tbuckley/cabot-search huggingface dataset:
Trend in incidence, first course of treatment, and survival in patients with glioblastoma.
Authors: Eunyoung Yang, Natalia Egorova, Gil Moskowitz, Nina A. Bickell
Journal: Journal of Clinical Oncology (2020)

e19178 Background: Glioblastoma (GBM) is the most common form of primary brain cancer and notoriously difficult to treat. Over the last 15 years, the population has been aging, yet, there are gaps in analysis of incidence of GBM associated with demographic changes. Further, several important treatment changes over time have led to 3 combined therapies becoming the standard of care since 2005, but their impact on GBM survival are not well established. Methods: The Surveillance, Epidemiology and End Results (SEER) database was analyzed from 2000-2015. We identified 30,955 GBM patients. We calculated the incidence rate and adjusted incidence rate using 2015’s population as a standard, then identified the trends in incidence and treatment using JoinPoint. Survival was analyzed with Kaplan-Meier and Cox proportional hazard models. Results: The incidence of GBM was highest among elderly (≥65yr), followed by adult (19-64yr) and pediatric population (≤18yr) (6.24, 1.64 and 0.10 per 100,000, respectively). The GBM incidence was significantly higher among white than black and other race (2.10 vs. 0.78 vs. 0.77 per 100,000; p &lt; 0.001) and among males than females (2.12 vs. 1.46 per 100,000; p &lt; 0.001). The incidence of GBM has increased from 1.63 to 1.96 (per 100,000) during this period with an annual percent change (APC) of 1.39 (p &lt; 0.001). After adjusting for patient age, the APC was 0.72 (p &lt; 0.001). Combination therapy has increased dramatically since 2000: from 29.3% to 60.9%. Those who underwent all three treatments had better overall survival than those who did not (p &lt; 0.001) after adjusting for comorbidities and demographics. Median survival increased from 7 months (2000-2003) to 11 months (2012-2015) (p &lt; 0.001). In the multivariable model, advanced age, stage, white race, and large tumor size were associated with worse survival, while combination treatment with improved survival (HR = 0.2; CL 0.22-0.24). Conclusions: While there appears to be a growth in the incidence of GBM, it is tempered by the aging of the population. Patients who underwent all three therapies had greater survival than those who did not. Efforts should focus on increasing the proportion of patients who undergo the standard care.
Is chronic refractory colitis from immune checkpoint inhibitor associated with good cancer outcome?
Authors: Weijie Ma, Anusha Thomas, Yinghong Wang
Journal: Journal of Clinical Oncology (2020)

e15102 Background: Immune checkpoint inhibitors (ICIs) are efficacious in treating many advanced malignancies. However, drug induced colitis limits their use significantly. We present cases with chronic refractory ICI colitis requiring long term immunosuppressive therapy and favorable cancer outcomes. Methods: We identified 3 cases who developed ICI colitis and persisted for longer than 6 months requiring long term immunosuppressant therapy. The patients’ clinical data was collected. Results: All patients were male, with median age of 55. Two had melanoma, one urothelial cancer. All patients received PD-1(L)-1 agents with colitis onset about 3-6 months after ICI treatment. All patients were taken off ICI permanently due to colitis over a duration of 19-30 months (peak grade of 3). Endoscopy of all three were grossly unremarkable, with lymphocytic colitis on pathology in all three. Patient A’s colitis achieved clinical and histological remission after 5 doses of vedolizumab, however recurred after 9 months with biopsy proven recurrence. Current management is anti-diarrheal medication given mild symptom. Patient B had more aggressive disease, with first recurrence after 2 doses of infliximab and steroid, achieved initial histological remission after 3 doses of vedolizumab and 2 additional infliximab, then had 2 nd recurrence after 3 months. Fecal microbiota transplantation as compassionate treatment was not effective. Thereafter, patient was resumed on vedolizumab ever since with clinical remission. Last histology evaluation showed persistent lymphocytic colitis 30 months after initial diagnosis. The third case had initial histological remission after 3 doses of vedolizumab, followed by recurrence after 4 months, which triggered another 3 doses of vedolizumab, with persistent grade 3 diarrhea despite resolution of histological inflammation after total 6 doses of vedolizumab. Patient was subsequently treated with steroid and ustekinumab with clinical remission. At the end of follow up, all three patients have sustained cancer remission over 19-31 months. Conclusions: IMC is a common adverse event from ICI, and could progress to a chronic inflammatory condition that require long term treatment. Histological remission does not preclude future recurrence of colitis. Persistent toxicity could be a surrogate marker for enduring ICI effect which may be associated with favorable cancer outcome. Long term immunosuppression can be essential for refractory ICI colitis cases for clinical remission.
糖尿病非酮症高渗综合征一例
Authors: 童朝阳, 高鑫
Journal: BMJ (2004)

