tbuckley/cabot-search huggingface dataset:
OP0115 Polymorphism at the type i collagen (colia1) and relative risk of osteoporosis and vertebral fractures in postmenopausal women
Authors: J Fernández-Melón, M Bernad, ML Gonzalez, C Gonzalez, MV Garces, E Martin-Mola, ME Martinez
Journal: Annals of the Rheumatic Diseases (2001)

<h3>Background</h3> Twin and family studies have demonstrated that an important degree of the population variance in bone mineral density (BMD) is attributable to genetic factors. <h3>Objectives</h3> A polymorphism in the collagen type I alpha 1 (COLIA1) gene has recently been associated with low bone mass and fracture incidence. <h3>Methods</h3> We analysed the relationship between COLIA1 gene polymorphism, lumbar spine and hip BMD, T-score and fracture incidence in a population of 319 postmenopausical women classified by WHO standards: 98 non-osteoporotic women (NOPW) (57.4 ± 6.2 yrs), 146 osteoporotic women without fracture (OPW without fracture: OPWnF)(60.0 ± 5.2) and 75 osteoporotic women with fracture (OPW with fracture: OPWwF) (61.2 ± 6.3 yrs). The COLIA1 genotype was assessed by polymerase chain reaction and Bal I endonuclease digestion. Genotype frequencies for the total group were 49.2% "SS" homozygotes, 39.5% "Ss" heterozygotes and 11.3% "ss" homozygotes. <h3>Results</h3> We found significant differences in the percentage of homozygous "ss" between NOPW and OPW (6.1% and 13.6% respectively). However, the incidence of genotype "ss" in OPWnF was 6.2% and 28% in OPWwF. We observed no associations between the COLIA1 genotype and lumbar and hip BMD. However, the lumbar spine T-scores were lower in the "ss" group than in the "Ss" and "ss" group. The incidence of fractures (64 vertebral and 11 colles) varied significantly by genotype: "SS" 21.7%; "Ss" 15.9%; and "ss" 58.3% (chi-square = 15.43; p &lt; 0.0001); this resulted in a fracture odds ratio of 5.96 (95% confidence interval 2.26–15.69). Logistic regression analysis of fracture prevalence showed that for prevalent fractures, the women with "ss" group had 4.17 times risk of the woman "SS"+ "Ss" groups. When prevalence was adjusted for BMD and T-scores, the respective fracture risk was 2.6 and 2.94 for the "ss" group versus the other genotypes (SS+Ss). <h3>Conclusion</h3> A slight association was found between lumbar T-score and gene COLIA1 polymorphism. Expression of the "ss" allele seems to be related with a higher incidence of fracture in postmenopausical women and was independent of bone mineral density.
上腹部手术后胃瘫14例分析
Authors: 李培生, 贲大刚, 程凯, 褚亮, 邓锐
Journal: BMJ (2007)

回顾分析我院1994年2月至2005年12月收治的14例上腹部手术后胃瘫患者的临床资料,探讨其发病机制、诊断和治疗方法.14例中,12例经非手术治疗后痊愈;2例手术治疗无效,经非手术治疗而愈.无死亡病例.提示,各种上腹部手术都可能发生胃瘫,其发病机制可能是多种因素共同作用的结果,应采取综合治疗的方法,非手术治疗多能治愈。
硝普钠对充血性心力衰竭患者肾功能影响的研究
Authors: 丁枭伟, 那开宪, 王华, 杨新春, 李桂芹, 崔亮, 张麟
Journal: BMJ (2004)

检测80例充血性心力衰竭患者(其中有33例合并有不同程度的肾功能不全)在静脉应用硝普钠或硝酸酯类药物(消心痛)前后的血尿素氮、肌酐水平,评价硝普钠对心力衰竭患者肾功能的影响. 结果显示其用药前后血浆尿素氮、肌酐的变化差异无显著性.提示短期、小剂量滴注并严密监测肾功能变化的情况下,应用硝普钠治疗心力衰竭是安全可行的。
Randomized phase III trial to evaluate omentum preserving gastrectomy for patients with resectable advanced gastric cancer: JCOG1711 (ROAD-GC).
Authors: Takanobu Yamada, Takaki Yoshikawa, Yuya Sato, Ryunosuke Machida, Junki Mizusawa, Hiroshi Katayama, Masanori Tokunaga, Yasunori Nishida, Jun Hihara, Masaya Watanabe, Yasuhiro Choda, Souya Nunobe, Junya Fujita, Masahide Kaji, Norimasa Fukushima, Seiji Ito, Narikazu Boku, Masanori Terashima
Journal: Journal of Clinical Oncology (2020)

