tbuckley/cabot-search huggingface dataset:
Outcome of immune checkpoint inhibitor (ICI) related diarrhea/colitis (IMDC) in cancer patients with superimposed GI infections.
Authors: Weijie Ma, Hamzah Abu-Sbeih, Yuanzun Peng, Pablo Okhuysen, Yinghong Wang
Journal: Journal of Clinical Oncology (2020)

e15166 Background: ICI therapies have revolutionized the landscape of cancer treatment. However, their increased use has also contributed to adverse events, e.g. IMDC. Clinically it is difficult to distinguish between infectious etiology or IMDC. It is unclear whether antimicrobial treatment substantially impacts the disease course. Here, we evaluated the characteristics and outcome of IMDC in cancer patients with superimposed diarrheagenic GI infections. Methods: We retrospectively evaluated cancer patients who received ICI with clinical symptoms of IMDC and confirmed stool microbiology of E. coli or non-CMV viral infections either at the time of IMDC, or within 60 days after IMDC diagnosis at MD Anderson Cancer Center 01/2011-08/2019. We described the disease course and outcome of IMDC based on their status of GI infection and antimicrobial treatment. Results: Total 72 patients were included, among them, 50 control patients with IMDC and no GI infection, 22 had diarrheagenic infections, composed of 17 E coli pathogens: Enteropathogenic, Enterotoxigenic, Enteroaggregative, and E coli 0157:H7 serotype; and 5 viral etiologies: Adenovirus, Norovirus, and Sapovirus. Patients in the infection group had higher grade of colitis (42.9% vs 18.4%, P = 0.041), and more frequent hospitalization (86.4% vs 62%, P = 0.052). 68.2% patients in the infection group received infliximab/vedolizumab add-on treatment compared to 40% in the no infection group (P = 0.078). Patients with GI infection and antimicrobial treatment had much higher IMDC recurrence rate than no antimicrobial treatment (50% vs 0, P = 0.015). GI infection was not associated with higher IMDC recurrence or worse overall survival of these patients. Conclusions: IMDC can occasionally be complicated by infection from common GI pathogens. Antimicrobial treatment was mostly used in severe IMDC cases and did not circumvent the need for immunosuppressant or improve the clinical outcomes. GI infection was not associated with higher IMDC recurrence or worse overall survival of these patients. [Table: see text]
Presenting international prognostic scoring system affects time to treatment: A retrospective single center review.
Authors: Sierra Sutcliffe, Indryas Woldie, Caroline M. Hamm
Journal: Journal of Clinical Oncology (2020)

e20058 Background: Diffuse large B cell lymphoma (DLBCL) is an aggressive form of non-Hodgkin’s lymphoma, which requires prompt initiation of chemotherapy to cure, as any delays can result in worse outcomes. A recent study in Japan found that patients with an IPI score ≥3 had a worse prognosis if their diagnosis was delayed, whereas with an IPI score &lt; 3, there was no effect. Methods: This study investigated how long Windsor patients wait to receive chemotherapy after diagnosis, and how this affects relapse status. A retrospective chart review was conducted, looking at all patients diagnosed with DLBCL who underwent treatment at the Windsor Regional Cancer Center from 2007 to 2018 (N = 317). Each chart was reviewed for variables relating to treatment and outcomes. Results: Overall survival within the studied time period was 71% with the median survival time of 11.99 years. The overall relapse rate was 19.24% with a mean relapse-free interval of 4.87 years. A longer time to initial treatment resulted in a decreased risk of relapse (p = 0.038); however, these patients tended to have a lower stage (p = 0.002), no family history of cancer (p &lt; 0.001), and lower IPI scores (p = 0.004). When broken down by IPI score, the mean times to treatment after diagnosis were: IPI 0 = 40 days; IPI 1 = 35 days; IPI 2 = 38 days; IPI 3 = 29 days; IPI 4 = 22 days; IPI 5 = 29 days. Conclusions: These results show that while DLBCL patients with worse prognostic measures are prioritized to receive treatment quicker, there is a large discrepancy in time to treatment between IPI scores. There was an 11-day delay between early and late IPI scores, likely driven by patient symptoms, rather than evidence of safety. The natural history of DLBCL is known to be aggressive, but more granular information is necessary to determine appropriate wait times for presenting IPI score. Further research should focus on identifying delays in the process, and if it can be streamlined to improve wait times for all patients, regardless of IPI score.
Efficacy and safety of IO103 a novel anti PD-L1 vaccine in basal cell carcinoma.
Authors: Nicolai Grønne Jørgensen, Jeanette Kaae, Jacob Handlos Grauslund, Özcan Met, Inge Marie Svane, Eva Ehrnrooth, Mads Hald Andersen, Claus Zachariae, Lone Skov
Journal: Journal of Clinical Oncology (2020)

