tbuckley/cabot-search huggingface dataset:
A phase I trial of nab-paclitaxel/bevacizumab (AB160) nano-immunoconjugate therapy for metastatic gynecological malignancies: MC1371 (NCT02020707).
Authors: Eleftheria Kalogera, Vera Jean Suman, Wendy Kay Nevala, Heidi Diann Finnes, Jill Schimke, Carrie Strand, Gretchen Glaser, Megan Grudem, Aminah Jatoi, Carolyn Klampe, Amanika Kumar, Carrie L Langstraat, Andrea Elisabeth Wahner Hendrickson, Saravut John Weroha, Joel M. Reid, Svetomir Markovic, Matthew Stephen Block
Journal: Journal of Clinical Oncology (2020)

e18097 Background: AB160 is a 160 nm nano-immunoconjugate consisting of nab-paclitaxel (NP) nanoparticles non-covalently coated with bevacizumab (BEV) for targeted delivery into tissues expressing high levels of vascular-endothelial growth factor (VEGF). Both taxanes (GOG-0129C, GOG-0126R, GOG-0127V) and BEV (GOG-0229E, AURELIA, GOG-0227C) have demonstrated clinical activity in previously treated metastatic endometrial cancer (EC), ovarian cancer (OC), and cervical cancer (CC), respectively. Methods: A 3+3 phase I trial was conducted in patients with EC, platinum-resistant OC and CC who had prior systemic treatment for metastatic disease to determine the maximum tolerated dose of AB160 administered intravenously on days 1, 8 and 15 of a 28-day cycle. The starting dose level (DL1) was NP at 125 mg/m 2 with BEV at 50 mg/m 2 . There were 2 higher dose levels: DL2 (NP at 150 mg/m 2 with BEV at 60 mg/m 2 ) and DL3 (NP at 175 mg/m 2 with BEV at 70 mg/m 2 ). Dose limiting toxicities (DLT) included grade (G) 4 neutropenia or anemia, PLT &lt; 25,000, serum creatinine ≥2 times baseline, G2-4 neurologic toxicity or G3-4 non-hematologic toxicities. Disease evaluations were conducted after every 2 treatment cycles using RECIST criteria. Patients were treated until disease progression or intolerability. Samples were collected for pharmacokinetic (PK) studies. Results: Nine women 41 – 74 years of age (median 57) have enrolled (5 with EC and 4 with OC); data are available for the first 8. No DLTs have been observed among the 3 women enrolled on DL1, 3 women on DL2, and 2 women on DL3. All 3 patients on DL3 continue on treatment. The other 6 patients have discontinued due to adverse reactions (3), progression (2), and patient choice (1). The median number of cycles administered is 6 (4-14). The most common severe (G3/4) toxicities include neutropenia (37.5%) and leukopenia (25%). There have been 5 partial responses (62.5%): 1 on DL1 and 2 each on DL2 and DL3. PK evaluation is pending. Conclusions: AB160 therapy is safe and demonstrates promising clinical activity in patients with previously treated metastatic gynecologic malignancies. Further clinical testing is being pursued in this patient population. Clinical trial information: NCT02020707.
Evaluation of treatment patterns and prognosis in correlation with age in patients with vulvar cancer: A subset analysis of the AGO-CaRE-1 study.
Authors: Katharina Prieske, Linn Lena Woelber, Mustafa Zelal Muallem, Christine Eulenburg, Julia Kathrin Jueckstock, Felix Hilpert, Nikolaus de Gregorio, Severine Iborra, Atanas Ignatov, Peter Hillemanns, Sophie Fuerst, Hans-Georg Strauss, Klaus Baumann, Falk Thiel, Alexander Mustea, Werner Meier, Philipp Harter, Pauline Wimberger, Jalid Sehouli, Sven Mahner
Journal: Journal of Clinical Oncology (2020)

