tbuckley/cabot-search huggingface dataset:
Phase II trial of the PARP inhibitor, niraparib, in BAP1 and other DNA damage response (DDR) pathway deficient neoplasms (NCT03207347).
Authors: azka ali, David L. DeRemer, Ji-Hyun Lee, Hiral D. Parekh, Stephen Staal, Merry Jennifer Markham, Karen Colleen Daily, Bruce K. Stechmiller, Dennie V. Jones, Julia Lee Close, Martina Cathryn Murphy, Frederic J. Kaye, Carmen Joseph Allegra, Robert A. Hromas, Thomas J. George
Journal: Journal of Clinical Oncology (2020)

e22061 Background: BRCA-associated protein-1 (BAP1) is a ubiquitin ligase associated with regulating cell cycle, cell proliferation, DNA damage pathway, and cell death. It also acts as a tumor suppressor gene as seen in hereditary cancer syndrome associated with germline mutations in BAP1. Preclinical studies have shown that PARP-inhibitor treatment of BAP1 mutant cell lines demonstrated significant synthetic lethality, independent of underlying BRCA status suggesting this mutation confers a BRCA-like phenotype. BAP1 is mutated, leading to a loss of functional protein, in up to 30% of several solid tumors including cholangiocarcinoma, mesothelioma, uveal melanoma, and clear cell renal cell carcinoma. Methods: This phase 2, open-label, single arm study aims to exploit the concept of synthetic lethality with the use of the PARP inhibitor niraparib in two biologically distinct cohorts. Eligible patients (pts) with measurable metastatic and incurable solid tumors are assigned to one of the two cohorts: Cohort A (histology-specific): tumors harboring suspected BAP1 mutations including cholangiocarcinoma, uveal melanoma, mesothelioma or clear cell renal cell carcinoma with tissue available for BAP1 mutational assessment via Next Generation Sequencing (NGS); or Cohort B (histology-agnostic): tumors with known DNA damage response (DDR) mutations (Table) confirmed by CLIA-approved NGS. Key inclusion criteria also include age ≥18 years, adequate cardiac, renal, hepatic function and ECOG PS of 0 to 1. Key exclusion criteria include known BRCA1 or BRCA2 mutations or prior PARPi exposure. Pts receive niraparib 200-300mg daily (depending on weight and/or platelet count) continuously. Primary endpoint is objective response rate (ORR), and secondary endpoints are progression free survival (PFS), overall survival (OS), toxicity and exploratory biomarker determinations. Radiographic response by RECIST criteria is measured every 8 weeks while on treatment. Cohort B enrollment is closed. Enrollment in Cohort A continues. A maximum of 47 evaluable subjects is planned with expansion cohorts allowable for histologic or molecular subtypes meeting pre-specified responses. Clinical trial information: NCT03207347. [Table: see text]
Germline and somatic mutations in 25 hereditary breast and ovarian cancer related genes and platinum-based chemotherapy response among Chinese patients with epithelial ovarian cancer.
Authors: Lei Li, Ming Wu, Changbin Zhu, Di Shao, Meng Liu
Journal: Journal of Clinical Oncology (2020)

e18088 Background: Insight on the germline and somatic mutation in BRCA1/2 was predictable on the sensitivity on platinum-based therapy. The therapeutic impact of mutations in other hereditary breast and ovarian cancer related genes is uncertain. Methods: We sought to investigate the germline and somatic deleterious mutations through all exons in 25 hereditary breast and ovarian cancer related genes in paired blood and frozen tumor samples from 235 Chinese women diagnosed with epithelial ovarian carcinomas. Results: Forty-seven subjects (24.6%) had a germline deleterious mutation, and 126 subjects (66%) had a somatic deleterious mutation. Thirty-four (17.8%) had both a germline and somatic mutation. Of the 203 germline and somatic deleterious mutations, 114 (56.2%) occurred in TP53, 41 (20.2%) in BRCA1, 11 (5.4%) in BRCA2 and 37 (23.6%) in 13 other genes: ATM, BARD1, BRIP1, CDH1, CHEK2, MLH1, MRE11A, MSH2, NF1, PALB2, PTEN, RAD51C and, STK11. In 235 patients, 215 (91.5%) and 20 (8.5%) cases were sensitive and resistant to the platinum-based chemotherapy. In the whole population, homologous recombination repair (HRR) mutations, non- homologous recombination repair(non-HRR) mutations, mismatch repair (MMR) mutations had no impact on the platinum-based chemotherapy response. No significant difference in platinum response were found in HRR, non-HRR and MRR mutation(P = 0.788). In 235 patients, ones with ATM (10), CHEK2(9), NF1(5), PALB2(8), PTEN (8) mutations were available for platinum response information; Among them, there were three patients with either ATM, CHEK2 or PALB2 mutation presented platinum resistance. Conclusions: Multi-gene panel testing of germline and somatic HBOC related gene mutations was feasible to characterize a comprehensive molecular profile of ovarian cancer and showed non-BRCA gene stratification potential value in predicting patient’s response for platinum-based chemotherapy.
Clinical analyses of laparoscopic hepatectomy for liver neoplasms: a report of 21 cases
Authors: Dong-fang Huang, Jian-huai Zhang, Jin-sheng Wu, Shao-chuang Wang
Journal: BMJ (2013)

