tbuckley/cabot-search huggingface dataset:
Clinical characteristics and outcomes of coronavirus 2019 disease (COVID-19) in cancer patients treated with immune checkpoint inhibitors (ICI)
Authors: Aljosja Rogiers, Carlo Tondini, Joe M. Grimes, Megan H. Trager, Sharon Nahm, Leyre Zubiri, Neha Papneja, Arielle Elkrief, Jessica Borgers, April Rose, Johanna Mangana, Michael Erdmann, Ines Pires da Silva, Christian Posch, Axel Hauschild, Lisa Zimmer, Paola Queirolo, Caroline Robert, Karijn Suijkerbuijk, Paolo A. Ascierto, Paul Lorigan, Richard Carvajal, Osama E. Rahma, Mario Mandala, Georgina V. Long
Journal: Clinical Cancer Research (2020)

Background: ICI are widely used in the treatment of various cancer types  It has been hypothesized that ICI couldconfer an increased risk of severe acute lung injury or other complications associated with severe acute respiratorysyndrome coronavirus 2 (SARS-CoV-2)  Methods: We analyzed data from 113 patients with laboratory-confirmed COVID-19 while on treatment with ICI without chemotherapy in 19 hospitals in North America, Europe, and Australia  Data collected included details onsymptoms, comorbidities, medications, treatments and investigations for COVID-19, and outcomes (hospitaladmission, ICU admission, and mortality)  Results: The median age was 63 years (range 27-86);40 (35%) patients were female  Most common malignancies were melanoma (n=64, 57%), non-small cell lung cancer (n=19, 17%), and renal cell carcinoma (n=11, 10%);30(27%) patients were treated for early (neoadjuvant/adjuvant) and 83 (73%) for advanced cancer  Most patientsreceived anti-PD-1 (n=85, 75%), combination anti-PD-1 and anti-CTLA-4 (n=15, 13%), or anti-PD-L1 (n=8, 7%) ICI Comorbidities included cardiovascular disease (n=31, 27%), diabetes (n=17, 15%), and pulmonary disease (n=14, 12%)  Symptoms were present in 68 (60%) patients;46 (68%) had fever, 40 (59%) cough, and 23 (34%) dyspnea Overall, ICI was interrupted in 58 (51%) patients  At data cutoff, 33 (29%) patients were admitted to hospital, 6 (5%)to ICU, and 9 (8%) patients died  COVID-19 was the primary cause of death in 7 patients, 3 of whom were admittedto ICU  Cancer types in patients who died were melanoma (2), non-small cell lung cancer (2), renal cell carcinoma(2), and others (3);all (9) patients had advanced cancer  Administered treatments were oxygen therapy (8), mechanical ventilation (2), vasopression (2), antibiotics (7), antiviral drugs (4), glucocorticoids (2), and anti-IL-6 (2) Of all hospitalized patients, 20 (61%) had been discharged and 4 (12%) were still in hospital at data cutoff  Conclusion: The mortality rate of COVID-19 in patients on ICI is higher than rates reported for the generalpopulation without comorbidities but may not be higher than rates reported for the cancer population  Despite thesepreliminary findings, COVID-19 patients on ICI may not have symptoms and a proportion may continue ICI Correlative analyses are ongoing and will be presented
Assessment and reporting of quality-of-life measures in pivotal clinical trials of hematological malignancies.
Authors: Samer Al Hadidi, Rammurti T. Kamble, George Carrum, Helen E. Heslop, Carlos Almeida Ramos
Journal: Journal of Clinical Oncology (2020)

