tbuckley/cabot-search huggingface dataset:
Real-world outcomes of elderly patients with relapsed/refractory (R/R) diffuse large B-cell lymphoma (DLBCL) treated with chimeric antigen receptor T-cell (CAR-T) therapy.
Authors: Lindsey Fitzgerald, Adam Kittai, Loretta J. Nastoupil, Alexandra Waller, Caron A. Jacobson, Anna Saucier, Manali K. Kamdar, Janet Spradley, Nathan Denlinger, Jonathan Chipman, Boyu Hu
Journal: Journal of Clinical Oncology (2020)

8039 Background: CAR-T has drastically improved outcomes for R/R DLBCL patients (pts). While CAR-T is now standard of care for the treatment of R/R DLBCL, little is known about its efficacy and toxicity in elderly pts. Methods: We conducted a multi-center retrospective analysis of pts age ≥ 70 years old with R/R DLBCL treated with either axicabtagene ciloleucel (axi-cel) or tisagenlecleucel (tisa-cel). Pt demographics, tumor characteristics, CAR-T data, survival and toxicity outcomes were collected at the time of T cell infusion and follow up. Comorbidities were measured using the cumulative illness rating score (CIRS) and hematopoietic cell transplantation-specific comorbidity index (HCT-CI). Results: A total of 77 pts were analyzed with a median age of 73 (range, 70-88); 30 (39%) pts were age ≥75. Most pts received axi-cel (n = 61, 79%). Unfavorable tumor characteristics included 27 (35%) pts with activated B-cell subtype and 12 (16%) with double/triple hit lymphomas. Median CIRS was 8 (range 0-25) and median HCT-CI was 2 (range 0-9) with significantly higher median CIRS and HCT-CI in pts age ≥75. With a median time to follow up of 5.2 months (m), median progression free survival (PFS) was 12m and median overall survival (OS) was 15.5m. There was no difference in PFS when comparing younger pts (age 70-74) to older pts (age ≥ 75), but median OS was significantly shorter for older pts (7.8m vs. not reached; hazard ratio [HR] 0.46, CI 0.21-0.98; p = 0.04). In a multivariate analysis (MVA) of PFS adjusting for baseline characteristics, HCT-CI &gt; 2 (HR 0.23, CI 0.07-0.77; p = 0.02) and use of axi-cel (HR 0.07, CI 0.02-0.32; p = &lt; 0.001) were associated with worse PFS. Grade 3/4 (Lee criteria) cytokine release syndrome (CRS) and CAR-related encephalopathy syndrome (CRES) were assessed in MVA adjusting for baseline characteristics. CRS was associated with CIRS ≥6 (odds ratio [OR] 3.92, CI 1.07-14.3; p = 0.002) and use of axi-cel (OR 44.9, CI 8.20-245.6; p = 0.006). CRES was associated with older age (OR 6.10, CI 1.86-20.0; p = 0.003), CIRS ≥6 (OR 3.92, CI 1.07-14.3; p = 0.04) and use of axi-cel (OR 44.9, CI 8.2-245.6; p = &lt; 0.0001). Conclusions: Pts age ≥75 treated with CAR-T had worse OS, but comparable PFS as compared to younger pts. Validated frailty measurements (CIRS) predicted for increased CRS and CRES. Use of axi-cel was associated with worse PFS and increased toxicities in the elderly, but propensity matched scoring analysis will need to confirm this. Additional pts and longer follow up are required to validate these results.
Prevalence of Familial Hypercholesterolemia Among the General Population and Patients With Atherosclerotic Cardiovascular Disease
Authors: Pengwei Hu, Kanika I. Dharmayat, Christophe A.T. Stevens, Mansour T.A. Sharabiani, Rebecca S. Jones, Gerald F. Watts, Jacques Genest, Kausik K. Ray, Antonio J. Vallejo-Vaz
Journal: Circulation (2020)

