tbuckley/cabot-search huggingface dataset:
A phase II single-arm, multicenter, open-label neoadjuvant study of pembrolizumab in combination with nab-paclitaxel followed by pembrolizumab in combination with epirubicin and cyclophosphamide in patients with triple-negative breast cancer: Neoimmunoboost.
Authors: Peter A. Fasching, Andreas Hartkopf, Hans-Christian Kolberg, Lothar Haeberle, Sarah Wetzig, Christine Mau, Tobias Engler, Matthias Rübner, Hanna Hübner, Anna-Katharin Theuser, Nadine Hummel, Sabrina Uhrig, Matthias W. Beckmann, Alexander Hein, Michael Untch
Journal: Journal of Clinical Oncology (2020)

e12647 Background: The NeoImmunoboost study (NCT03289819) was designed to evaluate the pathological complete response (pCR) rate and safety of a neoadjuvant combination of the PD-1 antibody pembrolizumab and nab-paclitaxel followed by pembrolizumab with epirubicin and cyclophosphamide in patients with early triple negative breast cancer (TNBC). Methods: This is a prospective, single-arm, multi-center, open-label phase II clinical trial. Female patients with early TNBC were eligible for trial participation. Patients received 12 cycles of weekly nab-paclitaxel intravenous (i.v.) 125 mg/m² body surface area (BSA) in combination with 4 cycles of pembrolizumab i.v. 200 mg q3w; followed by 4 cycles of epirubicin i.v. 90 mg/m² BSA and cyclophosphamide i.v. 600 mg/m² BSA q3w in combination with 4 cycles of pembrolizumab i.v. 200 mg q3w. After 25 patients the protocol was amended, with an initiation boost of 1 cycle of pembrolizumab i.v. 200 mg q3w monotherapy prior to the chemotherapy. Primary trial endpoint was pCR. Secondary endpoints included safety and clinical response rate. Results: Between March 2018 and October 2019, 53 patients were included into the trial. Until now, 47 patients have completed trial treatment and 6 patients are still receiving therapy. 28 patients have received the initiation boost with pembrolizumab, 25 patients did not receive the initiation boost. Up to now, 4 patients terminated the therapy prematurely. Conclusions: pCR data of all patients will be available at the meeting and results of the pCR rates and selected secondary endpoints will be presented at the meeting. Clinical trial information: NCT03289819.
Multiple Classes of Antibiotic Use in Infancy and Allergic Disease in Childhood
Authors: KunMin Xiao, SiXiang Liang, Yini Liu
Journal: JAMA Pediatrics (2020)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Pediatrics HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Pediatrics journal
Malignant risk index in evaluation of menopausal ovarian cystic and cystic-solid tumors
Authors: Wenli Wang, Yun Liu, Hua Duan
Journal: BMJ (2019)

Clinical data of 349 patients with postmenopausal ovarian cystic and cystic solid tumors undergoing surgical treatment in Beijing Obstetrics and Gynecology Hospital affiliated to Capital Medical University from May 2013 to May 2017 were retrospectively analyzed. Postoperative pathology confirmed 100 cases of malignant tumor, 228 cases of benign tumor, and 21 cases of borderline tumor. The malignant risk index (RMI) score was calculated based on the preoperative pelvic ultrasound and serum CA125 level, and the score<200 was classified as benign tumors and ≥200 as malignant tumors. The postoperative pathological results were used as gold standard, the sensitivity, specificity, accurate rate of RMI in diagnosis of malignant tumors was 0.840(84/100), 0.987 (225/228) and 94.2% (309/328), respectively. The consistency of RMI with pathological diagnosis was high (Kappa=0.858, P<0.05). The study suggests that RMI has a high degree of credibility for the evaluation of postmenopausal ovarian cystic and cystic solid tumors.


Key words: 
Menopause; Ovarian cysts; Risk of malignancy index
Utilization of online crowdfunding for alternative cancer treatments at home and abroad.
Authors: Joshua David Gruhl, John Stuart Peterson, Sydney Davis, Jaxon Carey Olsen, Matthew Parsons, Benjamin H Kann, Gregory J. Stoddard, Skyler B Johnson
Journal: Journal of Clinical Oncology (2020)

