tbuckley/cabot-search huggingface dataset:
Safety and efficacy of pembrolizumab monotherapy in patients with advanced colorectal MSI-h/dMMR cancers.
Authors: Vasiliki Michalaki, Andreas Polydorou, Nikolaos Dafnios, Theodosios Theodosopoulos, Antonios Vezakis, Konstantinos Iliakopoulos, Despina Karandrea, Christos Papadimitriou
Journal: Journal of Clinical Oncology (2020)

e16010 Background: Tumours that are deficient in DNA mismatch repair (dMMR) have high microsatellite instability (MSI-H) are likely to be immunogenic, triggering upregulation of immune checkpoint proteins. New therapeutic options are needed for patients with advanced colorectal cancer whose disease has progressed after 1 or more lines of therapy. We investigated the safety and efficacy of pembrolizumab, a monoclonal antibody to programmed cell death–1 protein (PD-1 in a cohort of colorectal MSI-H/dMMR cancers patients with previously treated with one line of therapy. Methods: Twenty two eligible patients with histologically/cytologically confirmed MSI-H/dMMR metastatic colorectal cancer who experienced failure with one line of prior therapy received pembrolizumab 200 mg every 3 weeks until disease progression or unacceptable toxicity The primary endpoint was objective response rate (ORR) per RECIST v1.1, as assessed by radiologic review and safety. Tumours were classified as MSI-H/dMMR when expression as detected by immunohistochemistry of at least one of four MMR proteins was absent, or when at least two allelic loci size shifts among the five analyzed microsatellite markers were detected by PCR. Results: Of 22 patients enrolled, median (range) age was 62 (39-78) years. Median follow-up was 15.6 months. The ORR was 36.8 % (95% CI, 29.3% to 42.8%). Median progression-free survival was5.3 months (95% CI, 2.9 to 5.9 months) and median overall survival was 21.5 months (95% CI, 12.8 months to not reached).Treatment-related adverse events occurred in 13 patients (59%). -Four patients (18%) had grade 3 to 5 treatment-related adverse events. There were no treatment-related fatal adverse events. Conclusions: Pembrolizumab monotherapy demonstrated durable clinical benefit and manageable safety in patients with metastatic MSI-H/dMMR colorectal cancer who had previously received 1 line of treatment. Further study of pembrolizumab for this group of patients is warranted.
A phase I combination study of vigil and atezolizumab in recurrent/refractory advanced-stage ovarian cancer: Efficacy assessment in BRCA1/2-wt patients.
Authors: Rodney Paul Rocconi, Erin E. Stevens, Justin N. Bottsford-Miller, Sharad A. Ghamande, Phylicia Aaron, Gladice Wallraven, Ernest Bognar, Meghan Manley, Staci Horvath, Luisa Manning, John J. Nemunaitis, Thomas J Herzog, Bradley J. Monk, Robert L. Coleman
Journal: Journal of Clinical Oncology (2020)

