tbuckley/cabot-search huggingface dataset:
Association of socioeconomic status and molecular testing in stage IV colorectal cancer.
Authors: Salman Rafi Punekar, Megan Marie Griffin, Lena Masri, Danil V. Makarov, Scott Sherman, Daniel Jacob Becker
Journal: Journal of Clinical Oncology (2020)

e19023 Background: The use of EGFR monoclonal antibodies extends life for patients with advanced colorectal cancers (CRC) whose tumors exhibit wild type KRAS. Research suggests that KRAS testing is underused, denying patients access to targeted therapy. We sought to study the role of socioeconomic factors in the application of KRAS testing. Methods: We identified subjects with stage IV colorectal adenocarcinoma diagnosed between 2010 and 2015 in the Surveillance Epidemiology and End Results (SEER) database. We identified clinical and demographic characteristics, including diagnosis year, race, ethnicity, sex, age, geography, median household income (MHI), insurance coverage, tumor grade, and tumor location. We used multivariable logistic regression models to evaluate associations between these factors and the rate of KRAS testing. We constructed Cox proportional hazard models to assess the impact of KRAS testing on survival. Results: We identified 37,676 patients with stage IV CRC, 31.1% of whom were tested for KRAS mutations. The rate of KRAS testing varied from 23.2% to 56.5% across geographic regions. Patients were more likely to be tested if they were younger (OR 5.10 for age 20-29 vs 80+, 95% CI 3.99-6.54, p &lt; 0.0001), diagnosed more recently (OR 1.92 for 2015 vs 2010, 95% CI 1.77-2.08, p &lt; 0.0001), or lived in an area of high MHI (OR 1.24 for MHI of &gt; $69,311 vs &lt; $49,265, 95% CI 1.14-1.35, p &lt; 0.0001). Patients were less likely to be tested if they had Medicaid (OR 0.83, 95% CI 0.77-0.88, p &lt; 0.0001), were unmarried (OR 0.78, 95% CI 0.75-0.82, p &lt; 0.0001), or had rectal cancer (OR 0.79, 95% CI 0.74-0.84, p &lt; 0.0001). The risk of death was decreased in patients who received KRAS testing (HR 0.77, 95% CI 0.75-0.80, p &lt; 0.0001). The median survival for patients who were tested was 20 months (95% CI 20-21), vs 11 months (95% CI 10-11) for patients not tested (p &lt; 0.001). Conclusions: We found a low rate of KRAS testing overall in CRC patients diagnosed between 2010 and 2015. Testing rates increased over the study period, but, even as of 2015, the majority of patients did not have KRAS testing.We found thatpatients with Medicaid and those who lived in areas of lowest income were less likely to have KRAS testing. Prior studies reported that Medicaid was associated with lower utilization of KRAS testing, but ours represents a more contemporary cohort and is the first to evaluate Medicaid and MHI simultaneously. Ideally Medicaid insurance would increase access to molecular testing for patients with limited resources, but our model suggests that income-based disparities persist despite Medicaid insurance.
A few points on guideline for primary care of bronchial asthma(2018)
Authors: Chunhua Chi
Journal: BMJ (2018)

简要介绍了本次《支气管哮喘基层诊疗指南（2018年）》的制定工作及其特色，并简述了与《支气管哮喘防治指南（2016年版）》及2013年颁布的《中国支气管哮喘防治指南（基层版）》比较，本版指南的关键更新点。
Urethral catheter balloon dilatation for severe intrauterine adhesion after hysteroscopic surgery
Authors: Liang-bin Xia, Ai-bin Li, Jing Yang, Jing Hu, Ming Li
Journal: BMJ (2008)

This study was to investigate the role of urethral catheter balloon dilatation(F16)in the treatment of intrauterine adhesion after hysteroscopic surgery.A total of 523 patients with severe intrauterine adhesion(IUA)following hysteroscopic surgery underwent urethral catheter balloon dilatation during April2000 and December 2005.During 3～15 months'follow-up,normal menses were seen in 340 patients (65.0％),nearly normal menses in 165 patients(31.5％),and menoschesis in 18 patients(3.4％).302 patients showed normal uterine cavity with no recurrent endometrial adhesion,203 patients(38.8％)were found slight IUA,and only 18 patients(3.4％)still presented with severe adhesion.No operative complication was reposed.and the pregnant rate was 47.6％.In summary.urethral catheter balloon dilatation.based therapeutic strategies is safe.effective and beneficial.