e14044 Background: The use of alternative cancer treatments has been associated with decreased survival. However, little is known about the types of individuals who seek out these therapies, the alternative therapies pursued, and the associated costs. We utilized GoFundMe campaigns to characterize the types of patients who sought alternative cancer treatments, the types of therapies pursued, and the associated costs. Methods: We queried GoFundMe ( www.gofundme.com ) for English language campaigns using the term “alternative cancer treatment” using custom code for web scraping on 10/25/2019. We identified 1000 campaigns between 2011-2019, of which, 795 had received donations and were used for analysis. We studied each individual campaign in detail and extracted relevant information. Results: The majority of patients were female (63.5%). The most common cancer types were breast (25.3%), colorectal (10.8%), and lung (5.5%) cancer. Of patients reporting cancer stage, 79.3% had stage IV disease. Of those reporting prior cancer treatment history, 34.8% had never undergone traditional cancer treatment; 42.1%, 46.8%, and 26.6% had undergone prior surgery, chemotherapy, and radiotherapy, respectively. The most common proposed alternative treatments were vitamins and minerals (23.4%), herbs and botanicals (16.1%), special diets (13.0%), supplements (10.8%), heat or light therapy (7.8%), IV infusions (7.8%), homeopathic/naturopathic therapies (7.2%), and hyperbaric oxygen therapy (5.9%). Among all campaigns, a total of $36,394,110 was requested and a total of $8,601,759 (23.9%) was raised. The median campaign fundraising goal was $25900 (US dollars; Interquartile range [IQR] $1000 – $50000); the median amount donated was $5805 (IQR $2595 – $12580). These costs include travel as 629 (79.1%) campaigns were for patients residing in the USA, 70 (8.8%) in Europe, 62 (7.8%) in Canada, and 34 (4.3%) in other regions, from which, 54.3% of patients stated that they planned to travel internationally—most commonly to Mexico—for their alternative cancer treatments. Conclusions: Millions of dollars have been requested and raised between 2011 and 2019 for alternative cancer treatments. The majority of patients sought treatment at alternative clinics internationally, were females, had stage IV disease and primary tumors of the breast, colon/rectum or lung, who had previously undergone traditional cancer therapies, and highlight a group of patients where improved communication/education between providers and patients appears to be needed.
脑桥中央髓鞘溶解症一例
Authors: 倪贵华, 田向阳, 赵卫东, 郭建一
Journal: BMJ (2010)

患者女,58岁,以烦躁不安3 d于2009年11月17日收住当地县医院.患者半个月前感冒后出现发热,体温最高达38.6℃,伴头痛、纳差,在当地一诊所治疗后(具体不详)热退,头痛缓解,纳差无好转.3 d前出现烦躁不安,四肢不能自主活动,被送至当地县医院查头颅CT未见异常,血钾2.2 mmol/L,钠86.6 mmol/L,氯54.2 mmol/L,给予快速补钠、纠正电解质紊乱及对症支持治疗,1 d后复查血钠110mmol/L,3 d后患者神志转清,四肢能自主活动,血钠128.8mmol/L.1周后出院,此时血钠133.8 mmol/L.出院3 d后患者突然出现不能言语、吞咽困难、四肢乏力、行动不便再次送至当地县医院,诊断为脑梗死,治疗后效果不佳,为进一步诊治于12月3日转入我院。
未来的医院——越大越好吗？关于集中二级医疗保健服务
Authors: John, Posnett
Journal: BMJ (2002)

仔细观察过去 1 0年英国国家医疗卫生服务体系 (ＮＨＳ)的情况之后 ,如果有以下的想法 ,是不足为奇的 :集中提供医院服务是为了满足ＮＨＳ管理者和医学专业的需要 ,而不是为了满足他们的服务对象———当地居民的需要。管理者面临降低单位成本 ,特别是管理本身“浪费”成本的压力。医学专业人士迫于进一步细分专业的压力 ,通过各自的皇家学院主张关闭或调整较小型的医疗机构。上述结果已造成一种压力 ,即通过调整和合并 连锁医院 ,实现更为集中的服务。从逻辑上的推理当然是 :通过规模经济运作 ,较大型的机构可减低平均成本 ,平均临床活动增加 ,从而改进治病效果。但遗憾的是 ,这种推理尚无证据支持。 理想
Association of serum uric acid level with non-alcohofic fatty fiver disease in health check-up subjects
Authors: 杨菊红, 王华, 孙丽荣
Journal: BMJ (2012)

A cross-sectional study was performed among 5134 health check-up subjects in Tianjin Municipality.Compared with control group [ (274 ± 76)μmol/L],patients with non-alcoholic fatty liver disease (NAFLD) had a higher level of serum uric acid[ (340 ± 81 )μmol/L]. Moreover,in NAFLD patients,along with the increase of the severity of fatty liver from mild,intermediate to severe,the serum levels of uric acid increased from (331 ±78),(347 ± 83) to (377 ±75 ) μmol/L ( F =19.68,P ＜0.01 ).Regression analysis found that sex(β=-0.43 ),serum triglyceride(β =0.53 ),fasting plasma glucose(β =-0.21 )and BMI(β =0.19) were associated with uric acid level in NAFLD patients; but insulin level and homeostasis model of assessment-insulin resistance were not associated with uric acid level. The results indicate that serum uric acid levels may be used as a biomarker for the severity of NAFLD.

