tbuckley/cabot-search huggingface dataset:
Evaluation of the Safety and Efficacy of Immunotherapy Rechallenge in Patients With Renal Cell Carcinoma
Authors: Praful Ravi, Charlene Mantia, Christopher Su, Karl Sorenson, Dean Elhag, Nityam Rathi, Ziad Bakouny, Neeraj Agarwal, Yousef Zakharia, Brian A. Costello, Rana R. McKay, Vivek Narayan, Ajjai Alva, Bradley A. McGregor, Xin Gao, David F. McDermott, Toni K. Choueiri
Journal: JAMA Oncology (2020)

Several immune checkpoint inhibitors (ICIs) are approved for use in patients with metastatic renal cell carcinoma (mRCC), but the efficacy and safety of ICI rechallenge in mRCC is unknown.To evaluate the safety and efficacy of ICI rechallenge in patients with mRCC.This multicenter, retrospective cohort study included consecutive patients with mRCC from 9 institutions in the US who received at least 2 separate lines of ICI (ICI-1, ICI-2) between January 2012 and December 2019.Receipt of an ICI (anticytotoxic T-lymphocyte-associated protein 4, anti-programmed cell death protein 1, or anti-programmed cell death ligand 1), alone or in combination with other therapies, in at least 2 separate lines of therapy for mRCC.Investigator-assessed best overall response and immune-related adverse events.A total of 69 patients were included. Median (range) age at diagnosis of mRCC was 61 (36-86) years. Of these, 50 were men and 19 were women. The most common therapies received at ICI-1 were single-agent ICI (n = 27 [39%]) or ICI in combination with targeted therapy (n = 29 [42%]), while at ICI-2, the most common therapies were single-agent ICI (n = 26 [38%]) or dual ICI (n = 22 [32%]). Most patients discontinued ICI-1 owing to disease progression (n = 50 [72%]) or toxic effects (n = 16 [23%]). The overall response rates at ICI-1 and ICI-2 were 37% and 23%, respectively. The likelihood of a response at ICI-2 was greatest among patients who had previously responded to ICI-1 (7 of 24 [29%]), although responses at ICI-2 were seen in those who had progressive disease as their best response following ICI-1 (3 of 14 [21%]) as well as in those who received single-agent ICI at ICI-2 (7 of 23 [30%]). Grade 3 or higher immune-related adverse events were seen in 18 patients (26%) and 11 patients (16%) at ICI-1 and ICI-2, respectively. There were no treatment-related deaths.The findings of this multicenter cohort study suggest that ICI rechallenge in patients with mRCC may be safe and reasonably efficacious, with an overall response rate of 23%. Data from prospective studies are needed to validate these findings and determine the role of sequential ICI regimens in treatment of mRCC.
HealthTree Patient Portal mediated myeloma patient reported diagnostic imaging and pathology testing.
Authors: Nathan W. Sweeney, Jenny Ahlstrom, Michael A. Thompson
Journal: Journal of Clinical Oncology (2020)

e20565 Background: Multiple myeloma (MM) prognostic risk factors include cancer genetics as well as imaging characteristics. In order to engage the patient (pt) community regarding genetic testing and diagnostic imaging we utilized a patient-centered platform, HealthTree (www.healthtree.org), to evaluate the patient understanding of cancer genetic characteristics as well as evaluation of radiology methods used to evaluate their disease. Methods: An investigator-submitted online survey asking pts about myeloma genetic testing and imaging was fielded via HealthTree to 4,944 pts from May 10, 2019, to January 9, 2020. De-identified responses were aggregated and reviewed. The study was determined to be exempt by the Western Institutional Review Board. Results: 558 MM pts participated in the surveys. Pts who received more than one imaging or genetic test were able to indicate by selecting more than one option, this total response is indicated in the tables. Abbreviated questions and simplified responses are noted in the Table including: 1. At your diagnosis (or any time), did you receive any of the following tests to better understand the genetic profile of your disease? 2. At diagnosis (or any time), what imaging (radiology) tests were performed? Conclusions: Patient self-reported data registries are limited by patient perception or recall; however, these engaged and online MM pts may also be more biased toward knowing more about their medical history than the average pt. There are certainly real or perceived gaps in optimized genetic and imaging testing, which may reflect a communication or education gap. Pt reported interventions via an online portal can help investigators survey the pt community and result in hypothesis generating research questions including the actual use of testing, communication and education about testing and testing options, and MD trends in testing. [Table: see text][Table: see text]
发热、咳嗽、胸痛一周
Authors: 邝海东, 史玲, 祝墡珠
Journal: BMJ (2012)

