tbuckley/cabot-search huggingface dataset:
Time delay barriers in diagnosis and treatment of gastrointestinal cancer in Nepal.
Authors: Soniya Dulal, Bishnu D. Paudel, Prakash C. Neupane, Bibek Acharya, Sandhya Chapagain Acharya, Ramila Shilpakar, Bishal Paudel, Albira Acharya, Rameej Revanta Thapa, Michael Gary Martin
Journal: Journal of Clinical Oncology (2020)

e19085 Background: Gastrointestinal (GI) cancers represent a major health challenge worldwide including in Nepal where patients (pts) often present with advanced disease and outcomes are poor. The purpose of this study was to quantify and to determine the causes of delay in diagnosis and treatment of GI cancer pts in Nepal. Methods: An IRB-approved cross sectional study was performed in pts with GI cancers at safety net Bir Hospital, Kathmandu, Nepal. All diagnosed consenting pts, both in- and out-pts, were enrolled. Pts were interviewed with a standardized questionnaire from July 2018 to June 2019. The caregivers were allowed to answer on behalf of illiterate pts. Diagnosis delay was defined as days from first symptoms to pathological diagnosis. Patient delay was defined as days from first symptoms to first medical consultation. Treatment delay was defined as days from diagnosis to surgery and/or treatment by medical/radiation oncologist. Differences in median times to delay were compared with two-tailed t-tests (Prism 8.0) based on the identified potential causes of delays. Results: The median age at diagnosis was 53.5 (22-77) years and 62% were males; 46% were farmers, 29% were housewives, and the rest had various occupations. 73% were outpatient at diagnosis. 46% had gastroesophageal cancer (gastric – 38%; esophagus – 8%) and 54% had colorectal cancer (left sided colon - 23%, right sided colon -13%; rectum 18%). No patients with anal or small bowel cancer were identified. 84% presented with Stage III/ IV disease. 68% were illiterate, 89% had a history of self-medication prior to first medical consultation, 74% were from rural areas with limited healthcare facilities and 79% were unaware of causes of GI cancers. Only self-medication was associated with delays in diagnosis and patient delays (Table). Conclusions: Self-medication rather than seeking help from medical professionals led to significant delays in the diagnosis of GI cancers in Nepal. Reasons for these decisions will be explored in future studies and may be amenable to efforts such as lay navigation. [Table: see text]
Implementation of Calgary-Cambridge consultation guide in family medicine practice
Authors: Lin-xi Pei, Dong-feng Guo, Jun-hua Zhong, Yun-peng Zhao, Sheng-nan Zhang, Ying-jun Xiang
Journal: BMJ (2013)

Five general practitioners were trained for application of the enhancing Calgary-Cambridge guide in consultation. The consultation time in 50 patients were recorded before and after training and the satisfaction degree of patients was investigated by questionnaire survey. Results showed that the length of consultation time after training was longer than that before training (490 s vs 277 s, P<0.05) and also longer than that of specialists (490 s vs 268 s, P<0.05). The overall satisfaction rate of patients was increased after training (72% vs 88%, P<0.05). The results indicate that training of Calgary-Cambridge guide for doctor-patient communication can improve the communication skills of general practitioners.


Key words: 
General practitioner; Physician-patient relations
Identification of malignant ascites using MR-based T1 mapping.
Authors: Fabian Kuetting, Alois Martin Sprinkart, Anton Faron, Lisa Meffert, Christian Jansen, Julian Luetkens, Ulrike Attenberger, Daniel Kuetting
Journal: Journal of Clinical Oncology (2020)

