tbuckley/cabot-search huggingface dataset:
Grief Symptoms in Relatives Who Experienced Organ Donation Requests in the ICU
Authors: Nancy Kentish-Barnes, Sylvie Chevret, Gaëlle Cheisson, Liliane Joseph, Laurent Martin-Lefèvre, Anne-Gaëlle Si Larbi, Gérald Viquesnel, Sophie Marqué, Stéphane Donati, Julien Charpentier, Nicolas Pichon, Benjamin Zuber, Olivier Lesieur, Martial Ouendo, Anne Renault, Pascale Le Maguet, Stanislas Kandelman, Marie Thuong, Bernard Floccard, Chaouki Mezher, Marion Galon, Jacques Duranteau, Elie Azoulay
Journal: American Journal of Respiratory and Critical Care Medicine (2018)

Studies show that the quality of end-of-life communication and care have a significant impact on the living long after the death of a relative and have been implicated in the burden of psychological symptoms after the ICU experience. In the case of organ donation, the patient's relatives are centrally involved in the decision-making process; yet, few studies have examined the impact of the quality of communication on the burden of psychological symptoms after death.To assess the experience of the organ donation process and grief symptoms in relatives of brain-dead patients who discussed organ donation in the ICU.We conducted a multicenter longitudinal study in 28 ICUs in France. Participants were the relatives of brain-dead patients who were approached to discuss organ donation. Relatives were followed-up by phone at three time points: at 1 month, to complete a questionnaire describing their experience of the organ donation process; at 3 months, to complete the Hospital Anxiety and Depression Scale and the Impact of Event Scale-Revised; and at 9 months, to complete the Impact of Event Scale-Revised and the Inventory of Complicated Grief.In total, 202 relatives of 202 patients were included, of whom 158 consented to and 44 refused organ donation. Interviews were conducted at 1, 3, and 9 months with 78%, 68%, and 58% of relatives, respectively. The overall experience of the organ donation process was significantly more burdensome for relatives of nondonors. They were more dissatisfied with communication (27% vs. 10%; P = 0.021), more often shocked by the request (65% vs. 19%; P < 0.0001), and more often found the decision difficult (53% vs. 27%; P = 0.017). However, there were no significant differences in grief symptoms measured at 3 and 9 months between the two groups. Understanding of brain death was associated with grief symptoms; our results show a higher prevalence of complicated grief symptoms among relatives who did not understand the brain death process than among those who did (75% vs. 46.1%; P = 0.026).Experience of the organ donation process varied between relatives of donor versus nondonor patients, with relatives of nondonors experiencing lower-quality communication, but the decision was not associated with subsequent grief symptoms. Importantly, understanding of brain death is a key element of the organ donation process for relatives.
UK ranks in the middle of European healthcare survey
Authors: Rory Watson
Journal: BMJ (2018)

The UK emerges in 15th place in a European survey of national healthcare systems in 35 countries, released on 29 January.1 The ranking places the UK just ahead of Slovenia, the Czech Republic, and Spain in the middle of the field—the same as the previous year—and narrowly behind Slovakia and Portugal.

Compiled by the Health Consumer Powerhouse, the 2017 Euro Health Consumer Index assesses national performances on the basis of 46 indicators grouped under six criteria: patient rights, information, and e-health; accessibility (waiting time for treatment); outcomes; range and reach of …
Variations in DNA repair genomic alterations and tumor mutation burden in biliary tract cancer (BTC) subtypes.
Authors: Reham Abdel-Wahab, Siraj Mahamed Ali, Mitesh J. Borad, Rachna T. Shroff, Lawrence Kwong, Jean-Nicolas Vauthey, Eugene Jon Koay, Mingxin Zuo, Asif Rashid, Alexa Betzig Schrock, Jeffrey S. Ross, Tanios S. Bekaii-Saab, Milind M. Javle
Journal: Journal of Clinical Oncology (2018)