158 Background: The importance of assessment and reporting of health related quality of life (QoL) has been increasingly recognized in the field of oncology. QoL measures, which reflect patient’s perceived benefits and satisfaction, might be especially important in hematological malignancies clinical trials, where the intervention may not result in cure with modest overall survival benefit. Methods: Data on health related QoL were obtained from studies’ protocols and product labeling available publicly at Drugs@FDA. Drugs approved from 2016 to 2020 were analyzed. On the basis of publicly available study protocols and Food and Drug Administration (FDA) reviews, the authors reviewed the assessment of health related QoL in 53 clinical trials supporting 50 drug approvals from 2016 to 2020. Those trials resulted in approval of medications to treat leukemia, non-Hodgkin lymphoma, Hodgkin lymphoma, myelodysplastic syndrome, and multiple myeloma. Results: A total of 14,819 patients were assessed in the 5 years period after exclusion of unpublished studies. We calculated the frequency of assessment of health related QoL and if QoL measures were reported in the subsequent publications. After exclusion of 7 unpublished studies, we analyzed 46 clinical trials for reporting of HRQOL. Thirty percent of the protocols included assessment of health related QoL with only 43% of them (13% of all the analyzed clinical trials) reported the results of health related QoL. The results were consistent across all subtypes of hematological malignancies and were similar regardless of the studied primary endpoint. Conclusions: QoL measures are under studied in clinical trials of hematological malignancies. Studies that measured health related QoL didn’t report the results in more than half of the time. Although results may be reported in separate future publications, improvement in assessing and reporting of QoL will help to incorporate QoL measures in patient care and therapy choice decision. [Table: see text]
A validated, real-time prediction model for favorable outcomes in hospitalized COVID-19 patients
Authors: Narges Razavian, Vincent J. Major, Mukund Sudarshan, Jesse Burk-Rafel, Peter Stella, Hardev Randhawa, Seda Bilaloglu, Ji Chen, Vuthy Nguy, Walter Wang, Hao Zhang, Ilan Reinstein, David Kudlowitz, Cameron Zenger, Meng Cao, Ruina Zhang, Siddhant Dogra, Keerthi B. Harish, Brian Bosworth, Fritz Francois, Leora I. Horwitz, Rajesh Ranganath, Jonathan Austrian, Yindalon Aphinyanaphongs
Journal: npj Digital Medicine (2020)

The COVID-19 pandemic has challenged front-line clinical decision-making, leading to numerous published prognostic tools. However, few models have been prospectively validated and none report implementation in practice. Here, we use 3345 retrospective and 474 prospective hospitalizations to develop and validate a parsimonious model to identify patients with favorable outcomes within 96 h of a prediction, based on real-time lab values, vital signs, and oxygen support variables. In retrospective and prospective validation, the model achieves high average precision (88.6% 95% CI: [88.4-88.7] and 90.8% [90.8-90.8]) and discrimination (95.1% [95.1-95.2] and 86.8% [86.8-86.9]) respectively. We implemented and integrated the model into the EHR, achieving a positive predictive value of 93.3% with 41% sensitivity. Preliminary results suggest clinicians are adopting these scores into their clinical workflows.
Pharmacotherapy for Weight Loss in Cirrhosis and Liver Transplantation: Translating the Data and Underused Potential
Authors: Sara A. Brown, Manhal Izzy, Kymberly D. Watt
Journal: Hepatology (2020)

Background and Aims Thirty percent of patients with cirrhosis are obese and the prevalence of obesity increases after transplant to &gt;40% post‐transplant. There are currently four weight loss medications approved by the FDA for treatment of obesity (orlistat, phentermine‐topiramate, naltrexone‐bupropion, and liraglutide). The aim of this review was to investigate the data on the use of these weight loss medications and alternative medicines in patients with cirrhosis and in liver transplant recipients (LTRs). Approach and Results While there is paucity of data for these medications in patients with cirrhosis and LTRs, Liraglutide appears to be generally safe in view of its pharmacokinetic properties. Phentermine‐topiramate seems to have the highest weight loss potential but special consideration should be given to neuropsychiatric disorders, cardiovascular comorbidities, and drug interactions. There are emerging data on use of alternative medicines for weight loss but more data are needed. Conclusions The use of weight loss medications is feasible in this patient population but the decision of which medication to prescribe should be individualized based on the degree of renal and hepatic impairment, other co‐morbidities, and concomitant medications.
Mutation Rate Variability across Human Y-Chromosome Haplogroups
Authors: Qiliang Ding, Ya Hu, Amnon Koren, Andrew G Clark
Journal: Molecular Biology and Evolution (2020)

A common assumption in dating patrilineal events using Y-chromosome sequencing data is that the Y-chromosome mutation rate is invariant across haplogroups. Previous studies revealed interhaplogroup heterogeneity in phylogenetic branch length. Whether this heterogeneity is caused by interhaplogroup mutation rate variation or nongenetic confounders remains unknown. Here, we analyzed whole-genome sequences from cultured cells derived from >1,700 males. We confirmed the presence of branch length heterogeneity. We demonstrate that sex-chromosome mutations that appear within cell lines, which likely occurred somatically or in vitro (and are thus not influenced by nongenetic confounders) are informative for germline mutational processes. Using within-cell-line mutations, we computed a relative Y-chromosome somatic mutation rate, and uncovered substantial variation (up to 83.3%) in this proxy for germline mutation rate among haplogroups. This rate positively correlates with phylogenetic branch length, indicating that interhaplogroup mutation rate variation is a likely cause of branch length heterogeneity.
Extreme Expiratory Flow Limitation in a Child due to a Double Aortic Arch
Authors: Marloes M. Ijland, Lisanne H. Roesthuis, Karin Kamphuis, J. Johannes G. van der Hoeven, Joris Lemson
Journal: American Journal of Respiratory and Critical Care Medicine (2020)

