Perceptions on diversity in cardiology: A survey of cardiology fellowship training program directors

Background The lack of diversity in the cardiovascular physician workforce is thought to be an important driver of racial and sex disparities in cardiac care. Cardiology fellowship program directors play a critical role in shaping the cardiology workforce. Methods and Results To assess program directors\u27 perceptions about diversity and barriers to enhancing diversity, the authors conducted a survey of 513 fellowship program directors or associate directors from 193 unique adult cardiology fellowship training programs. The response rate was 21% of all individuals (110/513) representing 57% of US general adult cardiology training programs (110/193). While 69% of respondents endorsed the belief that diversity is a driver of excellence in health care, only 26% could quote 1 to 2 references to support this statement. Sixty-three percent of respondents agreed that our program is diverse already so diversity does not need to be increased. Only 6% of respondents listed diversity as a top 3 priority when creating the cardiovascular fellowship rank list. Conclusions These findings suggest that while program directors generally believe that diversity enhances quality, they are less familiar with the literature that supports that contention and they may not share a unified definition of diversity. This may result in diversity enhancement having a low priority. The authors propose several strategies to engage fellowship training program directors in efforts to diversify cardiology fellowship training programs

IRE1α–XBP1 controls T cell function in ovarian cancer by regulating mitochondrial activity

Tumours evade immune control by creating hostile microenvironments that perturb T cell metabolism and effector function 1?4 . However, it remains unclear how intra-tumoral T cells integrate and interpret metabolic stress signals. Here we report that ovarian cancer?an aggressive malignancy that is refractory to standard treatments and current immunotherapies 5?8 ?induces endoplasmic reticulum stress and activates the IRE1α?XBP1 arm of the unfolded protein response 9,10 in T cells to control their mitochondrial respiration and anti-tumour function. In T cells isolated from specimens collected from patients with ovarian cancer, upregulation of XBP1 was associated with decreased infiltration of T cells into tumours and with reduced IFNG mRNA expression. Malignant ascites fluid obtained from patients with ovarian cancer inhibited glucose uptake and caused N-linked protein glycosylation defects in T cells, which triggered IRE1α?XBP1 activation that suppressed mitochondrial activity and IFNγ production. Mechanistically, induction of XBP1 regulated the abundance of glutamine carriers and thus limited the influx of glutamine that is necessary to sustain mitochondrial respiration in T cells under glucose-deprived conditions. Restoring N-linked protein glycosylation, abrogating IRE1α?XBP1 activation or enforcing expression of glutamine transporters enhanced mitochondrial respiration in human T cells exposed to ovarian cancer ascites. XBP1-deficient T cells in the metastatic ovarian cancer milieu exhibited global transcriptional reprogramming and improved effector capacity. Accordingly, mice that bear ovarian cancer and lack XBP1 selectively in T cells demonstrate superior anti-tumour immunity, delayed malignant progression and increased overall survival. Controlling endoplasmic reticulum stress or targeting IRE1α?XBP1 signalling may help to restore the metabolic fitness and anti-tumour capacity of T cells in cancer hosts.Fil: Song, Minkyung. Weill Cornell Medicine; Estados UnidosFil: Sandoval, Tito A.. Weill Cornell Medicine; Estados UnidosFil: Chae, Chang-Suk. Weill Cornell Medicine; Estados UnidosFil: Chopra, Sahil. Weill Cornell Medicine; Estados UnidosFil: Tan, Chen. Weill Cornell Medicine; Estados UnidosFil: Rutkowski, Melanie R.. University of Virginia; Estados UnidosFil: Raundhal, Mahesh. Dana Farber Cancer Institute; Estados Unidos. Harvard Medical School; Estados UnidosFil: Chaurio, Ricardo A.. H. Lee Moffitt Cancer Center & Research Institute; Estados UnidosFil: Payne, Kyle K.. H. Lee Moffitt Cancer Center & Research Institute; Estados UnidosFil: Konrad, Csaba. Weill Cornell Medicine; Estados UnidosFil: Bettigole, Sarah E.. Quentis Therapeutics Inc.; Estados UnidosFil: Shin, Hee Rae. Quentis Therapeutics Inc.; Estados UnidosFil: Crowley, Michael J. P.. Weill Cornell Graduate School of Medical Sciences; Estados UnidosFil: Cerliani, Juan Pablo. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; ArgentinaFil: Kossenkov, Andrew V.. The Wistar Institute; Estados UnidosFil: Motorykin, Ievgen. Weill Cornell Medicine,; Estados UnidosFil: Zhang, Sheng. Weill Cornell Medicine,; Estados UnidosFil: Manfredi, Giovanni. Weill Cornell Medicine,; Estados UnidosFil: Zamarin, Dmitriy. Memorial Sloan Kettering Cancer Center; Estados UnidosFil: Holcomb, Kevin. Weill Cornell Medicine,; Estados UnidosFil: Rodriguez, Paulo C.. H. Lee Moffitt Cancer Center & Research Institute; Estados UnidosFil: Rabinovich, Gabriel Adrián. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentina. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Química Biológica; ArgentinaFil: Conejo Garcia, Jose R.. H. Lee Moffitt Cancer Center & Research Institute; Estados UnidosFil: Glimcher, Laurie H.. Dana Farber Cancer Institute; Estados Unidos. Harvard Medical School; Estados UnidosFil: Cubillos-Ruiz, Juan R.. Weill Graduate School Of Medical Sciences; Estados Unidos. Weill Graduate School Of Medical Sciences; Estados Unido

