tbuckley/cabot-search huggingface dataset:
Safety of weight-based dosing of nivolumab with or without ipilimumab by body mass index (BMI) stratified by sex across 14 CheckMate clinical trials.
Authors: Jennifer Leigh McQuade, Hans J. Hammers, Helena Furberg, Andreas Engert, Thierry Andre, George Blumenschein, Nizar M. Tannir, Ari David Baron, James Larkin, Anthony B. El-Khoueiry, David Paul Carbone, John-Michael Thomas, Delphine Hennicken, Roberto Zoffoli, Daniel Reshef, Mary Coffey, Robert J. Motzer
Journal: Journal of Clinical Oncology (2020)

e15114 Background: Associations between obesity and cancer risk, prognosis, and therapeutic outcomes have been extensively researched. However, the impact of BMI on safety in patients receiving immunotherapy has not been well described. Methods: A descriptive, retrospective analysis examined associations between BMI (kg/m 2 ) (underweight/normal, BMI &lt; 25; overweight, 25 ≤ BMI &lt; 30; obese, BMI ≥ 30) and incidence of any-grade and grade 3/4 immune-mediated adverse events (imAEs) in patients receiving ≥ 1 dose of nivolumab 3 mg/kg as monotherapy (NIVO3; n = 2746). Data were pooled from CheckMate clinical trials across 8 tumor types. Data from nivolumab in combination with ipilimumab cohorts (n = 1026) and safety analyses by specific imAEs and tumor types will be presented. Results: Select NIVO3 monotherapy cohort patient demographics were: 68.5% male, median age of 61 years, median 10 doses received, and median BMI of 25.3 kg/m 2 . Results showed a trend towards higher incidence of any-grade, but not grade 3/4, imAEs in obese vs overweight and obese vs underweight/normal BMI patients (Table). BMI associations with imAE incidence were consistent with the overall trend across pre-defined subsets, including smoking status, age, and ECOG performance status. Both male and female patients had an increased incidence of any-grade imAEs with obesity; however, obese female patients had a higher incidence of grade 3/4 imAEs vs underweight/normal BMI (Table). Conclusions: This was a novel analysis of BMI and safety in 2746 patients across 8 tumor types in CheckMate clinical trials who were treated with nivolumab monotherapy. While obese patients showed a trend towards higher incidence of any-grade imAEs than those with overweight and underweight/normal BMI, incidence of grade 3/4 imAEs was consistent across BMI categories. Clinical trial information: CheckMate 017,026,057,025,039,205,040,066,067,141,275,142,016,214 (NCT numbers do not fit in field) . [Table: see text]
Randomized phase II trial of topotecan plus M6620 (VX-970) versus topotecan alone in patients with relapsed small-cell neuroendocrine cancers including small cell lung cancer.
Authors: Nobuyuki Takahashi, Rasa Vilimas, Samantha Nichols, Linda Sciuto, Santhana Webb, Seth M. Steinberg, Yves Pommier, Anish Thomas
Journal: Journal of Clinical Oncology (2020)

TPS3653 Background: Ataxia telangiectasia and Rad3-related (ATR) is an essential kinase that senses stressed replication forks and orchestrates the multifaceted replication stress response. Cancer cells under replication stress are particularly susceptible to ATR inhibition. Small-cell neuroendocrine cancers (SCNCs) are highly aggressive and arise in multiple tissues, most commonly lung (SCLC). We hypothesized that SCNCs are under replication stress and that exacerbating this stress could selectively kill SCNC by replicative damage. Based on promising data from a single-arm study, this study seeks to evaluate the improvement of progression free survival (PFS) by adding M6620 to topotecan in patients with SCNC. Methods: This study is an investigator-initiated, multicenter, open-label randomized phase 2 clinical trial. Key inclusion criterion are patients at age ≥18 with SCNCs that had relapsed after at least one prior chemotherapy, ECOG PS ≤ 2, and adequate organ function. Patents with asymptomatic brain metastasis, irrespective sensitivity with prior platinum-based chemotherapy, and previously treated with immune checkpoint inhibitors are eligible. The primary cohort consists of 54 patients with SCLC randomized 2:1 to receive either topotecan in combination with M6620 or topotecan alone. Topotecan is administered 1.25 mg/m 2 intravenously over 30 minutes every 23 hours on day 1 through 5, pegfilgrastim 6 mg subcutaneously on day 6 and M6620 is administered at 210 mg/m 2 intravenously over 60 minutes on day 2 and day 5 if the patient is randomized to the combination arm, in 21-day cycles. Patients randomized to the topotecan alone arm can cross-over to the combination arm at disease progression. An exploratory cohort will enroll 20 patients with SCNC. Primary endpoint is PFS improvement with the combination compared with topotecan alone. Secondary endpoints are ORR and overall survival. To evaluate the genomic features associated with clinical outcomes and to gain insight into the underlying mechanisms of ATR inhibitor response, we require mandatory biopsy before starting treatment. Clinical trial information: NCT03896503 .
睡眠呼吸暂停与高血压
Authors: 陈宝元
Journal: BMJ (2010)