"Extreme Expiratory Flow Limitation in a Child due to a Double Aortic Arch." American Journal of Respiratory and Critical Care Medicine, 202(12), pp. 1707–1709
Combinatorial treatment with menin and FLT3 inhibitors induces complete remission in AML models with activating FLT3 mutations
Authors: Hongzhi Miao, EunGi Kim, Dong Chen, Trupta Purohit, Katarzyna Kempinska, James Ropa, Szymon Klossowski, Winifred Trotman, Gwenn Danet-Desnoyers, Tomasz Cierpicki, Jolanta Grembecka
Journal: Blood (2020)
Papuloerythroderma of Ofuji
Authors: Sizhe Li, Xiaoling Yu, Tao Wang
Journal: JAMA Dermatology (2020)

This case report describes a man in his 80s with red-to-brown scaly, flat-topped papules that coalesced into plaques with a cobblestone-like appearance on the head, trunk, and extremities, sparing the face, flexures, and skin folds.
Trends in obesity among patients registered to SWOG cancer clinical treatment trials.
Authors: Riha Vaidya, Cathee Till, Heather Greenlee, Dawn L. Hershman, Joseph M. Unger
Journal: Journal of Clinical Oncology (2020)

126 Background: Rising obesity rates have been documented in the United States population since the 1980s. Several studies have shown links between obesity and the incidence of – and the outcomes of – specific cancer types. Few studies have examined the prevalence of obesity among cancer patients at the time of diagnosis or among those who participate in clinical trials. We examined the prevalence of obesity over a 35-year period among patients enrolled in clinical treatment trials conducted by the SWOG Cancer Research Network. Methods: We analyzed body mass index (BMI) at registration among patients enrolled in phase II or III clinical trials conducted by SWOG. Adult patients (age≥18) participating in trials in obesity-related cancers between 1985 and 2020 were included. Obesity was classified as BMI ≥ 30 kg/m 2 . Multivariable logistic regression was used to examine time trends, adjusting for age, sex, race, and treatment type. Time was defined as year of enrollment and examined in separate models as continuous years and as 5-year intervals. We examined trends among patient subgroups by sex and by treatment type (chemotherapy, immunotherapy, and targeted therapy). Results: 16,374 patients enrolled in SWOG clinical trials conducted between 1985 and 2020 were analyzed. Patients were most commonly enrolled in trials for breast cancer (n = 6,327, 38.6%), colon cancer (n = 2,408, 14.7%), multiple myeloma (n = 2,112, 12.9%), and rectal cancer (n = 1,785, 10.9%). Overall, 32% of patients were obese (n = 5,252). Unadjusted obesity rates among trial participants increased from 18% in 1985-1990 to 42% in 2016-2020, compared to an increase from 23% to 42% among US adults over a similar period. Obesity prevalence rates increased over time for all sex, age, and race subgroups. Overall, there was an increasing linear trend in obesity (OR = 1.36 for each 5-year increase, 95% CI: 1.33-1.39, p &lt; .0001). These trends persisted with adjustments for age, sex, race, and treatment type (OR = 1.35 per 5-year increase, 95% CI: 1.31-1.39, p &lt; .0001). Positive linear trends in obesity prevalence were observed for all subgroups by sex and treatment type. There was no evidence of difference in trends between males and females or between the three treatment types. Conclusions: We observed an increasing trend in obesity among patients participating in clinical trials for obesity-related cancers, mirroring US adult obesity rates. Our findings indicate good representation of obese patients in clinical treatment trials, which has favorable implications for the applicability of trial findings to this group of patients.
Spatiotemporal ATP Dynamics during AKI Predict Renal Prognosis
Authors: Shinya Yamamoto, Masamichi Yamamoto, Jin Nakamura, Akiko Mii, Shigenori Yamamoto, Masahiro Takahashi, Keiichi Kaneko, Eiichiro Uchino, Yuki Sato, Shingo Fukuma, Hiromi Imamura, Michiyuki Matsuda, Motoko Yanagita
Journal: Journal of the American Society of Nephrology (2020)

