tbuckley/cabot-search huggingface dataset:
Abstract 330: Intra-Arrest Cardioplegia Prevents the Diastolic Dysfunction Induced by Prolonged VF Arrest
Authors: Jason Allen, Matthias Riess, Jason Bartos
Journal: Circulation (2019)

Introduction: There are approximately 400,000 out-of-hospital cardiac arrests annually, including one-third with VT/VF as their initial rhythm. Approximately 60% of VF arrests are refractory to initial resuscitation requiring prolonged CPR and transport to an ECPR center where available. Limiting myocardial injury during this time is critical as it contributes CPR efficiency. The aim of this study was to investigate the effect of cardioplegia on preservation of cardiac function during cardiac arrest. Hypothesis: Following induction of VF, the administration of potassium-based cardioplegia will reduce energy utilization and prevent diastolic dysfunction with preservation of contractility following washout of cardioplegia. Methods: Hearts were isolated from male Brown Norway rats (n=8) and prepared on a Langendorff apparatus in Krebs solution. Left ventricular pressure was measured throughout the study. Hemodynamics were obtained for 15 min prior to 2 min of rapid pacing to induce VF. After 10 min of VF, cardioplegia was induced with a bolus of 160 μeq potassium. After 10 min, the potassium was washed out and the hearts were reperfused with Krebs-Henseleit solution. Hemodynamics were measured for another 60 min. Results: Baseline hemodynamics were similar between the control and cardioplegia groups. Cardioplegic hearts had significantly lower left heart pressures at the end of the VF time compared to control hearts (24 vs. 74 mmHg, p&lt;0.05). Following 60 min of reperfusion and cardioplegia washout, diastolic pressures remained lower in hearts receiving cardioplegia (39 vs 10 mmHg, p&lt;0.05). After 60 min of reperfusion, systolic pressures were the same among the groups, and while rate of contraction and relaxation were numerically faster in hearts receiving cardioplegia, these differences were not significant. Conclusions: Potassium cardioplegia, given during ongoing VF arrest, was effective at preventing diastolic dysfunction caused by prolonged ischemia. Washout of the cardioplegia at the time of reperfusion allowed for ROSC and preserved left ventricular relaxation. These studies suggest that the use of cardioplegia in refractory VT/VF arrest may be beneficial in reducing myocardial damage and preserving function during prolonged CPR.
Immunotherapy efficacy of programmed cell death 1 (PD-1) versus programmed death ligand-1 (PD-L1) inhibitors in non-small cell lung cancer (NSCLC) patients: A systematic review and meta-analysis.
Authors: Danrong Yang, Longgang Cui, Yuzi Zhang, Zhengyi Zhao, Yuezong Bai
Journal: Journal of Clinical Oncology (2020)

e21700 Background: Immune checkpoint inhibitors of programmed cell death-1 (PD-1) and its ligand (PD-L1) have been new standard of care for non-small cell cancer patients. However, little is known about the difference in efficacy between these two types of drugs. In this study, we aimed to assess the differences between anti-PD-1 and anti-PD-L1 in NSCLC treatment through a systematic review and meta-analysis. Methods: We systematically searched PubMed, CENTRAL, and Embase from January, 2000 to November, 2019. We also reviewed abstracts and presentations from all major conference proceedings. All randomized controlled trials that compared anti-PD-1/anti-PD-L1 with standard treatment in NSCLC cancer patients were selected as candidates. Studies with anti-PD-1 and anti-PD-L1 were screened and paired upon the mirror principle. The primary outcome was the difference in overall survival (OS). As the main results, indirect comparison of anti-PD-1 and anti-PD-L1 were calculated for each mirror group and then pooled using a random-effects model. Results: 16 randomized controlled trials were included for the meta-analysis. Overall, anti-PD-1 exhibited superior OS (HR 0.80, 95% CI 0.68-0.95, P= .01) over anti-PD-L1. Subgroup analysis showed that anti-PD-1 exhibited superior OS over anti-PD-L1 ICIs in combination therapy (HR 0.67, 95% CI 0.54-0.82, P &lt;.01), but not in monotherapy (HR 0.89, 95% CI 0.74-1.06), 2 nd line therapy (HR 0.84, 95% CI 0.66-1.06) or 1 st line therapy (HR 0.77, 95% CI 0.58-1.03). Conclusions: The results demonstrated that anti-PD-1 exhibited favorable survival outcomes compared to anti-PD-L1 in NSCLC treatment, which provides an important guide for clinicians.
The comprehensive methylation landscape of metastatic castration-resistant prostate cancer (mCRPC) identifies new phenotypic subtypes: Results from the West Coast Prostate Cancer Dream Team (WCDT).
Authors: Eric Jay Small, Shuang Zhao, William S. Chen, Haolong Li, Adam Foye, Martin Sjöström, Jun Jie Hua, Rahul Raj Aggarwal, Joshi J. Alumkal, Tomasz M. Beer, Martin Gleave, Matthew Rettig, Owen Witte, Primo Lara, Arul Chinnaiyan, Chris Maher, David A. Quigley, Felix Y Feng
Journal: Journal of Clinical Oncology (2020)

