tbuckley/cabot-search huggingface dataset:
Cell-free KRAS in pancreatic cancer as a rapid prognostic marker.
Authors: Patricia Saiz-Lopez, Raquel Alcaraz-Ortega, Ana Maria Lopez, Beatriz Llorente, Maria Soledad Diez-Ordoñez, Juan Carlos Pérez Álvarez, Maria José Cáceres Porras, Johanna Beatriz Palacios Ball, Celina Echevarria-Iturbe, Guillermo Crespo
Journal: Journal of Clinical Oncology (2020)

e15534 Background: KRAS mutations are present over 90% of patients with pancreatic cancer (PC). Liquid biopsies provide the opportunity to genotype alterations in a less invasive way and offer a possibility to monitor the molecular characteristics of a cancer through the course of treatment. We aim to establish an association between the mutational levels of KRAS detected in plasma with patient stage and evolution. Methods: Plasma samples were collected from patients with newly diagnosed PC, before any treatment and during one year. Diagnosis of any previous cancer was an exclusion criterion. Samples were frozen (-80ºC) until analysis of KRAS mutations in cell free DNA (cfDNA) by real time PCR. Specifically, Idylla TM technology was used due to the rapid capacity to report up to 21 KRAS mutations in exon 2, 3, and 4 (LOD = &lt; 5%), without necessity of cfDNA isolation. Mutation was considered present (categorical measurement), taking into account cycle quantification values (Cq) established by the commercial test. Cut-off values for Cq were studied by the ROC curve (receiver operating characteristic) with the Youden's J statistic. Paired tissue samples were analyzed when available. Results: A total of 23 patients were enrolled, median age 65 years old, 57% male, 100% adenocarcinoma, 18 (70%) metastatic. Sixteen patients could also be tested in tissue, being 15 (93.8%) positive for KRAS mutation. Plasma basal mutations were detected in 10 patients (43.5%), all in stage IV (p = 0.046), and interestingly, all with liver involvement (p = 0.003). Moreover, these patients also had metastasis in another organ apart from the liver. The most frequent mutation was G12V (5), followed by G12D (4) and G12R (1). Patients with basal KRAS mutations detected in plasma had a survival of 6.1 months (CI 95%, 3.7-8.5), and non-mutated 11.2 months (95% CI, 7.8-14.7) (p = 0.041). The presence of these cell-free KRAS mutations was more informative for survival than stage IV disease vs III (p = 0.054). Paying attention to KRAS wild type detection in plasma samples used as an internal control of the PCR, we could establish a Cq value cut-off of &lt; 21 Cq for mutant samples, with a sensitivity of 100% (95% CI, 75%-100%) and specificity of 50% (95% CI, 19%-81%), area under ROC curve 0.823 (95% CI, 0.649-0.997). Conclusions: Measurement of cell-free KRAS in plasma samples at diagnosis could be used to quickly predict metastasis and survival in patients with pancreatic adenocarcinoma.
The contribution of hereditary cancer-related germline mutations to lung cancer susceptibility.
Authors: Lele Song, Mengyuan Liu, Xinyi Liu, Suo Peisu, Tanxiao Huang, Yaru Chen, Yanqing Zhou, Guifeng Liu, Jianfei Yao, Shifu Chen, Mingyan Xu
Journal: Journal of Clinical Oncology (2020)