TPS4646 Background: Standard surgery for resectable advanced gastric cancer is D2 (standardized extended lymph node dissection) gastrectomy with omentectomy. The reason why omentectomy has been performed is as follows; (1) principal surgery for gastrointestinal cancers is en-block resection of mesothelium including regional lymph nodes. Omentum is a part of the mesothelium of the stomach. (2) Cancer cells implanted into the peritoneal cavity aggregated in the milky-spot of the omentum and formed peritoneal dissemination in an animal model. (3) By special staining, micrometastasis detected in the omentum. There is some arguments for this theory. (1) no prospective study showed survival benefit of omentectomy as compared with omentum preservation. (2) anatomically, milky-spot is found not only in the omentum but also in other mesothelium or Douglas pouch. (3) JCOG1001 phase III study showed no survival benefit of bursectomy against non-bursectomy although bursa is a part of mesothelium of the stomach. (4) Anti-immunity is accelerated by antigen presentation by macrophage in the milky-spot of the omentum. Preservation of the omentum may have several benefits; (1) decrease in blood loss and operation time, (2) preservation of physical function by omentum such as reaction to peritonitis and prevention of adhesion, and (3) overcoming difficulties in laparoscopic omentectomy and avoidance of organ injury during surgery. Methods: The study is multicenter randomized phase III trial designed to confirm non-inferiority of omentum preservation to omentectomy for resectable advanced gastric cancer. Patients aged 20-79 years, histologically proven gastric adenocarcinoma, clinical subserosal/serosal invasion, and expected R0 (curative) resection are randomly assigned (1:1) during surgery to either omentum preservation or omentectomy. Total or distal gastrectomy with D2 dissection is performed in both arms. Laparoscopic gastrectomy is not allowed. Intraoperative photographs of the dissected field are centrally reviewed for all patients for quality control. The primary endpoint is relapse-free survival (RFS) and the secondary endpoints are overall survival, blood loss, operation time, and adverse events. Sample size was set at 1050 considering expected 3-year RFS of 77% in both arms with non-inferiority margin of 5%, one-sided alpha of 5%, and power of 80%. Planned accrual and follow up period are 6.5 years and 3 years respectively. The trial was activated in March 2019, and 177 patients are enrolled as of January 2020. Clinical trial information: UMIN000036253 .
Updated 5-year local control (LC), metastasis-free survival (MFS), and overall survival (OS) data from a phase I study of nilotinib plus radiation (RT) in high-risk chordoma.
Authors: Gregory Michael Cote, Thomas F. DeLaney, Ruoyu Miao, Joseph H. Schwab, Kevin Raskin, Santiago Lozano Calderón, John Thomas Mullen, Alex Bernard Haynes, Francis J. Hornicek, Yen-Lin Chen, Edwin Choy
Journal: Journal of Clinical Oncology (2020)

