tbuckley/cabot-search huggingface dataset:
Daratumumab + bortezomib, thalidomide, and dexamethasone (D-VTd) in transplant-eligible newly diagnosed multiple myeloma (TE NDMM): Baseline SLiM-CRAB based subgroup analysis of CASSIOPEIA.
Authors: Cyrille Touzeau, Philippe Moreau, Aurore Perrot, Cyrille Hulin, Mamoun Dib, Mourad Tiab, Denis Caillot, Thierry Facon, Xavier Leleu, Niels W.C.J. van de Donk, Annemiek Broijl, Sonja Zweegman, Mark-David Levin, Michel Delforge, Lixia Pei, Veronique Vanquickelberghe, Carla De Boer, Tobias Kampfenkel, Jessica Vermeulen, Pieter Sonneveld
Journal: Journal of Clinical Oncology (2020)

8538 Background: In the phase 3 CASSIOPEIA study, D-VTd significantly improved outcomes vs VTd in TE NDMM pts at an 18.8-mo median follow-up. To allow earlier diagnosis and treatment of MM, the IMWG added 3 validated biomarkers (≥60% clonal bone marrow plasma cells, serum free light chain ratio ≥100, and &gt; 1 focal bone lesion by MRI; “slim”) to the conventional “CRAB” diagnostic criteria. We present a subgroup analysis of CASSIOPEIA based on baseline slimCRAB criteria. Methods: TE NDMM pts were randomized 1:1 to 4 pre-ASCT induction and 2 post-ASCT consolidation cycles of D-VTd or VTd. The “slim-only” subgroup excludes pts with ≥1 conventional CRAB criterion based on data collected at baseline; the remaining pts were included in the “CRAB” subgroup. Results: Of 1085 randomized pts (543 D-VTd; 542 VTd), 81 were included in the slim-only subgroup (36 D-VTd; 45 VTd) and 1004 were included in the CRAB subgroup. In slim-only vs CRAB pts, 22% vs 54% had an ECOG score of ≥1, 4% vs 16% had ISS Stage III disease, and 11% vs 16% had high-risk cytogenetics. For D-VTd vs VTd pts in the slim-only group, these rates were 22% vs 22%, 8% vs 0%, and 6% vs 16%, respectively. Overall response rates (ORR) and rates of sCR, ≥CR, and MRD negativity were similar between slim-only and CRAB pts; for slim-only pts, rates were significantly higher for D-VTd vs VTd (Table). After an 18.8-mo median follow-up, progression-free survival (PFS) was not significantly different in slim-only vs CRAB pts, or in D-VTd vs VTd slim-only pts (Table). For D-VTd vs VTd CRAB pts, 18-mo PFS rates were 92% vs 84%, and 24-mo PFS rates were 89% vs 76%. Conclusions: Baseline characteristics indicate that slim-only pts were slightly fitter and of lower risk status vs CRAB pts; however, response rates, MRD-negativity rates, and PFS did not differ significantly between these groups. Among slim-only pts, significantly higher response and MRD-negativity rates were achieved with D-VTd vs VTd. Among CRAB pts, PFS rates were higher with D-VTd vs VTd. Clinical trial information: NCT02541383 . [Table: see text]
Clinical observations of stand-alone MC + polyetheretherketone cage without anterior cervical plating in traumatic cervical disc herniation
Authors: Bing Jiang, Li-ming Liu, Yan-qing Cao, Xiao-jun Zhang
Journal: BMJ (2012)

Twenty patients of traumatic cervical disc herniation in mono-segment were reconstructed after discectomy with a cage filled with autogenous cancellous illict-bone graft.Neither fracture nor dislocation was found by radiograph or magnetic resonance imaging.The average follow-up period was 22 months (range:6 - 36 months) and the average duration of bone graft fusion 4.9 months.No complications of internal fixation occurred.With this new cage,traumatic cervical disc herniation might be safely treated.