5507 Background: While recent studies have delineated the genomic landscape of mCRPC, its epigenomic landscape has not been as well characterized. The goal of this study was to define the comprehensive methylation landscape of mCRPC. Methods: mCRPC patients (pts) underwent a metastasis biopsy as part of a multi-institutional study (NCT02432001). Deep whole-genome bisulfite sequencing (mean depth 46x) was performed on fresh frozen tissue from 100 mCRPC patients; data was paired with deep whole-genome and transcriptome sequencing from the same samples. Unbiased hierarchical clustering of the mCRPC methylome was undertaken, and the survival of patients in each cluster was calculated using the Kaplan Meier method. Results: Unbiased hierarchical clustering revealed several distinct subtypes. 22% of mCRPC samples exhibited a novel epigenomic subtype associated with hyper-methylation. This hypermethylated (HM) cluster was significantly associated with somatic mutations in genes known to be involved in methylation, eg TET2 and DNMT3B, as well as in genes in which mutations have been associated with hyper-methylation in other cancer types ( IDH1 in glioblastoma and BRAF in colon cancer). mCRPC survival was 56.1 mos in pts with HM cancers compared to 35.6 mos in non-HM (p = .055). Methylome clustering also identified a unique cluster comprised of all patients with treatment-induced small cell/neuroendocrine cancer, a subtype previously associated with poor survival. Conclusions: This integrated study of whole-genome, whole methylome and whole-transcriptome sequencing provides the first comprehensive overview of the important regulatory role of methylation in metastatic castration-resistant prostate cancer, and has identified at least two distinct subtypes. The clinical and therapeutic implications of methylation subtypes should be explored in future studies. Clinical trial information: NCT02432001 .
An artificial intelligence-enabled analysis of ECG changes after androgen deprivation therapy (ADT) for prostate cancer.
Authors: William Breen, Rickey Carter, Patrick Johnson, David M. Routman, Peter Noseworthy, Joerg Herrmann, Paul Friedman, Francisco Lopez-Jimenez, Zachi Itzhak Attia, Brad J. Stish, Suraj Kapa
Journal: Journal of Clinical Oncology (2020)

e17535 Background: Androgen Deprivation Therapy (ADT) is commonly used to treat prostate cancer (PC), but has been associated with cardiac morbidity and mortality. The exact mechanisms of this association are unclear. We sought to use an artificial intelligence (AI) enabled algorithm to identify ECG changes in PC patients who received ADT compared to PC patients who did not receive ADT. Methods: From 1,000,000 ECGs performed on 210,414 patients between 1993 and 2017 at our institution, a convolutional neural network was developed to detect predictive signatures for cardiac pathologies. During this process, the ability to predict “estimated sex” of the patient was developed, with output values ranging from 0 (female) to 1 (male). We applied this algorithm to 8,619 ECGs performed on 1,057 men age 75 or younger treated with radiation for high-risk or recurrent PC at our institution, and compared estimated sex after receiving ADT (n = 1,065) to ADT-naive ECGs (n = 7,554). We correlated ECG-identified estimated sex with serum testosterone levels using Spearman rank correlation. Results: Patients who had received ADT had a mean (SD) estimated sex value of 0.81 (0.26) compared to 0.92 (0.17) for those who did not (p &lt; 0.001). Difference between estimated sex in post-ADT ECGs and ADT-naive ECGs remained significant across age groups (Table). Decreased serum total testosterone correlated with decreased estimated sex values in men receiving ADT (R = .57, p &lt; 0.001). Conclusions: ADT for prostate cancer is associated with changes in AI-identified ECG parameters, including lower estimated male sex after receiving ADT. Lower ECG male sex estimate was associated with decreased serum testosterone. In this study, we provide preliminary proof of concept for a potential non-invasive means of monitoring treatment effect and physiologic change using ECGs. [Table: see text]
The association between drug industry payments and NCCN guideline panel membership.
Authors: Aaron Philip Mitchell, Akriti A. Mishra, Pranammya Dey, Michael A. Curry, Niti A. Trivedi, Michael Haddadin, Mohammed Rahman, Aaron N Winn, Stacie Dusetzina, Peter Bach
Journal: Journal of Clinical Oncology (2020)