由于高血压是一种高患病率、高致残率、高致死率的常见疾病,一直成为我国重点防治的疾病之一.睡眠呼吸暂停综合征是一种常见的睡眠呼吸疾病,因为它对机体多系统和多器官特别是对心血管系统的损害,对人类健康构成很大威胁。
Determination of biologic and prognostic feature scores from whole slide histology images using deep learning.
Authors: Okyaz Eminaga, Mahmoud Abbas, Axel Semjonow, James D Brooks, Daniel Rubin
Journal: Journal of Clinical Oncology (2020)

e17527 Background: In cancer, histopathology is a reflection of the underlying molecular changes in the cancer cells and provides prognostic information on the risk of disease progression. Therefore, whole slide images may harbor histopathological features that have a biological association and are prognostic. Methods: This study has extracted histopathological feature scores generated from hematoxylin and eosin (HE) histology images based on deep learning models developed for the detection of pathological findings related to prostate cancer (PCa). Correlation analyses between the histopathological feature scores and the most relevant genomic alterations related to PCa were performed based on the original results and diagnostic histology images from TCGA PRAD study (n = 251). We extracted feature scores from tumor lesions after applying tumor segmentation and several data transformation using five models developed for detection of cribriform or ductal morphologies, Gleason patterns 3 and 4, and the presumed tumor precursor. For prognostic evaluation, we performed survival analyses of 371 patients from the TCGA PRAD dataset with biochemical recurrence (BCR) using a Cox regression model, Kaplan Meier (KM) curves. We applied the bootstrapping resampling for the uncertainty evaluation and C-statistics for the randomness measurement. Results: The feature scores were significantly correlated with the androgen receptor protein expression, an androgen-signaling score, mRNA expression, and androgen receptor splice variant 7. In addition, feature scores were associated with SPINK1 overexpression, the heterozygous loss of TP53, and SPOP mutations. Additionally, the mRNA and miRNA clusters identified by the TCGA research team for PCa. These features were independent of Gleason grade and were non-random. The survival analyses revealed that a model, including three of five feature scores, achieved a c-index of 0.706 (95% CI: 0.606-0.779). The KM curve showed that these risk groups based on the Cox regression model are significantly discriminative (Log-rank P-value &lt; 0.0001). The low-risk group (n = 177) achieved a 2-year BCR-free survival rate (BFS) of 97.4% (95% CI: 94.9 - 100.0%) and a 5-year PFS of 88.3% (95% CI: 80.6 - 96.7%). In contrast, the high-risk group (n = 194) showed a 2-year PFS of 86.3% (95% CI: 81.1 - 91.8%) and a 5-year BFS of 66.9% (95% CI: 54.6 - 0.82.1%). Conclusions: Our findings uncover the potential of feature scores from histology images as digital biomarkers in precision medicine and as an expanding utility for digital pathology.
Have we lost the thinker in other minds? Human thinking beyond social norms
Authors: Nabil Bouizegarene
Journal: Behavioral and Brain Sciences (2020)

Abstract Veissière and colleagues suggest that thinking is entirely based on social norms. I point out that despite the fact that social norms are commonly used to alleviate cognitive processing, some individuals are willing and able to go about the costly process of questioning them and exploring other valuable ways of thinking.
Association of financial conflicts of interest with academic success among junior faculty in hematology and oncology.
Authors: Angela J. Fought, Andrew A. Davis, Melissa M. Shaw, Vinay Prasad, Suneel Deepak Kamath
Journal: Journal of Clinical Oncology (2020)