6090 Background: Despite an increasing incidence with simultaneous decreasing age of onset, the impact of age on prognosis and treatment patterns in primary squamous cell vulvar cancer (VSCC) has not extensively been studied yet. Methods: This is a subgroup analysis of the AGO-CaRE-1 study. Patients (pts) with VSCC (FIGO stage ≥1B), treated at 29 cancer centers in Germany from 1998-2008, were included in a centralized database (n = 1618). In this subgroup analysis pts were analyzed according to age ( &lt; 50yrs (n = 220), 50–69yrs (n = 506), ≥70yrs (n = 521)) with regard to treatment patterns and prognosis. Only pts with documented age, surgical groin staging and known nodal status were included (n = 1247). Median follow-up was 27.5 months. Results: At first diagnosis, women ≥70yrs presented with more advanced tumor stages ( &lt; 0.001), larger tumor diameter ( &lt; 0.001), poorer ECOG status ( &lt; 0.001), higher tumor grading (0.048), as well as a higher rate of nodal involvement ( &lt; 0.001). Older women ≥70yrs showed more commonly HPV negative tumors compared to the other age groups (54% vs. 36.5% in &lt; 50yrs vs. 47.9% in 50-69yrs, p = 0.03). Disease recurrence occurred significantly more often in elderly women (48% vs. 21% in &lt; 50yrs vs. 37.4% in 50-69yrs, p = 0.001). Particularly isolated vulvar recurrence was more frequent in the elderly in comparison to the younger groups (18.2% vs. 15.2% in 50-69yrs vs. 12.7% in &lt; 50yrs, p = 0.001). Age was an independent prognostic factor for disease-free survival (DFS) (HR: 1.7, 95%CI: 1.24-2.46, p = 0.001) with 2-year DFS being 81.1% (&lt; 50yrs), 65.8% (50–69yrs), and 59.3% (≥70yrs), respectively. Elderly women (age group ≥70) had a 221% higher risk for death or recurrence, compared to the youngest group (HR: 3.21, p &lt; 0.001). In a multivariate analysis ECOG, tumor stage, grading, and receipt of (chemo)radiation were further independent prognostic factors for recurrence. Conclusions: Older women with VSCC present with advanced tumor stages at first diagnosis and have an increased risk of recurrence as well as a decreased 2-year PFS in comparison to younger pts groups. Potential reasons for delayed time of diagnosis could be self-awareness and/or more aggressive tumor biology due to HPV negative disease.
Association between PD-L1 variants and PD-L1 expression: A pan-cancer analysis.
Authors: Xiang Wang, Ding Zhang, Guoqiang Wang, Anqi Duan, Xiang Ruan, Teng Zhao
Journal: Journal of Clinical Oncology (2020)

e13661 Background: Programmed cell death-1 (PD-L1) expression has become a predictive biomarker of response to immune checkpoint inhibitors (ICIs) in several types of solid tumors. Patients with high expression of PD-L1 can benefit more from immunotherapy. However, whether PD-L1 variants would influence the PD-L1 expression has not been fully studied. Methods: Patients with both mutation and immunohistochemistry results for PD-L1 expression from our dataset was analyzed. Patients with both mutation and RNA expression data were obtained from The Cancer Genome Atlas (TCGA) and also analyzed. Results: In our dataset, 10002 patients were included in the analysis. 101 (1%) patients harbored PD-L1 variants, including 24 with single nucleotide variant (SNV), 1 with fusion, 3 with copy-number reduction, 59 with copy-number gain, and 16 germline SNV. The PD-L1 positive rate was 42% in patients with SNV, 100% in fusion, 0% in copy-number reduction, 78% in copy-number gain, 19% in germline SNV and 39% in patients without PD-L1 variants. 32 studies of 10071 patients from TCGA were included for analysis. 244 (2.22%) patients harboring PD-L1 variants, including 2 with frame shift mutations, 3 with nonsense mutations, 38 with missense mutations, 2 with splices, 3 with fusions, 83 with copy-number reduction and 118 with copy-number amplification. The PD-L1 expression in patients with PD-L1 variants was significantly higher than patients without PD-L1 variants (P &lt; 0.001). Further analysis among PD-L1 variants groups showed that PD-L1 fusion and amplification were associated with higher PD-L1 expression. Conclusions: Our results suggested that the PD-L1 expression was associated with PD-L1 variants. Patients with PD-L1 fusion and copy-number amplification was associated with higher PD-L1 expression, while PD-L1 germline SNV and copy-number deletion was associated with lower PD-L1 expression.Our results suggested that the PD-L1 expression was associated with PD-L1 variants. Patients with PD-L1 fusion and copy-number amplification was associated with higher PD-L1 expression, while PD-L1 germline SNV and copy-number deletion was associated with lower PD-L1 expression.
Factors related to drug pipeline success for oncology companies using stock performance as a surrogate.
Authors: Matthew J. Ferris, Kai Sun, Corey Savard, Tejas Suresh, Mark Vikas Mishra
Journal: Journal of Clinical Oncology (2020)