病史摘要患者,女性,68岁.因发热、咳嗽、胸痛1周余于2010年6月本院门诊就诊.患者1周前出现左侧胸痛,与呼吸有关,伴干咳,无痰,时有发热,体温38℃左右.自服头孢拉定片等药物后胸痛稍有缓解,但仍有低热、干咳.病程中无咯血、气喘、不能平卧等,大小便正常,食欲、精神尚好.既往高血压病史10年,平时服用氨氯地平片等药物,血压控制在140/90 mm Hg(1 mm Hg =0.133 kPa);有高脂血症、乙型肝炎(乙肝)肝硬化史.否认糖尿病和慢性咳嗽史.否认嗜烟、酗酒史.否认疫水疫区接触史.已婚已育.否认家族遗传病史。
Validation of the reliability and clinical value of the simplified cough score
Authors: Ting Zhao, Zhi-hong Qiu, Lan Wang, Li Yu, Han-jing L, Zhong-min Qiu
Journal: BMJ (2012)

Objective To validate the repeatability of the simplified cough score and its responsiveness to effective treatment and investigate the relationship between the simplified cough score and cough symptom score.Methods A total of 119 patients with chronic cough referred to our respiratory clinic were recruited into the study between June 2010 and February 2011. Cough severity was evaluated by the simplified cough score,cough symptom score,Leicester cough questionnaire,and cough reflex sensitivity detection,and the correlations among them were analyzed.The change ratio,effect size,and standardized response mean of the simplified cough score were calculated after a 2-week course of effective treatment.The repeatability of the simplified cough score was assessed in 99 untreated patients with stable chronic cough.Results The intraclass correlation coefficient in a 3-day test-retest interval of simplified cough score was 0.90 ( 95 ％ CI =0.84 - 0.92,P =0.00 ) for daytime and 0.89 ( 95 ％ CI =0.91 - 0.96,P =0.00 ) for nighttime. There was an obvious positive linear correlation between the simplified cough score and cough symptom score ( daytime:r =0.82,P =0.00 ; nighttime:r =0.92,P =0.00 ),a significant negative linear correlation between the cough score and Leicester cough questionnaire,and a weak but significant negative correlation between the simplified cough score and cough threshold C2 or C5 to capsaicin. After a 2-week course of effective treatment,the change ratio,effect size,and standardized response mean were 46.71％,1.16,and 1.05 for daytime and 71.87％,1.09,and 1.10 for nighttime,respectively.Conclusion The simplified cough score is a reliable and valid tool for evaluation of cough severity in clinical practice.

Key words: 
Cough; Simplified cough score; Cough symptom score
Cancer risks associated with the HOXB13 c.251G&gt; A variant in men and women referred for hereditary cancer genetic testing.
Authors: Melanie Jones, Eric Thomas Rosenthal, Karen Copeland, John Kidd, Ryan Bernhisel, Matthew Comeaux, Randi Rawson, Debora Mancini-Dinardo
Journal: Journal of Clinical Oncology (2020)