2080 Background: Financial conflict of interest (COI) represents a complex issue in hematology and oncology. Little is known about when COIs develop during a career and if these correlate with early career success. We evaluated self-reported COIs for junior faculty members at 10 academic cancer centers and examined if these financial relationships with industry correlated with measures of academic career success. Methods: The study evaluated 229 assistant professors from the top 10 cancer centers based on the 2018 US News Cancer rankings. Faculty characteristics were determined from hospital websites including the number of years since completing fellowship. Data regarding National Institute of Health (NIH) funding were obtained. Industry funds (Sunshine Act funds; SAF) were identified from the Centers for Medicare &amp; Medicaid Services (CMS) Open Payments database from 2013-2017. Self-reported COIs were obtained from the American Society of Clinical Oncology (ASCO) or American Society of Hematology (ASH) disclosures databases, and through review of disclosures from recent publications. Measures of academic success included h-index and number of publications. We assessed the influence of number of COIs and SAF received on measures of academic success. Results: Of the 229 included faculty, 45% were female, 39% graduated fellowship in 2015 or later, 35% were double-boarded, 40% had dual degrees and 15% received NIH funding. Approximately 46% of faculty had at least 1 COI. COIs (ASCO/ASH) were positively correlated with COIs self-reported in publications and total SAF (Spearman correlations 0.57 and 0.54, both P &lt; 0.01). The development of COIs and the number of SAF increased with years in practice (Spearman correlations 0.37 and 0.28, both P &lt; 0.01). COIs and SAF correlated with h-index (Spearman correlation 0.40 and 0.41, both P &lt; 0.01). After adjusting for years since fellowship, linear regression demonstrated that log-transformed h-index and number of publications were associated with SAF (P &lt; 0.01) and COIs (ASCO/ASH) (P = 0.01). Conclusions: Financial COIs were present in nearly half of the faculty and increased with more time since completing fellowship. Measures of academic success were positively correlated with COIs (ASCO/ASH) and SAF. These data suggest that cultivating industry relationships may aid faculty in establishing early academic success.
Randomized trial of a perioperative geriatric intervention for older adults with cancer.
Authors: Carolyn L. Qian, Helen P. Knight, Cristina R. Ferrone, Hiroko Kunitake, Carlos Fernandez-del Castillo, Michael Lanuti, Motaz Qadan, Rocco Ricciardi, Keith D. Lillemoe, Emilia R. Kaslow-Zieve, Chinenye C. Azoba, Esteban Franco-Garcia, Terrence A. O'Malley, Vicki A. Jackson, Joseph A. Greer, Areej El-Jawahri, Jennifer S. Temel, Ryan David Nipp
Journal: Journal of Clinical Oncology (2020)

12012 Background: Older adults with gastrointestinal (GI) cancers undergoing surgery often experience poor outcomes, such as prolonged postoperative (post-op) length of stay (LOS), intensive care unit (ICU) use, and readmissions. Involvement of geriatricians in the care of older adults with cancer can improve outcomes. We conducted a randomized trial of a perioperative geriatric intervention in older adults with GI cancers undergoing surgery. Methods: We randomly assigned patients age ≥65 with GI cancers planning to undergo surgical resection to receive a perioperative geriatric intervention or usual care. Intervention patients met with a geriatrician preoperatively in the outpatient setting and post-op as an inpatient consultant. The geriatrician conducted a geriatric assessment and made recommendations to the surgical/oncology teams. The primary end point was post-op LOS. Secondary end points included post-op ICU use, readmission risk, and patient-reported symptom burden (Edmonton Symptom Assessment System [ESAS]) and depression symptoms (Geriatric Depression Scale). We conducted both intention-to-treat (ITT) and per protocol (PP) analyses. Results: From 9/13/16-4/30/19, we randomized 160 patients (72.4% enrollment rate; median age = 72 [65-92]). The ITT analyses included 137/160 patients who underwent surgery (usual care = 68/78, intervention = 69/82). The PP analyses included the 68 usual care patients and the 30/69 intervention patients who received both pre- and post-op intervention components. In ITT analyses, we found no significant differences between intervention and usual care in post-op LOS (7.2 v 8.2 days, P = .37), ICU use (23.3% v 32.4%, p = .23), and readmission rates within 90 days of surgery (21.7% v 25.0%, p = .65). Intervention patients reported lower depression symptoms (B = -1.39, P &lt; .01) at post-op day 5 and fewer moderate/severe ESAS symptoms at post-op day 60 (B = -1.09, P = .02). In PP analyses, intervention patients had significantly shorter post-op LOS (5.9 v 8.2 days, P = .02) and lower rates of post-op ICU use (13.3% v 32.4%, p &lt; .05), but readmission rates were not significantly different (16.7% v 25.0%, p = .36). Conclusions: Although this perioperative geriatric intervention did not have a significant impact on the primary end point in ITT analysis, we found encouraging results in several secondary outcomes and for the subgroup of patients who received the planned intervention. Future studies of this perioperative geriatric intervention should include efforts, such as telehealth visits, to ensure the intervention is delivered as planned. Clinical trial information: NCT02810652 .
Anatomic histological study of prostatic artery in elders
Authors: Wen Shen, Cheng Huang, Jun L, Ping Li, Li-chao Zhang, Jun Liu, Wei-lie Hu
Journal: BMJ (2012)

