tbuckley/cabot-search huggingface dataset:
Analysis of risk factors related to ventilator-associated tracheobronchitis
Authors: Rujie Chen, Mengxiang Lin, Benji Wang, Rong Zhuang
Journal: BMJ (2015)

A total of 178 patients with the time of mechanical ventilation beyond 48 hours in the second affiliated hospital of Wenzhou medical college from January 2010 to December 2013 were enrolled in this study, and there were fifty-six patients with ventilator-associated tracheobronchitis (VAT). The associated factors included age, sex, blood pressure, blood glucose, BMI, the time of mechanical ventilation, tracheal intubation methods, raise head to 30-45°, proton pump inhibitors (PPI), prophylactic antibiotic treatment, glasgow coma scale (GCS), acute physiology and chronic health evaluation(APECHE) Ⅱ score. The related factors of VAT were evaluated by using univariate logistical regression analysis, and the statistical significant variables were analyzed by using multivariate logistical regression analysis. By using univariate logistical regression analysis age, blood glucose, the time of mechanical ventilation, raise head to 30-45°, prophylactic antibiotic treatment, GCS and APECHE Ⅱ score were the important factors of VAT (P 0.05). By using multivariate logistical regression analysis the time of mechanical ventilation (OR=4.072, 95%CI 2.036-8.146), GCS[2.198(1.155-4.184)], age[2.128(1.119-4.046)], APECHE Ⅱ score [2.109(1.084-4.104)] and raise head to 30-45°[0.488(0.243-0.979)] were associated independently with the VAT. The time of mechanical ventilation, GCS, age over 60 years, APECHE Ⅱ score and raise head to 30-45°were the independent factors associated with VAT.


Key words: 
Bronchitis, ventilator-associated; Risk factors
食管异物608例临床分析
Authors: 贾淑萍
Journal: BMJ (2011)

食管异物是耳鼻咽喉科常见急症之一,及时诊断与治疗是预防并发症的关键,如延误治疗或治疗不当常引起各种并发症,尤其尖锐异物(如义齿)会引起食管严重损伤,如食管穿孔、纵隔感染、主动脉食管瘘等而导致死亡.现回顾分析我科2000年1月至2009年12月共收治的食管异物608例以加强认识。
Circulating tumor cells for comprehensive and multiregional non-invasive genetic characterization of multiple myeloma
Authors: Juan-José Garcés, Gabriel Bretones, Leire Burgos, Rafael Valdes-Mas, Noemi Puig, Maria-Teresa Cedena, Diego Alignani, Idoia Rodriguez, Diana Álvarez Puente, Miguel-García Álvarez, Ibai Goicoechea, Sara Rodriguez, Maria-Jose Calasanz, Xabier Agirre, Juan Flores-Montero, Luzalba Sanoja-Flores, Paula Rodriguez-Otero, Rafael Rios, Joaquin Martinez-Lopez, Pamela Millacoy, Luis Palomera, Rafael Del Orbe, Albert Pérez-Montaña, Halima El Omri, Felipe Prosper, Maria-Victoria Mateos, Laura Rosiñol, Joan Blade, Juan-Jose Lahuerta, Alberto Orfao, Carlos Lopez-Otin, Jesus F. San Miguel, Bruno Paiva
Journal: Leukemia (2020)
The association between STK11/LKB1 and/or KEAP1 mutations and response to PD-1/PD-L1 inhibitors in patients with advanced non-small cell lung cancer (NSCLC).
Authors: Meagan Elizabeth Miller, Meera Patel, Sandra K. Althouse, Nasser H. Hanna, Hirva Mamdani
Journal: Journal of Clinical Oncology (2020)

