tbuckley/cabot-search huggingface dataset:
Effect of Doxycycline on Aneurysm Growth Among Patients With Small Infrarenal Abdominal Aortic Aneurysms
Authors: B. Timothy Baxter, Jon Matsumura, John A. Curci, Ruth McBride, LuAnn Larson, William Blackwelder, Diana Lam, Marniker Wijesinha, Michael Terrin
Journal: JAMA (2020)

<h3>Importance</h3> Abdominal aortic aneurysms affect more than 3% of US older adults. <h3>Objective</h3> To test whether doxycycline reduces the growth of abdominal aortic aneurysm over 2 years as measured by maximum transverse diameter. <h3>Design, Setting, and Participants</h3> Parallel, 2-group, randomized clinical trial that was conducted at 22 US clinical centers between May 2013 and January 2017, and enrolled patients 50 years or older with small (3.5-5.0 cm for men, 3.5-4.5 cm for women) infrarenal aneurysms. The final date of follow-up was July 31, 2018. <h3>Interventions</h3> Patients were randomized to receive twice daily for 2 years doxycycline 100 mg orally (as capsules) (n = 133) or placebo (n = 128). <h3>Main Outcomes and Measures</h3> The primary outcome was change in abdominal aortic aneurysm maximum transverse diameter measured from CT images at baseline and follow-up at 2 years. Patients were assigned ranks based on the maximum transverse diameter (measured or imputed) of the aorta and also if they underwent aneurysm repair or died. The ranks were converted to scores having a normal distribution to facilitate the primary analysis (“normal scores”). <h3>Results</h3> Of 261 patients randomized, no follow-up CT scans were obtained on 7 (3%), leaving a final analysis set of 129 patients assigned to doxycycline and 125 to placebo (mean [SD] age, 71.0 years [7.4 years], 35 women [14%]). The outcome normal scores used in the primary analysis were based on maximum transverse diameter (measured or imputed) in 113 patients (88%) in the doxycycline group and 112 patients (90%) in the placebo group; aneurysm repair in 13 (10%) and 9 (7%), and death in 3 (2%) and 4 (3%), respectively. The primary outcome, normal scores reflecting change in aortic diameter, did not differ significantly between the 2 groups, mean change in normal scores, 0.0262 vs −0.0258 (1-sided<i>P</i> = .71). Mean (SD) baseline maximum transverse diameter was 4.3 cm (0.4 cm) for doxycycline and 4.3 cm (0.4 cm) for placebo. At the 2-year follow-up, the change in measured maximum transverse diameter was 0.36 cm (95% CI, 0.31 to 0.40 cm) for 96 patients in the doxycycline group vs 0.36 cm (95% CI, 0.30 to 0.41 cm) for 101 patients in the placebo group (difference, 0.0; 95% CI, −0.07 to 0.07 cm; 2-sided<i>P</i> = .93). No patients were withdrawn from the study because of adverse effects. Joint pain occurred in 84 of 129 patients (65%) with doxycycline and 79 of 125 (63%) with placebo. <h3>Conclusions and Relevance</h3> Among patients with small infrarenal abdominal aortic aneurysms, doxycycline compared with placebo did not significantly reduce aneurysm growth at 2 years. These findings do not support the use of doxycycline for reducing the growth of small abdominal aortic aneurysms. <h3>Trial Registration</h3> ClinicalTrials.gov Identifier:NCT01756833
Clinical application of MRI in the management of complex anal fistulas
Authors: Qunli Yao, Hao Meng, Zhiguo Zhang, Xiaoyu Chen, Yuping Zheng, Lei Zhang
Journal: BMJ (2014)

To explore the accuracy and clinical value of preoperative MRI for complex anal fistulas. The MRI status of internal/external opening, fistula track and perianal abscess was analyzed for 24 complex anal fistulas patients. Their outcomes were compared with the final surgical diagnoses. The accuracy rates of internal opening, external opening, fistula tracks and perianal abscess were 87%, 97%, 92% and 16/17 respectively. MRI is helpful for evaluating accurately the extent and complexity of anal fistulas and guiding surgical therapy.


