tbuckley/cabot-search huggingface dataset:
Using autoantibody signatures to predict immunotherapy discontinuation in melanoma patients.
Authors: Iman Osman, Keith M. Giles, Yingzhi Qian, Megan Wind-Rotolo, John Loffredo, Tyler Hulett, Jeffrey S. Weber, Hua Zhong
Journal: Journal of Clinical Oncology (2020)

3069 Background: Immune checkpoint inhibitors (ICIs), e.g., ipilimumab (IPI) and/or nivolumab (NIVO), produce durable survival benefit in a substantial proportion of melanoma patients but can also induce severe immune-related adverse events (irAEs) requiring treatment discontinuation. There is no biomarker to predict irAEs in ICI-treated melanoma patients. Given the similar clinical manifestation between irAEs and autoimmune disorders, we hypothesized that a subset of patients possess a subclinical baseline predisposition to developing irAEs that is characterized by specific autoantibodies (autoAbs). Methods: Pre-treatment melanoma patient sera from the CheckMate-238 Phase III trial of adjuvant IPI vs. NIVO were used for autoAb profiling with HuProt proteomic arrays (CDI Labs). The outcome of interest is to predict toxicity events that caused treatment discontinuation. For each treatment arm, we allocated patients to training and testing datasets in a 3:1 ratio. We calculated the area under the curve (AUC) of the receiver operating characteristic curve to select a probability threshold, which was applied to the testing dataset to assess accuracy, sensitivity, and specificity. Functional enrichment among autoAb protein targets was assessed using Metascape. Results: There were 707 irAEs among 597 patients (IPI = 423, NIVO = 174), of which 355 required treatment discontinuation (IPI = 287, NIVO = 68). In the training sets, we identified a 170 autoAbs signature consisting of 102 autoAbs for IPI treatment and 68 autoAbs for NIVO treatment. In the independent testing set, the signatures showed AUC of 0.85 (0.78, 0.92), 82% sensitivity, 78% specificity, and overall accuracy of 81% to predict IPI discontinuation, and AUC of 0.87 (0.74, 0.99), 75% sensitivity, 97% specificity, and overall accuracy of 88% to predict NIVO discontinuation. Enrichment of nuclear lumen-associated protein targets was identified among autoAb signatures that predict IPI or NIVO discontinuation. Conclusions: The identified signature within a large Phase III trial cohort highlights the potential utility of pre-treatment autoAbs for prediction of patients at high risk of developing irAEs in the adjuvant setting necessitating treatment termination. We are currently validating and refining toxicity-associated autoAb signatures with the goal of developing a Clinical Laboratory Improvement Amendments (CLIA)-certified assay to enable clinicians to optimize immunotherapy delivery and patient selection.
Sleep and sleep disorders
Authors: Fujun Jia
Journal: BMJ (2016)

睡眠是维持人体正常生理功能极其重要的生命活动，对精神、情感、机体免疫和细胞生长与修复等都有重要作用。睡眠障碍是临床常见的主诉之一。通过分析睡眠障碍分类和诊断标准新修订的内容，阐述睡眠障碍的评估方法和干预手段，为临床医生诊治睡眠障碍提供依据。
The clinical impact of the expression of the cancer stem cell marker CD44v9 in early triple negative breast cancer (TNBC).
Authors: Eriko Tokunaga, Wakako Tajiri, Katsumi Takizawa, Hideki Ijichi, Hiroki Ueo, Chinami Koga, Yoshiaki Nakamura, Kenichi Taguchi, Masahiro Okamoto
Journal: Journal of Clinical Oncology (2020)