Background: Contemporary studies suggest that familial hypercholesterolemia (FH) is more frequent than previously reported and increasingly recognized as affecting individuals of all ethnicities and across many regions of the world. Precise estimation of its global prevalence and prevalence across World Health Organization regions is needed to inform policies aiming at early detection and atherosclerotic cardiovascular disease (ASCVD) prevention. The present study aims to provide a comprehensive assessment and more reliable estimation of the prevalence of FH than hitherto possible in the general population (GP) and among patients with ASCVD. Methods: We performed a systematic review and meta-analysis including studies reporting on the prevalence of heterozygous FH in the GP or among those with ASCVD. Studies reporting gene founder effects and focused on homozygous FH were excluded. The search was conducted through Medline, Embase, Cochrane, and Global Health, without time or language restrictions. A random-effects model was applied to estimate the overall pooled prevalence of FH in the general and ASCVD populations separately and by World Health Organization regions. Results: From 3225 articles, 42 studies from the GP and 20 from populations with ASCVD were eligible, reporting on 7 297 363 individuals/24 636 cases of FH and 48 158 patients/2827 cases of FH, respectively. More than 60% of the studies were from Europe. Use of the Dutch Lipid Clinic Network criteria was the commonest diagnostic method. Within the GP, the overall pooled prevalence of FH was 1:311 (95% CI, 1:250–1:397; similar between children [1:364] and adults [1:303], P =0.60; across World Health Organization regions where data were available, P =0.29; and between population-based and electronic health records–based studies, P =0.82). Studies with ≤10 000 participants reported a higher prevalence (1:200–289) compared with larger cohorts (1:365–407; P &lt;0.001). The pooled prevalence among those with ASCVD was 18-fold higher than in the GP (1:17 [95% CI, 1:12–1:24]), driven mainly by coronary artery disease (1:16; [95% CI, 1:12–1:23]). Between-study heterogeneity was large ( I 2 &gt;95%). Tests assessing bias were nonsignificant ( P &gt;0.3). Conclusions: With an overall prevalence of 1:311, FH is among the commonest genetic disorders in the GP, similarly present across different regions of the world, and is more frequent among those with ASCVD. The present results support the advocacy for the institution of public health policies, including screening programs, to identify FH early and to prevent its global burden.
Characterization of 1,387 NSCLCs with MET exon 14 (METex14) skipping alterations (SA) and potential acquired resistance (AR) mechanisms.
Authors: Mark M. Awad, Jessica Kim Lee, Russell Madison, Anthony Classon, Jamie Kmak, Garrett M. Frampton, Brian Michael Alexander, Jeffrey Venstrom, Alexa Betzig Schrock
Journal: Journal of Clinical Oncology (2020)

9511 Background: METex14 SA are oncogenic drivers in NSCLC. Due to the numerous sites around ex14 that bind the spliceosome complex, many variations can result in deleterious alterations (alts). We present a comprehensive overview of these ex14 SA across 1,387 NSCLCs and characterized potential AR mechanisms. Methods: Hybrid-capture based comprehensive genomic profiling (CGP) was performed on samples from 60,495 NSCLC patients (pts). A scoring system was applied leveraging our large database of samples with METex14 SA to optimize accurate reporting of these variants. Paired samples were collected ≥ 60 days apart (median 462). Results: 1,393 METex14 SA were identified in samples (1,278 tissue, 109 circulating tumor DNA (ctDNA)) from 1,387 NSCLC pts (2.3%) spanning multiple functional sites: donor (42%), acceptor (4.7%), poly-pyrimidine tract (15%), acceptor and polypyrimidine tract (13%), D1010 (23%), Y1003 (2.1%), and whole exon deletions (0.3%). 6 samples (5 tissue, 1 ctDNA) harbored 2 METex14 SA, each including a mutation (mut) at the donor or acceptor site. MDM2 and CDK4 amplifications (amps) co-occurred in 32% and 19% of METex14 samples, respectively, but were more common with polypyrimidine tract (37% and 23%) vs donor site (32%, p = 0.07 and 18%, p = 0.07) alts. MET co-amp was present in 12% of cases and frequency did not significantly differ by functional site. 66 (4.8%) cases (57 tissue, 9 ctDNA) had known NSCLC co-drivers, including KRAS (68%) and EGFR (14%) mut, a subset of which may represent AR. Paired samples with a METex14 SA in the 1st sample were available for 36 pts. The METex14 SA was detected in the 2nd sample for 32 pts, excluding 3 with low ctDNA. 22/36 (61%) had reportable acquired alts detected including 9 with ≥1 acquired MET muts [D1228X (4), Y1230X (3), Y1003F (1), D1228A/E/H + L1195V (1)] and 3 with acquired MET amp. Other acquired alts included ERBB2 amp and mut (1 each), EGFR ex19ins (1), KRAS amp (1), PIK3CA mut (1), AKT2 amp (1) and others with unknown functional significance. Potential AR alts were present with primary METex14 SA spanning all functional sites. Conclusions: In a dataset of &gt; 60,000 advanced NSCLCs, METex14 SA were present in 2.3% of cases, and represented 6 major subtypes. Among paired cases, potential AR mechanisms included secondary MET alts (33%), and acquired alts in EGFR, ERBB2, KRAS, and PI3K pathways. Acquired alts were independent of the type of METex14 SA. Characterizing common co-occuring may be critical for predicting responses to MET inhibitors and informing rational combination strategies.
Quality of life and related factors in renal transplantation recipients of stable stage
Authors: Qiang Zhang, Xiaopeng Hu, Hui Shi, Hang Liu, Wenrui Xue, Yue Xu, Wei Wang, Xiaodong Zhang
Journal: BMJ (2016)