患者男,22岁,因乏力、口干1个月,呕吐5天,无尿半天来急诊,无腹痛腹泻史,无糖尿病、肾脏疾病史.体检:形体正常, 神志清楚,血压 90/60 mm Hg(1 mm Hg＝0.133 kPa),心率96次/min,律齐.实验室检查:血红蛋白199 g/L,白细胞16.4×109/L,尿酮(-)、尿糖(++++),尿蛋白(-).葡萄糖80 mmol/L,血酮(-)、钠130 mmol/L、钾4.4 mmol/L、氯81 mmol/L、肌酐447 μmol/L、尿素氮29.5 mmol/L.血气分析:pH 值7.342、二氧化碳分压38.6 mm Hg、氧分压 84 mm Hg、剩余碱-3.6 mmol/L。
Caspase-11–mediated enteric neuronal pyroptosis underlies Western diet–induced colonic dysmotility
Authors: Lan Ye, Ge Li, Anna Goebel, Abhinav V. Raju, Feng Kong, Yanfei Lv, Kailin Li, Yuanjun Zhu, Shreya Raja, Peijian He, Fang Li, Simon Musyoka Mwangi, Wenhui Hu, Shanthi Srinivasan
Journal: Journal of Clinical Investigation (2020)

Enteric neuronal degeneration, as seen in inflammatory bowel disease, obesity, and diabetes, can lead to gastrointestinal dysmotility. Pyroptosis is a novel form of programmed cell death but little is known about its role in enteric neuronal degeneration. We observed higher levels of cleaved caspase-1, a marker of pyroptosis, in myenteric ganglia of overweight and obese human subjects compared with normal-weight subjects. Western diet-fed (WD-fed) mice exhibited increased myenteric neuronal pyroptosis, delayed colonic transit, and impaired electric field stimulation-induced colonic relaxation responses. WD increased TLR4 expression and cleaved caspase-1 in myenteric nitrergic neurons. Overactivation of nitrergic neuronal NF-κB signaling resulted in increased pyroptosis and delayed colonic motility. In caspase-11-deficient mice, WD did not induce nitrergic myenteric neuronal pyroptosis and colonic dysmotility. To understand the contributions of saturated fatty acids and bacterial products to the steps leading to enteric neurodegeneration, we performed in vitro experiments using mouse enteric neurons. Palmitate and lipopolysaccharide (LPS) increased nitrergic, but not cholinergic, enteric neuronal pyroptosis. LPS gained entry to the cytosol in the presence of palmitate, activating caspase-11 and gasdermin D, leading to pyroptosis. These results support a role of the caspase-11-mediated pyroptotic pathway in WD-induced myenteric nitrergic neuronal degeneration and colonic dysmotility, providing important therapeutic targets for enteric neuropathy.
肝脏局灶结节性增生的CT和MRI诊断
Authors: 柴瑞新, 唐业欢, 叶慧义
Journal: BMJ (2012)