The clinical data were retrospectively analyzed for 21 cases of liver neoplasms undergoing laparoscopic hepatectomy from December 2007 to October 2012. Among 11 cases of borderline hepatocellular carcinoma (HCC) (1.0-9.0 cm), 6 of them were of micro hepatocellular carcinoma (MHCC) with a diameter ≤2 cm. There were 10 cases of borderline hepatic benign tumor, including liver hemangioma (n=7), hepatic adenoma (n=1), liver lymphoma (n=1) and liver focal necrosis (n=1). According to Couinaud's liver segmentation method, neoplasm was located on segment Ⅲ (n=13), segment Ⅳ (n=6), segment Ⅴ (n=1) and segment Ⅵ (n=1). Laparoscopic hepatectomy was successful in all patients. There was neither conversion into open approach nor postoperative complications of bile leakage, air embolism or perioperative mortality, etc. The mean operative duration was (120 ± 30) minutes, average hemorrhagic volume (165±79) ml and normal diet & ambulation at Day 1-2 post-operation. The average postoperative hospitalization stay was (16±10)days and 1-year survival rate 100%. The parameters of leucocyte, liver enzymes, albumin and bilirubin returned to normal at Week 1 post-operation. Once a reasonable surgical indication is selected, laparoscopic resection is both safe and effective for peripheral micro hepatocellular carcinoma.


Key words: 
Liver neoplasms; Laparoscopy
Abstract 282: Adropin Enhancement of Cardiac Insulin Sensitivity and Inhibition of Fatty Acid Oxidation are Associated With Improvement of Cardiac Function and Efficiency in Hearts From Fasted Mice
Authors: Tariq R Altamimi, Arata Fukushima, Liyan Zhang, Su Gao, Abhishek Gupta, Gary D Lopaschuk
Journal: Circulation Research (2016)

Impaired cardiac insulin signaling and high cardiac fatty acid oxidation rates are characteristics of diabetic cardiomyopathy. Potential roles for liver-derived metabolic factors in mediating cardiac energy homeostasis are underappreciated. Plasma levels of adropin, a liver secreted peptide, increase during feeding and decrease during fasting and diabetes. In skeletal muscle, adropin preferentially promotes glucose over fatty acid oxidation. We therefore determined what effect adropin has on cardiac energy metabolism, insulin signaling and cardiac efficiency. C57Bl/6 mice were fasted to accentuate the differences in adropin plasma levels between animals injected 3 times over 24 hr with either vehicle or adropin (450 nmol/kg i.p.). Despite fasting-induced predominance of fatty acid oxidation measured in isolated working hearts, insulin inhibition of fatty acid oxidation was re-established in adropin-treated mice (from 1022±143 to 517±56 nmol. g dry wt -1 . min -1 , p &lt;0.05) compared to vehicle-treated mice (from 757±104 to 818±103 nmol. g dry wt -1 . min -1 ). Adropin-treated mice hearts showed higher cardiac work over the course of perfusion (p&lt;0.05 vs. vehicle), which was accompanied by improved cardiac efficiency and enhanced phosphorylation of insulin signaling enzymes (tyrosine-IRS-1, AS160, p&lt;0.05). Acute addition of adropin (2nM) to isolated working hearts from non-fasting mice showed a robust stimulation of glucose oxidation compared to vehicle-treated hearts (3025±401 vs 1708±292 nmol. g dry wt -1 . min -1 , p&lt;0.05, respectively) with a corresponding inhibition of palmitate oxidation (325±61 vs 731±160 nmol. g dry wt -1 . min -1 , p&lt;0.05, respectively), even in the presence of insulin. Acute adropin addition to hearts also increased IRS-1 tyrosine-phosphorylation as well as Akt, and GSK3β phosphorylation (p&lt;0.05), suggesting acute receptor- and/or post-translational modification-mediated mechanisms. These results suggest adropin as a putative candidate for the treatment of diabetic cardiomyopathy.
Prevalence, screening, treatment, and complications of osteoporosis and osteopenia in Medicare patients with chronic lymphocytic leukemia (CLL).
Authors: Danielle M. Brander, Kevin C. Oeffinger, Melissa A. Greiner, Michaela Ann Dinan
Journal: Journal of Clinical Oncology (2020)