Key words: 
Rectal fistula; Magnetic resonance imaging
Effect of rehabilitation treatment using the assistive devices for children with cerebral palsy
Authors: Shu-xin Zhang, Qing Du, Huan Wang, Xuan Zhou, Nan Chen, Xiao-jie Li
Journal: BMJ (2012)

Objective To investigate the effect of the synthetic rehabilitation treatment using the assistive devices for children with cerebral palsy.Methods 60 outpatients (male 31,female 29) diagnosed as cerebral palsy in our hospital from June 2009 to June 2010 were divided into trial group (n =30) and control group (n =30).Both of the two groups received our rehabilitation treatment three times a week.Compared with the daily family rehabilitation training of the control group,trial group still received a daily rehabilitation treatment by their parents using the assistive devices under the guidance of the therapist.They were assessed with Gross Motor Function Measure 66 items version (GMFM-66)and 88 items version (GMFM-88) before and after 6 months treatment.Results The total score of GMFM-66 and each dimension score of GMFM-88 improved in both group after 6 months treatment,except the centrol group Lying & Rolling dimension.Trial group 51 ± 13 vs.44 ± 15,control group 42 ± 17 vs.38 ± 16 (t =-3.580,P =0.001).There was significant difference on the total score of GMFM-66 and the three dimensions score (Lying & Rolling,Sitting and Walking,Running & Jumping) of GMFM-88 between two group.Lying & Rolling:F =4.59,P =0.036; Sitting:F =6.40,P =0.014 ; Walking,Running & Jumping:F =4.35,P =0.041.Conclusion The synthetic rehabilitation treatment in Medical institutions associate with family rehabilitation treatment using the assistive devices can effectively improve the recovery of gross motor function in children with cerebral palsy.

Key words: 
Self-help devices; Cerebral palsy; Recovery of functions
A first-in-human phase I/II study of HL-085, a MEK Inhibitor, in Chinese patients with NRASm advanced melanoma.
Authors: Xuan Wang, Lu Si, Lili Mao, Chuanliang Cui, Zhihong Chi, Xinan Sheng, Xue Bai, Li Zhou, BIN LIAN, Bixia Tang, Xieqiao Yan, Siming Li, Yan Kong, Jun Guo
Journal: Journal of Clinical Oncology (2020)

10047 Background: MEK inhibitors have confirmed effects on malignant tumors, especially for those induced by RAS/RAF dysfunction. There is no effective drug in clinic for NRASm advanced melanoma. HL-085 is a selective MEK inhibitor, showing good safety and efficacy in preclinical studies. This study is a phase I/II study to evaluate the safety, tolerability, pharmacokinetic and preliminary anti-cancer activity of HL-085 in patients(pts) with NRASm advanced Melanoma. Methods: The phase I/II study is conducted using a “3+3” regimen for dose escalation. The pts are treated with HL-085 at a starting dose of 0.5mg BID to 18mg BID. Adverse events (AEs) are reported per NCI CTCAE version 5.0. Preliminary anti-cancer activity is evaluated by ORR, DCR, PFS and DoR. Results: Total 33 pts were enrolled in the study. The histologic types were acral (51.4%), mucosal (27.2%) and other (21.2%). The NRAS mutation types were Q61 (72.7%), G12 (18.2%) with half for G12D, and G13 (9.1% ). Most AEs were G1 or G2, and the most common drug-related AEs were rash, increased creatine phosphokinase, peripheral edema, increased alanine aminotransferase and aspartate aminotransferase. No dose-limited toxicity was observed. PK analysis was shown linear PK profile with no obvious accumulation. Among 12 evaluable pts over 9 mg, 4 pts were at the stage of M1c with 1 liver metastasis. Average targeted tumor size was 74.6mm with the largest 184 mm. 10 pts achieved tumor shrinkage [ 60% with Q61, 20% with G12D, 10% each with G12S and G13R]. 4 pts ( 2 acral, 1 mucosal and 1 other, each pt has mutaiton type of Q61R,Q61L, Q61K and G12S respectively ) had confirmed partial response(PR) [median treatment duration 26.6 weeks (wks) with longest 47.6 wks]). 6 pts achieved stable disease (SD) (median treatment duration 15.72 wks with longest 24 wks), and 66.7% were over 14 wks . The median PFS was 17.4 wks, and confirmed best ORR was 33.3% with DCR 83.3% . Conclusions: Our data demonstrated that HL-085 is well tolerated, with manageable side-effects and promising anti-cancer activity in pts with NRASm advanced melanoma. Clinical trial information: NCT 03973151.
Breakthrough cancer pain clinical features and differential opioids response: A machine learning approach in 4,016 cancer patients of IOPS-MS study.
Authors: Francesco Pantano, Paolo Manca, Grazia Armento, Tea Zeppola, Angelo Onorato, Daniele Santini, Bruno Vincenzi, Giuseppe Tonini
Journal: Journal of Clinical Oncology (2020)