Key words: 
Cage; Intervertebral disc displacement,cervical vertebral
Association of serum soluble intercellular cell adhesion molecule-1, soluble vascular cell adhesion molecule-1 and hypersensitivity-CRP levels with peripheral vascular disease of lower limbs in patients with type 2 diabetes mellitus
Authors: Qing-ying Tan, Jing Wang, Yun Ruan, Yong Ruan, Xiu-jing Wang, Jia-qi Yao
Journal: BMJ (2013)

Objective
To investigate the association of serum levels of soluble intercellular cell adhesion molecule-1(sICAM-1), soluble vascular cell adhesion molecule-1(sVCAM-1) and high sensitivity C-reactive protein (hs-CRP) with peripheral vascular disease of lower limbs in patients with type 2 diabetes mellitus (T2DM).


Methods
One hundred and thirty T2DM patients admitted from October 2011 to October 2012, and 30 age/sex-matched healthy subjects were enrolled in the study. The serum levels of sICAM-1, sVCAM-1, hs-CRP and other clinical parameters were measured; the peripheral blood vessels of lower limbs were examined with color Doppler ultrasonography. Based on the extent of angiopathy of lower limbs T2DM patients were classified as normal vascular group (n=26), mild angiopathy group (n=45), moderate/severe angiopathy group (n=59).


Results
The serum levels of sICAM-1 and sVCAM-1 in moderate/severe angiopathy group of T2DM patients were higher than those in mild angiopathy group, normal vascular group and healthy controls (t: 4.15-8.93, all P<0.05); the serum levels of hs-CRP in moderate/severe angiopathy group were higher than those in mild angiopathy group, normal vascular group and healthy controls (t: 2.18-4.27, all P<0.05). The serum sICAM-1 level was positively correlated with total cholesterol (TC), low density lipoprotein cholesterol (LDL-C) and sVCAM-1. The serum sVCAM-1 level was positively correlated with course of disease, systolic blood pressure and CRP.


Conclusions
Serum levels of sICAM-1, sVCAM-1 and hs-CRP are correlated with the extent of angiopathy of lower limbs in T2DM patients, and the elevated sICAM-1; sVCAM-1 and hs-CRP levels are also associated with hyper blood pressure, dislipidemia and chronic inflammation.


Key words: 
Diabetes mellitus, type 2; Intercellular adhesion molecule-1; Vascular cell adhesion molecule-1; C-reactive protein; Diabetic angiopathies
An elderly woman with purple urine bag syndrome: a case report
Authors: Jiatang Zheng, Chunhua Chi, Aimei Dong, Yuxia Kong, Xiuwen Fei
Journal: BMJ (2018)

紫色尿袋综合征(PUBS)是长期留置导尿管后尿袋和/或尿管中的尿液呈蓝紫色色素沉淀的一种罕见临床现象，通常认为与导管相关尿路感染有关。文章对1例老年女性PUBS的危险因素、病生理机制、病原学评估和管理策略进行分析。
Opioid prescribing patterns among generalists &amp; oncologists for Medicare Part D beneficiaries from 2013-2017.
Authors: Trevor Joseph Royce, Andrew Roberts, Stacie Dusetzina, Ankit Agarwal
Journal: Journal of Clinical Oncology (2020)

2070 Background: In response to the opioid crisis, recent policies aiming to reduce opioid prescribing, misuse, &amp; abuse have generated concern that patients with cancer pain may unintentionally experience reduced access to necessary opioid therapy. It is unknown how opioid prescribing patterns have changed between generalists and oncologists during this era. Methods: We conducted a longitudinal repeated cross-sectional study estimating adjusted annual national trends in opioid prescribing among generalists &amp; oncologists using the Medicare Part D Prescriber Public Use Files 2013-2017. Poisson models estimated annual adjusted predicted mean rates of opioid prescribing-per-1,000 total prescriptions &amp; long-acting opioid prescribing per-1,000 opioid prescriptions. Poisson models estimated adjusted incidence rate ratios (aIRRs) to quantify annual changes in prescribing rates. Results: From 2013-2017 the annual adjusted predicted mean rate of opioid prescriptions per 1,000 total prescriptions decreased from 53.4 to 41.3 among generalists (aIRR = 0.78; p &lt; 0.01) and from 133.2 to 105.9 among oncologists (aIRR = 0.83; p &lt; 0.01). The rate of long-acting opioid fills per 1,000 opioid prescriptions decreased from 96.0 to 87.0 (aIRR = 0.87; p &lt; 0.01) and 235.1 to 222.5 (aIRR = 0.95; p &lt; 0.01) for generalists &amp; oncologists, respectively (Table). Conclusions: We found large declines in overall opioid prescribing rates among generalists (-22%) and oncologists (-17%) from 2013-2017. Long-acting opioid prescribing rates decreased over 2.5-times more among generalists than oncologists. Opioid policy &amp; advocacy have been effective in reducing the extent of opioid prescribing in the Medicare population but how much of the decrease in prescribing by oncologists is ‘appropriate’ versus ‘inappropriate’ deserves further investigation. [Table: see text]
社区医生应掌握的胆囊结石处理原则
Authors: 牟洪超, 冯晓燕, 牟红臻
Journal: BMJ (2004)

