tbuckley/cabot-search huggingface dataset:
A geriatric assessment (GA) intervention to reduce treatment toxicity in older patients with advanced cancer: A University of Rochester Cancer Center NCI community oncology research program cluster randomized clinical trial (CRCT).
Authors: Supriya Gupta Mohile, Mostafa Refaat Mohamed, Eva Culakova, Huiwen Xu, Kah Poh Loh, Allison Magnuson, Marie Anne Flannery, Erika E. Ramsdale, Richard Francis Dunne, Nikesha Gilmore, Spencer Obrecht, Amita Patil, Sandy Plumb, Lisa M Lowenstein, Michelle Christine Janelsins, Karen Michelle Mustian, Judith O. Hopkins, Jeffrey L. Berenberg, Rakesh Gaur, William Dale
Journal: Journal of Clinical Oncology (2020)

12009 Background: GA evaluates aging-related domains (e.g., function) known to be associated with cancer treatment toxicity. In this CRCT, we evaluated if providing a GA summary with management recommendations to oncologists can reduce toxicity in older patients (pts) with advanced cancer receiving chemotherapy and/or other agents with a high reported prevalence of grade 3-5 toxicity. Methods: Pts aged &gt; 70 with incurable solid tumors or lymphoma and &gt; 1 impaired GA domain starting a new treatment regimen were enrolled. Community oncology practices were randomized to intervention (oncologists received GA summary/recommendations for impairments) or usual care (none given). The primary outcome was proportion of pts who experienced any grade 3-5 toxicity (CTCAE v.4) within 3 months. Practice staff prospectively captured toxicities; blinded oncology clinicians reviewed medical records to verify. Secondary outcomes included 6 month overall survival (OS) and treatment intensity (standard vs reduced). Outcomes were analyzed using generalized linear mixed/Cox models with Arm as a fixed effect, controlling for practice. Results: From 2013-19, 718 pts were enrolled from 41 practices. Age (mean 77 yrs), sex (43% women), number of impaired GA domains (median 4/8), and treatment type (chemotherapy 88%) were not different by Arm. More pts in intervention were Black (12% vs 3%, p&lt;0.01), had GI cancer (38% vs 31%, p&lt;0.01), and had prior chemotherapy (31% vs 23%, p=0.02). Pts in intervention experienced a lower proportion of grade 3-5 toxicity (175/349; 50%) than pts in usual care (262/369; 71%). The relative risk (RR: intervention vs usual care) of grade 3-5 toxicity was 0.74 (95% CI: 0.63-0.87; p=0.0002); the difference was mostly driven by non-heme toxicities (RR 0.73; 95% CI: 0.53-1.0, p&lt;0.05). OS was not significantly different (71% vs 74%, p=0.3). More pts in intervention received reduced intensity treatment at cycle 1 (49% vs 35%, RR 0.81, p=0.01). Dose modifications due to toxicity were lower in intervention (42% vs 58%, p&lt;0.0001), but results were not significant after controlling for practice (RR 0.85; 95% CI: 0.67-1.08, p=0.2). Conclusions: Providing GA information to oncologists reduces the proportion of older pts who experience grade 3-5 toxicity from high-risk palliative cancer treatment, without compromising OS. Reduced treatment intensity at cycle 1 may explain these results. Funding: R01CA177592, U01CA233167, UG1CA189961. Clinical trial information: NCT02054741 .
Defining the role of neoadjuvant systemic therapy in high-risk retroperitoneal sarcoma: A multi-institutional TARPSWG study.
Authors: William W. Tseng, Francesco Barretta, Lorenzo Conti, Giovanni Grignani, Francesco Tolomeo, Markus Albertsmeier, Martin K Angele, Piotr Rutkowski, Jacek Skoczylas, Antonino De Paoli, Federico Navarria, James S Hu, Chandrajit P Raut, Mark Fairweather, Jeffrey M. Farma, Carolyn Nessim, Neha Goel, Ty Subhawong, Valerie Patrice Grignol, Alessandro Gronchi
Journal: Journal of Clinical Oncology (2020)