263 Background: DNA repair genomic alterations (GAs) have been identified in 12% of Intrahepatic cholangiocarcinoma (IHCCA), 26% of extrahepatic CCA (EHCCA) and 8% of gallbladder cancer (GBC) patients (pts) ( Cancer 2016;122:3838–3847). Recently, the Cancer Genome Atlas (TCGA) has described more than 20 mutated DNA repair genes, many of which were not previously represented in prior reports. DNA repair GAs including MSI are associated with higher tumor mutational burden (TMB). Our study aim is to identify variations in the frequency of DNA repair GAs in IHCCA, EHCCA, and GBC. Methods: Hybrid capture-based next-generation sequencing of 422 fixed formalin paraffin embedded (FFPE) tissue blocks of BTC including; 270 IHCCA, 60 EHCCA, and 92 GBC was performed. We included 20 DNA repair genes and classified them as "direct" DNA repair genes ( ATM, ATR, BRCA1, BRCA2, FANCA, FANCD2, MLH1, MSH2, MSH6, PALB2, POLD1, POLE, PRKDC, RAD50, SLX4) and "caretaker" genes that induce genomic instability ( BAP1, CDK12, MLL3, TP53, BLM). We calculated TMB on 1.1 Mb of sequenced DNA in 205 tissue specimens [138 IHCCA, 23 EHCCA, and 44 GBC] and classified into three groups; high (TMB-H; ≥ 20 mut/Mb), intermediate (TMB-I; 6-19mut/Mb) and low (TMB-L; &lt; 6mut/Mb). Results: A distinct pattern of DNA repair GAs in each tumor type was detected. (Table 1). DNA repair GAs were more commonly noted in both EHCCA and GB (63%) as compared with IHCAA (45.2%) (p= .002). Direct DNA repair GAs were highest within EHCCA (25%), while indirect DNA GAs were predominant in GBC (59.8%) (p= 0.04 and 0.001, respectively). The frequency of TMB-H and TMB-I differed significantly between BTC subtypes. Pts with EHCCA and GBC had significantly higher TMB-H and TMB-I versus IHCCA. Conclusions: The frequency of DNA repair GA’s is higher in EHCCA and GBC as compared with IHCCA. These results may have implications for clinical trials with DNA repair inhibitors and immune checkpoint blockers. [Table: see text]
Patient-Reported Distress in Myelodysplastic Syndromes and Its Association With Clinical Outcomes: A Retrospective Cohort Study
Authors: Jesse D. Troy, Carlos M. de Castro, Mary Ruth Pupa, Greg P. Samsa, Amy P. Abernethy, Thomas W. LeBlanc
Journal: Journal of the National Comprehensive Cancer Network (2018)

Background: NCCN defines distress as a multifactorial, unpleasant emotional experience of a psychological nature that may interfere with patients' ability to cope with cancer symptoms and treatment. Patients with myelodysplastic syndromes (MDS) are at risk for distress due to the largely incurable nature of this hematopoietic malignancy and its symptom burden, yet associations with clinical outcomes are unknown. Methods: We retrospectively reviewed patient-reported distress data from adult ambulatory patients with MDS visiting a single, tertiary care medical center from July 2013 to September 2015. Demographic, diagnostic, treatment, and comorbidity information were abstracted from records along with NCCN Distress Thermometer (DT) and Problem List (PL) scores. Survival was analyzed using the Kaplan-Meier method and Cox proportional hazards regression. Results: We abstracted 376 DT scores (median, 1; range, 0–10) from 606 visits and 110 patients (median, 2 DT scores/patient; range, 1–16). NCCN Guidelines suggest that patients with DT scores ≥4 should be evaluated for referral to specialty services to address unmet needs. A total of 54 patients (49%) had at least 1 DT score ≥4 and 20 (18%) had 2 or more DT scores ≥4; 98 patients (89.1%) reported 1,379 problems during 23,613 person-days of follow-up (median, 4 problems/patient/visit; range, 1–23). The 5 most frequently reported problems were fatigue (181 times; 78 patients), pain (95 times; 46 patients), worry (80 times; 45 patients), sleep (78 times; 41 patients), and tingling hands/feet (68 times; 33 patients). After adjustment for risk stratification at diagnosis, a single point increase on the DT was associated with an increased risk of death (hazard ratio, 1.18; 95% CI, 1.01–1.36). Conclusions: Patients with MDS experience a high burden of distress, and patient-reported distress is associated with clinical outcomes. Distress should be further studied as a prognostic variable and a marker of unmet needs in MDS.
Refractory or relapsed aggressive B-cell lymphoma failing (R)-CHOP: an analysis of patients treated on the RICOVER-60 trial
Authors: B. Glass, A.J. Dohm, L.H. Truemper, M. Pfreundschuh, A. Bleckmann, G.G. Wulf, A. Rosenwald, M. Ziepert, N. Schmitz
Journal: Annals of Oncology (2017)
Language Matters—Dermatologists Should Speak Out Against a Word Ban at Centers for Disease Control and Prevention
Authors: Misha Rosenbach, Kenneth A. Katz
Journal: JAMA Dermatology (2018)