胆囊结石如果得到适时合理地处理,可避免很多并发症,降低病死率. 1.无症状胆囊结石处理原则:其目的在于防止胆囊结石并发症发生和胆绞痛的急性发作.无症状性胆囊结石急性症状发作时再进行胆囊切除并不增加病死率,不必进行预防性胆囊切除,以下情况考虑手术:①合并糖尿病:此时胆囊结石一旦发生并发症,病死率比无糖尿病患者高5倍;②无功能胆囊。
经皮体外起搏在急性严重缓慢性心律失常治疗中的应用
Authors: 郑燕列, 吕新志, 肖阳娥, 徐华, 黄建华
Journal: BMJ (2004)

目前大多数医院主要开展经静脉临时心脏起搏,而经皮体外无创性临时心脏起搏(external noninvasive cardiac pacing,ENCP)应用相对较少,但其临床应用价值已肯定[1-3].我院近几年共开展ENCP抢救急性严重缓慢性心律失常18例,现报告如下。
Inflammatory and insulinemic dietary patterns: Influence on circulating biomarkers and prostate cancer risk in the prostate, lung, colorectal and ovarian cancer (PLCO) cohort.
Authors: Desmond Aroke, Edmund Folefac, Qi Jin, Ni Shi, Steven K. Clinton, Fred Tabung
Journal: Journal of Clinical Oncology (2020)

e17561 Background: Prostate cancer (PCa) is common in countries with affluent dietary patterns and represents a heterogeneous collection of subtypes with varying behavior. Reductionist strategies focusing on individual nutrients or foods have not clearly defined risk factors. We have developed mechanisms-based dietary patterns focusing upon inflammation and chronic insulin hypersecretion, processes that are hypothesized to impact prostate carcinogenesis. Methods: First, we examined associations of the empirical dietary index for hyperinsulinemia (EDIH) and empirical dietary inflammatory pattern (EDIP) scores with circulating concentrations of relevant biomarkers, to assess the validity of these two dietary patterns. Secondly, we investigated associations of the EDIH and EDIP with risk of PCa (total, low-grade, high-grade, advanced and lethal). EDIH and EDIP dietary scores calculated from food frequency questionnaire data for 3,517 men and women who provided a blood sample at enrollment, were used to validate dietary patterns against known relevant biomarkers. A separate sample of 49,317 men was used to evaluate the associations of EDIH and EDIP with prostate cancer risk. We used multivariable-adjusted linear regression to compute the percent change and 95% confidence intervals (95%CI) in biomarker concentrations, and Cox regression to estimate hazard ratios (HR) and 95%CI for PCa risk; in dietary score quintiles, using the lowest quintile as reference. Results: Compared to the lowest quintile, participants in the highest EDIH quintile (most hyperinsulinemic diets) had significantly higher concentrations of C-peptide, insulin, CRP, and TNF-R2 and lower adiponectin. Those consuming the most pro-inflammatory diets (EDIP) had significantly higher concentrations of IL-6, TNF-R2, C-peptide and insulin with lower adiponectin. Men classified in EDIH quintile 5 compared to 1, were also at higher total PCa risk: HR, 1.11; 95%CI, 1.01, 1.23; P-trend = 0.03, especially high-grade cancer: HR, 1.18; 95%CI, 1.02, 1.37; P-trend = 0.06; whereas the EDIP was not associated with risk. Conclusions: EDIH and EDIP predicted concentrations of biomarkers relevant to the insulinemic and inflammatory potential of diet in PLCO. EDIH predicted future PCa risk and may suggest a dietary pattern for PCa prevention.
Association of hospital type with prices, spending, and acute care utilization among privately insured patients undergoing cancer surgery.
Authors: Samuel U Takvorian, Laura Yasaitis, Manqing Liu, Daniel J. Lee, Rachel M. Werner, Justin E. Bekelman
Journal: Journal of Clinical Oncology (2020)