肝脏局灶结节性增生(FNH)是常见的肝细胞来源的肝脏良性肿瘤样病变,由正常或接近正常的肝细胞异常排列形成,内可有小胆管,但不与大胆管相通,有库普弗(Kupffer)细胞,但常没有功能.随着多排螺旋CT及MRI技术的发展和应用,影像学检查对FNH的诊断具有越来越重要的作用,MRI已成为可准确诊断的方法。
Learning relevant H&amp;E slide morphologies for prediction of colorectal cancer tumor mutation burden using weakly supervised deep learning.
Authors: Rohan P. Joshi, Andrew J. Kruger, Lingdao Sha, Madhavi Kannan, Aly A. Khan, Martin Stumpe
Journal: Journal of Clinical Oncology (2020)

e15244 Background: Tumor mutation burden (TMB) is the number of non-synonymous mutations present in a cancer exome. In colorectal cancer (CRC), high TMB is associated with microsatellite instability (MSI), POLE mutations, and response to immunotherapy. TMB prediction from whole-slide images (WSIs) could aid workflows that determine MSI and POLE status. Deep learning has previously been used to predict MSI status from WSIs. This approach assumed the morphologies of all regions within the tumor are equally associated with MSI. Here, we predict TMB using a weakly supervised deep learning framework that relaxes this assumption and automatically learns relevant regions within the tumor that are most associated with TMB, potentially uncovering morphological associations. Methods: Weakly supervised learning methods facilitate classification of samples that contain many individual instances, only some of which are related to the sample label. Here, a given WSI has a single TMB-high or -low label and contains individual regions that may or may not be associated with TMB status. We implemented a ResNet18 attention-based, multiple-instance learning (MIL), convolutional neural network to simultaneously learn which tiles are important for prediction of the slide-level TMB and the tile features that are associated TMB-high and -low. We determined performance through 8-fold cross-validation within a Tempus dataset using a 75%-12.5%-12.5% split of ~940 WSIs for training, validation, and testing folds. Results: In the cross-validation, we observed a receiver operating characteristic area under the curve of 0.854 (95% CI 0.776-0.932), an average precision of 0.723 (95% CI 0.580-0.865), and an accuracy of 0.889 (95% CI 0.833-0.945) in the held-out test sets. Morphologies predicted as irrelevant for TMB include adipose tissue and WSI artifacts. Visualizations of model weights show morphologies determined to be most associated with TMB-high and -low, such as high tumor/lymphocyte content and vasculature/red blood cells, respectively. Conclusions: Attention-MIL shows high performance for the prediction of TMB in CRC from H&amp;E images and potentially reveals the morphologies of CRC that are most associated with TMB. Future directions include further investigation of morphological associations, generalizing this model beyond Tempus acquired data, and re-training on the entire Tempus dataset.
Real-world healthcare resource utilization (HRU)/costs associated with venetoclax treatment among chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL) patients.
Authors: Kerry Anne Rogers, Bruno Emond, Ameur M Manceur, Frederic Kinkead, Marie-Hélène Lafeuille, Patrick Lefebvre, Qing Huang
Journal: Journal of Clinical Oncology (2020)

