tbuckley/cabot-search huggingface dataset:
Microbiota as Predictor of Mortality in Allogeneic Hematopoietic-Cell Transplantation
Authors: Jonathan U. Peled, Antonio L.C. Gomes, Sean M. Devlin, Eric R. Littmann, Ying Taur, Anthony D. Sung, Daniela Weber, Daigo Hashimoto, Ann E. Slingerland, John B. Slingerland, Molly Maloy, Annelie G. Clurman, Christoph K. Stein-Thoeringer, Kate A. Markey, Melissa D. Docampo, Marina Burgos da Silva, Niloufer Khan, André Gessner, Julia A. Messina, Kristi Romero, Meagan V. Lew, Amy Bush, Lauren Bohannon, Daniel G. Brereton, Emily Fontana, Luigi A. Amoretti, Roberta J. Wright, Gabriel K. Armijo, Yusuke Shono, Míriam Sanchez-Escamilla, Nerea Castillo Flores, Ana Alarcon Tomas, Richard J. Lin, Lucrecia Yáñez San Segundo, Gunjan L. Shah, Christina Cho, Michael Scordo, Ioannis Politikos, Kasumi Hayasaka, Yuta Hasegawa, Boglarka Gyurkocza, Doris M. Ponce, Juliet N. Barker, Miguel-Angel Perales, Sergio A. Giralt, Robert R. Jenq, Takanori Teshima, Nelson J. Chao, Ernst Holler, Joao B. Xavier, Eric G. Pamer, Marcel R.M. van den Brink
Journal: New England Journal of Medicine (2020)

Relationships between microbiota composition and clinical outcomes after allogeneic hematopoietic-cell transplantation have been described in single-center studies. Geographic variations in the composition of human microbial communities and differences in clinical practices across institutions raise the question of whether these associations are generalizable.
Slow Progress toward Gender Equality in Critical Care Medicine
Authors: Maryellen C. Antkowiak, Polly E. Parsons, Renee D. Stapleton
Journal: American Journal of Respiratory and Critical Care Medicine (2020)

In this issue of the Journal (pp.840-847), Vranas and colleagues examine gender differences in authorship of critical care literature (1).They describe several findings of gender disparity in authorship, including low rates of first and senior authorship, a tendency toward publication in lower-impact journals than those in which male authors are published, and slow growth in female authorship over the last decade (1).These findings add to a growing list of examples of the persistence of gender disparity not only in critical care medicine but also in academic medicine as a whole (2, 3).The authors acknowledge several limitations, including potential confounding by journal and search term selection, gender misclassification, author bias, and lack of a denominator of female academic intensivists worldwide.Although recognizing these limitations, Vranas and colleagues report findings that echo trends reported across a multitude of medical specialties (4-9).The underrepresentation of female authors in academic medicine is of significant concern, given the importance of publication in both the growth of academic careers and furthering the science of medicine.This phenomenon has been described as "both a reflection and a cause of women's under-representation and disadvantage in other areas of the scientific enterprise" (10), leading to a "vicious circle" of reduced research funding and publication rates (3).It is important to continue to investigate this trend, not only to avoid losing sight of this issue but also to help us get to the root cause and ultimately develop strategies to improve the presence of women in academic publishing.Vranas and colleagues keep this issue at the forefront with their present study while also being the first, to our knowledge, to describe this phenomenon in our own discipline.The authorship gender disparity in critical care literature may in part be explained by the continued male predominance of the specialty.Although the gender gap in medical school admissions and matriculations closed in the last two decades, many specialties remain predominantly male (11).A 2018 study found that only 37% of members of critical care professional societies were women.In addition, despite comprising about one-third of the critical care workforce internationally, women remain underrepresented in leadership positions, including society presidents, board and council members, and symposia chairs (12).Other reports have noted that although in some regions women may actually represent closer to 50% of practicing intensivists, they continue to be less likely to chair committees, serve on editorial and guideline boards, or hold academic leadership positions (13,14).Authorship disparity not only correlates with but also may partially explain the paucity of women among academic leaders.Individuals in leadership positions often have strong research funding histories (4-7, 9).
Model for End‐Stage Liver Disease‐Lactate and Prediction of Inpatient Mortality in Patients With Chronic Liver Disease
Authors: Naveed Sarmast, Gerald O. Ogola, Maria Kouznetsova, Michael D. Leise, Ranjeeta Bahirwani, Rakhi Maiwall, Elliot Tapper, James Trotter, Jasmohan S. Bajaj, Leroy R. Thacker, Puneeta Tandon, Florence Wong, K. Rajender Reddy, Jacqueline G. O'Leary, Andrew Masica, Ariel M. Modrykamien, Patrick S. Kamath, Sumeet K. Asrani
Journal: Hepatology (2020)