Academic-community partnerships improve outcomes in pediatric trauma care

BackgroundTo address the specialized needs of injured children, pediatric trauma centers (PTCs) were established at many large, academic hospitals. This study explores clinical outcomes observed for injured children treated at an academic-sponsored community facility.MethodsIn partnership with an academic medical center in a major metropolitan area, a not-for-profit community hospital became a designated Level II PTC in October 2010. Data for injured children <15 years old treated prior to PTC designation from January 2000 to September 2010 were prospectively collected using the Trauma and Emergency Medicine Information System and compared to data collected after PTC designation from January 2011 to December 2013.ResultsOverall, 681 injured children were treated at the community hospital from January 2011 to December 2013. Children treated after PTC designation were less likely to undergo computed tomography (CT) (50.9% vs. 81.3%, p<0.01), even when controlling for age, gender, injury type, injury severity, and year (OR 0.18, 95%CI 0.08-0.37). Specifically, fewer head (45.7% vs. 68.7%, p<0.01) and abdominal CTs (13.2% vs. 26.5%, p<0.01) were performed. Hospital length of stay was significantly shorter (2.8 ± 3.7 days vs. 3.7 ± 5.9 days, p<0.01). Mortality was low overall, but also decreased after PTC designation (0.4% vs. 2.0%, p=0.02).ConclusionsThese results indicate that academic-community partnerships in pediatric trauma care are a feasible alternative and may lead to improved outcomes for injured children

Shared genetic risk between eating disorder- and substance-use-related phenotypes:Evidence from genome-wide association studies

First published: 16 February 202

Duration of androgen deprivation therapy with postoperative radiotherapy for prostate cancer: a comparison of long-course versus short-course androgen deprivation therapy in the RADICALS-HD randomised trial

