tbuckley/cabot-search huggingface dataset:
Underdiagnosis and undertreament of modifiable cardiovascular risk factors: A Childhood Cancer Survivor Study (CCSS) report.
Authors: Eric Jessen Chow, Yan Chen, Gregory T. Armstrong, Laura-Mae Baldwin, Todd M. Gibson, Melissa M. Hudson, Aaron McDonald, Paul C. Nathan, Karen L Syrjala, Emily S. Tonorezos, Kevin C. Oeffinger, Yutaka Yasui
Journal: Journal of Clinical Oncology (2020)

10515 Background: Survivors of childhood cancer exposed to cardiotoxic therapies are at increased risk of heart disease. Hypertension, dyslipidemia, and diabetes are modifiable cardiovascular risk factors (CVRFs) that synergistically increase this risk. Therefore, we aimed to determine the prevalence of and predictors associated with CVRF underdiagnosis and undertreatment in this population. Methods: CCSS participants at increased risk of heart disease due to prior cancer therapy were enrolled in an ongoing randomized intervention trial (NCT03104543) to improve CVRF identification and treatment. Participants completed a baseline survey (CVRF status, lifestyle habits, attitudes towards healthcare), anthropometry, and blood draw. Blood pressure, low density lipoprotein, triglyceride, glucose and Hgb A1c were measured and classified as normal/abnormal per standard clinical criteria. Multivariable logistic regression estimated odds ratios (OR [95% confidence intervals]) associated with predictors and risk of CVRF underdiagnosis and undertreatment. Results: As of January 2020, 522 participants (43% male) were available for analysis (47% response), with a median age 38y (range 20-65) and 28y (18-49) from original cancer treatment (75% anthracycline, 47% chest radiation). With mean measured BMI 27.3±6.5 kg/m 2 , self-reported prevalence rates were hypertension 27%, dyslipidemia 33%, and diabetes 9%. While 90% of participants had a routine check-up ≤2y ago, 58% had a measured CVRF in the abnormal range. Specifically, among previously undiagnosed participants, we observed rates of abnormal blood pressure (26%), lipids (17%), and glucose tolerance (27%). Among those with pre-existing hypertension, dyslipidemia, and diabetes, 11%, 49%, and 54%, respectively, had measurements outside of the usual therapeutic target range. In multivariable analysis, BMI ≥25 kg/m 2 (vs &lt; 25) was associated with risk of underdiagnosis (OR 1.8 [1.2-2.8]). For undertreatment, significant adverse factors included older age ( &gt; 35 vs ≤35y: OR 2.5 [1.2-5.1]), BMI ≥30 kg/m 2 (vs &lt; 25: OR 3.3 [1.7-6.4]), and greater perceived reliance on others for healthcare decisions (OR 1.7 [1.2-2.4]). Those with greater health-related self-efficacy were less likely to be undertreated (OR 0.5 [0.3-0.96]). Conclusions: CVRF underdiagnosis and undertreatment among childhood cancer survivors at increased risk of heart disease was common. Greater awareness among survivors and primary care providers and more aggressive control of CVRFs may mitigate this risk.
Phase I study of mesothelin-targeted immunotoxin LMB-100 given as a long infusion with or without nab-paclitaxel.
Authors: Guillaume Joe Pegna, Mehwish Iqra Ahmad, Yunkai Yu, Akira Yuno, Min-Jung Lee, Cody J. Peer, Seth M. Steinberg, Liang Cao, Jane B Trepel, William Douglas Figg, Raffit Hassan, Ira Pastan, Christine Campo Alewine
Journal: Journal of Clinical Oncology (2020)