Key words: 
Adhesions; Hysteroscopy
Retrospective analysis of immune-related adverse events (irAE) in metastatic renal cell carcinoma (mRCC) patients treated with first-line ipilimumab and nivolumab (I+N).
Authors: Kunal Desai, Lisa A. Rybicki, Amanda Nizam, Laura S. Wood, Kimberly D. Allman, Allison Martin, Cassandra Calabrese, Timothy D. Gilligan, Shilpa Gupta, Moshe Chaim Ornstein
Journal: Journal of Clinical Oncology (2020)

e17094 Background: Incidence of irAEs has grown with increasing use of immunotherapies and can affect multiple organ systems: I+N followed by N maintenance is approved as front-line therapy for intermediate &amp; poor-risk mRCC. Most common associated irAEs are gastrointestinal, dermatologic &amp; hepatic. The purpose of this retrospective, single-institution analysis is to describe irAE incidence and identify risk factors in mRCC pts treated with I+N. Methods: Patients with mRCC started on first-line I+N at the Cleveland Clinic between March 2018 and April 2019 were retrospectively reviewed. Patient demographics, tumor characteristics, radiologic response and irAE history were collected. IRAE incidence was estimated with cumulative incidence. Risk factors for IRAE were assessed with Fine and Gray competing risk regression. Results: Of forty-six (N = 46) pts with mRCC treated with 1L I+N, median age 60 (range: 34-81): 95% clear cell histology; IMDC risk 20%/56%/24% favorable/intermediate/poor respectively. 67% (N = 31) experienced ≥ 1 irAE with total of N = 44 irAEs. Most common systems affected included Gastrointestinal (27%), Musculoskeletal (23%), Dermatologic (14%) &amp; Renal (9%). Most common irAEs were colitis (23%), arthralgia (16%), transaminitis (9%). 82% of irAEs were treated with front-line glucocorticoids and 14% required additional immunosuppressants. 82% of irAEs were attributed to the I+N induction phase and 32% required discontinuation of I+N. 1 pt died as result of irAEs. Incidence of irAEs at 1, 3 and 6 months was 20%, 52%, 59% respectively. Among 31 pts who developed irAEs, median onset from start of I+N was 1.6 months (range 0-11.7). None of the variables examined (i.e. age at I+N initiation, gender, race, IMDC risk, ECOG status, stage at diagnosis, prior nephrectomy, prior radiation therapy) were identified as statistically-significant risk factors for irAEs. Development of irAEs was not associated with progression-free survival (PFS). Conclusions: IRAEs from I+N in mRCC tend to occur early in treatment course and are associated with high rates of treatment discontinuation and need for corticosteroids and other immunosuppressants. The lack of association between baseline factors and development of irAEs should increase physician alertness to potential irAEs with any change in clinical status.
Clinical effect of sequential therapy of LEN combination with anti-PD1 antibody in uHCC patients who progressed on LEN treatment: A real-world data in China.
Authors: Yi Chen, Lan Zhang, Ningling Ge, Yanhong Wang, Zhenggang Ren
Journal: Journal of Clinical Oncology (2020)

