tbuckley/cabot-search huggingface dataset:
Lower-dosing ponatinib in pre-treated GIST: Results of the POETIG phase II trial.
Authors: Johanna Falkenhorst, Rainer Hamacher, Peter Reichardt, Philipp Ivanyi, Bernd Kasper, Peter Hohenberger, Barbara Hermes, Karina Kostbade, Daniel Pink, Heiko Sülberg, Martin Metzenmacher, Martina Crysandt, Sebastian Bauer
Journal: Journal of Clinical Oncology (2020)

11536 Background: Despite long-lasting responses to imatinib most metastatic gastrointestinal stromal tumors (GIST) eventually progress and subsequent treatments are associated with limited duration of disease control. Ponatinib is a potent KIT inhibitor with a strong activity against secondary mutations in exon 17, including the highly resistant D816 mutations of KIT. Based on the dose-depending toxicity profile we sought to evaluate the safety and activity of lower dosing (30mg) ponatinib in pretreated patients with KIT-mutant GIST. We here report safety data for the whole cohort and first efficacy data for the last line cohort within a planned interim analysis. Methods: This multicenter phase 2 trial (NCT03171389) recruited patients with advanced, unresectable GIST progressing after imatinib (Cohort A/B: absence/presence of KIT Exon 13/14 mutations by plasma sequencing) or imatinib, sunitinib and regorafenib (Cohort C). Patients were treated with 30mg oral ponatinib daily in 4-week-cycles. The primary endpoint was the clinical benefit rate at 16 weeks as measured by mRECIST1.1 criteria. Results: At the cutoff date of 31 st Jan 2020, 39 patients were evaluable for safety analysis (25 male, 14 female, median age 60 (38-86) years). Median duration of treatment was 65 (14-699) days. 66.7% of all patients observed Grade 3/4 adverse events (AEs), most common were pain (10/39), hypertension (6/39), GGT or lipase increase (both 5/39), and fever (3/39). One AE of special interest was observed (myocardial infarction, rated not related to study drug) and 20/39 patients experienced at least 1 severe AE (6/39 possibly related to ponatinib). Within the last line cohort, 20 patients were evaluable for efficacy. Clinical benefit rate was 35% (CI 15.4-59.2%). Median progression-free survival was 86 days with single patients yielding long-lasting responses (75% quartile 210 days, maximum: 420 days). Conclusions: Treatment with ponatinib was tolerable at a dose of 30mg qd with a toxicity profile comparable to other TKIs used in GIST. The majority of grade 3/4 AEs were hypertension or asymptomatic increases of laboratory values and thromboembolic events were rare. In a heavily pretreated patient population that lacks alternative treatment options the clinical activity was notable. An updated analysis including predictive biomarkers will be presented. Clinical trial information: NCT03171389 .
Analyzing the outcome of clostridium difficile infection in cancer patients.
Authors: Kamal Kant Sahu, Ajay Mishra, Susan V George, George Abraham, Ahmad Daniyal Siddiqui
Journal: Journal of Clinical Oncology (2020)