3553 Background: LMB-100 recombinant immunotoxin consists of a mesothelin-binding Fab for targeting a modified Pseudomonas exotoxin A payload. Previous Phase 1 clinical testing of a 30-minute LMB-100 “short” infusion format identified a serum half-life of ~1 hour. Pre-clinical data suggested that extending infusion time could improve anti-tumor efficacy by increasing tumor cell duration of exposure to LMB-100. The primary objective of this study was to determine the safety and tolerability of administering LMB-100 in a long infusion format over 24-48 hours alone or with nab-paclitaxel chemotherapy in patients with mesothelin-expressing solid tumors. Methods: Patients (n = 15) with pancreatic adenocarcinoma and other mesothelin-expressing solid tumors (n = 3; mesothelioma, colon, and ampullary cancers) treated on 3 dose levels received long infusion of LMB-100 (65 or 100 mcg/kg/day) for 24 hour on Days 1 and 4 (n = 6) or 48 hour on Day 1 (n = 9) with or without a loading dose (40 mcg/kg over 30 minutes) for up to 2 cycles. In the second arm, patients (n = 5) with pancreatic adenocarcinoma were treated with LMB-100 over 24 hours on Day 1 concurrently with nab-paclitaxel (125 mg/m 2 ) for up to 3 cycles. Results: DLT of proteinuria (grade 3) in one patient and acute kidney injury (grade 1) in one patient were observed amongst patients receiving 100 mcg/kg/day over 48 hours and 24 hours, respectively. No objective responses were seen but all patients receiving nab-paclitaxel had &gt; 50% decrease in CA 19-9. Patients at all single agent dose levels (8 of 10 evaluable) developed high titer anti-drug antibodies (ADAs) against LMB-100. Those with ADAs (8 of 8) had undetectable cycle 2 peak plasma LMB-100 concentration. Development of high titer ADAs occurred more frequently with long infusion than seen previously with “short” infusion LMB-100. Most long infusion patients (19 of 20) developed increased serum IL-6 within 24 hours of LMB-100 infusion. However, the systemic inflammatory response to LMB-100 (as measured by increased serum CRP) which occurs in most “short” infusion patients was not observed. Conclusions: Long infusion format LMB-100 is generally well tolerated but immunogenicity limits treatment to 1 effective cycle. No anti-tumor efficacy of the single agent was observed. Clinical trial information: NCT02810418 .
Serum levels of fatty cytokines in hepatitis B patients with liver fibrosis
Authors: Wenli Xu, Wenbin Yuan, Jian Ding, Wenjun Jin
Journal: BMJ (2017)

Objective
To investigate the serum levels of fatty cytokines in hepatitis B patients with liver fibrosis.


Methods
Fifty six hepatitis B patients with liver fibrosis admitted in Wenzhou Central Hospital from April 2014 to March 2016 were recruited as case group and 65 healthy subjects as control group. Serum cytokines including omentin, leptin, adiponectin and visfatin were detected in both two groups and glutamyl endopeptidase (ALT), aspartate aminotransferase (AST) and hepatitis B virus DNA were detected in the case group. Liver biopsy was performed in the case group and histologic activity (HA) and histologic fibrosis (HF) stage were evaluated.


Results
The level of omentin in the case group was significantly higher than that in the control group [(358±119) vs. (305±108) μg/L, t=2.236, P=0.037]. Serum omentin, visceral fat hormone, leptin and adiponectin were not associated with liver function and HBV-DNA (P>0.05). There was no significant difference in adipocytokines levels between the low and high HA group (P>0.05). The level of omentin in high HF stage group was significantly higher than that in low HF stage group [(398±130) vs. (292±120)μg/L, t=2.648, P=0.009], while the other fatty cytokines did not show significantly differences between high and low HF groups (P>0.05).


Conclusion
Serum omentin level is elevated in hepatitis B patients with liver fibrosis and is associated with liver fibrosis severity.


Key words: 
Liver cirrho; Hepatitis B; Cytokine, adipocytes
自然妊娠单卵三胎一例并文献复习
Authors: 王雅琴, 杨菁, 徐望明, 谢青贞, 赵庆红
Journal: BMJ (2012)

自然妊娠单卵三胎比较罕见,胎儿不良结局发生率高,选择性减胎术可有效降低流产率和围产儿病死率,但可能导致剩余胎儿的丢失,治疗方案应慎重.对单卵多胎者一经超声诊断则应密切监测,发现异常应积极干预。
Relationship between high sensitive C-reactive protein and stroke subtype according to Chinese Ischemic Stroke Subclassification criteria in patients with acute cerebral infarction
Authors: Xinhong Xue, Lifeng Qi, Hong Liu, Haixin Yang, Jiangli Su
Journal: BMJ (2014)