e16654 Background: Lenvatinib (LEN) has been used in clinical practice because of its high response rate since administrated in China. However, no recommendation is available as second-line agents after LEN treatment. The combination therapy of anti-programmed death-1(PD1) antibodies with LEN have demonstrated promising clinical efficacy in advanced HCC. Some patients were used this combination treatment after progressed on LEN in real world settings in China. Preclinical studies also showed the immune-moderate effects of LEN. This study was retrospectively analyzed the efficacy and safety of 26 unresectable HCC patients treated with LEN and anti-PD1 antibody after progressed on LEN. Methods: Unresectable HCC (uHCC) patients who treated with the combination of LEN with anti-PD1 antibody after progressed on LEN were enrolled. Patients who combine other loco-treatment and systemic therapy during the LEN combination with PD-1 antibody treatment period were excluded. The efficacy of LEN and anti-PD1 antibody was evaluated by mRECIST criteria after 2 cycles of combination treatment. AE data were recorded during the combination treatment period. Results: From October 2018 to October 2019, 26 patients were finally enrolled. As of January 10, 2020, median follow-up was 6.7±3.19 months. Median age was 56.15±11.9 years old, 80.77% (21/26) was Child-pugh(CP) A while 19.23% (5/26) was CPB7 and 88.5% (23/26) was BCLC stage C. Before combination therapy, 11 patients (42.31%) used LEN only and the other 15 patients (57.69%) were experienced sorafenib/chemotherapy before LEN. Drugs of PD1 antibodies were Keytruda and Toripalimab. The median duration of combination treatment was 6.7±3.15months. The ORR was 26.9% in total 26 cases. 2 cases of them were complete response, and the disease control rate (DCR) was 88.5% (23/26). The most common adverse events (AEs) of combination treatment were hypertension (42.31%), diarrhea (38.46%), hypothyroidism (38.46%) and anorexia (34.62%). Grade 3 or higher AEs occurred in 6 (23.08%) patients. Conclusions: This was the first real-world data of sequential therapy of LEN combination with anti-PD1 followed LEN in uHCC patients. For advanced patients who have progressed after LEN treatment, the results were promising, showing high DCR and well tolerated. 2 cases even achieve complete response. Sequential therapy may be an option for these patients. The efficacy of combination treatment needs random clinical trial to be further studied.
Cobimetinib plus gemcitabine is an active combination in KRAS G12R-mutated in previously chemotherapy-treated and failed pancreatic patients.
Authors: Bach Ardalan, Jared Addison Cotta, Miriam Gombosh, Jose Ignacio Azqueta
Journal: Journal of Clinical Oncology (2020)

4642 Background: he KRAS proto-oncogene is involved in the RAS/MAPK pathway. Various G12X mutations have been examined with the most common mutations being G12D (40%), G12V (30%), and G12R (15-20%) in pancreatic cancer patients. Throughout the course of studying the G12X mutations, we have observed that not all KRAS mutations are equal. Preclinical data shows G12R is impaired in pI3Kα signaling, as compared to KRAS G12V/D. This mechanism is important in PDAC as it allows tumor growth to be sustained. In preclinical studies, PDX derived tumors were transplanted in mice and were treated with a MEK inhibitor plus chemotherapy, which demonstrated a greater tumor regression than either agent alone. Therefore, we have decided to treat patients with Gemcitabine alongside a 2 nd generation MEK inhibitor (Cobimetinib). Methods: In our single arm study, 13 KRAS mutated pancreatic patients (KRAS G12D, G12V, and G12R) received the combination of Cobimetinib 20mg BID weekly for three weeks alongside Gemcitabine at 1000mg/m 2 weekly, followed by one week of rest. The above constitutes one cycle. Results: Patients were divided into two groups; Group 1 consists of seven patients that were KRAS G12D/G12V mutated, and Group 2 included six KRAS G12R mutated patients. In Group 1, seven patients on treatment progressed and died within two months on the study. In Group 2, one achieved PR and others stable disease. Median progression-free survival was 6.0 months (95% CI 3-9.3 months) and median OS has not been reached. All patients are alive at 8 months. Common adverse reactions include rash, fatigue, nausea, and vomiting. Cancer antigen 19-9 decreased in ≥ 50 of all patients in the latter group. We would like to report our positive study to the society. Moreover, we intend to confirm the study in a larger patient cohort. Conclusions: Pancreatic cancer patients that demonstrate KRAS G12R mutations are treatable with a new active combination chemotherapy.
Checkpoint inhibitor-associated immune-related adverse events as harbinger of favorable clinical outcome: Systematic review and meta-analysis.
Authors: Robin Park, Laércio Lopes da Silva, Anwaar Saeed
Journal: Journal of Clinical Oncology (2020)