Key words: 
Fatty liver; Uric acid
A phase I/II first-in-human study of a novel anti-MAGE-A4 TCR/anti-CD3 bispecific (IMC-C103C) as monotherapy and in combination with atezolizumab in HLA-A*02:01-positive patients with MAGE-A4-positive advanced solid tumors (IMC-C103C-101).
Authors: George R. Blumenschein, Diwakar Davar, Rodolfo Gutierrez, Neil Howard Segal, Melissa Lynne Johnson, Mohammed M. Dar, Shannon Marshall
Journal: Journal of Clinical Oncology (2020)

TPS3165 Background: ImmTAC bispecifics are unique T cell receptor (TCR)/anti-CD3 bispecific molecules that are designed to redirect polyclonal T cells against intracellular antigens, in contrast to antibody-based therapies, which are limited to extracellular antigens. ImmTAC molecules recognize a specific peptide presented on defined Class I HLA molecules via an affinity enhanced, engineered, soluble TCR. Through the addition of an anti-CD3 scFv effector domain fused to the TCR targeting domain, ImmTAC molecules redirect T cell activity against cancer cells, regardless of the specificity of the T cell. IMC-C103C is an ImmTAC being investigated against MAGE-A4, which is among the most commonly expressed cancer testis antigens in solid malignancies, but with minimal to absent expression on normal tissues and/or hematopoietic cells. The most advanced ImmTAC in development, tebentafusp (IMCgp100), directed against melanocyte-associated lineage antigen gp100, has shown monotherapy activity in uveal melanoma and PD-1 refractory advanced cutaneous and uveal melanoma. Tebentafusp is being further evaluated in combination with durvalumab and tremelimumab. Methods: IMC-C103C-101 is a multi-center, open-label, Phase 1/2 first-in-human study of IMC-C103C as monotherapy and combination with atezolizumab in HLA-A*02:01-positive patients with MAGE-A4-positive advanced cancers. The study includes IMC-C103C monotherapy (Q1W) dose escalation, followed by expansion into indication specific arms to test for efficacy in defined patient cohorts. Concurrently, combinations with atezolizumab are planned. Primary objectives of dose escalation are to identify the MTD/RP2D, and characterize safety/tolerability. Secondary objectives include an assessment of efficacy (best overall response by RECIST v1.1), PK, PD, and ADA. IMC-C103C monotherapy dose escalation is in progress. Clinical trial information: NCT03973333 .
Urinary cell-free DNA analysis for tumor mutation detection in patients with oligometastatic colorectal cancer.
Authors: Bruna Pellini, Nadja Pejovic, Peter Harris, Wenjia Feng, Abul Usmani, Faridi Qaium, Ryan Fields, Aadel Chaudhuri
Journal: Journal of Clinical Oncology (2020)

e15545 Background: Cell-free DNA (cfDNA) analysis from blood is a useful liquid biopsy strategy. However, it requires phlebotomy and moderate volumes of plasma. Here, we explored the feasibility of urinary cfDNA (ucfDNA) analysis in patients with oligometastatic colorectal cancer (CRC). Methods: We applied error-corrected targeted next-generation sequencing (NGS) (AVENIO ctDNA surveillance assay) to 10 patients with oligometastatic CRC to the liver who underwent curative-intent surgery. 40 paired samples (tumor, plasma, urine supernatant, peripheral blood mononuclear cells (PBMCs)) were collected, from which DNA was extracted. Plasma and urine cfDNA samples (acquired preoperatively) were sequenced to a median de-duplicated depth of 8,065X with on-target rate of 71%. Similarly high depth targeted NGS was applied to tumor and PBMC samples. Variants were called from plasma cfDNA and tumoral DNA and queried in ucfDNA using methods derived from CAncer Personalized Profiling by deep Sequencing (CAPP-Seq) with integrated digital error suppression (iDES). Clonal hematopoiesis was accounted for by removing mutations also present in PBMCs. Results: Patients had a median of 2 tumors resected (range 1-7) with average sum of longest diameters of 8.7 cm (range 0.6-11). We used an average of 10 ml of blood and 37 ml of urine for cfDNA extraction. Circulating tumor DNA (ctDNA) was detected in all preoperative plasma samples (n = 10) at a mean mutant allele fraction (MAF) of 2.35% (range 0.09-11.78). Plasma ctDNA MAFs correlated significantly with tumor SLD (Pearson r = 0.81, P = 0.03). The average number of single nucleotide variants detected in plasma cfDNA, tumor and ucfDNA was 8 (range 1-42), 4 (range 1-7) and 2 (range 0-11), respectively. Indicative of concordance, 79% of the mutations called in tumor were detected in plasma. Tumor-derived DNA was detected in the preoperative urine of 6 patients (60%) with a MAF of 0.05% (range 0.03-0.12), ~35-fold less than in plasma (MAF of 1.78%, range 0.09-7.94) (P = 0.004). 38% of mutations identified in tumor and 26% from plasma were detected in ucfDNA for these 6 patients. In two patients, targetable mutations (BRAF p.Asp594Gly and PIK3CA p.Glu545Lys) present in tumor were also detected in ucfDNA, with the latter not detected in plasma. Conclusions: Our results indicate that ucfDNA analysis in patients with oligometastatic CRC is feasible; however, the mutational levels and detection sensitivity were much lower than from plasma. Yet, there may be situations where actionable mutations are missed in plasma but detected in urine.
Incidence and outcomes of immune checkpoint inhibitor-related myositis.
Authors: Jeffrey Aldrich, Xerxes Pundole, Sudhakar Tummala, Clark Andersen, Mahran Shoukier, Noha Abdel-Wahab, Nicolas Palaskas, Anita Deswal, Maria E. Suarez-Almazor
Journal: Journal of Clinical Oncology (2020)