e16719 Background: Non-invasive identification of malignant ascites is a challenge in clinical practice.Thus, we decided to assess if an MR-based T1 mapping approach allows non-invasive differentiation of malignant and non-malignant effusions. Methods: In-vitro and ex-vivo MR-examinations were performed on a clinical 1.5T MR-system. T1 mapping was performed with spectroscopy and an adapted modified Look-Locker inversion-recovery (MOLLI) acquisition. For in-vitro experiments 13 titrated solutions with varying albumin content (0 to 200 g/l) were examined. For ex-vivo evaluation 27 ascites/pleural effusion samples from patients with malignancy (19 with histologic tumor confirmation in effusion) and 18 samples from patients without malignancy were examined. All samples underwent histological and laboratory testing. Samples were classified as malignant-positive histology, malignant-negative histology and non-malignant negative histology. Lab values were correlated with T1 maps and receiver operating characteristic (ROC) analysis was used to determine the optimal T1-value threshold to differentiate malignant and non-malignant ascites. Results: In in-vitro analysis both methods showed a high correlation with albumin-content (MOLLI: r = -0.97; Spectroscopy: -0.98). T1-values derived from the reference standard (Spectroscopy) and the MOLLI technique had a high agreement (intraclass correlation single measures: 0,9889, 95% CI: 0,52 to 0,99; average measures: 9,994, 95% CI 0,69 to 0,99). Bland-Altman analysis showed a strong agreement between both methods: 62.5 ± 35 (95% CI: 41.2 to 83.8) Ex-vivo analysis revealed significant differences between T1 values from patients with malignant+ histology (median: 2237; IQR: 2132 to 2327.5) and patients with non malignant- negative histology (median: 2611; IQR: 2548 to 2803, p &lt; 0.0001) as well as between malignant+ histology and all other included patients (median: 2585; IQR: 2503 to 2710, p &lt; 0.0001) Multiple regression analysis of in-vivo results revealed that only albumin content correlated with MOLLI based T1 measurements (p &lt; 0.0001; r = -0.65) ROC analysis for differentiation between malignant and non-malignant effusions (malignant+ histology vs. all other) showed an AUC of 0.897; 95% CI: 0.769 to 0.967). Malignant+ histology vs. non-malignant- histology showed an AUC of 1.000 (cut off Lolli &gt; 2419; 95% CI: 0.905 to 1). Conclusions: T1 Mapping shows excellent correlation with protein content of fluids.MR- T1 mapping allows for non-invasive differentiation of malignant and non-malignant effusions in an ex-vivo set up.
全科医生要提高鉴别诊断能力
Authors: 金世红
Journal: BMJ (2011)

全科医学的一个主要特点就是知识范围很宽,要处理的临床问题多种多样,涉及到各个器官、系统及各种年龄人群.当全科医生遇到一个临床症状时,要想到各种可能性,做完整的鉴别诊断,这是全科医生要掌握的很重要的能力之一.我自己也是在全科医疗的实践经历里,通过不断学习、经验的积累,甚至通过误诊或漏诊的教训而不断提高做鉴别诊断的能力。
抗血栓治疗基础知识（二）抗血栓治疗的出血危险性
Authors: DavidAFitzmaurice, AndrewDBlann, GregoryYHLip, 邓朝胜, 杨媛华
Journal: BMJ (2004)

许多常见的心血管疾病(特别是老年人)与血栓形成相关，如缺血性心脏病、心房纤颤、瓣膜疾病、高血压及动脉粥样硬化性血管病，都需要抗血栓治疗。这就产生了在老年病人中如何恰当应用抗血栓治疗的问题，尤其是在使用华法林抗凝治疗时需要定期监测国际标准化比值(INR，反映出血倾向和出血危险性的一项监测指标)。因为老年病人同时
Obesity-related glomerulopathy
Authors: Mi Wang
Journal: BMJ (2017)

近年来肥胖相关性肾小球病(ORG)的发病率明显提高。ORG发病机制尚不完全明确，可能与肾血流动力学改变、肾素－血管紧张素－醛固酮系统及交感神经系统过度激活、胰岛素抵抗等有关。临床上表现为蛋白尿，伴或不伴血尿、高血压及肾功能异常。病理表现为肾小球肥大伴或不伴局灶节段性肾小球硬化。目前缺乏特异而有效的治疗方法，临床上主要针对ORG可能的发病机制采取相应的治疗，以减少蛋白尿、延缓肾功能恶化。
Distinct molecular profiles of interval and screen-detected tumors in a real-world breast cancer registry.
Authors: Sharon Wilks, Kristi McIntyre, Linda K. Han, Michelina Marie Cairo, Julie Barone, Josien Haan, Lorenza Mittempergher, Erin Yoder, Andrea Menicucci, Shiyu Wang, William Audeh
Journal: Journal of Clinical Oncology (2020)