2068 Background: The high frequency of financial relationships between the pharmaceutical industry and influential oncologists who author clinical practice guidelines may influence guideline recommendations. Therefore, we assessed the financial relationships held by NCCN Guidelines panelists before and after joining the panel, compared to those held by a matched set of oncologists. Methods: Membership of NCCN Guidelines panels for the 20 most common cancers was obtained from archival guidelines and linked manually to Open Payments records of industry payments. We identified physicians who newly joined an NCCN panel during the August 2013-December 2018 study period, and we included medical oncologists who had at least 1 year of Open Payments data before and after joining. These medical oncologists who joined an NCCN panel (panelists) were matched 1:2 to medical oncologists with the same gender, institutional affiliation, and medical school graduation year, who did not join an NCCN panel (non-panelists). The dollar value of industry payments was then calculated over the 1 year before (pre-join) and after (post-join) the date that each panelist joined. We used generalized linear models to assess differences in industry payments between the panelists and matched non-panelists in the pre-join period. We used difference-in-difference estimation (DiD) to assess whether joining an NCCN panel was associated with increased payments in the post-join period. Results: There were 54 panelists and 108 non-panelists (matched from 1447 eligible oncologists at NCCN institutions). Mean per-oncologist payments among panelists were greater than non-panelists in the pre-join period ($11,259 vs $3,427, p = 0.02). From the pre-join to post-join period there was a similar increase in mean per-oncologist payments among panelists and non-panelists ($2,236 vs. $1,569, DiD estimate +$667, p = 0.77). Conclusions: Medical oncologists who were selected to an NCCN Guidelines panel had greater financial ties to industry compared to peer oncologists who were not selected. This difference was present prior to joining; oncologists did not experience a greater increase in financial payments from industry in the 1-year period after joining an NCCN panel. These results suggest an opportunity to reduce the potential influence of industry in oncology clinical practice guidelines through the selection of guideline panelists with fewer ties to industry.
治疗心力衰竭药物的合理应用
Authors: 许玉韵, 孙淑红
Journal: BMJ (2004)

近年来,由于分子生物学的发展和国际大样本、多中心临床试验结果的公布,对心力衰竭的认识逐步深入.现认为心力衰竭发生发展的基本机制是心室重塑,肾素-血管紧张素-醛固酮系统(RAAS)和交感神经的过度活化在心肌重塑中起着关键的作用,因而,心力衰竭的治疗概念有了根本性的转变,即:从短期血流动力学/药理学措施转变为长期的、修复性的策略,目的是改变衰竭心脏的生物学性质.以往,强心、利尿、扩血管一直被认为是心力衰竭的经典治疗,现今已被新的常规治疗所取代,即:以神经内分泌拮抗剂为主的三大类或四大类药物的联合应用,也就是利尿剂、血管紧张素转换酶抑制剂(ACEI)、β受体阻滞剂的联合应用,必要时再加地高辛.我们从以下几个方面介绍治疗慢性心力衰竭药物的合理应用。
Immunogenomic characterization of advanced clear cell renal cell carcinoma treated with PD-1 blockade.
Authors: David A. Braun, Yue Hou, Ziad Bakouny, Miriam Ficial, Miriam Sant'Angelo, Petra Ross-Macdonald, Opeyemi Jegede, Maxine Sun, Megan Wind-Rotolo, Jean-Christophe Pignon, Donna S. Neuberg, Paul J. Catalano, Gordon J. Freeman, Arlene Sharpe, David F. McDermott, Eliezer Mendel Van Allen, Sabina Signoretti, Catherine J. Wu, Sachet A. Shukla, Toni K. Choueiri
Journal: Journal of Clinical Oncology (2020)