Background Previous evidence supports androgen deprivation therapy (ADT) with primary radiotherapy as initial treatment for intermediate-risk and high-risk localised prostate cancer. However, the use and optimal duration of ADT with postoperative radiotherapy after radical prostatectomy remains uncertain. Methods RADICALS-HD was a randomised controlled trial of ADT duration within the RADICALS protocol. Here, we report on the comparison of short-course versus long-course ADT. Key eligibility criteria were indication for radiotherapy after previous radical prostatectomy for prostate cancer, prostate-specific antigen less than 5 ng/mL, absence of metastatic disease, and written consent. Participants were randomly assigned (1:1) to add 6 months of ADT (short-course ADT) or 24 months of ADT (long-course ADT) to radiotherapy, using subcutaneous gonadotrophin-releasing hormone analogue (monthly in the short-course ADT group and 3-monthly in the long-course ADT group), daily oral bicalutamide monotherapy 150 mg, or monthly subcutaneous degarelix. Randomisation was done centrally through minimisation with a random element, stratified by Gleason score, positive margins, radiotherapy timing, planned radiotherapy schedule, and planned type of ADT, in a computerised system. The allocated treatment was not masked. The primary outcome measure was metastasis-free survival, defined as metastasis arising from prostate cancer or death from any cause. The comparison had more than 80% power with two-sided α of 5% to detect an absolute increase in 10-year metastasis-free survival from 75% to 81% (hazard ratio [HR] 0·72). Standard time-to-event analyses were used. Analyses followed intention-to-treat principle. The trial is registered with the ISRCTN registry, ISRCTN40814031, and ClinicalTrials.gov , NCT00541047 . Findings Between Jan 30, 2008, and July 7, 2015, 1523 patients (median age 65 years, IQR 60–69) were randomly assigned to receive short-course ADT (n=761) or long-course ADT (n=762) in addition to postoperative radiotherapy at 138 centres in Canada, Denmark, Ireland, and the UK. With a median follow-up of 8·9 years (7·0–10·0), 313 metastasis-free survival events were reported overall (174 in the short-course ADT group and 139 in the long-course ADT group; HR 0·773 [95% CI 0·612–0·975]; p=0·029). 10-year metastasis-free survival was 71·9% (95% CI 67·6–75·7) in the short-course ADT group and 78·1% (74·2–81·5) in the long-course ADT group. Toxicity of grade 3 or higher was reported for 105 (14%) of 753 participants in the short-course ADT group and 142 (19%) of 757 participants in the long-course ADT group (p=0·025), with no treatment-related deaths. Interpretation Compared with adding 6 months of ADT, adding 24 months of ADT improved metastasis-free survival in people receiving postoperative radiotherapy. For individuals who can accept the additional duration of adverse effects, long-course ADT should be offered with postoperative radiotherapy. Funding Cancer Research UK, UK Research and Innovation (formerly Medical Research Council), and Canadian Cancer Society

Adding 6 months of androgen deprivation therapy to postoperative radiotherapy for prostate cancer: a comparison of short-course versus no androgen deprivation therapy in the RADICALS-HD randomised controlled trial

Background Previous evidence indicates that adjuvant, short-course androgen deprivation therapy (ADT) improves metastasis-free survival when given with primary radiotherapy for intermediate-risk and high-risk localised prostate cancer. However, the value of ADT with postoperative radiotherapy after radical prostatectomy is unclear. Methods RADICALS-HD was an international randomised controlled trial to test the efficacy of ADT used in combination with postoperative radiotherapy for prostate cancer. Key eligibility criteria were indication for radiotherapy after radical prostatectomy for prostate cancer, prostate-specific antigen less than 5 ng/mL, absence of metastatic disease, and written consent. Participants were randomly assigned (1:1) to radiotherapy alone (no ADT) or radiotherapy with 6 months of ADT (short-course ADT), using monthly subcutaneous gonadotropin-releasing hormone analogue injections, daily oral bicalutamide monotherapy 150 mg, or monthly subcutaneous degarelix. Randomisation was done centrally through minimisation with a random element, stratified by Gleason score, positive margins, radiotherapy timing, planned radiotherapy schedule, and planned type of ADT, in a computerised system. The allocated treatment was not masked. The primary outcome measure was metastasis-free survival, defined as distant metastasis arising from prostate cancer or death from any cause. Standard survival analysis methods were used, accounting for randomisation stratification factors. The trial had 80% power with two-sided α of 5% to detect an absolute increase in 10-year metastasis-free survival from 80% to 86% (hazard ratio [HR] 0·67). Analyses followed the intention-to-treat principle. The trial is registered with the ISRCTN registry, ISRCTN40814031, and ClinicalTrials.gov, NCT00541047. Findings Between Nov 22, 2007, and June 29, 2015, 1480 patients (median age 66 years [IQR 61–69]) were randomly assigned to receive no ADT (n=737) or short-course ADT (n=743) in addition to postoperative radiotherapy at 121 centres in Canada, Denmark, Ireland, and the UK. With a median follow-up of 9·0 years (IQR 7·1–10·1), metastasis-free survival events were reported for 268 participants (142 in the no ADT group and 126 in the short-course ADT group; HR 0·886 [95% CI 0·688–1·140], p=0·35). 10-year metastasis-free survival was 79·2% (95% CI 75·4–82·5) in the no ADT group and 80·4% (76·6–83·6) in the short-course ADT group. Toxicity of grade 3 or higher was reported for 121 (17%) of 737 participants in the no ADT group and 100 (14%) of 743 in the short-course ADT group (p=0·15), with no treatment-related deaths. Interpretation Metastatic disease is uncommon following postoperative bed radiotherapy after radical prostatectomy. Adding 6 months of ADT to this radiotherapy did not improve metastasis-free survival compared with no ADT. These findings do not support the use of short-course ADT with postoperative radiotherapy in this patient population