3002 Background: Recent studies have shown poor clinical outcomes and limited survival advantage to checkpoint inhibitors (CIs) in advanced stage ovarian cancer (OvC). Vigil is a personalized precision vaccine constructed from autologous tumor tissue transfected with a DNA plasmid encoding GM-CSF and bi-shRNA-furin thereby creating TGFβ expression control and enhancing immune activation. Phase 1 and 2 trials in OvC demonstrate safety, functional immune activation and clinical response benefit. Combining Vigil with CIs may broaden responsiveness of immunotherapy in OvC. Methods: This is a randomized, 3-part safety Phase 1 study of Vigil in combination with Atezolizumab in recurrent OvC patients. Part 2 is a randomized, intra-patient crossover study of Vigil first (VF) or Atezolizumab first (AF) for two cycles followed by sequence of the combination of the two agents. Vigil (1 x 10 6 or 1 x 10 7 cells/ml) or Atezolizumab (1200mg) were administered 1x every 21 days each cycle until progression or untoward adverse event. We now report the preliminary results of part 2 of the study. Results: Twenty-one patients were randomized (1:1) to VF (n = 11) or AF (n = 10), groups were similar in demographics. Grade 3/4 toxic events occurred in 17% of AF patients compared to 3% in VF patients. Median OS of VF patients (n = 11) was not reached vs. AF (n = 10) 10.8 months suggested modest advantage to VF (HR 0.33, one-sided p 0.097). However, the subset analysis of BRCA1/2 wild type (wt) demonstrated more significant overall survival benefit in VF (n = 7) median OS not reached vs. AF (n = 7) 5.2 months (HR 0.12, one-sided p 0.015). Conclusions: The combination of Vigil immunotherapy and checkpoint inhibitor atezolizumab in recurrent OvC demonstrated safety and suggest a lower toxicity profile and a significant OS advantage in recurrent BRCA1/2-wt OvC patients treated with Vigil first followed by the combination of Vigil and Atezolizumab. Clinical trial information: NCT03073525 . [Table: see text]
Imaging sectional anatomy study on the optic canal by 64-slice spiral CT
Authors: Peng-fei Jiang, Ying Sun, Yuan-bin Li, Xiu-yu Dai
Journal: BMJ (2011)

This study was aimed to evaluate the application of64-slice spiral CT in imaging anatomy of the normal optic canal. The optic canals of 100 healthy subjects were examined by 64-slice spiral CT,and the imaging measurement of the anatomy structures were performed by the multi-planar reconstruction. The longest and the shorzest walls of the optic canal were the medial wall and the inferior wall, respectively.Results indicate that the imaging anatomic measurement of the optic canal can be accurately and easily performed by means of multi-planar reconstruction of 64-slice spiral CT.

Key words: 
Optic nerve;  Tomography,spiral computed
ATPIII有关高血脂治疗的新修订建议
Authors: 廖丰
Journal: BMJ (2005)

根据近2～3年来完成的5个大规模随机抽样、对照治疗的临床研究结果,美国高血脂症治疗指南--NCEP第三次成人治疗计划(ATP Ⅲ)于2004年7月发表了最新修订建议(简称新修订)[1,2],建议进一步强化心血管病高危人群降低胆固醇的治疗。
Results of emotional burnout study among oncologists in Russia.
Authors: Tatiana Semiglazova, Sufia Safina, Ilya Tsimafeyeu, Vera V. Karaseva, Gulnara Mukhamediarova, Aigul Fairushina, Sergey Tjulandin
Journal: Journal of Clinical Oncology (2020)

11011 Background: Emotional burnout (EB) is a syndrome caused by chronic work-related stress. This is a non-adaptive reaction to chronic stress resulting from professional activities and leading to the depletion of emotional and personal resources. Oncologists have high burnout risk, because involuntarily involved in the negative experiences of patients and get emotional stress. So it is important to develop measures to prevent EB for medical oncologists. Aim: The aim is to study the prevalence and severity of EB among oncologists and to develop preventive measures. Methods: A screening survey of the Russian Society of Clinical Oncology (RUSSCO) was conducted among 389 oncologists in various regions of Russia. The Maslach Burnout Inventory and online self-administered questionnaire were used. The questionnaire was sent out in November 2019. The questionnaire was based on a multi-factor model, which includes the following components: emotional exhaustion, depersonalization, reduction of professional achievements. Results: The average age of the respondents was 49.5 years, 61% of them were female. Chemotherapists made up 47.5%, 28% were surgeons, 8.5% were radiotherapists, 7% were diagnostic profile specialists, administrators made up 3%, 14.5% of the respondents had related specialties: clinical psychologists, pathologists, palliative care doctors. 30% of respondents had scientific degree. The results of the study were the following. 71.6% of specialists have expressed EB syndrome; 28% at EB formation stage, 1% have no signs of EB. There wasn’t a significant difference in EB rates across oncologists of various specialties. All stages of EB were identified. Female specialists are more likely to have manifestations of EB. EB severity was the same for doctors of inpatient and outpatient care. The extreme mode of work did not show significant differences of EB among both male and female specialists. First 5 years and more than 15 years of professional activity are most vulnerable to development of EB. EB was least affected by specialists over 65 years old with extensive experience. Conclusions: Hight level of EB was revealed among oncologists. Study results should be used during EB prevention, development of psychotherapeutic assistance and in educational programs.
Clinical characteristics of patients with primary pulmonary lymphoma
Authors: Lan-fang Li, Hua-qing Wang, Qian Fan, Hui-lai Zhang, Xian-ming Liu
Journal: BMJ (2011)

