tbuckley/cabot-search huggingface dataset:
Rate of durable complete response in ALL, NHL, and CLL after immunotherapy with optimized lymphodepletion and defined composition CD19 CAR-T cells.
Authors: Cameron John Turtle, Laila-Aicha Hanafi, Carolina Berger, Theodore Gooley, Colette Chaney, Sindhu Cherian, Lori Soma, Xueyan Chen, Cecilia CS Yeung, Keith Loeb, Brent L. Wood, Michael Hudecek, Daniel Sommermeyer, Daniel Li, Kevin Anthony Hay, Shelly Heimfeld, Stanley R. Riddell, David G. Maloney
Journal: Journal of Clinical Oncology (2016)

102 Background: We are conducting a phase I/II trial in which patients (pts) with relapsed or refractory (R/R) CD19+ B cell malignancies receive CD19 CAR-T cells comprised of a defined ratio of CD8+ and CD4+ CAR-T cells. Methods: Pts received lymphodepleting chemotherapy followed by infusion of a 1:1 ratio of CD8+:CD4+ CAR-T cells at one of 3 dose levels (2x105 to 2x107 CAR-T cells/kg). No pts were excluded due to lymphopenia (ALC < 0.5 in 22% of pts), circulating tumor or poor in vitro T cell proliferation. Results: Ninety pts with ALL (n = 36), NHL (n = 41) or CLL (n = 13) received CAR-T cells. Thirty-one of 33 ALL pts (94%) that have had restaging achieved CR by marrow flow cytometry. Two of 31 pts had molecular MRD. In vivo CAR-T cell expansion and persistence, and DFS were superior in pts who received cyclophosphamide (Cy) and fludarabine (Flu) lymphodepletion compared to those who received Cy without Flu. CAR-T cell persistence was limited in patients not receiving Flu by immune responses to the murine scFv of the CAR. In NHL, the ORR for pts treated with Cy/Flu and CAR-T cells at the maximally tolerated cell dose (n = 19; 2x106/kg) was 84% (47% CR). CAR-T cell expansion and persistence, and OS and PFS were better in Cy/Flu pts compared to those who received Cy alone (ORR 50%, CR 8%, n = 12). Remissions are ongoing in 9 of 10 Cy/Flu treated pts who achieved CR (range 1-9 months follow-up). All CLL pts had received prior ibrutinib. CAR-T cell therapy eliminated CLL from the marrow in 10 of 12 restaged pts (83%) and 6 (50%) achieved CR (Lugano criteria). None of the CLL pts who achieved CR has relapsed. In 87 pts evaluated for toxicity the rates of severe cytokine release syndrome (sCRS) and grade ≥ 3 neurotoxicity were 16% and 31%, respectively. Four pts (4%) died of complications of CRS and 1 pt experienced irreversible neurotoxicity. We identified serum biomarkers on day 1 after CAR-T cell infusion that correlated with subsequent sCRS or grade ≥ 3 neurotoxicity in ALL and NHL pts, allowing rational design of early intervention studies in high-risk pts. Conclusions: Adoptive therapy with CD19 CAR-T cells of defined subset composition results in durable CR in a high fraction of pts with R/R ALL, NHL and CLL. Clinical trial information: NCT01865617.
Efficient and Durable Gene Marking of Hematopoietic Progenitor Cells in Nonhuman Primates After Nonablative Conditioning
Authors: M. Rosenzweig, T.J. MacVittie, D. Harper, D. Hempel, R.L. Glickman, R.P. Johnson, A.M. Farese, N. Whiting-Theobald, G.F. Linton, G. Yamasaki, C.T. Jordan, H.L. Malech
Journal: Blood (1999)
Website of the week: Persistent vegetative state
Authors: Alison Tonks
Journal: BMJ (2001)

This week, two articles discuss the problems encountered by relatives and professionals caring for people in the persistent vegetative state (pp 352 and 372). This high profile and ethically challenging form of coma has thousands of web pages devoted to it, some crankier than others. If you want a professional view it's always best to start at the top, and the US based National Institute of Neurological Disorders and Stroke has an information page plus links to care organisations at www.ninds.nih.gov. It's also the starting point for an interesting diversion to the National Library of Medicine's new register of clinical trials at www.Clinicaltrials.gov.