Academic-community partnerships improve outcomes in pediatric trauma care.

BackgroundTo address the specialized needs of injured children, pediatric trauma centers (PTCs) were established at many large, academic hospitals. This study explores clinical outcomes observed for injured children treated at an academic-sponsored community facility.MethodsIn partnership with an academic medical center in a major metropolitan area, a not-for-profit community hospital became a designated Level II PTC in October 2010. Data for injured children <15 years old treated prior to PTC designation from January 2000 to September 2010 were prospectively collected using the Trauma and Emergency Medicine Information System and compared to data collected after PTC designation from January 2011 to December 2013.ResultsOverall, 681 injured children were treated at the community hospital from January 2011 to December 2013. Children treated after PTC designation were less likely to undergo computed tomography (CT) (50.9% vs. 81.3%, p<0.01), even when controlling for age, gender, injury type, injury severity, and year (OR 0.18, 95%CI 0.08-0.37). Specifically, fewer head (45.7% vs. 68.7%, p<0.01) and abdominal CTs (13.2% vs. 26.5%, p<0.01) were performed. Hospital length of stay was significantly shorter (2.8 ± 3.7 days vs. 3.7 ± 5.9 days, p<0.01). Mortality was low overall, but also decreased after PTC designation (0.4% vs. 2.0%, p=0.02).ConclusionsThese results indicate that academic-community partnerships in pediatric trauma care are a feasible alternative and may lead to improved outcomes for injured children

Academic-community partnerships improve outcomes in pediatric trauma care.

BackgroundTo address the specialized needs of injured children, pediatric trauma centers (PTCs) were established at many large, academic hospitals. This study explores clinical outcomes observed for injured children treated at an academic-sponsored community facility.MethodsIn partnership with an academic medical center in a major metropolitan area, a not-for-profit community hospital became a designated Level II PTC in October 2010. Data for injured children <15 years old treated prior to PTC designation from January 2000 to September 2010 were prospectively collected using the Trauma and Emergency Medicine Information System and compared to data collected after PTC designation from January 2011 to December 2013.ResultsOverall, 681 injured children were treated at the community hospital from January 2011 to December 2013. Children treated after PTC designation were less likely to undergo computed tomography (CT) (50.9% vs. 81.3%, p<0.01), even when controlling for age, gender, injury type, injury severity, and year (OR 0.18, 95%CI 0.08-0.37). Specifically, fewer head (45.7% vs. 68.7%, p<0.01) and abdominal CTs (13.2% vs. 26.5%, p<0.01) were performed. Hospital length of stay was significantly shorter (2.8 ± 3.7 days vs. 3.7 ± 5.9 days, p<0.01). Mortality was low overall, but also decreased after PTC designation (0.4% vs. 2.0%, p=0.02).ConclusionsThese results indicate that academic-community partnerships in pediatric trauma care are a feasible alternative and may lead to improved outcomes for injured children