11513 Background: Surgery is the mainstay of treatment for patients with retroperitoneal sarcoma (RPS), but this can be challenging, and recurrence rates are high. Novel treatment approaches are needed. In this study, we sought to 1) determine the frequency and potential predictors of radiologic tumor response and 2) assess clinical outcomes in patients with primary high risk RPS who were treated at sarcoma referral centers with neoadjuvant systemic therapy followed by surgery. Methods: Clinicopathologic data was retrospectively collected for eligible patients treated from 2008-2018 at 13 institutions within the Transatlantic Australasian Retroperitoneal Sarcoma Working Group (TARPSWG). For each patient, preoperative objective response (RECIST1.1) was reported by each institution. Univariable and multivariable logistic models were performed to determine predictors of response. Kaplan-Meier plots were constructed for overall survival (OS) and cumulative incidences of local recurrence (LR) and distant metastasis (DM). Results: In total, 158 RPS patients were included in this study. A median of 3 cycles (IQ range 2-4) of neoadjuvant systemic therapy were given. No complete responses were observed. Partial response (PR) was seen in 37 patients (23%), stable disease (SD) in 88 (56%) and progressive disease (PD) in 33 (21%). Subtype-specific differences were seen including PR in 5 out of 11 (45%) patients with undifferentiated pleomorphic sarcoma. Overall, higher number of cycles given was positively associated with PR (p = 0.005). No other factors including receipt of neoadjuvant radiation therapy were predictive of PR. All patients underwent complete (R0/R1) resection with a major complication (Clavien-Dindo ≥3) rate of 23%. Differences in OS were observed based on preoperative response type (p = 0.005). In grade 3 dedifferentiated liposarcoma, patients who received adriamycin-ifosfamide versus another regimen had decreased LR and improved OS. In leiomyosarcoma, patients who received adriamycin-DTIC versus another regimen had a higher PR rate (37% vs. 16%), decreased LR, DM and improved OS. Limited by low numbers, these subtype-specific data did not reach statistical significance. Conclusions: In patients with high risk RPS, response to neoadjuvant systemic therapy is overall modest and may be regarded as an indicator of disease biology to predict survival after surgery. Subtype-specific regimens should be further validated and incorporated into prospective trials of neoadjuvant systemic therapy in RPS (e.g. STRASS2).
Exploring glocalization in the construction and implementation of global curricula.
Authors: Meredith Elana Giuliani, Janneke Frambach, Erik Driessen, Maria Athina (Tina) Martimianakis
Journal: Journal of Clinical Oncology (2020)

11020 Background: Despite proposed advantages of global oncology curricular harmonization including physician mobility and improving the quality of care the challenges and unintended consequences require greater study. The aim of this study was to problematize the concept and implementation of global oncology curricula and their relationship to local contexts of power and culture. Methods: Fourteen international participants involved in the development and implementation of global oncology curricula completed in-depth, one-on-one semi-structured interviews lasting 40-60 minutes. Snowball sampling was employed. The participant sample was representative of different geographic regions, genders and professional scopes of practice to ensure diverse perspectives were sought. Through iterative analyses, using an abductive approach, the study team discussed and reviewed the data and made revisions through collaborative analysis to enhance comprehensiveness and to improve credibility. In the final analysis the meaning and implication of the themes were discussed yielding a conceptual analysis. Results: Our data have articulated 5 key challenges for global curricula including 1) Ambiguous or conflicting perspectives on the purpose and scope of Global Oncology Curricula 2) Insufficient representation of diverse perspectives and realities in the creation of the final curricula 3) A rigid conceptualization of competency requirements 4) A mismatch between the curricular requirements and local context and 5) The influence of power relationships and decision makers. Leveraging the strengths of diversity including fostering representation, addressing power differentials and factoring local contexts may be an approach to mitigating these challenges. Conclusions: Global oncology curricula may serve important advocacy roles within the healthcare system. Leveraging diversity may positively impact the common challenges in the construction and implementation of global oncology curricula.
Pregnancy-Pancytopenia-Splenic vein thrombosis
Authors: Xueying Chu, Lu Zhang, Wei Qiu, Yuchao Guo
Journal: BMJ (2017)