It's hard to think about the persistent vegetative state for long without considering the nature of awareness, since these patients are defined only by their lack of it. David Chalmers' website at the University of Arizona (www.u.arizona.edu/∼chalmers/index.html) is a wonderful resource for beginners. As a professor of philosophy and an associate director of the university's centre for consciousness studies, he is a good guide to an emerging discipline that links many others, including philosophy, cognitive science, and neurophysiology. Browse through some of his 722 online papers to appreciate just how controversial it can be to define abstract concepts such as awareness.

Many of these articles were originally published in the Journal of Consciousness Studies, which has a web presence, including full text articles, at www.imprint.co.uk/jcs/. The journal's editors claim it is written in plain English, and some of it is. But for stopping conversation at a dinner party, try saying: “A self, according to my theory, is not any old mathematical point, but an abstraction defined by the myriads of attributions and interpretations (including self-attributions and self-interpretations) that have composed the biography of the living body whose Center of Narrative Gravity it is” (Journal of Consciousness Studies 1996;3:350-6).
Abstract 2140: Infrequent Need for Pacing Following Implantable Cardioverter-Defibrillator Shocks: Analysis of the Sudden Cardiac Death in Heart Failure Trial
Authors: Jordan M Prutkin, Jeanne E Poole, George Johnson, Jill Anderson, Daniel B Mark, Kerry L Lee, Gust H Bardy
Journal: Circulation (2008)

Background: Implantable cardioverter-defibrillators (ICD) are routinely programmed to pace after a shock to prevent possible asystole. In those with no prior history of bradycardia, there is little data regarding the prevalence and characteristics of those who use post-shock pacing (PSP). Methods: We analyzed the occurrence of pacing within the first nine beats after the first successful ICD shock for ventricular tachycardia (VT) or ventricular fibrillation (VF) in the Sudden Cardiac Death in Heart Failure Trial (SCD-HeFT). All ICDs were single lead with the first PSP delivered at 1400msec and all subsequent stimuli delivered at 1200msec. We excluded patients with pacing during pre-shock rhythms and those who had pacing rates different than the protocol default rate of 50bpm (1200 msec). Results: There were 2521 patients enrolled in SCD-HeFT, of which 811 received an ICD. A total of 153 shock events were examined; 36 (23.5%) had at least one of the first nine beats paced post-shock, though only 4 (2.5%) had greater than 4 out of the 9 beats paced. No subjects needed pacing for all nine beats and only 8 (5.2%) paced for greater than 5 seconds. There were no differences in age, gender, etiology of cardiomyopathy, or NYHA class between those with PSP or not. The prevailing heart rate pre-shock was predictive of PSP; the mean cycle length of the baseline rhythm pre-shock was longer (slower rate) for those who used PSP (735 ± 228msec vs. 624 ± 158msec, P=0.001). More often, VF (vs. VT) was the rhythm shocked in those using PSP (P=0.015). A trend also was seen toward increased frequency of PSP in those receiving 30J shocks (16 of 49) versus ≤20J shocks (20 of 104, P=0.068). Conclusion: Patients infrequently require multiple paced beats post-shock for VT or VF. Patients using PSP have a slower baseline heart rate and are more likely to have VF as the shocked rhythm. While 1 or 2 paced beats out of the first nine occurred occasionally, these patients also had rapid return of their native rhythm for which the hemodynamic contribution of 1 or 2 paced beats is unclear. These data suggest that for most patients receiving a primary prevention ICD programmed for shock-only therapy, the need for PSP is limited. PSP use may reflect convention and the assumption that minor post-shock pauses are detrimental.
Insights From Molecular Profiling of Adult Glioma
Authors: Phedias Diamandis, Kenneth D. Aldape
Journal: Journal of Clinical Oncology (2017)