e19340 Background: Clostridium difficile infection (CDI) is a considerable health burden, and now identified as the leading cause of acquired diarrhea in patients receiving antibiotics. Cancer patients are more prone to acquire CDI, owing to their frequent exposure to risk factors. This study aims to investigate the factors affecting the outcome of Clostridium Difficile Infection in patients with cancer at our community center. Methods: This is a retrospective study that included a total of 59 cancer patients who were hospitalized for clostridium difficile infection. Results: The median age of the study population was 79 years with 39 males and 20 females. The patients were suffering from cancer located at the following sites: Prostate (25), lung (19), colon (7), bladder (4), breast (3) and renal (1). There were 52 cases of 1st and 7 cases of recurrent CDI admissions. 40 patients detected to have CDI at presentation while 19 patients developed CDI during hospitalization. CDI categories were as follows: Non-severe (29), severe (28), and very severe (3). There were 33 and 20 patients on chemotherapy and radiotherapy respectively. 27 patients had a recent history of cancer care-related procedures or interventions. 29 patients were from either rehab or nursing facility. There were 39 recent hospitalizations with 29 patients receiving antibiotics. Almost half of the patients were on PPI (29) and 12 were on steroids (20.3%) at the time of developing CDI. Patients with a high-risk qSOFA Score of 2 or more (p-value = 0.008) or a high white blood cell count of &gt; 15 X 10 9 /L (p-value = 0.016) were found to have higher in-hospital mortality. Critical care data suggested that 9 patients required intensive care, 7 patients required vasopressor support, and 6 needed mechanical ventilation. Patients were treated with either vancomycin alone (13), or metronidazole alone (25), or combination therapy with vancomycin + metronidazole (21). The median duration of hospital stay was 6 days with 11 fatalities (18.64%). Conclusions: CDI causes significant morbidity in cancer patients. Factors like high qSOFA score and leukocytosis can help to prioritize and intensify the care and in prognosticating the patients.
First-in-human data of ALLO-501 and ALLO-647 in relapsed/refractory large B-cell or follicular lymphoma (R/R LBCL/FL): ALPHA study.
Authors: Sattva Swarup Neelapu, Javier Munoz, Frederick Lundry Locke, David Bernard Miklos, Robert Brown, Jennifer T. McDevitt, Armen Mardiros, Eren Demirhan, Cyril Konto, Michael Timothy Tees
Journal: Journal of Clinical Oncology (2020)

8002 Background: Allogeneic (off the shelf) chimeric antigen receptor (CAR) T cell therapy addresses the logistical challenges and variable product quality of autologous CAR T therapy. ALLO-501 is a genetically modified anti-CD19 CAR T cell product in which the TCR alpha constant gene is disrupted to reduce the risk of graft-versus-host disease (GvHD) and the CD52 gene is disrupted to permit the use of ALLO-647, an anti-CD52 mAb, for selective and prolonged host lymphodepletion. Methods: This is an open-label, Phase 1 trial (NCT03939026) in adults with R/R LBCL/FL who have received ≥ 2 prior lines of therapy; prior anti-CD19 cell therapy is allowed. Patients (pts) receive fludarabine (flu) 90 mg/m 2 , cyclophosphamide (cy) 900 mg/m 2 , and ALLO-647 39 or 90 mg followed by ALLO-501 at 1 of 3 dose levels (DL) in a 3+3 design: 40, 120, and 360 × 10 6 CAR+ T cells. Results: As of 20 January 2020, 12 pts were enrolled: 9 received ALLO-501 at 3 DLs (4, 4 &amp; 1 pts in DL1, DL2 and DL3 respectively), 1 pt discontinued due to kidney injury prior to lymphodepletion and 2 are starting treatment. Of the 9 treated pts aged 42 to 70 years: 5 had LBCL, 2 were female, 3 had primary refractory disease, and 3 had prior autologous stem cell transplants. The median number of prior lines of therapies was 3 (range 2 to 4). All treated pts received 39 mg of ALLO-647. No DLTs or GvHD have been observed to date. Most common Grade (Gr) ≥ 3 adverse events were neutropenia (55.6%), leukopenia (33.3%) and anemia (22.2%). Two pts (22.2%) developed cytokine release syndrome (1 Gr1 and 1 Gr2) that resolved within 72 hrs without steroids or tocilizumab. One pt developed Gr1 neurotoxicity that resolved without treatment. Infections included upper respiratory tract infection (Gr2), CMV (Gr3) and EBV viremia (Gr1), all reported in a single pt and resolved. One pt had a Gr2 infusion reaction to ALLO-647 which resolved with antihistamines. The overall response rate is 78% (95% exact CI: 40%, 97%): 3 complete and 4 partial responses. With a median follow up of 2.7 mos, 4 pts have ongoing responses and 3 pts progressed at 2, 4 and 6 mos. ALLO-501 cell expansion by qPCR was observed in 4 of 6 pts in varying degrees. Conclusions: These early data suggest that ALLO-501 and ALLO-647 have a manageable safety profile. ALLO-647 may be an effective and selective lymphodepleting agent with CD52 gene editing, and ALLO-501 shows evidence of clinical activity in pts with advanced NHL. Enrollment is ongoing, and updated safety, efficacy, PK/PD data will be presented including pts treated with increasing doses of ALLO-647. Clinical trial information: NCT03939026 .
高压电损伤患者血清黏附因子及凝血相关因子的变化
Authors: 毕波, 赵虎, 朱志祥, 朱志军, 邱明昕, 刘天一
Journal: BMJ (2011)