e15587 Background: Interval breast cancers (BC) are detected between routine screening mammograms and are associated with worse prognosis, requiring more aggressive treatment compared to screen-detected BC identified during scheduled mammograms. Identifying molecular differences between interval BC and screen detected BC may lay the foundation for developing novel therapies. In this study, we compared gene expression profiles of interval BC to screen-detected BC. Methods: This analysis included a subset of 2260 patients enrolled in the FLEX Registry (NCT03053193), an ongoing, prospective study evaluating primary tumor samples from stage I-III BC patients who receive 70-gene risk of recurrence testing (70GS), 80-gene molecular subtyping (80GS), and consent to collection of clinically annotated full genome data. Interval BC were diagnosed &lt; 12 months following a normal screening mammogram. Breast tumors were classified by 70GS as having a Low Risk (LR) or High Risk (HR) of distant metastases. Tumors were classified as Luminal, HER2, or Basal type by 80GS. Differential gene expression analysis was performed with limma and subsequent pathway analysis with DAVID and GSEA. Differences in the proportion of 70GS or 80GS results, 70GS index, and Ki67 were assessed by Chi-squared test or t-test. Results: In this study, 81% (1834/2260) of patients had screen-detected BC and 19% (426) had interval BC. A higher proportion of interval BC (51%) were HR compared to screen-detected BC (44%; p = 0.01). Most LR tumors were invasive ductal carcinoma (78% interval and 73% screen-detected) and over 99% were Luminal type. Between the two LR groups, 70GS indices were similar and there was no significant difference in transcriptional profiles. Basal and HER2 subtypes were more frequent among HR interval BC compared to screen-detected BC (p = 0.03). HR interval BC had 70GS indices of higher risk compared to HR screen-detected BC (p = 0.02). Differentially expressed genes in HR interval BC compared to HR screen-detected BC were associated with MYC signaling and mitosis, which was concordant with higher Ki67 by IHC (p = 0.007). Conclusions: This real-world data analysis shows interval BC are not all biologically High Risk and can be further stratified by the 70GS, aiding in treatment decisions. Preliminary results suggest that following 70GS LR classification, there is no biological difference between interval BC and screen-detected BC. In contrast, there are distinct biological processes associated with HR interval BC, which may have implications in the management of these cancers. Clinical trial information: NCT03053193.
Abstract 14375: Mitral Regurgitation in Acute Heart Failure: Impact on Left Atrial Dynamics and Response to Treatment
Authors: Maurizio Losito, Monica Barki, Andrea Giammarresi, valentina labate, Maria Michela Caracciolo, Francesco Bandera, Alessandro Vella, Eleonora Alfonzetti, Marina Rovida, Marco Guazzi
Journal: Circulation (2019)

Introduction: The deterioration of left atrial (LA) mechanics represents a precipitant factor triggering acute decompensated heart failure (ADHF). Significant mitral regurgitation (MR) may worsen L...
Risk factors for acute myeloid leukemia in adults: a hospital-based case-control study
Authors: Xing Wang, Xiao-qin Wang, Jing-wen Gu, Guo-wei Lin
Journal: BMJ (2011)