e19405 Background: Developing oncology drugs demands substantial investment despite high uncertainty of success and ultimate market value. High drug costs have become subject to recent controversy. We sought to analyze factors influencing success in bringing new drugs to market using stock performance as a surrogate. Methods: Stock screeners and lists of initial public offerings (IPOs) captured small and mid-cap drug companies with share price ≥ $1.00 on major US indices. Share price was obtained from IPO to 03/09/2019. Company websites provided: headquarters (HQ) location, number/nature of drug programs (oncology vs. not, immunotherapy, gene editing, RNA-targeted, CAR-T). Funding to physicians and teaching hospitals (CMS funding) was acquired via CMS.gov Open Payments, and categorized into contributions &lt; or ≥ $100,000. Stock performance was considered good (+ ≥25%), average (+/- 25%), or poor (- ≥25%). Univariate and multivariate associations were assessed for all companies; a subset analysis included only oncology-focused companies. Results: 420 companies were included. 101 companies (24%) had good, 76 average (18%), and 243 poor (58%) performance. Associated with performance in univariate analysis: IPO price ( P &lt; 0.001), time from IPO ( P &lt; 0.001), number of drug programs ( P = 0.019), and CMS funding ( P = 0.00013), with a strong trend for diverse pipelines that included both oncology and non-oncology programs ( P = 0.069). On multivariable analysis, IPO price was inversely associated ( P &lt; 0.0001), while CMS funding ( P &lt; 0.0001) and greater number of drug programs ( P = 0.0025) were positively associated with performance. Within the sub-analysis of oncology companies, 178 were included. 44 (24.7%) had good, 30 (16.9%) average, and 104 (58.4%) poor performance. The following were associated with performance on univariate analysis: IPO price ( P &lt; 0.001), time from IPO ( P &lt; 0.001), HQ location ( P = 0.009), diverse pipelines (P = 0.016), and CMS funding ( P &lt; 0.001). On multivariable analysis, IPO price was inversely associated ( P &lt; 0.0001), while California HQ location ( P &lt; 0.01), diverse pipelines ( P = 0.028), and CMS funding ( P = 0.0002) were positively associated with performance. Conclusions: The majority of included companies had lackluster stock performance suggestive of low potential for drug success and high probability of financial disaster during development. Diverse pipelines and academic collaboration seem to be strongly related to success. This is the first study to demonstrate association between CMS funding and pharmaceutical stock performance.
Regaining a satisfactory quality of life and predicting functional decline after major cancer surgery in older adults: The Geriatric Oncology Surgical Assessment and Functional rEcovery after Surgery (GOSAFE) study.
Authors: Isacco Montroni, Giampaolo Ugolini, Nicole Saur, Antonino Spinelli, Siri Rostoft, Giorgio Ercolani, Michael T. Jaklitsh, Barbara Van Leeuwen, Nicola de Liguori Carino, Giovanni Ferrari, Federico Ghignone, Anna Garutti, Francesca Rita Di Candido, Ponnandai Somasundar, Flavia Foca, Bernadette Vertogen, Oriana Nanni, Riccardo Audisio
Journal: Journal of Clinical Oncology (2020)