Prostatic artery of 12 elder and 9 younger cadavers were isolated and transected.Vascular inner diameter and thickness of vascular wall of these cross sections were observed microscopically.Atherosclerotic plaque could be seen in the prostatic artery of 12 elders.And there were the thickening of tunica intima and the narrowing of inner diameter.The inner diameter of elderly prostatic artery was (452 ± 97) μm,the thickness of their tunica intima (228 ± 82) μm and inner diameter/thickness 3.14 ± 0.68.Tunica intima of 9 younger prostatic arteries were glabrate.The inner diameter of younger prostatic artery was (864 ± 17)μm,the thickness of their tunica intima (57 ± 4)μm and inner diameter/thickness 15.52 ± 0.18.Statistically significant differences existed between elder and younger cadavers in the above 3 parameters.As compared with younger counterpart,prostatic artery of elders was more stenotic and its tunica intima tended to he thicker.

Key words: 
Prostatic artery;  Anatomy,regional
食管源性胸痛50例临床分析
Authors: 陈健, 乔瑞敏
Journal: BMJ (2006)

对96例已排除心源性及食管器质性病变的胸痛患者,经食管测压、食管pH值监测和临床表现调查后,有50例(52.1%)诊断为食管源性胸痛,其中31例(62.0%)符合胃食管反流病(有15例合并食管运动异常),25例(50.0%)为非特异性食管运动障碍,4例(8.0%)为胡桃夹食管,3例(6.0%)为弥漫性食管痉挛,2例(4.0%)为贲门失弛缓症.提示食管运动障碍所致胸痛以胃食管反流病引起的最多,其临床表现与心源性胸痛相似,有时仅从症状上难以鉴别。
Effectiveness of guideline-oriented training for community health-care workers with "Applied Standards for Hypertension Prevention and Control at the Grassroots"
Authors: Wei-qin Li, Yang-feng Wu
Journal: BMJ (2011)

Objective To evaluate effectiveness of guideline-oriented training for community healthcare workers (HCWs) with The Applied Standards for Hypertension Prevention and Control at the Grassroots to provide guidance to hypertension management in communities. Methods In 2003, four community health-care service centers in Beijing were selected and assigned as intervention (one at urban and one at rural) and control (one at urban and one at rural ) groups, respectively. HCWs in the intervention group received guideline-oriented training based on The Applied Standards for Hypertension Prevention and Control at the Grassroots, while HCW in the control group did not. All HCWs participated in tests of the knowledge of hypertension management using the same questionnaire before and after the training to analyze their changes in awareness scores with a full of 32. Results There were 39 and 33 HCWs in the intervention group and 15 and 16 HCWs in the control group, respectively at urban, and 30 and 33 HCWs in the intervention group and 21 and 22 HCWs in the control group, respectively at rural before and after the training were involved in the tests, respectively. After training, overall knowledge scores of hypertension prevention and control in HCWs in the intervention group at urban increased obviously, with an average score of 26 of 32 ( 81.0% ) after training from 15 of 32 (45. 6% ) before it ( P ＜ 0. 01 ) , with a net increase of 28.5% (9/32), as compared to HCWs in the control group. Those at rural increased to 6. 6% (20/32) after training from 40. 7% (13/32) before it ( P ＜ 0.01 ), with a net increase of 22. 2 percent (7/32), as compared to HCWs in the control group. Their awareness of knowledge of hypertension prevention and control significantly improved, with the most obviously in the target of blood pressure control (51.7% vs. 31.5% ) and principles of pharmaceutical therapy (42. 2% vs. 27. 6% ). Conclusions Guideline-oriented training based on The Applied Standards for Hypertension Prevention and Control at the Grassroots can effectively improve community HCWs' awareness of knowledge of hypertension management and should be widely promoted in communities.