5010 Background: Immune checkpoint inhibitors targeting the PD-1 pathway have transformed the management of many advanced malignancies, including clear cell renal cell carcinoma (ccRCC), but the drivers and resistors of PD-1 response remain incompletely elucidated. Further, the common paradigm in solid tumor immunology that pre-existing CD8+ T cell infiltration, in combination with high numbers of nonsynonymous mutations (which, in the context of diverse HLA class I alleles, may be presented as neoantigens) drives response to PD-1 blockade, has not been thoroughly explored in ccRCC. Methods: We analyzed 592 tumors collected from advanced ccRCC patients enrolled in prospective clinical trials (CheckMate 009, CheckMate 010, CheckMate 025) of treatment with PD-1 blockade (n = 362) or mTOR inhibition (as control arm; n = 230) by whole-exome (n = 454) and RNA-sequencing (n = 311), integrated with CD8 immunofluorescence analysis (n = 219), to uncover the immunogenomic determinants of therapeutic response and survival. Wilcoxon rank-sum test was used to compare somatic alteration burden between clinical benefit (CB) v.s no CB (NCB); Fisher’s exact test was used to compare mutations and copy number alteration by infiltration state; and hazard ratio (HR) was calculated from Cox PH model for progression-free (PFS) and overall survival (OS) endpoints. All tests were at a significance level of p &lt; 0.05. Results: Conventional genomic markers (tumor mutation burden, p = 0.81; neoantigen load, p = 0.47 for CB vs. NCB) and degree of CD8+ T cell infiltration (p = 0.88 for PFS; p = 0.65 for OS) were not associated with clinical response or altered survival with PD-1 blockade. These advanced ccRCC tumors were highly CD8+ T cell infiltrated, with only 22% having an immune desert phenotype and 5% with an immune excluded phenotype. Our analysis revealed that CD8+ T cell infiltrated tumors are depleted of clinically favorable PBRM1 mutations (p = 0.013) and enriched for unfavorable chromosomal losses of 9p21.3 (p &lt; 0.001) when compared to non-infiltrated tumors. When found within infiltrated tumors, del(9p21.3) was associated with worse CB rate (36% (9/25) for del(9p21.3) vs. 88% (7/8) for wildtype at that locus, p = 0.017) and worse survival (HR = 2.38, p = 0.01 for PFS; HR = 2.44, p = 0.01 for OS) with PD-1 blockade. Conclusions: These data demonstrate how the potential interplay of immunophenotypes with somatic mutations and chromosomal alterations impacts therapeutic efficacy in advanced ccRCC.
右腰疝一例
Authors: 吴宝强, 江勇
Journal: BMJ (2012)

对1例77岁老年女性的右腰部可复性肿块进行详细的病史询问及体格检查,结合CT表现诊断为右侧腰疝,予无张力疝修补术.结合相关文献认为,外科手术是腰疝的主要治疗手段,而微创手术是目前治疗的趋势。
Clinical trial awareness in oncology patients of diverse ethnic background: A single-institution analysis.
Authors: Gautam Valecha, Nishitha Thumallapally, Sandy El Bitar, Terenig O. Terjanian, Louise Madrigal, Laura Longo, Sarah Vaiselbuh
Journal: Journal of Clinical Oncology (2020)