Objective To determine risk factors of environment and lifestyles involved in acute hematology departments of 29 secondary-care and tertiary-care hospitals in Shanghai. There were 206 hospitalized patients with de novo AML during June 2003 to April 2007 meeting the diagnostic criteria for AML by the World Health Organization, excluding those with definite history of radiotherapy or chemotherapy, and 412 age- and gender-matched controls with non-hematological other diseases from the same hospitals. All the participants were interviewed face-to-face using a standard structured questionnaire,including personal medical history, family medical history, history of medications, traditional Chinese herb medicines, exposure to occupational hazards, lifestyle factors, etc. in the past five years prior to onset of the disease. Conditional univariate and multivariate logistic regression analyses were performed to identify risk factors for AML. Results Logistic regression analysis showed that taking traditional Chinese herb medicine might be a protective factor for AML, with an odds ratio (OR) of 0. 39 and its 95% confidence interval (CI) of 0. 16-0. 98. Potential risk factors for AML included history of diabetes and taking hypoglycemic agents ( OR: 1.39, 95% CI: 0.67 -2. 87), occupational exposure to metal ( OR: 1.73, 95% CI: 0. 77 -3. 91 ), glue, paint and other coating materials, etc. ( OR: 1.72, 95% CI: 0. 93 - 3.2), raising animals (OR: 1.33, 95% CI: 0. 79 -2. 24). No association of living within a distance of 100 meters from high voltage power transmission lines, home renovation and decoration in the past year, hair dyeing, smoking,alcohol drinking with AML in adults was found. Conclusions Factors mentioned above such as occupational exposure to metal, glue, paint and other coating materials potentially increase risk for AML in adults,however taking traditional Chinese herb medicine is possibly a protective factor for it.

Key words: 
Leukemia, myeloid;  Risk factor;  Questionnaire
Effects of radiation therapy on clonal hematopoiesis.
Authors: Leslie Ann Modlin, N. Ari Wijetunga, Minal Patel, Teng Gao, Ryan Ptashkin, Michael R Sullivan, Daniel W. Kelly, Nicole Caltabellotta, David B. Solit, Michael F. Berger, Martin S. Tallman, Luis A. Diaz, Ahmet Zehir, Elli Papaemmanuil, Ross L. Levine, Kelly L Bolton, Lior Zvi Braunstein
Journal: Journal of Clinical Oncology (2020)

12062 Background: Clonal hematopoiesis (CH), characterized by recurrent somatic mutations in blood, is a common age-associated condition that portends an increased risk of myeloid neoplasms and cardiac disease. Oncologic therapies appear to promote CH, including ionizing radiation therapy (RT) (OR = 1.4, p &lt; 10 −6 ) and systemic DNA-damaging agents (OR = 1.2, p = 8x10 −4 ). How various RT parameters (e.g. target site, dose, fractionation, modality) may influence CH is unknown. Methods: CH mutations were identified via targeted, deep-coverage next-generation sequencing from paired peripheral blood and tumor samples (MSK-IMPACT). CH was defined as a somatic blood mutation with a minimum variant allele frequency of 2%. Putative driver mutations (CH-PD) were identified from OncoKB and other published sources. Clinical and RT characteristics were abstracted from medical records. To account for differences in RT dose and fractionation, equivalent radiation dose in 2 Gy fractions (EQD 2 ) with an α/β ratio of 3 for late effects was calculated. Univariate and logistic regression modeling for associations between clinical and treatment parameters and CH were performed. Results: We identified 2,195 patients who received RT before blood draw and 7,832 who did not, encompassing 57 histologies. A median of 267 days elapsed between the end of RT and blood draw. After RT, 22% of patients had at least one CH-PD mutation (n = 486). The most common single anatomic sites radiated were pelvis, chest wall/breast, and head and neck. Conventional RT was used in 2% (n = 46), 3D-conformal in 14% (n = 308), intensity modulated RT in 36% (n = 787), volumetric modulated arc RT in 12% (n = 263), multiple techniques in 26% (n = 560), and unknown in 11% (n = 231). There was no association between RT modality and presence of CH-PD (p &gt; 0.05 for all between group comparisons of modality). On multivariate regression after controlling for age, race, time from diagnosis to blood draw, smoking status, and for chemotherapy class, cytotoxic, immune, or targeted therapies in the entire cohort, EQD 2 was associated with CH-PD (p = 0.012x10 −3 ). Evaluating EQD 2 by irradiated anatomic site, total pelvic dose by EQD 2 in 10 Gy increments remained significantly associated with CH-PD (OR = 1.07, p = 0.0046), as was head and neck EQD 2 (OR = 1.046, p = 0.032). Conclusions: CH-PD was associated with higher radiation dose for pelvic or head and neck RT, but not other anatomic sites after controlling for systemic therapies. RT modality was not associated with CH-PD. Ongoing work will directly evaluate the bone marrow dosimetry of various treatment approaches using phantom-based modeling.
PD-L1 expression as a prognostic marker in patients with advanced biliary tract cancer.
Authors: Hyera Kim, Jung Yong Hong, Jeeyun Lee, Se Hoon Park, Joon Oh Park, Young Suk Park, Ho Yeong Lim, Won Ki Kang, Seung Tae Kim
Journal: Journal of Clinical Oncology (2020)