e24050 Background: Despite treatment advances, patients (pts) with CLL, a common chronic cancer affecting the elderly, often experience adverse outcomes due to their comorbidities and frequent lack of routine health maintenance. We examined osteoporosis/osteopenia (OSTEO) prevalence, rates of bone mineral density (BMD, g/cm2) screening by dual-energy x-ray absorptiometry (DXA), use of bisphosphonates, and fragility fractures among Medicare pts with CLL. Methods: We identified a cohort of CLL pts &gt;65 years with Medicare fee-for-service between 1/1/2011-12/31/2015 using the Medicare 5% national sample. Controls (5:1) were matched based on age, sex, race, and year of eligibility. Among those with OSTEO, we compared rates of bisphosphonates. Chi-square tests for categorical variables and Wilcoxon Rank-sum tests for continuous variables were used to compare CLL vs controls. Cumulative incidence of BMD screening and fragility fractures were estimated using the cumulative incidence function and compared to controls using Gray tests. For fragility fractures, we compared among subgroups with and without OSTEO. Results: Baseline characteristics are in the Table. Compared to controls, CLL pts were more likely to have OSTEO (p &lt; .001) but less bisphosphonate use (p = .006). The 3-yr cumulative incidence of fragility fractures was higher among CLL pts (8.0%, 95% CI 7.5%-8.6%) vs controls (7.2%, 6.9%-7.4%; p = .002) as well as among those without an OSTEO diagnosis (p = .02). Cumulative 3-yr DXA use was higher among CLL pts vs controls ( &lt; .001); however, DXA 3-yr incidence was lower in CLL pts who had chemotherapy (13.2%, 11.4%-15.4%) vs none (17.0%, 16.2%-17.9%, p = .002). Conclusions: It appears that CLL pts may have a higher risk of osteoporosis and higher rates of fragility fractures than non-CLL individuals. Fragility fractures are higher even in the subgroup of CLL pts without OSTEO, suggesting that pts may be underdiagnosed. [Table: see text]
Long-term follow-up for duration of response (DoR) after weekly <i>nab</i>-sirolimus in patients with advanced malignant perivascular epithelioid cell tumors (PEComa): Results from a registrational open-label phase II trial, AMPECT.
Authors: Andrew J. Wagner, Vinod Ravi, Richard F. Riedel, Kristen N. Ganjoo, Brian Andrew Van Tine, Rashmi Chugh, Lee D. Cranmer, Erlinda Maria Gordon, Jason L. Hornick, David J. Kwiatkowski, Heng Du, Berta Grigorian, Anita N. Schmid, Shihe Hou, Katherine Harris, Neil Desai, Mark Andrew Dickson
Journal: Journal of Clinical Oncology (2020)