The comprehensive molecular profiling of cancer has resulted in new insights into the biology and classification of numerous tumor types. In the case of primary brain tumors that commonly affect adults, an emerging set of disease-defining biomarker sets is reshaping existing diagnostic entities that had previously been defined on the basis of their microscopic appearance. Substantial progress has been made in this regard for common primary brain tumors in adults, especially diffuse gliomas, where large-scale profiling efforts have led to the incorporation of highly prevalent molecular alterations that promote a biologically based classification as an adjunct to the traditional histopathologic approach. The growing awareness that histologically indistinguishable tumors can be divided into more precise and biologically relevant subgroups has demanded a more global routine approach to biomarker assessment. These considerations have begun to intersect with the decreasing costs and availability of genome-wide analysis tools and, thus, incorporation into routine practice. We review how molecular profiling already has led to an evolution in the classification of brain tumors. In addition, we discuss the likely trajectory of incorporation of global molecular profiling platforms into the routine clinical classification of adult brain tumors.
Development and validation of the International Hidradenitis Suppurativa Severity Score System ( <scp>IHS</scp> 4), a novel dynamic scoring system to assess <scp>HS</scp> severity
Authors: C.C. Zouboulis, T. Tzellos, A. Kyrgidis, G.B.E. Jemec, F.G. Bechara, E.J. Giamarellos‐Bourboulis, J.R. Ingram, T. Kanni, I. Karagiannidis, A. Martorell, Ł. Matusiak, A. Pinter, E.P. Prens, D. Presser, S. Schneider‐Burrus, E. von Stebut, J.C. Szepietowski, H.H. Zee, S.M. Wilden, R. Sabat, R. Sinclair, D. Vekic, P. Haes, V. Marmol, A. Alavi, W. Gulliver, A. Nassif, G. Nikolakis, M. Podda, C. Antoniou, F.S. Delli, C. Dessinioti, A. Patsatsi, A.P. Trigoni, C. Zisimou, V. Bettoli, S. Garcovich, J. Boer, B. Horváth, G. Ingvarsson, L. Puig, R.E. Hunger, L. Emtestam, F.W. Danby, A.B. Kimball
Journal: British Journal of Dermatology (2017)

A validated tool for the dynamic severity assessment of hidradenitis suppurativa/acne inversa (HS) is lacking. To develop and validate a novel dynamic scoring system to assess the severity of HS. A Delphi voting procedure was conducted among the members of the European Hidradenitis Suppurativa Foundation (EHSF) to achieve consensus towards an initial HS Severity Score System (HS4). Strengths and weaknesses of HS4 were examined by a multicentre prospective study. Multivariate logistic regression, discriminant analysis and receiver operating characteristic curves, as well as examination for correlation (Spearman's rho) and agreement (Cohen's kappa) with existing scores, were engaged to recognize the variables for a new International HS4 (IHS4) that was established by a second Delphi round. Consensus HS4 was based on number of skin lesions, number of skin areas involved and Dermatology Life Quality Index (DLQI), and was evaluated by a sample of 236 patients from 11 centres. Subsequently, a multivariate regression model calculated adjusted odds ratios for several clinical signs. Nodules, abscesses and draining tunnels resulted as the scoring variables. Three candidate scores were presented to the second Delphi round. The resulting IHS4 score is arrived at by the number of nodules (multiplied by 1) plus the number of abscesses (multiplied by 2) plus the number of draining tunnels (multiplied by 4). A total score of 3 or less signifies mild, 4–10 signifies moderate and 11 or higher signifies severe disease. Cohen's kappa was fair (κ = 0·32) compared with Hurley classification, and moderate (κ = 0·49) compared with Expert Opinion. Correlation was good (ρ > 0·6) with Hurley classification, Expert Opinion, Physician's Global Assessment and Modified Sartorius score, and moderate for DLQI (ρ = 0·36). The novel IHS4 is a validated tool to dynamically assess HS severity and can be used both in real‐life and the clinical trials setting.
Clinicopathological features of patients with breast cancer aged 70 years and older: A single center experience.
Authors: Aydin Aytekin, Suleyman Sahin, Fatih Karatas, Gokmen umut Erdem, Ali Riza Sever, Kadri Altundag
Journal: Journal of Clinical Oncology (2016)

e12060 Background: It is well-known that the risk of breast cancer (BC) increases in parallel with aging. In addition, life expectancy is increasing worldwide.Despite this disease burden in elderly patients, there is still a great uncertainty regarding how to manage BC disease in the older population.We aimed to report clinicopathological features and treatment outcomes of our experience in BC patients aged over 70 years. Methods: Medical records of 4413 patients with BC followed between 1994 – 2015 were retrospectively analyzed. Of these, 238 patients (stage 1-3) aged 70 years and older at BC diagnosis were enrolled in the study. Patients were divided into 2 groups according to age as group 1 (between 70 – 79, n = 192) and group 2 (80 and older, n = 46). Clinicopathological features of patients including tumor histology,grade, estrogen and progesteron receptor, HER2 status, tumor size, lymph node involment, clinical stage, type of treatments and comorbid diseases along with familial history were evaluated. Results: The median age was 74 for group 1 (70 - 79) and 82 for group 2 (80 - 92). Number of patients with a familial breast cancer history was significantly greater in group 1 in comparison to group 2 (P = 0.028). Patients in group 2 more frequently presented with greater tumor size (P = 0.014). Modified radical mastectomy and adjuvant chemotherapy treatments were more commonly performed in group 1 (P = 0.001, P = 0.001, respectively). In contrast, neoadjuvant treatment was more frequently applied in group 2 (P = 0.003). While there was no difference in disease free survival between the groups, median overall survival was significantly higher in group 1 (P = 0.03). In addition, there was no difference in other clinicopathologic features between two groups. Conclusions: Given the increasing life time of older population in BC patients, it is apparently necessary to establish the most appropriate algorithms for treatment options in this group of patients. In order to set up a better treatment algorithm for this population, more comprehensive studies including large number of older patients with a complete geriatric assessments should be performed.
Skeletal muscle area and density as predictors of chemotherapy toxicity and outcomes in metastatic breast cancer.
Authors: Shlomit Strulov Shachar, Allison Mary Deal, Marc Weinberg, Kirsten A Nyrop, Grant Richard Williams, Tomohiro F. Nishijima, Julia M. Benbow, Hyman B. Muss
Journal: Journal of Clinical Oncology (2016)