e24150 Background: A large proportion of patients with cancer suffer from Breakthrough cancer pain (BTcP). Several unmet clinical needs concerning BTcP treatment, like optimal opioids dosage, are being investigated. We explored with an unsupervised learning algorithm whether distinct subtypes of BTcP exist and whether they can provide new insights into clinical practice. Methods: We used partitioning around medoids algorithm on a large dataset of patients with BTcP previously collected by the IOPS group in order to identify possible subgroups of BTcP; the input of the algorithm consisted of different BTcP features, like its duration or its intensity. Silhouette statistics was used to pick an optimal number of clusters. Resulting clusters were analyzed in terms of BTcP therapy satisfaction, clinical features and usage of basal pain and rapid onset opioids. Opioids dosages were converted to a unique scale and BTcP-opioids-to-basal-pain-opioids ratio (OpR) was calculated for each patient. Polynomial logistic regression was used to catch non-linear relationships between therapy satisfaction and opioids usage. Results: The cohort comprised 4016 patients with controlled basal pain and suffering from BTcP. Our algorithm identified 12 distinct BTcP clusters. Optimal OpRs differed across the clusters, ranging from 15% to 50%. In the whole cohort, OpR was more clearly associated with therapy satisfaction compared with BTcP opioids or basal pain opioids alone. The majority of the clusters were linked to peculiar association of certain drugs with therapy satisfaction or dissatisfaction. A free online tool was created for new patients cluster computation ( https://mancapaolo.shinyapps.io/UCBM_BTcPclusters/ ) in order to validate these clusters in future studies and to provide a possible, handy indications for personalized BTcP therapy. Conclusions: This work proposes a classification for BTcP and identifies subgroups of patients with unique efficacy of different pain medications. This work supports the theory that the optimal dose of BTcP opioids depends on the dose of basal opioids and identifies novel values, possibly useful for future trials.
胸内结节病并下呼吸道超鞭毛虫感染一例
Authors: 周一平, 刘慧, 朱新建
Journal: BMJ (2007)

患者男,53岁,个体建筑业主.因颈部压迫感、胸闷、低热1个月于2004年11月23日人院.有时伴咽喉发痒而引起干咳,无盗汗、纳差,感觉易疲劳.在原籍江西生活30余年,来深圳已13年.体检:身体强壮,体温37.2 ℃,全身浅表淋巴结无肿大,心肺腹无异常。
Culture and the plasticity of perception
Authors: Michael Lifshitz, T. M. Luhrmann
Journal: Behavioral and Brain Sciences (2020)

Abstract Culture shapes our basic sensory experience of the world. This is particularly striking in the study of religion and psychosis, where we and others have shown that cultural context determines both the structure and content of hallucination-like events. The cultural shaping of hallucinations may provide a rich case-study for linking cultural learning with emerging prediction-based models of perception.
Survival outcomes among older adults (OA) receiving second-line therapy for metastatic CRC (mCRC): 5,289 patients (pts) from the ARCAD Clinical Trials Program.
Authors: Nadine Jackson McCleary, William S. Harmsen, Eric VanCutsem, Alberto F. Sobrero, Richard M. Goldberg, Josep Tabernero, Matt Seymour, Leonard B. Saltz, Bruce J. Giantonio, Arnold Dirk, Mace L. Rothenberg, Miriam Koopman, Hans-Joachim Schmoll, Henry C. Pitot, Paulo Marcelo Hoff, Alfredo Falcone, Aimery De Gramont, Qian Shi
Journal: Journal of Clinical Oncology (2020)