Compared to other chronic diseases, patients with chronic liver disease (CLD) have significantly higher inpatient mortality; accurate models to predict inpatient mortality are lacking. Serum lactate (LA) may be elevated in patients with CLD due to both tissue hypoperfusion as well as decreased LA clearance. We hypothesized that a parsimonious model consisting of Model for End-Stage Liver Disease (MELD) and LA at admission may predict inpatient mortality in patients with CLD.We examined all patients with CLD in two large and diverse health care systems in Texas (North Texas [NTX] and Central Texas [CTX]) between 2010 and 2015. We developed (n = 3,588) and validated (n = 1,804) a model containing MELD and LA measured at the time of hospitalization. We further validated the model in a second cohort of 14 tertiary care hepatology centers that prospectively enrolled nonelective hospitalized patients with cirrhosis (n = 726). MELD-LA was an excellent predictor of inpatient mortality in development (concordance statistic [C-statistic] = 0.81, 95% confidence interval [CI] 0.79-0.82) and both validation cohorts (CTX cohort, C-statistic = 0.85, 95% CI 0.78-0.87; multicenter cohort C-statistic = 0.82, 95% CI 0.74-0.88). MELD-LA performed especially well in patients with specific cirrhosis diagnoses (C-statistic = 0.84, 95% CI 0.81-0.86) or sepsis (C-statistic = 0.80, 95% CI 0.78-0.82). For MELD score 25, inpatient mortality rates were 11.2% (LA = 1 mmol/L), 19.4% (LA = 3 mmol/L), 34.3% (LA = 5 mmol/L), and >50% (LA > 8 mmol/L). A linear increase (P < 0.01) was seen in MELD-LA and increasing number of organ failures. Overall, use of MELD-LA improved the risk prediction in 23.5% of patients compared to MELD alone.MELD-LA (bswh.md/meldla) is an early and objective predictor of inpatient mortality and may serve as a model for risk assessment and guide therapeutic options.
Troponin as a biomarker for mortality in stable COPD
Authors: Ulf Nilsson, Lowie E.G.W. Vanfleteren
Journal: European Respiratory Journal (2020)

<b>High sensitive cardiac troponins are important predictive cardiovascular biomarkers for all-cause mortality in COPD. Underlying causes to elevated troponin are still unclear, but elevated troponin might identify COPD phenotypes suitable for CVD prevention.</b> http://bit.ly/35EKAqW
The effect of AKR1C3 on the switch from prednisone to dexamethasone in metastatic castration-resistant prostate cancer patients receiving abiraterone.
Authors: Yuchao Ni, Jinge Zhao, Junru Chen, Guangxi Sun, Sha Zhu, Xingming Zhang, Jindong Dai, Zhipeng Wang, Haoran Zhang, Xudong Zhu, Ni Chen, Pengfei Shen, Hao Zeng
Journal: Journal of Clinical Oncology (2020)

133 Background: Abiraterone is the first-line treatment for men with metastatic castration-resistant prostate cancer (mCRPC) and is recommended to be used with prednisone. Previous studies had demonstrated that the switch from prednisone to dexamethasone in some mCRPC patients can reverse abiraterone-resistance. However, it remains uncertain which group of patients will benefit from such switching. AKR1C3 is a critical enzyme contributing to the drug-resistance of abiraterone. Here, we aim to explore the significance of AKR1C3 in predicting the therapeutic efficacy of the corticosteroid switching in mCRPC patients receiving abiraterone. Methods: In total, 43 PCa patients treated with abiraterone after mCRPC between 2016 and 2018 in our institution were included. After biochemical progression in abiraterone plus prednisone, all cases received a corticosteroid switch to abiraterone plus dexamethasone. The expression of AKR1C3 was detected by immunohistochemical staining from re-biopsy (re‐Bx) of primary prostate lesions at the time of mCRPC. Kaplan‐Meier curves were used to analyze the association between AKR1C3 and treatment outcomes. Results: Totally, AKR1C3 was positive in 19 of 43 (44.19%) cases. In the corticosteroid switch treatment, 30% PSA decline was confirmed in 18/43 (41.86%) patients, while the median PSA progression‐free survival (PSA-PFS) and overall survival (OS) was 4.93 Mo and 31.57 Mo, respectively in the whole cohort. AKR1C3 expression was associated with statistically shorter median PSA-PFS (4.50 Mo vs 7.73 Mo; p =0.010) and numerically lower median OS (25.43 Mo vs 39.37 Mo, p =0.274). While the 30% PSA decline rate was numerically comparable between those with and without AKR1C3 expression (31.6% vs 50.0%, p =0.224). Conclusions: This study showed AKR1C3 detection in tissues from prostate re‐Bx at mCRPC was associated with poor PSA-PFS in the corticosteroid switch from abiraterone plus prednisone to abiraterone plus dexamethasone. These results would be helpful in making optimal personalized treatment decisions for patients with mCRPC, facilitating physicians predicting the effectiveness of corticosteroid switch treatment.
Association of checkpoint inhibitor monotherapy with less cardiac toxicity than combination therapy.
Authors: Eugene Blanchard Cone, Stephen Reese, Maya Marchese, Junaid Nabi, Kerry L. Kilbridge, Quoc-Dien Trinh
Journal: Journal of Clinical Oncology (2020)