e19354 Background: Ibrutinib (Ibr) is an established standard of care in CLL/SLL patients across lines, regardless of age, comorbidities and risk status. With the introduction of venetoclax (Ven) in the treatment landscape, there is a need to understand the real-world treatment sequencing of targeted oral agents, and the implication of sequencing on HRU/costs. This retrospective study evaluated HRU/costs associated with Ven treatment in various sequencing scenarios, including prior use of Ibr. Methods: Optum Clinformatics Extended DataMart De-Identified Databases (4/11/2015-6/30/2019) were used to identify adults with CLL/SLL treated with Ven (excluding investigational combination therapies). The index date was the start of the first Ven-based line of therapy (index LOT) and the baseline period was the 12-month period pre-index. Mean all-cause HRU/costs per patient per month (PPPM) were calculated during the index LOT and the Ven ramp-up period (first 30 days post-index). Results: Among a total of 11,861 CLL/SLL patients receiving ≥1 LOT, 121 patients (1.0%) were treated with Ven, including 25 patients (64.0% single agent) using Ven in first line (1L cohort), 30 (90.0% single agent) in second line (2L cohort), and 66 (83.3% single agent) in third line or later (3L+ cohort). Mean age was 71.6 years; 33.1% were female; mean baseline Quan-Charlson Comorbidity Index score was 4.7; median follow up from the start of 1L was 25.3 months; median duration of index LOT was 4.2 months. The majority of 2L+ Ven patients were previously treated with Ibr (2L: 56.7%, 3L+: 74.2%). Patients in all 3 cohorts had frequent outpatient (OP) visits PPPM during their index LOT (1L: 4.58; 2L: 4.75; 3L+: 5.71). Total costs PPPM during the index LOT were highest in the 1L cohort (1L: $21,762; 2L: $17,697; 3L+: $20,900), driven by higher OP costs (1L $9,402; 2L: $5,633; 3L+: $7,701). Increased total costs PPPM were observed during Ven ramp-up (1L: $31,707; 2L: $21,036; 3L+: $25,362). Compared to the overall 2L cohort, those treated with Ibr in 1L had lower total costs PPPM (index LOT: $15,350; V ramp-up: $15,882). Conclusions: In this descriptive study, the highest costs PPPM were observed for Ven treatment in the 1L. Prior treatment with Ibr was common among 2L and 3L+ CLL/SLL patients treated with Ven. Among 2L Ven patients, those previously treated with Ibr in 1L had $2,347 and $5,154 lower costs PPPM during 2L and Ven ramp-up, respectively, suggesting that previous Ibr treatment may help reduce costs in subsequent V treatment.
数字减影血管造影引导下球囊扩张术治疗食管癌术后早期幽门梗阻性胃排空障碍
Authors: 石维平, 束余声, 王书祥, 孙超, 史宏灿, 陆世春, 王康, 贺建胜, 缪乾兵, 金卫国
Journal: BMJ (2011)

食管癌切除术后早期幽门梗阻是常见的并发症之一.本研究对我院2005年1月至2010年1月经颈、胸、腹三切口行食管癌切除术后发牛幽门梗阻的10例患者,行数字减影血管造影(digital subtraction angiography,DSA)引导下幽门球囊扩张术,现总结报告如下。
Bosutinib in patients with chronic phase chronic myeloid leukemia intolerant to prior tyrosine kinase inhibitors: Analyses from the BYOND study.
Authors: Susanne Saussele, Carlo Gambacorti-Passerini, Valentin García Gutierrez, Camille N. Abboud, Simon Purcell, Andrea Viqueira, Eric Leip, Thomas Ernst, Frank Giles, Andreas Hochhaus
Journal: Journal of Clinical Oncology (2020)