Significance Statement ATP depletion is central in kidney disease pathogenesis, but technology has not effectively monitored in vivo ATP dynamics. Experiments using a novel mouse strain that incorporates an ATP biosensor to visualize spatiotemporal ATP dynamics at single-cell resolution revealed the crucial difference between cells of the proximal tubules (PTs) and those of the distal tubules (DTs). Mitochondrial changes were consistent with the differing ATP dynamics in cells of the two regions, explaining the different sensitivity to ischemic reperfusion injury. A strong correlation emerged between ATP recovery of PT cells in acute phase and renal fibrosis in the chronic phase. Cold ischemia enhanced ATP recovery, providing a proof of concept for the possible protective value of renal hypothermia. Background Depletion of ATP in renal tubular cells plays the central role in the pathogenesis of kidney diseases. Nevertheless, inability to visualize spatiotemporal in vivo ATP distribution and dynamics has hindered further analysis. Methods A novel mouse line systemically expressing an ATP biosensor (an ATP synthase subunit and two fluorophores) revealed spatiotemporal ATP dynamics at single-cell resolution during warm and cold ischemic reperfusion (IR) with two-photon microscopy. This experimental system enabled quantification of fibrosis 2 weeks after IR and assessment of the relationship between the ATP recovery in acute phase and fibrosis in chronic phase. Results Upon ischemia induction, the ATP levels of proximal tubule (PT) cells decreased to the nadir within a few minutes, whereas those of distal tubule (DT) cells decreased gradually up to 1 hour. Upon reperfusion, the recovery rate of ATP in PTs was slower with longer ischemia. In stark contrast, ATP in DTs was quickly rebounded irrespective of ischemia duration. Morphologic changes of mitochondria in the acute phase support the observation of different ATP dynamics in the two segments. Furthermore, slow and incomplete ATP recovery of PTs in the acute phase inversely correlated with fibrosis in the chronic phase. Ischemia under conditions of hypothermia resulted in more rapid and complete ATP recovery with less fibrosis, providing a proof of concept for use of hypothermia to protect kidney tissues. Conclusions Visualizing spatiotemporal ATP dynamics during IR injury revealed higher sensitivity of PT cells to ischemia compared with DT cells in terms of energy metabolism. The ATP dynamics of PTs in AKI might provide prognostic information.
Use of artificial intelligence for tailored routine urine analyses
Authors: Olivier Dauwalder, Agathe Michel, Cécile Eymard, Kevin Santos, Laura Chanel, Anatole Luzzati, Pablo Roy-Azcora, Jean François Sauzon, Marc Guillaumont, Pascale Girardo, Christine Fuhrmann, Gérard Lina, Frédéric Laurent, François Vandenesch, Chantal Sobas
Journal: Clinical Microbiology and Infection (2020)
A prospective testing SARS-Cov-2/COVID-19 in cancer patients with antitumor treatment
Authors: Kathan D. Mehta, Elizabeth Wulf-Burchfield, Natalie Streeter, Anup Kasi, Adam H. AlDouri, Roy Jensen, Andrew K. Godwin, Terry Tsue, Weijing Sun
Journal: Clinical Cancer Research (2020)

Background: The oncology community faces unprecedented challenges in balancing a delay in cancer treatmentagainst the risk for a potential COVID-19 infection and associated complications  An early retrospective analysisreported that cancer patients with COVID-19 infection have a much higher death rate than those infected but withouta cancer diagnosis, likely because of their immunocompromised disease from cancer and treatment  Even thoughCOVID-19 is known to have a long incubation period (∼14 days), there were no clear guidelines for screeningasymptomatic cancer patients who are planning to have and having antitumor treatment as of April 2020  Methods: We developed a protocol to screen asymptomatic cancer patients for COVID-19 who are scheduled toreceive cancer-directed treatment (i e , chemotherapy, targeted therapy, immunotherapy, anticancer monoclonalantibody, endocrine therapy, or investigational agent)  The protocol was developed and activated within 2 weeksthrough the Cancer Center Investigator Initiated Trial Program  FDA-authorized CDC 2019-Novel Coronavirus(2019-nCoV) Real-Time RT-PCR Diagnostic Panel EUA kit was performed at Sinochips Diagnostics  The primaryobjective was to determine COVID-19 status in participants prior to initiating anticancer treatment  The secondaryobjective was to evaluate COVID-19 related adverse events (AEs) in recovered COVID-19-positive participants for30 days after initiation of anticancer therapy  Results: We enrolled 507 patients and tested for COVID-19 from 4/28/20 to 5/8/20 through coordinated efforts within the CTO and Biospecimen Repository Core Facility  The research study was stopped when the KU HealthSystem was able to test this population as standard of care  Median age was 65 years, 110 patients (22%) wereaged 75 years or older, and 274 (54%) patients were female  387 patients (76 3%) were Caucasians, 35 (6 9%)African American, 7 (1 4%) Asian, and 437 (86 2%) non-Hispanic  Based on the catchment of zip codes, 7% oftested patients came from more than 60 miles and 1 6% from more than 100 miles  Zero patients had a positiveCOVID-19 test  Conclusions: The prevalence of COVID19 in asymptomatic cancer patients is low, likely because of goodcompliance with the social distance policy  Screening for COVID19 may help reduce AEs related to COVID-19 inpatients receiving cancer-directed treatment  Studying COVID-19 test results in a larger patient pool is warranted  Asimilar study to test asymptomatic patient-facing oncology staff is pending
“When offered to participate”: A systematic review and meta-analysis of patient agreement to participate in cancer clinical trials.
Authors: Joseph M. Unger, Dawn L. Hershman, Cathee Till, Lori M. Minasian, Raymond U Osarogiagbon, Mark Fleury, Riha Vaidya
Journal: Journal of Clinical Oncology (2020)