e21538 Background: Advanced non-small cell lung cancer (NSCLC) patients with tumors harboring STK11/LKB1 or KEAP1 mutations have inferior treatment outcomes when treated with PD-1/PD-L1 blockade, regardless of KRAS status, PD-L1 score, or TMB score (Skoulidis et al, Cancer Discovery 2018, ASCO abstract 102, 2019). Methods: Retrospective clinical databases from Indiana University and Karmanos Cancer Institute were queried to identify patients from 2008-2019 with advanced NSCLC treated with PD-1/PD-L1 monotherapy (group A) or concurrent chemotherapy + PD-1/PD-L1 inhibitors (group B) whose tumors harbored STK11/LKB1 and/or KEAP1 mutations. Patients were characterized by best response, progression of disease (PD) or non-PD (complete response (CR) + partial response (PR) + stable disease (SD)). Patient and disease characteristics, response, and duration of response (&gt; vs. &lt; 6 months) were recorded. Results: A total of 77 patients met the above criteria (55 in group A, 22 in group B). 52 of 55 patients in group A received prior chemo. Patient and disease characteristics and outcomes are summarized in the table. Conclusions: STK11/LKB1 and/or KEAP1 mutations are independent of PD-L1/TMB status, although most patients had PD-L1 of &lt;1%. Nearly ½ of patients with STK11/LKB1 and/or KEAP1 mutations achieve at least SD with PD-1/PD-L1 inhibitor monotherapy and more than 50% of those with non-PD maintain that response status for &gt; 6 mos. The frequency and duration of non-PD in this population is higher in patients receiving chemotherapy + PD-1/PD-L1 concomitantly. [Table: see text]
Fruquintinib combination with sintilimab in refractory metastatic colorectal cancer patients in China.
Authors: Miaomiao Gou, Huan Yan, Liu Tie E, Zhikuan Wang, Haiyan Si, Shiyun Chen, Yuting Pan, Runjia Fan, Niansong Qian, Guanghai Dai
Journal: Journal of Clinical Oncology (2020)

4028 Background: Fruquintinib, a vascular endothelial growth factor receptor (VEGFR) inhibitor, is a new anti-cancer targeting drug independently developed in China for refractory metastatic colorectal cancer (mCRC). Because Regorafenib combined with nivolumab has a promising future in patients with refractory mCRC, we aim to evaluate the efficiency of combination of Fruquintinib with Sintilimab (a highly selective, fully human monoclonal antibody PD-1 mAb) in these patients. Methods: Fifty-two patients with refractory mCRC were given fruquintinib (3mg orally, once daily for 3 weeks, followed by 1 weeks off in 4 weeks cycles) and sintilimab (200mg intravenously, once every 3 weeks). Before treatment, peripheral blood samples were collected and next-generation sequencing was performed to detect the gene profile of patients. Results: The ORR was 15.38% (8/52), DCR was 57.6% (30/52), and mPFS was 108 days. The patients was divided into two groups according to their PFS: PFS ≥ 90 days and PFS &lt;90 days. PFS was significantly worse in patients with the following mutations: AMER1 ( p=0.0073), DNMT3A ( p=0.0075), ETV5 ( p=0.012), EWSR1 ( p=0.016), FANCA ( p=0.019), IKBKE ( p=0.0073), NOTCH1 ( p=0.015), STAG2 ( p=0.012) and TCF7L2 ( p=0.0073). It was also significantly worse in the patients had the abnormalities of complexity and coagulation cascades ( p = 0.026) and pancreatic cancer pathway ( p = 0.0098). Conclusions: Fruquintinib combined with Sintilimab seemed not resulted in a significant increase in ORR, DCR and OS in refractory mCRC. Certain mutational genes and abnormal pathway caused by some frameshift mutations may affect the efficacy. It is suggested that targeting these mutational genes and signaling pathway may be helpful to improve the efficacy of Fruquintinib combination with Sintilimab.
A phase I trial of pomalidomide in combination with liposomal doxorubicin in patients with Kaposi sarcoma with or without other KSHV-associated diseases.
Authors: Ramya Ramaswami, Kathryn Anne Lurain, Anaida Widell, Priscila Hermont Goncalves, Irene Ekwede, William Douglas Figg, Cody J. Peer, Ralph Mangusan, Jomy George, Seth M. Steinberg, Vikram Khetani, Denise Whitby, Thomas S. Uldrick, Robert Yarchoan
Journal: Journal of Clinical Oncology (2020)

