tbuckley/cabot-search huggingface dataset:
New-onset diabetes mellitus and risk of pancreatic cancer: A systematic review and meta analysis.
Authors: Anas Albawaliz, Adam Bataineh, Bara El Kurdi, Sumbal Babar, Abdulrahman Abonofal, Ammar Alhabhbeh, Mohammad Alomari, Abdulraheem M.S. Qasem, Madhusudhan Sanaka
Journal: Journal of Clinical Oncology (2020)

e16778 Background: Several epidemiologic studies have illustrated a general association between diabetes mellitus and pancreatic cancer (PC). Very few, however, described a temporal association between the new onset of diabetes mellitus, particularly within the first 2 years of diagnosis, and the development of PC. We sought to systematically review the literature and perform the first meta-analysis to study the risk of PC among patients with new-onset diabetes mellitus (NOD). Methods: A systematic literature search was conducted in PubMed, MEDLINE, EMBASE, and Cochrane databases from inception through November 2019 to identify studies evaluating the relationship between NOD and PC. NOD was defined as diabetes mellitus diagnosed within 3 years or less prior to diagnosis of PC. Studies were examined and relevant data was extracted and analyzed using Comprehensive Meta-Analysis software. A random effect meta-analysis approach was used to pool the data and odds ratio was used to calculate the overall effect estimate. Results: A total of 283 articles were identified by the search but only 4 relevant studies met our inclusion criteria and they examined a total of 42055 cases and 2402213 controls. The odds ratio of pancreatic cancer development among patients with NOD was 3.021 (CI 2.192- 4.165) compared to controls with significant heterogeneity (I 2 = 90%). Meta regression evaluating relevant variables such as mean age, race and smoking were not able to explain the heterogeneity. A meta-regression model accounting for sample size as an independent factor showed that sample size was inversely correlated to the OR of PC in patients with NOD and was able to explain 93% of the noted heterogeneity between studies. Conclusions: Our meta-analysis has shown a significant temporal association between NOD and pancreatic cancer. Diabetes mellitus, being mostly diagnosed in an outpatient setting by primary care physicians (PCPs), can be the first clue to detect pancreatic cancer at an early stage, and thus contribute to more favorable outcomes. These findings might guide PCPs to consider pancreatic cancer in the differential diagnosis in high risk patients. Further studies are needed to discern the role of NOD in pancreatic cancer screening. Attention is required to the possible inflationary effect of low sample sizes on the odds of developing PC after NOD.
是浅表性胃炎吗
Authors: 杨桂霞
Journal: BMJ (2010)

我在门诊曾遇到一位农村老年患者,在外院诊断为浅表性胃炎. 患者男性,61岁,病程已1年余,主诉:厌食,偶伴有呕吐,乏力,体重下降.病初并未引起重视,只是服用一些助消化的药物,患者精神状态逐渐变差,体重下降明显。
Treatment for patient with chronic postherpetic neuralgia
Authors: Liping Song, Hui Li, Yinnan Guo
Journal: BMJ (2018)

Fifty postherpetic neuralgia (PHN) patients with a course ≥3 years and the Pain Numeric Rating scale (NRS)≥5 were included in the analysis. All patients were treated with nerve block and subcutaneous injection in the affected area. The paravertebral nerve blocks were performed by injecting 5 ml lidocaine in the concentrations of 0.3%; the concentration of lidocaine for branch blockage and peripheral nerves was 1.0%, and that for subcutaneous injection was 0.3%, respectively; 2 mg dexamethasone and 0.5 mg vitamin B12 were added in the injections. The NRS scores and quality of life scores were documented before and after the treatment. The NRS score was significantly decreased at different time points of treatment (F=279.6, P<0.01). At the end of the treatment and at 1 month, 3months, 6months of follow-up, the scores were significantly lower than those before the treatment. All patients showed enormous improvement in the quality of life at 1, 3 and 6 months after treatment. The pain relief was excellent or good in 38 cases. The efficacy of treatment is associated with skin scar and allodynia. The study indicates that nerve block and subcutaneous injection has a satisfactory efficacy in treatment of chronic postherpetic neuralgia.