e13653 Background: The HOXB13 c.251G &gt; A (p.G84E) variant is associated with increased prostate cancer risk, possibly at younger ages. Studies on this variant have focused primarily on men, although genetic testing for hereditary cancer risk is most often performed in women. There remains a need to assess whether male and female carriers of this variant have increased risk for other cancers. Methods: We identified male and female carriers of the HOXB13 c.251G &gt; A (p.G84E) variant among individuals referred for hereditary cancer panel genetic testing from October 2018 – December 2019. Non-carriers had no pathogenic variants in any gene or variants of uncertain significance in HOXB13. Personal and family (1 st - and 2 nd -degree relative) cancer histories were obtained from provider-completed test request forms. Multivariable logistic regression (MLR) models were conducted separately for males and females to estimate cancer risks for the variant as odds ratios (ORs), and 95% Wald confidence intervals (CIs) adjusted for age, ancestry and personal/family cancer history. Results: The analysis included 197,978 patients: 4.5% (8,998/197,978) male and 95.5% (188,980/197,978) female. The HOXB13 variant was present in 0.44% (40/8,998) of tested males, 45% (18/40) of whom had a diagnosis of prostate cancer. The variant was present in 0.32% (621/188,980) of tested females. Male carriers with prostate cancer were diagnosed at younger ages (median, 56; Interquartile ratio [IQR], 52, 62) than non-carriers (median, 63; IQR, 57,70), but this difference was not statistically significant. The MLR model calculated a 3.30 OR for prostate cancer in male carriers of c.251C &gt; A ( P = 0.01; 95% CI 1.30-8.39). In an analysis combining males and females, carriers were significantly more likely to report prostate cancer in a family member than non-carriers ( P = 3.5 x 10 −7 ; OR 1.61, 95% CI 1.34-1.93). There was no apparent association with increased risk for other cancers among carriers versus non-carriers, or among relatives of carriers compared with relatives of non-carriers. Conclusions: The HOXB13 c.251G &gt; A (p.G84E) variant was associated with significantly increased risk of prostate cancer, confirming previously published studies. We found no evidence of association with other cancers. For unaffected male carriers, who may frequently be identified through testing of a female relative, identification of this HOXB13 variant provides an opportunity for more precise prostate cancer risk stratification and screening.
Exome scale liquid biopsy characterization of putative neoantigens and genomic biomarkers pre- and post anti-PD-1 therapy in squamous cell carcinoma of the head and neck.
Authors: Charles Abbott, Nikita Bedi, Simo V Zhang, Robin Li, Rachel Pyke, Eric Levy, Rebecca Chernock, Mena Mansour, John B. Sunwoo, A. Dimitrios Colevas, Richard Chen, Sean Michael Boyle
Journal: Journal of Clinical Oncology (2020)

6557 Background: The reduced scope, and number of genes profiled by typical liquid biopsy panels can result in missed biomarkers including neoantigens, which may change with treatment, as well as potentially undetected resistance mechanisms and pathways beyond the scope of targets typically captured by panels. To address these limitations, we used a whole-exome scale liquid biopsy monitoring platform, NeXT Liquid Biopsy, to analyze head and neck squamous cell carcinoma (HNSCC) patients that have received anti-PD1 therapy. Presently, we sought to (1) monitor neoantigen changes in cfDNA as a complement to tumor biopsy-derived neoantigens, (2) compare the impact of tumor escape mechanisms, including HLA-LOH, on neoantigens identified in tissue and cfDNA and (3) to identify novel biological signatures that combine information from both solid tumor and liquid biopsies. Methods: Pre- and post-intervention matched normal, tumor and plasma samples were collected from a cohort of 12 patients with HNSCC. Following baseline sample collection all patients received a single dose of nivolumab, followed by resection approximately one month later when feasible, or a second biopsy where resection was impractical. Solid tumor and matched normal samples were profiled using ImmunoID NeXT, an augmented exome/transcriptome platform and analysis pipeline. Exome-scale somatic variants were identified in cfDNA from plasma samples using the NeXT Liquid Biopsy platform. Data from these two platforms were compared with corresponding clinical findings. Results: Concordant somatic events were detected between plasma and tumor at pre- and post-treatment timepoints. Neoantigens predicted to arise from these somatic events were reduced in solid tumor post-treatment, but increased in cfDNA, when compared to pre-treatment timepoints. HLA LOH was identified in a number of subjects, likely resulting in reduced neoepitope presentation in those cases. Immune cell infiltration increased in the tumor following treatment, with no changes to the CD8 + /Treg cell ratio, suggesting consistent immunoregulation. Conclusions: Exome-wide neoantigen burden was reliably predicted from cfDNA, providing additional insight complementing data from solid tumor. Analyzing HLA LOH, and neoantigen burden from both solid and liquid biopsies together over the course of treatment creates a more comprehensive profile of therapeutic response and resistance mechanisms in HNSCC patients missed with typical liquid biopsy panels.
Efficacy of platinum-based chemotherapy in platinum-resistant ovarian cancer: A systematic review with pooled analysis of outcomes.
Authors: Alexey Rumyantsev, Alexandra Tyulyandina, Mikhail Fedyanin, Ilya Pokataev, Elena Glazkova, Vladislav Nikulin, Sergei Tjulandin
Journal: Journal of Clinical Oncology (2020)