11552 Background: Kaposi sarcoma herpesvirus (KSHV, also known as human herpesvirus 8 [HHV-8]), is the causative agent of Kaposi sarcoma (KS), a multicentric angioproliferative tumor, a form of multicentric Castleman disease (KSHV-MCD), and KSHV inflammatory cytokine syndrome (KICS). KS can be difficult to treat when it occurs with KSHV-MCD or KICS; resulting in high mortality rates. Liposomal doxorubicin (LD) is an FDA-approved treatment for KS. Pomalidomide, an oral immunomodulatory drug, is safe and has demonstrated activity in KS, but the activity of the combination (pomalidomide+LD) in KS alone or with KSHV-associated diseases is unknown. Methods: The primary objective was to evaluate safety and tolerability of pomalidomide+LD in two groups of patients with KS requiring systemic therapy: Group I (GI)- KS alone; Group II (GII)- KS with concurrent KSHV-MCD or KICS. Patients received LD at 20 mg/m 2 intravenously on day 1 of a 28-day cycle combined with pomalidomide once daily on days 1 to 21 at escalating dose levels (DL) (I - 2mg, II - 3mg, or III- 4mg) in a 3+3 design until plateau of response or other pre-specified criteria. Patients received 81mg of aspirin daily as thromboprophylaxis. KS responses were evaluated using the modified AIDS Clinical Trial Group criteria. Results: Thirty-four cisgender men, all with T1-stage KS [21 patients (62%) in GI and 13 patients (38%) in GII] were treated; 32 (94%) were HIV-infected and 22 (65%) had prior chemotherapy for KS (15/21 GI and 7/13 GII). There were no dose-limiting toxicities (DLTs) at DLIII for GI, and additional patients were treated at DLIII. In GII, grade 3 rash and pharyngeal edema were DLTs observed at 3mg of pomalidomide. Overall a median of 6 cycles were administered; the most common grade 3/4 toxicity was neutropenia. Among evaluable patients receiving &gt;2 cycles,17/21 patients in GI had a response (all partial) (81% [95% confidence interval (CI) 58-95%]) and 5/10 patients in GII had a response (4 partial and 1 complete) (50% [95% CI 19-81%]). Conclusions: Pomalidomide+LD was well-tolerated and active in heavily pretreated patients with KS alone. In patients with KS and other KSHV-associated diseases, activity was noted but less well-tolerated. Clinical trial information: NCT02659930 .
Older patients with mantle cell lymphoma (MCL): Practice patterns and predictors of survival in the rituximab era.
Authors: Reem Karmali, Jeffrey M. Switchenko, Subir Goyal, Veronika Bachanova, James Gerson, Stefan K. Barta, Alexey Valeryevich Danilov, Natalie Sophia Grover, Narendranath Epperla, Madelyn Burkart, Yazeed Sawalha, Nilanjan Ghosh, David Alan Bond, Kami J. Maddocks, Talha Badar, Timothy Fenske, Jin Guo, Mary-Kate Malecek, Peter Martin, Jonathon Brett Cohen
Journal: Journal of Clinical Oncology (2020)

e20064 Background: Therapeutic intensity poses a challenge for older or medically unfit pts with untreated MCL. We assessed clinical outcomes and predictors of survival in older MCL pts treated in the rituximab era. Methods: We included pts ≥ 65 yrs of age with newly diagnosed MCL treated between 2000 and 2015. The primary objective was to characterize practice patterns and survival outcomes in older pts and secondarily to assess predictive factors of survival. Results: Data were collected from 12 centers for 1168 pts. For 465 pts ≥ 65 yrs of age (median 70; range 65-100), variable denominators indicate missing data: 305 of 444 pts (69%) were male; 23 (8%), 110 (39%) and 148 (53%) of 281 pts had low, intermediate and high-risk MIPI respectively. Median time from diagnosis to first treatment was 31 days (range 0-2611 days). In 407 older pts with initial treatment data, 148 (36%) received BR, 65 (16%) a cytarabine containing regimen, 9 (2%) lenalidomide, and 92 (23%) other treatments that excluded BTK inhibitors (BTKi). 68 of 365 pts (19%) were enrolled on clinical trial for initial therapy, 88 of 369 pts (24%) received autologous transplant (AHCT) in first remission, and 155 of 351 pts (44%) received maintenance rituximab (MR). Median f/u was 2.7 yrs. 41 of 465 pts (9%) had primary refractory disease (POD6); 107 (23%) progressed within 24 months (POD24). Treatment data were available for 157 relapsing pts: 58 (37%) were treated with BTKi/BTKi combinations. PFS and OS rates were compared across young and older age cohorts: 2 yr PFS rates were 79%, 69%, and 66% and 2 yr OS rates were 92%, 87%, and 84% for age &lt; 65, age 65-69, and age ≥ 70 respectively (p &lt; 0.001). In the older cohort: on UVA, ECOG ≥2, BM involvement, blastoid histology, &gt; 3 cytogenetic abnormalities and lack of MR were associated with inferior PFS and OS (p = 0.012 – &lt; 0.001). POD6 and POD24 were associated with decreased OS (p &lt; 0.001). AHCT in first remission did not impact PFS or OS. After MVA, MR remained significantly associated with improved PFS and OS (p &lt; 0.001). 2 yr PFS rates were 81% and 58% and 2 yr OS rates were 96% and 80% with and without MR respectively (p &lt; 0.001). Conclusions: In this large cohort of older pts in the rituximab era, survival outcomes remain inferior to younger pts. MR is associated with improved PFS and OS but AHCT does not yield better survival. A small number of pts received BTKi salvage therapy. As such, our data does not reliably reflect the potential advancements in survival achieved with the introduction of BTKis. Focused clinical trials are necessary to identify effective therapeutics in this population.
Abstract 10326: Hyperuricemia is Associated With Target Vessel Revascularization After Percutaneous Coronary Intervention for Chronic Total Occlusion
Authors: Yoshiyuki Okuya, Yuichi Saito, Takefumi Takahashi, Koichi Kishi
Journal: Circulation (2019)