671 Background: Immune checkpoint inhibitors (ICIs) demonstrate impressive clinical benefit across a variety of cancers. NCCN guidelines for several cancers including renal cell carcinoma now support ICI monotherapy and combination therapy with ipilimumab. Cardiac toxicity is a rare but catastrophic adverse event associated with ICIs. We sought to define the comparative cardiac risk profile of ICI combination versus monotherapy in a real world setting. Methods: We used VigiBase, the World Health Organization database of case safety reports, which collects data from more than 130 countries to identify drug-associated adverse events. Using Medical Dictionary for Regulatory Activities terminology, we identified cardiac adverse events (AE) related to monotherapy (nivolumab, ipilimumab, pembrolizumab) or combination therapy (ipilimumab/nivolumab). To explore a possible relationship we used the reporting odds ratio (ROR), a surrogate measure of association using all other reactions as non-cases. A lower bound of a 95% confidence interval of ROR &gt; 1 reflects a disproportionality signal that more AEs are observed than expected due to chance. Results: We found 7,644, 25,016, and 14,681, and 5,191 AEs for ipilimumab, nivolumab, pembrolizumab, and combination therapy respectively. No signal existed for overall cardiac events, but combination therapy was associated with significantly higher odds of pericarditis or myocarditis (ROR 6.9, 95% CI 5.7—8.3) versus pembrolizumab (5.6, 4.9—6.4), nivolumab (5.1, 4.6-5.7), or ipilimumab monotherapy (1.9, 1.4-2.7). Pericarditis and myocarditis with combination therapy was fatal for 23% of reported AEs, compared to 14%, 14%, and 20% for ipilimumab, nivolumab, and pembrolizumab (p = 0.003) respectively. Conclusions: Using validated pharmacovigilance methodology, we found significantly increased odds of myocarditis and pericarditis for all ICI, with the highest odds for combination therapy. These adverse events were often fatal. Further research is needed to identify patients at high risk for immunotherapy related cardiac toxicity.
Integrated safety profile of selinexor in multiple myeloma: experience from 437 patients enrolled in clinical trials
Authors: Maria Gavriatopoulou, Ajai Chari, Christine Chen, Nizar Bahlis, Dan T. Vogl, Andrzej Jakubowiak, David Dingli, Robert F. Cornell, Craig C. Hofmeister, David Siegel, Jesus G. Berdeja, Donna Reece, Darrell White, Suzanne Lentzsch, Cristina Gasparetto, Carol Ann Huff, Sundar Jagannath, Rachid Baz, Ajay K. Nooka, Joshua Richter, Rafat Abonour, Terri L. Parker, Andrew J. Yee, Philippe Moreau, Sagar Lonial, Sascha Tuchman, Katja C. Weisel, Mohamad Mohty, Sylvain Choquet, T. J. Unger, Kai Li, Yi Chai, Lingling Li, Jatin Shah, Sharon Shacham, Michael G. Kauffman, Meletios Athanasios Dimopoulos
Journal: Leukemia (2020)