12051 Background: Older cancer patients value quality of life (QoL) and functional outcomes as much as survival but surgical studies lack specific data. The international, multicenter GOSAFE study (ClinicalTrials.gov NCT03299270) aims to evaluate patients’ QoL and functional recovery (FR) after cancer surgery and to assess predictors of FR Methods: GOSAFE prospectively collected functional and clinical data before and after major elective cancer surgery on senior adults (≥70 years). Surgical outcomes were recorded (30, 90, and 180 days post-operatively) with QoL (EQ-5D-3L) and FR (Activities of Daily Living (ADL), Timed Up and Go (TUG) and MiniCog), 26 centers enrolled patients from February 2017 to April 2019. Results: 942 patients underwent a major cancer resection. Median age was 78 (range 70-95); 52.2% males, ASA III-IV 49%. 934 (99%) lived at home, 51% lived alone, and 87% were able to go out. Patients dependent (ADL &lt; 5) were 8%. Frailty was detected by means of G8 ≤14 in 68.8% and fTRST ≥2 in 37% of patients. Major comorbidities (CCI &gt; 6) were reported in 36% and 21% had cognitive impairment according to MiniCog (2.2% self-reported). 25% had &gt; 3 kg weight loss, 27% were hospitalized in the last 90 days, 54% had ≥3 medications (6% none). Postoperative overall morbidity was 39.1% (30 day) and 22.5% (90 day), but Clavien-Dindo III-IV complications were only 13.4% and 6.9% respectively. 30/90/180-day mortality was 3.6/6/8.9% (10/30/33% in patients with severe functional disability). At 3 months after surgery, QoL was stable/improved (mean EQ-5D index 0.78 was equivalent before vs. after surgery, while the EQ-5D VAS score &gt; 60 raised from 74.3% at baseline to 80.2%, p &lt; 0.01). 76.6% experienced postoperative FR/stability. Logistic regression analysis showed that ASA 3-4, CCI≥7 and CD III-IV complications are significantly associated with functional decline while a G8 &gt; 14 has a positive association with functional recovery. Age is not associated with functional outcomes. Conclusions: The largest prospective study on older patients undergoing structured frailty assessment before and after major elective cancer surgery has shown that QoL remains stable/improves after cancer surgery. The majority of patients return to independence and G8 can predict functional recovery. Older patients with multiple comorbidities, high ASA score or postoperative severe complications are likely to functionally deteriorate after oncologic surgery Clinical trial information: NCT03299270 .
反复咳嗽、咳痰伴活动后气促5年
Authors: 江孙芳, 任雪雷, 蔡映云, 祝墡珠
Journal: BMJ (2010)

病史摘要 患者,女性,60岁.因反复咳嗽、咳痰伴活动后气促5年,加重1周入院.患者2003年8月开始出现咳嗽、咳少量白痰,伴发热,体温在38.5℃左右.经抗生素治疗1个月后症状缓解不明显,并渐出现活动后气急。
心房颤动与脑卒中
Authors: 孙艺红
Journal: BMJ (2006)

脑卒中是心房颤动(房颤)患者常见且最严重的并发症,其年发生率平均为5%,不同亚组间差异很大0.5%～12%[1].房颤占所有脑卒中原因的15%～20%,在房颤基础上发生的卒中与无房颤患者相比导致严重功能障碍和致死的比例更高.应根据危险分层合理选择抗栓治疗的适应证,在有效预防血栓栓塞事件的同时,减少不适当抗凝造成的出血危险和经济负担。
Cardiotoxicity manifestations in metastatic breast cancer patients treated with trastuzumab as first line.
Authors: Shira Sherman, Tamar Barkan, Rinat Yerushalmi
Journal: Journal of Clinical Oncology (2020)

