tbuckley/cabot-search huggingface dataset:
A new PMS2 gene variant of unknown significance: How pathogenic is it?
Authors: Clarissa Gondim Picanço-Albuquerque, Maria Júlia Barbosa Bezerra, Paulo Goberlanio de Barros Silva, Rosane Oliveira Sant'Ana, Maria Claudia dos Santos Luciano, Isabelle Joyce de Lima Silva-Fernandes, Marcos Venicio Alves Lima
Journal: Journal of Clinical Oncology (2020)

e13532 Background: The Lynch syndrome (LS) is the most common inherited syndrome associated with colorectal cancer (CRC). The hallmark of LS is DNA mismatch repair deficiency. The amount of variants of uncertain significance (VUS) in suspected LS confounds diagnosis, requiring surveillance of variant reclassifications. In this paper we describe a new and most likely pathogenic VUS in PMS2. Methods: Patient screened for personal and familial cancer and evaluated with NGS gene panels for 31 genes. The protein structure was analyzed with the software Pymol. Results: A woman diagnosed with breast cancer (BC) at 60 years and CRC at 65 years was investigated due to her extensive family history of cancer (21 maternal relatives), including 6/9 siblings [gastric n = 1, lung n = 1, BC n = 4 (one of whom with BC, endometrium and CRC)], 8/12 aunts and uncles, all of whom died of cancer (gastric n = 4, CRC n = 1, CNS n = 1, BC n = 1; uterus/gallbladder n = 1), and 7 cousins (CNS n = 3, lung n = 1, gastric n = 2, suspected ovary n = 1). The new PMS2 gene variant c.134A &gt; G(p.Asn45Ser), which was also detected in two sisters with CRC submitted to segregation analysis, occupied the same locus as a known pathogenic variant, c.134A &gt; C(p.Asn45Thr). The structural analysis showed that the mutated locus encodes a serine instead of an asparagine in position 45 at the enzyme’s active site. Asn 45 is a conserved amino acid that binds to ATP in protein structure (PDB = 1EA6). Interestingly, this is close to position 42-44, for which another potentially pathogenic VUS (p.Leu42_Glu44del) has been described. Conclusions: Based on our patient’s personal and family history and on the locus variant and protein structure analysis, the new PMS2 gene variant described in this paper is most likely pathogenic.
A single-arm, open-label, phase I study of CPI-613 (Devimistat) in combination with gemcitabine and nab-paclitaxel for patients with locally advanced or metastatic pancreatic adenocarcinoma.
Authors: Angela Tatiana Alistar, Bonny Morris, Lawrence Harrison, Kai Bickenbach, Lee Starker, Nancy Ginder, Laura McIlwain, Sanjeev Luther, Timothy S. Pardee, Justin Alpert
Journal: Journal of Clinical Oncology (2020)

