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Goal: The purpose of the research is to explore, through the lens of organizational performance and staff satisfaction, the characteristics of administrative leaders working as dyad partners with physician leaders. Methods: All 54 administrative leaders from 71 clinical departments at the three US Mayo Clinic sites were invited to participate in the study. We used an unsupervised cluster analysis machine learning method to group the leaders based on their characteristics, as measured by the 32-dimension Occupational Personality Questionnaire (OPQ 32r), and we used a three-cluster model to explore the relationships between the clusters and the performance outcome. We took the department performance data from the previous year and compared the percentage of departments with the upward changes among the clusters. For staff survey data, we calculated the percentage of departments with scores that were above average among the three clusters for both physician and administrative staff responses. Principal Findings: Analysis of personality data revealed three different clusters. Cluster 1 leaders were caring and democratic, forward-thinking, strategic, optimistic, and trusting of others. Cluster 2 leaders were extremely hardworking and authoritative. Cluster 3 leaders were caring, modest, and rule-following. Cluster 1 leaders showed the best financial performance and sense of belonging among their followers, cluster 2 leaders elicited high engagement from their departments, and cluster 3 leaders encouraged lower burnout among staff members. Practical Applications: From this study, we obtained empirical evidence of administrative leaders’ characteristics that showed positive relationships with financial and staff-satisfaction metrics. The results showed that distinct types of leaders influence administrative staff and physician staff differently and that different situations require different styles of leadership. We can also conclude that implementing robust, scientifically validated tools to assess leadership traits and tendencies can positively affect leadership and organizational performance for healthcare organizations.

BACKGROUND: “Days at home up to 30 days” is a novel patient-centered outcome metric that measures the number of days patients spend at home 30 days after surgery. It encompasses inpatient stay from index admission, interhospital transfers and step-downs, and readmissions across different hospitals. OBJECTIVE: Comparison of days at home up to 30 days and established outcome metrics after robotic versus 3-dimensional laparoscopic colorectal surgery. DESIGN: Prospective cohort study of consecutive patients. SETTING: Townsville University Hospital and Mater Private Hospital, Townsville, Queensland, Australia. PATIENTS: Adult patients undergoing robotic and 3-dimensional laparoscopic colorectal surgery. MAIN OUTCOME MEASURES: Days at home up to 30 days, 30-day readmission rate, index admission length, and 30-day postoperative complication rates. RESULTS: Of 82 patients, 32 (39%) underwent robotic and 50 (61%) underwent 3-dimensional laparoscopic colorectal surgery. Robotic ultralow and low anterior resection, as well as abdominoperineal resection, resulted in significantly more days at home (23 vs 15 days at home, p = 0.05) and a shorter length of index admission (7 vs 15 days in hospital, p = 0.0003). However, there was no significant difference in major postoperative complications and 30-day readmission rate. No significant differences were found between robotic and 3-dimensional laparoscopic right hemicolectomy or high anterior resection. LIMITATIONS: Unrandomized study. Patient selection for robotic and 3-dimensional laparoscopic surgery was at the surgeons’ discretion. CONCLUSIONS: Patients undergoing robotic ultralow and low anterior resection, as well as abdominoperineal resection, spent more days at home 30 days after index surgery due to a reduction in the length of the index hospital admission. Days at home up to 30 days may enhance the informed consent and complement traditional end points in future clinical trials. See Abstract Video. DÍAS EN CASA HASTA 30 DÍAS DESPUÉS DE LA CIRUGÍA COLORRECTAL ROBÓTICA FRENTE A LA LAPAROSCÓPICA ANTECEDENTES: «Días en el hogar hasta 30 días» es una nueva métrica de resultados centrada en el paciente que mide el número de días que los pacientes pasan en su hogar 30 días después de la cirugía. Abarca la estancia hospitalaria desde el ingreso inicial, los traslados entre hospitales y los traslados a unidades de cuidados intermedios, así como los reingresos en diferentes hospitales. OBJETIVO: Comparación de los días en casa hasta 30 días y las métricas de resultados establecidas tras la cirugía robótica frente a la cirugía laparoscópica tridimensional. DISEÑO: Estudio prospectivo de cohortes de pacientes consecutivos. ENTORNO: Hospital Universitario de Townsville y Hospital Privado Mater, Townsville, Queensland, Australia. PACIENTES: Pacientes adultos sometidos a cirugía colorrectal robótica y laparoscópica tridimensional. PRINCIPALES MEDIDAS DE RESULTADO: Días en el domicilio hasta 30 días, tasa de reingresos a los 30 días, duración de la admisión inicial y tasas de complicaciones postoperatorias a los 30 días. RESULTADOS: De los 82 pacientes, 32 (39 %) se sometieron a cirugía robótica y 50 (61 %) a cirugía colorrectal laparoscópica tridimensional. La resección anterior robótica ultrabaja y baja, así como la resección abdominoperineal, dieron lugar a un número significativamente mayor de días en el domicilio (23 frente a 15 días en el domicilio, p = 0,05) y a una menor duración de la hospitalización inicial (7 frente a 15 días en el hospital, p = 0,0003). Sin embargo, no se observaron diferencias significativas en las complicaciones postoperatorias graves ni en la tasa de reingresos a los 30 días. No se encontraron diferencias significativas entre la hemicolectomía derecha robótica y laparoscópica tridimensional, así como la resección anterior alta. LIMITACIONES: Estudio no aleatorizado. La selección de los pacientes para la cirugía robótica y laparoscópica tridimensional se realizó a criterio de los cirujanos. CONCLUSIÓN: Los pacientes sometidos a resección anterior robótica ultrabaja y baja, así como a resección abdominoperineal, pasaron más días en casa 30 días después de la cirugía índice debido a la reducción de la duración de la hospitalización índice. Los días en casa hasta 30 días pueden mejorar el consentimiento informado y complementar los criterios de valoración tradicionales en futuros ensayos clínicos. (AI-generated translation)