e13594 Background: Germline variations may contribute to lung cancer susceptibility besides environmental factors. The susceptibility of germline mutations and their correlation with somatic mutations has not been systematically investigated in lung cancer patients. Methods: Germline mutations from 1090 lung cancer patients were analyzed with a 58-gene NGS panel containing known hereditary cancer-related genes, and were categorized based on ACMG guidelines in pathogenicity, and the corresponding somatic mutations were analyzed using a 605-gene NGS panel containing known cancer-related genes. Results: Genetic susceptibility was found in 4.5% of lung cancer patients, in which 14 patients with pathogenic mutations and 35 patients with likely-pathogenic mutations were identified. Significantly stronger family history was found with the pathogenic group than other groups. Pathogenic mutations fell most commonly in BRCA2 (6/14), followed by CHEK2 (3/14) and ATM (2/14). Likely-pathogenic mutations fell most commonly in NTRK1 mutations (4/35) and EXT2 mutations (4/35), followed by BRIP1 (3/35) and PALB2 (3/35). These genes are involved in DNA repair (BRCA1 and BRCA2, BLM, RAD50, BRIP1, MLH3), cell cycle regulation (such as CHEK2, ATM, NTRK1 and EPCAM) and tumor suppressor (such as PALB2). The overall odds ratio (OR) value of the pathogenic group was 17.93 (95% CI: 9.74 to 33.01), and was 15.86 (95% CI: 5.999 to 133.2) for the likely-pathogenic group, suggesting that the pathogenic or the likely-pathogenic germline mutations as a whole were risk factors for lung cancer. Somatic mutation analysis revealed no significant difference in TMB among the groups, although a trend of lower TMB in the pathogenic group was found. The SNV/INDEL mutation rate of TP53 in the pathogenic group was significantly lower. Pathway enrichment analysis found no significant difference in aberrant pathways among the groups. Conclusions: 4.5% of patients carrying germline variants may be linked to increased susceptibility to lung cancer. The susceptibility is mainly reflected in family history and morbidity risk without significant influence on aberrant pathways.
Conditional survival of patients with nonmetastatic bone osteosarcoma.
Authors: Ruoyu Miao, Haotong Wang, Edwin Choy, Gregory Michael Cote, Kevin Raskin, Joseph H. Schwab, Francis J. Hornicek, Thomas F. DeLaney, Yen-Lin Chen
Journal: Journal of Clinical Oncology (2020)

e23511 Background: Conditional survival provides a dynamic prediction of prognosis for patients surviving a defined period of time after diagnosis. This study aimed to determine the conditional survival and prognostic factors over time among patients with non-metastatic bone osteosarcoma. Methods: We reviewed 714 bone osteosarcoma patients treated from 1985 to 2016. Patients with metastatic disease at diagnosis or limited follow up were excluded, resulting in 587 cases for analysis. Clinical and pathological variables were recorded. Predictive variables included age at diagnosis, gender, previous radiation history, tumor site, tumor size, histologic subtype, histologic grade, resection margin, chemotherapy, and radiation therapy. The multivariate Cox proportional hazards regression was used to analyze prognostic factors of conditional overall survival and progression-free survival at baseline and 5 years after diagnosis. Results: The estimated 5-year conditional overall survival increased from 71.0% (95% CI: 67.5%-75.0%) at baseline to 86.9% (95% CI: 82.6%-90.5%) at 5 years, which means if a patient with non-metastatic bone osteosarcoma survived 5 years, the chance of surviving another 5 years was 86.9%. If the patient was progression-free for 5 years, the 5-year conditional overall survival was even higher, 93.2% (95% CI: 89.5%-96.4%), and the 5-year conditional progression-free survival improved from 57.1% (95% CI: 53.3%-61.0%) at baseline to 91.2% (95% CI: 87.5%-94.6%) at 5 years. Prognostic factors for mortality and disease progression change as survival time increases. At baseline, age (p &lt; 0.001 and p = 0.003), histologic subtype (p &lt; 0.001 and p = 0.001), grade (p &lt; 0.001 and p &lt; 0.001), tumor size (p = 0.002 and p = 0.002), resection margin (p &lt; 0.001 and p &lt; 0.001) and chemotherapy (p = 0.001 and p = 0.001) were predictive of both overall survival and progression-free survival. However, only age (p &lt; 0.001) and histologic subtype (p = 0.015) remained significant for mortality and resection margin (p = 0.001) for disease progression at 5 years. Conclusions: The survival probability of osteosarcoma improves as survival time increases. Estimates of conditional survival can provide useful information for individualized surveillance strategies, risk evaluation, patient counseling, and making clinical decisions.
微创胸膜腔留管并尿激酶灌注治疗结核性包裹性胸腔积液
Authors: 孙小军, 方孙阳, 赵宝珊
Journal: BMJ (2005)