4635 Background: Glycolic and mitochondrial metabolism are aberrant in pancreatic cancer and translate into chemoresistance. Inhibition of glutamine metabolism can potentially synergize with therapies that increase intracellular reactive oxygen species, such as nab-paclitaxel. CPI- 613 is a novel antimitochondrial agent developed by Rafael Pharmaceuticals that showed promising clinical activity in combination with modified FOLFIRINOX in patients with stage IV pancreatic cancer. Preclinical data suggested possible synergy of CPI-613 with nab-paclitaxel. Methods: Single arm, open-label, phase I study of CPI-613 with gemcitabine and nab-paclitaxel in patients with locally advanced or metastatic pancreatic cancer to determine MTD, safety, and preliminary efficacy of CPI-613 in combination with chemotherapy. Key eligibility criteria included: histologically documented and measurable locally-advanced or metastatic, PDAC. ECOG performance status 0-2; and first line systemic treatment. CPI-613 was infused intravenously with a starting dose of 500 mg/m 2 followed by modified dose nab-paclitaxel (100mg/m2) and gemcitabine ( 800 mg/m2) on Days 1, 8, and 15 of a 28-day cycle. The the primary endpoint, the MTD of CPI-613 was determined by a two-stage, dose-escalation schema, with 6-month treatment duration for patients exhibiting treatment response. Secondary endpoints were treatment-related adverse events, complete response (CR) and partial response (PR). Results: From February 2018 to 2020, 26 patients were screened, (23 metastatic and 3 locally advanced), 22 patients enrolled and 18 patients underwent a restaging scan. As of the time of submission 3 patients are still on active treatment. Patient demographics were: median age of 65, ECOG was 0-1, The MTD of CPI- 613 was determined to be 1500 mg/m 2 . The dose limiting toxicities were not achieved. Overall the treatment was well tolerated with toxicities mainly related to chemotherapy; most common grade 3 and 4 toxicities were hematologic toxicity and neuropathy. 1 patient achieved CR, 9 PR, 8 stable disease and 1 progressive disease for an objective response rate of 50% with a CR rate of 5.5%. Conclusions: The results demonstrate that CPI 613 can be safely administered with gemcitabine and nab-paclitaxel at doses up to 1,500 m/g2. Efficacy data suggest synergy with chemotherapy. Further clinical studies of CPI-613 efficacy in pancreatic cancer are in progress. Clinical trial information: NCT03435289 .
Willingness of local residents to accept paid influenza vaccine in Chongqing and its influencing factors: a survey
Authors: Xin Luo
Journal: BMJ (2013)

A total of 450 residents from three neighborhood committees of Ba'nan were selected to assess their willingness to accept paid influenza vaccine and the influencing factors. Among them, 273 (60.7%) were willing to accept paid influenza vaccine. Age, economic status, health, flu recognition and vaccine approval were the major influencing factors of vaccination.


Key words: 
Influenza vaccines; Questionnaires
回盲部非霍奇金淋巴瘤一例误诊分析
Authors: 严兴敬
Journal: BMJ (2010)

患者男性,15岁.因右下腹疼痛10 d,伴恶心、呕吐,于2008年8月17日入院.入院查体:体温36.4℃,脉搏72次/min,呼吸18次/min,血压110/90 mm Hg(1 mm Hg=0.133 kPa)。
MRI characters of 52 cases of septate uterus
Authors: Shi-jia Wang, Zhi-gang Han, Xiao-mei Tian, Jie-lin Xie, Meng-wei Zhang, Di Zhang, Guo-fi Zhang
Journal: BMJ (2012)

Magnetic resonance imaging (MRI) findings of 52 patients with septate uterus were retrospectively analyzed.There were 19 cases of complete septate uterus and 32 cases of partial septate uterus confirmed by hysteroscopy or hysteroscopy combined with laparoscopy,and 1 case without surgery.According to MRI findings,19 cases were diagnosed as complete septate uterus,32 cases as partial septate uterus and 1 case as intrauterine adhesion.The results indicated that MRIcan be used in diagnosis of septate uterus.

Key words: 
Uterus diseases;  Magnetic resonance imaging
她为什么口渴多尿
Authors: 曾昭耆
Journal: BMJ (2008)

一位女教师,39岁,诉口渴多尿已3个月.患者既往体健,喜欢运动.近3个月来感觉特别口干、躁热,常需大量喝凉开水和冷饮;多尿,给学生上一节课(45分钟)即需小便,排出尿量较多,晚间饮水也多,夜尿3次以上,每次排尿后也需饮一大杯水.患者丈夫在医院工作,曾请该院医生看过。
Staging work up in chondrosarcoma: Is a bone scan warranted for the metastatic workup of chondrosarcoma?
Authors: Ashish Gulia, Ajay Puri, Vineet Kurisunkal, Srinath Gupta
Journal: Journal of Clinical Oncology (2020)