7009 Background: Survival outcomes of 2 nd line mCRC therapy for OA are poorly understood. We evaluated the rates and survival outcomes of 2 nd line therapy among OA age 70+ compared to younger adults (YA) age &lt; 70 following progression on 1 st line clinical trials. Methods: Associations between clinical characteristics of pts with available treatment data after progression on 10 of 23 1 st line ARCAD trials, time to initial progression (TTiP) and 2 nd line therapy were evaluated. Time to progression (TTP) and overall survival (OS) were compared between OA and YA enrolled on 2 nd line trials by Cox regression, adjusting for age, sex, ECOG PS, number of metastatic sites, presence of metastasis in lung/liver/peritoneum. Results: Sixteen percent of 1 st line ARCAD trial participants were age 70+ (n = 870). Data for 2 nd line therapy was available for 60.6% pts (3206/5289). Each additional decade of life was associated with 11% lower odds of receiving 2 nd line therapy in multivariate analysis (p = 0.0117). OA participating in 2 nd line trials (7.9% age 75+ of 7921) experience similar TTP and OS to YA (mTTP: 5.1 vs. 5.2mos; mOS 11.6 vs 12.4mos, respectively). Conclusions: We did not observe a statistical difference in survival outcomes by age following 2 nd line mCRC therapy. Further study is needed to examine unmeasured comorbidity and use of geriatric assessment to select OA likely to benefit from 2 nd line therapy. [Table: see text]
肾病综合征
Authors: 吴东, 蔡建芳, 陈嘉林
Journal: BMJ (2011)

一、血白蛋白水平是肾病综合征的病情睛雨表 肾病综合征是一组以大量蛋白尿(＞3.5g/d)和血白蛋白减少(＜30g/L)为主要表现的临床综合征.该病可见于原发性或继发性肾小球病变.前者按肾脏病理学区分,包括膜性肾病、微小病变、局灶节段性肾小球硬化、膜增殖性肾小球肾炎及系膜增殖性肾小球肾炎等;后者按病因区分,包括了代谢(如糖尿病肾病)、免疫(如系统性红斑狼疮)、感染(如乙肝相关性肾炎)、肿瘤(如多发性骨髓瘤)以及中毒(如重金属中毒)等继发的肾病。
Prevalence of and Changes in Tooth Loss Among Adults Aged ≥50 Years with Selected Chronic Conditions — United States, 1999–2004 and 2011–2016
Authors: Marcia L. Parker, Gina Thornton-Evans, Liang Wei, Susan O. Griffin
Journal: MMWR Morbidity and Mortality Weekly Report (2020)

Extensive tooth loss can lead to poor diet resulting in weight loss or obesity (1). It can also detract from physical appearance and impede speech, factors that can restrict social contact, inhibit intimacy, and lower self-esteem (1). Chronic medical conditions and oral conditions share common risk factors (2). Persons with chronic conditions are more likely to have untreated dental disease, which can result in tooth loss. Three measures of tooth loss during 1999-2004 and 2011-2016 were estimated by comparing data from the National Health and Nutrition Examination Survey (NHANES) for each period among adults aged ≥50 years with selected chronic conditions.* The three measures were 1) edentulism (having no teeth); 2) severe tooth loss (having eight or fewer teeth) (3); and 3) lacking functional dentition (having <20 teeth out of 28, which is considered a full set for the purpose of NHANES assessments) (4). During 2011-2016, prevalences of edentulism and severe tooth loss were ≥50% higher among adults with fair or poor general health, rheumatoid arthritis, asthma, diabetes, emphysema, heart disease, liver condition, or stroke than among those with those adults without the chronic condition. Lack of functional dentition was also more prevalent among adults with chronic conditions than among persons without these conditions. Tooth loss is preventable with self-care and routine dental visits (1). To encourage these behaviors, public health professionals can educate the public about the association between having a chronic condition and tooth loss, and primary care providers can educate their patients about the importance of healthy behaviors and screen and refer them for needed dental care.
类风湿关节炎治疗的新观念
Authors: 张卓莉
Journal: BMJ (2005)