Clinical data of 13 patients with primary pulmonary lymphoma(PPL),treated in Tianjin Medical University Cancer Hospital from January 1999 to December 2009,were retrospectively reviewed.There were 8 patients with mucosa-associated lymphoid tissue(MALT)marginal zone lymphoma,2 patients with diffuse large B cell lymphoma,1 patient with NK/T cell lymphoma,1 patient with nodular sclerosis Hodgkin's lymphoma,and 1 patients with lymphocytic predominance Hodgkin's lymphoma.The main clinical symptoms were cough,fever,night sweat and weight loss.Two patients did not have any symptoms.Pulmonary consolidation shadows and multiple nodules were the main findings of CT scan.An air bronchogram was often seen in the consolidation imaging.The overall 5-year survival rate was 9/13 for all patients;while that was 7/8 for MALT marginal gone lymphoma.

Key words: 
Lymphoma; Pulmonary lymphoma
Bianca: Phase II, single-arm, global trial to determine efficacy and safety of tisagenlecleucel in pediatric/young adult (YA) patients (Pts) with relapsed/refractory B-cell non-Hodgkin lymphoma (R/R B-NHL).
Authors: Veronique Minard, Shannon L. Maude, Jochen Buechner, Joerg Krueger, Franco Locatelli, Andishe Attarbaschi, Theodore Willis Laetsch, Berta González Martínez, Cristina Diaz de Heredia Rubio, Rakesh Awasthi, Simon Newsome, Jaclyn Davis, Lida Bubuteishvili-Pacaud, Birgit Burkhardt
Journal: Journal of Clinical Oncology (2020)

e22504 Background: Pediatric/YA pts with r/r B-NHL are rare and have heterogenous, aggressive histology and poor prognosis. We report early results for tisagenlecleucel (anti-CD19 CAR-T cell therapy) in pediatric/YA pts with r/r B-NHL. Methods: BIANCA (NCT03610724) is a phase 2, single-arm, global, open-label trial of tisagenlecleucel in pediatric/YA pts with CD19+ r/r B-NHL. Pts must have confirmed mature B-NHL r/r to ≥1 prior lines of therapy and no active CNS involvement. Primary endpoint is ORR. Secondary outcomes include DOR, EFS, safety and pharmacokinetics. Results: As of Nov 4, 2019, 8 pts were enrolled, of whom 4 had large B-cell lymphoma (LBCL), 3 Burkitt lymphoma (BL), and 1 gray zone lymphoma (GZL) (Table). Five pts had ≥2 lines of prior therapy. Suitable apheresis product was harvested in all 8 pts. Five pts were infused and 3 were pending infusion at data cut off. Product was successfully manufactured within specifications for all infused pts. Median time from enrollment to infusion was 33 days (range 30-67). All 5 pts have ≥28 days follow up; 2 pts have ≥3 months follow up (median [range] 85 days [69-97]). All 8 pts received bridging chemotherapy (including 1 pt who also had surgery and 1 who also had radiotherapy). Tisagenlecleucel dose range was 0.3-1.1 × 10 8 CAR+ viable T cells (weight-based: 0.9-1.7 × 10 6 CAR+ viable T cells/kg). C max (range: C max = 8520-14,200 copies/µg; time to C max = 2-21 days; n = 4) was within range of expansion observed in pediatric/YA acute lymphoblastic leukemia and adult diffuse LBCL. All 5 pts had CRS; no grade ≥3 CRS was recorded. Three pts had neurologic events, including 2 grade 3/4 events. One pt died due to disease progression. Conclusions: Pediatric/YA pts with r/r B-NHL (including BL) were successfully infused with tisagenlecleucel in the BIANCA trial with a manageable safety profile. Apheresis/manufacturing were feasible in this cohort of rapidly progressing disorders. Tisagenlecleucel was shown to expand in vivo. BIANCA provides the first systematic data on CAR-T cell therapy in highly aggressive, pediatric/YA B-NHL. Planned enrollment is 35 pts (26 infused and evaluable). Clinical trial information: NCT03610724. [Table: see text]
Relationship between pulse wave velocity and blood pressure classification and cardiovascular risk factors stratification in patients with essential hypertension
Authors: 谢圣兰, 郭静, 宁新惠, 周喆, 魏宁, 赵航, 向小平
Journal: BMJ (2006)