e12566 Background: The adhesion molecule CD44 is expressed in cancer stem-like cells (CSCs). CD44 variant 9 (CD44v9), a splicing variant of CD44, has emerged as a novel marker of cancer stemness. CD44v9 was reported to be associated with the resistance to chemotherapy in several malignancies. We recently reported that the high expression of CD44v9 is associated with the poor prognosis of the patients with triple negative breast cancer (TNBC), who received neoadjuvant chemotherapy (NAC). In this study, we investigated the clinical impact of the expression of CD44v9 in early TNBC who underwent surgery without NAC. Methods: Among 2257 primary breast cancer patients at clinical stage I-III who underwent surgery without NAC form 2002 to 2015, 201 patients with TNBC were included in this study. The expression of CD44v9 was analyzed immunohistochemistry (IHC). The associations between the CD44v9 expression and the clinicopathological characteristics and the prognosis were investigated. The tumors with the positive staining in more than two third of the cancer cells were regarded to be high expression of CD44v9. Results: CD44v9 high expression was observed in 62 cases (30.8%) and the low expression was in 139 cases (69.2%). Many of the CD44v9 high tumors were low grade than the tumors with low CD44v9. There were no significant associations between the expression levels of CD44v9 and the tumor size, lymph node metastasis and the pathological stage (pStage). There were no differences in the prognosis between the high and low CD44v9 expression in pStage I. However, in the patients with the tumors with pT1c or more (pT2, pT3) and the patients with pStage 2 and more, the high CD44v9 expression was significantly associated with the poor prognosis in terms of distant recurrence-free survival (DRFS) and overall survival (OS). In addition, high CD44v9 was associated with significantly shorter survival after recurrence. Many of these patients received various chemotherapy in the adjuvant setting and after recurrence. Therefore, CD44v9 high expression is considered to be associated with the poor prognosis due to the resistance to various chemotherapeutic agents. Conclusions: The prognosis of the TNBC patients with the high expression of CD44v9 is poor, which might be induced by the resistance to various chemotherapeutic agents. These results suggest that CD44v9 might be a novel therapeutic target for TNBC.
Progress in rheumatic diseases-related peripheral neuropathy
Authors: Liuqing Wang, Yuelan Xiao, Weiwei Zhao, Shoucheng Zhang, Hong Wang, Bei Shao
Journal: BMJ (2018)

Rheumatic diseases such as rheumatoid arthritis and Sjogren′s syndrome can be associated with a wide range of peripheral neuropathy. The diagnosis and treatment are more difficult in rheumatic diseases combined with peripheral neuropathy due to the complex etiology and clinical manifestations. This article reviews the recent progress in the diagnosis and treatment of rheumatic diseases-related peripheral neuropathy.


Key words: 
Rheumatic diseases; Peripheral nervous system diseases
Clinical and genomic features of high tumor mutation burden in patients with non-small cell lung cancer.
Authors: Yuan Qiu, Haihong Yang, Hanzhang Chen, Qiuhua Deng, Liping Liu, Dakai Xiao, Di Shao, Weiwei Li, Wenxi Jiang, Changbin Zhu, Yongping Lin, Jianxing He
Journal: Journal of Clinical Oncology (2020)

e21023 Background: TMB is associated with mono-immunotherapy efficacy for patients with advanced or metastatic non-small-cell lung cancer (NSCLC). For early-stage NSCLC or EGFR mutated non-resectable NSCLC, TMB-H predicted better prognosis or poor response to TKIs. This research might develop potential predictive parameters for distinguishing NSCLC with high or low TMB. Methods: Samples of surgically resected, cancer tissues were collected from 499 patients with NSCLC: 29 (5.8%) lung squamous cell carcinoma (LUSC) and 468 (94.2%) lung adenocarcinoma (LUAD). The mutations and TMB were confirmed by target region capture sequencing (Oseq™-508). Results: According to the median value (3.08), TMB is divided into high (N = 244) and low (N = 255). Interactions between TMB and sex, age, location, histology, pathological subtype, lymph node, parabronchial lymph node, LVI, neuro-invasive, stage and mutation status were evaluated. The distribution of TMB-H was significantly (p &lt; 0.001) correlated with sex, age, histology, pathological subtype, stage (TN stage) and partial mutations. Among all mutations, 6 genes (TP53 / FAT3 / KMT2D / TSHZ3 / NAV3 / EPHA3) were confirmed to be significantly related to TMB-H in NSCLC. We also found that TMB-H was significantly affected by mutation status of KRAS gene (P. G12X, p &lt; 0.001) and missense mutations in FAT3 (p &lt; 0.001). The Kruskal–Wallis H test results showed that the mutation types of FAT3, KRAS, TP53 and PIK3CA were closely related to TMB-H. Lasso linear regression analysis was applied and resulted the better predictors of TMB status including TSHZ3, KMT2D, TP53, gender and T stage. Conclusions: Instead of comprehensive genomic profiling to evaluate TMB, clinical characteristics and special mutation types may help to effectively screen and predicate patients with TMB-H status. [Table: see text]
Characteristics of breast cancer in Slovenian patients with germline CHEK2 c.444+1G&gt;A mutation.
Authors: Nikola Besic, Ana Blatnik, Tea Nizic-Kos, Srdjan Novakovic, Mateja Krajc
Journal: Journal of Clinical Oncology (2020)