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 Dermatology 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 Dermatology journal
Real world treatment patterns of first-line combination therapies among BRAF+ metastatic melanoma patients.
Authors: Sameer Ghate, Jackson Tang, Zhiyi Li, Antonio Reis Nakasato
Journal: Journal of Clinical Oncology (2018)

197 Background: For patients (pts) with metastatic melanoma (MM) and BRAF V600 mutation (BRAF+), options for first-line (1L) systemic combination therapy include immunotherapy (IO) or targeted therapy (TT). This study describes real world treatment patterns among BRAF+ MM pts treated with 1L ipilimumab+nivolumab (I+N) or dabrafenib+trametinib (D+T). Methods: This retrospective observational analysis used Flatiron Health’s electronic health record-derived database from Oct 2015 - Jul 2016. Oct 2015 was chosen as the start date as both combo use of I+N and D+T had been approved by the FDA. Pts were aged ≥18 years with a MM diagnosis, tested BRAF+ prior to therapy, and treated with either I+N or D+T as 1L therapy. Baseline demographic and clinical characteristics, and treatment patterns were collected from structured data and unstructured data in physician notes, and were descriptively assessed. Kaplan-Meier (KM) analysis measured time to discontinuation. Statistical inferences were not planned in this study. Results: Among 76 BRAF+ pts, 62% (47) were treated with D+T as 1L, and 38% (29) were treated with I+N as 1L. Compared to D+T pts, lower proportion of I+N pts had a history of brain metastases (31% vs. 34%) and elevated ( &gt; 333 IU/L) lactate dehydrogenase (10% vs. 19%), while a higher proportion of I+N pts reported ECOG performance status score of zero (38% vs. 23%). The two cohorts were similar in age, gender and baseline comorbidities. Discontinuation among D+T and I+N was 43% (20) and 48% (14) respectively. The primary reason for discontinuation was progression among D+T pts (10/20) vs. toxic effects of therapy among I+N pts (8/14). KM median time to discontinuation was 213 days for D+T pts vs. 196 days for I+N pts. 55% of I+N pts did not complete full induction of 4 doses of ipilimumab, citing toxic effects of therapy. Conclusions: 1L D+T patients had higher tumor burden, elevated LDH levels, and higher ECOG performance status score, but lower discontinuation rate and longer time to treatment discontinuation relative to BRAF+ 1L I+N pts.
Efficacy and Safety of Guselkumab, an Anti–interleukin 23 Monoclonal Antibody, for Palmoplantar Pustulosis
Authors: Tadashi Terui, Satomi Kobayashi, Yukari Okubo, Masamoto Murakami, Keiichiro Hirose, Hiroshi Kubo
Journal: JAMA Dermatology (2018)