We report 3-year follow-up results from TRANSFORM comparing lisocabtagene maraleucel (liso-cel) versus standard of care (SOC) for second-line primary refractory/early relapsed (≤12 months) large B-cell lymphoma (LBCL). Adults eligible for autologous stem cell transplantation (N = 184) were randomly assigned 1:1 to liso-cel (100 × 10 6 chimeric antigen receptor–positive T cells) or SOC. Results are reported descriptively. With a median follow-up of 33.9 months, median (95% CI) event-free survival was 29.5 months (9.5 to not reached [NR]) for liso-cel versus 2.4 months (2.2 to 4.9) for SOC (hazard ratio [HR], 0.375; 95% CI, 0.259 to 0.542). Median progression-free survival was NR (12.6-NR) for liso-cel versus 6.2 months (4.3-8.6) for SOC (HR, 0.422; 95% CI, 0.279 to 0.639) with 36-month rates of 51% versus 26.5%. Median overall survival (OS) was NR for both arms (HR, 0.757; 95% CI, 0.481 to 1.191), with 66% of patients crossing over to receive liso-cel; 36-month OS rate was 63% for liso-cel versus 52% for SOC. OS HR (0.566 [95% CI, 0.359 to 0.895]) favored liso-cel when accounting for the treatment effect of crossover. Safety results were consistent with previous reports. At 3-year follow-up, liso-cel confirmed superior, more durable efficacy versus SOC with a favorable safety profile and no new safety signals. These data support liso-cel as an effective second-line treatment with curative potential for relapsed/refractory LBCL.

CDK12 primarily functions as a transcription regulatory cyclin-dependent kinase (CDK) that controls mRNA elongation, splicing, and polyadenylation. The CDK12 gene is implicated in human cancers since it is frequently mutated and/or deleted in prostate and ovarian cancer but paradoxically amplified in breast cancer. Here, we demonstrate that CDK12 promotes serine-933 phosphorylation of DNA2, a nuclease/helicase critical for replication fork stress regulation, and the phosphorylation subsequently facilitates DNA2 polyubiquitination and degradation mediated by the APC/C CDC20 E3 ubiquitin ligase. CDK12 inactivation induces but amplification suppresses genome-wide expression of interferon response and antigen processing and presentation machinery genes in ovarian and breast cancer cells, respectively. Besides causing aberrant DNA2 stabilization, replication stress, genomic instability, and cytosolic double-stranded DNA (dsDNA) accumulation, CDK12 loss also triggers cGAS–STING activation and innate immune response, which can be reversed by forced expression of replication protein A (RPA) subunits or DNA2 depletion. Our findings identify DNA2 as a phosphorylation substrate of CDK12, connecting CDK12 to cell cycle regulation. These data also reveal DNA2 protein destruction as a critical mechanism that dictates genomic instability, cGAS–STING signaling activation, and innate immune response in CDK12-deregulated cancers.