e18076 Background: Current management of recurrent ovarian cancer (OC) is based on the amount of time between the completion of penultimate platinum-based treatment and the detection of relapse. Patients with platinum-free interval (PFI) &lt; 6 mo. are considered to be platinum-resistant (PROC) and to have low response rate (RR) probability to platinum-based chemotherapy. Methods: We searched PubMed database for all prospective and retrospective full-text articles and abstracts on the treatment of patients with PROC for all years between 01/01/2000 and 01/06/2019 in English language. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) tool was used to ensure transparent reporting of the results. Study inclusion criteria were: 1) morphologically confirmed epithelial ovarian cancer; 2) standard definition of PROC as a disease that recurred within 6 months after completion of platinum-based chemotherapy; 3) treatment with platinum- or non-platinum chemotherapy with agents that are routinely used for OC; 4) no concomitant therapy with targeted or investigational agents; 5) clearly defined RR for patients with PROC and criteria used for response assessment. Pooled analysis of outcomes and multiple linear regression analysis was conducted to assess the impact of platinum salts on probability of response. Results: We identified 7156 articles and screened them for title and abstract. After the review process we selected 197 studies for further analysis. Of them, 52 (n = 1320) and 145 (n = 6937) trials assessed efficacy of platinum- and non-platinum based chemotherapy respectively. Among patients treated with platinum-based and non-platinum chemotherapy RR was 36.04% (95% CI 33.45-38.63) and 14.85% (95% CI 14.01-15.68) respectively. Pooled median progression-free survival was 5.8 mo. and 3.75 mo. respectively. In multiple linear regression model administration of platinum-based chemotherapy was the strongest predictor of objective response with B value 0.503 (p &lt; 0.001). Among platinum agents cisplatin (RR 39.9%: 95% CI 35.8-44.0%) and carboplatin (RR 42.3%; 95% CI 37.0-47.6%) were associated with better rates of objective response compared to oxaliplatin (RR 28.1%; 95% CI 23.9-32.3). Conclusions: This systematic review shows that patients with 'platinum-resistant' ovarian carcinoma may derive significant benefit from reintroduction of platinum agents and their value should be evaluated in further randomized trials.
Bariatric Surgery and Long-term Survival in Patients With Obesity and End-stage Kidney Disease
Authors: Kyle H. Sheetz, Laura Gerhardinger, Justin B. Dimick, Seth A. Waits
Journal: JAMA Surgery (2020)

<h3>Importance</h3> Obesity rates in patients with end-stage kidney disease are rising, contribute to excess morbidity, and limit access to kidney transplant. Despite this, there continues to be controversy around the use of bariatric surgery in this patient population. <h3>Objective</h3> To determine whether bariatric surgery is associated with improvement in long-term survival among patients with obesity and end-stage kidney disease. <h3>Design, Setting, and Participants</h3> Retrospective cohort study and secondary analysis of previously collected data from the United States Renal Data System registry (2006-2015). We used Cox proportional hazards analysis to evaluate differences in outcomes for patients receiving bariatric surgery (n = 1597) compared with a matched cohort of nonsurgical patients (n = 4750) receiving usual care. Data were analyzed between September 3, 2019, and November 13, 2019. <h3>Exposure</h3> Receipt of bariatric surgery. <h3>Main Outcomes and Measures</h3> All-cause mortality at 5 years. Secondary outcomes included disease-specific mortality and incidence of kidney transplant. <h3>Results</h3> Surgical and nonsurgical control patients had similar age, demographics, and comorbid disease burden. The mean (SD) age was 49.8 (11.2) years for surgical patients vs 51.7 (11.1) years for nonsurgical patients. Six hundred fifteen surgical patients (38.5%) were black vs 1833 nonsurgical patients (38.6%). Surgery was associated with lower all-cause mortality at 5 years compared with usual care (cumulative incidence, 25.6% vs 39.8%; hazard ratio, 0.69, 95% CI, 0.60-0.78). This was driven by lower mortality from cardiovascular causes at 5 years for patients undergoing bariatric surgery compared with nonsurgical control patients (cumulative incidence, 8.4% vs 17.2%; hazard ratio, 0.51; 95% CI, 0.41-0.65). Bariatric surgery was also associated with an increase in kidney transplant at 5 years (cumulative incidence, 33.0% vs 20.4%; hazard ratio, 1.82; 95% CI, 1.58-2.09). However, at 1 year, bariatric surgery was associated with higher all-cause mortality compared with usual care (cumulative incidence, 8.6% vs 7.7%; hazard ratio, 1.45; 95% CI, 1.13-1.85). <h3>Conclusions and Relevance</h3> Among patients with obesity and end-stage kidney disease, bariatric surgery was associated with lower all-cause mortality compared with usual care. Bariatric surgery was also associated with an increase in kidney transplant. Bariatric surgery may warrant further consideration in the treatment of patients with obesity and end-stage kidney disease.
A retrospective analysis of venous thromboembolism trends in chemotherapy-induced anemia.
Authors: Emily Jane Bryer, Michael J. Kallan, Ting-Shan Chiu, Katharina M. Scheuba, David H. Henry
Journal: Journal of Clinical Oncology (2020)