e23508 Background: To assess the value of a bone scan in the metastatic workup of a patient diagnosed with chondrosarcoma of bone. Methods: Retrospective analysis. 480 patients of extremity chondrosarcomas were identified with the help of nuclear imaging records and pathology department data base over a period of 12 years. Their clinical, radiological and histopathological details were retrieved from case files and electronic medical records. All cases were staged with a CT scan of thorax and bone scan or a whole body PET-CT. All reported and suspicious cases of metastasis were reviewed again by an experienced radiologist for this study. 53 patients had to be excluded from the study due to incomplete staging modalities. Results: 427 patients were available for final evaluation. Grade was not available for 3 patients. No grade I chondrosarcoma (53) had evidence of metastasis. In the remaining high grade chondrosarcomas (374), isolated lung metastasis was seen in 9% (35 cases) (grade II-31, grade III-4), combined lung and bone metastasis was seen in 0.5% (2 cases) (all grade II) and isolated bone metastasis was seen in 1 % (4 cases) (all grade II). Conclusions: The present study shows that the incidence of bony metastasis in extremity chondrosarcomas is extremely low. A non-contrast CT thorax would be adequate for staging in conventional chondrosarcomas. In light of the present results we feel bone scan may be omitted from the staging work up of conventional skeletal chondrosarcomas. It may be reserved for only symptomatic patients.
Correlation of response with progression-free (PFS) and overall (OS) survival in relapsed/refractory Ewing sarcoma (RR-ES): Results from the rEECur trial.
Authors: Keith Wheatley, Bryar Kadir, Maria Khan, Nicola Fenwick, Nathalie Gaspar, Jukka Kanerva, Thomas Kuehne, Alessandra Longhi, Cristina Mata, Marianne Phillips, Kirsten Hall, Akmal Safwat, Claudia Valverde Morales, Andrew J. Westwood, Mark Winstanley, Abigail Evans, Sandra J Strauss, Uta Dirksen, Jeremy Whelan, Martin G. McCabe
Journal: Journal of Clinical Oncology (2020)

11524 Background: Survival for RR-ES at 5 years remains &lt; 15%, so novel treatments are needed. Almost all Phase II trials for RR-ES use response as the primary outcome measure. It is unclear whether response is a valid surrogate for survival outcomes. Methods: Patients (pts) were eligible if they had RR-ES and were evaluable for imaging response (primary outcome) if they had measurable disease by RECIST 1.1. The randomization was initially between four chemotherapy regimens: topotecan-cyclophosphamide, irinotecan-temozolomide, gemcitabine-docetaxel (GD), high-dose ifosfamide. Response was assessed after 2, 4 (primary) and 6 cycles of therapy and was classified as complete response (CR), partial response (PR), stable disease (SD), progressive disease (PD). PFS and OS were secondary outcomes. Survival from each assessment point by response status was analyzed, by Cox models, with hazard ratios (HR) given for PR v. SD and CR+PR v. SD. Results: From 2015-19, 241 pts with response data were entered. The relationship between response status and PFS and OS is shown in the table (HR &lt; 1.0 indicates better outcome for PR or CR+PR than SD). Both PFS and OS were similar for pts with PR or CR+PR compared to those with SD. OS was inferior for patients with PD (all p &lt; 0.01) (PFS is by definition zero for patients with PD at that timepoint). Small numbers mean CR results are not reliable. Results were consistent across all treatments and between refractory and relapsed disease. At the first interim assessment the GD arm was dropped, with risk ratios for response compared to the other three arms (blinded as still open) of 0.3, 0.5 and 0.5. If a new outcome – disease control (CR+PR+SD) – is defined, the risk ratios are 0.7, 0.8 and 0.7; i.e. still inferior for GD, but less so. Conclusions: Response does not correlate with survival outcomes in RR-ES, so considering PR, or even CR, a success and SD a failure when evaluating treatments may be misleading. We propose PFS as a better primary outcome for future trials and it will be introduced as such in the rEECur trial. Clinical trial information: ISRCTN36453794 . [Table: see text]
Effect of significant incidence of Braf p.V600E mutations in esophageal cancer on potential use of tyrosine kinase inhibitors.
Authors: Thurai Moorthy, Chrishanthi Rajasooriyar, Anusha Ginige, Niluka Ranatunge, Rajendra Surenthirakumaran
Journal: Journal of Clinical Oncology (2020)