目的 探讨原发性高血压患者血压分级以及危险因素分层与主动脉脉搏波速度(PWV)的关系.方法 应用脉搏波速度(PWV)自动测量系统测定入选的390例原发性高血压患者的颈动脉-股动脉PWV值,并对患者进行危险因素分层,比较不同血压水平及危险程度患者的动脉硬度.结果 1级与2级高血压患者的PWV差异无统计学意义[(10.8±1.7)m/s比(11.9±1.2)m/s,P=0.398];伴有一种以上心血管危险因素者的PWV显著高于单纯高血压患者[(10.4±1.4)m/s比(11.7±1.4)m/s,P=0.018].结论 存在一种或一种以上心血管危险因素的高血压患者PWV值明显高于无危险因素的高血压患者,心血管危险因素对动脉硬度的影响可能较大。
Metastatic behavior of mixed invasive ductal lobular carcinoma (mIDC/ILC).
Authors: Azadeh Nasrazadani, Yujia Li, George Tseng, Jennifer Xavier, Adrian V. Lee, Peter C. Lucas, Steffi Oesterreich, Norman Wolmark
Journal: Journal of Clinical Oncology (2020)

1085 Background: Mixed invasive ductal lobular carcinoma (mIDC/ILC) is a poorly described subtype of invasive breast cancer, characterized by its composition of both ductal and lobular histopathology. It is unclear if individual or both components drive metastasis. Literature is sparse regarding sites of metastatic spread of this elusive subtype of invasive breast cancer. Methods: Cohorts of patients with mIDC/ILC, invasive ductal carcinoma (IDC), and invasive lobular carcinoma (ILC) were identified from the UPMC Network Cancer Registry. Among these, 46 patients with mIDC/ILC, 1,131 patients with IDC, and 145 patients with ILC seen at UPMC Magee Women’s Hospital from 1990 – 2017 were found to have developed distant metastasis during the course of their disease. The metastatic pattern of spread was compared between the cohorts. Formalin-fixed, paraffin-embedded patient samples from the metastatic sites of a portion of the mIDC/ILC cases (n = 19) was acquired and evaluated by H&amp;E staining. Results: Patients with IDC were more likely than patients with ILC to have metastasis to the liver (p = 0.001) and lung (p &lt; 0.001), and less likely to have metastasis to the peritoneum (p &lt; 0.001). Patients with mIDC/ILC were more likely than patients with IDC to have peritoneal metastasis (p = 0.01), similar to patients with ILC. Compared to patients with ILC, patients with mIDC/ILC were more likely to have liver metastasis (p = 0.001), similar to patients with IDC. Evaluation of the metastatic lesions originating from mIDC/ILC displayed a spectrum of histopathology including mixed histology (n = 3), pure IDC (n = 3), pure ILC (n = 5), and indeterminate lesions with features of both IDC and ILC (n = 6). Two cases were uninterpretable due to significant crush artifact. Metastatic mIDC/ILC lesions with retained mIDC/ILC histology were found in vertebral, pleural, and skin tissues. Metastatic mIDC/ILC lesions with IDC histology were found in a cerebellar, liver, and chest wall lesion; whereas, those with ILC histology were found in bowel, omental fat, ovary, bone, and sacrum. Indeterminate histology metastatic lesions were found at liver, chest wall, cerebellar, and bone sites. Conclusions: mIDC/ILC metastasizes to a range of distant sites with a higher preference to the liver and peritoneum as compared to ILC and IDC, respectively. Metastatic lesions arising from mIDC/ILC tumors showed a spectrum of histologies, including mIDC/ILC, IDC, ILC and indeterminate lesions with features of both IDC and ILC. Ongoing genomics studies will provide further insight into development of metastases from mIDC/ILC tumors.
Sphingolipid, fatty acid and phospholipid metabolites are associated with disease severity and mTOR inhibition in lymphangioleiomyomatosis
Authors: Leonardo Bottolo, Suzanne Miller, Simon R Johnson
Journal: Thorax (2020)