e19376 Background: With annual cancer spending estimated to surpass $170 billion in 2020, national attention has focused on the prices and utilization of cancer care. This is particularly important for privately insured patients, for whom healthcare prices are negotiated between insurers and providers and price transparency is lacking. Among privately insured patients undergoing common cancer surgery, we examined the relation between hospital type and prices, spending, and utilization. Methods: We conducted a retrospective study using Health Care Cost Institute’s multipayer national commercial claims data. The study population included patients with breast, colon or lung cancer undergoing cancer surgery from 2011-2014. The exposure was hospital type at which surgery was performed: National Cancer Institute (NCI), academic, or community. Spending outcomes were surgery-specific prices paid and 90-day total episode spending. Utilization outcomes were length of stay (LOS), emergency department (ED) use, and hospital readmission within 90 days. We estimated mean risk-adjusted spending and utilization outcomes for each hospital type using generalized linear mixed-effects models, adjusting for patient, hospital and region characteristics. Results: We identified 66,878 patients with incident breast (53.5%), colon (32.0%), or lung (14.5%) cancer undergoing cancer surgery at 2,995 hospitals (8.3% at NCI; 16.3% academic; 75.4% community). Treatment at NCI cancer centers was associated with higher surgical prices paid ($18,310 at NCI v $14,703 at community hospitals; diff +$3,607; p &lt; 0.001) and 90-day total episode spending ($46,462 v $41,274; diff +$5,188; p = 0.008). There were no significant differences in LOS, ED use or hospital readmission within 90 days. Conclusions: Among privately insured patients undergoing cancer surgery, NCI cancer centers had higher surgical prices and episode spending without differences in utilization, compared to community hospitals. A better understanding of the drivers of prices and spending at NCI cancer centers is needed. [Table: see text]
鼻-鼻窦炎诊断要点和治疗原则的进展
Authors: 顾之燕
Journal: BMJ (2006)

鼻-鼻窦炎(rhino-sinusitis)是几种鼻部疾病的总称,它包括鼻炎(变应性与非变应性)、鼻窦炎(变应性、感染性或混合性)、鼻息肉和鼻息肉病;狭义的鼻-鼻窦炎专指鼻窦炎,为一个、多个或全鼻窦的炎症.鼻-鼻窦炎的命名较鼻窦炎更为恰当,因为鼻窦炎均继发于鼻炎(除牙源性上颌窦炎外),两者的临床症状、体征、影像学检查等均有高度的相关性和不可分割性.有研究证明,两者黏膜的组织病理学也无明显差异性.2000年国际鼻科学术会议(Washington D.C.)有学者报道,对行内镜鼻窦手术的鼻-鼻窦炎患者术中分别取前筛和鼻中隔黏膜做常规病理组织学检查,发现两者炎性细胞浸润程度,特别是嗜酸性粒细胞浸润程度呈正相关。
对鼻后滴流综合征的新认识
Authors: 张荣葆
Journal: BMJ (2007)

