Publications by Year: 2026

BACKGROUND: Next-generation sequencing (NGS) tests are integral to oncology care. To address the need for clinical and NGS data management, interpretation, and reporting, we developed iCatalog for the multi-institutional Individualized Cancer Therapy 2/Genomic Assessment Informs Novel Therapy Consortium (GAIN) pediatric precision oncology (PO) study.

METHODS: We designed iCatalog as a secure, web-based clinical decision support application that stores and integrates clinical, specimen, and molecular data from multiple sources at the patient level. The knowledge base (KB) and centralized patient/test database are intended to manage information for the 825 patients expected to enroll in the GAIN study. User permissions and access are controlled. Gene- and variant-level interpretation is facilitated through linked external resources and an internal KB that can be updated during application use. iCatalog generates editable, study-specific patient reports for each molecular test.

RESULTS: Launched to support the GAIN study, iCatalog integrates genomic data from eight NGS platforms, generates 1002 clinical interpretation reports, and stores data for 1194 tests involving 777 patients with pediatric solid tumors across 133 diagnoses. The KB contains pediatric cancer-specific curations, authored by the research team, spanning 581 genes and 2659 variants (including 2146 single-nucleotide variants and insertions-deletions, 235 copy-number variants, 278 structural variants).

CONCLUSIONS: iCatalog is a robust tool designed and proven to support a PO study. It integrates clinical and genomic data to facilitate the clinical interpretation and reporting of variants identified through NGS testing while maintaining a pediatric-specific KB generated during the study. As a scalable, modular platform, iCatalog can accelerate clinical decision-making and elevate PO insights across studies.

BACKGROUND: Despite the known clinical benefit of endocrine therapy (ET) after surgery for ductal carcinoma in situ (DCIS), ET uptake remains low. In April 2021, the authors initiated a surgeon-led DCIS program. This report evaluates the impact of the DCIS program on ET uptake.

METHODS: Patients undergoing surgery for DCIS were identified from prospectively maintained databases. Patients treated from January 2016 to March 2021 formed the historical cohort, and those treated from April 2021 to July 2024 formed the DCIS program cohort. Chi-square analyses were used to compare ET uptake and trends between the cohorts.

RESULTS: The study identified 1856 patients, with 1026 patients forming the historical cohort and 830 patients forming the DCIS program cohort. The median patient age was 59 years. Most of the patients (69.9 %) were postmenopausal, and 1573 (84.8 %) had estrogen receptor-positive (ER+) DCIS. Overall, ET uptake among the patients with ER+ DCIS did not differ between the cohorts (45.7 % and 45.1 %, respectively; p = 0.33). When analyzed by type of surgery, ET uptake among those undergoing breast-conserving surgery (BCS) also was similar (54.5 % and 52.1 %, respectively; p = 0.44). In postmenopausal women with ER+ DCIS undergoing BCS, use of aromatase inhibitors (AIs) decreased (67.3 % to 43.1 %) and use of tamoxifen increased (31.1 % to 56.9 %) in the DCIS program cohort (p < 0.001), with 91.9 % of eligible patients taking low-dose tamoxifen after its introduction in 2023.

CONCLUSIONS: Endocrine therapy uptake remained stable after initiation of a surgeon-led DCIS program. Prescribing patterns for postmenopausal women in the DCIS program favored tamoxifen over AI, driven largely by the introduction of low-dose tamoxifen.

BACKGROUND: Suicide attempts in young people in India are a major public health concern but the reasons for these remain unclear. The aim of this study was to explore factors associated with suicide attempts in persons aged 15–29 years in India.

METHODS: We conducted a matched case–control study at a public hospital in the urban region of Pimpri-Chinchward, Pune, between 2019 and 2023. 15–29-year-olds who were admitted to the hospital following a suicide attempt (cases) were compared with 151 outpatients who presented at the general medicine department of the same hospital (controls). We administered a comprehensive semi-structured interview to participants in both groups and analysed the data using cox regression models.

RESULTS: There were eight factors independently associated with suicide attempts. At the individual-level, these were: clinically significant depressive or anxiety symptoms over the last two weeks, previous suicide attempt, impulsivity, and low SES; alcohol use was significant only for males. Among the social factors, lack of exposure to suicide-related information in the last month, lack of social interactions over the last 12 months, and presence of interpersonal negative life events involving partners or family in the last 12 months were associated with suicide attempts. Descriptive data on life events revealed several relationship adversities, and the importance of acute interpersonal stressors in precipitating suicide attempts.

CONCLUSION: A range of factors are associated with suicide attempts in young people in India which calls for a multifactorial approach towards suicide prevention.

CLINICAL TRIAL NUMBER: Not applicable.

SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12888-025-07680-9.

OBJECTIVE: We describe the origin, program design, and evaluation activities of Partners in Contraception Choice and Knowledge (PICCK), a statewide contraceptive access and quality initiative in Massachusetts, United States from 2018 to 2023.

METHODS: PICCK primarily worked to improve contraceptive care at the state's birth hospitals and their affiliated outpatient practices using a champion model. In addition to hospital-level quality improvement activities, PICCK implemented statewide programming to engage audiences beyond the partnered sites, including a webinar series, annual conference, and resource development.

RESULTS: Champions at each hospital led coordination and implementation of customized programming for their site with support from PICCK staff. We conducted presentations and trainings by videoconference when in-person activities were restricted during the COVID-19 pandemic. Implementation periods ranged from 56 to 1323 days (average = 517.5 days). At the statewide level, we conducted 31 webinars, hosted three virtual annual conferences, and created 97 patient- and clinician-facing resources.

CONCLUSION: PICCK was innovative in our dual approach to implementation, with both hospital-based and statewide activities. The structure of PICCK could be adapted to implement other public health quality improvement programs in clinical settings or statewide, given the adaptability and broad reach of the program.

BACKGROUND: We aimed to conduct a qualitative prospective preference assessment (PPA) to assess participants’ willingness to enroll in a planned randomized controlled trial (RCT). The planned RCT would enroll participants with meniscal tear with persistent knee pain following a course of physical therapy (PT) and would compare outcomes of arthroscopic partial meniscectomy (APM) vs. enhanced conservative care.

METHODS: We identified participants 45–85 years old with suspected meniscal tear who were referred to PT. After 10 weeks of PT, participants were sent a questionnaire that assessed knee pain. We asked participants reporting persistent knee pain to participate in a follow-up interview. We conducted semi-structured interviews and coded and analyzed transcripts to identify themes related to enrollment in our planned RCT.

RESULTS: We analyzed transcripts from twenty participants (mean age (SD): 61.6 (6.16); 60% male, 100% White). 70% said they would participate in the trial. Willingness to enroll was associated with participants’ preferences for treatment modality and most were willing to continue PT, despite reporting persistent pain. Of those unwilling to enroll, all were averse to surgery or did not believe they needed surgery. Others had concerns about oral medications and injections, but these were not “dealbreakers” for willingness to enroll. Provider trust was a dominant decision-making factor in respondents’ willingness to enroll.

CONCLUSION: These findings suggest that investigators should consider additional education for participants regarding the benefits and risks of all treatment options at the time of enrollment invitation. Additionally, the trial should be introduced by a trusted provider.

SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12891-026-09521-6.

MOTIVATION: Genome-wide association studies (GWAS) at biobank scale are computationally intensive, especially for admixed populations requiring robust statistical models. SAIGE is a widely used method for generalized linear mixed-model GWAS but is limited by its CPU-based implementation, making phenome-wide association studies impractical for many research groups.

RESULTS: We developed SAIGE-GPU, a GPU-accelerated version of SAIGE that replaces CPU-intensive matrix operations with GPU-optimized kernels. The core innovation is distributing genetic relationship matrix calculations across GPUs and communication layers. Applied to 2068 phenotypes from 635 969 participants in the Million Veteran Program, including diverse and admixed populations, SAIGE-GPU achieved a 5-fold speedup in mixed model fitting on supercomputing infrastructure and cloud platforms. We further optimized the variant association testing step through multi-core and multi-trait parallelization. Deployed on Google Cloud Platform and Azure, the method provided substantial cost and time savings.

AVAILABILITY AND IMPLEMENTATION: Source code and binaries are available for download at https://github.com/saigegit/SAIGE/tree/SAIGE-GPU-1.3.3. A code snapshot is archived at Zenodo for reproducibility (DOI: [10.5281/zenodo.17642591]). SAIGE-GPU is available in a containerized format for use across HPC and cloud environments and is implemented in R/C++ and runs on Linux systems.

OBJECTIVE: The International Study Group of Pancreatic Surgery (ISGPS) aimed to uniform the definition and classification of mortality following pancreatic resections, to guide strategies for reducing preventable deaths and standardize reporting.

BACKGROUND: Reported rates of mortality after pancreatic surgery vary widely depending on patient comorbidities, case mix, and institutional expertise and resources. Conventional reporting lacks granularity and fails to capture the mechanisms leading to death. A standardized classification rooted in causal analysis may provide a more meaningful framework to appraise outcomes and design targeted interventions.

METHODS: A systematic review of the literature, focusing on mortality rates, causes of death, and existing classification systems after pancreatectomy was conducted. A consensus definition and tripartite classification were developed through iterative discussions, revisions, and final approval by the ISGPS board members.