The purpose of this article is to analyze the factors related to quality of life(QOL) in renal transplantation recipients of stable stage. The QOL of 255 renal transplantation recipients in stable stage, including 153 males and 102 females aged 21-81 years, was evaluated by 36-Item Short Form Health Survey (SF-36). The related factors to QOL were analyzed with multivariate regression method. Results showed that the scores of 5 items in SF-36 of recipients after transplantation were low than those in general population in Sichuan province: physical function (80.8±2.0), role physical (62.9±5.2), bodily pain (77.0±2.4), general health (53.7±2.9) and role emotional (68.2±5.2) (t=-9.9, -6.3, -4.5, -9.3 and -3.1, all P<0.05); while there were no differences in scores of 3 items in SF-36 between recipients and general population in Sichuan province: vitality (69.4±2.0), social function (86.5±3.0) and mental health (70.8±2.1). Multivariate regression revealed that serum creatinine level(β=-0.2), bone mineral density(β=0.2), hemoglobin (β=0.3)and BMI(β=-0.2) were associated with QOL (all P<0.05 ). The study indicates that QOL of renal transplantation recipients is still lower than that of general population and various factors affect QOL of renal transplantation recipients.


Key words: 
Kidney transplantation; Quality of life; Questionnaires
Relationship described by bereaved caregivers (BCGs) between blood transfusions and hospice utilization for loved-ones (LOs) who died from acute myeloid leukemia (AML).
Authors: Larry Dean Cripe, Layla Baker, Katie Sargent, Caroline Martin, Ann H. Cottingham
Journal: Journal of Clinical Oncology (2020)

e24002 Background: Patients with AML may under-utilize hospice due to a reluctance to discontinue potentially life-sustaining transfusions. Transfusions while on hospice are a proposed solution. Methods: Nineteen BCGs completed brief surveys and participated in semi-structured interviews. Interviews were audio-recorded, transcribed and qualitatively analyzed for content related to transfusions and hospice enrollment. Results: Surveys: Four out of 16 BCGs reported their LOs received transfusions until death. The time between last transfusion and death was within 2 weeks (12/19) and more than 1 month (3/19). BCGs reported the purpose of transfusions in the last month of life was to live longer (6) and/or to feel better (10). Interviews: The research team identified 5 points relevant to any connections between transfusions and hospice enrollment: 1. Only 2 of 19 BCGs described a decision to delay hospice enrollment due to inability to continue transfusions while on hospice. Both reported gaining enhanced knowledge about their LOs prognosis and coming to agreement that transfusions were burdensome and not justified. 2. The majority of BCGs described becoming aware that the doctor discontinued transfusions rather than reporting that the discontinuation of transfusions was a decision made by their LO. 3. BCGs described a “logical” and accepted transition from chemotherapy and transfusions to transfusions alone to no transfusions. 4. BCGs’ perspectives on transfusions evolved from transfusions as necessary to may be helpful to no longer indicated. They recall experiencing and accepting this progression rather than discussing the transition with providers. 5. Several impediments to hospice unrelated to transfusions were identified: rapid decline of LO, no perceived need for hospice, equating hospice with a home-based service, and bias against hospice due to past experiences. Conclusions: The desire for ongoing transfusion support is not a major impediment to hospice enrollment in the experience of BCGs. Providing transfusions on hospice may not address the low rates of hospice utilization.
不同性别早发冠心病患者代谢综合征特征分析
Authors: 陈忠, 马根山, 黄峻, 冯毅, 朱铁兵, 杨志健, 张晓黎
Journal: BMJ (2006)

