tbuckley/cabot-search huggingface dataset:
Nivolumab + ipilimumab versus platinum-doublet chemotherapy as first-line treatment for advanced non-small cell lung cancer: Three-year update from CheckMate 227 Part 1.
Authors: Suresh S. Ramalingam, Tudor Eliade Ciuleanu, Adam Pluzanski, Jong-Seok Lee, Michael Schenker, Reyes Bernabe Caro, Ki Hyeong Lee, Bogdan Zurawski, Clarisse Audigier-Valette, Mariano Provencio, Helena Linardou, Sang-We Kim, Hossein Borghaei, Matthew David Hellmann, Kenneth John O'Byrne, Luis G. Paz-Ares, Martin Reck, Faith Ellen Nathan, Julie R. Brahmer
Journal: Journal of Clinical Oncology (2020)

9500 Background: In the phase 3 CheckMate 227 Part 1 (NCT02477826; minimum follow-up, 29.3 mo), 1L NIVO + IPI significantly improved overall survival (OS) vs chemo in treatment-naive patients (pts) with aNSCLC and tumor PD-L1 expression ≥ 1% (primary analysis) or &lt; 1% (pre-specified descriptive analysis). Here we report data with 3-y minimum follow-up. Methods: Pts with stage IV / recurrent NSCLC and PD-L1 ≥ 1% (n = 1189) were randomized 1:1:1 to NIVO (3 mg/kg Q2W) + IPI (1 mg/kg Q6W), NIVO (240 mg Q2W) alone, or chemo. Pts with PD-L1 &lt; 1% (n = 550) were randomized to NIVO + IPI, NIVO (360 mg Q3W) + chemo, or chemo. Primary endpoint was OS with NIVO + IPI vs chemo in pts with PD-L1 ≥ 1%. An exploratory analysis of OS in pts by response status (CR/PR, SD, progressive disease [PD]) at 6 mo was conducted. Results: After a median follow-up of 43.1 mo (database lock, 28 Feb 2020), pts with PD-L1 ≥ 1% continued to derive OS benefit from NIVO + IPI vs chemo (HR: 0.79; 95% CI, 0.67–0.93); 3-y OS rates were 33% (NIVO + IPI), 29% (NIVO), and 22% (chemo). At 3 y, 18% of pts with PD-L1 ≥ 1% treated with NIVO + IPI remained progression-free vs 12% with NIVO and 4% with chemo; 38% of confirmed responders remained in response in the NIVO + IPI arm at 3 y vs 32% in the NIVO arm and 4% in the chemo arm. In pts with PD-L1 &lt; 1%, OS HR for NIVO + IPI vs chemo was 0.64 (95% CI, 0.51–0.81); 3-y OS rates were 34% (NIVO + IPI), 20% (NIVO + chemo), and 15% (chemo); 13%, 8%, and 2% of pts remained progression-free; and 34%, 15%, and 0% of confirmed responders remained in response, respectively. Pts with PD-L1 ≥ 1% with either CR/PR at 6 mo had longer subsequent OS with NIVO + IPI vs chemo; pts with SD or PD at 6 mo had generally similar subsequent OS between treatments (Table); results in PD-L1 &lt; 1% pts will be presented. Any-grade / grade 3–4 treatment-related AEs were observed in 77% / 33% of all pts treated with NIVO + IPI, and 82% / 36% with chemo. Conclusions: With 3 y minimum follow-up, NIVO + IPI continued to provide durable and long-term OS benefits vs chemo for pts in 1L aNSCLC. Pts with PD-L1 ≥ 1% who achieved CR/PR at 6 mo had marked OS benefit with NIVO + IPI vs chemo. No new safety signals were identified for NIVO + IPI. Clinical trial information: NCT02477826. [Table: see text]
Boosting the apoptotic response of high-grade serous ovarian cancers with CCNE1-amplification to paclitaxel by targeting APC/C and the pro-survival protein MCL-1.
Authors: Sven Becker, Klaus Strebhardt, Ranadip Mandal, Mourad Sanhaji
Journal: Journal of Clinical Oncology (2020)