类风湿关节炎(RA)是以慢性滑膜炎症为特征的自身免疫性疾病,具体病因和发病机制仍不清楚,目前尚无治愈的方法.如果不积极有效地治疗,约50%的患者在起病2年内发生骨关节破坏,大多数患者可以造成不同程度的残疾,甚至引起死亡,因此,RA是常见而且致残率很高的疾病.目前,对RA的治疗主要采取理疗、药物治疗和手术矫形等方法,以达到控制关节炎症、校正机械性或结构性异常的目的.传统治疗RA的药物有3类:非甾类抗炎药(NSAIDs)、糖皮质激素(GCs)以及改善病情抗风湿药(DMARDs).近年来,人们对三类传统药物在RA治疗中的作用和应用有了新的认识。
Results of venous resections in cancer of the pancreatic head.
Authors: Oleg I. Kit, Oksana V. Katelnitskaya, Andrey A. Maslov, Aleksey Yu. Maksimov, Evgeniy N. Kolesnikov, Yuriy A. Gevorkyan, Vladimir S. Trifanov, Mikhail A Kozhushko, Aleksandr V. Snezhko, Dmitry S. Petrov, Yuriy A. Fomenko
Journal: Journal of Clinical Oncology (2020)

e16785 Background: Studies have shown that pancreaticoduodenal resection (PDR) with resection and reconstruction of the venous segment does not interfere with surgical treatment for ductal pancreatic adenocarcinoma with suspected venous invasion. Venous resection improves survival compared to palliative interventions. However, the advantages and disadvantages of marginal resection, segmental resection with direct anastomosis, and venous segment prosthetics are not reflected. Methods: The study included 52 patients (23 women, 29 men) undergoing PDR with venous resection and reconstruction for cancer of the pancreatic head in 2015-2019. The average tumor size was 3.8 cm. Results: Superior mesenteric vein reconstruction (PTFE grafts) was performed in 17 patients (32.7%), sleeve resection with direct anastomosis - 24 (46.2%), marginal resection - 11 (21.1%). Venous reconstruction was planned in 78.8% of patients before the surgery. In the early postoperative period, thrombosis of the reconstructed zone was developed in two patients (3.8%), bleeding from the pancreatic bed - in one case (1.9%). Postoperative mortality was 5.8% (3 patients). After the final pathological examination, macroscopically incomplete resection was diagnosed only in the group with marginal resection and amounted to 3.8%. Microscopically incomplete resection was diagnosed in 9.6% of the studied preparations (in marginal resection of the vein wall - 3.8%, with direct anastomosis - 1.9%, SMV prosthetics - 3.8%). Most often, R1 resection was detected in the retroperitoneal resection margin (80%). The lowest 1-year survival was observed in the group with marginal resection (36.4%). No significant differences in survival rates were found in patients with direct venous anastomosis (62.5%) and venous prosthetics (64.7%) (RR 1.69; 95% CI 0.69-4.12, p &gt; 0.05). Microscopically complete resection R0 improved the survival (RR 2.7; 95% CI 1.45-5.04, p &lt; 0.05). Planning the venous resection was an additional risk factor affecting the completeness of resection (RR 4.6; CI 95% 1.5-14.5, p &gt; 0.05). Conclusions: Expanding the surgery volume in PDR due to venous resection and reconstruction shows acceptable rates of postoperative morbidity and mortality. Planning the venous resection enhances the results of radical surgery.
Irinotecan with or without capecitabine as a beyond 2<sup>nd</sup> line regime for esophago-gastric adenocarcinomas.
Authors: Sonal Brindley Hapuarachi, Mohammed Dawod, Jamie Weaver, Fadhel Shaheen, Adeel Khan, Richard Hubner, Tom Waddell, Wasat Mansoor
Journal: Journal of Clinical Oncology (2020)