By analyzing the clinical data of 216 cases of acute cerebral infarction (ACI) from 2012 January to 2013 June retrospectively, we found that the serum levels of high sensitive C-reactive protein (hs-CRP) in patients were significantly higher than those in 186 controls (P 8 were higher than that in those with NIHSS score ≤8 (P<0.05). The hs-CRP level of patients of large artery atherosclerosis were (6.32±4.12) mg/L and the positive rate of hs-CRP was 85.7%(84/98). All were respectively higher than those in patients of penetrating artery disease [(1.97±0.86) mg/L, 7/71], cardiogenic stroke [(3.70±2.76) mg/L, 14/24], undetermined etiology [(3.43±3.52) mg/L, 5/11] and other etiologies [(3.41±3.25) mg/L, 5/12] (all P<0.05). Logistic regression analysis was performed for the risk factors of ACI. The correlative factors of ACI included hypertension, diabetes mellitus, atrial fibrillation, smoking, total cholesterol, homocysteine and high sensitive C-reactive protein (OR=1.56, 1.19, 1.23, 1.17, 3.08, 1.34, 1.25, all P<0.01). The serum levels of hs-CRP increased significantly in ACI patients and were correlated with the degree of neural function defect.


Key words: 
Cerebral infarction; C-reactive protein; Homocysteine; Chinese Ischemic Stroke subclassification
An Indurated Plaque on the Eyelid
Authors: Jiawen Chen, Hong Yu, Zhirong Yao
Journal: JAMA Dermatology (2020)

A man in his 60s presented with a pruritic, red plaque on his eyelid; biopsy results showed perifollicular lymphocytic infiltrates and exocytosis of atypical lymphocytes, as well as mild follicular mucin deposition. What is your diagnosis?
Effect of evidence-based nutrition educational intervention on adherence to dietary guidelines (ADG) and weight management among early-stage breast cancer (EBC) patients (pts): A prospective trial.
Authors: Ilaria Trestini, Isabella Sperduti, Alberto Caldart, Clelia Bonaiuto, Elena Fiorio, Veronica Parolin, Daniela Tregnago, Alice Avancini, Sara Pilotto, Massimo Lanza, Giovanni Scambia, Giampaolo Tortora, Michele Milella, Emilio Bria, Luisa Carbognin
Journal: Journal of Clinical Oncology (2020)

12056 Background: Excess adiposity is linked to an increased risk of worse outcome among EBC pts. Pts undergoing EBC treatment are susceptible to change in nutrition status. However, implementation and assessment of the adherence to lifestyle interventions have been limited. This prospective trial aimed to evaluate the impact of an evidence-based nutrition intervention, according to the ADG, in terms of body composition changes in EBC pts. Methods: Entry criteria: EBC pts candidate to neoadjuvant/adjuvant therapy. At study entry, pts received a nutrition evidence-based tailored intervention. Dietary and anthropometric assessments were evaluated at baseline and after 12-months nutritional intervention. Waist circumference (WC) was assessed as a surrogate measure of fat distribution. ADG was estimated by Med-Diet 14-item questionnaire. Health-Related Quality of Life was analysed with EORTC QLQ-C30. Descriptive statistics was adopted. Associations between variables and groups according to nutritional variables were analysed (Chi-square test). Results: From February 2016 to December 2019, 243 pts were enrolled (median age 49 years): 27.6%/48.6% neoadjuvant/adjuvant treatment. At baseline, 38.3% of pts were overweight and 23.9% were obese. Notably, tumor size was significantly correlated with WC in the whole population (p = 0.003). Moreover, pts with central obesity were more likely to present HER2-negative tumors (57.4% vs. 42.5%, p = 0.03). Most pts reported relevant nutrition impact symptoms and symptoms affected QoL. Particularly, dyspepsia and constipation were more prevalent in overweight and obese pts (p &lt; 0.0001 and p = 0.009, respectively), as well as in pts who gained ≥5% of weight (p = 0.04 and p = 0.02, respectively). At baseline, there was low ADG. After the 12-months intervention, ADG significantly increased (median Med-Diet score: 6 vs.12, p &lt; 0.0001). A high ADG (defines as a Med-Diet score ≥10) significantly correlated with: 1) loss of weight ≥5% from the baseline weight (p = 0.003); 2) change in terms of BMI; 3) prevalence of central obesity. Conclusions: A tailored evidence-based nutritional intervention for EBC pts represents a tool to improve their ADG, weight management and, thus, to potentially influence the disease outcome. [Table: see text]
Deep learning to identify high-risk smokers for lung cancer screening from chest radiographs.
Authors: Vineet Raghu, Thomas Mayrhofer, Hugo Aerts, Udo Hoffmann, Michael T Lu
Journal: Journal of Clinical Oncology (2020)