分析276例早发冠心病患者的血糖、血脂参数、体重指数,并将其分为男性、女性早发冠心病组进行对比.结果显示早发冠心病比例男性(199例;72.1%)多于女性(77例,27.9%).男性组吸烟比例高于女性组(P＜0.01).女性组甘油三酯水平[(1.73±0.62)mmol/L比(1.68±0.54)mmol/L,P＜0.05]、体重指数[26.5±2.0比25.1±1.9,P＜0.05]、患高血压比例(68.8%比52.3%,P＜0.05)、代谢异常指标数[(2.1±1.1)比(1.6±1.0),P＜0.05]和患代谢综合征比例(48.1%比26.1%,P＜0.01)高于男性组;其血压异常、高甘油三酯血症、腹部肥胖(以腰围超标表示)比例均高于男性组(P＜0.01).提示女性早发冠心病患者中代谢异常指标数、代谢综合征患病率高于男性组,男性早发冠心病患者吸烟比例高于女性组。
Daratumumab-induced lymphopenia predicts adverse events and outcomes in patients with myeloma.
Authors: Francesca Cottini, Nita Williams, Naresh Bumma, Abdullah Mohammad Khan, Maria Chaudhry, Srinivas S. Devarakonda, Yvonne Adeduni Efebera, Don M. Benson, Ashley Elizabeth Rosko
Journal: Journal of Clinical Oncology (2020)

e20534 Background: Daratumumab, a monoclonal antibody against CD38, is very effective in patients with Multiple Myeloma (MM). CD38 is expressed on MM cells but also on normal lymphocytes. Therapy-induced lymphopenia has been reported in 30-40% of patients; however its clinical significance is vastly unexplored. Methods: Here, we report the baseline characteristics and clinical course of 100 relapsed/refractory MM patients treated at the Ohio State University with Daratumumab as single agent or in combination. Data pertaining to patient demographics, MM characteristics, absolute lymphocyte count-ALC, infections, and hospital stays were collected. ALC of less or equal to 500 cells/µL is considered severe lymphopenia. Results: Fifty-nine percent of patients who completed treatment with Daratumumab (59%) developed severe lymphopenia. MM type (LLC and IgA), combination with immunomodulatory drugs (IMIDs), and lower baseline ALC count were statistically associated with severe lymphopenia, while stage, age, cytogenetics, number of prior lines of treatment, and autologous stem cell transplant were not. Patients with severe lymphopenia had higher rates of infections (52.5% versus 41.4%) and required hospital stays more frequently (83.8% versus 52.9%) than patients without severe lymphopenia. Upper respiratory tract infections and pneumonias were the most common infections. Sixty-one percent of severely lymphopenic patients recovered to ALC &gt; 500 lymphocyte/μL while on therapy. The median time to recover was 14 days (average 43 days). Older patients have longer ALC recovery time (average: 52 days versus 24 days). No statistically significant difference in progression-free survival (PFS), overall survival (OS), or overall response rate (ORR) was noted between patients who did or did not develop severe lymphopenia. However, when the severe lymphopenic group was stratified based on ALC recovery, those with persistent lymphopenia had worst OS (p = 0.0019) and PFS (p &lt; 0.0001), possibly due to better immune-mediated anti-tumoral effects. Conclusions: In our patient population, we discovered an elevated rate of severe lymphopenia, hospital utilization, and infections. Persistent severe lymphopenia is associated with shorter PFS and worst OS. Combination with IMIDs and low baseline ALC count are risk factors for severe lymphopenia while patients older than 65 has a longer ALC recovery time. These findings underline the importance of monitoring lymphocyte count and considering prophylactic measures in high-risk patients treated with Daratumumab.
Dual anti-CTLA-4 and anti-PD-1 blockade in metaplastic carcinoma of the breast: Dart (SWOG S1609, Cohort 36).
Authors: Sylvia Adams, Megan Othus, Sandip Pravin Patel, Young Kwang Chae, Kathy Miller, Rashmi Chugh, Scott Schuetze, Elad Sharon, Larissa A. Korde, Robert James Gray, Edward Mayerson, Melissa Plets, Razelle Kurzrock
Journal: Journal of Clinical Oncology (2020)