e22070 Background: Basal cell carcinoma (BCC) is the most frequent malignancy. Case reports have described effect of immune checkpoint blocking antibodies (ICB) against PD-1 in BCC (Cannon et al. 2018, Chang et al. 2017, Ikeda et al. 2016, Winkler et al. 2017). Autoimmune side effects of ICB are well known and limits a wider use in BCC. IO103 is a peptide vaccine against major programmed death (PD) ligand 1 (PD-L1). In a first-in-man study of IO103 in patients with multiple myeloma (NCT03042793) regression of co-existing BCC was observed in two patients which prompted the current study. Methods: A single arm phase IIa study of subcutaneous IO103 (q2w six times followed optionally by q4w an additional 3 times) with the adjuvant Montanide for patients with BCC (NCT03714529). Eligible patients had at least one biopsy verified BCC suitable for sequential biopsies, and no severe autoimmune comorbidity. The primary endpoints were categorical clinical responses of target tumors, percent change in largest diameter of target tumor and immune responses to the vaccine. Secondary endpoint was safety. One tumor per patient was designated target tumor, if more than one tumor the remaining were designated non-target tumors. Only target tumors were sequentially biopsied during vaccinations. Results: Ten patients were included at the department of Dermatology, Herlev and Gentofte Hospital, Denmark between November 19 th , 2018 and October 21 st , 2019. Based on target lesion assessment, one patient achieved partial response. Two additional patients achieved CR in non-target lesions, including one lesion that had recurred after previous surgery. Categorical clinical responses are given in table. Adverse events were max CTCAE Grade 2 and related events were only CTCAE Grade 1 reversible reactions. Vaccine induced immune responses against PD-L1 were detected in blood samples from eight of ten patients and vaccine specific skin-infiltrating lymphocytes from five of eight tested patients. Conclusions: In this exploratory study, one target tumor achieved partial response. Nonetheless, the two clearances and one partial response of non-target tumors suggest that IO103 may be effective against BCCs. The vaccine was well tolerated. Understanding the underlying molecular mechanisms would be needed to select patients for further studies with IO103. Clinical trial information: NCT03714529. [Table: see text]
Clinical significance of nasopharyngeal bacterial colonization in children with acute bronchiolitis
Authors: Zheng-rong Chen, Yu-qing Wang, Yong-dong Yan, Can-hong Zhu, Li Huang, Mei-juan Wang
Journal: BMJ (2013)

Objectives
To explore the effects of nasopharyngeal bacterial colonization in children with acute bronchiolitis due to respiratory syncytial virus (RSV).


Methods
Hospitalized children of acute bronchiolitis were enrolled to detect pathogen and bacterial colonization. Their clinical data and laboratory results were collected and analyzed. Cases of elective surgery were also obtained as control group.


Results
Fifty-five percent of all children with bronchiolitis had a lower positive rate of nasopharyngeal bacterial culture (55.0% vs. 74.1%, P<0.01). Children with nasopharyngeal bacterial colonization had a higher rate of severe bronchiolitis (13.8% vs. 4.2%, P=0.018), presented dyspnea more frequently (19.8% vs. 9.5%, P=0.037) and had a longer hospital duration (8.2 vs.7.5 days, P=0.036) as compared with those without bacterial colonization. In terms of laboratory results, a higher proportion of C-reactive protein was found in children with bacterial colonization than those with non-bacterial colonizations (17.2% vs. 4.2%, P=0.003).