e18065 Background: Ovarian cancer exhibits the highest mortality rate among gynecological malignancies. Antimitotic agents, such as paclitaxel, are frontline drugs for the treatment of ovarian cancer. They inhibit microtubule dynamics and their efficiency relies on a prolonged mitotic arrest and the strong activation of the spindle assembly checkpoint (SAC). Although ovarian cancers respond well to paclitaxel, the clinical efficacy is limited due to an early onset of drug resistance, which may rely on a compromised mitosis exit associated with weakend intrinsic apoptosis. Accordingly, we aimed at overcoming SAC silencing that occurs rapidly during paclitaxel-induced mitotic arrest. Methods: To do this, we used a specific anaphase-promoting complex/ cyclosome (APC/C) inhibitor to prevent a premature mitotic exit upon paclitaxel treatment. Furthermore, we investigated the role of the anti-apoptotic BCL-2 family member MCL-1 in determining the fate of ovarian cancer cells with CCNE1-amplification that are challenged with clinically relevant dose of paclitaxel. Results: Using time-laps microscopy we demonstrated that APC/C and MCL-1 inhibition under paclitaxel prevents mitotic slippage in ovarian cancer cells and restores death in mitosis (DIM). Consistent with this, the combinatorial treatment reduced the survival of ovarian cancer cells in 2D and 3D cell models. Since a therapeutic ceiling has been reached with taxanes, it is of utmost importance to develop alternative strategies to improve the patient´s survival. Conclusions: Our study provides not only elements to understand the causes of taxane resistance in CCNE1-amplified ovarian cancers but also suggests a new combinatorial strategy that may improve paclitaxel efficacy in this highly lethal gynecological disease.
Safety Run-In Phase (SRP) cohorts 1 and 2 of the IMMUNIB trial (AIO-HEP-0218/ass): An open-label, single-arm phase II study evaluating safety and efficacy of immunotherapy with PD-L1/L2 inhibition (nivolumab) in combination with receptor tyrosine kinase inhibition (lenvatinib) in advanced stage hepatocellular carcinoma (HCC).
Authors: Daniel Wilhelm Mueller, Gabriele Margareta Siegler, Enrico de Toni, Udo Lindig, Jurgen Siebler, Martin Walker, Salah-Eddin Al-Batran, Arndt Vogel
Journal: Journal of Clinical Oncology (2020)

e16601 Background: Immuno-oncology (I-O) drug nivolumab binds to T-cell PD-1 receptor and overcomes tumor induced inhibition of T-cell proliferation and cytokine release caused by PD-L1/L2 interaction. It so enhances the immune system’s natural tumor erasing capacity. In combination with selective targeting of oncogenic signaling pathways by receptor tyrosine kinase inhibitor (TKI) lenvatinib, a markedly improved response rate is expected in patients suffering from advanced stage HCC. Methods: This investigator-initiated phase II trial is designed as a signal generating, single-armed trial. 50 patients are planned in total. Primary endpoints are efficacy (objective response rate acc. to investigator assessed RECIST 1.1) and safety of combination treatment. The trial comprises two successive Safety Run-in Phase (SRP) cohorts, each consisting of 3 consecutively recruited patients, to evaluate safety of defined dose level 0: 240 mg nivolumab i.v. q2w along with 12 mg (≥ 60 kg bw) respectively 8 mg ( &lt; 60 kg bw) lenvatinib p.o. qd. This abstract focuses on safety data from SRP cohort 1 and 2 (6 patients) in which all AEs were evaluated after patients received 2 cycles of IMP in dose level 0. In total, 10 patients have been enrolled into the trial up to now. Results: Summarized over both SRP cohorts, no dose limiting toxicities (DLTs) i.e. selected grade 4 events occurred in the six evaluated patients. 2 SAEs (abdominal infection; not IMP-related; grade 3 / fever; IMP-related; grade 1) and 21 AEs have been documented in 6 patients (most common AEs: hypertension [3x (14%); IMP-related], pain [3x (14%) (flank; extremity; unspecified); not IMP-related] - in total 12 AEs IMP-related and 9 AEs not IMP-related). No grade 5 AE, one grade 4 AE (AST increase; IMP-related) and three grade 3 AEs (Abdominal infection and hepatic encephalopathy; not IMP-related / ALT increase; IMP-related) in two patients have been reported. All other AEs were of grades 1 or 2. No patient discontinued treatment during SRP. Conclusions: Combination treatment with nivolumab 240 mg and lenvatinib 12/8 mg was assessed as safe and well tolerated from the data obtained from 6 patients in two cohorts, each received two combination cycles. Regular recruitment was thus opened in January 2020 and is planned to be completed in Q3/2020. Clinical trial information: NCT03841201 .
儿童心肌炎误诊病例分析
Authors: 吴明昌
Journal: BMJ (2008)