Background Lymphangioleiomyomatosis (LAM) is a rare multisystem disease almost exclusively affecting women which causes loss of lung function, lymphatic abnormalities and angiomyolipomas. LAM occurs sporadically and in people with tuberous sclerosis complex (TSC). Loss of TSC gene function leads to dysregulated mechanistic target of rapamycin (mTOR) signalling. As mTOR is a regulator of lipid and nucleotide synthesis, we hypothesised that the serum metabolome would be altered in LAM and related to disease severity and activity. Methods Ultrahigh performance liquid chromatography-tandem mass spectroscopy was used to examine the serum metabolome of 79 closely phenotyped women with LAM, including 29 receiving treatment with an mTOR inhibitor and 43 healthy control women. Results Sphingolipid, fatty acid and phospholipid metabolites were associated with FEV 1 in women with LAM (eg, behenoyl sphingomyelin adjusted (adj.) p=8.10 × 10 -3 ). Those with higher disease-burden scores had abnormalities in fatty acid, phospholipid and lysolipids. Rate of loss of FEV 1 was associated with differences in acyl-carnitine, acyl-glycines, acyl-glutamine, fatty acids, endocanbinoids and sphingolipids (eg, myristoleoylcarnitine adj. p=0.07). In TSC-LAM, rapamycin affected modules of interrelated metabolites which comprised linoleic acid, the tricarboxylic acid cycle, aminoacyl-tRNA biosynthesis, cysteine, methionine, arginine and proline metabolism. Metabolomic pathway analysis within modules reiterated the importance of glycerophospholipid metabolites (adj. p=0.047). Conclusions Women with LAM have altered lipid metabolism. The associations between these metabolites, multiple markers of disease activity and their potential biological roles in cell survival and signalling, suggest that lipid species may be both disease-relevant biomarkers and potential therapeutic targets for LAM.
Association of radiation treatment failure in head and neck cancer with differential immune infiltrate.
Authors: Mohamed Abdelhakiem, Riyue Bao, Robert L Ferris, Curtis R. Pickering, Heath Devin Skinner
Journal: Journal of Clinical Oncology (2020)