e16679 Background: Biliary tract cancer (BTC) is associated with poor prognosis because of its aggressive and heterogeneous nature. Programmed death ligand 1 (PD-L1) has been considered as a novel biomarker for prognosis and response of immune checkpoint inhibitors in various tumors. However, there are limited data reporting on the role of PD-L1 in advanced BTC patients. Methods: We analyzed 186 patients with advanced BTC who received palliative gemcitabine and platinum between May 2010 and December 2019. All patients were evaluated for PD-L1 expression by combined positive score (CPS) positivity. Results: In all 186 patients, the median age was 62 years (range 38-82), and the primary tumor location was intrahepatic cholangiocarcinoma (IH-CCC) in 72 patients (38.7%), extrahepatic (EH)-CCC in 90 (48.4%), and gallbladder (GB) cancer in 24 (12.9%). There were 158 (84.9%) patients with recurrent disease and 28 (15.1%) with metastatic disease. Among the 186 patients, 53 (28.5%) had PD-L1 CPS positivity, and 133 were CPS negative. The median overall survival (OS) of patients with PD-L1 CPS positivity or negativity was 12.1 and 15.4 months, respectively. The median progression-free survival (PFS) in patients with PD-L1 positivity or negativity was 5.7 and 7.1 months, respectively. The OS and PFS were not statistically different between groups. In sub-group analysis, EH-CCC patients with PD-L1 negativity had more favorable OS (17.2 vs. 11.6 months, p= 0.002) and PFS (7.8 vs. 5.4 months, p= 0.005) than those that were PD-L1 negative. However, this finding was not reproduced in patients with IH-CCC or GB cancer. Univariate analysis of the association between PD-L1 expression and OS in patients with advanced BTC indicated that PD-L1 CPS positivity has a prognostic role in sub-populations older than 60 years (HR 1.743, CI 1.001-3.034, p = 0.050), those with EH-CCC (HR 2.449, CI 1.355-4.426, p = 0.003), and those with liver metastasis (HR 2.511, CI 1.362-4.626, p = 0.003). Conclusions: This study demonstrated that PD-L1 expression might be a novel prognostic biomarker in patients with EH-CCC but not for patients with IH-CCC or GB cancer.
Neoantigen load and HLA-class I expression identify a subgroup of tumors with a T-cell-inflamed phenotype and favorable prognosis in homologous recombination-proficient high-grade serous ovarian carcinoma
Authors: Hirokazu Matsushita, Kosei Hasegawa, Katsutoshi Oda, Shogo Yamamoto, Kayo Asada, Takahiro Karasaki, Akira Yabuno, Akira Nishijima, Takahide Nejo, Yukari Kobayashi, Sho Sato, Yuji Ikeda, Manami Miyai, Yusuke Takahashi, Rui Yamaguchi, Keiichi Fujiwara, Hiroyuki Aburatani, Kazuhiro Kakimi
Journal: Journal for ImmunoTherapy of Cancer (2020)