1021 Background: Sarcopenia, or severe skeletal muscle loss, is associated with poor cancer outcomes including increased toxicity and reduced survival. This study investigates body composition indices including muscle quantity and quality in patients with metastatic breast cancer (MBC) receiving first line taxane-based chemotherapy and compares these indices to treatment toxicity and related outcomes. Methods: Skeletal muscle area (SMA) and density were measured at the level of the third lumbar vertebrae using computerized tomography (CT) images taken for the evaluation of disease burden. Sarcopenia was defined as Skeletal Muscle Index (SMI = SMA / height^2) < 41(Martin et al, JCO, 2013). Skeletal Muscle Integrated Density (SMID), a novel marker of body composition was created by multiplying SMI x Mean Muscle Density. Fisher’s exact and t-tests were used to compare groups, hazard ratios (HR) were estimated for time to event outcomes. Results: MBC patients (N = 46) who had CT scans within 45 days of starting chemotherapy. Mean age was 56 (range 34-80). 59% were sarcopenic; median SMID was 1208 (range: 372-2499). Grade 3-4 toxicity (CTCAE version 4.0) was reported in 56% of sarcopenic vs 21% of non-sarcopenic patients (p= 0.03). Toxicity-related hospitalizations were significantly higher in sarcopenic patients (33% vs 5%, p= 0.031). Any adverse event (grade 3-4 chemotherapy-related toxicities, hospitalizations, dose reductions, and dose delays) was significantly higher in sarcopenic patients (74% vs 37%, p= 0.016). Low SMID was significantly associated with hospitalization (p= 0.03) and approached significance with G3-4 toxicity (p= 0.06) and any adverse event (p= 0.08). For each 100 unit increase in SMID, a patient’s risk of treatment failure (progression or toxicity) decreased by 8% (p= 0.035, HR = 0.92, 95% CI 0.85-0.99) and risk of death decreased by 7% (p= 0.055, HR = 0.93, 95% CI 0.87-1.00). Conclusions: Skeletal muscle indices, including a novel measure SMID, are associated with toxicity outcomes and survival. Further studies are needed to explore how routinely obtained CT scans can be used to individualize dosing and other elements of the oncologic treatment plan.
Гастроінтестинальні ускладнення залежно від селективності нестероїдного протизапального препарату
Authors: G.V. Dzyak, Yu.M. Stepanov, I.V. Kushnirenko
Journal: GASTROENTEROLOGY (2013)

Стаття присвячена проблемі гастроінтестинальних ускладнень при застосуванні нестероїдних протизапальних препаратів, що широко призначаються для лікування цілого спектра станів, зокрема при ревматологічних захворюваннях. Наведені результати власних досліджень, що дозволили визначити особливості змін стану секреторної функції шлунка на фоні прийому неселективного та селективного нестероїдного протизапального засобу та дати їх порівняльну характеристику. Отримані дані дозволили зробити певний внесок у формування уявлень про механізми розвитку ускладнень із боку шлунково-кишкового тракту при прийомі препаратів вищевказаної групи.
Risk stratification of clinical stage I (CSI) non-seminomatous germ cell testicular tumors (NSGCT): A retrospective analysis of experience at Indiana University (IU).
Authors: Sushma Tatineni, Greg Andrew Durm, Girish Chandra Kunapareddy, Natraj Reddy Ammakkanavar, Edward F. Dropcho, Sandra Althouse, Nasser H. Hanna, Lawrence H. Einhorn, Costantine Albany
Journal: Journal of Clinical Oncology (2016)