报道1例青年妊娠20周的女性，以上腹痛起病，检查发现全血细胞减少及脾静脉血栓，伴有血乳酸脱氢酶及网织红细胞升高等溶血性贫血证据，抗凝治疗后症状缓解，后经一系列筛查最终诊断阵发性睡眠性血红蛋白尿，予患者低分子肝素抗凝好转后出院。
Expression of Syk gene and the methylation of its promoter in cervical carcinoma
Authors: Shu-ping Zhao, Gui-xia Sun, De-hua Ma, Rong-hui Chen
Journal: BMJ (2009)

Reverse transcription-PCR and methylation-specific PCR (MSP) were used to determine the expression levels of Syk gene and the methylation status of its promoter in tissue samples from 60 patients with cervical cancer, 50 patients with cervical intraepithelial neoplasia (CIN), and 20 normal controls. We also analyzed the association of the methylation status and expression levels of Syk gene with linicopathological features of patients. The expression rates of Syk gene in 20 normal cervical tissue samples and 18 CIN Ⅰ samples were both 100% ; those of CIN Ⅱ- Ⅲ and cervical carcinoma were 56% (18/32)and 35% (21/60) respectively. Among cervical carcinoma patients, the expression of Syk mRNA was detected in one out of 13 cases with lymph node metastasis (1/13) and in 20 out of 47 cases with no lymph node metastasis (43%). The methylation of Syk gene in promoter region was detected in 34 out of 60 cases of cervical carcinoma (57%) ; while there was no methylation in CIN cases. In 13 cases with lymph node metastasis, 11 were found to have the methylation of Syk gene. The methylation rate of Syk promoter in cervical carcinoma was higher than that of CIN tissue( x~2 = 7. 13, P ＜0. 01 ). The methylation status of Syk gene was correlated with the lymph node metastasis ( P＜ 0. 05 ), but not with other clinicopathological parameters ( P ＞ 0. 05). There was a significant correlation between methylation status and expression level of Syk gene ( P ＜ 0. 05 ). The hypermethylation leads to silencing of the Syk gene in human cervicalcarcinoma. Syk hypermethylation may be associated with oncngenesis, metastasis of cervical carcinoma.

Key words: 
Uterine cervical neoplasms;  Gene;  suppressor
Letter to the Editor: Cilofexor in Patients With Nonalcoholic Steatohepatitis (NASH): Is It Really Effective?
Authors: Ankur Jindal, Shiv K. Sarin
Journal: Hepatology (2020)

Potential conflict of interest: Nothing to report. TO THE EDITOR: We read with interest the article by Patel et al. highlighting the safety and efficacy of a nonsteroidal farnesoid X receptor (FXR) agonist, cilofexor, in patients with nonalcoholic steatohepatitis (NASH).(1) The researchers concluded that cilofexor for 24 weeks was well tolerated and provided significant reductions in hepatic steatosis, abnormal liver biochemistry, and serum bile acids. However, the study has a few major methodological flaws, which limit the interpretation of results and the clinical application. First, 24 weeks of treatment is not long enough to have a major impact in NASH. In previous studies, including the recent study on obeticholic acid use, patients were randomized into the treatment arm for 72(2) or 96 weeks.(3) With NASH being a slowly progressive disease that evolves over years, it would be interesting to know how long the beneficial effects of treatment with 24 weeks of cilofexor last. A paired liver biopsy or repeat magnetic resonance imaging proton density fat fraction (MRI‐PDFF) after 72 or 96 weeks would be ideal. Second, it was surprising to note that there was no improvement in aspartate aminotransferase and alanine aminotransferase levels in the treatment arm, nor was there a significant impact on fibroblast growth factor‐19 levels despite the fact that cilofexor is an FXR agonist. Moreover, the researchers observed higher reductions in total bile acid and primary bile acid levels in the cilofexor 30‐mg arm compared to the 100‐mg arm, which points toward a dose‐independent effect of cilofexor on bile acids. More studies are needed to better illustrate the mechanism of cilofexor in NASH. Third, treatment response at 24 weeks as defined by relative reductions in MRI‐PDFF ≥30% should have been determined independent of body‐weight reduction. Patients with higher treatment response lost more weight (−2.2 [−5.3, 0.7] kg) compared to nonresponders (−0.4 [−2.1, 1.3] kg), and it is possible that responders may be more motivated with physical activities and a recommended diet plan. The above facts need more clarification because 13% of patients on placebo also had relative reductions in MRI‐PDFF ≥30% that were comparable to patients in the cilofexor 30‐mg arm. Fourth, despite no systemic FXR agonism, 14% of patients on cilofexor 100 mg developed grade ≥2 treatment‐emergent adverse effects—mainly pruritus, which is a concern in NASH patients without cirrhosis who are otherwise asymptomatic. In view of these limitations, long‐term prospective studies of cilofexor in NASH are needed to assess clinical benefit, both as monotherapy and in combination with other agents.
Lymph nodes dissection along bilateral recurrent laryngeal nerve for patients with esophageal carcinoma: thoracoscopic esophagectomy versus open thoracic esophagectomy
Authors: Chao Sun, Weiping Shi, Shichun Lu, Xiaolin Wang, Xiaoxia Lyu
Journal: BMJ (2017)