吴明昌:常见一些家长带孩子来看病说:这孩子老是长出气、憋气、胸闷、胸疼,是不是得了心肌炎?这时大夫会问他在这之前是不是有过感冒(上呼吸道感染),因为在病毒感染以后出现这些症状很容易怀疑是心肌炎;如果没有感冒,则另当别论。
Relationship between atrial fibrillation and obstructive sleep apnea
Authors: Li Li, Weihua Guo, Changsheng Ma
Journal: BMJ (2016)

Atrial fibrillation (AF) is the most common arrhythmia, but its pathogenesis is still unclear. With the development of sleep medicine, obstructive sleep apnea (OSA) is found to associate with the occurrence of AF and recurrence after catheter ablation. This article reviews the pathophysiology of OSA, and relationship between OSA and the occurrence of AF, and its mechanism. It indicates that clinicians should pay close attention to the existence of OSA during diagnosis and treatment of AF.


Key words: 
Atrial fibrillation; Sleep apnea, obstructive
A clinical study on treatment for nonalcoholic steatohepatitis with L-ornithine-L-aspartate
Authors: 尹合坤, 李启祥, 谢汝缓, 周伟
Journal: BMJ (2004)

目的 探讨左旋门冬氨酸鸟氨酸(雅博司)治疗非酒精性脂肪性肝炎及降低血清甘油三酯水平的效果.方法30例经肝功能、B超检查及肝穿病理学检查确诊为非酒精性脂肪性肝炎患者,应用左旋门冬氨酸鸟氨酸10 g加入10%葡萄糖中静脉滴注,每日1次,持续21 d,疗程结束后复查血清丙氨酸转氨酶(ALT)、天冬氨酸转氨酶(AST)及甘油三酯.结果30例患者中,29例(96.7%)血清ALT和AST恢复正常,28例(93.3%)血清甘油三酯水平恢复正常,治疗期间无明显毒副作用.结论左旋门冬氨酸鸟氨酸是一种治疗非酒精性脂肪性肝炎安全有效的药物,同时可降低血清甘油三酯水平。
Utilizing an advanced practice provider (APP) led acute care clinic to improve access to high quality, patient centered, cost effective cancer care.
Authors: Megan Spradlin, Kasey Bowden, Sarena Zabilla, Elizabeth R Kessler
Journal: Journal of Clinical Oncology (2020)

