCLUSIONS AND RELEVANCE: Findings of this cohort study highlight that breast cancer risk varies substantially by progestin content in hormonal contraceptives, providing valuable insights to support more informed contraceptive prescription.

PMID:41165687 | DOI:10.1001/jamaoncol.2025.4480

JAMA Oncol. 2025 Oct 30. doi: 10.1001/jamaoncol.2025.4343. Online ahead of print.

NO ABSTRACT

PMID:41165677 | DOI:10.1001/jamaoncol.2025.4343

Neuromodulation. 2025 Oct 30:S1094-7159(25)01041-4. doi: 10.1016/j.neurom.2025.09.315. Online ahead of print.

ABSTRACT

OBJECTIVES: Deep brain stimulation (DBS) is an effective surgical procedure for the treatment of Parkinson disease (PD) and other movement disorders. Immediate and delayed complications after DBS surgery have been described. Perilead edema (PLE) is a DBS-related complication for which the etiology remains unknown. Moreover, PLE frequency and long-term effects are subjects of ongoing debate. Our study aims to elucidate the long-term clinical and neuropsychologic effects of PLE and to find possible etiologic correlates.

MATERIALS AND METHODS: We retrospectively collected clinical and neuropsychologic data from 51 patients with PD before and 1 year after DBS. PLE visualized on fluid attenuated inversion recovery magnetic resonance imaging (MRI) sequence was manually segmented. Using appropriate statistical tests, continuous and categorical variables were compared in patients with and those without PLE. A multivariate regression model was used to analyze the contribution of clinical variables to edema volume changes.

RESULTS: Overall, 68.62% of patients presented with PLE at the immediate postoperative MRI. Patients with PLE were significantly older (p < 0.001) and had more frequent postoperative confusion episodes (p = 0.025). Furthermore, more microelectrode recording (MER) tracks (p < 0.001) were used in patients with PLE. Multiple MER tracks were directly correlated with edema volume and were the only significant predictors of edema volume changes in a multivariate regression model. No differences were found in other clinical and neuropsychologic variables.

CONCLUSIONS: PLE is a frequent postsurgical event and may cause transient postoperative confusion. It seems linked to older age and multiple MER tracks. Although it does not influence global motor and neuropsychologic outcomes, PLE contributes to postoperative confusion episodes. To avoid PLE sequelae, using multiple MER tracks in older patients should be discouraged.

PMID:41165632 | DOI:10.1016/j.neurom.2025.09.315

J Perianesth Nurs. 2025 Oct 29:S1089-9472(25)00164-9. doi: 10.1016/j.jopan.2025.05.016. Online ahead of print.

ABSTRACT

PURPOSE: To explore the effects of different warming temperatures on the incidence of hypothermia, comfort, and satisfaction of patients after a cesarean section.

DESIGN: A randomized controlled trial.

METHODS: A simple random sampling method was used to select 100 puerpera who underwent cesarean section surgery at the Anesthesia and Operating Department of a 3-class hospital from August 1, 2024 to October 31, 2024. They were randomly divided into a control group (49 cases) and an experimental group (51 cases). Observation indicators: changes in body temperature, comfort level, satisfaction level, incidence and intensity of chills.

FINDINGS: There was no significant difference in baseline data and body temperature between the two groups (P > .05). The incidence of postoperative shivering in the control group was 0%, which was lower than 3.92% in the experimental group. The control group’s comfort score was significantly higher than that of the experimental group, with statistical significance (P < .001). There was no significant difference in satisfaction evaluation or in the incidence of hypothermia between the two groups (P > .05).

CONCLUSIONS: The active and passive composite warming method can effectively prevent the occurrence of hypothermia and shivering in patients after cesarean section and improve their satisfaction. When the warming temperature is set at 38 to 40 ℃, postoperative comfort of patients is the best. However, short-term (30 minutes) postoperative warming has no significant effect on the postoperative body temperature of patients, and some patients still have a decrease in body temperature after short-term warming, suggesting that it is necessary to continue to promote warming measures to ensure the patient’s body temperature recovery after leaving the postanesthesia care unit and entering the ward.

PMID:41165620 | DOI:10.1016/j.jopan.2025.05.016