Abstract Selinexor is an oral, small molecule inhibitor of the nuclear export protein exportin 1 with demonstrated activity in hematologic and solid malignancies. Side effects associated with selinexor include nausea, vomiting, fatigue, diarrhea, decreased appetite, weight loss, thrombocytopenia, neutropenia, and hyponatremia. We reviewed 437 patients with multiple myeloma treated with selinexor and assessed the kinetics of adverse events and impact of supportive care measures. Selinexor reduced both platelets and neutrophils over the first cycle of treatment and reached a nadir between 28 and 42 days. Platelet transfusions and thrombopoietin receptor agonists were effective at treating thrombocytopenia, and granulocyte colony stimulating factors were effective at resolving neutropenia. The onset of gastrointestinal side effects (nausea, vomiting, and diarrhea) was most common during the first 1–2 weeks of treatment. Nausea could be mitigated with 5-HT3 antagonists and either neurokinin 1 receptor antagonists, olanzapine, or cannbainoids. Loperamide and bismuth subsalicylate ameliorated diarrhea. The primary constitutional side effects of fatigue and decreased appetite could be managed with methylphenidate, megestrol, cannabinoids or olanzapine, respectively. Hyponatremia was highly responsive to sodium replacement. Selinexor has well-established adverse effects that mainly occur within the first 8 weeks of treatment, are reversible, and respond to supportive care.
Comprehensive genomic profiling (CGP) in post-systemic treatment (Post) metastatic sites (MET) and pretreatment (Pre) primary tumors (PT) of metastatic prostate cancer (mPC).
Authors: Andrea Necchi, Petros Grivas, Gennady Bratslavsky, Oleg Shapiro, Joseph Jacob, Ethan Sokol, Jo-Anne Vergilio, Keith Killian, Douglas I. Lin, Shakti H. Ramkissoon, Eric Allan Severson, Amanda Hemmerich, Jon Chung, Brian Michael Alexander, Prasanth Reddy, Kimberly McGregor, Julia Andrea Elvin, Alexa Betzig Schrock, Natalie Danziger, Jeffrey S. Ross
Journal: Journal of Clinical Oncology (2020)

175 Background: CGP was performed on Pre PT and Post MET including bone (BO), liver (LIV), lung (LU), brain (BN), lymph node (LN) and soft tissue (ST) mPC. Methods: 1,294 mPC underwent hybrid-capture based CGP. Tumor mutational burden (TMB) was determined on up to 1.1 Mbp of sequenced DNA and microsatellite instability (MSI) was determined on 114 loci. PD-L1 expression was determined by IHC (Dako 22C3). Results: GA in AR were lowest in the Pre PT (2%) and highest in Post LU (24%) and LIV (50%). GA/tumor was significantly higher in BN (8.0) compared to PT (3.8). BR MET also featured higher PTEN GA than PT. BRCA2 GA varied from 0% in BR to 7-9% in PT, BO, LU, LN and ST to a high of 15% in LI MET. ATM GA were significantly higher in LU MET and RAD21 GA highest in LN MET. Potential predictors of IO drug response included high CDK12 GA in LU MET, MSI high status at 29% in BR MET associated with higher TMB levels, but virtual absence of high PD-L1 expression. ERBB2 GA appeared to be increased in the MET group compared with PT but BRAF GA were not. RB1 GA were significantly increased in LIV MET cases. Conclusions: CGP of mPC PT and MET demonstrates significant differences likely linked to exposure to systemic therapies. These findings suggest that, in the future, liquid biopsies may have advantages over individual MET site biopsies in their ability to capture the entire range of therapeutic opportunities for patients with advanced mPC.[Table: see text]
A novel clinical decision aid to support personalized treatment selection for patients with CT1 renal cortical masses: Results from a multi-institutional competing risks analysis including performance status and comorbidity.
Authors: Sarah P. Psutka, Roman Gulati, Michael A.S. Jewett, Kamel Fadaak, Antonio Finelli, Todd Matthew Morgan, Phillip M. Pierorazio, Mohamad E. Allaf, Jeph Herrin, Christine M. Lohse, R. Houston Thompson, Stephen A. Boorjian, Thomas D. Atwell, Grant Schmit, Brian Addis Costello, Laura Legere, Nilay Shah, Bradley C. Leibovich
Journal: Journal of Clinical Oncology (2020)