1073 Background: Immune checkpoint blockade, specifically anti-CTLA-4 and anti-PD-1-directed approaches, has improved outcomes in various tumors and is being tested in SWOG S1609 in rare solid tumors (DART=Dual Anti-CTLA-4 &amp; Anti-PD-1 blockade in Rare Tumors). Metaplastic breast cancer (MpBC) is a rare subtype of breast cancer with poor response to cytotoxics and median survival of &lt; 1 year for metastatic disease. A MpBC stratum was added based on promising activity of immunotherapy in a patient with MpBC (Adams, npj Breast Cancer 2017). Here, we report the MpBC cohort of S1609 DART. Methods: In this prospective, open-label, multicenter phase II trial patients received ipilimumab (1mg/kg q6 weeks) plus nivolumab (240mg intravenously every 2 weeks). Eligibility for cohort 36 required histologically confirmed MpBC, measurable disease, and ECOG PS 0-2. Prior anti-CTLA4 or anti-PD-1/PD-L1 treatment (but not both) was permitted as well as treated brain metastases. The primary endpoint was overall response rate (ORR, confirmed CR, PR) by RECIST v1.1; 2 or more responses in 16 patients was considered a success. Secondary endpoints: toxicity (CTCAE v4.0), PFS and ORR by immune-related RECIST (iRECIST), overall survival (OS). Biomarker analyses are ongoing. Results: Nineteen patients were registered to the cohort and seventeen eligible patients received therapy. The median age was 60 (range 26-85), most tumors were high grade, triple negative and had a high ki67 (median 87%), median prior therapy = 2 lines. The ORR was 12% (RECIST 1.1) and 18% (iRECIST), with ongoing responses at 23, 18 and 11 months, respectively; SD was seen in 24%, none &gt; 6 months (Table). Median OS was 12 months. AEs were observed in 11 patients (65%), with 3 patients (18%) having Grade 3/4 AEs and 1 patient with a fatal AE (myocarditis). The most common toxicities were LFT abnormalities and fatigue. Conclusions: Cohort 36 met its primary endpoint: ipilimumab plus nivolumab was clinically active in advanced MpBC, with durable responses observed in 3/17 patients. Further investigation of this combination is warranted. Clinical trial information: NCT02834013 . [Table: see text]
福建省全科医师岗位培训现状调查分析
Authors: 郑学展, 陈莉莉
Journal: BMJ (2004)

对基层医疗单位在职医务人员进行转岗培训是全科医学人才培训的重点,福建省全科医师培训中心已成功地举办了两期全科医师岗位培训班,共836人参加.我们以这些学员调查对象,就全科医师培训的效果、影响等进行调查、分析和评价,以期进一步提高培训质量,使之更加具有针对性。
Uses of half-dose gonadotropin-releasing hormone agonist with different treatment cycles after conservative laparoscopic surgery in the treatment of endometriosis
Authors: Qin Zhu, Hong-xia Zhang, Xia Liu
Journal: BMJ (2013)

To explore the efficacy of using gonadotropin-releasing hormone agonist (GnRH-a) with different cycles after conservative laparoscopic surgery in the treatment of endometriosis. Research was conducted on 108 patients with endometriosis Ⅲ or Ⅳ diagnosed by conservative laparoscopy from January 2010 to June 2011. Among them, 57 patients (group A) were managed with GnRH-a postoperatively for 3 months and the others (group B) 6 months. Clinical efficacy, relapse rate and pregnancy rate after withdrawal were compared between two groups. The clinical efficacy rate of groups A and B were 73.7% and 90.2% respectively. And there were significant statistical differences between them. However, the relapse rate of groups A and B were 14.0% and 5.9% and the pregnancy rate of two groups 45.0% and 4/12 respectively. And there were no statistical differences. A 6-month regimen of GnRH-a can reduce and delay the recurrence of endometriosis and improve the clinical efficacy. A short-term dosing of GnRH-a is indicated for those patients with fertility requirements.