高压电损伤通常会发生血液流变学异常,导致全血流动性降低,黏滞性增强,微循环栓塞,组织缺血缺氧以致坏死,以电流直接通过的肢体部位最为明显[1-4].同时,还会导致血清中各种细胞因子及细胞表面大分子物质的变化[5].细胞间黏附分子-1(ICAM-1)和血管细胞黏附分子-1(VCAM-1)广泛参与调节炎症反应、免疫反应、伤口凝血、肿瘤细胞浸润等病理过程,在高压电损伤后的变化尤为明显.本研究对1999年至2009年间复旦大学附属华东医院、深圳市第二人民医院和青岛大学医学院附属市立医院收治的16例高压电损伤患者的临床资料行回顾分析,观察伤后血清黏附因子浓度变化以及纤维蛋白原(Fg)、血小板的变化,探讨其在损伤发生和发展过程中的变化规律及对损伤评估的意义。
Chronic opioid therapy among a high-risk cancer survivor population.
Authors: Talya Salz, Jessica A. Lavery, Allison Lipitz-Snyderman, Denise Boudreau, Natalie Moryl, Erin F. Gillespie, Deborah Korenstein
Journal: Journal of Clinical Oncology (2020)

e19107 Background: Head and neck cancer (HNC) survivors are at increased risk of opioid dependence, due to exposure to opioids during treatment, history of tobacco and alcohol use, and substantial pain after treatment. Chronic opioid therapy (COT) is a risk factor for dependence, and rates of COT vary widely between populations of cancer survivors. We hypothesized that COT use is greater among HNC survivors than among those who never had cancer. Methods: We used SEER-Medicare to identify adults ≥66 years diagnosed with HNC between 2008 and 2015. HNC survivors were matched 1:3 at date of diagnosis on age, sex, comorbidity, and region with cancer-free controls. Survivors and controls had complete coverage with fee-for-service Medicare Parts A, B, and D for each year after matching. Survivors and controls with no COT in the year prior to matching date and were followed for COT use through 2016. The presence of claims for opioid dispensings over ≥90 consecutive days (COT) was calculated for each year after cancer diagnosis among survivors alive at the start of each year and for controls. We computed odds ratios (OR) for COT use for HNC survivors compared to matched controls in each year after matching date, using a hierarchical logistic regression model accounting for matching and repeated measurements across years. Results: The population of HNC survivors declined from 5,107 in the year after diagnosis to 604 in Year 6. Among HNC survivors, COT use remained relatively steady each year after diagnosis. (Table). For the first 5 years after matching date, rates of COT among HNC survivors exceeded that of controls, with the difference between survivors and controls declining each year (OR 4.36 for Year 1, OR 2.60 for Year 2, OR 2.18 for Year 3, OR 1.85 for Year 4, and OR 1.35 for Year 5, all p-values &lt; 0.05). By Year 6, rates of COT use did not differ between HNC cases and controls. Conclusions: In the first year after diagnosis, HNC survivors have more than 4 times the odds of COT use compared to cancer-free controls. Cancer-associated COT use declines over time. Strategies for appropriate pain management for HNC survivors should balance the risk of opioid dependence, particularly in the early years after diagnosis, with the benefit of improved comfort and function. [Table: see text]
Safety profile of baricitinib for the treatment of rheumatoid arthritis over a median of 3 years of treatment: an updated integrated safety analysis
Authors: Mark C Genovese, Josef S Smolen, Tsutomu Takeuchi, Gerd Burmester, Dennis Brinker, Terence P Rooney, Jinglin Zhong, Mo Daojun, Chadi Saifan, Anabela Cardoso, Maher Issa, Wen-Shuo Wu, Kevin L Winthrop
Journal: The Lancet Rheumatology (2020)
Definition of home-based rehabilitation mode for patients with stroke
Authors: Lei Cheng, Jianping Wu, Hong Zhang, Dongsun Wu, Yongxiang Zhou, Xiaoqing Li
Journal: BMJ (2017)