6558 Background: Previously we have shown that PD-L1 expression is associated with treatment failure in Head and Neck Cancer (HNSCC) treated with radiation. We have further evaluated the effect of pre-treatment immune infiltrate on treatment failure following radiation. Methods: A total of 75 patients with HPV negative HNSCC treated with surgery and post-operative radiation were included in this study. Pre-treatment tumors were examined via RNA-Sequencing utilizing an Illumina platform. These data were then subjected to immune profiling utilizing publicly available software (xCell) to infer relative enrichment of immune cell infiltrate per sample. Each immune cell type detected at any level in at least 15 tumors was then evaluated for effect on loco-regional recurrence using Cox-regression analysis. Clinical variables included in this analysis include tumor stage, nodal stage and treatment site. Survival analysis was performed utilizing the method of Kaplan Meier, with log rank statistics used to test for significant comparisons. Results: The majority of HNSCCs analyzed in this study were from the oral cavity (65.3%), followed by the larynx and hypopharynx (28%) and oropharynx (6.7%). The total median dose of radiation delivered was 60 Gy (range: 36-79.2) and median follow up in living patients was 80.5 months (range: 7-190). On univariate analysis, no measured clinical variable was significantly associated with loco-regional recurrence (LRR). Similar to our previous studies in other HNSCC cohorts treated with radiation, PD-L1 expression was negatively associated with LRR (p = 0.005). Additionally, multiple immune cell infiltrates were negatively associated with LRR including: Th2 helper cells (p = 0.007), CD8+ central memory T cells (p = 0.02), immature dendritic cells (p = 0.037), CD4+ memory T cells (p = 0.043). In a multivariate model including these immune cell subsets, Th2 helper cells, CD8+ central memory T cells and immature dendritic cells remained significantly negatively associated with LRR following radiation. Conclusions: This analysis demonstrates the importance of pre-treatment immune infiltrate on outcomes in HNSCC and points to potential avenues to explore to augment response to radiation.
Effects of Sustained Treatment With Lixisenatide on Gastric Emptying and Postprandial Glucose Metabolism in Type 2 Diabetes: A Randomized Controlled Trial
Authors: Christopher K. Rayner, Linda E. Watson, Liza K. Phillips, Kylie Lange, Michelle J. Bound, Jacqueline Grivell, Tongzhi Wu, Karen L. Jones, Michael Horowitz, Ele Ferrannini, Domenico Tricò, Silvia Frascerra, Andrea Mari, Andrea Natali
Journal: Diabetes Care (2020)

OBJECTIVE Tachyphylaxis for slowing of gastric emptying is seen with continuous exposure to glucagon-like peptide 1 (GLP-1). We therefore aimed to establish whether prolonged use of a “short-acting” GLP-1 receptor agonist, lixisenatide, achieves sustained slowing of gastric emptying and reduction in postprandial glycemia. RESEARCH DESIGN AND METHODS A total of 30 patients with metformin-treated type 2 diabetes underwent assessment of gastric emptying (scintigraphy) and glucose metabolism (dual tracer technique) after a 75-g glucose drink, before and after 8 weeks’ treatment with lixisenatide (20 μg subcutaneously daily) or placebo, in a double-blind randomized parallel design. RESULTS Gastric retention of the glucose drink was markedly increased after lixisenatide versus placebo (ratio of adjusted geometric means for area under the curve [AUC] over 240 min of 2.19 [95% CI 1.82, 2.64], P &amp;lt; 0.001), associated with substantial reductions in the rate of systemic appearance of oral glucose (P &amp;lt; 0.001) and incremental AUC for blood glucose (P &amp;lt; 0.001). Lixisenatide suppressed both glucagon (P = 0.003) and insulin (P = 0.032), but not endogenous glucose production, over 120 min after oral glucose intake. Postprandial glucose lowering over 240 min was strongly related to the magnitude of slowing of gastric emptying by lixisenatide (r = −0.74, P = 0.002) and to the baseline rate of emptying (r = 0.52, P = 0.048) but unrelated to β-cell function (assessed by β-cell glucose sensitivity). CONCLUSIONS Eight weeks’ treatment with lixisenatide is associated with sustained slowing of gastric emptying and marked reductions in postprandial glycemia and appearance of ingested glucose. Short-acting GLP-1 receptor agonists therefore potentially represent an effective long-term therapy for specifically targeting postprandial glucose excursions.