ImportanceUptake of human papillomavirus (HPV) vaccination varies by characteristics, exposing some children to higher HPV cancer risks than others.ObjectiveTo examine whether the effectiveness of a multilevel intervention on HPV vaccination differed by race and ethnicity, rurality, and Area Deprivation Index (ADI) in children ages 11 to 12 years.Design, Setting, and ParticipantsA stepped-wedge cluster randomized trial was conducted from April 2018 to August 2022 among children at 6 Mayo Clinic primary care practices in Minnesota to improve HPV vaccination. This secondary analysis was performed from March to June 2024.InterventionA multilevel intervention that included parent reminder/recall letters, which alerted parents of children due or past due for vaccination, and health care professional audit/feedback reports, which alerted health care professionals of their own vaccination rates.Main Outcome and MeasureVaccine initiation (first dose of the 2-dose HPV vaccine) and vaccine completion (second dose) were the primary study outcomes. In this secondary analysis, the effect of the intervention on HPV vaccine initiation and completion by race and ethnicity, rurality, and ADI quartiles (Qs) was assessed.ResultsA total of 6232 children aged 11 to 12 years (3285 [52.7%] male; 3481 [55.9%] aged 11 years and 2751 [44.1%] aged 12 years) were included in the analysis. Of the study participants, 304 (4.9%) were Asian, 561 (9.0%) Black, 146 (2.3%) Hispanic, 4501 (72.2%) White, and 720 (11.6%) other, including American Indian or Alaskan Native, Native Hawaiian or Pacific Islander, Other Pacific Islander, Samoan, unable to provide, unknown, chose not to disclose, or other unspecified. A total of 5434 participants (87.2%) were urban residents, and 2794 (44.8%) resided in ADI Q2 areas. With usual care, HPV vaccine initiation and completion rates were significantly lower with each increasing ADI quartile (initiation: Cochran-Armitage test for trend [SE], −0.02 [0.01]; P < .001; completion: Cochran-Armitage test for trend [SE], −0.05 [0.01]; P < .001) but did not differ by children’s race and ethnicity or rurality. With the intervention, vaccine initiation increased significantly for most children (range of rates, 9.2% [95% CI, 5.2%-13.3%] to 24.0% [95% CI, 7.5%-40.6%]) except those with Black race, in rural settings, and in ADI Q4 (highest area deprivation); vaccine completion increased significantly for most children (range of rates, 19.4% [95% CI, 5.5%-33.3%] to 31.2% [95% CI, 12.1%-50.3%]) except for those in ADI Q4.Conclusions and RelevanceIn this secondary analysis of a cluster randomized trial, a multilevel intervention was associated with increased HPV vaccination for most children but had limited effect for those residing in areas of highest deprivation. Future research should explore other intervention strategies that would effectively promote HPV vaccination among families in socioeconomically disadvantaged areas to reduce HPV vaccination disparities.Trial RegistrationClinicalTrials.gov Identifier: NCT03501992

ImportanceEtiologic heterogeneity in breast carcinogenesis needs to be well characterized for targeted prevention. Associations between menopausal hormonal therapy (MHT) and oral contraceptive (OC) use and breast cancer intrinsic-like subtypes are not well understood.ObjectiveTo examine whether exogenous hormone use is differentially associated with breast cancer subtypes and to evaluate heterogeneity by intrinsic-like subtypes.Design, Setting, and ParticipantsThis study pooled data from 31 nested and population-based case-control studies involved in the Breast Cancer Association Consortium. The study population included individuals with breast cancer and control participants from 13 case-control studies nested in prospective cohorts (recruited between 1982 and 2011) and 18 population-based case-control studies (recruited between 1990 and 2013). Data analysis was performed in June 2024.ExposureMHT use (estrogen-progestin therapy [EPT] or estrogen-only therapy [ET]) in postmenopausal women and OC use in premenopausal women (never, past use, or current use).Main Outcomes and MeasuresBreast cancer intrinsic-like subtypes (luminal A–like, luminal B–like, luminal B–ERBB2 [formerly HER2 or HER2/neu]-like, ERBB2 enriched–like, or triple-negative) were determined by immunohistochemistry of tumor sections. Polytomous logistic regression was performed to estimate the association between exogenous hormones and risk of breast cancer by intrinsic-like subtypes. Analyses by subtypes were stratified by body mass index (BMI [calculated as weight in kilograms divided by height in meters squared]; healthy weight, 18.5-<25; overweight, 25-<30; or obesity, ≥30).ResultsThis study included 42 269 individuals with breast cancer (11 901 [28.2%] premenopausal and 30 368 [71.8%] postmenopausal; 23 353 [55.2%] had a known intrinsic-like subtype) and 71 072 control participants. The mean (SD) age of all participants was 57.9 (10.9) years. In postmenopausal women, associations between current MHT use (EPT or ET) and breast cancer differed by subtype. Current EPT users with healthy weight were more likely to be diagnosed with luminal A–like (odds ratio [OR], 2.51 [95% CI, 2.26-2.80]) or luminal B–ERBB2-like (OR, 1.95 [95% CI, 1.61-2.37]) subtypes. These associations were attenuated but remained for individuals with overweight (OR, 1.40 [95% CI, 1.02-1.92]) or obesity (OR, 1.68 [95% CI, 1.01-2.78]). EPT use increased the odds of being diagnosed with luminal B–like tumors solely in women with healthy weight (OR, 1.47 [95% CI, 1.17-1.86]). Current ET use was positively associated with luminal A–like disease in women with healthy weight only (OR, 1.16 [95% CI, 1.01-1.32]), showing inverse associations with higher BMI (obesity: OR, 0.65 [95% CI, 0.50-0.85]). In premenopausal women, recent OC use was associated with luminal B–ERBB2-like (OR, 1.50 [95% CI, 1.09-2.08]), ERBB2 enriched–like (OR, 2.33 [95% CI, 1.55-3.51]), and triple-negative (OR, 1.75 [95% CI, 1.33-2.29]; P < .04 for heterogeneity) tumors.Conclusions and RelevanceIn this study, clear differences were observed in associations between current EPT use and luminal-like breast cancer subtypes and other subtypes. EPT users with healthy weight were more likely to be diagnosed with luminal-like breast cancer compared with nonusers. Subtype heterogeneity was less apparent in associations of OC and ET use. Future studies on contemporary formulations, patterns of use, and routes of administration of exogenous hormone usage are warranted.