e16591 Background: Routine diagnosis of esophageal cancer varies from locally advanced to metastatic at presentation. Most of these patients are cachectic at presentation and physically not suitable for radical tri-modality treatment as per the CROSS trial. Hence, the prognosis of esophageal cancer remains guarded. Presently, tyrosine kinase inhibitors (TKI) are successfully used in treating melanoma, non-small cell lung cancer, and a possibility for treating esophageal cancer. Allele Specific Multiplex Sequencing (ASMS) detects somatic mutations in samples with low mutant copies and in the presence of overwhelming wild type. Hence, we have re-evaluated and are reporting the findings of the incidence of Braf p.V600E in esophageal cancer using ASMS. Methods: DNA was extracted from 40 formalin fixed paraffin embedded tumor tissue (FFPE) samples that were collected from patients with squamous-cell carcinoma of the esophagus. The Braf p.V600E/K mutations were analyzed using ASMS. All positive results were confirmed by bi-directional ASMS. The results were correlated with patients’ demographic and pathological data. Results: Overall incidence of Braf p.V600E was 92.5% and was present in all stages (IB, IIB, IIIA, IIIB, IIIc and IV) of esophageal cancer. There was no difference in the incidence of Braf p.V600E between patients who smoke, consume alcohol, chew betel or any combination, and those who do not. There is also no gender difference in the incidence of Braf p.V600E. Conclusions: Braf p.V600E is a pivotal driver mutation in the MAPK pathway. Firstly, the data shows incidence of Braf. p.V600E is higher than what is reported in literature and paves the way for follow up with further studies for possible use of TKI targeted chemotherapies. Secondly, incidence of Braf p.V600E mutations could be independent of known cancer etiology (e.g. smoking, consumption of alcohol, chewing betel).
慢性阻塞性肺疾病急性加重期继发肺部真菌感染临床分析
Authors: 杨云桥, 杨志彦, 郑颖妮, 邓淑娇
Journal: BMJ (2012)

回顾性分析2007年12月至2010年3月住院的30例慢性阻塞性肺疾病急性加重期患者的资料.白色念珠菌为主要致病菌,占90％(27例);感染高峰时间在疗程的第7天左右,主要症状为咳出拉丝样痰(47％,14例)和气喘(37％,11例)。
Circadian variation in nivolumab efficacy in patients with advanced non-small cell lung cancer.
Authors: Abdoulaye Karaboué, Laurence Bisseux, Ida Pavese, Thierry Collon
Journal: Journal of Clinical Oncology (2020)

e21585 Background: Despite efficacy of human checkpoint inhibitors, only 20 to 30% of treated patients present long term benefits. Circadian variations of the delivery of nivolumab to patients with advanced non-small-cell lung cancer (NSCLC) are proposed here as a factor potentially influencing the efficacy. Methods: A total of 1318 courses of nivolumab were administered in 57 consecutive patients with advanced NSCLC from September 2015 to December 2019 in Medical Oncology Unit of Montfermeil hospital. Percentage of total dose per patient delivered before and after 12:00 pm was computed and corelated to objective response rate (ORR), progression free survival (PFS) and overall survival (OS). Results: Twenty eight patients (49%) received ≥ 50% of their treatment before 12:00 pm (morning group) and 29 patients (51%) after 12:00 pm (afternoon group). ORR was 53.6% in morning group and 31.0% in afternoon group; p = 0.083. Both PFS and OS were significantly longer in morning group as compared to afternoon group. Median PFS was 18.6 months [95%CL, 8.6 – 28.7] and 3.5 months [2.9 – 4.1] in morning and afternoon group respectively; p &lt; 0.001. After a maximum follow-up of 48 months, median OS was not reached in morning group whereas it was 14.4 months [0.0 – 29.5] in afternoon group; p = 0.004. Conclusions: The significant difference in the efficacy of nivolumab between morning and afternoon group is indirect evidence of the influence of circadian rhythm on the metabolism of this checkpoint inhibitor. The application of this finding in clinical practice should allow an increase of nivolumab efficacy in patients with advanced NSCLC.
KEYNOTE-048: Progression after the next line of therapy following pembrolizumab (P) or P plus chemotherapy (P+C) vs EXTREME (E) as first-line (1L) therapy for recurrent/metastatic (R/M) head and neck squamous cell carcinoma (HNSCC).
Authors: Kevin Joseph Harrington, Danny Rischin, Richard Greil, Denis Soulieres, Makoto Tahara, Gilberto Castro, Amanda Psyrri, Neus Baste, Prakash C. Neupane, Åse Bratland, Thorsten Fuereder, Brett Gordon Maxwell Hughes, Ricard Mesia, Nuttapong Ngamphaiboon, Tamara Rordorf, Wan Zamaniah Wan Ishak, Yayan Zhang, Burak Gumuscu, Ramona F. Swaby, Barbara Burtness
Journal: Journal of Clinical Oncology (2020)