对30例出现胸腔积液不超过6周、已产生包裹的结核性胸膜炎患者采用微创胸膜腔留置导管、一次性单向活瓣放液和尿激酶胸膜腔灌注方法治疗,将结果与同期采用其他方法治疗的59例比较.证明该法能显著增加胸腔积液引流量、减少胸穿次数和缩短胸腔积液消失时间,有效降低胸膜粘连与肥厚,且该方法安全、有效。
Hydroxychloroquine: balancing the needs of LMICs during the COVID-19 pandemic
Authors: Soumya Banerjee
Journal: The Lancet Rheumatology (2020)

SARS-CoV-2 antibodies (table ). It should be noted, however, that these sera were only analysed using one kit and other kits with different test operating characteristics might produce different results.In conclusion, the serological test we assessed showed no cross-reactivity with autoantibodies present in patients with autoimmune disease.Asymptomatic carriers could spread SARS-CoV-2, 5 and this type of test could make large scale screening of asymptomatic SARS-CoV-2 carriers possible.We propose that serological testing of IgM and IgG antibodies, along with RT-PCR, in clinical prac tice should help provide an accurate COVID-19 diagnosis, including in patients with autoimmune disease.
An exploratory study of fruquintinib as second-line treatment for patients with advanced or metastatic biliary tract cancer.
Authors: Qiu Li, Pengfei Zhang
Journal: Journal of Clinical Oncology (2020)

TPS4657 Background: Biliary tract cancer (BTC) is a relatively uncommon but highly fatal malignancy and most patients with BTC are diagnosed at advanced stages. Currently, no standard second-line treatment has been established following recurrence from the first-line treatment. VEGF is highly expressed in more than 50% of BTC, which indicates anti-angiogenesis might be a potentially effective method to improve the outcome in BTC. Fruquintinib is a novel small molecule tyrosine kinase inhibitor targeting VEGFR1, VEGFR2, and VEGFR3 and is currently being evaluated in clinical trials for multiple cancers including lung cancer, gastric cancer and colorectal cancer, and showed strong anti-tumor activity. However, the effect and safety of fruquintinib has not been investigated in the setting of second-line treatment for BTC. Methods: The study is a multicenter, single-arm, phase 2 trial of fruquintinib (5 mg, po, for 3 weeks, followed by 1 week off, 4 weeks for a cycle) for patients with advanced or metastatic BTC who have failed to first-line chemotherapy. The primary endpoint is progression-free survival (PFS) with the null hypotheses of 8 weeks, and the median PFS≥15 weeks as evidence of the study drug activity (α=0.05, 80% power, one-sided). The number of patients required to complete the study is 27. Allowing for 20% expulsion rate, the study needs 33 patients. The secondary endpoints include objective response rate (ORR), disease control rate (DCR), overall survival (OS), safety and quality of life (QoL). Meanwhile, the study also set an exploratory objective to evaluate the mutation status of related genes in plasma (cfDNA) and tumor tissue and explore the interplay between mutation patterns with efficacy. Major eligibility requirements: Age ≥18 years; Histologically or cytologically confirmed diagnosis of advanced or metastatic biliary tract adenocarcinoma; First-line chemotherapy failed (tumor progression or intolerable adverse events); No less than 3 months of expected survival; ECOG PS≤1; At least one measurable lesion according to RECIST 1.1 criteria; Adequate organ function. Eligible patients with advanced or metastatic BTC refractory to first-line chemotherapy will be enrolled at 7 medical centers in China. The study is open and actively enrolling at time of submission. Clinical trial information: NCT04156958 .
Different methods for bowel preparation in elderly patients with constipation before colonoscopy
Authors: Yuanzhi Wang, Jiehua Zhi, Bin Deng, Guanghuai Yao, Qiang She, Jian Wu
Journal: BMJ (2014)