Palmoplantar pustulosis (PPP) is a recalcitrant skin disease with no biologics currently approved for treatment. The involvement of interleukin 23 (IL-23) and cytokines of the type 17 helper T cell lineage in the pathogenesis of PPP has been recently postulated.To evaluate the efficacy and safety of guselkumab, an anti-IL-23 monoclonal antibody, in Japanese patients with PPP.This double-blind, randomized, placebo-controlled, parallel-group, 24-week trial was conducted between May 14, 2013, and September 27, 2014, at 11 centers in Japan. Participants were patients with moderate to severe PPP that did not respond adequately to conventional treatments.Patients were randomized 1:1 to receive guselkumab, 200 mg, by subcutaneous injection or matching placebo at weeks 0 and 4.Changes in total scores of skin-related outcomes from baseline at the end of week 16 (primary clinical cutoff) and through week 24 were measured. Serum biomarker analyses were performed at baseline, week 4, and week 16, and safety was monitored through week 24.Of 49 randomized patients (35 [71%] women; median [range] age, 52 [28-77] years), 41 completed the study at week 24. Mean (SD) PPP severity index total scores (primary end point) improved significantly from baseline in guselkumab-treated patients (-3.3 [2.43]) vs placebo (-1.8 [2.09]) (least squares mean difference, -1.5; 95% CI, -2.9 to -0.2; P = .03). At week 16, PPP area and severity index scores (least squares mean difference, -5.65; 95% CI, -9.80 to -1.50; P = .009) and proportion of patients achieving 50% reduction in these scores (difference in proportion, 39.2; 95% CI, 14.0-64.3; P = .009) improved significantly. A numerically higher proportion of patients had a physician's global assessment score of 1 or less in the guselkumab group vs placebo. Improvement in efficacy scores was maintained through week 24 in the guselkumab group. Significant reductions from baseline in serum IL-17A and IL-17F cytokine levels were observed at weeks 4 and 16. Frequency of treatment-emergent adverse events was comparable between the guselkumab group (19 of 25 patients [76%]) and the placebo group (18 of 24 patients [75%]). Frequent adverse effects included nasopharyngitis (14 patients [29%]), headache (3 patients [6%]), contact dermatitis (3 patients [6%]), and injection site erythema (3 patients [6%]). No major safety concerns emerged during the study.Targeting IL-23 and its associated immune cascade with guselkumab may be a safe and useful therapeutic option for treatment of PPP.clinicaltrials.gov Identifier: NCT01845987.
Augmentation of NAD+ levels by enzymatic action of NAD(P)H quinone oxidoreductase 1 attenuates adriamycin-induced cardiomyopathy
Authors: D. Khadka, G.-S. Oh, H.-J. Kim, S.-H. Lee, A. Shen, S.-B. Lee, A. Pandit, S. Sharma, S.-H. Yang, H.-S. So
Journal: Annals of Oncology (2018)
Expression of PD-L1 in periampullary adenocarcinoma: Relationship with morphological type, the immune microenvironment and prognosis.
Authors: Bahar Matilda Rastegar Nezhad, Margareta Heby, Sebastian Lundgren, Bjorn Nodin, Karin Leandersson, Jacob Elebro, Emelie Karnevi, Karin Jirstrom
Journal: Journal of Clinical Oncology (2018)

268 Background: Overall survival for patients with periampullary adenocarcinoma, including pancreatic cancer, continues to be poor. Pancreatic cancer is characterized by a largely immunosuppressive microenvironment, but blockade of the programmed death ligand 1 (PD-L1) pathway has still not been effective. Reports on the prognostic value of PD-L1 expression in pancreatic and in particular periampullary cancer are sparse. The aim of this study was therefore to analyze PD-L1 expression in periampullary adenocarcinoma, with specific reference to morphological type, tumor-infiltrating immune cells, and survival. Methods: PD-L1 expression in tumor cells (TC) and immune cells (IC) was assessed by immunohistochemistry on tissue microarrays with primary tumors from a retrospective consecutive cohort of 175 patients with resected periampullary adenocarcinoma, 65 of intestinal(I)-type and 110 of pancreatobiliary(PB)-type. Correlations with various immune cells were calculated with non-parametric tests. Cox proportional hazards models were applied to calculate hazard ratios (HR) and 95% confidence intervals (CI) for death. Results: TC PD-L1 expression was not associated with any clinicopathological factors nor with survival. IC PD-L1 ( &gt; 10%) expression was higher in I-type than in PB-type tumors (p &lt; 0.001), and correlated with defect mismatch repair (p = 0.012) and lymph node negativity (p = 0.016). IC PD-L1 was not prognostic in PB-type tumors. High IC PD-L1 was associated with a prolonged survival in the entire cohort (HR = 0.59, CI 0.40-0.88), and in I-type tumors (HR = 0.38, CI 0.18-0.81), but not after adjustment for other prognostic factors. In I-type tumors, high IC PD-L1 correlated with high density of T cells (CD3+, CD8+, FoxP3+), but not with B cell or macrophage density. There were no significant associations between IC PD-L1 expression and any other immune cells in PB-type tumors. Conclusions: High PD-L1 expression in IC is associated with a T cell dense tumor microenvironment and a prolonged survival in I-type, but not in PB-type, periampullary adenocarcinoma, thus indicating that the effect of immune-modulating therapies may differ by morphological type.
ASSOCIATION BETWEEN ELEVATED B-TYPE NATRIURETIC PEPTIDE, DISEASE PROGRESSION, AND CLINICAL OUTCOMES AMONG PATIENTS WITH ATRIAL FIBRILLATION
Authors: Taku Inohara, Sunghee Kim, Karen Pieper, Rosalia Blanco, Larry Allen, Gregg C. Fonarow, Bernard Gersh, Michael Ezekowitz, Peter Kowey, James A. Reiffel, Gerald Naccarelli, Paul Chan, Kenneth Mahaffey, Daniel Singer, James Freeman, Benjamin Steinberg, Eric D. Peterson, Jonathan Piccini
Journal: Journal of the American College of Cardiology (2018)
Targeting the MALAT1/PARP1/LIG3 complex induces DNA damage and apoptosis in multiple myeloma
Authors: Yi Hu, Jianhong Lin, Hua Fang, Jing Fang, Chen Li, Wei Chen, Shuang Liu, Sarah Ondrejka, Zihua Gong, Frederic Reu, Jaroslaw Maciejewski, Qing Yi, Jian-Jun Zhao
Journal: Leukemia (2018)
A novel morphologic and metabolic feature fused treatment response evaluation pipeline for pancreatic adenocarcinoma patients.
Authors: Yi Lao, John David, Arman Torosian, Wensha Yang, Richard Tuli
Journal: Journal of Clinical Oncology (2018)