咳嗽通常按时间分为急性咳嗽、亚急性咳嗽和慢性咳嗽.急性咳嗽时间＜3周,亚急性咳嗽3～8周,慢性咳嗽≥8周.咳嗽变异型哮喘、鼻后滴流综合征、嗜酸粒细胞性支气管炎和胃食管反流性咳嗽,占呼吸内科门诊慢性咳嗽患者的70%～95%。
TRK xDFG Mutations Trigger a Sensitivity Switch from Type I to II Kinase Inhibitors
Authors: Emiliano Cocco, Ji Eun Lee, Srinivasaraghavan Kannan, Alison M. Schram, Helen H. Won, Sophie Shifman, Amanda Kulick, Laura Baldino, Eneda Toska, Amaia Arruabarrena-Aristorena, Srushti Kittane, Fan Wu, Yanyan Cai, Sabrina Arena, Benedetta Mussolin, Ram Kannan, Neil Vasan, Alexander N. Gorelick, Michael F. Berger, Ofra Novoplansky, Sankar Jagadeeshan, Yi Liao, Uwe Rix, Sandra Misale, Barry S. Taylor, Alberto Bardelli, Jaclyn F. Hechtman, David M. Hyman, Moshe Elkabets, Elisa de Stanchina, Chandra S. Verma, Andrea Ventura, Alexander Drilon, Maurizio Scaltriti
Journal: Cancer Discovery (2020)

Abstract On-target resistance to next-generation TRK inhibitors in TRK fusion–positive cancers is largely uncharacterized. In patients with these tumors, we found that TRK xDFG mutations confer resistance to type I next-generation TRK inhibitors designed to maintain potency against several kinase domain mutations. Computational modeling and biochemical assays showed that TRKAG667 and TRKCG696 xDFG substitutions reduce drug binding by generating steric hindrance. Concurrently, these mutations stabilize the inactive (DFG-out) conformations of the kinases, thus sensitizing these kinases to type II TRK inhibitors. Consistently, type II inhibitors impede the growth and TRK-mediated signaling of xDFG-mutant isogenic and patient-derived models. Collectively, these data demonstrate that adaptive conformational resistance can be abrogated by shifting kinase engagement modes. Given the prior identification of paralogous xDFG resistance mutations in other oncogene-addicted cancers, these findings provide insights into rational type II drug design by leveraging inhibitor class affinity switching to address recalcitrant resistant alterations. Significance: In TRK fusion–positive cancers, TRK xDFG substitutions represent a shared liability for type I TRK inhibitors. In contrast, they represent a potential biomarker of type II TRK inhibitor activity. As all currently available type II agents are multikinase inhibitors, rational drug design should focus on selective type II inhibitor creation. This article is highlighted in the In This Issue feature, p. 1
Value of prenatal ultrasonography in diagnosis of Pentalogy of Cantrell
Authors: Peng An, Jiaqi Zhang, Jinzhi Xu, Wei Feng, Lan Yu, Wenting Lei, Yuanying Liang
Journal: BMJ (2018)

Four cases of Pentalogy of Cantrell were diagnosed by prenatal ultrasonography and confirmed by autopsy after labor induction. There were 1 case of complete Pentalogy of Cantrell and 3 cases of incomplete Pentalogy. In 3 cases of incomplete Pentalogy of Cantrell, 1 case presented with high umbilical cord prolapse, extraspectoral heart, partial defect of the lower part of the sternum, partial defect of the pericardium, single umbilical artery and cervical lymphatic cyst; 1 case presented with high umbilical cord prolapse, extraspectoral heart, thoracic fissure and ventricular septal defect; and 1 case presented with umbilical cord, extraspectoral heart, partial inferior sternal segment defect, ventricular septal defect and bilateral clubfoot varus. In 1 case of complete Pentalogy of Cantrell, there were high umbilical cord bulge, extraspectoral heart, chest fissure and inferior segment defect, anterior diaphragm and pericardium defect, total forebrain deformity, right 12th ribs loss and ventricular septal defect. Ectopic heart and omphalocele are typical echographic features of Pentalogy of Cantrel and prenatal ultrasonography is of important value in early diagnosis of this congenital malformation.