One hundred and thirty patients with esophageal carcinoma were randomly asigned into two groups: 62 cases received thoracoscopic esophagectomy (TE group) and 68 cases received open thoracic esophagectomy group (OE group). All patients underwent lymph nodes dissection along bilateral recurrent laryngeal nerve. Compared with OE group, TE group had a less blood loss during the lymph nodes dissection (P 0.05). The study suggests that lymph nodes dissection along bilateral recurrent laryngeal nerve can be succesfully completed by thoracoscopic esophagestomy, and it has the advantage of less intraoperative blood loss and lower incidence of pulmonary infection, compared to open thoracic surgery.


Key words: 
Thoracoscopy; Esophageal neoplasms; Recurrent laryngeal nerve
Selective targeting of HER2-overexpressing solid tumors with a next-generation CAR-T cell therapy.
Authors: Jenny Mu, Justin Edwards, Liubov Zaritskaya, Jeffrey Swers, Ankit Gupta, David LaFleur, David Hilbert, Laura Richman
Journal: Journal of Clinical Oncology (2020)

3041 Background: Conventional chimeric antigen receptor T cell (CAR-T) therapies have achieved limited clinical success in the treatment of solid tumors, in part due to the challenges of identifying tumor antigen(s) that are uniquely expressed on tumor cells. The dearth of such targets requires that current CAR-T therapies be re-engineered to preferentially target tumor cells thereby mitigating potential on-target off-tumor toxicity to normal cells. Herein we describe a novel cell therapy platform comprising Antigen Receptor Complex T (ARC-T) cells that are readily activated, silenced, and reprogrammed in vivo by administration of a novel tumor-targeting soluble protein antigen-receptor X-linker (sparX). The formation of the ARC-T, sparX, and tumor complex is required for the ARC-T to kill the tumor. Because ARC-T activity is entirely dependent on the dose of sparX administered, therapeutic doses of sparX may be defined that preferentially target cells over-expressing a target antigen and thus limit coincident kill of normal cells expressing lower levels of target antigen. Methods: We have created a library of sparX that bind different cell surface antigens, including HER2. The HER2 sparX was tested as both monovalent and bivalent constructs in vitro by assessing ARC-T cell activation, cytokine release and target cell cytotoxicity. In vivo efficacy models utilized NSG mice and incorporated tumor volume measurements and histopathologic assessments to evaluate tumor clearance. Results: In vitro studies demonstrate that co-culture of ARC-T cells, sparX-HER2 and HER2-expressing target cells drives T cell activation, expansion, cytokine secretion and cytotoxicity of target cells in a dose-dependent manner. Furthermore, by affinity tuning the HER2 binding domain and bivalent formatting of sparX-HER2, we achieved selective killing of HER2-overexpressing breast cancer cells with minimal effect on cells expressing HER2 levels representative of normal tissues. In vivo proof-of-principal studies with ARC-T/sparX-HER2 similarly demonstrate complete eradication of HER2-overexpressing solid tumor cells. Conclusions: These results demonstrate that a single intravenous dose of ARC-T cells can traffic to a solid tumor site and induce tumor eradication upon systemic administration and co-localization of tumor-targeting sparX in a mouse model. Bivalent formatting of sparX-HER2 further enabled ARC-T sensitivity to target antigen density to avoid the on-target off-tumor toxicity that has hindered conventional monovalent CAR-T treatments.
Abstract 12009: Micro-RNA-93 Enhances Endothelial Cell and Myocyte Survival and is a Powerful Inducer of Angiogenesis in Peripheral Arterial Disease
Authors: Surovi Hazarika, Ayotunde O Dokun, R J Lye, Charles R Farber, Brian H Annex
Journal: Circulation (2012)