Based on the experiences in Quyang Community Health Service Center, and through focus group discussions and literature research, the home-based rehabilitation mode for stroke patients in community was developed. With the principles of safety and effectiveness, rehabilitation physicians and family physicians are responsible for rehabilitation program, while rehabilitation therapists and community nurses implement the rehabilitation program. The rehabilitation services are provided for patients and their families at home with the community service resources, including counseling services, rehabilitation aids and other cares according to their needs and demands. The definition and contents of the mode provide a basis for further clarification and operation of home-based rehabilitation for stroke patients in community.


Key words: 
Stroke; Rehabilitation; Community health service
Guidelines for completion colonoscopy after polyps are found at flexible sigmoidoscopy for investigation of haemorrhoidal-type rectal bleeding
Authors: Philip Bagshaw, Brian Cox, Francis Antony Frizelle, James M Church
Journal: Gut (2020)

We read with interest the paper by Rutter et al on surveillance guidelines after colonoscopic polypectomy and postcolorectal cancer resection.1 However, like all similar recognised guidelines, they do not address the issue of following up polyps found on a flexible sigmoidoscopy (FS) done to investigate rectal bleeding. With colonoscopy services in short supply in many countries, FS is often used at rectal bleeding clinics in cases where other known personal risk factors for colorectal neoplasia are absent.

At FS, the finding of a normal rectum and sigmoid combined with a likely anal cause of the bleeding excludes significant left-sided neoplasia. However, the appropriate follow-up of an adenoma found in the rectum or sigmoid colon has been a topic of much study and debate, centred on the likelihood of detecting significant proximal colonic neoplasia.

One of the most …
Epidemiology of adenoid cystic carcinoma in the United States.
Authors: Tirza Areli Calderón Boyle, Samantha St. Laurent, Simon Semus, Nedra Joseph
Journal: Journal of Clinical Oncology (2020)