Key words: 
Hypertension;  Intervention study;  Health-care worker, community
Risk factors of surgical incision infection in patients with gastrointestinal perforation
Authors: Zhang Guoqiang, Wang Ping, Zhao Dongming, Jin Maohe, Ma Xiangming
Journal: BMJ (2019)

The clinical data of 288 patients with gastrointestinal perforation undergoing surgical treatment from Jul 2014 to Jul 2017 were retrospectively analyzed, among whom the surgical incision infection occurred in 112 patients(38.9%). The risk factors of the incision infections were examined with logistic regression analysis. The univariate analysis showed that preoperative albumin level (≤30 g/L), body mass index (>24.0 kg/m2), duration of abdominal pain(>24 h), extension of incision, preoperative shock, colostomy, preoperative antibiotic use and the operation time were associated with incision infections(P 0.05). The multivariate logistic regression analysis showed that the body mass index(OR=1.61, P<0.01), gastrointestinal perforation site(colon and rectum, OR=5.60, P<0.01), extension of incision (OR=3.94,P<0.01) and operation time(OR=1.04,P=0.02)were independent risk factors of theincision infection. The results suggest that the full preoperative preparation, intensive treatment of underlying diseases, avoiding incision extension and shortening operation time may be able to reduce the surgical incision infections for patients with the gastrointestinal perforation.


Key words: 
Intestinal perforation; Stomach rupture; Surgical wound infection; Risk factors
Effect of a Patient-Centered Decision Support Tool on Rates of Trial of Labor After Previous Cesarean Delivery
Authors: Miriam Kuppermann, Anjali J. Kaimal, Cinthia Blat, Juan Gonzalez, Mari-Paule Thiet, Yamilee Bermingham, Anna L. Altshuler, Allison S. Bryant, Peter Bacchetti, William A. Grobman
Journal: JAMA (2020)

<h3>Importance</h3> Reducing cesarean delivery rates in the US is an important public health goal; despite evidence of the safety of vaginal birth after cesarean delivery, most women have scheduled repeat cesarean deliveries. A decision support tool could help increase trial-of-labor rates. <h3>Objective</h3> To analyze the effect of a patient-centered decision support tool on rates of trial of labor and vaginal birth after cesarean delivery and decision quality. <h3>Design, Setting, and Participants</h3> Multicenter, randomized, parallel-group clinical trial conducted in Boston, Chicago, and the San Francisco Bay area. A total of 1485 English- or Spanish-speaking women with 1 prior cesarean delivery and no contraindication to trial of labor were enrolled between January 2016 and January 2019; follow-up was completed in June 2019. <h3>Interventions</h3> Participants were randomized to use a tablet-based decision support tool prior to 25 weeks' gestation (n=742) or to receive usual care (without the tool) (n=743). <h3>Main Outcomes and Measures</h3> The primary outcome was trial of labor; vaginal birth was the main secondary outcome. Other secondary outcomes focused on maternal and neonatal outcomes and decision quality. <h3>Results</h3> Among 1485 patients (mean age, 34.0 [SD, 4.5] years), 1470 (99.0%) completed the trial (n = 735 in both randomization groups) and were included in the analysis. Trial-of-labor rates did not differ significantly between intervention and control groups (43.3% vs 46.2%, respectively; adjusted absolute risk difference, –2.78% [95% CI, –7.80% to 2.25%]; adjusted relative risk, 0.94 [95% CI, 0.84-1.05]). There were no statistically significant differences in vaginal birth rates (31.8% in both groups; adjusted absolute risk difference, –0.04% [95% CI, –4.80% to 4.71%]; adjusted relative risk, 1.00 [95% CI, 0.86-1.16]) or in any of the other 6 clinical maternal and neonatal secondary outcomes. There also were no significant differences between the intervention and control groups in the 5 decision quality measures (eg, mean decisional conflict scores were 17.2 and 17.5, respectively; adjusted mean difference, –0.38 [95% CI, –1.81 to 1.05]; scores &gt;25 are considered clinically important). <h3>Conclusions and Relevance</h3> Among women with 1 previous cesarean delivery, use of a decision support tool compared with usual care did not significantly change the rate of trial of labor. Further research may be needed to assess the efficacy of this tool in other clinical settings or when implemented at other times in pregnancy.
非酒精性脂肪肝的临床特征及危险因素分析
Authors: 甘小玲, 陈庆瑜, 洪俊, 叶枫, 刘小珍
Journal: BMJ (2010)

近年来非酒精性脂肪肝(non-alcoholic fatty liver,NAFL)的发病率正逐年上升,并成为人们普遍关注的一个公共健康问题~([1]).现对NAFL的临床特征及危险因素进行分析.