e15129 Background: Recent studies have observed an association between immune-related adverse events (irAE) and favorable clinical outcomes in the setting of cancer treatment with immune checkpoint inhibitors (ICI). However, results have been variable and inconclusive. Therefore, we have conducted a pan-cancer meta-analysis evaluating the relationship between irAEs and clinical outcomes. Methods: The search included PubMed, Embase, and Web of Science from conception to 12.28.2019 as well as abstracts published in the ASCO and ESMO meetings from 2015 to 2019. Studies were included if ICI was used in advanced or metastatic cancer settings and excluded if data contained only combination therapy regimens or contained anti-CTLA-4. Pooled sensitivity (SN), specificity (SP), positive (PPV) and negative predictive values (NPV), and odds ratios (ORs) were calculated using the 2 x 2 table and logit transformed proportions; and summary receiver operating curve (sROC) was generated using the bivariate approach for ORR. Pooled HRs were calculated using the means weighted by inverse of the variance for OS and PFS. Heterogeneity was assumed and random effects model was used throughout analyses. Results: Final analysis included 32 studies encompassing non-small cell lung cancer, melanoma, gastric cancer, renal cell carcinoma, urothelial carcinoma, and head and neck cancer. With respect to ORR, pooled SN, SP, PPV and NPV, and OR were 0.522 [0.423-0.619], 0.810 [0.771-0.844], 0.516 [0.413-0.618], 0.819 [0.764-0.864], and 4.59 [3.24-6.50] respectively. The area under the curve (AUC) derived from the sROC was 0.773. HR for OS and PFS were 0.47 [95% CI 0.37-0.60] and 0.46 [95% CI 0.37-0.56] respectively. Between-study publication bias was present for ORR, OS, and PFS but results remained significant after trim-fill analysis. Conclusions: irAEs predict OR, OS, and PFS across different types of cancer and may represent useful biomarkers in the clinical setting. [Table: see text]
Correlation Between N95 Extended Use and Reuse and Fit Failure in an Emergency Department
Authors: Nida F. Degesys, Ralph C. Wang, Elizabeth Kwan, Jahan Fahimi, Jeanne A. Noble, Maria C. Raven
Journal: JAMA (2020)

This cross-sectional study examines prevalence of fit test failure of 2 types of N95 mask (dome-shaped and duckbill) during extended use or reuse among health care workers over 2 days in April 2020 in the UCSF emergency department.
Long-lasting, irreversible and late-onset immune-related adverse events (irAEs) from immune checkpoint inhibitors (ICIs): A real-world data analysis.
Authors: Eleonora Ghisoni, Alexandre M Wicky, Sofiya Latifyan, Nuria Neisy Mederos Alfonso, Berna C. Özdemir, Michel A Cuendet, Martina Imbimbo, Laura Marandino, Julie Delyon, Camille Lea Gerard, Erica Tavazzi, Roberto Gatta, Giorgio Valabrega, Massimo Aglietta, Michel Obeid, George Coukos, Solange Peters, Massimo Di Maio, Hasna Bouchaab, Olivier Michielin
Journal: Journal of Clinical Oncology (2020)