11516 Background: Malignant PEComa is a rare, aggressive sarcoma, with no approved medical treatment. Cytotoxic chemotherapies have limited benefit for patients with advanced disease. The AMPECT trial measured the effects of nab-sirolimus (ABI-009) and is the first prospective study in advanced malignant PEComa. nab-Sirolimus is a nanoparticle albumin-bound mTOR inhibitor with significantly higher intratumoral drug levels, mTOR target suppression, and anti-tumor activity in animal models versus other mTOR inhibitors. This report presents long-term follow-up of DoR after the primary analysis. Methods: Patients (N=34) received nab-sirolimus (100mg/m 2 IV, weekly, 2/3 weeks) until progression or unacceptable toxicity. Primary endpoint: ORR by IRR. Key secondary endpoints included DoR, PFS6, OS, and safety. Exploratory endpoints included correlation of tumor genotype and outcome. The sample size of 30 efficacy-evaluable patients was based on an estimated ORR of 30% and the lower bound of the 95%CI of ORR to exclude values less than 14.7%. The primary analysis was conducted when all patients were treated ≥6 months (May 22, 2019). This report updates the primary response analysis and DoR with an additional 8.5-month of follow-up. Results: As of Feb 06, 2020, of the 31 efficacy-evaluable patients, the confirmed ORR by IRR was 39% (12/31, 95%CI: 21.8, 57.8), with 1 complete response (CR) and 11 partial responses (PR), 52% stable disease (SD, 16/31, with 10/16 SD ≥12 weeks), and 10% progressive disease (3/31); the disease control rate (CR+PR+SD ≥12 weeks) was 71%. PFS6 was 71% (95%CI: 47.7, 85.1). The majority of responses (67%) were reached at the first post-baseline scan at week 6, with a median time to response of 1.4 months (95%CI: 1.3 to 2.8). The median DoR by IRR was not yet reached (range 5.6-38.7+ months; calculated median 22.2+ months) with 8/12 (67%) responders still on treatment for &gt;1 year and 5/12 (42%) &gt;2 years. Mutational analysis available for 25 patients identified that TSC2 loss-of-function mutations significantly correlated with response; 8/9 (89%) patients with TSC2 had a confirmed response. Conclusions: Responses of advanced malignant PEComa to nab-sirolimus were highly durable and occurred in 39% of patients based on independent review. The high disease control rate with manageable toxicities suggest that nab-sirolimus is effective and represents an important new treatment option for these patients. NCT02494570. Clinical trial information: NCT02494570 .
月经过多的诊治分析
Authors: 吴瑞瑾, 江桥英
Journal: BMJ (2011)

育龄妇女的正常月经具有周期性,每次月经持续2～7d,总失血量为30 ～60 ml.如经期超过7d和(或)月经量多于80 ml则属病理现象,称为月经过多;月经量大于200 ml,则属重度月经过多.月经过多是生育年龄和围绝经期妇女的常见症状,严重影响着妇女的生存质量[1],也是子宫切除术的主要原因之一.在英国、美国分别有20％和30％的妇女在60岁以前切除子宫,其中50％的患者具有月经过多的症状[2]。
Correlation of blood lipids and insulin resistance in patients with impaired glucose tolerance
Authors: Chun-yan Shan, Bao-cheng Chang, Miao-yan Zheng, Ying Wang, Ju-hong Yang, Hui-zhu Ren
Journal: BMJ (2013)

Blood lipid level and its associations with insulin resistance were studied in patients with impaired glucose tolerance (IGT). Two hundred and twenty first degree relatives of type 2 diabetes mellitus were grouped into normal glucose tolerance (NGT) and IGT groups according to results of oral glucose tolerance test. Compared with the NGT group, the IGT patients had higher serum levels of total triglyceride (TG), total cholesterol (TC), low density lipoprotein-C (LDL-C) but a lower serum level of high density lipoprotein-C (HDL-C). Homeostasis model of assessment for insulin resistance index (HOMA-IR) and area under curve of insulin (AUCI) also increased. A positive relationship was found between TG and HOMA-IR (or AUCI), but a negative relationship existed between HDL-C and HOMA-IR. In conclusion, abnormal blood lipid metabolism is present in IGT patients and it has a close correlation with insulin resistance.