Key words: 
Neuralgia, postherpetic; Nerve block; Injections, subcutaneous
Efficacy analyses of capsules Shugan-jieyu and paroxetine in patients with poststroke depression and anxiety
Authors: Yun-hua Yue, Xiao-ning Zhang, Li-ping Zhang, Xiao-ying Yang, Jie-ping Mao
Journal: BMJ (2013)

A total of 192 poststroke patients with depression and anxiety were assigned randomly into study group (n=96) and control group (n=96). The study group received both capsules Shugan-jieyu and paroxetine while the control group paroxetine alone. Compared with the control group, scores of both Hamilton depression scale (HAMD) and Hamilton anxiety scale (HAMA) were significantly different at the end of week 2 and 6 in the study group (P<0.05). The HAMD and HAMA deduction rate and the scores of mangled extremity severity, mini-mental state examination and modified Barthel index at the end of week 6 of the study group were better than those of the control group (all P<0.05). The combined use of capsules Shugan-jieyu and paroxetine could improve symptoms of depression and anxiety, offer a higher safety and accelerate the rehabilitation of extremity function.


Key words: 
Poststroke depression and anxiety; Shugan-jieyu
Efficacy and safety of crizotinib in treatment of ALK-positive advanced NSCLC patients
Authors: Xiaowen Jiang, Junhua Zhang, Wenxian Wan, Yiping Zhang
Journal: BMJ (2016)

Objective
To investigate the efficacy and tolerability of crizotinib in treatment of EML4-ALK-positive advanced non-small cell lung cancer(NSCLC)patient.


Methods
Clinical data of 47 NSCLC patients with positive ALK fusion gene receiving crizotinib (250 mg, q12h) treatment in Zhejiang Cancer Hospital from September 2013 to October 2015 were retrospectively analyzed. The efficacy and tolerability of crizotinib were evaluated.


Results
Among the 47 patients who were included in final analysis, 4.3%(2/47)achieved complete remission (CR), 66.0%(31/47)achieved partial remission (PR), 21.3%(10/47)achieved stable disease (SD) and 8.5%(4/47)was with progressive disease (PD). Objective response rate (ORR) was 70.2%(33/47), the disease control rates (DCR) was 91.5%(43/47). The overall progress free survival (PFS) of patients was 12.8 months.The median PFS of the first line group and the second line or above was 12.8 months and 11.6 months, respectively (χ2=0.004, P=0.947). The median PFS of patients with and without brain metastases before crizotinib treatment were 11.63 months and 13.6 months (χ2=0.023, P=0.881). Grade Ⅰ-Ⅱ adverse reactions occurred in 39 patients; gastrointestinal reactions were most frequent adverse effects, including nausea and vomiting (40.4%, 19/47) , diarrhea (19.1%, 9/47), followed by visual disturbance (42.6%, 20/47 ). Ⅲ-Ⅳ degree of elevated aminotransferase occurred in 6 patients (12.8%) and Ⅲ-Ⅳ degree of bone marrow suppression occurred in 2 patients (4.3%) .


Conclusion
Crizotinib demonstrates a high response rate and favorable tolerability profile in treatment of EML4-ALK-positive advanced NSCLC patients as a target therapy; and the first line and the second line or above patients can benefit from it.


Key words: 
Carcinoma, non-small-cell lung; Treatment outcome; Crizotinib; Anaplastic lymphoma kinase
Effect of Gastric Bypass vs Best Medical Treatment on Early-Stage Chronic Kidney Disease in Patients With Type 2 Diabetes and Obesity
Authors: Ricardo Vitor Cohen, Tiago Veiga Pereira, Cristina Mamédio Aboud, Tarissa Beatrice Zanata Petry, José Luis Lopes Correa, Carlos Aurélio Schiavon, Carlos Eduardo Pompílio, Fernando Nogueira Quirino Pechy, Ana Carolina Calmon da Costa Silva, Fernanda Lendimuth Gomes de Melo, Lívia Porto Cunha da Silveira, Pedro Paulo de Paris Caravatto, Helio Halpern, Frederico de Lima Jacy Monteiro, Bruno da Costa Martins, Rogerio Kuga, Thais Mantovani Sarian Palumbo, Neil Gerard Docherty, Carel Wynand le Roux
Journal: JAMA Surgery (2020)