e15128 Background: Data from immune checkpoint inhibitor (ICI) clinical trials show a higher incidence of ICI-related myositis with single agent ICI compared to combination therapy, but the true frequency in clinical practice is unknown. We sought to determine the incidence and clinical course of patients with ICI-related myositis at our institution. Methods: We performed a retrospective cohort study of patients treated with ICIs at MD Anderson Cancer Center between 2016 and 2019. Suspected cases of ICI-related myositis were identified using International Classification of Disease version 10 codes and confirmed by reviewing medical records, muscle enzymes and pathology. Patients treated with single agent anti-programmed death-1/ligand-1 (monotherapy) were compared to patients treated with nivolumab and ipilimumab (combination therapy) with Fischer’s exact tests, t tests, and Kaplan Meier analysis. Results: A total of 8,705 patients received ICI (7,428 monotherapy and 1,277 combination therapy), of which 31 (0.36%) were diagnosed with myositis. Estimated incidence of myositis was 0.28% and 0.78% (p=0.004), in the monotherapy and combination therapy groups, respectively. One patient was treated with ipilimumab alone (excluded from pooled data). Overall median age was 69 years (range: 40-95) with median follow up of 4 months after presentation for myositis. Thirteen (43%) patients had myositis alone and 17 (57%) had overlap with myasthenia gravis or myocarditis or both. After myositis resolution, 5 (17%) patients were rechallenged on ICI, of which 1 (20%) patient experienced a myositis flare. Differences between combination and monotherapy are summarized in the table. Patients treated with combination had shorter time to symptoms, but similar symptom grade at presentation, median length of hospitalization, and initial tumor response, compared to patients given monotherapy. Median overall survival (OS) was longer in combination vs monotherapy. Conclusions: Patients receiving combination ICI therapy had higher incidence of myositis with earlier onset than monotherapy; however, no differences in cancer outcomes or hospitalizations were observed between groups. Creation of multi-center databases are needed to develop treatment guidelines for ICI-related adverse events that will improve outcomes. [Table: see text]
Patient-reported health literacy and numeracy among new patients seeking consultation at a comprehensive cancer center.
Authors: Nadine Jackson McCleary, Jessica Cleveland, Sunyi Zhang, Eva M. Lepisto, Sherry Lee, Michael J. Hassett, Deborah Schrag
Journal: Journal of Clinical Oncology (2020)

