tbuckley/cabot-search huggingface dataset:
Palliative care access for hospitalized patients with end‐stage liver disease across the United States
Authors: Barret Rush, Keith R. Walley, Leo A. Celi, Neil Rajoriya, Mayur Brahmania
Journal: Hepatology (2017)

Patients with end-stage liver disease (ESLD) often have a high symptom burden. Historically, palliative care (PC) services have been underused in this population. We investigated the use of PC services in patients with ESLD hospitalized across the United States. We used the Nationwide Inpatient Sample to conduct a retrospective nationwide cohort analysis. All patients >18 years of age admitted with ESLD, defined as those with at least two liver decompensation events, were included in the analysis. A multivariate logistic regression model predicting referral to PC was created. We analyzed 55,208,382 hospitalizations from the 2006-2012 Nationwide Inpatient Sample, with 39,349 (0.07%) patients meeting study inclusion. PC consultation was performed in 1,789 (4.5%) ESLD patients. The rate of PC referral in ESLD increased from 0.97% in 2006 to 7.1% in 2012 (P < 0.01). In multivariate analysis, factors associated with lower referral to PC were Hispanic race (odds ratio [OR], 0.77; 95% confidence interval [CI], 0.66-0.89; P < 0.01) and insurance coverage (OR, 0.74; 95% CI, 0.65-0.84; P < 0.01). Factors associated with increased referral to PC were age (per 5-year increase, OR, 1.05; 95% CI, 1.03-1.08; P < 0.01), do-not-resuscitate status (OR, 16.24; 95% CI, 14.20-18.56; P < 0.01), treatment in a teaching hospital (OR, 1.25; 95% CI, 1.12-1.39; P < 0.01), presence of hepatocellular carcinoma (OR, 2.00; 95% CI, 1.71-2.33; P < 0.01), and presence of metastatic cancer (OR, 2.39; 95% CI, 1.80-3.18; P < 0.01). PC referral was most common in west coast hospitals (OR, 1.81; 95% CI, 1.53-2.14; P < 0.01) as well as large-sized hospitals (OR, 1.49; 95% CI, 1.22-1.82; P < 0.01).From 2006 to 2012 the use of PC in ESLD patients increased substantially; socioeconomic, geographical, and ethnic barriers to accessing PC were observed. (Hepatology 2017;66:1585-1591).
Efficacy, quality of life, and tolerability of BP-C1, a benzene-poly-carboxylic acids complex with cis-diammineplatinum (II) dichloride, in patients with stage IV breast cancer: A randomized double-blinded placebo controlled study.
Authors: Stig Larsen, Alexey Manikhas, Ekaterina Trishkina, Elena Vladimir Poddubskaya, Marina P. Matrosova, Steen Lindkaer Jensen
Journal: Journal of Clinical Oncology (2014)