Introduction:MicroRNAs (miRs) are key regulators of gene expression during development and in response to injury, but there is limited knowledge of their role in peripheral arterial disease (PAD). ...
艾滋病的实验室诊断
Authors: 李敬云
Journal: BMJ (2006)

艾滋病(AIDS)是由于感染人类免疫缺陷病毒(HIV)而导致的以免疫缺陷为主要表现的传染性疾病.诊断艾滋病首先要明确是否有HIV感染,在此基础上结合临床表现和CD4+细胞计数检测结果,才能判断受检者处于HIV感染的哪一个时期以及是否发展到艾滋病期。
Comparison of mutational landscape of non-alcoholic fatty liver disease, viral hepatitis, and alcohol consumption related hepatocellular carcinoma.
Authors: Jinrong Qiu, Weifeng Wang, Yingmei Li, Shifu Chen
Journal: Journal of Clinical Oncology (2020)

e16614 Background: Hepatocellular cancer (HCC) is the seventh most common cancer and the fourth leading cause of cancer-related death worldwide. The most common risk factors of HCC have traditionally included hepatitis B virus (HBV), hepatitis C virus (HCV), and alcohol-related liver disease (ALD). Recently, Non-Alcoholic Fatty Liver Disease (NAFLD) has emerged as the fastest growing risk factor for the development of HCC. This study reports the mutation landscape of NAFLD-related hepatocellular carcinoma (HCC) versus other etiologies. Methods: Mutation data of 219 HCC samples were collected from TCGA database, including 13 NAFLD, 87 HBV, 37 HCV, and 82 ALD-related samples. We analyzed mutations for different type of HCC samples using GDC level 3 mutation data. Driver mutations were called by applying software MuSig2CV. Results: In 219 samples, a total of 32189 mutations were identified, including 3163 in NAFLD, 11430 in HBV, 6390 in HCV, and 11206 in ALD-related HCC samples. Driver genes shared by viral hepatitis and ALD-related samples were TP53 (32% for ALD, 33% for HBV, 42% for HCV) and CTNNB1(32 % for HCV, 26% for HBV,29% for ALD), while TP53 was not among the highest frequency of mutations in NAFLD-related samples. As lack of NAFLD-related HCC samples (n = 13), most frequently mutated genes in NAFLD-related HCC samples were computed instead of driver genes. Top 5 mutated genes in NAFLD-related HCC samples were TTN (36%), CACNA1B (27%), DSCAM (27%), GLI2 (27%), and BEB (27%). Conclusions: From our results, TP53 has a lower mutation frequency in NAFLD-related HCC samples than in other types of HCC. To further validate this finding, a larger size of NAFLD-related HCC samples is essential.
NAPOLI-3: An open-label, randomized, phase III study of first-line liposomal irinotecan + 5-fluorouracil/leucovorin + oxaliplatin versus nab-paclitaxel + gemcitabine in patients with metastatic pancreatic ductal adenocarcinoma.
Authors: Zev A. Wainberg, Tanios S. Bekaii-Saab, Richard Hubner, Teresa Macarulla, Andrew Scott Paulson, Eric Van Cutsem, Fiona Maxwell, Yan Moore, Haofei Tiffany Wang, Bin Zhang, Eileen Mary O'Reilly
Journal: Journal of Clinical Oncology (2020)