e16545 Background: Purpose: The aim of this retrospective study was to assess the efficacy and toxicity of irinotecan +/- capecitabine for patients with metastatic esophago-gastric (EG) adenocarcinomas previously treated with at least two chemotherapy regimens including platinum-based, fluoropyramidines and taxanes. Introduction: Treatment for metastatic EG cancer beyond 2 nd line remains controversial. Recently, the TAGS phase III trial (Shitara et al., 2018) showed overall survival benefit with Trifluridine/tipiracil of 2.1 months compared to placebo as a third line. Apatinib is also approved for use as third line in China (Li et al., 2013). Based on minimal evidence (Kang et al., 2013), irinotecan in combination with capecitabine is used in the UK. We performed a retrospective study to assess the efficacy and toxicity of irinotecan as a beyond 2 nd line regime in metastatic EG adenocarcinomas in one of Europe’s largest cancer centres, The Christie. Methods: Data was collected retrospectively from all metastatic EG adenocarcinoma patients who were treated with irinotecan +/- capecitabine as a beyond 2 nd line palliative treatment at the Christie Hospital from January 2014 to December 2019. Irinotecan was either given 2 or 3 weekly at dose of 180 mg/m² with or without capecitabine 800 mg/m². Response rate (RR) was calculated according to RECIST version 1.1, overall survival measured and toxicity data collected. Results: Fifty-six patients received irinotecan as beyond 2nd line palliative chemotherapy. Out of the thirty-seven patients with measurable disease on their scans, the overall response rate was 8.1% and the disease control rate was 51.4% as per RECIST 1.1. Median overall survival was 5 months (95% CI 4.2-5.8). The presence of grade 3-4 toxicities was 16% (9 patients) and included neutropenia, fatigue, nausea and diarrhea. On average, 3.7 cycles were administered, 32% (18 patients) required dose reductions, mainly secondary to grade 2 diarrhea and fatigue. Conclusions: Irinotecan in combination with capecitabine is efficacious as a beyond 2 nd line regime in metastatic EG with an acceptable toxicity profile with a limited role in patients with resistant disease to first line platinum-based chemotherapies with fluoropyramidines.
Association of LRP1B pathogenic genomic alterations with favorable outcomes with immune checkpoint inhibitors across multiple tumor types.
Authors: Landon Carter Brown, Ramy Sedhom, Eric B Schwartz, Jason Zhu, Chester Kao, Matthew D Tucker, Matthew Labriola, Rajan T. Gupta, Daniele Marin, Yuan Wu, Tian Zhang, Michael Roger Harrison, Daniel J. George, Ajjai Shivaram Alva, Emmanuel S. Antonarakis, Andrew J. Armstrong
Journal: Journal of Clinical Oncology (2020)

3007 Background: Low-density lipoprotein receptor-related protein 1b (LRP1b) is a putative tumor suppressor and one of the most frequently altered genes in cancer. Our prior single-center work suggested that LRP1B alterations may enrich for responses to immune checkpoint inhibitors (ICI) in solid tumors including prostate cancer; however, validation of these findings is needed. Methods: We conducted a multicenter, retrospective analysis of patients with LRP1B alterations (on tissue-based next-generation sequencing panels) treated with ICI at Duke, Johns Hopkins (JHU), and University of Michigan (UM). The primary objective was to assess the association between objective response rate (ORR) to ICI and pathogenic LRP1B alterations, defined as deletions or truncating alterations, when compared with LRP1B variants of undetermined significance (VUS), defined as missense mutations not predicted to be pathogenic in COSMIC. Missense changes with a COSCMIC FATHMM score of &gt; 0.8 were categorized separately as likely pathogenic. Summary statistics, ORR, progression free survival (PFS), and overall survival (OS) were calculated. Results: 101 patients (44 Duke, 35 JHU, 22 UM) with LRP1B alterations were treated with ICI. Median age was 61 (range 32-82). The most common tumor types by alteration (pathogenic or likely pathogenic/VUS%) were lung (33/47%), GI (17/13%), prostate (11/7%), sarcoma (2/9%), melanoma (11/0%), and others (26/24%). 93% of patients received single-agent PD-(L)1 inhibition. The ORR for patients with either pathogenic/likely pathogenic alterations, or VUS alterations was 57% and 18%, respectively. After excluding MSI-high or TMB-high ( &gt; 10 mut/Mb) tumors, ORR was 14/25 (56%) and 6/36 (17%), respectively. Pathogenic or likely pathogenic LRP1B alterations were associated with longer PFS (HR 0.39, 95% CI 0.24-0.63) and OS (HR 0.58, 95% CI 0.36-0.95). Conclusions: This multicenter study shows impressive and durable objective response rates to ICI for patients harboring pathogenic LRP1B alterations when compared to those with LRP1B VUS, independent of TMB/MSI status. Further mechanistic insights and prospective validation studies are warranted. [Table: see text]