610 Background: Personalized treatment for clinical T1 renal cortical masses (RCMs) should account for competing risks related to tumor and patient characteristics. Using a contemporary multi-institutional cohort, we developed treatment-specific prediction models for cancer-specific mortality (CSM), other-cause mortality (OCM), and 90-day complication rates for patients managed with surgery, thermal ablation (TA), and active surveillance (AS). Methods: Preoperative clinical and radiological features were collected for eligible patients aged 18-91 years treated at four academic centers from 2000-2016. Prediction models used competing risks regressions for CSM and OCM and logistic regressions for 90-day Clavien &gt;3 complications, adjusting for tumor size as well as patient age, sex, ECOG performance status (PS), and Charlson comorbidity index (CCI). Predictions accounted for missing data using multiple imputation. Results: After excluding 25 patients with no follow-up, the cohort included 4995 patients treated with radical nephrectomy (RN, n=1270), partial nephrectomy (PN, n=2842), thermal ablation (n=479), or active surveillance (n=404). Median follow-up was 5.1 years (IQR 2.5-8.5). Predictions from the fitted model are shown in an online calculator ( https://rgulati.shinyapps.io/rcc-risk-calculator ). To illustrate the use of this calculator for a specific patient, a 70-year-old female with a 5.5 cm RCM, PS of 2, and CCI of 3 has a predicted 5-year CSM of 4-7% across treatments, 5-year OCM of 34-49%, and 90-day risk of Clavien ≥3 complications of 4%, 10%, and 6% for RN, PN, and TA respectively. Conclusions: Personalized treatment selection for cT1 RCM is challenging. We present a competing risk calculator that incorporates pretreatment features to quantify competing causes of mortality and treatment-associated complications. Pending validation, this tool may be used in clinical practice to provide patients with estimated individualized treatment-specific probabilities of competing causes of death and complication risks to facilitate shared decision-making.
Cognitive Impairment in Never-Medicated Individuals on the Schizophrenia Spectrum
Authors: Rodolfo Solís-Vivanco, Felipe Rangel-Hassey, Pablo León-Ortiz, Alejandra Mondragón-Maya, Francisco Reyes-Madrigal, Camilo de la Fuente-Sandoval
Journal: JAMA Psychiatry (2020)

Cognitive Impairment in Never
Results after two years of follow up after intravesical thermochemotherapy with heated mitomycin 40 in patients with high-risk superficial bladder cancer.
Authors: Thomas Alexander Voegeli, Eric Frank, Christian Bach, Catejan Nzeh
Journal: Journal of Clinical Oncology (2020)

512 Background: Standard management of high risk TCC is either BCG or radical cystectomy, alternative treatment options are limited. It is known that the anti-tumor effect of heated mitomycin is 10 fold higher than at room temperature, which is the standard of intravesical therapy. We herein report the first 2 year follow up (FU) after intravesical therapy with heated mitomycin in a cohort of patients with high risk superficial bladder cancer (TCC). Methods: Treatment was performed for 1 hour with machine bladder irrigation (COMBAT) which maintaines temperature of mitomycin (40 mg) exactly at 43 C. Patients underwent therapy with a 6 week course of weekly treatment and were than followed by cystoscopy every 3 month and if necessary biopsy. Results: We identified 62 patients out of a total group of 108 patients who met the inclusion criteria for high risk TCC according to the EAU Guidelines and who got the complete 6 courses of treatment. 2 were lost of follow up, 1 died due to cardiac problems and 1 from metastatic prostate carcinoma. The remaining 58 patients had a mean FU of 26 month (16-54 m) and included 20 non-responders to BCG. 48/58 patients had CIS or pT1 Tumors or both, 10 patients had pTa+CIS. There were 5 recurrences, all superficial stage pTa, one in the rigth ureter, all could be managed without cystectomy. 8 patients had progressive or recurrent CIS/pT1 or were progressive to pT2 after therapy and underwent cystectomy. Conclusions: In this high risk cohort of 58 patients with a high rate of BCG non-responders only 8 patients had to undergo cystectomy during a 2 year follow up. Intravesical therapy with heated mitomycin is safe and well tolerated and may be an additional alternative treatment before cystectomy is performed in high risk patients with high risk TCC or BCG non responders.
Abstract 12075: Recurrent Admissions for Acute Decompensated Heart Failure Among Patients With and Without Peripheral Artery Disease: The Atherosclerosis Risk in Communities Study
Authors: Zainali Chunawala, Patricia Chang, Andrew P DeFilippis, Michael E Hall, Kunihiro Matsushita, Melissa Caughey
Journal: Circulation (2019)

Introduction: Peripheral artery disease (PAD) is both a common comorbidity and a contributing factor to heart failure. Although PAD has been associated with mortality and all-cause hospitalizations...