Key words: 
Glucose intolerance; Insulin resistance; Dyslipidemias
Ruxolitinib in treatment of severe coronavirus disease 2019 (COVID-19): A multicenter, single-blind, randomized controlled trial
Authors: Yang Cao, Jia Wei, Liang Zou, Tiebin Jiang, Gaoxiang Wang, Liting Chen, Liang Huang, Fankai Meng, Lifang Huang, Na Wang, Xiaoxi Zhou, Hui Luo, Zekai Mao, Xing Chen, Jungang Xie, Jing Liu, Hui Cheng, Jianping Zhao, Gang Huang, Wei Wang, Jianfeng Zhou
Journal: Journal of Allergy and Clinical Immunology (2020)

Accumulating evidence proposed Janus-associated kinase (JAK) inhibitors as therapeutic targets warranting rapid investigation.
新型数字化健康服务社区的探索
Authors: 任菁菁, 刘颖, 严亚青, 张玲珍, 王战坤, 杜亚平, 金瓯, 李兰娟
Journal: BMJ (2012)

浙江大学附属第一医院良渚门诊部建立了新的数字化健康服务模式,利用计算机信息化技术,实现了建立电子健康档案、三级医院与社区中心双向转诊、建立远程会诊系统、“健康面对面”IP视频电话、移动门诊输液系统等多项功能。
Survey of first permanent molars of 7 - 12-year-old students in Huairou district, Beijing in 2010
Authors: Shu-yan Fan, Hai-feng Wang
Journal: BMJ (2012)

The first permanent molar caries and current status of sealant of 7 - 12-year-old students were surveyed in Huairou district of Beijing.Based on the World Health Organization and national oral health survey standards,cluster and stratified random sampling methods were used.The prevalence rate of deciduous tooth caries was 17.34％ with a decayed/missing/filled teeth (dmft) index of 0.30.The caries rate of females was higher than that of males (20.60％ vs.14.08％ ).The incidence of mandible was higher than that of maxillary.And there was no significant difference around the jaw.The rate of fissure sealant was 51.36％.The current status of first permanent molar caries in this district was in accordance with the characteristics of general epidemiological caries disease.An overall policy of early discovery,early diagnosis and early treatment should be practiced.

Key words: 
Dental caries ;  Molars
Liddle syndrome: case report and literature review
Authors: Xiaofang Zhang, Yuhong Zhan, Chu Zhang
Journal: BMJ (2019)

The clinical data and the genetic study results of a patient with Liddle syndrome were reported. The genomic DNA of peripheral blood mononuclear cells was extracted and the mutation sites of all the exons in 36 genes related to hypokalemia were screened by high-throughput sequencing. Genetic validation of patients and their parents was performed by direct sequencing. The patient presented with severe hypokalemia, low aldosterone and hypertension. The results of gene sequencing showed that the SCNN1B gene exon 13 584 codon 1751C-T, and the corresponding encoded amino acid changed from alanine to valine (A-V). Eleven families and 33 cases of Liddle syndrome diagnosed by genetic analysis were reported in Chinese literature from 1998 to June 2018. The literature review showed that all patients had hypertension, 87% (28/32) had hypokalemia and 85% (23/27) had low aldosterone. The onset age of 21 patients was<20 year, among whom cerebral stroke occurred in 3 patients. The normal blood pressure can be achieved by low-salt diet and administration of amiloride or triamterene. The most common mutations were missense mutations (7/11). Liddle syndrome is a controllable and treatable disease, early detection, diagnosis and treatment can avoid serious complications.


Key words: 
Liddle syndrome; SCNN1B; Hypertension; Hypokalemia
Treatment workload by stage and subtype in patients with breast cancer: A SEER-Medicare analysis.
Authors: Alex Cheng, Jeremy Lyle Warner, Mia Alyce Levy
Journal: Journal of Clinical Oncology (2020)