Background: Elevated serum uric acid (SUA) level is reportedly associated with subsequent cardiovascular events including revascularization in patients with coronary artery disease. However, the im...
Checkpoint inhibitor treatment-related cutaneous adverse events in skin of color patients at Memorial Sloan Kettering Cancer Center.
Authors: Amaris Geisler, Dulce M. Barrios M.S, Sarah J. Noor, Mario E. Lacouture
Journal: Journal of Clinical Oncology (2020)

3076 Background: The advent of immune checkpoint inhibitors (CPIs) for the management of advanced malignancies has led to unintended consequences of nonspecific immune activation. Cutaneous immune related adverse events (irCAEs) are the most common and first to manifest, on average within 3.6 weeks of treatment initiation. irCAEs may require CPI treatment dose reduction or discontinuation and negatively impact patient quality of life. There is substantial variability in the reporting of these toxicities and inadequate reporting in skin of color patients (SOC), who are often underrepresented in oncology clinical trials. The purpose of this study is to characterize irCAEs in SOC cancer patients. Methods: A single center retrospective analysis of electronic medical records from 2009-2020 was conducted. SOC was defined as African American, Hispanic, Native American/Pacific Islander, or Asian. irCAEs were graded using the Common Terminology Criteria for Adverse Events (CTCAE) v5.0. Results: Of 1459 SOC patients that presented to our institution and received CPIs during the study period, 175 (12%) presented to dermatology for irCAEs [African American (56, 32%); Asian (98, 56%); Hispanic (20,11%); Native American (1, 0.5%)]. Patients’ toxicities were stratified by CPI mechanism: anti-PD-1/L1 (139, 79%), combination of anti-PD-1/L1 plus anti-CTLA-4 (29, 17%), and anti-CTLA-4 therapy (7, 4%). Of 376 irCAEs, pruritus (62, 16%), xerosis (42, 11%), maculopapular rash (40, 11%), and cutaneous hyperpigmentation (36, 10%) were most frequently diagnosed. There were 86 (23%) grade 1, 93 (25%) grade 2, and 18 (5%) grade 3 events. Average time from CPI-treatment initiation to irCAE onset was 6.5 months (SD 7.9). Fifteen (9%) patients required CPI dose reduction or discontinuation due to skin toxicity. Topical corticosteroids (133, 76%) were the most frequently used treatment for all irCAEs. Conclusions: Our findings suggest that irCAEs occur frequently in SOC cancer patients. Furthermore, a 6.5-month delay in time to diagnosis highlights a need for increased surveillance of these cutaneous toxicities in darkly pigmented skin. Generally, SOC patients present unique diagnostic and management challenges due to differences in skin biology and propensity toward hyperpigmentation; however, in SOC cancer patients, the mechanisms of oncologic immunotherapy must be considered in developing successful treatment strategies and management of dermatologic health in this population.
Tumor response score with neoadjuvant FLOT versus FOLFOX in gastric cancer patients: Results from a United States-based cohort.
Authors: James Pereira De Andrade, Hye Seong Ahn, Joseph Chao, Laleh Golkar Melstrom, Isaac Benjamin Paz, Yuman Fong, Byrne Lee, Yanghee Woo
Journal: Journal of Clinical Oncology (2020)