Conclusion
Bacterial colonization may be a predictor for severe bronchiolitis.


Key words: 
Bronchiolitis; Respiratory syncytial virus; Child, preschool
心脑血管疾病与眼科手术的关系
Authors: 孙述兰, 刘爱英
Journal: BMJ (2006)

随着人们生活水平的不断提高,心脑血管疾病已经成为目前人类面临的主要疾病.同时,眼科手术医生也面临着严峻的挑战,患有心脑血管疾病的患者急需手术时,医生和患者双方都要对手术的可靠性和安全性做出判断。
Clinical value of tumor biomarkers in ascitic fluid and serum in differentiating benign from malignant ascites and their correlation
Authors: Wei Tan, He-sheng Luo
Journal: BMJ (2010)

Objective To evaluate clinical value of tumor biomarkers in ascitic fluid and serum in differentiating benign from malignant ascites and their correlation. Methods From July 2006 to July 2009,67 patients with ascites undergone abdominal paracentesis in Renmin Hospital of Wuhan University were enrolled in the study and divided into malignant and benign groups according to their etiology. Levels of tumor biomarkers in ascitic fluid and serum were determined and their correlation were analyzed. Diagnostic sensitivity and specificity of tumor markers were evaluated. Results There was statistically significant difference in levels of cancer antigen 199 (CA199) in serum and ascitic fluid between the malignant group and the benign one ( P ＜ 0. 01 ), and level of cancer embryonic antigen (CEA) significantly increased in ascitic fluid (P ＜ 0.05 ). Levels of CA199 and CEA in serum were significantly higher than those in ascetic fluid in the benign group (P ＜ 0. 01 and P ＜ 0. 05 ), and level of CA125 was significantly lower in serum than that in ascitic fluid (P ＜ 0. 01 ). Level of alpha-fetal protein (AFP) in serum significantly correlated with that in ascitic fluid in the benign group (r =-0. 992, P ＜0. 01 ). In the malignant group, levels of CA199, CEA and CA125 were significantly higher in ascitic fluid than those in serum (P ＜0.05 or P ＜0. 01 ). Levels of CA199 and CEA in serum significantly correlated with those in ascetic fluid in the malignant group (r =0. 746 and 0. 572, respectively, P ＜0. 01 ), and level of AFP in serum also correlated with that in ascetic fluid (r=0. 384, P ＜0. 05). Ratios of levels of CA199 and CEA in ascetic fluid to those in serum (F/S) were significantly higher in the malignant group than those in the benign group (P ＜0.05 or P ＜0.01). Use of combination of CA199, CEA and CA125 determinations showed a higher sensitivity and specificity in differential diagnosis for benign and malignant ascites (P ＜0.05). Conclusions Determinations of CA199 and CEA are beneficial for differentiating benign ascites from malignant one. Determinations of tumor biomarkers in serum can not fully replace those in ascetic fluid. Combined determinations of CA199, CEA and CA125 can increase their sensitivity and specificity in diagnosis for malignant ascites.

Key words: 
Tumor marker, biological;  Ascites;  Serum
Standardized patients in assessment for clinical competencies of trainees in general practice training
Authors: Juan Shou, Shan-zhu Zhu, Sun-fang Jiang, Xiang-jie Zhang, Ming-hui Peng
Journal: BMJ (2009)