e23505 Background: Chordomas are malignant tumors arising from remnant notochordal tissue. Despite improved local control with preoperative/postoperative RT, progression-free survival and OS remain poor in patients (pts) with high-risk features. Chordoma has been identified to express and activate platelet-derived growth factor receptor signaling. We conducted a phase 1 trial to identify the maximum tolerated dose (MTD), safety, and feasibility of nilotinib with RT as either preoperative or definitive treatment for patients with high-risk chordoma. Enclosed is an updated report on LC, MFS, and OS. Methods: We recruited 23 pts with nonmetastatic chordoma to the phase I and dose expansion arms of the study. High-risk was defined as the presence of any of the following: local recurrence after surgery, previous intralesional resection, unplanned incomplete resection, unresectable/marginally resectable disease, or declining surgery due to excessive morbidity. Pts were treated with nilotinib and concurrent RT to 50.4 Gy relative biological effectiveness (RBE) followed by surgery and postoperative RT to a cumulative dose up to 70.2 Gy RBE or definitively up to 77.4 Gy RBE without surgery. On completion of RT, pts were eligible to continue nilotinib until disease progression. Results: The dose escalation arm of the study identified nilotinib 200 mg daily as the maximum tolerated dose (MTD). Eighteen evaluable pts were treated with nilotinib plus RT at the MTD. The objective best response rate was 6% (1 of 18 pts). The 4 and 5-year LC rates were 94.3% (95% CI 83.2-100) and 70.7% (95% CI 20.8-100), respectively. The MFS rate was 74.3 at 4 and 5 years (95% CI 51.8-96.7). The 4 and 5-year OS rates were 70.2% (95% CI 44.4-95.9) and 54.6% (95% CI 20.5-88.6). Conclusions: In updated data from a cohort of high-risk chordoma pts nilotinib 200 mg/d with RT +/- surgery, with long-term follow-up, local control and distant metastasis free survival remains favorable. Clinical trial information: NCT01407198 . [Table: see text]
Depth of response to isatuximab, carfilzomib, lenalidomide, and dexamethasone (Isa-KRd) in front-line treatment of high-risk multiple myeloma: Interim analysis of the GMMG-CONCEPT trial.
Authors: Katja Weisel, Anne Marie Asemissen, Britta Besemer, Mathias Haenel, Igor W. Blau, Martin Goerner, Yon-Dschun Ko, Jan Dürig, Peter Staib, Christoph Mann, Raphael Lutz, Markus Munder, Ullrich Graeven, Rudolph Peceny, Hans Salwender, Manola Zago, Axel Benner, Diana Tichy, Carsten Bokemeyer, Hartmut Goldschmidt
Journal: Journal of Clinical Oncology (2020)

8508 Background: High-risk (HR) multiple myeloma (MM) still has a significant impaired prognostic outcome. Addition of CD38 monoclonal antibodies to standard-of-care regimens significantly improved response rates and depth of response in newly diagnosed (ND) and relapsed/refractory MM patients (pts). Here, we report the prespecified end of induction interim analysis (IA) of the investigator-initiated GMMG-CONCEPT trial (NCT03104842), evaluating the quadruplet regimen isatuximab plus carfilzomib, lenalidomide and dexamethasone (Isa-KRd) in HR NDMM pts. Methods: 153 pts with HR NDMM are planned to be included into the trial. HR MM is defined by the presence of del17p or t(4;14) or t(14;16) or &gt; 3 copies 1q21 and ISS 2 or 3 stage disease. Pts receive 6 cycles of Isa-KRd induction, 4 cycles of Isa-KRd consolidation and Isa-KR maintenance. Transplant eligible pts (arm A) undergo high-dose therapy. Transplant ineligible pts (arm B) receive 2 additional cycles of Isa-KRd induction. The primary endpoint is MRD negativity measured by next-generation flow after consolidation. This IA reports on overall response rates (ORR) after induction. Additional MRD analysis will be presented. Results: 50 pts (46 arm A, 4 arm B) were included in the IA population for ORR. HR MM was defined by del17p in 52%, t(4;14) in 38%, t(14;16) in 12% and &gt; 3 copies 1q21 in 42%. 39/46 pts in arm A and 4/4 pts in arm B completed induction treatment. ORR was 100%, with 5 pts (10.0%) showing partial response (PR), 22 (44.0%; including 4 in arm B) very good partial response (VGPR) and 23 (46.0 %) complete response (CR). Median stem cell yield was 6.6 × 10 6 CD34+ cells/kg. Grade 3/4 treatment-emergent adverse events (≥ 10%) with Isa-KRd included neutropenia (34.0%), leukopenia (26.0%) and thrombocytopenia (14.0%). Main non-hematologic toxicities grade 3/4 were hypertension (12.0%) and infection (8.0%). Conclusions: To the best of our knowledge, we report for the first time on a trial investigating solely HR NDMM and Isa-KRd quadruplet treatment. Isa-KRd induction induces deep responses in HR MM pts. The overall safety profile of Isa-KRd is expected and consistent with previous reports. The study is ongoing, with pts continuing to be included. Clinical trial information: 03104842 .
贯彻《国务院关于建立全科医生制度的指导意见》倡议书
Authors: 中华医学会, 中国医师协会
Journal: BMJ (2011)