7551 Background: Bosutinib (BOS) is approved for patients (pts) with Philadelphia chromosome (Ph)+ chronic myeloid leukemia (CML) resistant/intolerant to prior therapy and in newly diagnosed pts in chronic phase (CP). Methods: The ongoing phase 4 BYOND study is further evaluating efficacy and safety of BOS (starting dose 500 mg/d) for CML resistant/intolerant to prior tyrosine kinase inhibitors (TKIs). We report findings in pts intolerant to all prior TKIs. Data are reported ≥1 y after the last enrolled pt (~85% TKI-intolerant pts had ≥2 y follow-up). Results: Of 163 pts who received BOS, 156 had Ph+ CP CML. 73 pts entered the study due to intolerance; 29, 26 and 18 had 1 (CP2L), 2 (CP3L) and 3 (CP4L) prior TKIs, respectively. After a median follow-up of 30.4 mo, median treatment duration across all 3 cohorts (CP2L, CP3L, CP4L, respectively) was 25.3 mo (29.2, 24.6, 17.6) and median dose intensity was 292.0 mg/d (304.5, 284.8, 272.1). Across CP CML cohorts (CP2L, CP3L, CP4L, respectively), 84.9% of patients (82.8%, 88.5%, 83.3%) had ≥1 dose reduction and 83.6% (79.3%, 84.6%, 88.9%) had ≥1 dose interruption due to adverse events (AEs). At the data cutoff, 53.4% (CP2L 65.5%, CP3L 42.3%, CP4L 50.0%) were still receiving BOS. The most common reason for discontinuation was AEs (28.8%). The most common ( &gt; 40%) treatment-emergent AEs (TEAEs) were diarrhea (87.7%) and nausea (43.8%). Grade 3/4 TEAEs in &gt; 10% of pts were diarrhea (16.4%), increased alanine aminotransferase (19.2%) and increased lipase (12.3%). Most pts with a valid baseline assessment achieved major molecular responses (MMR) across therapy lines (Table). Deaths occurred in 4 pts (CP2L 1, CP3L 3, CP4L 0); none were related to BOS or CML. Overall survival rate (95% CI) at 2 y in TKI-intolerant pts was 97.2% (89.2–99.3); rates were 96.4% (77.2–99.5), 96.0% (74.8–99.4) and 100% (100–100) in CP2L, CP3L and CP4L pts, respectively. Conclusions: A long duration of treatment and high response rate were observed in TKI-intolerant pts treated with BOS. Despite being intolerant to all prior therapies, ≥50% of pts in the overall intolerant cohort remained on BOS treatment at the data cutoff and &gt; 80% achieved/maintained MMR. These results further support BOS use in pts with Ph+ CP CML and intolerance to all prior TKIs. Clinical trial information: NCT02228382 . [Table: see text]
A phase II open-label, single-center, nonrandomized trial of Y90-radioembolization in combination with nivolumab in Asian patients with advanced hepatocellular carcinoma: CA 209-678.
Authors: Wai Meng David Tai, Kelvin Siu Hoong Loke, Apoorva Gogna, Sze Huey Tan, David Chee Eng Ng, Tiffany Priyanthi Hennedige, Farah Irani, Joycelyn Jie Xin Lee, Chow Wei Too, Matthew C.H. Ng, Chee Kian Tham, Justina Yick Ching Lam, Si-Lin Koo, Alexander Chung, Han Chong Toh, Choon Hua Thng, Kiat Hon Lim, Joe Poh Sheng Yeong, Chung Yip Chan, Su Pin Choo
Journal: Journal of Clinical Oncology (2020)

4590 Background: Nivolumab (N) and Y90-radioembolization (RE) are both therapeutic options in advanced hepatocellular carcinoma (aHCC). Increasing evidence suggests that radiotherapy synergizes with immune checkpoint inhibitors to augment anti-tumour effects. Methods: Eligible Child-Pugh A aHCC patients (pts) were treated with Y90-RE followed by N 240mg, 21 days after Y90-RE and every 2 weeks thereafter. Pre- and on-treatment tumor biopsies together with circulating biomarkers were obtained. Primary end-point was overall response rate (ORR) (per RECIST v 1.1). Overall response was defined as the composite overall response observed for the lesions within Y90-RE field and outside Y90-RE field. Key secondary end points included disease control rate (DCR), progression free survival (PFS), overall survival (OS), and safety. 36 evaluable pts were needed to assess whether the addition of N improved the ORR of Y90-RE from 21% to 41% as determined by Simon two-stage optimal design with 80% power and one sided significance level of 0.05. Results: Forty pts were enrolled of which 36 were evaluable. At baseline: 63.9% were HepB in aetiology; 63.9% BCLC stage C; 47.2% had AFP &gt; 400ng/mL; number of liver lesions – median 5 (range 1- 20); size of largest liver lesion – median 80mm (range 14-177mm); 27.8% had prior TACE; and 13.9% had prior systemic therapy. ORR was 31% (95% CI 16.4 - 48.1%). Eight out of 11 responders had not progressed at study cut-off. DCR was 58.3%. 81% of target lesions within Y90-RE field regressed. With a median follow up of 16.4 months, median PFS and OS were 4.6 months (95% CI 2.3m - 8.4m) and 15.1 months (95% CI 7.8m - NE) respectively. Six- and 12-month PFS rates were 44.2% (95% CI 27.3% - 59.9%) and 26.1% (95% CI 11.2% - 43.8%) respectively. Overall, N+ Y90-RE was well tolerated and safe; only 11% had grade 3/4 treatment related adverse events (AEs). Responders demonstrated significant alterations of LIF, MIG and Eotaxin3 levels in the pre-treatment cytokine analyses. Conclusions: Combination N+Y90-RE resulted in an encouraging ORR of 31% (95% CI 16.4 - 48.1%) in aHCC. 81% of target lesions within Y90-RE field regressed suggesting synergy in combining Y90-RE with nivolumab. This combination is safe and tolerable with low G3/4 treatment related AEs of 11%. Further biomarker analyses will be presented at the meeting. Clinical trial information: NCT03033446 .
PTPRD/PTPRT mutations as potential positive predictor for response of immune checkpoint inhibitors in non-small cell lung cancer (NSCLC).
Authors: Jian Zeng, Guoqiang Wang, Zhengqing Yan, Hao Zheng, Jianqiang Li, Feng Tao
Journal: Journal of Clinical Oncology (2020)