Early-stage chronic kidney disease (CKD) characterized by microalbuminuria is associated with future cardiovascular events, progression toward end-stage renal disease, and early mortality in patients with type 2 diabetes.To compare the albuminuria-lowering effects of Roux-en-Y gastric bypass (RYGB) surgery vs best medical treatment in patients with early-stage CKD, type 2 diabetes, and obesity.For this randomized clinical trial, patients with established type 2 diabetes and microalbuminuria were recruited from a single center from April 1, 2013, through March 31, 2016, with a 5-year follow-up, including prespecified intermediate analysis at 24-month follow-up.A total of 100 patients with type 2 diabetes, obesity (body mass indexes of 30 to 35 [calculated as weight in kilograms divided by height in meters squared]), and stage G1 to G3 and A2 to A3 CKD (urinary albumin-creatinine ratio [uACR] >30 mg/g and estimated glomerular filtration rate >30 mL/min) were randomized 1:1 to receive best medical treatment (n = 49) or RYGB (n = 51).The primary outcome was remission of albuminuria (uACR <30 mg/g). Secondary outcomes were CKD remission rate, absolute change in uACR, metabolic control, other microvascular complications, quality of life, and safety.A total of 100 patients (mean [SD] age, 51.4 [7.6] years; 55 [55%] male) were randomized: 51 to RYGB and 49 to best medical care. Remission of albuminuria occurred in 55% of patients (95% CI, 39%-70%) after best medical treatment and 82% of patients (95% CI, 72%-93%) after RYGB (P = .006), resulting in CKD remission rates of 48% (95% CI, 32%-64%) after best medical treatment and 82% (95% CI, 72%-92%) after RYGB (P = .002). The geometric mean uACRs were 55% lower after RYGB (10.7 mg/g of creatinine) than after best medical treatment (23.6 mg/g of creatinine) (P < .001). No difference in the rate of serious adverse events was observed.After 24 months, RYGB was more effective than best medical treatment for achieving remission of albuminuria and stage G1 to G3 and A2 to A3 CKD in patients with type 2 diabetes and obesity.ClinicalTrials.gov Identifier: NCT01821508.
Real-world performance of blood-based host immune profiling in first-line immunotherapy treatment in advanced-stage non-small cell lung cancer.
Authors: R. Brian Mitchell, Patricia Rich, Paul R. Walker, Eric S Schaefer, Jiahuai Tan, Nagaprasad Nagajothi, John W. Dubay, Jason Keith Boyd, David N. Oubre, Nadeem Ikhlaque, Ray D. Page, Mazen Khalil, Suman Sinha, Hafez Halawani, S. Scott Boniol, Edgardo S. Santos, James Michael Orsini, Emily K. Pauli, Wallace L. Akerley
Journal: Journal of Clinical Oncology (2020)

9545 Background: Immune checkpoint inhibition (ICI) has improved outcomes for many treatment-naïve advanced non-small cell lung cancer (NSCLC) patients. However, better biomarkers are needed to predict patient response and guide treatment decisions considering added toxicity and higher cost of combination treatments. A prospectively designed, observational study assessed the ability of a clinically validated, blood-based, host immune classifier (HIC) to predict ICI therapy outcomes. Methods: The study (NCT03289780) includes 33 US sites having enrolled over 3,000 NSCLC patients at any stage and line of therapy. All enrolled patients are tested and designated HIC-Hot (HIC-H) or HIC-Cold (HIC-C) prior to therapy initiation. An interim analysis of secondary and exploratory endpoints was performed after 12- 18 months (mo) follow-up with the first 2,000 enrolled patients. We report the overall survival (OS) of HIC-defined subgroups comprising advanced stage (IIIB and higher) NSCLC patients treated with first-line regimens (284 ICI containing treatments, 877 total first-line patients). Results: In a real-world clinical setting, OS of advanced stage NSCLC treatment-naïve patients receiving platinum-based chemotherapy (n = 392) did not differ significantly from patients receiving any type of ICI containing regimen (n = 284); 11.7 mo vs. 14.4 mo; hazard ratio (HR) = 0.94 [95% confidence interval (CI): 0.76–1.17], p = 0.59. HIC-H patients experienced longer survival than HIC-C across multiple regimens, including ICI. For all ICI, median OS (mOS) was not reached for HIC-H (n = 196, CI: 15.4 mo–undefined) vs. 5.0 mo (n = 88, CI: 2.9 mo–6.4 mo) for HIC-C patients (HR = 0.38 [CI: 0.27–0.53], p &lt; 0.0001). Similar results were seen in the ICI only (16.8 mo vs. 2.8 mo; n = 117, HR = 0.36 [CI: 0.22–0.58], p &lt; 0.0001) and ICI/chemotherapy combination subgroups (unreached vs. 6.4 mo; n = 161, HR = 0.41 [CI: 0.26–0.67], p = 0.0003). In the PD-L1 high cohort (PD-L1 ≥50%), mOS for HIC-H was not reached (n = 81, CI: 13.9 mo–undefined) vs. 3.9 mo (n = 41, CI: 2.1 mo–7.8 mo) for HIC-C (HR: 0.39 [CI: 0.24-0.66], p = 0.0003). HIC results were independent of PD-L1 score (p = 0.81) and remained predictive of OS in first-line ICI-treated patients when adjusted for PD-L1 and other covariates by multivariate analysis (HR = 0.40 [CI: 0.28-0.58], p &lt; 0.0001). Conclusions: Blood-based host immune profiling may provide clinically meaningful information for selecting NSCLC patients for two common ICI containing regimens independent of and complementary to PD-L1 score.
超量利福平与异烟肼联用致死亡一例
Authors: 梁君, 李艳
Journal: BMJ (2004)