2011年6月22日,温家宝总理主持国务院常务会议,决定建立全科医生制度.2011年7月2日, (以下简称 )印发. 指出,到2020年在我国初步建立起具有生机和活力的全科医生制度,基本形成统一规范的全科医生培养模式和首诊在基层的服务模式,基本建立全科医生与城乡居民比较稳定的服务关系,基本实现城乡每万居民有2～3名合格的全科医生,以适应人民群众基本医疗卫生服务需求。
Relationship between serum uric acid concentration and metabolic syndrome in elderly Chinese
Authors: GE-Xin Zhu, Ning Sun, Ming Li, Yun Zhang
Journal: BMJ (2010)

A cross sectional study was conducted based on the data collected from annual health check in 2007-2008 in our hospital. Total 911 subjects, including 681 men and 230 women aged over 50, with no history of smoking and alcohol consumption less than 1-2 times/month were enrolled in the study. Subjects were excluded, if they had history of severe cardiocerebral vascular disease, diabetes mellitus under drug treatment,hypertension with diuretics or anti-hyperlipidemie treatment for last 3 month,and hepatic and/or renal dysfunction. The results showed that the prevalence of hyperuricemia in this population was 20.56% (140/681) and 22. 17% (51/230) for men and women respectively, and the prevalence of metabolic syndrome by NCEP criteria was 35. 83% ( 244/681 ) and 32. 17% ( 74/230) . Correlation analysis demonstrated that serum uric acid levels were positively correlated with waist circumference (r =0. 331), systolic BP (r =0. 219), diastolic BP (r =0.208) , TG(r =0. 181 ) , and negatively correlated with HDL-C (r= -0.375). Serum uric acid levels increased significantly with the numbers of metabolic syndrome components. Logistic analysis showed that higher serum uric acid concentrations significantly increased the risk of metabolic syndrome.

Key words: 
Uric acid; Metabolic syndrome
人工流产致子宫破裂大肠撕脱伤一例
Authors: 吴秀君
Journal: BMJ (2005)

患者女,37岁,因孕3个半月于当地卫生院行人工流产术.术中用产钳钳夹宫内组织时,拽出约50 cm长的肠管状组织,由于患者腹痛难忍急送我院.入院检查,患者中度贫血貌,脉搏细,约140次/min,血压70/40 mm Hg(9.3/5.3 kPa),腹胀,全腹压痛(+),伴肌紧张及反跳痛,肠音听诊弱,阴道有鲜血流出.腹腔穿刺抽出血性液及凝血块.立即予以输血,快速输液等抗休克治疗,并于全身麻醉下行剖腹探查术。
The clinical impact of ASCO “choosing wisely” recommendations on staging imaging for early stage breast cancers: An interrupted time-series analysis utilizing SEER-Medicare data.
Authors: Alan Baltz, Issam Makhoul, Eric R Siegel
Journal: Journal of Clinical Oncology (2020)

2078 Background: The “Choosing Wisely” (CW) list, released by the American Society for Clinical Oncology (ASCO), highlights low-value procedures. In 2012, the CW recommendations advised against the use of staging imaging, including Positron Emission Tomography (PET), Computerized Tomography (CT) and radionuclide bone scans, for the staging of early breast cancer at low risk for metastasis. The objective of this study was therefore to assess the impact of the ASCO CW recommendations on staging imaging among early stage breast cancers. Methods: Women above the age of 66 with an early stage incident breast cancer diagnoses between 2010 and 2015 were identified within the linked SEER-Medicare data. The primary outcome of interest was the proportion of patients with a claim for staging imaging in the six months following the breast cancer diagnosis. Negative binomial regression, adjusting for pre-recommendation trends, was performed to estimate the changes in the rate of imaging staging within each year following the release of the recommendation. Results: A total of 50,004 women were identified during the study period. Prior to the release of the recommendations in 2012, the staging imaging rates among women newly diagnosed with early stage breast cancers were 5% greater in 2010 (p&lt;.01) and 4% greater in 2011 (p&lt;.01). Following the release of the recommendations, staging imaging rates did not decrease significantly in 2013 (2%;p=0.18). Imaging rates did, however, significantly decrease by 13% in 2014 (p&lt;0.01) and by 16% in 2015 (p&lt;0.01). Conclusions: The CW recommendation was associated with a significant decrease in unadvised staging imaging among incident early stage breast cancer diagnosis in the second and third year following its release. These findings demonstrate an improvement in the proportion of potentially inappropriate staging imaging in early stage breast cancers. The creation and dissemination of resources, such as the CW recommendations, serves as a powerful tool to improve clinical practice, quality of care, and patient safety from secondary malignancies, anxiety, and overdiagnosis.
Phase I/II study to evaluate systemic durvalumab + intraperitoneal (IP) ONCOS-102 in patients with peritoneal disease who have epithelial ovarian (OC) or metastatic colorectal cancer (CRC): Interim phase I clinical and translational results.
Authors: Dmitriy Zamarin, Kunle Odunsi, Brian M. Slomovitz, Linda R. Duska, John J. Nemunaitis, Matthew Reilley, Yonina Bykov, Aliya Holland, Vanessa M. Hubbard-Lucey, Lisa Shohara, Paul Schwarzenberger, Toni Ricciardi, Mary J. Macri, Aileen Ryan, Magnus Erik Jaderberg, Ralph Rudolph Venhaus
Journal: Journal of Clinical Oncology (2020)