e14007 Background: The medical oncology patient population is at high risk for adverse effects and complications related to anti-cancer treatments. The cost of oncology care is projected to reach almost $160 billion in 2020. The ongoing cost trajectory has placed a significant financial burden on patients, families, and society as a whole. The Centers for Medicare and Medicaid Service (CMS) has developed a new payment and delivery model that identifies potentially preventable conditions for ED visits/rehospitalizations among patients that are receiving anti-cancer therapies. Proposed CMS changes have created increased urgency around avoiding preventable ED visits/rehospitalizations. In response to the need for high quality, patient centered, cost effective care, we have established an APP-led acute care clinic that specializes in oncology care. Methods: The Clinical Assessment and Rapid Evaluation (CARE) Clinic offers acute care and symptom management catered to the oncology population. Patients are able to receive lab and imaging work up in addition to intervention with IV fluids, anti-emetics, opioids, electrolytes or antibiotics, as well as blood/platelets as warranted. To assess patient satisfaction, we created an anonymous four question survey delivered to CARE clinic patients over a two month period. Results: Seventy five surveys were collected. Pain and nausea were the leading reasons for encounters. 91% of patients rated their care as excellent, while 9% of patients rated their care as good. 33% of patients reported they would have been seen in the ED if the CARE Clinic was not available. Conclusions: The CARE Clinic represents a unique, one of the first of its kind, acute care and symptom management entity that utilizes an APP model to provide high quality care at a low cost. More research is needed to identify if this model can create statistically significant reduction in ED visits and rehospitalizations, however current data suggests that patients are highly satisfied with this unique method of care delivery. Sources Handley NR, Schuchter LM, Bekelman JE. Best Practices for Reducing Unplanned Acute Care for Patients With Cancer. Journal of Oncology Practice. 2018;14(5):306-313. doi:10.1200/jop.17.00081.
Real-world survival outcomes of using neoadjuvant chemotherapy in pancreatic cancer patients: Findings from the PURPLE clinical registry.
Authors: Belinda Lee, Vincent Witmond, Amanda Pereira-Salgado, Koen Degeling, Julia Shapiro, Benjamin N Thomson, Sumitra S Ananda, Sue-Anne McLachlan, Brett Knowles, Adrian Fox, Rachel Wong, Matthew E. Burge, Kate Clarke, Sharon Tracy Pattison, Mehrdad Nikfarjam, Adnan Nagrial, Rob Zielinski, Cheng Ean Chee, Peter Gibbs, Maarten J. IJzerman
Journal: Journal of Clinical Oncology (2020)

e16755 Background: Only a minority of pancreatic cancer patients (pts) are surgical candidates at presentation. Neoadjuvant chemotherapy (NAT) is proposed to increase the proportion of surgical candidates. This study investigates the impact of NAT in routine care of pancreatic cancer. Three cohorts were analysed, patients with early-stage resectable (ER), borderline resectable (BR) and locally advanced (LA) pancreatic cancer. Within these groups, survival outcomes of those undergoing immediate resection (IR) was compared to those receiving NAT with nab-paclitaxel and Gemcitabine (nabPGem) and NAT with FOLFIRINOX. Methods: The PURPLE registry consists of 1492 pancreatic cancer pts from 27 hospitals in Australia, New-Zealand and Singapore, collated between 2016-2019. After exclusion of LA unresectable and metastatic pts (n = 809), 683 pts were included. Kaplan-Meir curves estimated survival between groups with 95% confidence intervals. Multivariable cox proportional hazards models adjusted for age, gender and ECOG performance status. Results: Of 683 pts, 107 received NAT and 576 underwent IR. Those in the NAT group had favourable characteristics, including younger age (mean 63 vs. 66 yrs, p &lt; 0.01) and higher proportion of ECOG 0 vs. ≥1 (64% vs 46%) than those undergoing IR. Of those that received NAT, 64 received FOLFIRINOX and 35 nabPGem. Those receiving FOLFIRINOX were younger (mean: 60 vs. 67 yrs, p &lt; 0.01) and were more likely ECOG 0 compared to those receiving nabPGem (72% vs. 46%, p = 0.02). Resection rates for pts undergoing IR vs. NAT were 88% vs. 50% in ER and 16% vs. 43% in BR. Rates of R0 resection margins in pts undergoing IR vs. NAT were 54% vs. 25% in ER and 6% vs. 21% in BT. Comparing ER to BR, mOS was 29.9 vs. 20.3 mths (HR: 0.54, p &lt; 0.01). Within BR, mOS was 20.3 vs. 17.2 mths for NAT vs. IR (HR: 1.11, p = 0.74). Comparing those receiving FOLFIRINOX vs. nabPGem over all groups, mOS was 22 mths vs. 12 mths (HR: 0.31, p &lt; 0.01). Conclusions: Real-world data confirms the use of NAT remains infrequent in this Asia-Pacific population. The use of FOLFIRINOX was associated with better survival than nabPGem based on this observational study. Improved methods for treatment selection are required. Potential biomarkers including circulating tumor DNA are being explored in the DYNAMIC-Pancreas clinical trial.
Enabling variant calling in challenging FFPE samples by coupling a novel library preparation chemistry with exome sequencing.
Authors: Bosun Min, Ushati Das Chakravarty, Manqing Hong, Ekaterina Star, Hsiao-Yun Huang, Tim Barnes, Tzu-Chun Chen, Ramses Lopez, Karissa Scott, Lynette A Lewis, Steve Groenewold, Longhui Ren, Jinglie Zhou, Kevin Lai, Jessica Sheu, Xiaohui Wang, Patrick J Lau, Steven Henck
Journal: Journal of Clinical Oncology (2020)