92 Background: Patient participation in clinical trials (CTs) is vital for knowledge advancement and outcomes improvement. The rate of CT participation for adult cancer patients is between 5%-8%; many CTs fail due to poor accrual. Although patient decision-making is a common focus of studies examining barriers to CT participation, the rate of trial participation for patients actually offered a CT is unknown. Methods: We conducted a systematic review and meta-analysis using PubMed, Web of Science, and Ovid Medline search engines to identify studies over 20 years (1/1/2000-1/1/2020) that examined CT participation. Studies must have been conducted in the United States and specified the number of patients offered a CT and the number enrolled. We conducted a meta-analysis of single proportions using random effects. Rates were examined for both treatment trials and cancer control (CC) studies. We also compared the rates of enrollment between Black, Hispanic, and Asian patients versus White patients. Clinical care setting (academic vs community) was examined as a potential moderator. Results: We screened 3,241 unique citations and identified 35 (30 treatment and 5 CC) studies among which n = 9,759 patients were offered CT participation. Overall, 55.0% (95% CI: 49.4%-60.5%) of patients offered a CT agreed to enroll. Trial participation rates did not differ between treatment (55.0%, 95% CI: 48.9%-60.9%) and CC trials (55.3%, 95% CI: 38.9%-71.1%, p = .98); however, participation rates were significantly higher at academic centers (58.4%, 95% CI: 52.2%-64.5%) versus community centers (45.0%, 95% CI: 34.5%-55.7%, p = .04). In common studies, Black patients agreed to participate at similar rates (58.4%, 95% CI: 46.8%-69.7%) compared to White patients (55.1%, 95% CI: 44.3%-65.6%, p = .88). Results were also similar comparing White versus Hispanic or Asian patients. The main reasons for non-participation were treatment choice or lack of interest. Conclusions: More than half of all cancer patients who are offered CTs do participate; results were consistent between major race/ethnicity groups. This finding upends several conventional beliefs about cancer clinical trial participation, including that Black patients are less likely to agree to participate and that patient decision-making is the primary barrier to participation. Policies and interventions to improve CT participation should focus more on modifiable systemic structural and clinical barriers, such as improving access to existing trials and broadening trial eligibility.
Holding on to Junk Bonds: Intron Retention in Cancer and Therapy
Authors: Geoffray Monteuuis, Ulf Schmitz, Veronika Petrova, Padraic S. Kearney, John E.J. Rasko
Journal: Cancer Research (2020)

Intron retention (IR) in cancer was for a long time overlooked by the scientific community, as it was previously considered to be an artifact of a dysfunctional spliceosome. Technological advancements made in the last decade offer unique opportunities to explore the role of IR as a widespread phenomenon that contributes to the transcriptional diversity of many cancers. Numerous studies in cancer have shed light on dysregulation of cellular mechanisms that lead to aberrant and pathologic IR. IR is not merely a mechanism of gene regulation, but rather it can mediate cancer pathogenesis and therapeutic resistance in various human diseases. The burden of IR in cancer is governed by perturbations to mechanisms known to regulate this phenomenon and include epigenetic variation, mutations within the gene body, and splicing factor dysregulation. This review summarizes possible causes for aberrant IR and discusses the role of IR in therapy or as a consequence of disease treatment. As neoepitopes originating from retained introns can be presented on the cancer cell surface, the development of personalized cancer vaccines based on IR-derived neoepitopes should be considered. Ultimately, a deeper comprehension about the origins and consequences of aberrant IR may aid in the development of such personalized cancer vaccines.