3017 Background: Metastasis to the peritoneal cavity is associated with end-stage disease in many cancers, including OC and CRC, both of which exhibit poor responses to checkpoint inhibitors. Locoregional treatment with oncolytic viruses may be used to improve the efficacy of checkpoint inhibitors at both treated and distant tumor sites. This study evaluates the combination of IP-administered ONCOS-102, an oncolytic adenovirus encoding for granulocyte macrophage colony stimulating factor (GMCSF), with systemic durvalumab, an anti PD-L1 antibody, in patients with peritoneal disease who have histologically confirmed OC or metastatic CRC and have failed prior standard therapies. Methods: This ongoing Phase 1/2, open-label study (NCT02963831) evaluates safety and antitumor/biologic activity of durvalumab (1500 mg IV, every 4 weeks x 12) + ONCOS-102 (IP, weekly x 6); cyclophosphamide is given pre first ONCOS-102 dose. Phase 1 uses a 3+3 design to evaluate the ONCOS-102 dose (1 or 3 x 10 11 VP) to be given with durvalumab. Phase 2 evaluates the activity of the combination using Simon’s 2-stage MINIMAX design. Safety, response rate by RECIST 1.1, and immunological effects in tumors were evaluated for Phase 1; the current abstract reports on the phase 1 results. Results: Enrollment opened 7 Sep 2017; data cutoff, 1 Nov 2019. There were 17 patients treated in Phase 1: 8 CRC, 9 ovarian; 94% female; median age, 56 [37-77] years; ECOG PS0, 47%; ECOG PS1, 53%. There were no DLTs. Grade 3 treatment-related AEs included hypokalemia (n = 2); anemia, myocarditis, increased GGT, and influenza like illness (n = 1 each). There were 4 deaths due to PD. One patient had durable confirmed partial response and remains on treatment &gt; 1 year; 4 patients had stable disease as best overall response. Two patients remained on treatment at data cutoff. Analysis of pre- and on-treatment tumor biopsies revealed changes in the tumor-infiltrating immune cells and PD-L1 expression, including an increase in tumor-infiltrating CD8 T cells in 5 of 11 evaluable patients. Conclusions: Combination of durvalumab and IP ONCOS-102 was safe, and no DLTs were observed. Preliminary analyses demonstrate evidence of biologic and clinical activity. Phase 2 enrollment is ongoing. Clinical trial information: NCT02963831 .
Early Cardiac Remodeling Promotes Tumor Growth and Metastasis
Authors: Shimrit Avraham, Soraya Abu-Sharki, Rona Shofti, Tali Haas, Ben Korin, Roy Kalfon, Tom Friedman, Avinoam Shiran, Walid Saliba, Yuval Shaked, Ami Aronheim
Journal: Circulation (2020)