Key words: 
Endometriosis; Gonadotropin-releasing hormone
Anatomical and histological observation of ileocecal Treves fold and its clinical significance
Authors: Wenjun Wang, Zhanwu Li, Xiaoyu Zhang, Xiaozhou Wang, Lei Jiang, Qiang Liu, Fengyi Wang
Journal: BMJ (2018)

From December 2011 to August 2017, 56 patients with acute abdomen surgery were treated in Affiliated Zhongshan Hospital of Dalian University. The anatomical structure of ileocecal Treves folds was observed during operation, and 15 samples of Treves folds were taken for histological examination. The mean length of the fold was (5.56±0.18) cm for males and (5.22±0.05) cm for female, the width was (1.82±0.04) cm for males and (1.78±0.06) cm for females; the thickness was (0.18±0.02) cm. HE and verhoeff staining showed that Treves fold was mainly composed of elastic fiber, collagen fiber and smooth muscle with abundant blood supply. Thirty patients were repaired with their own Treves folds, including the fixation with overlay suture to the stump of appendectomy in 26 cases, repairing for perforation of colonic diverticulum in 3 case, and repairing for perforation of colonic diverticulum in 1 case. There were no complications such as fecal fistula, intestinal obstruction and intussusception after operation. The Treves fold has a constant location, which can be used as a clear sign of ileal terminal. It has abundant blood supply, and is suitable for the repair and reconstruction in ileocecal operation.


Key words: 
Ileum; Cecum; Treves plica; Biological materials
Prevalence of metabolic syndrome in population at high-risk for diabetes in Changfeng community of Shanghai
Authors: Xu-sheng Chen, Jian-hua Sheng, Xu-ying Shen, Hai-dong Kuang, Yue-hong Shi, Yun Lei, Lan Jin, Ting Zhou, Jing Zhu, Xin Gao
Journal: BMJ (2008)

Objective To investigate prevalence of metabolic syndrome (MS) in population at high-risk for diabetes in Changfeng community of Shanghai. Methods Totally, 982 persons aged 40-79 years without previous history of diabetes, but with risk factors for diabetes from Changfeng community in Shanghai were screened by questionnaire, physical examinations, lipid profile and oral glucose tolerance test. Prevalence of MS and its clinical characteristic were observed. Results Overall prevalence of MS was 44. 6% (438/982) in Changfeng community, significantly higher in women of 48.6% (341/701) than that in men of 34. 5% (97/281) (P 0.05). Components of MS ranking from high to low were hypertension of 66. 5% (653/982), abdominal obesity of 62.8% (617/982), decreased high-density lipoprotein-cholesterol (HDL-C) of 49. 4% (485/982), increased triglyceride (TG) of 46. 0% (452/982) and increased fasting glucose of 35.7% (351/982). There were 55.9% (245/438) of MS patients with three or more MS components in addition to abdominal obesity. Conclusions Prevalence of MS is higher in community population at high-risk for diabetes and more than half of the MS patients have three or more risk factors for cardiovascular disease.

Key words: 
Metabolic syndrome;  Mass screening;  Risk factors
Tomoscintigraphic characteristics of silent myocardial ischemia in men
Authors: 李小东, 赵洪刚, 王钦, 张遵城, 郭永涛, 董萍, 董华
Journal: BMJ (2006)

目的 采用单光子发射计算机断层显像(SPECT)观察男性无症状性心肌缺血的心肌血流灌注和心室舒缩功能的变化特点.方法对31例男性无症状性心肌缺血(SMI组)、21例正常男性(对照组)和62例男性陈旧心肌梗死(OMI组)分别进行心肌灌注断层显像和门控心室功能显像,并应用统计学方法对各组的SPECT图像和功能参数进行检验分析和比较.结果 SMI组心肌摄取异常病灶多为单发,且总的异常节段数低于OMI组(P 0.05),但是明显好于OMI组(P<0.01);SMI组的射血分数与峰值充盈速率、峰值收缩速率存在着线性回归关系(P<0.05).结论 SMI对心肌的损害较轻,对心脏舒缩功能无显著性影响。