e16573 Background: A recent RCT comparing FLOT and ECF regimens for locally advanced gastric cancer found FLOT to be superior in pathologic complete response (PCR) rates: 16% versus 6%. We evaluated patients who underwent resection after FLOT and FOLFOX in a diverse US population. Methods: Patients diagnosed with gastric adenocarcinoma at a single institution who underwent preoperative chemotherapy either with FLOT or FOLFOX between 2017 and 2019 were evaluated for pathologic response. Results: Fifty-nine patients underwent gastrectomy for adenocarcinoma. Of these, 59% underwent neoadjuvant chemotherapy: FLOT 20 patients, FOLFOX 12 patients, ECF 1 patient, other regimen 2 patients. Racial/ethnic background of patients were 20% non-Hispanic white, 23% Hispanic/Latino, 40% Asian, 6% black, and 6% other. Three patients (8.6%) had PCR, two received FLOT and one FOLFOX. Four patients had a near complete response (tumor regression score 1), all of whom received FLOT. In total, 16 of 20 patients who received FLOT had at least a partial response whereas only 5 of 12 patients who received FOLFOX had any tumor response (p = 0.027). Among all patients receiving neoadjuvant chemotherapy, 66% had poorly differentiated tumors. Only 1 of these patients experiencing a complete or near complete response compared to 50% of patients with non-poorly differentiated tumors (p = 0.001). Conclusions: In an ethnically diverse US population, tumor regression rates were improved with FLOT when compared to FOLFOX. For medically appropriate patients, strong consideration should be given for FLOT in the neoadjuvant setting.
Expression of the type 3 inositol 1, 4, 5-trisphosphate receptor according to the chronic liver disease etiology in hepatocellular carcinoma.
Authors: Paulo Henrique Costa Diniz, Marcone Loiola dos Santos, Andressa França, Antônio Carlos Melo Lima Filho, Paula Vieira Teixeira Vidigal, Teresa Cristina de Abreu Ferrari, Maria de Fátima Leite
Journal: Journal of Clinical Oncology (2020)

e16604 Background: The expression of type 3 isoform of the inositol 1, 4, 5-trisphosphate receptor (ITPR-3), an intracellular calcium (Ca 2+ ) channel reported in liver cancer cells, is important in the Ca 2+ signalling. Thus, it may be involved in the many events of hepatocarcinogenesis. Here, we investigated the ITPR-3 expression in hepatocellular carcinoma (HCC) and its association with clinicopathological parameters and long-term outcomes, according to the etiology of underlying chronic liver disease (CLD). Methods: Clinical and laboratory data from patients (n = 53) who underwent orthotopic liver transplantation for HCC treatment in a Brazilian referral center were retrospectively collected. After pathological reviewing of their explanted liver samples, ITPR-3 expression in both tumor and underlying cirrhosis were assessed by immunohistochemistry, and quantified using density histograms in the ImageJ software. Event (tumor recurrence or death from any cause) occurrence and event-free survival (EFS) were analysed. Results: Hepatitis C virus (HCV) (n = 31), alcohol abuse (n = 16) and cryptogenic cirrhosis (n = 6) were the underlying CLD etiology, and the groups were, in general, well balanced regarding clinicopathological indices. Median EFS was 78.9 months (range, 63.6-94.1). The ITPR-3 expression profile was cytoplasmatic, predominantly perinuclear, and was stronger in tumor than in adjacent cirrhosis, considering all etiologies together (intensity 9.1% higher in tumors, p &lt; 0.001) However, analyzing each etiologic group, the cryptogenic was the only one in which there was no difference between tumor and underlying CLD. Comparing the ITPR-3 expression only in tumors, there was no difference regarding the etiology of CLD. The tumor ITPR-3 higher intensity was correlated with higher serum aspartate alanine-transferases (ALT) levels (p = 0.018) and lower mitotic index ( &lt; 5 per 10 high power fields) (p = 0.009). There was no association between receptor expression and event occurrence or EFS. Conclusions: The ITPR-3 was expressed in HCC, regardless of the underlying CLD etiology. Its correlation with mitotic index, a cell proliferation marker, was demonstrated, but there were no associations with clinical outcomes. Apart from cryptogenic cirrhosis, ITPR-3 expression was more intense in tumors than in underlying cirrhosis. These findings suggest that ITPR-3 could have a role in carcinogenesis. However, the prognostic and therapeutic implications need to be investigated.
糖尿病患者的个体化健康教育
Authors: 黄萍, 姜民慧
Journal: BMJ (2011)