患者男,23岁,因乏力7 d,加重1 d入院.入院前7 d因胸痛、发热求治于某医院,诊断为结核性胸膜炎?,给予利福平、异烟肼治疗.患者服药时,利福平的剂量为450 mg/ 次 ,3次/d,药量明显超量;服异烟肼量为100 mg/次,3次/d.服药1 d后,开始出现全身乏力,并于1 d前病情加重,尿失禁,尿呈橘红色.体格检查:体温36.8℃,脉搏74次/min,血压120/90 mm Hg(1 mm Hg＝0.133 kPa).消瘦,嗜睡,表情冷漠,扶入病室,步态不稳,查体欠合作.皮肤、巩膜黄染;心肺无异常,肝、肾未扪及,双下肢无水肿;生理反射存在,病理征未引出.既往无肝炎病史。
Outcomes of patients (pts) with advanced gastro-intestinal stromal tumors (GIST) treated with multi-kinase inhibitors other than imatinib (IM) as first-line treatment.
Authors: Alice Boileve, Armelle Dufresne, Ali N. Chamseddine, Sarah Naomie Dumont, Medhi Brahmi, Julien Adam, Etienne Rouleau, Marie Karanian, Veronique Haddad, Matthieu Faron, Charles Honoré, Pierre Meeus, Axel Le Cesne, Jean-Yves Blay, Olivier Mir
Journal: Journal of Clinical Oncology (2020)

11532 Background: IM is the standard first-line therapy in advanced GIST, with a median progression-free survival (PFS) of 30 months. Recent multi-kinase inhibitors (MKIs) such as nilotinib, dasatinib or masitinib have been tested as first-line therapies in phase II/III studies. This might theoretically result in increased PFS (by the addition of a new line of treatment), or in early emergence of resistance to approved MKIs. Methods: A retrospective chart review was performed in GIST pts who received investigational MKIs (in phase II/III trials) as first-line treatment, followed by IM as second line. Data on demographics, molecular profile, PFS, and overall survival (OS) were collected in two French referral centers. Results: Of 47 pts, (57% females), 22 (47%) had a KIT exon 11 mutation, one a KIT exon 9 mutation (2%), one a PDGFR D842V mutation (2%). Five patients were wild-type for KIT and PDGFR. The mutational status was unknown in 18 pts (38 %). From 2005 to 2011, 21 pts (45%) received masitinib, 18 (38%) received dasatinib and 8 pts (17%) received nilotinib. Median PFS on first-line treatment was 18.9 months [95%IC: 9.0-26.0]. Median time-to-failure (TTF) with IM was 19.7 months [95%IC: 14.8-53.4]. Median time to second relapse was 50.2 months [95%IC: 31.2-92.2]. Thirty-five patients (74.5%) were dead at the end of follow-up. The median OS from time of initial diagnosis was 5.9 years [95%IC: 4.5-8.2]. Conclusions: GIST pts who received MKIs other than IM as first-line treatment and IM as second-line had a time to second relapse longer than that observed historically with IM in first line. This suggests that using MKIs other than IM in first line does not decrease IM efficacy in second line. Further comparative studies are needed to confirm these findings, but this is encouraging to further develop studies with other MKIs in the first line setting.
Combating Discrimination in Medical Education—Reply
Authors: Katherine A. Hill, Cary P. Gross, Dowin Boatright
Journal: JAMA Internal Medicine (2020)