e15095 Background: ICIs are effective in many tumors, but can cause severe irAEs, with potential long-term impact. Description of irAEs in literature is often insufficient, especially in terms of irAEs duration, and in terms of incidence of late-onset events. Namely, duration of irAEs and proportion of patients (pts) with toxicity still ongoing at data cut-off were not specified in 52 (89.6%) of 58 publications of trials leading to ICIs approval by US FDA and/or EMA up to August 2019. Real-world data are urgently needed to integrate this information. Methods: We retrieved the medical charts of all pts affected by lung cancer (LC) and melanoma (Mel) treated consecutively with approved ICIs at the Centre Hospitalier Universitaire Vaudoise (CHUV) from Jan 2012 to Dec 2019. We collected the following data: treatment setting, ICIs received, duration of each treatment, incidence of any irAEs of grade (G) ≥ 2 (according to CTCAE v5.0), time to onset and duration of irAEs. Pts with follow-up (FU) ≤ 28 days were excluded. Results: 345 pts were included (166 LC, 179 Mel), for a total of 455 ICIs treatment lines. 33 pts (7%, all with Mel) were treated in the adjuvant setting, while all the others were treated for advanced disease. 228 pts (50%) received anti-PD1, 43 (9%) anti-PD-L1, 56 (12%) anti-CTLA-4, 100 (22%) ICI-ICI combinations and 28 (6%) ICI–chemotherapy combinations. Median FU was 369 days (range 29-2903). Median duration of treatment was 71 days (range 1-1625). 196 pts (57%) experienced at least 1 G≥2 irAE for a total of 277 irAEs (22% skin, 18% gastro-intentinal [GI], 13% pneumonitis, 12% thyroid disorders, 11% hyphophisitis and 8% hepatitis). With 122/277 (44%) irAEs still on-going at our data cut-off, median duration of irAEs was 98 days; 104/277 irAEs (37%) lasted more than 6 month, of them 89% were considered irreversible. Out of 76 pts still on ICIs treatment at 6 months, incidence of G≥2 irAE with onset after 6 months was 51% (26% pneumonitis, 26% endocrine disorders, 15% skin disorders, 8% hepatitis and GI). Out of 32 pts still on ICIs treatment at 12 months, incidence of G≥2 irAE with onset after 12 months was 41% (38% pneumonitis, 23% endocrine and 15% skin disorders, 8% hepatitis and GI). Conclusions: Our real-world analysis shows that long-lasting and late-onset irAEs represent an important issue during ICIs treatment. A better description of toxicities in clinical trials is needed to allow a proper evaluation of treatment value and the impact on patients' quality of life.
重度硫化氢中毒六例
Authors: 魏兵, 李春盛
Journal: BMJ (2009)

硫化氢(H2S)为剧毒无色易燃的有害气体,广泛存在于自然界.在修理地下管道、矿井、蓄粪池、沼气池过程中容易出现急性中毒,呼吸道吸入是急性中毒的主要途径.2000年6月至2008年6月期间我科救治重度硫化氢中毒患者6例,报道如下。
iStopCancer: A database of 6,016 low pass whole genome sequencing of minimal invasive samples from 21 cancer types of Chinese population.
Authors: Min Yuan, Qian Ziliang, Juemin Fang, Zhongzheng Zhu, Jianguo Wu, Xianling Guo, Weixing Liu, Hong Qian, Qing Xu
Journal: Journal of Clinical Oncology (2020)

7062 Background: Cancer is a group of genetic diseases that result from changes in the genome of cells in the body, leading them to grow uncontrollably. Recent researches suggest Chromosome instability (CIN), which is defined as an increased rate of chromosome gains and losses, manifests as cell-to-cell karyotypic heterogeneity and drives cancer initiation and evolution. Methods: In the past two years, we initiated iStopCancer project, and characterized 4515 ‘best available’ minimal-invasive samples from cancer patients and 1501 plasma samples from non-tumor diseases by using low-pass whole genome sequencing. DNA from ‘best available’ minimal-invasive samples, including peripheral plasma, urines, pancreatic juice, bile and effusions were analyzed by low coverage whole genome sequencing followed by the UCAD Bioinformatics workflow to characterize the CINs. In total, 32T bp nucleotide (coverage =1.7X for each sample) were collected. All the data can be visualized on website: http://www.istopcancer.net/pgweb/cn/istopcancer.jsp . Results: 3748(83%) of tumors present detectable CIN (CIN score&gt;1000) in minimal-invasive samples. The missed cancer patients were majorly from patients with either tumor size less than 2cm or less-aggressive cancers, including thyroid cancer, low-grade urothelial carcinoma, lung cancer in-situ, et al. Of the 1501 non-tumor individuals, 30(2.0%) present detectable CIN (|Z|&gt;=3) at the time of sample collection, 24(80.0%) was diagnosed as tumor patient in 3-6 months follow-up. There were 9 (0.59%) of non-cancer individuals without detectable CIN were also reported as tumor patients during 6-month following up. In summary, the positive and negative prediction value is 80.0% and 99.4% respectively. The false alarms were majorly from patients with EBV activations, which indicates virus may interference chromosome stability and drove virus-associated carcinogenesis. For the patient with repeated detections, plasma cfDNA CIN dynamics predicted clinical responses and disease recurrences. Quick clearance of plasma cfDNA CIN in 2-3 weeks was found in 153 (83.6%) patients. Meanwhile, no quick clearance was found in majority of SDs/PDs (73/88=83.0%). Furthermore, cfDNA CIN predicts clinical response 2-8 weeks ahead of traditional biomarkers (CEA, CA15-3, CA199, AFP et al). Conclusions: Large-scale low coverage whole genome sequencing data provides useful information for cancer detection and managements.
Myodystonia caused by dopa reaction
Authors: 谢卉, 吴志英
Journal: BMJ (2005)