One hundred and forty six elderly patients with constipation undergoing colonoscopy during March 2012 and August 2013 were randomly assigned to trial and control groups. Seventy patients in trial group received Macrogol electrolytes powder combined with Chinese herb medicine Simo decoction for bowel preparation and 76 patients in control group received macrogol electrolytes powder only. The first defecation, times of defecation and tolerance of patients were compared between two groups. The quality of bowel preparation was evaluated by endoscopists with Boston Bowel Preparation Scale(BBPS). The first defecation time was shorter in trial group than that in control group (55.7±27.9 vs. 72.9±34.8, P<0.05) . However, no statistical significance was found in the times of defecation and tolerance of patients between two groups. The mean BBPS score in trial groups was higher than that in control group (7.87±1.08 vs. 6.97±0.96, P<0.05). Chinese herb medicine Simo decoction combined with conventional method shows satisfactory result for bowel preparation in elderly patients with constipation undergoing colonoscopy.


Key words: 
Constipation; Bowel preparation
<i>KEAP1/NFE2L2</i> mutations to predict local recurrence after radiotherapy but not surgery in localized non-small cell lung cancer.
Authors: Michael S Binkley, Young-Jun Jeon, Monica Nesselbush, Everett J Moding, Barzin Nabet, Diego S Almanza, Christopher Yoo, David Matthew Kurtz, Susie Grant Owen, Leah Monique Backhus, Mark F. Berry, Joseph B Shrager, Kavitha Ramchandran, Sukhmani Kaur Padda, Millie Das, Joel W. Neal, Heather A. Wakelee, Ash A. Alizadeh, Billy W. Loo, Maximilian Diehn
Journal: Journal of Clinical Oncology (2020)

9012 Background: Tumor genotyping in localized non-small cell lung cancer (NSCLC) is not broadly performed due to lack of actionable associations of mutations with treatment or outcome. We sought to identify recurrent mutations in localized NSCLC that are associated with local recurrence (LR) after radiotherapy (RT) or surgery. Methods: We identified consecutive patients with NSCLC treated with chemoradiotherapy (CRT), stereotactic ablative radiotherapy (SABR) or surgery from 2009-2018 at our institution with stage IA1-IIIC NSCLC who had genotyping performed on tumor tissue using a targeted gene panel. Our primary objective was to identify somatic tumor mutations that predicted LR after RT but not surgery. We also performed functional screening assays by expressing open reading frame constructs harboring patient-derived mutations in knock-out cell lines generated by CRISPR-Cas9 and evaluating effects on in vitro radioresistance. Results: We identified 232 consecutive patients with localized NSCLC (87.1% adenocarcinoma, 10.3% squamous, 2.3% other) who received tumor biopsy or resection specimen and underwent tumor genotyping. 47 patients with locally advanced NSCLC received CRT, 50 patients with early stage NSCLC received SABR, and 135 patients with early stage NSCLC underwent surgical resection. Of all recurrent mutations ( &gt; 5% mutation frequency), only mutations in Kelch-like ECH-associated protein 1 ( KEAP1) or Nuclear Factor Erythroid 2-Related Factor 2 ( NFE2L2) genes (K/N MUT ) were significantly associated with LR after CRT or SABR, with 2-year LR in the combined RT cohort of 42.4% for K/N MUT versus 12.5% for wildtype (P = 0.005). Furthermore, K/N MUT were present in nearly half of all LR events. Strikingly, there was no significant difference in LR for K/N MUT tumors following CRT versus SABR (P = 0.47). Local recurrence was rare for patients who received surgery (n = 2) and was not associated with K/N mutation status (P = 0.60). Functional evaluation by expression of K/N mutations in knock-out cell lines revealed that LR only occurred in patients with mutations that induced radioresistance (i.e. pathogenic) but not passenger mutations (P = 0.04). In contrast to genotyping, NFE2L2 target gene expression analysis via RNA-seq did not predict LR (P = 0.93). Conclusions: Our findings suggest that KEAP1/NFE2L2 mutations are a predictive biomarker of clinical radioresistance and a dominant cause of LR after RT. Genotyping for KEAP1/NFE2L2 mutations could therefore facilitate treatment personalization in localized NSCLC.
Implications of a prognostic 40-gene expression profile (40-GEP) test for high-risk cutaneous squamous cell carcinoma (cSCC) on staging-based risk assessment and adjuvant therapy trial design.
Authors: Chrysalyne Schmults, Kyle R. Covington, Sarah J. Kurley, Robert W. Cook
Journal: Journal of Clinical Oncology (2020)