1519 Background: Appearance on chest radiography may inform selection of high-risk smokers for lung cancer screening CT, beyond Centers for Medicare &amp; Medicaid Services (CMS) eligibility criteria. Methods: A convolutional neural network (CXR-LC) predicting 12-year incident lung cancer from the chest radiograph image, age, sex, and smoking status (current/former) was developed in 41,856 persons aged 55-74 from the Prostate, Lung, Colorectal &amp; Ovarian trial (PLCO). The final model was tested in held-out smokers from PLCO (n=5,615, 37.9% CMS eligible, 12-year follow-up), and externally in the National Lung Screening Trial (NLST, n=5,493, all CMS eligible, 6-year follow-up). Sensitivity was compared at a fixed screening population size defined by CMS eligibility. Ordinal CXR-LC risk score (low/indeterminate/high/very high) was based on development dataset 12-year probability thresholds (&lt;2%/2-&lt;3.3%/3.3-&lt;8%/≥8%). Results are provided in test datasets only. Results: In the PLCO test dataset, CXR-LC was more sensitive than CMS eligibility at a fixed screening population size (74.9% vs. 63.8%, p=0.01) and missed 30.8% fewer lung cancers. CXR-LC risk groups were associated with incident lung cancer in PLCO test dataset smokers (very high vs. low CXR-LC risk: 12.4 vs 1.1 lung cancers/1,000 person-years) with external testing in NLST (all CMS eligible: 12.7 vs 2.3) (Table). This association was robust to adjustment for radiologist findings and the PLCOm2012 risk score. Conclusions: CXR-LC identified smokers at high risk of incident lung cancer, beyond CMS eligibility. [Table: see text]
Survey on satisfaction with community health service among residents in Beijing Yuetan subdistrict
Authors: Ning Li, Xueping Du
Journal: BMJ (2018)

Objective
To survey on the satisfaction with community health service among residents in Beijing Yutan subdistrict and its influencing factors.


Methods
From February 2017 to April 2017, a questionnaire survey was carried out among 829 residents over 15 years old in Beijing Yuetan community. The overall satisfaction with the community health service was surveyed, and its correlations with sex, age, educational level, occupation, medical insurance type, family per capita income, and chronic diseases of residents were analyzed.


Results
The satisfaction rates with various items of community health services were all above 75%, except that of drug types and facilities. The satisfaction with nursing service, service attitude, communication, equipment, convenience, waiting time and institutional environment was correlated with the age of the residents (χ2=14.913、16.144、13.966、14.279、15.208、23.590、13.746, P 0.05). There were significant differences in satisfaction with nursing service, convenience, waiting time and institutional environment among residents with different occupations (χ2=7.379, 14.837, 9.471, 14.837, P<0.05); there was significant difference in satisfaction with drug types among the residents with different payment methods (χ2=11.405, P<0.05), and there was significant difference in the satisfaction with image accuracyandthe facilities among residents with different family income (χ2=9.808, 10.117, P<0.05). The satisfaction degree with medical care, nursing service, communication, image accuracy, equipment, andwaiting time was significantly different among residents with different chronic diseases (χ2=4.387, 5.285, 9.908, 11.622, 3.903, 6.285, P<0.05).