e13536 Background: Different CHEK2 germline pathogenic variants/likely pathogenic variants (PV/LPV) are associated with distinct immunophenotypic molecular subtypes of breast cancer (BC). The aim of our study was to explore the characteristics of Slovenian BC patients with CHEK2 c.444+1G &gt; A variant. Methods: Germline CHEK2 pathogenic PV/LPV were identified in 76 individuals from 50 families who underwent genetic counseling and testing using a multigene panel at our institution from year 2014 to 2019. The data on 41 Slovenian BC patients with CHEK2 PV/LPV were retrospectively collected and analyzed, with an emphasis on c.444+1G &gt; A variant carriers. Results: BC in our CHEK2 positive patients was diagnosed in 40 females and one male. Mean age at BC diagnosis was 42.8 years (range 21-63). Four recurrent CHEK2 PV/LPV were found in 80% (33/41) of our BC patients: c.444+1G &gt; A (12/41; 29%; 11 females, one male), c.349A &gt; G (9/41; 22%). deletion of exons 9-10 (7/41; 17%) and c.1100delC (5/41; 12%). There was a trend for c.444+1G &gt; A carriers to develop BC at younger age in comparison to patients with other CHEK2 PV/LPV (mean age 39.3 vs. 44.2 years; p = 0.089). None of the patients with the c.444+1G &gt; A variant had invasive lobular carcinoma. Median tumor size in patients with c.444+1G &gt; A variant was 34 mm and median number of positive lymph nodes was 2.67 (range 1-8). Patients with c.444+1G &gt; A variant had a luminal A subtype in 2 cases, luminal B in 7 cases, HER2+ subtype in 3 cases, while none of patients had a triple negative BC. Mastectomy, tumorectomy and axillary lymphadenectomy was performed in 8, 4 and 12 patients, respectively. All c.444+1G &gt; A carriers had to be treated with chemotherapy and external beam irradiation. Patients with the c.444+1G &gt; A variant were more often treated with chemotherapy (p = 0.038) and/or external beam irradiation (p = 0.014) in comparison to patients with other PV/LPV. Distant metastases were diagnosed in two patients at age 45 and 47. Conclusions: Mutation c.444+1G &gt; A was detected in 29% of Slovenian patients with CHEK2 PV/LPV. Distant dissemination was diagnosed despite aggressive treatment at a young age in 16% of these patients.
Targeting non-engrafting IL-2 activated intentionally mismatched donor lymphocytes with monoclonal or bispecific antibodies for treatment of otherwise incurable cancer.
Authors: Shimon Slavin
Journal: Journal of Clinical Oncology (2020)