RESULTS: Postpancreatectomy mortality (PPM) was defined as death occurring within 90 days of any pancreatic resection, directly or indirectly attributable to a surgical complication and retrospectively linked to it through root-cause analysis. Three categories were established: PPM 1, vascular/technical complexity-related mortality (15-30%); PPM 2, pancreatectomy-specific complication-related deaths, mainly due to postoperative pancreatic fistula (POPF) and secondary systemic deterioration (45-65%); and PPM 3, cardiopulmonary and cerebrovascular deaths (10-25%). Each category reflects distinct mechanisms, timing of onset, intervention windows, and opportunities for rescue.

DISCUSSION: The proposed ISGPS classification of mortality enables the development of targeted strategies to reduce potentially preventable deaths and provides a more robust framework for the appraisal and benchmarking of surgical outcomes. Prospective validation is warranted to standardize this newly defined quality metric, ensuring its consistent use in future reporting and ultimately enhancing surgical quality and patient safety on a global scale.

OBJECTIVE: To examine the associations of long term engagement in individual physical activities and physical activity variety with the risk of death.

DESIGN: Prospective cohort studies.

SETTING: Nurses' Health Study (1986-2018) and Health Professionals Follow-Up Study (1986-2020).

PARTICIPANTS: 70 725 women and 40 742 men who were free of diabetes, cardiovascular disease, cancer, respiratory disease, or neurological disease and had complete physical activity information at baseline (leisure time physical activity was biennially updated using validated questionnaires during follow-up; the variety of physical activity was measured as the total number of individual physical activities in which participants consistently engaged).

MAIN OUTCOME MEASURES: All cause and cause specific mortality.

RESULTS: During 2 431 318 person years of follow-up, 38 847 deaths were recorded, with 9901 from cardiovascular disease, 10 719 from cancer, and 3159 from respiratory disease. Total physical activity and most individual physical activities, except for swimming, were associated with lower mortality with non-linear dose-response relations. The pooled multivariable adjusted hazard ratios for all cause mortality in the highest categories of physical activity levels, compared with the lowest, were 0.83 (95% confidence interval 0.80 to 0.85) for walking, 0.89 (0.85 to 0.94) for jogging, 0.87 (0.80 to 0.93) for running, 0.96 (0.93 to 0.99) for bicycling, 1.01 (0.97 to 1.05) for swimming, 0.85 (0.80 to 0.89) for tennis or squash, 0.90 (0.87 to 0.93) for climbing stairs, 0.86 (0.84 to 0.89) for rowing or callisthenics, and 0.87 (0.82 to 0.91) for weight training or resistance exercises. Higher physical activity variety was associated with lower mortality. After adjustment for total physical activity levels, participants in the group with the highest physical activity variety score (group 5), compared with those in the lowest group (group 1), had a 19% lower all cause mortality and 13-41% lower mortality from cardiovascular disease, cancer, respiratory disease, and other causes (all P for trend <0.001).

CONCLUSIONS: Habitual engagement in most types of physical activity was associated with lower mortality. The variety of physical activity was inversely associated with mortality, independent of total physical activity levels. Overall, these data support the notion that long term engagement in multiple types of physical activity may help extend the lifespan.

The Perturbation Complexity Index-State Transitions (PCIST) measures the complexity of the brain's response to transcranial magnetic stimulation (TMS) using electroencephalography (EEG) and is sensitive to consciousness, such as minimally conscious states. Individuals with early-stage Alzheimer's disease (AD) show dysfunction of conscious processes, such as attention, working memory, episodic memory, and executive function, with relatively spared unconscious processes, such as procedural memory, operant conditioning, and priming. We sought to test the hypothesis that PCIST would be reduced in AD compared to healthy aging. We assessed 28 participants with AD and 27 healthy controls (HC), measuring cognition with the Montreal Cognitive Assessment (MoCA) and disease severity with the Clinical Dementia Rating scale-Global (CDR-Global) and Sum of Boxes (CDR-SB). Results indicated lower PCIST in the AD group (M = 20.1) compared to controls (M = 28.2) across both the motor cortex (M1) and inferior parietal lobule (IPL) TMS stimulation sites, suggesting that PCIST may reflect the impaired conscious cognitive processes and functional capacity seen in AD. We therefore speculate that cortical dementias involve alterations in cortical complexity that may relate to deterioration of their conscious processes. This research opens the avenue for future studies in individuals with cortical dementia to examine the relationship between conscious processes, global measures of consciousness, and their underlying neuroanatomical correlates, in addition to enhancing our understanding of dementia and suggesting possible therapeutic strategies.