e19328 Background: Patients with breast cancer experience significant disruption to their daily lives when undergoing treatment. When treatment workload exceeds the capacity to manage that treatment, patients are less likely to adhere to care plans and likelier to have worse outcomes. The purpose of this study was to assess treatment workload in patients with operable breast cancer in the SEER-Medicare dataset. Methods: Operable (stage I-III) breast cancer patients diagnosed from 2010-2016, &gt; 65 years old at diagnosis, and with 18 months of continuous Medicare part A, B, and D coverage after diagnosis were included in the cohort. We calculated the number of outpatient appointment days, total cumulative inpatient lengths of stay, and distance traveled for patients in the cohort in the 18 months following diagnosis. We compared treatment workload outcomes between patients with stage I and stage III disease and between patients with HER2+ and HER2-/ER+ disease. Results: 35,071 patients met the inclusion criteria. Compared to stage I patients, stage III patients had more median outpatient appointment days (71 vs 50), more median inpatient days (2 vs 0), and greater median distance traveled (1846 vs 1332 miles). Compared to patients with HER2-/ER+ disease, patients with HER2+ disease had more median outpatient appointment days (70 vs 51), and greater median distance traveled (1775 vs 1350 miles). All comparisons were with Mann Whitney U and were statistically significant with P &lt; .001. Conclusions: Patients with operable breast cancer experience a high amount of treatment workload in the first 18 months after diagnosis. These workload measures derived from SEER-Medicare claims differentiate significantly by stage and subtype, with stage III and HER2+ patients experiencing greater treatment workload than stage I and HER2-/ER+ patients respectively. We suspect that greater treatment workload in stage III is attributed to higher intensity of treatment for later stage cancer and associated complications, while greater treatment workload in HER2+ patients is attributed to the use of trastuzumab. [Table: see text]
Maximum tumor dimension and tumor volume as prognostic factors in patients with newly diagnosed localized Ewing sarcoma (ES)- a report from the Children’s Oncology Group (COG).
Authors: Leo Mascarenhas, Allen Buxton, Steven G. DuBois, Dian Wang, Nadia N. Laack, Kenneth L.B. Brown, Bruce Pawel, Helen Ruth Nadel, Justin Davis, Douglas S. Hawkins, Holcombe E. Grier, Richard B. Womer, Del Stringham, Damon R. Reed, Katherine A. Janeway, Richard Greg Gorlick, Neyssa Marina, Mark L. Bernstein, Mark D. Krailo, Patrick Leavey
Journal: Journal of Clinical Oncology (2020)

11529 Background: Maximum tumor dimension &gt; 8 cm. and large tumor volume have been reported to be adverse prognostic factors in patients with ES but have not been prospectively evaluated in the context of a phase 3 clinical trial with interval compressed chemotherapy. Methods: COG AEWS1031 (NCT01231906) was a randomized phase 3 clinical trial comparing interval compressed chemotherapy regimens in patients with newly diagnosed localized ES of bone and soft tissue. A correlative objective of AEWS1031 was to evaluate tumor size and volume as prognostic factors. Institution-reported dimensions of the primary tumor from baseline imaging were prospectively collected. For inclusion in this analysis, patients had to have at least 1 tumor dimension reported for tumor size analyses and dimensions in 3 axes for tumor volume analyses. Maximum dimension was dichotomized as less than vs. &gt; / = 8cm. Tumor volume was dichotomized as less than vs. &gt; / = 200 mL. Event-free (EFS) and overall survival (OS) from enrollment were calculated using Kaplan-Meier methods and compared between groups using a two-sided log-rank test. Hazard ratios (HR) and confidence intervals (CI) were calculated using the Cox model. Results: The 5-year EFS and OS of the 629 eligible patients was 78% (95% CI: 75-81%) and 87% (95% CI: 84-90%) respectively and there was no significant difference in both EFS and OS between the randomized interval compressed chemotherapy arms of AEWS1031. 590 of 629 (94%) patients were evaluable for maximum tumor dimension and 307 (52%) had tumors &gt; / = 8 cm. Patients with tumors &gt; / = 8 cm were at significantly increased risk for EFS events (p = 0.016) with estimated 5-year EFS of 73.7% (95% CI: 68.1 vs.78.4%) vs. 82.9% (95% CI 77.7-87.1%) for patients with tumors &lt; 8 cm [HR: 1.53 (1.08-2.17)]. For tumor volume, 586 of 629 patients (93%) were evaluable and 180 (31%) had tumors &gt; / = 200 mL. Patients with tumor volume &gt; / = 200 mL were at significantly increased risk for EFS events (p = 0.003) with estimated 5-year EFS of 70% (95% CI: 62.3-76.4%) vs. 81.6% (95% CI: 77.2-85.2%) for patients with tumors &lt; 200 mL [HR: 1.69 (1.2-2.39)]. Conclusions: Maximum tumor dimension and tumor volume as defined are both prognostic in patients with newly diagnosed localized ES treated with interval compressed chemotherapy. Clinical trial information: NCT01231906 .