Objective To assess clinical competencies of trainees with standardized patients(SPs)and explore reform in methods of assessment for trainees at their completion in standardized training for general practice.Methods Totally,52 trainees in clinical training bases for general practice in Shanghai attended the examinations.Their skills in commanication skills,information and data gathering,comprehensive consultation,clinical thinking and decision-making in diagnosis and treatment were examined by rotation of three serial assessment stations in a specified time to perform standardized tasks,including medical history-taking,physical examinations(PE),medial record writing and oral tests.Results Scoresof history-taking,PE and skills of communication with SPs were higher than those agsessed by examiners themselves.but they both correlated each other with a P-value less than 0.01,with the highest coefficient of correlation of 0.774 between score of PE and that assessed by examiners.There was significant difference in average score among all clinical skills(F=9.867,P＜0.01),with the lowest one of comprehensive consultation skills of 64±22(P＜0.01).Skills of communication with patients had the highest correlation with data gathering ability(r=0.582,P＜0.01).Results of analysis for influential factors showed no significant difference in average score for all skills between men and women trainees(P＜0.05).Average score of comprehensive consultation ability in those with work experience was lower than that in thoge without it(P＜0.05)and no significant difference in scores of all the other skills wag found between those with varied length of working(P＞0.05).There was significant difiefence in average scores of communication skills,medical record writing,and case analysis between various trainees(P＜0.01).In addition,average scores of information collecting and medical record writing also differed among trainees from varied bases for general practice training(P＜0.05).Conclusions Clinical skills,ability to direct teaching work,and improvement of teaching model can be assessed in a comprehensive and objectively way using standardized patients in general practice training.

Key words: 
Teaching;  Standardized patients;  Objective structured clinical examination(OSCE); Clinical skills
Perioperative FLOT (fluorouracil, leucovorin, oxaliplatin and docetaxel) versus EOX/EOF (epirubicin, oxaliplatin and capecitabine or fluorouracil) for locally advanced, resectable gastric or gastro-oesophageal junction (GOJ) adenocarcinoma: A regional center experience.
Authors: Emily Wong, Alvin Boon Tee Tan
Journal: Journal of Clinical Oncology (2020)

e16556 Background: The FLOT4-AIO trial demonstrated a survival benefit in patients with resectable gastric or GOJ adenocarcinoma who received FLOT compared to ECX/ECF (epirubicin, cisplatin, capecitabine or fluorouracil) chemotherapy, but there has been no direct comparison made between FLOT and EOX/EOF regimens in randomised trials to date. Methods: Patients with locally advanced, resectable gastric or GOJ adenocarcinoma treated between December 2012 to December 2019 with FLOT or EOX/EOF in the Midland region were identified. FLOT patients received four preoperative and four postoperative 2-week cycles of 50 mg/m2 docetaxel, 85 mg/m2 oxaliplatin, 200 mg/m2 leucovorin and 2600 mg/m2 fluorouracil as 24-h infusion on day 1. The EOX/EOF patients received three preoperative and three postoperative 3-week cycles of 50 mg/m2 epirubicin, 130 mg/m2 oxaliplatin on day 1 plus either 200 mg/m2 fluorouracil as continuous intravenous infusion or 1250 mg/m2 capecitabine orally on days 1 to 21. We compared the pathological response and tolerability of these regimens. Results: 38 patients received FLOT and 36 patients received EOX/EOF chemotherapy. The median age was 60 and 63.5 respectively. R0 resection was achieved in 31 out of 35 FLOT patients (89%), and 32 out of 35 EOX/EOF patients (91%) who proceeded with surgical resection following pre-operative chemotherapy. AJCC tumour regression score 0-1 was seen in 14 (37%) FLOT patients and 12 (33%) EOX/EOF patients. 30 (79%) FLOT patients and 29 (80%) EOX/EOF patients completed their planned preoperative courses. In the postoperative phase, 20 (56%) FLOT patients and 9 (25%) EOX/EOF patients completed their planned course. Dose reductions occurred in 27% of FLOT patients and 15% of EOX/EOF patients. Grade 3/4 adverse events occurred in 30% of FLOT cycles, and 19% of EOX/EOF cycles administered. Conclusions: Perioperative FLOT and EOX/EOF chemotherapy had similar pathological response, with higher completion of postoperative chemotherapy with FLOT regime.
Combination immunotherapy with ipilimumab and nivolumab in patients with advanced biliary tract cancers.
Authors: Oliver Klein, Damien Kee, Adnan Nagrial, Ben Markman, Craig Underhill, Michael Michael, Caroline Lum, Andreas Behren, Jodie Palmer, Niall C. Tebbutt, Matteo S. Carlino, Jonathan S. Cebon
Journal: Journal of Clinical Oncology (2020)