Background: Recent evidence suggests that cancer and cardiovascular diseases are associated. Chemotherapy drugs are known to result in cardiotoxicity, and studies have shown that heart failure and stress correlate with poor cancer prognosis. However, whether cardiac remodeling in the absence of heart failure is sufficient to promote cancer is unknown. Methods: To investigate the effect of early cardiac remodeling on tumor growth and metastasis colonization, we used transverse aortic constriction (TAC), a model for pressure overload–induced cardiac hypertrophy, and followed it by cancer cell implantation. Results: TAC-operated mice developed larger primary tumors with a higher proliferation rate and displayed more metastatic lesions compared with controls. Serum derived from TAC-operated mice potentiated cancer cell proliferation in vitro, suggesting the existence of secreted tumor-promoting factors. Using RNA-sequencing data, we identified elevated mRNA levels of periostin in the hearts of TAC-operated mice. Periostin levels were also found to be high in the serum after TAC. Depletion of periostin from the serum abrogated the proliferation of cancer cells; conversely, the addition of periostin enhanced cancer cell proliferation in vitro. This is the first study to show that early cardiac remodeling nurtures tumor growth and metastasis and therefore promotes cancer progression. Conclusions: Our study highlights the importance of early diagnosis and treatment of cardiac remodeling because it may attenuate cancer progression and improve cancer outcome.
Phase II study of pembrolizumab (pembro) plus platinum doublet chemotherapy and radiotherapy as first-line therapy for unresectable, locally advanced stage III NSCLC: KEYNOTE-799.
Authors: Salma K. Jabbour, Ki Hyeong Lee, Nicolaj Frost, Dariusz Kowalski, Valeriy Vladimirovich Breder, Theodore Pollock, Noemi Reguart, Baerin Houghton, Xavier Quantin, Steven M. Keller, Hong Liu, Bilal Piperdi, Martin Reck
Journal: Journal of Clinical Oncology (2020)

9008 Background: KEYNOTE-799 (NCT03631784) evaluates pembro plus concurrent chemoradiation therapy (CCRT) in pts with unresectable, locally advanced stage III NSCLC. Methods: In this phase 2, nonrandomized, open-label trial, pts with previously untreated, unresectable, pathologically confirmed stage IIIA–C NSCLC with measurable disease (RECIST 1.1) received up to 17 cycles of pembro 200 mg Q3W starting with cycle 1 plus standard thoracic radiotherapy (60 Gy in 30 daily 2-Gy fractions) in cycles 2–3 and investigator’s choice of paclitaxel 200 mg/m 2 + carboplatin AUC 6 Q3W for cycle 1, then paclitaxel 45 mg/m 2 + carboplatin AUC 2 QW for cycles 2–3 (cohort A), or cisplatin 75 mg/m 2 + pemetrexed 500 mg/m 2 Q3W (nonsquamous only) in cycles 1–3 (cohort B). Primary endpoints were ORR (CR/PR per RECIST 1.1 by blinded independent central review) and rate of grade ≥3 pneumonitis (per NCI CTCAE v4.0). CIs were estimated using the Clopper-Pearson method. Safety was assessed in all treated patients; efficacy was assessed in pts with ≥15 wks follow-up. Results: As of Jan 3, 2020, 112 and 73 pts have been enrolled in cohorts A and B, respectively; 63 in cohort A and 52 in cohort B continue on treatment. Median (range) follow up was 8.3 (0.7–14.0) mo in cohort A and 5.8 (0.2–13.7) mo in cohort B. ORR (90% CI) was 67.0% (58.9%–74.3%) in cohort A and 56.6% (44.4%–68.2%) in cohort B (Table). Grade ≥3 pneumonitis occurred in 9 pts (8.0%; 90% CI, 4.3%–13.6%) in cohort A and 4 pts (5.5%; 90% CI, 1.9%–12.1%) in cohort B. Treatment-related grade ≥3 AEs occurred in 72 pts (64.3%) in cohort A and 30 pts (41.1%) in cohort B. 4 pts had treatment-related grade 5 pneumonitis (all in cohort A). Enrollment is complete for cohort A and ongoing in cohort B. Conclusions: Pembro plus CCRT shows promising antitumor activity in pts with unresectable, locally advanced stage III NSCLC. Toxicity was as anticipated with pembro plus CCRT. Clinical trial information: NCT03631784. [Table: see text]
健康管理在中国的历史、现状和挑战
Authors: 黄建始, 陈君石
Journal: BMJ (2007)

健康管理在中国的出现不到十年,实践应用先行于理论研究.自2001年国内第1家健康管理公司注册到今天,健康管理走过了艰难而重要的五年.2003年SARS危机的出现和2005年健康管理师国家职业的设立,有力地推动了健康管理在中国的发展[1]。