Conclusion
The overall satisfaction with the community health service among Yuetan residents is high; however, more attention should be paid to the health management for women and elderly patients and patients with chronic disease and low income.


Key words: 
Community health services; Patient satisfaction; Influencing factors
Efficacy and safety of carfilzomib, dexamethasone, daratumumab (KdD) twice-weekly at 56 mg/m<sup>2</sup> and once-weekly at 70 mg/m<sup>2</sup> in relapsed or refractory multiple myeloma (RRMM): Cross-study comparison of candor and MMY1001.
Authors: Xavier Leleu, Meral Beksac, Takaaki Chou, Meletios A. Dimopoulos, Sung-Soo Yoon, H. Miles Prince, Ludek Pour, Tatiana Shelekhova, Ajai Chari, Monica Khurana, Mihaela Obreja, Ming Qi, Albert Oriol, David Samuel DiCapua Siegel
Journal: Journal of Clinical Oncology (2020)

8526 Background: CANDOR, a randomized phase 3 study, showed significantly improved progression-free survival (PFS) and overall response rate (ORR) for twice-weekly KdD 56 mg/m 2 (TW KdD56) vs Kd in RRMM, with a 37% risk reduction in disease progression or death (Usmani, 2019). The benefit of once-weekly carfilzomib (K) at 70mg/m 2 for the same triplet, KdD (OW KdD70), in RRMM was shown in the nonrandomized MMY1001 study. We performed robust cross-study comparisons to investigate how TW KdD56 compares to OW KdD70. Methods: For alignment of inclusion criteria, the primary analysis set for this cross-study comparison included individual data from CANDOR pts with prior exposure to bortezomib and immunomodulatory drug, and all pts in MMY1001. Propensity score method (Rambaldi, 2019; Kumar, 2019) allowed reliable cross-study comparison, controlling for baseline prespecified covariates such as age, creatinine clearance, performance status, prior treatment exposure/refractoriness, and time from initial diagnosis and relapse. Propensity score adjustment based on inverse probability of treatment weighting (IPTW) was implemented on efficacy endpoints, while safety was evaluated side-by-side. Results: The unadjusted and adjusted propensity score comparison of CANDOR and MMY1001 showed similar efficacy in terms of ORR and PFS in the TW KdD56 and OW KdD70 groups (Table). As propensity score comparisons were for efficacy only, safety comparisons between CANDOR and MMY1001 included differing sample sizes and treatment duration (Table). The safety of KdD56 and KdD70 was consistent with the known safety profiles of individual study treatments. Conclusions: OW KdD70 is an efficacious dosing option with favorable benefit-risk, comparable to TW KdD56. The OW KdD70 dosing option represents a more convenient regimen that might encourage adherence and potentially lead to better outcomes for RRMM pts. Clinical trial information: NCT03158688 . [Table: see text]
Residual circulating tumor DNA (ctDNA) after two months of therapy to predict progression-free and overall survival in patients treated on S1403 with afatinib +/- cetuximab.
Authors: Philip C. Mack, Mary Weber Redman, James Moon, Sarah B. Goldberg, Roy S. Herbst, Mary Ann C. Melnick, Zenta Walther, Fred R. Hirsch, Katerina A. Politi, Karen Kelly, David R. Gandara
Journal: Journal of Clinical Oncology (2020)