e15033 Background: Cure of certain resistant cancers by donor lymphocyte infusion (DLI) following allogeneic stem cell transplantation (SCT) suggests that alloreactive lymphocytes can eliminate otherwise resistant cancer. First patient with resistant relapse following supra-lethal chemoradiotherapy treated with DLI is alive &amp; well &gt; 34 years; &gt; 400 patients with hematological malignancies confirmed DLI efficacy for prevention &amp; treatment of relapse. Using murine leukemia (BCL1) &amp; metastatic breast cancer (4T1), IL-2 activated mismatched lymphocytes with no prior SCT eliminated otherwise lethal minimal residual disease (MRD). Using anti-EpCAM x anti-CD3 bispecific antibody (BSA) lethal melanoma was eliminated, also resulted in long-lasting immunity against lethal tumor challenge. Graft-vs-host disease (GVHD) was prevented by consistent rejection of mismatched lymphocytes. Accordingly, our goal was to develop effective immunotherapy of cancer using non-engrafting intentionally mismatched Allogeneic Targeted Activated Cancer Killer cells (ATACK) using relevant monoclonal antibodies (MoAb) or BSA. Methods: Patients with multiple myeloma &amp; lymphoma and advanced solid tumors were treated with haploidentical or unrelated donor lymphocytes pre-activated 5 days with IL-2, following non-myeloablative conditioning with endoxan or fludarabine and IL-2 injection x5 days for in vivo lymphocyte activation. ATACK with no MoAb was investigated in 40 patients with different cancers. Safety of ATACK with MoAb was investigated in 16 patients with resistant NHL, metastatic breast, lung &amp; colorectal cancer, using commercial MoAbs against CD20, Her-2, EGFR or VEGF, respectively, or using anti-EpCAM BSA. Results: Protocols were well-tolerated with mild transient toxicity following ATACK and BSA. No patient developed GVHD. Disease-free survival &gt; 15 years was documented in 2/2 patient with multiple myeloma and 2/2 patients with lymphoma. Longterm progression-free survival was observed in 5/31 evaluable patients with advanced metastatic solid tumors treated with no MoAbs. Minor toxicity in targeted ATACK recipients was manageable in outpatient clinic. Conclusions: Intentionally mismatched IL-2 activated killer cells guided by MoAbs or BSA represents a promissing approach for treatment, possibly even cure, of cancer patients with MRD while avoiding GVHD.
人工受精妊娠合并急性粟粒性肺结核一例分析
Authors: 曾勉, 唐朝霞, 关开泮, 郭禹标
Journal: BMJ (2010)

我国2000年的结核病流行病学抽样调查结果显示,全国至少有5亿人曾感染结核杆菌,其中有10%发生结核病~([1]).全球现有结核病患者2000万,一半是妇女~([2]),育龄妇女在妊娠时罹患结核病的比例呈逐渐上升趋势.现报道我们收治的1例妊娠合并粟粒性肺结核的病例并结合文献复习。
Liposomal irinotecan plus fluorouracil/leucovorin versus FOLFIRINOX as the second-line chemotherapy for patients with metastatic pancreatic cancer: Multicenter study of the Korean Cancer Study Group (KCSG).
Authors: Hongjae Chon, Hyung Soon Park, Beodeul Kang, Hyeon-Su Im, Choong-kun Lee, Ilhwan Kim, Myoung Joo Kang, Jun-Eul Hwang, Woo Kyun Bae, Jaekyung Cheon, Jung Yong Hong, Jung Hun Kang, Jung Hoon Kim, Sung Hee Lim, Jin Won Kim, Ji-Won Kim, Changhoon Yoo, Hye Jin Choi, Joon Oh Park
Journal: Journal of Clinical Oncology (2020)

4624 Background: There is no clear consensus on the second-line treatment for patients with metastatic pancreatic cancer (mPC). The aim of this study was to compare the efficacy and tolerability between liposomal irinotecan (nal-IRI) plus fluorouralcil/leucovorin (FL) and FOLFIRINOX (oxaliplatin/irinotecan/leucovorin/fluorouracil) in patients who failed to first-line gemcitabine-based therapy. Methods: In this retrospective study, 378 mPC patients who received nal-IRI/FL (n = 104) or FOLFIRINOX (n = 274) as the second-line treatment across 11 institutions from January 2015 to August 2019 were analyzed. The primary end point was progression free survival (PFS), and secondary end points were overall survival (OS), overall response rate, and tolerability. Results: There were no significant differences between the two groups in terms of baseline characteristics, except first-line regimen (previous gemcitabine/nab-paclitaxel, nal-IRI/FL, 85.6% vs. FOLFIRINOX, 51.5%; previous gemcitabine monotherapy, 5.8% vs. 24.5%). The median follow-up time was 6.0 months. The median PFS (nal-IRI/FL, 3.7 months vs. FOLFIRINOX, 5.0 months) and OS (nal-IRI/FL, 7.7 months vs. FOLFRINOX, 9.7 months) were comparable between two groups (P = 0.40 and 0.13, respectively). The overall response rate was not significantly different between two groups (nal-IRI/FL, 14% vs. FOLFRINOX, 16%; P = 0.644). In multivariate analysis, poor ECOG status, presence of liver metastasis, high NLR, and high CA19-9 were independent prognostic factors for PFS and OS, but chemotherapy regimen (nal-IRI/FL vs. FOLFRINOX) was not. In a subgroup analysis of patients with liver metastasis, FOLFIRINOX exerted significant PFS (median: 2.1 months vs. 4.1 months for nal-IRI/FL vs. FOLFIRINOX, respectively; P = 0.02) and OS (median: 6.7 months vs. 8.4 months for nal-IRI/FL vs. FOLFIRINOX, respectively; P = 0.04) benefit compared with nal-IRI/FL. Grade 3 neutropenia or higher were more frequently observed in FOLFIRINOX (47.2%) than nal-IRI/FL (35%) (P = 0.033). Grade 3 peripheral neuropathy was also common in FOLFIRIONX (5.9%) group compared with nal-IRI/FL (1.0%) (P = 0.049). Conclusions: In second-line setting for mPC after progression on gemcitabine-based therapy, both nal-IRI/FL and FOLFIRINOX regimen showed comparable efficacy and acceptable safety outcomes. FOLFIRINOX regimen might be preferentially considered in patients with liver metastasis.
Factors influencing antibiotics dosage adjustment in continuous renal replacement therapy
Authors: Qi Liu, Ruihua Wang
Journal: BMJ (2019)