e19217 Background: Clinical trials offer several advantages to the patients including access to innovative treatments with improved survival rates, closer monitoring and follow-up with removal of health disparity; and aim to advance the science of medicine. Yet, worldwide enrollment rates in cancer clinical trials have been only about 5 percent, despite the fact that a significantly higher percentage of Americans have a desire to participate in clinical trials [1, 2]. We conducted a single institution study to gain knowledge about clinical trial awareness in our cancer patient population as well as to identify the barriers within provider-consumer communication that prevent enrollment. Methods: A 10-question survey was distributed by medical assistants and surveys (n=222) were collected at the end of each clinic visit. Responders included racial/ethnic minorities and underserved patients, representative of the ethnic diversity in the Staten Island Borough of New York City. Demographic data including age, gender, zip code, race and ethnicity were recorded. Additionally, Charlson comorbidity index and tumor stage was also recorded. Results: 159/222 patients (71.62%) completed the survey. Of these patients, 47 (29.55%) answered every question on the survey, while 112/159 patients (70.44%) answered only few of the questions. The completed surveys are linked by zip code to the different boroughs of Staten Island, which allows us to identify hubs with lack of clinical trial awareness knowledge. Conclusions: Despite the several advantages for patients and medical field, enrollment rates in clinical trials remain very low. Our study results help in gaining knowledge about clinical trial awareness among oncology patients, correlated to comorbidity and tumor stage. In addition, demographic hubs with lack of knowledge are identified as targets for community outreach and education. A multilevel approach will be developed to address identified barriers that exist for patients, and will be implemented at community level, to reduce ethnic bias in trial enrollment and increase trial participation among an ethnically diverse population. References: 1. Unger JM, Cook E, Tai E, Bleyer A: The Role of Clinical Trial Participation in Cancer Research: Barriers, Evidence, and Strategies. Am Soc Clin Oncol Educ Book. 2016, 35:185-198. 10.1200/EDBK_156686 2. Comis RL, Miller JD, Aldigé CR, Krebs L, Stoval E: Public attitudes toward participation in cancer clinical trials. J Clin Oncol. 2003, 21:830-835. 10.1200/JCO.2003.02.105.
心房扩大与心室肥厚的心电图表现
Authors: 张红, 朱天刚
Journal: BMJ (2009)

临床上有很多疾病均可引起心房扩大及心室肥厚,如风湿性心脏病二尖瓣狭窄可以引起左心房扩大及右心室肥厚;慢性阻塞性肺病可引起右心房扩大及右心室肥厚;长期患高血压病、主动脉瓣狭窄等疾病可导致左心室扩大或肥厚;先天性心脏病可致全心扩大等.这些病变在心电图检查中可表现出一些特异性的改变,并可为临床诊断和治疗决策提供客观依据。
Comparative quantitative safety profiles of PD-1 and PD-L1 checkpoint inhibitor monotherapies: A Bayesian model-based meta-analysis.
Authors: Boris Shulgin, Alexandra Smirnova, Yuri Kosinsky, Gabriel Helmlinger, Kirill Peskov
Journal: Journal of Clinical Oncology (2020)