e15515 Background: Anemia is a common and unfortunate consequence of chemotherapy. Patients receiving a variety of chemotherapy regimens often develop chemotherapy–induced anemia (CIA), which contributes to poor outcomes, including increased mortality. Prompt and effective treatment of CIA is essential to prevent fewer chemotherapy dose delays and reductions. Despite the baseline coagulopathies present in patients with malignancy, administration of RBC transfusions is associated with venous thromboembolism (VTE). It remains unknown whether the risk of VTE in patients with CIA is greater among patients who receive single or multiple RBC transfusions. Methods: A retrospective study analyzed 10,269 University of Pennsylvania Health System patients with malignancies of various type, stage, and histopathology who developed CIA between 5/1/08-12/31/17. We analyzed rates of VTE development after adjusting for RBC intervention with a 95% confidence interval during the 90 days following CIA diagnosis. Results: Among the 10,269 patients with CIA, 2,008 patients (19.6%) received only RBC transfusion as anemia treatment; of that group, 545 (27.1%) developed a VTE. Transfusion of 2+ units RBC compared with 1 unit of RBC was associated with an increase in VTE development (RR = 1.37, 95% CI 1.09-1.72). The relationship of higher VTE development with increasing number of transfusions is displayed below. Conclusions: While RBC transfusion in patients with CIA is independently associated with VTE, our data further suggests an exponential risk of VTE development with increasing numbers of RBC transfusions. [Table: see text] [Table: see text]
Status and influencing factors of signing combination contract for primary care among elder residents in Shanghai communities
Authors: Cuiling Huang, Juan Shou, Yaling Li, Yao Liu
Journal: BMJ (2019)

Objective
To investigate the signing status of combination contract( 1+1+1 contract) for primary care among elderly residents in Shanghai communities and its influencing factors.


Methods
The policy of combination contract for primary care has been implemented in Shanghai since 2015, the residents signed a service contract with general practitioners in community health service center as well as with one of the secondary or tertiary hospitals ( 1+1+1 ). The questionnaire survey on the signing status of 1+1+1 contract was conducted among residents over 60 years in 6 communities in Shanghai which were selected by stratified and convenience sampling method from September 2017 to November 2017. The questionnaire was designed based on the previous research results of the qualitative interviews. The contents of the questionnaire included the basic characteristics, health status, understanding of the 1+1+1 signing policy, the status and reasons for contract signing, and so on. The date were analyzed by descriptive method, chi-square test, and binary logistic regression.


Results
Total 574 questionnaires were distributed and 564 valid questionnaires were retrieved with a recovery rate of 98.25%. Among all participants, 300 (53.2%) had signed and 264 (46.8%) had not signed. Univariate analysis showed that age, self-evaluated health status, chronic disease, medication, visits to the community health service center, the purpose of this visit,satisfaction with the community health service center, medical examination, concerning health knowledge, the willingness of community doctor as gatekeeper, the willingness of community referral, whether or not know the 1+1+1 contract policy, influence the rate of signing were associated with the signing of the contract (all P<0.05). Multivariate analysis showed that whether or not know the 1+1+1 contract policy, the willingness of community referral, and self-evaluation health status were independent factors affecting 1+1+1 contract signing (all P<0.05). The reason for signing the contract were convenience to visit doctor (69.00%, 207/300), and having a good relationship with family doctor (29.33%, 88/300). The reasons for not signing the contract were not understanding the policy (65.15%, 172/264), lack of help for signing (25.38%, 67/264), and restricted choice of seeking medical services (7.58%, 20/264).


Conclusion
Whether or not know the 1+1+1 contract policy, the willingness of community referral, and self-evaluation health status are the main influencing factors of signing 1+1+1 contract for primary care among elderly residents in Shanghai communities.


Key words: 
Hierarchical medical; Family doctor; Influencing factors
女病人的隐私
Authors: 曾昭耆
Journal: BMJ (2007)

在心内科门诊,不时会涉及到一些病人,特别是女病人某些与性有关的隐私问题.因为这类潜在的问题通常在患者身上就表现为胸闷、憋气等症状.有些病人虽然自己明白问题所在,但不便说明,或怀疑已引起器质性病变后果,故来心内科就诊.下面举几个例子。