Continuous renal replacement therapy (CRRT) will eliminate antibiotics while eliminating water and solutes from the body, so adjusting antibiotics dose timely is important for patients undergoing CRRT. Pharmacological characteristics of antimicrobials, pathological and physiological statues of the patients, effects of CRRT on antibiotics clearance and other factors would affect the pharmacokinetics of antibiotics. In order to achieve the desired therapeutic effect, the monitoring of drug concentration and individualizing the dosage of antibiotics are cecessary.


Key words: 
Continuous renal replacement therapy; Anti-bacterial agents; Influencing factors
现代中药丹参酮的作用机制和临床应用
Authors: 王远芬, 于春秋, 石乃玉
Journal: BMJ (2008)

当今中药的发展进入了日新月异阶段.研究深度和中药提取成分已达到分子水平,某些现代中药的研发、制药工艺已不亚于西药.丹参酮胶囊具有明确的化学结构式、清晰的治病机制和大量的临床研究,弥补了西药抗生素耐药和不良反应重的不足。
Headache and comorbidity
Authors: 于生元
Journal: BMJ (2010)

头痛是临床上极为常见主诉,是全球范围前十位失能性疾患[1].包括原发性头痛与继发性头痛.继发性头痛通常是某些疾病的临床症状之一,具有明确的病因,如脑肿瘤、脑血管病、脑膜炎等等;而原发性头痛是指目前尚未明确病因的一组头痛疾患,包括偏头痛、紧张型头痛、丛集性头痛及其他原发性头痛,它们被视为独立的疾患。
Analysis of incidence and its influencing factors of allergic dermatosis among college students
Authors: Guang-hua Wan
Journal: BMJ (2013)

During September-October 2012, random cluster sampling method was employed to recruit 871 students from 29 classes at East China Normal University to conduct a questionnaire survey. The overall prevalence of skin diseases was 33.5% (292/871) and those of eczema, urticaria, drug eruption and atopic dermatitis were 16.4% (143/871), 9.8% (85/871), 2.2% (19/871) and 0.2% (2/871) respectively. These diseases showed no statistically significant gender differences. The prevalence of contact dermatitis was 16.9% (147/871) and there was statistically significant gender difference (P<0.01).


Key words: 
Skin diseases; Prevalence
Exome Sequencing Identifies Genes and Gene Sets Contributing to Severe Childhood Obesity, Linking PHIP Variants to Repressed POMC Transcription
Authors: Gaëlle Marenne, Audrey E. Hendricks, Aliki Perdikari, Rebecca Bounds, Felicity Payne, Julia M. Keogh, Christopher J. Lelliott, Elana Henning, Saad Pathan, Sofie Ashford, Elena G. Bochukova, Vanisha Mistry, Allan Daly, Caroline Hayward, Nicholas J. Wareham, Stephen O’Rahilly, Claudia Langenberg, Eleanor Wheeler, Eleftheria Zeggini, I. Sadaf Farooqi, Inês Barroso
Journal: Cell Metabolism (2020)