9532 Background: ctDNA from patient plasma has demonstrated diagnostic utility in non-small cell lung cancer (NSCLC). Longitudinal changes in mutant allele frequency (MAF) have great potential to refine clinical management on targeted therapies. Methods: S1403 was a first-line phase II study of afatinib w or w/o cetuximab in pts with EGFR-mutant NSCLC. Between March, 2015 and April, 2018, 174 pts were randomized with 168 determined to be eligible. The study closed early due to futility. Plasma specimens were prospectively collected at baseline, Cycle 3 Day 1 (C3D1; 8 weeks) and at progression, and processed for batch analysis of ctDNA by next-generation sequencing (Guardant 360). A complete case analysis approach was used. The Kaplan-Meier method was used to estimate survival distributions, a Cox model to estimate hazard ratios and confidence bounds, and the log-rank test to compare distributions. A landmark analysis was used to assess predictive value of ctDNA clearance at C3D1. Results: 104 patients (62%) had analyzable baseline plasma specimens available, with EGFR mutations detected in 83 (80%). PFS was significantly shorter for pts with EGFR ctDNA positivity at baseline (p = 0.03) (Table) compared to those with no detectable ctDNA, likely a prognostic effect. Kinetic changes in ctDNA MAFs were analyzed in 79 pts with matching baseline and C3D1 specimens. Of 62 cases with detectable ctDNA at baseline, 68% (42/62) became undetectable at C3D1 (“ctDNA clearance”); ctDNA clearance relative to residual ctDNA was associated with significantly longer PFS (p = 0.00001) and OS (0.003) (Table). To date, 29 pts had matching at-progression samples. T790M mutations were observed at progression in 6/29 (24%) cases. Other putative emergent resistance factors include: a TACC3-FGFR3 and an EML4-ALK fusion, MET exon 14 skipping, multiple MET amplifications and NF1 frameshift mutations. Conclusions: Clearance of EGFR ctDNA after 60 days of therapy was associated with a substantial and statistically significant improvement in subsequent PFS and OS. Incorporation of ctDNA kinetics into routine clinical care represents a promising platform to identify patients with inferior outcomes on TKIs and detect targetable emergent resistance mechanisms. [Table: see text]
Risk factors for myocarditis associated with immune checkpoint inhibitors using real-world clinical data.
Authors: Prantesh Jain, Jahir Gutierrez Bugarin, Avirup Guha, Chhavi Jain, Tingke Shen, Ilya Stanevich, Seunghee P Margevicius, Pingfu Fu, Fang Liu, Vipan Nikore, Ankit Mangla, Marcos J.G. De Lima, Vamsidhar Velcheti, Jill Barnholtz-Sloan, Afshin Dowlati
Journal: Journal of Clinical Oncology (2020)

e15100 Background: Immune checkpoint inhibitors (ICIs) can cause unique, high-grade immune-related adverse events. Although rare, ICI related myocarditis has the highest fatality rate (~50%). Cardiovascular monitoring is not routinely performed in patients on ICI treatment, thus risk factors remain unknown. Characterizing rare but fatal cardiac toxicities requires integration of real-world data. Methods: U.S claims data (IBM MarketScan) of over 30 million commercially insured individuals was leveraged to identify 2,687,301 cancer patients between 2011-2018. Patients ≥18 years of age treated with ICIs (targeting CTLA4 (ipilimumab) and/or the PD1 (nivolumab, pembrolizumab)/PDL1 (atezolizumab, avelumab, durvalumab) alone or in combination with ICI and/or chemotherapy were identified and followed until disenrollment. Myocarditis, comorbidities, and treatment details were identified using diagnosis and billing codes. Analyses included descriptive statistics and Cox proportional hazards regression. Results: 16,541 ICI treated cancer patients were included (median age 60; 58% male). Myocarditis was identified in 252 (1.5%) patients, majority (90%) ≥50 years old (median 63) with 12,040 person-years of follow up. 62% received anti-PD1 monotherapy, 12% anti-CTLA4, and 15% received combination treatment with other ICIs and/or chemotherapy. Most common cancer types were lung (48%), melanoma (25%), and renal cancer (14%). Cumulative incidence of myocarditis at 1 year was 2.06%; 95% CI (1.78-2.37), median onset of 80.5 days, 42% occurring within 60 days of treatment. By univariate analyses, age, cancer type, diabetes (DM), hypertension (HTN), kidney, liver disease, atrial fibrillation (AF) were related to myocarditis. Risk was lower in patients who received anti-CTLA4 monotherapy (HR: 0.490; 95% CI: 0.26-0.92; p = 0.0251). On multivariable regression analyses only age, cancer type (renal, lung cancer), comorbidities DM and liver disease were significantly associated with myocarditis (Table). Conclusions: This is the largest real-world longitudinal study for ICI associated myocarditis showing higher than reported incidence and identifiable risk factors. [Table: see text]