黄萍:很多慢性疾病和生活方式密切相关,而健康生活方式的建立与保持对于慢性病康复往往起着举足轻重的作用,这就需要医患沟通来帮助患者重视和改变不良生活方式.在门诊如何对患者进行适时的、个体化的健康教育?通过分析几个病例来探讨健康教育。
Improving FOLFIRINOX safety in pancreatic cancer patients through multidimensional remote monitoring and proactive care using a domomedecine mobile platform.
Authors: Mohamed Bouchahda, Sandra Komarzynski, Ayhan Ulusakarya, Amal Attari, Alban Duprès, Gabrièle Breda, Agnès Fritsch, René Adam, Francis Levi
Journal: Journal of Clinical Oncology (2020)

TPS4673 Background: Pancreatic cancer is a poor prognosis and fast-growing cancer, whose five-year survival is 6% in Europe and the US. FOLFIRINOX has been established as the reference medical treatment for this disease worldwide, yet it also causes leuko-neutropenia, thrombocytopenia, diarrhea, anorexia, asthenia, weight loss, and peripheral sensory neuropathy. Its indication is usually limited to patients having a WHO performance status of 0 or 1. This treatment is often interrupted once Grade 3-4 clinical or hematological toxicities occur, resulting in poor patient performance status and quality of life. Presently, no prospective study monitor and evaluate the qualitative and quantitative effects of FOLFIRINOX on the daily life of pancreatic cancer patients in real-time. Such monitoring would provide early warning signals for the identification of any improvement or deterioration of the patient condition. Whenever necessary, proactive interventions would be triggered to avoid emergency hospitalization for severe adverse events and to enhance treatment compliance. Methods: Our study involves the use of the mobile e-Health platform PiCADo (JMIR 2018) to track and analyse circadian rhythms, symptoms, and body weight in real time in 45 advanced pancreatic cancer patients at 4 centres. The patients are continuously telemonitored for rest-activity, temperature and 3D-orientation via a BLE sensor during the six weeks following the first FOLFIRINOX course. Patients weigh themselves daily on a BLE scale and self-rate their symptoms using a touchscreen on GPRS tablet. Alerts are generated according to preset yet modifiable thresholds of automatically computed critical parameters. From these data, we will evaluate the rate of emergency hospital admissions and the admission-free survival, the rates of severe adverse events, patients’ symptoms dynamics, and their relations with the disruption of the patients’ circadian rhythm. Patient satisfaction and research experience will also be assessed, since engagement is at the core of the success of the approach. The results will guide a future randomized trial comparing standard pancreatic cancer patient care with a personalized FOLFIRINOX approach, including chronotherapy delivery. Support: Ramsay-Sante, Altran.
Acute drug-induced myodystonia
Authors: 杨丽, 程焱
Journal: BMJ (2005)

急性药源性肌张力障碍以急性发作的骨骼肌异常运动为特征,常由抗精神病药物引起,亦见于其他药物.由于服用某种药物后出现肌肉间歇、持续的收缩,造成患者重复不自主运动和异常扭转的姿势,常使患者痛苦、焦虑甚至恐惧,这不仅容易使医患之间产生不必要的矛盾,而且可能使患者失去对治疗的依从性[1].急性药源性肌张力障碍发作突然,而一旦诊断明确,药物治疗并不困难,故应引起基层医院急诊和全科医师的高度重视.本文对该病的流行病学特点、临床表现、病理生理机制、诊断和治疗等方面作一综述。