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The safety and efficacy of immune-checkpoint inhibitor therapy in HIV infected cancer patients.
Authors: Phyo Thazin Myint, Faisal S. Ali, Dhiran Verghese, Taha Alrifai, Aye Mon Thet, Kelley Elizabeth Kozma
Journal: Journal of Clinical Oncology (2020)

e15141 Background: The clinical utility and safety of immune-checkpoint inhibitors (ICIs) in HIV infected cancer patients has not been well studied. Methods: We conducted a systematic search of Medline and Embase from inception to December 2019 to identify case reports and case series of ICI use in HIV infected cancer patients. Data were pooled utilizing a pre-specified protocol, and descriptive statistics were employed to report findings. Results: We identified 79 cases with a mean age of 52.5 (SD 11.65), 50 of whom were males. The most common cancers were NSCLC followed by Melanoma. Nivolumab was used in 54 patients whereas Pembrolizumab was used in 15 patients, with a mean of 25.7 months to ICI initiation from cancer diagnosis, and with a mean of 1.6 prior systemic lines of chemotherapy. 72 patients were on antiretroviral therapy. The mean baseline CD4 count was 385 (227.03), with a median baseline viral load of 40 (IQR 10.75-95.39). Mean CD4 count and median viral load during ICI therapy were 344.87 (SD 209.7) and 20 (0-400), respectively. 28 patients experienced and irAE; 63.2% and 63.6% of patients who experienced a decreased or increased CD4 count while on ICI therapy experienced an irAE, respectively. 27 patients experienced progressive disease (PD); 50% of patients who experienced a decrease in their CD4 count while on ICI therapy had PD. 13 patients experienced a complete response to ICI therapy; none of the patients who had a decreased CD4 count while on ICI therapy achieved complete response to ICI therapy, whereas 25% and 33% of patients who had an increased and stable CD4 count while ICI therapy experienced a complete response to therapy. The mortality rate was 24; 75% of patients who had a decreased CD4 count on ICI therapy suffered mortality, as opposed to 37.5% and 20% of patients with increased or stable CD4 count while on ICI therapy, respectively. Conclusions: Patients with a declining CD4 count while on ICI therapy may have poor outcomes with ICI therapy. The current body of evidence is weak, and further studies are needed to reach to a strong conclusion.
Genetic landscape of 43 patients with dMMR gastric cancer and its clinical implications.
Authors: Dongliang Wang, Nana Hu, Quan Xu, Erhong Meng, Zhongwu Li, Lin Shen
Journal: Journal of Clinical Oncology (2020)

e16501 Background: The FDA has approved immune checkpoint inhibitors for dMMR/MSI-H patients with solid tumors, but the efficacy varies greatly, so that more molecular biomarkers are needed to guide the clinical practice. Methods: In this study, the gene status of tumor tissues of 43 patients with dMMR gastric cancer previously identified by immunohistochemistry (IHC) was measured using TSO500, and the gene profile was preliminarily determined. Results: The genetic landscape is different between these 43 dMMR gastric cancer and TCGA as well as 200 cases of ordinary gastric cancer in China. The top five mutational genes in patients with dMMR gastric cancer were LRP1B (65.12%), RNF43 (62.79%), TP53 (58.14%), ARID1A (58.14%), BRCA2 (44.19%). In TCGA, the top five mutational genes were TP53 (48.1%), MUC16 (41.8%), SYNE1(32.1%), ARIDIA (31.4%) and LRP1B (30.7%). In 200 cases of patients with ordinary gastric cancer in China, the top five mutational genes were MUC6 (86.6%), MUC16 (84.6%), MACF1 (68.7%), DST (66.2%) and ZFHX4 (65.7%). The frequently abnormal signaling pathways in patients with dMMR gastric cancer were RTK/RAS (84%), P53 (77%), PI3K (74%), Notch (74%), Wnt (70%), Myc (47%),TGF-β(40%) signaling pathway. In addition, it was found that 40% of patients with dMMR gastric cancer were microsatellite-stable (MSS). Among the four dMMR biomarkers, 91.11% MLH1 negative or 86.67% MSH6 negative patients with dMMR gastric cancer were microsatellite-instable(MSI)–H, while only 11.11% MSH2 negative or 6.67% MSH6 negative patients with dMMR were MSI-H. Conclusions: This study provided important novel insight into the biology of dMMR gastric cancer and identified clinically genetic features for the future improvement management of patients with dMMR gastric cancer. It also suggested that in clinical practice, IHC is only suitable for preliminary screening. [Table: see text]