4588 Background: Patients (pts) with advanced biliary tract cancers (BTC) have a poor prognosis with first and second line chemotherapy resulting in modest survival benefits. Immunotherapy using single agent anti-PD-1 therapy has also shown low activity with an objective response rate (ORR) of less than 10%. Combined CTLA-4/PD-1 blockade using ipilimumab (ipi) and nivolumab (nivo) has demonstrated superior efficacy compared to single agent anti-PD-1 therapy in pts with advanced melanoma and renal cell carcinoma. To date, no trials in BTC pts with ipi/nivo therapy have been reported. Methods: 39 pts with metastatic BTCs were enrolled into the CA 209-538 clinical trial for rare cancers. Patients received nivo 3mg/kg and ipi 1mg/kg q 3 weekly for 4 doses, followed by nivo 3mg/kg q 2 weekly. Treatment continued for up to 96 weeks, or until disease progression or the development of unacceptable toxicity. Response (RECIST 1.1) was assessed every 12 weeks. The primary endpoint was clinical benefit rate (CBR = CR +PR + SD). Exploratory endpoints include correlation of efficacy with biomarkers including PD-L1 expression and tumour mutation burden. Results: 39 pts with BTC were enrolled and 33 pts (85%) had received at least one prior line of systemic treatment (0-2 lines). The ORR was 24% and the CBR 45% with the median duration of response not been reached (range 2-26+months). Responses were observed in 3/14 intrahepatic, 1/10 extrahepatic, 0/2 unspecified cholangiocarcinoma and 5/13 gallbladder ca pts. None of the responding pts had a microsatellite instable tumour. 2 pts with durable partial responses were subsequently rendered surgically free of disease. Median OS and PFS were 6.1 and 3.1 months respectively. 22 (56%) pts experienced an immune –related adverse event (irAE) with grade3/4 irAEs being observed in 8 (20%) pts. Conclusions: Combination immunotherapy with ipi/nivo demonstrates significant clinical activity in a subset of patients with advanced microsatellite stable BTC. The response rate compares favourably to clinical trials investigating single agent anti-PD-1 therapy. Clinical trial information: NCT02923934 .
Characterization of heterogeneity in three lung cancer patients with multiple nodules by whole exome sequencing.
Authors: Dongcheng Liu, Shixuan Li, Jiaqing Wang, Xuefeng Sun, Guofeng Li, Bin Peng, Peikun Ding, Zhiqiang Cheng, Chang Zou, Guangsuo Wang
Journal: Journal of Clinical Oncology (2020)

e21530 Background: Tumor heterogeneity is an important characteristic of malignant tumors that reflects the high complexity and diversity in the process of evolution. It can lead to differences in tumor growth rate, invasion, metastasis, drug sensitivity and prognosis. At present, there exist few genome-wide studies on heterogeneous cases of multiple nodules for patients with non-small-cell lung cancer (NSCLC). Methods: In this study, we performed genetic profiling using a combination of targeted panel and whole exon genome sequencing (WES) on all lesions of three NSCLC patients with multiple nodules. Results: Driver gene alterations were detected in all lesion samples of the three patients. One patient presented with three nodules, which harbored EGFR L858R, ERBB2 exon 20 insertion and a EML4-ALK fusion. Evolutionary analysis showed strong heterogeneity among the three lesions. The three lesions of patient 2 showed EGFR L858R in two lesions (2A and 2C), and a ERBB2 exon 20 insertions in the other (2B). Mutational signatures and cluster analysis of somatic mutations also showed commonality between sample 2A and 2C, suggesting that they might arise from the same clone. Patient 3 had seven lesions. Analysis of somatic mutations and copy number variations revealed possible route of metastasis. Conclusions: Detailed analysis of genetic mutation characteristics and biological evolution trees showed that there were substantial heterogeneity and distinct evolutionary relationships among the different lesions of the same individual. Consequently, such information could aid in the determination of primary and metastasis of tumor lesions and guide the selection of treatment options.
Issues of concern regarding the development and interpretation of Chinese guidelines and consensus
Authors: Dayi Hu
Journal: BMJ (2017)