肌张力障碍是指因持续性肌肉收缩而引起的肢体扭曲、重复运动或姿势异常综合征.多巴反应性肌张力障碍(dopa-responsive dystonia,DRD)以应用左旋多巴有效为特征,是一种较为少见的遗传性锥体外系疾病.因DRD发病率低,临床表现多种多样,常易误诊为脑瘫、脑炎、帕金森病等,故临床医师有必要提高对本病的认识,减少误诊,从而避免因长期肌张力障碍所致的畸形,减轻患者的痛苦。
心尖肥厚型心肌病诊治进展
Authors: 邵兴慧, 杨艳敏
Journal: BMJ (2011)

心尖肥厚型心肌病(apical hypertrophy cardiomyopathy,AHCM)是非梗阻性肥厚型心肌病的一个亚型,心肌肥厚主要局限于左室乳头肌水平以下的心尖部[1].1976年由sakamoto等人首次报道,1979年yamaguchi对此病进行详细描述,并命名为“日本心肌病”[2].根据既往资料来看,此病在日本人中发病比例较高,约占所有肥厚型心肌病的25％,但是在非亚洲人种中的比例较低,为1％～2％[3-5].由于AHCM在临床中为少见病[6],心电图改变极易与冠心病、心肌梗死相混淆,超声心动图如不仔细观察心尖部容易漏诊,所以加强对此病的认识尤为重要。
Hirayama disease: a report of two cases and literature review
Authors: Xing-yong Chen, Ming-feng Chen, Rui-ling Zhou
Journal: BMJ (2011)

To analyze clinical, neuro-electrophysiologocal, imaging and pathological characteristics of Hirayama disease (HD) and review its relevant literatures to improve its diagnosis. Clinical data of two HD cases admitted to Fujian Provincial Hospital, Fuzhou during 2005 to 2008 were analyzed with literatures review. HD occurred more in males, often onset at their adolescence with muscular weakness and atrophy in one or two upper limbs, but without sensory dysfunction or pyramidal signs. Neuro-electrophysiology showed neurogenic abnormality in the body areas dominated by the 4th cervical vertebra to the 1 st thoracic vertebral (C4-T1) spinal nerves in all the patients. Magnetic resonance imaging (MRI) showed slight atrophy of the lower cervical spinal cord at routine position and its compression and forward displacement to varied extent at flexion position, with posterior epidural capsular space widening, crescent or striped high signal, and voids of vessels in some patients. Enhancement magnetic resonance scanning showed crescent sign enhanced in some patients. Biopsies of the inflicted muscles appeared slight neurogenic abnormality in some cases, and normal in other cases. HD is rarely seen clinically, but it can usually be diagnosed according to its symptoms, neuro-electrophysiology and MRI.

Key words: 
Mascular atrophy;  Magnetic resonance imaging