e22091 Background: Deaths due to cSCC are expected to exceed melanoma-specific deaths. With the demonstration of effective therapies for advanced cSCC, and as treatment of patients in the adjuvant setting is considered, accurate prognosis is critical. For improved identification of ‘high-risk’ patients, with biologically aggressive disease capable of metastasis, a prognostic 40-gene expression profile (40-GEP) test was validated using an independent cohort of patients with high-risk cSCC and known clinical outcomes. The test identified three groups with increasing metastasis risk profiles: Class 1 (low risk), Class 2A (high risk), and Class 2B (highest risk) having metastasis rates of 8.9%, 20.4%, and 60%, respectively. Multivariable analysis demonstrated prognostic efficacy of the 40-GEP test alone and in combination with clinicopathological staging systems. This study evaluated risk stratification with concurrent consideration of the 40-GEP result and the Brigham and Women’s Hospital (BWH) stage. The primary objective was evaluation of the potential impact of the 40-GEP on adjuvant clinical trial design. Methods: To determine if a 40-GEP Class 2B result could optimize clinical trial accrual, metastasis rates of BWH high-risk T stage patients (T2b-T3) alone and in combination with 40-GEP results from the validation cohort were used for two-arm trial sample size calculations. Results: Metastasis rates for cases with T2b-T3 tumors increased from 35.1% to 71.4% when selecting for T2b-T3 cases with a 40-GEP Class 2B result. To provide 80% power to detect hazard ratio of 0.6 with 3 years of follow-up (alpha = 0.05), in line with improvement rates by addition of radiation to surgery, 434 T2b-T3 patients are required for randomization. However, sample size could be reduced by 51% to 214 patients by focusing enrollment on T2b-T3 patients with a 40-GEP Class 2B result. Conclusions: These results support the incorporation of the 40-GEP test into selection processes for patients with T2b-T3 tumors who are at the highest risk for metastasis and appropriate for adjuvant clinical trials.
急诊胸、腹手术成功救治严重胸腹联合伤一例
Authors: 姜波, 董建伟, 于炳强, 戴学军
Journal: BMJ (2012)

报告1例严重胸腹联合伤的救治体会.患者双侧多发肋骨骨折、血气胸,右侧连枷胸、胸廓内动脉断裂,左侧膈肌破裂、脾脏粉碎性破裂并疝入胸腔,同时合并肝破裂.先后急诊行双侧开胸及剖腹手术,故及时急诊手术是救治成功的关键。
Effect of acupuncture combined with rehabilitation therapy to improve comprehensive function among patients with stroke in communities
Authors: Xiao Cui, Cui-xia Zhou, Pei-yu Qu, Huan-huan Ni, Hui-ling Zeng, Chun-shui Huang, Jun-chao Shi
Journal: BMJ (2009)