e13600 Background: Adenoid cystic carcinoma (ACC) is a rare malignancy of the secretory glands, accounting for approximately 1% of head and neck cancers and 10% of salivary gland neoplasms. ACC primarily occurs in the major and minor salivary glands; however, it is found in other sites of the head and neck, breast, female genital tract, prostate and skin. There is limited scientific literature on the epidemiology of ACC and no published incidence or prevalence estimates across all anatomic sites. Methods: Using data from the Surveillance, Epidemiology, and End Results (SEER) 18 registries, ACC cases were identified by International Classification of Diseases for Oncology 3 rd Edition histology codes. Data from 2012-2016 were used to estimate age-adjusted incidence rates (IR) and 5-year limited duration prevalence (LDP). Data from 2000-2016 were used to approximate 16-year LDP. IR and LDP were estimated overall and by age, sex and race. IR was calculated for each anatomic site. Total incident and prevalent cases were projected using the 2020 US Census population. Analyses were conducted in SEER*Stat (v8.3.6) and SAS 9.4. Results: In the US, ACC age-adjusted IR was 0.35 per 100,000 and 5- and 16-year LDP were 1.48 and 3.24 per 100,000, respectively (Table). ACC IR and LDP (per 100,000) were highest in those aged 75-79 years (IR 1.45; 5-year LDP 5.82; 16-year LDP 14.25) and in females, and lowest among Native Americans/Alaska Natives. ACC IR (per 100,000) were highest in the oral cavity and pharynx (IR 0.19), salivary glands (IR 0.12), respiratory system (IR 0.07) and breast (IR 0.05). As of January 1, 2020, 10,777 patients were living with ACC in the US who had been diagnosed 2000-2016. Conclusions: This study describes the US epidemiology of ACC across all anatomic sites and provides incidence and prevalence estimates not currently published in the literature. Improving understanding of the epidemiology of this rare cancer has important implications for the development of effective clinical and public health interventions. [Table: see text]
A phase II/III study of perioperative nivolumab and ipilimumab in patients (pts) with locoregional esophageal (E) and gastroesophageal junction (GEJ) adenocarcinoma: A trial of the ECOG-ACRIN Cancer Research Group (EA2174).
Authors: Jennifer Rachel Eads, Michelle Weitz, Michael K. Gibson, Lakshmi Rajdev, Onkar V Khullar, Steven H. Lin, Constantine Gatsonis, Ignacio Ivan Wistuba, Aravind Sanjeevaiah, Al Bowen Benson, Nathan Bahary, Kristen Renee Spencer, Nabil F. Saba, Stanley R. Hamilton, Charles A. Staley, Anuradha Bapsi Chakravarthy, Terence Z. Wong, Peter J. O'Dwyer
Journal: Journal of Clinical Oncology (2020)

TPS4651 Background: E/GEJ adenocarcinoma has a high mortality rate despite curative intent treatment. A pathologic complete response (pCR) is associated with better overall survival (OS) but occurs in less than 30% of pts. Immunotherapy is effective in the metastatic setting. Here we aim to evaluate the contribution of immunotherapy in the neoadjuvant and adjuvant settings in pts with locoregional E/GEJ cancer. Methods: This is a multi-center, randomized phase II/III trial. Surgical candidates with locoregional E/GEJ adenocarcinoma receive carboplatin AUC 2 IV and paclitaxel 50 mg/m2 IV, both weekly x 5 during concurrent radiation (50.4 Gy) either with or without nivolumab 240 mg IV during weeks 1 and 3, followed by surgery. Pts with no post-operative disease receive nivolumab 240 mg IV every 2 weeks for 12 cycles either with or without ipilimumab 1 mg/kg IV every 6 weeks for 4 cycles. Eligibility criteria include pts with T1-N1-3M0 or T2-3N0-2M0 disease whom are candidates for surgery, no prior chemotherapy or radiation for this disease, no prior immunotherapy, no significant autoimmune disease. Pts must be disease free for adjuvant treatment. Primary neoadjuvant endpoint is pCR rate; primary adjuvant endpoint is disease free survival (DFS). Secondary endpoints include toxicity, DFS and OS. Pre- and mid-treatment diffusion weighted imaging MRI will be conducted during the neoadjuvant portion of the study. A neoadjuvant safety run in of 30 pts is underway. Overall, 278 pts will be needed to detect an absolute improvement of 15% in pCR rate in pts receiving and not receiving neoadjuvant nivolumab and 236 pts will be needed to detect a HR of 0.65 in favor of adjuvant ipilimumab/nivolumab over nivolumab (90% power, one sided alpha of 0.10). Accrual is expected over 34 months at a rate of 8 patients per month. If favorable at interim analysis. Clinical trial information: NCT03604991 .
Prognostic value of ischemic modified albumin for patients with non-ST-segment elevation acute coronary syndrome undergoing percutaneous coronary intervention
Authors: Ya Liu, Shan Yan, Shao-jun Wen, Jie-lin Liu, Zuo-guang Wang
Journal: BMJ (2013)