7038 Background: Health literacy and numeracy are essential for patients to make informed cancer treatment decisions. Oncologists do not typically evaluate literacy and numeracy and vary in their ability to adapt health discussions to meet patients’ needs. Systematic ascertainment of literacy and numeracy may provide oncologists with useful information to help guide initial oncology consultations. Methods: We deploy an electronic new patient intake questionnaire (NPIQ) that includes health literacy and numeracy, basic demographics and cancer risk screening. Patients are considered to have limited health literacy and/or numeracy if they respond with either “somewhat”, “a little bit” or “not at all” to a single question: “How confident are you filling out medical forms?” or “How confident are you in understanding medical statistics?” respectively. Results: Between January 2018 and August 2019, 8418 (24.6%) of patients presenting for a new patient consultation responded to the NPIQ. Among respondents with non-missing data, limited health literacy was reported by 19.4% respondents with 13.9% reporting “not at all” and 33.1% reporting “not at all” or only “a little bit” of confidence completing medical forms. Limited health numeracy was reported by 33.2% respondents with 9.1% reporting “not at all”. Nearly 20% of respondents reported both limited health literacy and numeracy. Patients reporting lack of confidence completing medical forms or understanding medical statistics were older (20.3%, 30.7% ³ 70 years old), male (20.2%, 30.1%), and non-white (21.3%, 32.1%). Conclusions: A substantial proportion of cancer patients report lack of confidence in their ability to complete medical forms or understand medical statistics, potentially limiting the ability to actively engage in shared decision-making. Prospective identification of these social determinants of health prior to consultations may provide oncologists with information necessary to tailor health discussions and to provide materials that promote understanding and informed decision-making. [Table: see text]
Retrospective analysis of ribociclib and letrozole as first-line therapy in patients with hormone receptor (HR) positive metastatic breast cancer (MBC) within a managed access program (MAP) in Turkey.
Authors: Gul Basaran, Umut Demirci, Fatih Yildiz, Irfan Cicin, Burak Yasin Aktas, Banu Ozturk, Sema Sezgin Goksu, Hasan Senol Coskun, Basak Oyan, Ozlem Sonmez, Yesim Eralp, Erhan Gokmen, Seyda Gunduz, Taner Korkmaz, Mehmet Ali Nahit Sendur, Serkan Keskin
Journal: Journal of Clinical Oncology (2020)

e13055 Background: The combination of ribociclib with ET significantly increased progression free survival (PFS) and OS compared with ET in first line treatment of HR positive HER2 negative MBC. We aimed to evaluate the efficacy and safety of ribociclib and letrozole within Turkish MAP in order to present clinical outcome with the real-world use of ribociclib, outside of clinical trial setting. Methods: Turkish MAP enabled access to ribociclib in combination with letrozole as first-line therapy for MBC patients with HR positive and Her-2 negative tumors. Adequate bone marrow reserve, a normal QTc interval, normal renal and liver functions were required for eligibility. Patients received 600 mg ribociclib once daily for 3 wks followed by 1wk off. A retrospective chart review of patient demographics, clinical and treatment characteristics have been performed. Results: Between July and November 2017, 178 patients were included from 47 institutions in Turkey. We report the results of first 101 patients analyzed. The median age was 53 years (33–81 years) and median follow up was 16 months. Forty-six patients had de novo disease, 78% patients were postmenopausal, 22% had ovarian function suppression. Thirty-six % patients had adjuvant chemotherapy, 49% received adjuvant ET. Forty % had visceral disease. Thirty patients had grade 3 neutropenia, 3 patients had febrile neutropenia, 5 patients have grade 2-3 elevation of liver function tests. There was no QT prolongation. Dose reduction to 400 mg was required for 16 patients. Four patients discontinued ribociclib due to toxicity, 22 patients due to progression, one patient refused treatment. Twelve patients had complete remission as their best response. Median PFS was 24.12 months (95%CI 22.2-26.2). None of the clinical and pathologic factors were significantly associated with prolonged PFS. Conclusions: The efficacy and toxicity of first-line ribociclib and letrozole within Turkish MAP is similar to the results from randomized clinical studies for patients with HR positive, Her-2 negative MBC.
Predicting bioavailability of monoclonal antibodies after subcutaneous administration: Open innovation challenge
Authors: Manuel Sánchez-Félix, Matt Burke, Hunter H. Chen, Claire Patterson, Sachin Mittal
Journal: Advanced Drug Delivery Reviews (2020)

Despite the increasing trend towards subcutaneous delivery of monoclonal antibodies, factors influencing the subcutaneous bioavailability of these molecules remain poorly understood. To address critical knowledge gaps and issues during development of subcutaneous dosage forms for monoclonal antibodies, the Subcutaneous Drug Delivery and Development Consortium was convened in 2018 as a pre-competitive collaboration of recognized industry experts. One of the Consortium's eight problem statements highlights the challenges of predicting human bioavailability of subcutaneously administered monoclonal antibodies due to a lack of reliable in vitro and preclinical in vivo predictive models. In this paper, we assess the current landscape in subcutaneous bioavailability prediction for monoclonal antibodies and discuss the gaps and opportunities associated with bioavailability models for biotherapeutics. We also issue an open challenge to industry and academia, encouraging the development of reliable models to enable subcutaneous bioavailability prediction of therapeutic large molecules in humans and improve translation from preclinical species.