e15112 Background: Immune checkpoint inhibitors (ICIs) have demonstrated positive results in non-small cell lung cancer (NSCLC) patients, with durable responses and prolonged overall survival (OS). Nevertheless, the response rate to immunotherapy is still limited. It is necessary to identify clinically useful biomarkers that can distinguish patients who can respond to ICIs. PTPRD/PTPRT are the phosphatases of JAK-STAT signaling, which may be associated with response to ICIs. Here we aimed to demonstrate the association between PTPRD/PTPRT and ICIs. Methods: Genomic and survival data of NSCLC patients administrated with anti–PD-1/PD-L1 or anti–CTLA-4 antibodies (Rizvi2015; Hellmann2018; Rizvi2018 Samstein2019) were retrieved from publicly accessible data. Genomic, survival and mRNA data of 1007 patients with NSCLC was obtained from The Cancer Genome Atlas (TCGA). Association between PTPRD/PTPRT mutation and progression-free survival (PFS) and overall survival (OS) were analyzed. Gene set enrichment analysis (GSEA) was used to determine potentially relevant gene expression signatures between specific subgroups. Results: PTPRD/PTPRT mutations were significantly associated with better PFS in Rizvi2015 cohort (HR = 0.16; 95% CI, 0.02-1.17; P = 0.03), Hellmann2018 cohort (HR, 0.49; 95% CI, 0.26-0.94; P = 0.03) and Rizvi2018 cohort (HR = 0.64; 95% CI, 0.44-0.92; P = 0.01). PTPRD/PTPRT mutation was also significantly associated with better OS in Samstein2019 cohort (HR, 0.66; 95% CI, 0.45-0.97; P = 0.03). In TCGA, no association between PTPRD/PTPRT mutations and OS was observed (P = 0.91), suggesting that PTPRD/PTPRT mutations were not prognostic factor. PTPRD/PTPRT mutations were associated with increased TMB (P &lt; 0.0001). The mRNA expression of STAT1 and CD4 was higher in patients with PTPRD/PTPRT mutant type than PTPRD/PTPRT wild type. Gene Set Enrichment Analysis revealed prominent enrichment of signatures related to inflammatory response, interferon gamma response and antigen processing and presentation in patients with PTPRD/PTPRT mutation. Conclusions: Our results suggest that PTPRD/PTPRT mutation is associated with better PFS and OS in NSCLC patients receiving ICIs by increasing immune-related gene signatures. The role of PTPRD/PTPRT in immunotherapy is needed to be further studied.