e15167 Background: Anti-cancer therapies with immune checkpoint inhibitors (ICIs) are associated with immune-mediated adverse events (imAEs). The objective of this study was to use a Bayesian model-based meta-analysis, to compare safety profiles of PD-1 and PD-L1 checkpoint inhibitor monotherapies. Methods: We performed an exhaustive search through PubMed and TrialTrove databases, ASCO and ESMO abstracts to identify relevant ICI safety data. A Bayesian meta-analysis (BMA) was performed for all-grade and high-grade (Grades 3-4) treatment-related AEs (trAEs) and immune-mediated AEs (imAEs). The analysis was performed for total AEs and individual AEs affecting different organs: dermatological (rash, pruritus), gastrointestinal (diarrhea, colitis), hepatic (AST, ALT), respiratory (pneumonitis), and endocrine (hyperthyroidism, hypothyroidism). Software STAN along with the brms package in R software were used for the BMA. Results: A total of 145 articles were identified, covering 30,737 patients in 153 cohorts treated with anti PD-1 and anti PD-L1 monotherapies. For total all-grade and grade 3&amp;4 trAEs, anti PD-L1 demonstrated lower AE rates vs. anti PD-1 (65% vs. 69% and 12% vs. 16%, respectively). Results were similar for total all-grade and high-grade imAEs (19% vs. 26% and 4% vs. 7%, respectively). The analysis of all-grade individual trAEs showed that anti PD-L1 exhibited lower AE rates vs. anti PD-1 for rash (8% vs. 10.5%), pruritus (9% vs. 12%), diarrhea (8.5% vs. 11%), colitis (1.0% vs. 1.6%), AST (3.0% vs. 5.5%), ALT (3.5% vs. 5.6%), pneumonitis (3.0% vs. 3.9%), hyperthyroidism (0.8% vs. 4.0%) and hypothyroidism (6.0% vs. 8.0%). For grade 3&amp;4 trAEs, differences between anti PD-L1 and anti PD-1 were: 0.6% vs. 1.3% for diarrhea, 0.7% vs. 1.4% for colitis, and 0.9% vs 1.6% for pneumonitis. All-grade imAEs were less frequent for anti PD-L1 vs. anti PD-1 for: rash (6.5% vs. 10%), colitis (1.0% vs. 2.0%), AST (3.5% vs. 3.9%), ALT (2.9% vs. 4.0%), pneumonitis (2.0% vs. 4.0%), hyperthyroidism (2.5% vs. 4.0%) and hypothyroidism (5.5% vs. 9.0%). Similar results were obtained for grade 3&amp;4 imAEs incidences: rash (0.5% vs. 0.9%), diarrhea (0.5% vs. 1.5%), colitis (0.5% vs. 1.1%) and pneumonitis (0.9% vs. 1.4%). Conclusions: Significant differences in trAEs and imAEs rates were shown for anti PD-L1 vs. anti PD-1 monotherapies. Anti PD-L1 demonstrated more favorable safety profiles for total and individual AE rates. Notably, AE rates for pneumonitis and colitis were twice as high for anti PD-1 vs. anti PD-L1 therapies.
The evolution of financial toxicity in patients with lung cancer.
Authors: Cole Friedes, Sarah Hazell, Wei Fu, Chen Hu, Beverly Lee, K Ranh Voong, Josephine Louella Feliciano, Lauren Nicholas, Todd R. McNutt, Peijin Han, Russell K. Hales
Journal: Journal of Clinical Oncology (2020)

e19406 Background: Financial toxicity (FT), or the cost-related side effect of cancer therapy, has been linked to poor clinical outcomes, greater symptom burden, and worse quality of life. While the repercussions of FT have been thoroughly explored, the longitudinal patient relationship with FT in the initial course of therapy is unknown. Methods: Patients with stage II – IV lung cancer were recruited in a prospective longitudinal non-interventional study between July 2018 and January 2020. FT was measured via the COST score, a validated questionnaire for benchmarking FT, at a) the time of cancer diagnosis and then later at b) 6-month follow up (6MFU). In this model, a lower COST score indicates increased financial hardship. Completed 6MFU data was compared to corresponding baseline data for each patient. Linear regression analysis was used to compare patient characteristics with baseline COST (COST base ) and 6-month COST (COST 6M ) scores. Results: At the time of analysis, 209 patients were screened and 194 (95.1%) patients agreed to participate and complete the baseline survey. Subsequently, 93 patients completed the 6MFU survey, 32 patients had died, and 7 patients were lost to follow up. The remaining 62 patients have not met the study end point to date. Of the 93 patients that completed the 6MFU and baseline survey, the median age was 65 (range 35-89), 50.5% were male, and 76.3% were Caucasian. Over the first six months of therapy 36.5% overestimated OOP expenses by &gt; $1000 and 22.5% reported a decrease in total monetary savings, but only 4.3% of patients made decisions about health care based on cost of care. FT was present at both time points but was worse at diagnosis than at 6MFU (median COST base 25 [range 1-44] vs. median COST 6M 27 [range 0-44]; p = 0.04). Linear regression correlated risk factors with FT at baseline ( &lt; 1 month monetary savings, employed but on sick leave, and inability to afford basic necessities; all p &lt; 0.001) that were different from risk factors at 6MFU (paying much more than expected OOP and sacrificing spending to meet medical costs; p &lt; 0.001). There was no significant difference between estimated OOP costs at baseline (median $2550 [range $0 - $500,000]) and actual OOP costs (median $2496 [range $0 – 25,900]; p = 0.25). Conclusions: FT toxicity is pervasive at both diagnosis and at 6-month follow up, however, the magnitude of toxicity changes with time. Few patients are willing to sacrifice medical care regardless of the cost. Risk factors for FT evolve, suggesting that different groups may benefit from financial intervention at diagnosis versus 6MFU.