There is increasing evidence for the benefit of poly ADP ribose polymerase (PARP) inhibitors in a subset of high-grade serous ovarian carcinoma (HGSC) patients, especially those with homologous recombination (HR)-deficient tumors. However, new treatment strategies, such as immune checkpoint inhibition, are required for patients with HR-proficient tumors.A total of 80 cases of HGSC were analyzed in this study. Whole exome and RNA sequencing was performed for these tumors. Methylation arrays were also carried out to examine BRCA1 and RAD51C promoter methylation status. Mutations, neoantigen load, antigen presentation machinery, and local immune profile were investigated, and the relationships of these factors with clinical outcome were also analyzed.As expected, the numbers of predicted neoAgs were lower in HR-proficient (n=46) than HR-deficient tumors (n=34). However, 40% of the patients with HR-proficient tumors still had higher than median numbers of neoAgs and better survival than patients with lower numbers of neoAgs. Incorporation of human leukocyte antigen (HLA)-class I expression status into the survival analysis revealed that patients with both high neoAg numbers and high HLA-class I expression (neoAghiHLAhi) had the best progression-free survival (PFS) in HR-proficient HGSC (p=0.0087). Gene set enrichment analysis demonstrated that the genes for effector memory CD8 T cells, TH1 T cells, the interferon-γ response, and other immune-related genes, were enriched in these patients. Interestingly, this subset of patients also had better PFS (p=0.0015) and a more T-cell-inflamed tumor phenotype than patients with the same phenotype (neoAghiHLAhi) in HR-deficient HGSC.Our results suggest that immune checkpoint inhibitors might be an alternative to explore in HR-proficient cases which currently do not benefit from PARP inhibition.
Circulating tumor DNA to detect minimal residual disease, response to adjuvant therapy, and identify patients at high risk of recurrence in patients with stage I-III CRC.
Authors: Noelia Tarazona, Tenna V Henriksen, Juan Antonio Carbonell-Asins, Thomas Reinert, Shruti Sharma, Desamparados Roda, Svetlana Shchegrova, Marisol Huerta, Susana Roselló, Derrick Renner, Himanshu Sethi, Bernhard Zimmermann, Alexey Aleshin, Andres Cervantes, Claus Lindbjerg Andersen
Journal: Journal of Clinical Oncology (2020)

4009 Background: The clinical utility of tracking circulating tumor DNA (ctDNA) as a non-invasive biomarker for detecting minimal residual disease (MRD) and stratifying patients based on their risk of developing relapse has been well established in colorectal cancer (CRC). This study evaluates the detection and longitudinal monitoring of ctDNA in CRC patients pre- and post-operatively, during and after adjuvant chemotherapy (ACT). Methods: The prospective, multicenter cohort study recruited patients (n = 193) diagnosed with resected stage I-III CRC. Plasma samples (n = 1052) were collected at various timepoints with a median follow up of 21.6 months (4.6-38.5 months). Individual tumors and matched germline DNA were whole-exome sequenced and somatic mutations identified. Multiplex PCR assays were designed to 16 tumor-specific single-nucleotide variants to track ctDNA in plasma samples. The study evaluated the relationship between ctDNA status and clinical outcomes including radiologic imaging. Cox regression was used to calculate recurrence-free survival (RFS) in patients stratified by ctDNA status postoperatively and post-ACT. Multivariable analysis was performed with all clinical variables. Best model was selected according to Akaike Information Criterion. Results: Pre-operatively ctDNA was detected in 90% (n = 166/185) of the patients. Post-operative ctDNA status prior to ACT was assessed in 152 patients, of which 9.2% (14/152) were identified to be MRD-positive and 78.5% (11/14) eventually relapsed. In contrast, 10.1% (14/138) of MRD-negative cases relapsed (HR: 16.53; 95% CI: 7.19-38.02; p &lt; 0.001). Longitudinal ctDNA-positive status, post-ACT (n = 84) and post definitive therapy (n = 139) was associated with a 27.92 HR (95% CI: 9.16-85.11; p &lt; 0.001) and a 47.52 HR (95% CI: 17.34-130.3.; p &lt; 0.001), respectively. In the multivariable analysis, longitudinal ctDNA status was the only significant prognostic factor associated with RFS (HR: 53.19, 95% CI: 18.87-149.90; p &lt; 0.001). Serial ctDNA analysis detected MRD up to a median of 9.08 months (0.56-16.5 months) ahead of radiologic relapse with a sensitivity of 79.1% and specificity of 99%. Conclusions: Postoperative ctDNA analyses detect patients with high-risk of recurrence, with near 100% specificity. Early detection of MRD and longitudinal monitoring of ctDNA could guide treatment decisions. Intervention trials to assess the clinical benefit of ctDNA use are underway.