Two hundred and fourteen patients with non-ST-segment elevation acute coronary syndrome (NSTEACS) underwent percutaneous coronary intervention (PCI). Serum ischemic modified albumin (IMA) levels were measured in patients at admission. The major adverse cardiac events (MACE), including cardiac death, nonfatal myocardial infarction (MI) and recurrent ischemia leading to urgent revascularization were observed during 1-y period of follow-up. Receiver operating characteristic (ROC) curves, Kaplan-Meier analysis and Cox regression were used to assess the prognostic value of IMA for 1-y MACE. Twenty one patients experienced major adverse cardiac events during 1-y follow up period, including 6 cases of cardiac death, 8 cases of new or recurrent MI, 7 cases of target vessel/lesion revascularization or coronary artery bypass grafting (CABG). ROC showed that the area under the ROC curve (AUC) was 0.667, and when IMA was used to predict 1-y major adverse cardiac events, the cut-off value of 65.3 kU/L was most effective. Kaplan-Meier analysis showed that IMA was significantly correlated with the occurrence of 1-y MACE (P<0.01). But Cox regression model showed that IMA levels were not independent risk factor for 1-y MACE in NSTEACS patients, when adjusted with other risk factors.


Key words: 
Coronary disease; Ischemic modified albumin
Does CNS metastases reduce systemic therapy lines for NSCLC patients with EGFR mutation?
Authors: Danilo Giffoni, Maria Luisa Romero, Mark Doherty
Journal: Journal of Clinical Oncology (2020)

e21558 Background: The latest generation tyrosine kinase inhibitor (TKI), Osimertinib, targets the epidermal growth factor receptor (EGFR) despite the T790M mutation status in non-small-cell lung cancer (NSCLC). In cases where there is a detected EGFR mutation on the exon 19-deletion and on the exon 21-L858R in the NSCLC population, studies have demonstrated that Osimertinib has a positive benefit in overall survival and delayed progression of central nervous system (CNS) metastases. Methods: From January 2010 to December 2018, 56 patients with the metastatic NSCLC-EGFR mutation, treated with Osimertinib 80 mg once daily, were included in this analysis. Retrospective data was extracted through the internal administrative databases located at Sunnybrook Hospital. All patients had EGFR mutation positivity by cytology, plasma or tissue sampling. The primary endpoint was to evaluate whether NSCLC patients who were exposed to Osimertinib and had brain metastases underwent fewer systemic therapy lines as compared to those who did not have metastases involving the brain. Results: Eligible patients were analyzed and the median age at the initial diagnosis was 65 years old; 50% (n = 28) of the patients had brain metastases. The median of systemic treatment lines for patients without CNS metastasis was two and for those who have metastases to the brain was three. 82,2% of this cohort received Osimertinib in 2nd line, after development of acquired resistance to first or second TKI generation. Conclusions: Results from this study did not demonstrate that EGFR mutated, NSCLC patients with CNS metastases received less systemic therapy lines to those without metastases involving the brain. A larger cohort for further investigation is warranted.
门诊检验报告单的风险管理
Authors: 林荣海, 赵玉新, 高丽红, 李林倩, 贾荣娟
Journal: BMJ (2012)

分析管理前3610例患者的7208份报告单和管理后3860例患者的7936份报告单未领取情况、患者满意度及因此所致投诉情况,两次结果比较,差异均有统计学意义.提示加强管理可明显降低医疗风险,提高门诊医疗护理质量。
更年期常见心理障碍及其对策
Authors: 施慎逊
Journal: BMJ (2004)

更年期是人生命周期的必然过程,根据国际公认的标准,更年期从41岁开始,历时15～20年.男女更年期年龄不同,女性多在45～55岁,男性多在50～60岁.这个时期各种应激增加,心理(精神)压力增大,易产生各种心理(精神)问题.下面介绍更年期常见的心理(精神)障碍和对策。