311 Background: Adaptive radiation therapy for pancreatic adenocarcinoma (PA) relies on accurate treatment response assessment. Traditional RECIST criteria poorly characterize tumors with complex morphological features, while PET imaging inefficiently detects tumors with intrinsically low standardized uptake value (SUV). Here, we performed regional comparisons of 3D intact PA surfaces pre and post chemoradiotherapy (CRT) utilizing surface measurements containing both morphological and metabolic features to better assess response. Methods: Twenty-one locally advanced PA patients with pre- and 6-8 week post-CRT 18F FDG-PET/CT scans were evaluated. Boundaries of initial and post-CRT tumors were manually defined on respective CT images. On each of the tumors, 3D meshes were generated, followed by surface based registration to achieve vertex-wise correspondence. For each surface vertex, a multivariate vector was formed from two components: anatomic (deformation tensors resulted from surface registration), and metabolic (regional SUV obtained from radius to surface projections). To assess tumor response, paired mahabanobis distance (M dist ) between pre- and post-CRT tumor surfaces with previously formed multivariate vectors were calculated for each patient. M dist was evaluated using Cox analysis correlated with overall survival (OS) and compared with measurements based on serum CA19-9, volume, SUV max and SUV mean . Results: Among all the tested parameters, M dist is the best predictor of OS, with a hazard ratio of 0.437 (p = 0.036). Post-CRT versus pre-CRT ratios based on volume and SUV max both reached borderline significance (p = 0.0769 and 0.0799, respectively), while CA19-9 and SUV mean failed in predicting OS in our small cohort of patients. Conclusions: We introduced a PET/CT-based novel morphologic and metabolic pipeline for post-CRT response evaluation in locally advanced PA. The fused M dist outperformed traditional morphologic, metabolic, and physiological measurements in OS prediction. The presented fused model may serve as a new biomarker to better characterize the heterogeneity of tumor response to CRT and a predictive marker for surgical resection.
4-1BB costimulation induces T cell mitochondrial function and biogenesis enabling cancer immunotherapeutic responses
Authors: Ashley V. Menk, Nicole E. Scharping, Dayana B. Rivadeneira, Michael J. Calderon, McLane J. Watson, Deanna Dunstane, Simon C. Watkins, Greg M. Delgoffe
Journal: The Journal of Experimental Medicine (2018)

Despite remarkable responses to cancer immunotherapy in a subset of patients, many patients remain resistant to these therapies. The tumor microenvironment can impose metabolic restrictions on T cell function, creating a resistance mechanism to immunotherapy. We have previously shown tumor-infiltrating T cells succumb to progressive loss of metabolic sufficiency, characterized by repression of mitochondrial activity that cannot be rescued by PD-1 blockade. 4-1BB, a costimulatory molecule highly expressed on exhausted T cells, has been shown to influence metabolic function. We hypothesized that 4-1BB signaling might provide metabolic support to tumor-infiltrating T cells. 4-1BB costimulation of CD8+ T cells results in enhanced mitochondrial capacity (suggestive of fusion) and engages PGC1α-mediated pathways via activation of p38-MAPK. 4-1BB treatment of mice improves metabolic sufficiency in endogenous and adoptive therapeutic CD8+ T cells. 4-1BB stimulation combined with PD-1 blockade results in robust antitumor immunity. Sequenced studies revealed the metabolic support afforded by 4-1BB agonism need not be continuous and that a short course of anti–4-1BB pretreatment was sufficient to provide a synergistic response. Our studies highlight metabolic reprogramming as the dominant effect of 4-1BB therapy and suggest that combinatorial strategies using 4-1BB agonism may help overcome the immunosuppressive metabolic landscape of the tumor microenvironment.