TPS4661 Background: Liposomal irinotecan administered with 5-fluorouracil/leucovorin (5-FU/LV) is approved in the USA for metastatic pancreatic ductal adenocarcinoma (mPDAC) following progression with gemcitabine-based therapy. A phase 1/2 study in previously untreated locally advanced/metastatic PDAC showed promising anti-tumor activity with liposomal irinotecan 50 mg/m 2 free base + 5-FU 2400 mg/m 2 + LV 400 mg/m 2 + oxaliplatin (OX) 60 mg/m 2 on days 1 and 15 of a 28-day cycle (Wainberg et al. Ann Oncol 2019;30 Suppl 4: SO-005). Herein, we present the design of the phase 3 NAPOLI-3 study investigating the efficacy and safety of this regimen as first-line therapy in patients with mPDAC. Methods: NAPOLI-3 (NCT04083235) is a phase 3, open-label, randomized, global study in adults with histologically/cytologically confirmed pancreatic adenocarcinoma not previously treated in the metastatic setting. Patients are required to have one or more metastatic tumors measurable with computed tomography/magnetic resonance imaging and an Eastern Cooperative Oncology Group performance status score of 0–1. Site activation began in Dec 2019 and enrollment is ongoing. Random allocation (1:1) of 750 patients is planned to liposomal irinotecan + 5-FU/LV + OX (regimen as per phase 1/2 study) or nab-paclitaxel 125 mg/m 2 + gemcitabine 1000 mg/m 2 on days 1, 8 and 15 in a 28-day cycle. The primary endpoint is overall survival (OS). Secondary endpoints (progression-free survival [PFS] and overall response rate assessed with Response Evaluation Criteria in Solid Tumors v1.1 criteria) will be compared only if the primary endpoint shows superiority for liposomal irinotecan + 5-FU/ LV + OX over nab-paclitaxel + gemcitabine. Safety assessments include adverse-event monitoring. Patients will continue treatment until disease progression, unacceptable toxicity or study withdrawal, and will then be followed for survival every 2 months until death or study end (when all patients have died, withdrawn consent or are lost to follow-up). Clinical trial information: NCT04083235 .
Expression of micro RNA-125b in female patients with nodular goiter and Hashimoto′s thyroiditis
Authors: Tingxian Yang
Journal: BMJ (2017)

Twenty four female patients underwent thyroidectomy between June 2015 and August 2016, among whom 11 cases were pathologically diagnosed as nodular goiter (NG group), and 13 cases were diagnosed as nodular goiter complicated with Hashimoto′s thyroiditis (NG+ HT group); meanwhile, 17 female patients with Hashimoto′s thyroiditis (HT group) and 20 healthy females (control group) were also recruited in the study. The expression of micro RNA( miR)-125b was evaluated by quantitative real-time PCR(qRT-PCR), the expression level of tumor necrosis factor α (TNF-α) was analyzed by Western blotting in thyroid nodules and adjacent thyroid tissue in NG and NG+ HT groups. Serum expression of miR123b was detected in all 4 groups. qRT-PCR results showed that the expression of miR-125b was down regulated by 0.55 fold in thyroid nodules of NG+ HT group compared to NG group (t=2.873, P<0.01). The serum expression levels of miR-125b in control group, NG group, HT group and NG+ HT group were 1.00, 1.06, 0.92 and 0.79, respectively, the expression level in NG+ HT group was significantly lower than that of control group (q=4.717, P<0.01). Western blot showed that the expression of TNF-α in thyroid nodules of NG+ HT group was significantly higher than those in nodules of NG group and adjacent thyroid tissues of both groups. The results suggest that miR-125b might serve as a promising diagnostic biomarker of Hashimoto′s thyroiditis in patients with nodular goiter.


Key words: 
Hashimoto′s disease; Goiter, nodular; miR-125b