中国临床指南和共识的制定与解读，一要结合中国的临床实际，要有学术自信和临床实践自信，避免盲目照搬照抄国外指南的教条主义；二要坚持公益，避免商业利益干扰；三要贴近中国临床，接地气，穿中国鞋，走中国路，为中国的患者服务，圆中国的健康梦。
Abstract 15488: Cardiac Magnetic Resonance T1 Mapping of Left Atrial Myocardium
Authors: Roy Beinart, Irfan M Khurram, Hirad Yarmohammadi, Henry R Halperin, Hugh Calkins, Stefan L Zimmerman, Saman Nazarian
Journal: Circulation (2012)

Introduction: Magnetic resonance imaging (MRI) T1 mapping is an emerging tool for objective assessment of myocardial fibrosis. Hypothesis: T1 mapping for left atrial (LA) myocardium in patients wit...
Genomic and transcriptomic profiles of gynecologic neuroendocrine carcinoma are distinct from pulmonary neuroendocrine small cell carcinoma.
Authors: Haider Mahdi, Amy Joehlin-Price, Afshin Dowlati, Ata Abbas
Journal: Journal of Clinical Oncology (2020)

6093 Background: High-grade neuroendocrine carcinoma (NEC) of the cervix and other gynecologic origins are rare and aggressive cancers that unfortunately affect young women with high mortality. Treatment recommendations are often extrapolated from their counterpart, small cell carcinoma of the lung (SCLC). In the present study, we have performed comprehensive genomic and transcriptomic analyses in a cohort of patients with NEC of the cervix and other gynecologic origins and compared them to SCLC. Methods: We have identified 27 patients diagnosed with NEC of gynecologic origin from 1998-2019. Of them, we were able to obtain archival tissue from 14 patients (17 samples), including seven cervical NEC, three ovarian NEC, and two endometrial NEC. Two ovarian and one cervical patient have recurrent tumors. Whole exome sequencing (WES) and RNA-seq were successfully performed in 14 and 13 samples, respectively. BWA-MEM was used for mapping (hg38), and GATK Haplotype Caller was used for WES analysis. Ensemble-VEP was used for variant annotation, and SIFT and PolyPhen-2 were used for pathogenic prediction of missense mutations. Stranded pair-end RNA-seq data were analyzed using STAR and DESeq2. SCLC data from cBioPortal and EBI (accession number EGAS00001000334) were used to compare mutation and transcriptomic profiles. Results: We found that TP53 is not mutated in our cohort, and RB1 is mutated only in 1 (7%) tumor. TP53 and RB1 are the most frequently mutated genes in small cell lung carcinoma. However, LRP1B, the third most mutated gene in SCLC was also mutated in 4 (29%) tumors. We observed that WNT, RTK-RAS, NOTCH, and MYC are among the top mutated pathways in our cohort. Among the top 20 mutated genes, only four genes, MUC4, KMT2C, MAP3K1, and HLA-A, were common in cervical, ovarian, and endometrial tumors suggesting a high diversity within the NEC of gynecologic origin. Our RNA-seq analysis revealed a distinct transcriptional signature when compared to SCLC, especially the expression pattern of SCLC molecular subtypes defining ASCL1, NEUROD1, POU3F2, and YAP1 genes. Surprisingly, we observed a high expression of the YAP1 gene in all of the 13 tumors. However, the YAP1+ subtype represents a minority in SCLC and known to predict chemotherapy resistance and lower survival. Conclusions: Our results suggest a unique mutational profile and transcriptional signature that are distinct compared to SCLC tumors. Therefore, there is an urgent need to re-evaluate the therapeutic options and targets for NEC of gynecologic origin.