e16052 Risk Stratification of Clinical Stage I (CSI) Non-Seminomatous Germ Cell Testicular Tumors (NSGCT): A Retrospective Analysis of Experience at Indiana University (IU) Background: Nearly 50% of testicular germ cell tumors are NSGCT. For those with CSI disease, standard treatment options include active surveillance, retroperitoneal lymph node dissection (RPLND), or adjuvant chemotherapy. The cure rate is 99% regardless of which approach is chosen. However, there exists a need for better risk stratification of CSI into low and high risk of recurrence. We aim to evaluate the risk factors for relapse in CSI patients on surveillance, comparing histopathological risk factors of embryonal carcinoma predominance (EC) and lymphovascular invasion (LVI). Methods: This study is a retrospective analysis of all pts with CSI NSGCT seen at diagnosis at IU from January 2000- 2015. Results: We identified 424 consecutive pts of which 170 (40%) had surveillance. 50 (29%) had recurrence on surveillance. 76% relapsed in pelvic and retroperitoneal lymph nodes, 14% had pulmonary metastasis, and 6% with only rising tumor markers. Median time to relapse is 0.5 years (0.2-6 yrs). Only four pts had late relapse > 2 yrs. Six pts were salvaged with RPLND and the rest cured with 3 courses of Bleomycin, Etoposide, and Cisplatin. Recurrence rates were higher in those with EC (40%) than without (21%) (p = 0.0066) and in those with LVI (52%) than without (18%) (p < 0.001). However, EC without LVI and LVI without EC did not demonstrate statistically higher relapse rates (22%, p = 0.2877; 43%, p = 0.1124, respectively). Those with both EC and LVI had a higher recurrence rate on surveillance than those with neither present (58% vs. 16%, respectively, p < 0.001). Conclusions: In this cohort of CSI NSGCT, the combination of EC and LVI at orchiectomy is associated with a significant increase in relapse rate. Absence of both is associated with a significantly lower relapse rate. Neither EC nor LVI alone had a statistically significant increase in relapse rates in this cohort. This data may be used in detailed counseling of patients to ensure appropriate follow up on surveillance as a part of their treatment.
Pemetrexed in combination with cisplatin versus carboplatin as first-line therapy in patients with advanced-stage malignant pleural mesothelioma (MPM): A systematic review and meta-analysis.
Authors: Samer Ali Srour, Julie A. Stoner
Journal: Journal of Clinical Oncology (2016)

8554 Background: Pemtrexed/cisplatin (PCisp) remains the standard frontline treatment for advanced-stage MPM. However, a majority of patients are older and too fragile to tolerate PCisp. Because of better tolerance, pemetrexed/carboplatin (PCarb) is being used. To compare efficacy and safety of PCarb versus PCisp in MPM, we conducted a comprehensive systematic review and meta-analysis. Methods: Medline, EMBASE, and Cochrane databases were searched, in addition to proceedings from major meetings. Comparative and single-arm studies were included. Primary endpoints were overall survival (OS), progression-free survival (PFS), objective response rate (ORR) & disease control rate (DCR). Secondary safety endpoints were analyzed. Study heterogeneity, publication bias, and sensitivity analysis were assessed. Risk ratio (RR), HR, and 95% CI were calculated using random-effects models. Results: Initial search identified 972 studies; 23 [11 prospective (5 randomized), 12 retrospective] with a total of 3170 patients (82% men) were eligible for final analysis. Pooled median OS and PFS estimates were 14.9 (95% CI: 12.1-17.8) and 6.2 (95% CI: 5.2-7.3) months for PCisp, and 15.7 (95% CI: 9.9-21.5) and 6.8 (95% CI: 6.1-7.5) months for PCarb, respectively. For the 5 studies with comparative arms (1615 patients), there was no statistically significant difference in OS (HR = 1.04, 95% CI: 0.90-1.21) or PFS (HR = 0.90, 95% CI: 0.66-1.22). The ORR (CR + PR) was significantly higher for PCisp (RR = 1.23; 95% CI 1.04-1.47, p = 0.017), but was not significant when stable disease was added (DCR). Safety analysis suggested better non-hematologic toxicity profile for PCarb. A majority of studies were at high risk of bias. Conclusions: PCarb is not significantly different from PCisp in advanced-stage MPM in terms of DCR, PFS, and OS. Available evidence suggests that PCarb is an alternative to PCisp, especially for older or unfit patients given the better tolerance. Additional prospective randomized trials are needed.