Key words: 
Ultrasonography, prenatal; Pentalogy of Cantrell
An ultra-sensitive multiplexed enrichment of rare DNA variants via toehold exchange principle.
Authors: Yue Pu, Qianwen Wang, Rui Lin, Tao Wang
Journal: Journal of Clinical Oncology (2020)

e13658 Background: As a major type of liquid biopsy, circulating tumor DNA (ctDNA) provides important somatic mutation information, but the feature of rare allele frequency of mutation in ctDNA hampers its wide application. Methodology with high sensitivity, cost effectiveness, and multiplexing capability is needed for analyzing ctDNA samples. Methods: We have developed a novel methodology, termed MTEA (Multiplexed Toehold Exchange Amplification), which selectively amplifies and enriches all sequence variants (including SNV and deletion) 1000-fold over the wild-type sequence within ~20-nucleotide window. The amplified products are detected by Sanger sequencing or next-generation sequencing (NGS). This novel approach takes advantage of toehold exchange principle in which PCR amplification of wild-type rather than mutants would be greatly reduced due to the formation of a duplex of wild-type sequence with a blocker targeting to the wild-type rather than the mutant alleles. Results: Using circulating cell-free DNA (cfDNA) reference standards, we demonstrated that the major driver mutations of lung adenocarcinomas, including EGFR L858R and exon 19 deletion, KRAS G12X, and BRAF V600E, were enriched and detected simultaneously with MTEA technology at abundance as low as 0.01-0.05%. The clinical implications of MTEA technology were further validated using ctDNA from liquid biopsy specimens of 29 non-small cell lung cancer patients, and results were compared with those collected from the NGS and ddPCR analysis. Consistent results were obtained from all of the three platforms, which indicated 100% accuracy. The MTEA method has advantages over ddPCR since the later lacks the multiplexing detection ability. The MTEA technology can also save cost compared with NGS method. Conclusions: MTEA technology can enrich ctDNA from cancer patients to detect ultra-low abundance of clinically relevant mutations. Upon validation using a larger cohort, the technology may have wide application in precision medicine and guide clinicians for therapeutic decisions.
关于高血压新的美国指南JNC7
Authors: Claude Lenfant, 戴玉华
Journal: BMJ (2004)

美国心肺血液研究所(national heart ,lung,and blood Institute, NHLBI)公开发表了新的高血压临床指南JNC7(美国预防、检测、评价和治疗高血压的全国联合委员会第7次报告).2003年5月21日美国医学会杂志(JAMA, 2003,289:2560-2572)上刊登的是报告的摘要,更详尽全面的报告将在2003年晚些时候发表。
系统性红斑狼疮合并隐球菌脑膜炎临床分析
Authors: 张娜, 魏蔚, 周蕾, 董笑影, 陈明, 巩路
Journal: BMJ (2012)

隐球菌感染,特别是脑膜炎,是系统性红斑狼疮(SLE)患者少见的机会性感染,隐袭起病,如不能及时诊断并给予有效抗真菌治疗,死亡率很高[1].现报道我科2000年至2010年收治的4例SLE合并隐球菌脑膜炎患者如下. 关键词：红斑狼疮;系统性
Micro-invasive surgery for the treatment of intracerebral hemorrhage in hypertensive patients
Authors: Lai-gao Song, Lin-jing Fei, Pei-ru Liu, Wei-bin Ma
Journal: BMJ (2008)

From January 2000 to December 2006, 78 hypertensive patients with intracerebral hemorrhage(80～130 ml)underwent minimally invasive surgery(n=41)or small bone window craniotomy(n=37). Neurological deficit scores and mortality were estimated to evaluate the therapeutic efficacy among those two group patients. The success rate was significantly higher in the micro-invasive surgery group than the small bone window craniotomy group(P＜0. 05). However, no significantly lower mortality was detected in the micro-invasive surgery group(P＞0. 05). In summary, micro-invasive surgery may reduce the mortality, largely increase the success rate of treatment, and improve patients' quality of life. 

Key words: 
Intracranial hemorrhage,hypertensive; Neurosurgical procedures
PD-1 Blockade in Chinese versus Western Patients with Melanoma
Authors: Alexander N. Shoushtari, Riyue Bao, Jason J. Luke
Journal: Clinical Cancer Research (2020)

In this trial of programmed cell death-1 (PD-1) blockade with toripalimab in previously treated Chinese patients with melanoma, unique histologic and molecular features may explain why the objective response rate is lower than those defined in Western populations. This work suggests future avenues for investigating mechanisms of melanoma formation and resistance to PD-1 blockade.See related article by Tang et al., p. 4250.