e15584 Background: Comprehensive tumor profiling using NGS is fundamentally transforming oncology research. However, converting archival tissue samples into libraries is often challenging due to the low quantity and quality of DNA. Here we present accurate detection of variants in the human exome using the novel chemistry of the xGen Prism DNA library preparation kit, optimized for low-input and degraded samples, with xGen Research Exome v2.0 hybrid-capture enrichment. Methods: The IDT Exome v2 panel was used to carry out targeted sequencing of Prism DNA libraries generated from archival FFPE samples. The unique library preparation is enabled by an engineered mutant ligase and proprietary adapters that prevent chimeras and suppress dimer-formation, thereby maximizing the conversion of input DNA to sequencing libraries. Results: We achieved high yields of library (300-400 ng) from input amounts as low as 25 ng for severely damaged FFPE samples (DIN 1-3), &gt; 90% on-target rates and uniform depth of coverage ( &gt; 96% bases covered at &gt; 20X and &gt; 98% bases covered at &gt; 10X) for FFPE samples across a wide range in quality. We also observed minimal exon drop-outs in difficult-to-target genes for severely damaged FFPE material. To validate the variant calling performance of the Prism-Exome workflow, we used the Horizon OncoSpan FFPE reference control which contains 1-92% AF SNVs and Indels and achieved &gt; 98% sensitivity across ~250 SNVs and Indels. Conclusions: This study demonstrates that the xGen Exome Research v2, when combined with xGen Prism DNA library preparation, provides researchers with a complete human exome FFPE-sequencing solution with robust performance across FFPE samples of varying quality.
Anesthesia in large volume whole lung lavage for treatment of pneumoconiosis patients combined with chronic obstructive pulmonary disease
Authors: 王贤裕, 秦成名, 刘菊英, 涂明利
Journal: BMJ (2010)

Sixty-eight patients with pneumoconiosis combined with chronic obstructive pulmonary disease underwent large volume lavage in one lung under double cavity tracheal intubation and intravenousinhalant anesthesia. The vital signs of patients were recorded before, 10, 30min after and at the end of lavage. Results showed that the vital signs were stable during the lavage; and after the lavage all patients had relief significantly from the symptoms of dyspnea, polypnea and cough. Our results indicate that general anesthesia with bilateral lung ventilation are a safe and effective method in large volume whole lung lavage for treatment of pneumoconiosis patients combined with chronic obstructive pulmonary disease.

Key words: 
Pneumoconiosis ;  Bronchoalveolar lavage ;
Characteristics of obesity in teenage with a family history of type 2 diabetes
Authors: Bo-wei Liu, Fu-zai Yin, Chun-ming Ma, Dong-hui Lou, Xiao-li Liu, Jun-ru Liu, Qiang Lu
Journal: BMJ (2010)

A cross-sectional study was conducted on 1619 youngsters aged 13-15.They were divided into two groups:one with family history of diabetes (FHD~+) and another without a family history of diabetes (FHD~-).Measurements included height,weight,waist circumference (WC) and hip.FHD~+ group had significantly higher WC measurement,waist-to-hip ratio (WHR) and waist-to-height ratio (WHtR) when compared with FHD~-group (P ＜0.01).The abdominal obesity rate defined by WC measurement in FHD+ group was higher than that in FHD~-group (P＜0.01).The rate of overweight and obesity defined by body mass index (BMI) were no significant difference between two groups.After adjusting the gender and age,logistic regression analysis showed that the odds ratios of WC alone and BMI+WC for FHD~+ were 2.029 and 1.364 (95% CI:1.211-3.400,1.043-1.784,P＜0.05) respectively.Our data suggest that teenage with a family history of type 2 diabetes has a tendency of overweight characterized by the abdominal obesity.