e13011 Background: Trastuzumab is a monoclonal antibody that targets the human epidermal growth factor receptor-2 (HER2). Its use may result in cardiotoxicity. There are no formal guidelines for left ventricular ejection fraction (LVEF) monitoring in patients with metastatic disease treated with trastuzumab. Our local guideline include an echocardiogram every 3 months for these patients. Methods: We collected data from electronic records and hard copy files of patients treated with Trastuzumab as first line, between the years 2011-2014. Results: One hundred patients met the inclusion criteria. Median treatment duration of all patients was 30 months, with an average of 12 echocardiogram follow-ups per patient. Ninety-nine patients (99%) received additional chemotherapy. Thirty patients (30%) also received Pertuzumab. Ten (10%) of the eligible 100 patients showed significant decline in EF (≥10%) to a final LVEF of &lt; 50%. The median follow-up duration of these patients was 52 months. Median EF at the beginning of treatment was 61.5% in all patients. Cardiotoxicity occurred at an average of 23 months [median 18 months] after beginning of Trastuzumab treatment (range; 3-54 months), with an average EF decline of 14% (range; 10-18%). Three patients (30%) required treatment change due to the decline in EF. Temporary cessation of treatment was necessary in 4 (40%) of the patients for a period of time between 4 weeks to 8 months. The remaining 3 patients (30%), although developing significant decline in EF, did not require treatment cessation or change. None of the 10 patients presented any other clinical sign of cardiotoxicity. In the group with cardiac events, there were no previous reports of congestive heart failure (CHF), ischemic heart failure (IHF), myocardial infraction (MI) or diabetes. Only one patient was a smoker and another received hormone replacement therapy. The average age of this group at the time of diagnosis of metastatic disease was younger (50.6 vs. 55.8, P-value 0.5). Conclusions: Monitoring heart function by trimonthly echocardiogram does not seem to be the optimal monitoring modality in metastatic breast cancer patients who receive a trastuzumab-containing regimen as first line. This study results suggest that less frequent monitoring may be sufficient, thus diminishing patients' inconvenience and allowing better allocation of health care resources.
肾性血尿的中医辨证论治
Authors: 杨彦芳, 董葆
Journal: BMJ (2011)

血尿为泌尿系疾病常见的临床表现,根据其来源可分为肾性血尿和非肾性血尿.肾性血尿(即肾小球源性血尿)是指排除尿路感染、结石、结核、肿瘤等肾外出血因素,由原发或继发性肾小球疾病所引起的肉眼或镜下血尿.临床以肾性血尿为主要表现者常见于IgA肾病、急慢性肾炎、紫癜性肾炎、狼疮性肾炎等.由于肾性血尿的病因较多,目前现代医学主要针对原发疾病进行治疗,对于临床表现为单纯的镜下血尿或伴少量蛋白尿(24 h尿蛋白<0.5 g/d)者,常无有效的干预措施,此时采用中医辨证论治可获得较好的疗效。
Monoclonal Immunoglobulin Deposition Disease: Light Chain and Light and Heavy Chain Deposition Diseases and Their Relation to Light Chain Amyloidosis
Authors: Joel N. Buxbaum, Joseph V. Chuba, Gerard C. Hellman, Alan Solomon, Gloria R. Gallo
Journal: Annals of Internal Medicine (2020)

Abstract Monoclonal immunoglobulin deposition occurs in tissues as Congo Red binding fibrils in light chain amyloidosis, as less structured deposits in light chain deposition disease, and as simila...
Diagnosis for smear- or culture-positive pulmonary tuberculosis in 50 patients admitted to a general hospital-A retrospective analysis
Authors: 侍效春, 刘晓清, 高凤莉, 邓国华
Journal: BMJ (2010)

Objective To investigate clinical characteristics of smear- or culture-positive pulmonary tuberculosis (TB) in patients hospitalized at a general hospital to improve its diagnosis. Methods Clinical data of smear- or culture-positive pulmonary TB diagnosed in 50 patients hospitalized at Peking Union Medical College Hospital, Beijing during 2006 to 2009 were analyzed retrospectively. Results Seventeen (34%) of 50 cases of smear- or culture-positive pulmonary TB aged more than 60 years, with 30 males (32%), 16 retirees and nine farmers (18%). Their main symptoms included fever (80%), cough (94%) and sputum expectoration (92%), with elevated erythrocyte sedimentation rate (ESR) in 38 of 45 patients (84%). Chest X-ray examinations showed that lesions located mostly in the upper lobes or in both of the lungs diffusedly, with patchy infiltrations, nodular opacities and cavities. Acid-fast bacilli were demonstrated on sputum smear in 41 ( 82% ) and in specimens of six ( 12% ) cases obtained through bronchoscopy with brush or bronchoalveolar lavage fluid ( BALF), and M. Tuberculosis was cultured from sputum specimens in three (6%). Mean time interval between admission and diagnoses averaged 14 days.Conclusions Basic knowledge about prevention and control of pulmonary tuberculosis should be publicized comprehensively in general hospital keeping alert in its diagnosis with acid-fast staining for sputum smear as a routine test for patients with respiratory symptoms, and in some cases, bronchoscopy procedures ( brush or BALF) are reasonable options to improve its detection.