Obesity is genetically heterogeneous with monogenic and complex polygenic forms. Using exome and targeted sequencing in 2,737 severely obese cases and 6,704 controls, we identified three genes (PHIP, DGKI, and ZMYM4) with an excess burden of very rare predicted deleterious variants in cases. In cells, we found that nuclear PHIP (pleckstrin homology domain interacting protein) directly enhances transcription of pro-opiomelanocortin (POMC), a neuropeptide that suppresses appetite. Obesity-associated PHIP variants repressed POMC transcription. Our demonstration that PHIP is involved in human energy homeostasis through transcriptional regulation of central melanocortin signaling has potential diagnostic and therapeutic implications for patients with obesity and developmental delay. Additionally, we found an excess burden of predicted deleterious variants involving genes nearest to loci from obesity genome-wide association studies. Genes and gene sets influencing obesity with variable penetrance provide compelling evidence for a continuum of causality in the genetic architecture of obesity, and explain some of its missing heritability.
急性左主干闭塞心肌梗死患者的心电图特点
Authors: 朱磊, 汪凡
Journal: BMJ (2010)

左主干闭塞的急性ST段抬高型心肌梗死患者病情重,预后差.对这部分患者必须早期诊断并进行积极治疗.现对比分析急性左主干闭塞和前降支、回旋支、右冠状动脉近端病变导致急性心肌梗死患者的心电图,探讨心电图在早期识别急性左主干闭塞中的价值。
The adjuvant radiotherapy benefits on pure mucinous breast carcinoma patients in different age stages: A SEER-based study.
Authors: Xiaoqing Wei, Li ping Dian, Fan Tang, Huijun Zhao, Honglin Situ, Rui Xu, Liping Ren, Yuzhu Zhang, Qianjun Chen
Journal: Journal of Clinical Oncology (2020)

e12519 Background: The aim of this analysis is to study the prognostic impacts of adjuvant radiotherapy on pure mucinous breast carcinoma patients in different age stages. Methods: Patients diagnosed pure mucinous breast carcinoma between 1998 and 2015 were identified from the Serveillance,Epidemiology,and Results End database. Chi-square, Kaplan-Meier method, Multivariate Cox proportional hazards models were used for statistical analysis. Results: We enrolled 10656 patients, including 5758 (54.0%) and 4898 (46.0%) in the with radiotherapy and without radiotherapy cohorts, respectively.The K-M method shows age is an independent prognostic factor in pure mucinous breast carcinoma patients with radiotherapy( p= 0.000 ). Compared with the younger groups (&lt;45y and 46-54y),the older groups (55-64y, 65-75y and &gt;75y) show a greater benefits with radiotherapy. The multivariate Cox proportional hazards model shows significant difference (all p= 0.000), the group 55-64y((HR = 0.58, 95%CI:0.453–0.742),the group 65-75y(HR = 0.709, 95% CI: 0.610–0.825),the group&gt;75y (HR = 0.613, 95% CI: 0.543–0.691), which indicates a better radiotherapy benefits in older groups(especially in 65-75y). Conclusions: This study shows a better benefits of postoperative adjuvant radiotherapy in pure mucinous breast carcinoma older patients. Owing to the common incompleteness of systematic basic treatments in older breast cancer patients,our real world analysis results may be helpful for the clinical decision-making.
Terminal life of dying patient and their in-house caring guidance requirements for residents in city center of Shanghai
Authors: Juanjuan Xu, Yuhua Zou
Journal: BMJ (2014)

From members in this local district from January 2011 to December 2013, a total of 150 patients with malignant cancer and chronic disease patients of lost of functions and their carers were recruited. A self-tailored interview was conducted via face-to-face communications. And according to 112(74.7%) carers, as compared to hospitalization, the patients were more likely willing to be looked after at home. The 95(63.3%) carers had a lack of professional caring knowledge and their caring techniques were insufficient. And 97(64.7%) carers were willing receive professional training in nursing and protecting dying patients. In-house terminal care is indeed required by the patients. However its service is best supported by the following aspects. The supports from local medical services and resources; professional training organized by a local social (neighborhood) committee and providing the guidance of in-house caring techniques and information of the relevant disease management. Building up a mutual terminal care group and finalizing the caring standards as soon as possible are essentials.


Key words: 
Terminal care; Nursing care