Key words: 
Obesity; Diabetes mellitus,type 2
Survey on training for general practice backbone mentors in tertiary hospitals of Hebei province
Authors: Rongying Wang, Ran Qi, Zhenyin He, Xixi Wan, Xiao Zhi, Feng Li, Jinyan Wang, Wenwen Zhao
Journal: BMJ (2018)

Objective
To survey on training for general practice backbone mentors in tertiary hospitals of Hebei province.


Methods
A questionnaire survey on training status was conducted among general practice backbone mentors in tertiary hospitals of Hebei Province. The survey items included the basic information, knowledge of general practice and its training, suggestions for mentors training and general practice discipline construction in tertiary hospitals.


Results
Total 208 questionnaires were distributed and 208 were retrieved with a recovery rate of 100%. Among 208 participants, all of them were over the age of 30; 202 (97.1%) had bachelor degree or above; 202 (97.1%) were attending doctors or above; 165 (79.3%) had worked for more than 10 years; 169 (81.3%) had no or little knowledge of general practice; 159 (76.4%)had not received general practice training before; 124 (59.6%) thought that general practitioners were not qualified as gatekeeper at present; and 192 (92.3%) worked in the hospitals providing standardized residency training. The training contents in general section were prioritized as clinical skills, community health service development and policy, rules for general practice standardized training, theoretical training, the present situation and countermeasure of general teaching, the doctor-patient relationship and medical ethics. The contents in training method section were prioritized as lecture series of clinical medicine, case discussion, seminar, distance education with classroom teaching. The suggestions for mentors training included: the exploration of standardized training model, perfecting continuing education system for general practice mentors, more attention to the training at community health service centers and the consummation of general practice system. The suggestions for general practice discipline construction were that more attentions should be paid by the government and the hospitals leaders, the general practice departments in tertiary hospitals should closely cooperate with community health service centers in training of qualified general practitioners.


Conclusions
The specialists in tertiary hospitals of Hebei province do not have enough knowledge about general practice and do not quite understand the necessity of establishment of general practice department, so the training for general practice mentors should be strengthened and improved. Properly policy and more social resources from the government and the hospitals leaders will be helpful for construction of general practice discipline in general hospital.


Key words: 
Teacher training; Questionnaires; General practice
Changes of physical activity status of residents in Beijing Yayuncun community
Authors: Wan-xiang Xiao, Feng Xiao, Rui-li Li, Bo-wen Chen
Journal: BMJ (2010)

Objective To evaluate the changes of physical activity status of residents in Beijing Yayuncun(Asian Games Village)Community.Methods A total of 1765 permanent residents over 15 from 600 families living in Yayuncun Communities since 2000 were selected in this prospective study.Thebaseline survey was carried out with the Questionnaire for Residents of Beijing Typical Community in 2004 and 2005.From 2006 to 2008,same questionnaire was used for the follow-up survey,and 1412 residents were responded to the questionnaire.Results The knowledge levels related to physical exercise of Yayuncun residents elevated(P＜0.01).The source of knowledge gain from Olympics Games promotion,specialized community lectures and intemet increase significantly(P＜0.01),that from other media decreased(P＜0.01).The exercise rate in community was higher than in other sites(P＜0.01)and increased significantly (P＜0.05);while doing exercise in charged sites decreased(P＜0.05).Logistic regression analysis showed that regular physical exercise was related to age,BMI,exercise-related knowledge,exercise sites,attitude for sport facilities and chronological order.Conclusion During the preparation for the Beijing Olympic Games.the status of physical exercise of residents in Yayuncun Community presented the positive trends.

Key words: 
Sports; Community Participation