Abstract Checkpoint inhibitors (CPIs) have shown remarkable efficacy in Hodgkin lymphoma (HL), and are now used routinely. While allogeneic hematopoietic cell transplantation (allo-HCT) remains a curative option for HL, there are concerns prior CPIs may exacerbate post–allo-HCT complications, particularly graft-versus-host disease (GVHD), and lead to worse outcomes. Given the relative paucity of data, we performed a Center for International Blood and Marrow Transplant Research/European Society for Blood and Marrow Transplantation study to examine the impact of prior CPIs in allo-HCT. We included 2186 adult patients aged >18 years who received a first allo-HCT using a matched related, unrelated, or haploidentical donor from 2008 to 2023. Twenty-seven percent of patients received prior CPIs. GVHD prophylaxis was posttransplant cyclophosphamide (PTCy) in 55.8% of patients in the CPI cohort, and 35% in the non-CPI cohort. Median follow-up among survivors was longer for the non-CPI (39 months) than CPI cohort (16.5 months). In multivariate analysis, prior CPI exposure did not affect overall survival (OS) or nonrelapse mortality, but resulted in improved progression-free survival (non-CPI vs CPI hazard ratio [HR], 0.81; 0.67-0.98; P = .03) and lower relapse incidence (HR, 0.58; 0.45-0.76; P < 001). While grade 2 to 4 (HR, 1.26; 1.04-1.53; P = .02) and 3 to 4 (HR, 1.41; 1.04-1.92; P = .03) acute GVHD (aGVHD) were increased, differences in chronic GVHD (cGVHD) were not significant. PTCy–based GVHD prophylaxis resulted in improved OS, lower grade 2 to 4 aGVHD, and cGVHD in patients with prior CPI exposure. In summary, allo-HCT should still be considered a curative option for patients with HL in the era of CPIs.

Abstract Background Patients with inflammatory bowel disease (IBD) are at increased risk of herpes zoster (HZ) infection due to innate immune abnormalities and use of immunosuppressive therapy. The recombinant zoster vaccine (RZV) is recommended, but its efficacy in preventing recurrent HZ among patients with IBD is not well established. Methods Using data from the TriNetX Linked Network, we conducted a retrospective cohort study of adults (≥18 years) with IBD and a prior uncomplicated HZ episode. Patients with IBD who received RZV were propensity score-matched 1:1 with those who did not. The primary outcome was subsequent HZ complications. Secondary outcomes included subtypes of HZ complications and recurrent uncomplicated HZ. Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated via Cox proportional hazards models. Results After matching, 1260 vaccinated and 1260 unvaccinated patients with IBD were included. Compared to the unvaccinated cohort, patients receiving RZV had a significantly reduced incidence of HZ complications (7.4% vs. 14.5%; HR, 0.75; 95% CI, 0.58–0.97; P = .028). Postherpetic neuralgia was notably decreased (5.8% vs. 12.5%; HR, 0.66; P = .010), and no central nervous system involvement occurred among vaccinated patients. Protective effects were more pronounced in patients with ulcerative colitis, females, and those not receiving immunosuppressive therapy. Conclusions RZV substantially lowers the risk of HZ complications in patients with IBD, offering significant clinical benefits to those at high risk due to immunosuppression. These findings underscore the importance of RZV as part of preventive care strategies in patients with IBD.