Objective To Btudy effect of standardized acupuncture combined with rehabilitation therapy (function training)on improvement of comprehensive function among patients with stroke in communities,Changning District of Shanghai.Methods One hundred and seventy-six stroke patients were divided into rehabilitation therapy group(88 cases)and control group(88 cages)with block randomization.Patients in rehabilitation therapy group were treated with standardized acupuncture combined with function training in addition to regular medical treatment,and patients in control group regular medical treatment only.All the patients were evaluated with functional comprehensive assessment(FCA)scale by the end of 2-and 5-month of treatment,respectively.Results By the end of 5-month of treatment,scores of FCA in both groups increased significantly (P＜0.01),as compared to those before treatment,more in rehabilitation therapy group than that in control group(P＜0.05).Conclusions Effect of standardized acupuncture combined with rehabilitation therapy Can obviously improve their comprehensive function among stroke patients in communities.

Key words: 
Acupuncture; Recovery of function; Cerebrovascular accident
Multisite randomized trial of integrated palliative and oncology care for patients with acute myeloid leukemia (AML).
Authors: Areej El-Jawahri, Thomas William LeBlanc, Alison Kavanaugh, Jason Webb, Vicki A. Jackson, Toby Christopher Campbell, Nina O'Connor, Selina M. Luger, Ellin Gafford, Jillian Gustin, Bhavana Bhatnagar, Amir Tahmasb Fathi, Gabriela Hobbs, Julia Foster, Showly Nicholson, Debra M. Davis, Hilena Addis, Dagny Vaughn, Nora K. Horick, Jennifer Temel
Journal: Journal of Clinical Oncology (2020)

12000 Background: Patients with AML receiving intensive chemotherapy experience substantial decline in their quality of life (QOL) and mood during their hospitalization for induction chemotherapy and often receive aggressive care at the end of life (EOL). We sought to examine the effect of integrated palliative and oncology care on QOL, mood, post-traumatic stress (PTSD) symptoms, and EOL outcomes in patients with AML. Methods: We conducted a multi-site randomized trial of integrated palliative and oncology care (n = 86) versus usual oncology care (n = 74) for patients with AML undergoing intensive chemotherapy. Patients assigned to the intervention were seen by palliative care clinicians at least twice per week during their hospitalization for induction chemotherapy and all subsequent hospitalizations. Patients completed the Functional Assessment of Cancer Therapy-Leukemia, the Hospital Anxiety and Depression Scale, and the PTSD Checklist to assess their QOL, mood, and PTSD symptoms at baseline, weeks 2, 4, 12, and 24. The primary endpoint was QOL at week-2. We used analysis of covariance and mixed linear effect models, controlling for baseline scores, to assess the effect of the intervention on patient-reported outcomes. Results: Between 1/2017 and 7/2019, we enrolled 160/235 (68.1%) of eligible patients. Compared to those receiving usual care, intervention patients reported better QOL (107.59 vs. 116.45, P = 0.039) and lower depression (7.20 vs. 5.68, P = 0.021), anxiety (5.94 vs. 4.53, P = 0.018), and PTSD symptoms (31.69 vs. 27.79, P = 0.009) at week 2. Intervention effects were sustained up to week 24 for QOL (B = 2.35, P = 0.048), depression (B = -0.42, P = 0.039), anxiety (B = -0.38, P = 0.042), and PTSD symptoms (B = -1.43, P = 0.002). Among deceased participants, those receiving the intervention were more likely to report discussing their EOL care preferences with their clinicians (75.0% vs. 40.0%, P = 0.009) and less likely to receive chemotherapy in the last 30 days of life (34.9% vs. 65.9%, P = 0.008). There was no difference in hospice utilization or hospitalization at the EOL. Conclusions: The integrated palliative and oncology care model for patients with AML receiving intensive chemotherapy led to substantial improvements in patients’ QOL, psychological distress, and EOL care. Thus, palliative care should be considered a new standard of care for patients with AML. Clinical trial information: NCT02975869 .