6505 Background: 1L P vs E improved OS in PD-L1 CPS ≥20 and CPS ≥1 populations, and led to noninferior OS in the total population, with favorable safety; 1L P+C vs E had superior OS in CPS ≥20, CPS ≥1, and total populations with comparable safety in the phase 3 KEYNOTE-048 study (NCT02358031) in patients with R/M HNSCC. Neither P vs E nor P+C vs E improved PFS in the PD-L1 CPS ≥20, CPS ≥1, or total populations. Here, we present the progression after the next line of therapy (PFS2) to assess the effect of 1L P or P+C and subsequent anticancer therapy on patient outcomes. Methods: Patients with locally incurable R/M HNSCC and no prior systemic therapy in the R/M setting were randomly assigned 1:1:1 to P, P+C, or E. PFS2 was defined as time from randomization to objective tumor progression on next-line therapy or death from any cause. PFS2 was estimated using the Kaplan-Meier method as an exploratory outcome confined to those receiving subsequent therapy after 1L P. HR and 95% CIs were based on a Cox regression model with Efron’s method of tie handling with treatment as a covariate (stratified by ECOG performance status [PS], HPV status, and PD-L1 for CPS ≥1 and total populations; by ECOG PS and HPV status for CPS ≥20 population). Data cutoff: Feb 25, 2019. Results: Of 882 (301 [P]; 281 [P+C]; 300 [E]) treated patients,422 (P: 148 [49.2%]; P+C: 115 [40.9%]; E: 159 [53.0%]) received subsequent anticancer therapy after 1L P, most commonly C (P: 135 [44.9%]; P+C: 88 [31.3%]; E: 102 [34.0%]); EGFR inhibitor (P: 59 [19.6%]; P+C: 37 [13.2%]; E: 19 [6.3%]); and immune checkpoint inhibitor (P: 6 [2.0%]; P+C: 12 [4.3%]; E: 50 [16.7%]); patients may have received more than one type of subsequent therapy. Median PFS2 is reported in Table. Conclusions: In patients with R/M HNSCC, longer median PFS2 was observed in the CPS ≥20 and CPS ≥1 populations for P vs E, and in the CPS ≥20, CPS ≥1, and total populations for P+C vs E. These data further support use of 1L P or P+C in patients with R/M HNSCC. Clinical trial information: NCT02358031 . [Table: see text]
The emergency management of hematochezia caused by non-ulcerous duodenum diseases
Authors: Yi Ma
Journal: BMJ (2008)

The clinical data of 23 cases with emergent hematochezia endoscopically diagnosed as non-ulcerous duodenum diseases were retrospectively analyzed.Majority of cases were misdiagnosed and delayed to transfer to emergency room because of lack of knowledge and experiences of local medical workers.After referral to our emergency department,all 23 cases obtained appropriate management and cured successfully.