Key words: 
Mycobacterium tuberculosis ;  Tuberculosis,pulmonary ;  Diagnostic techniques and procedures ;
Type 1 conventional dendritic cells are systemically dysregulated early in pancreatic carcinogenesis
Authors: Jeffrey H. Lin, Austin P. Huffman, Max M. Wattenberg, David M. Walter, Erica L. Carpenter, David M. Feldser, Gregory L. Beatty, Emma E. Furth, Robert H. Vonderheide
Journal: The Journal of Experimental Medicine (2020)

Type 1 conventional dendritic cells (cDC1s) are typically thought to be dysregulated secondarily to invasive cancer. Here, we report that cDC1 dysfunction instead develops in the earliest stages of preinvasive pancreatic intraepithelial neoplasia (PanIN) in the KrasLSL-G12D/+ Trp53LSL-R172H/+ Pdx1-Cre-driven (KPC) mouse model of pancreatic cancer. cDC1 dysfunction is systemic and progressive, driven by increased apoptosis, and results in suboptimal up-regulation of T cell-polarizing cytokines during cDC1 maturation. The underlying mechanism is linked to elevated IL-6 concomitant with neoplasia. Neutralization of IL-6 in vivo ameliorates cDC1 apoptosis, rescuing cDC1 abundance in tumor-bearing mice. CD8+ T cell response to vaccination is impaired as a result of cDC1 dysregulation. Yet, combination therapy with CD40 agonist and Flt3 ligand restores cDC1 abundance to normal levels, decreases cDC1 apoptosis, and repairs cDC1 maturation to drive superior control of tumor outgrowth. Our study therefore reveals the unexpectedly early and systemic onset of cDC1 dysregulation during pancreatic carcinogenesis and suggests therapeutically tractable strategies toward cDC1 repair.
Statin use is associated with a lower risk of diffuse large B-cell lymphoma: A systematic review and meta-analysis.
Authors: Ben Ponvilawan, Nipith Charoenngam, Patompong Ungprasert
Journal: Journal of Clinical Oncology (2020)

e13585 Background: Statin use is associated with decreased risk of several types of cancer such as hepatocellular carcinoma, colorectal cancer and hematologic malignancy, although the data on diffuse large B-cell lymphoma (DLBCL) is still inconclusive. The current systematic review and meta-analysis was conducted to summarize all available data on this association. Methods: A systematic review was performed using EMBASE and MEDLINE database from inception to October 2019 with search strategy that included terms for “statin” and “DLBCL”. Eligible studies could be either cohort or case-control studies that reported the association between statin use and risk of DLBCL. Eligible cohort studies must include patients with history of statin use and comparators with no history of statin use, then follow them for incident DLBCL and report the relative risk, hazard risk ratio, or standardized incidence ratio and associated 95% confidence intervals (CI) comparing the incidence of DLBCL between the two groups. Eligible case-control studies must include cases with DLBCL and controls without DLBCL, then search for prior statin use and report the odds ratio and associated 95% CI for this association. Point estimates along with standard errors were extracted and combined together for the calculation of the pooled effect estimate using the random effect, generic inverse variance method. Results: A total of 1,139 articles were identified using the search strategy. Six studies satisfied the inclusion criteria and were included into the meta-analysis. Statin use was associated with a significantly reduced risk of DLBCL with the pooled relative risk of 0.70 (95% CI, 0.56 – 0.88; I 2 = 70%). Funnel plot was fairly symmetric and was not suggestive of presence of publication bias. Conclusions: This systematic review and meta-analysis found that patients with history of statin use had a significantly lower risk of DLBCL compared to individuals without history of statin use.