Key words: 
Gastrointestinal hemorrhage; Emergency medical service
Alliance A151804: Establishment of a national biorepository to advance studies of immune-related adverse events.
Authors: David E. Kozono, Elad Sharon, Jennifer Le-Rademacher, Erin Twohy, Tyler J. Zemla, Yujia Wen, Mark Watson, Elie G. Dib, John M. Kirkwood, Gary H. Lyman, Jarushka Naidoo, Andrew B. Nixon, Elizabeth A. Mittendorf
Journal: Journal of Clinical Oncology (2020)

TPS3154 Background: Immune-related Adverse Events (irAEs) are rare but serious sequelae of treatment with immuno-oncology (IO) therapeutics. These therapeutics, including monoclonal antibodies targeting programmed cell death protein 1 (PD-1), programmed death-ligand 1 (PD-L1) and cytotoxic T-lymphocyte-associated protein 4 (CTLA-4), have had transformative effects on outcomes for patients (pts) with advanced cancers. Although most pts tolerate the therapies well, a few experience irAEs ranging in severity up to life-threatening. These irAEs involve diverse organs including the heart, kidney, liver and lung, and gastrointestinal, musculoskeletal, central and peripheral nervous systems. Because of the relatively low incidence and wide variety of irAEs due to various immunotherapies for multiple tumor types, establishment of an efficient centralized repository for acquisition and organized distribution of well-annotated biospecimens is vital for translational studies that improve understanding of the molecular pathogenesis and treatment of these significant toxicities. Methods: This multi-institutional study is open at sites across the National Clinical Trial Network to pts who received ≥ 1 IO therapeutics (e.g., CTLA-4, PD-1 or PD-L1 inhibitor) and experienced 1) ≥ 1 serious (grade 3–5) adverse events that are likely immune-related, 2) rare infection or 3) tumor hyperprogression. IrAEs of interest include myocarditis, colitis, hepatitis, nephritis, myositis, pneumonitis, meningitis/encephalitis, dermatitis, endocrinopathies and neuropathy. Pts may be on an NCTN or non-NCTN IO trial or be receiving standard-of-care therapy. Registration must occur ≤ 72 hours after confirmation of the irAE event. Clinical data are collected at registration, 1 month after registration and for up to 1 year. Biospecimens (tumor blocks, biopsies of inflammatory tissues used to establish irAE diagnosis, and serial blood samples for isolation of plasma, serum and peripheral blood mononuclear cells) are collected at 1-2 timepoints. Stool samples are collected from pts experiencing colitis. Imaging data are collected for pts with hyperprogression or pneumonitis. Goal accrual is 240 pts. Biospecimens and data will be made available to investigators following future submission and approval of proposals. Support: U10CA180821, U10CA180882, U24CA196171; U10CA180820 (ECOG-ACRIN); U10CA180888 (SWOG); U10CA180868 (NRG); https://acknowledgments.alliancefound.org; Clinical trial information: NCT04242095 .
Long-term effect of Fu Fang Jiang Ya Pian on patients with stage 1 or 2hypertension
Authors: 李振华, 王丽华, 张纪荣, 刘兆军, 延军, 袁振祥, 陈善华, 郎咸泉, 崔晓亮
Journal: BMJ (2005)

目的 观察服用复方降压片2年的1或2级原发性高血压患者的降压效果及该药对血糖、胰岛素、尿酸、血脂水平的影响.方法复方降压片以小剂量开始逐渐加量至血压稳定24周后,再逐渐减药,最终以最小的剂量、最少服药次数保持稳定的正常血压;在治疗前后进行血糖、胰岛素、血钾、总胆固醇、甘油三酯、尿酸等检测.结果98例轻中度高血压病患者2年血压控制有效率为74.5%(73/98),服药次数每日1次者48例(49%),每日2次者33例(33.7%),每日3次者17例(17.3%);治疗前后血糖、胰岛素、血钾、总胆固醇、甘油三酯、尿酸等无明显变化(P>0.05),患者无心脑血管并发症发生.结论复方降压片长期应用降压效果良好,半数病例每日1次服药可获得满意的降压效果,不良反应少。