e12016 Background: The aim was to compare the efficacy, tolerability and quality of life of BP-C1versus Placebo in stage IV breast cancer. Methods: A randomized, double blind placebo controlled multicenter study with a sequential parallel group design with treatment duration of 32 days was performed. Placebo group was switched to BP-C1 at the end of the study. Twenty-nine stage IV breast cancer patients were allocated to either BP-C1 or Placebo. Patients were given daily i.m. injections of 0.035 mg/kg BW of BP-C1 or Placebo, continuously for 32 days. CT was performed at screening, after 32 days and 28 days after the last injection. Lesions were measured and classified with the RECIST criteria. EORTC QOL-C30 and BR23 were used for QOL registration, and NCI Bethesda (CTC-NCI) for tolerability. Results: Mean sum diameter of lesions increased non-significantly with 0.8 % (CI: -7.7 – 9.3%) in the BP-C1 group and significantly with 12.7% (CI: 4.1 – 21.1%) in the placebo group. The difference was significant in favor of BP-C1 (p=0.02). The placebo patients were hereafter switched to BP-C1 treatment for an additional 32 days and a non-significant increase of 3.8% (CI:-0.4 – 8.0 %) in the sum diameter was detected. Compared to the increase in the prior placebo period, this was found significant (p=0.036). The Max CTC-NCI was found to increase with one score in 3 patients and reduced in 2 patients in the BP-C1 group. Similarly, one patient was increased and one reduced in the placebo group during the 32 days of treatment. The sum CTC-NCT score increased with 9.2% (CI: -14.3 – 32.7%) in the BP-C1 group and with 21.7% (CI:-8.6 – 52.0%) in the placebo group. The placebo patients were switched to BP-C1 treatment for additionally 32 days and an increase in sum CTC-NCI of 5.9% (CI:-26.7 – 38.4 % (NS) was detected. Differences in increase in QOL in favor of BP-C1 were detected for all variables. Conclusions: BP-C1 has a significant effect compared to placebo on tumor growth. Treatment improved QOL and was well tolerated, whilst only few mild adverse events were detected. BP-C1 seems to be a promising treatment of advanced solid tumors.
Efficacy of tenofovir-based rescue therapy for chronic hepatitis B patients with resistance to lamivudine and entecavir
Authors: Hee-Jeong Jeon, Seok Won Jung, Neung Hwa Park, Yujin Yang, Jin-Hee Noh, Jae-Sung Ahn, Hyung Rae Kim, Jae Ho Lee, Jung Woo Shin
Journal: Clinical and Molecular Hepatology (2017)

See the commentary-article "Is tenofovir monotherapy a sufficient defense line against multi-drug resistant hepatitis B virus?" on page 219.
Physicians Interrupting Patients
Authors: Richard M. Frankel, Howard B. Beckman
Journal: JAMA (2017)

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 HomeNew OnlineCurrent IssueFor Authors 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) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More 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 journal
Hidradenitis suppurativa and electrocardiographic changes: a cross‐sectional population study
Authors: C.R. Juhl, I.M. Miller, G.B. Jemec, J.K. Kanters, C. Ellervik
Journal: British Journal of Dermatology (2017)

Hidradenitis suppurativa (HS) is a chronic, inflammatory skin disease, recently associated with metabolic syndrome, subclinical atherosclerosis and increased risk of cardiovascular disease.To investigate the hitherto unknown electrocardiographic (ECG) changes associated with HS, which have recently been associated with significant cardiovascular burden.Data were obtained from the cross-sectional Danish General Population Study (GESUS). HS diagnosis was based on a validated self-reported questionnaire; 404 individuals met the HS diagnosis criteria and 19 001 controls without HS were identified. Severity of HS was staged according to a modified Hurley score. The ECG parameters of heart rate (HR), PR interval, QRS duration, JTc interval and QTc interval were obtained from 12-lead resting ECGs. We investigated the difference in means by unpaired t-test or anova.HR was significantly higher [mean difference 2·3 beats per min (bpm), 95% confidence interval (CI) 1·2-3·4; P < 0·01] when adjusting for age and sex, but when adjusting for multivariates, there was no significant difference (0·3 bpm, 95% CI -0·7 to 1·4; P = 0·52). Severe HS was significantly associated with increased HR across all models (2·9 bpm, 95% CI 0·7-5·1; P = 0·01). Mean QRS duration was significantly shorter in the group with mild HS but not in the groups with moderate and severe HS.Mean resting HR in patients with severe HS was significantly higher compared with controls. Given that resting HR is associated with increased risk of all-cause and cardiovascular mortality, and that patients with HS have increased risk of cardiovascular events, this finding is potentially important, easily testable and intervenable.
Abstract LB-291: Identification of CMTM6 and CMTM4 as PD-L1 protein regulators
Authors: Chong Sun, Riccardo Mezzadra, Lucas T. Jae, Raquel Gomez-Eerland, Evert de Vries, Wei Wu, Yanling Xiao, Albert J. Heck, Jannie Borst, Thijn R. Brummelkamp, Ton N. Schumacher
Journal: Cancer Research (2017)

Abstract The clinical benefit in patients with diverse types of metastatic cancers that is observed upon blockade of the PD-1 - PD-L1 interaction has highlighted the importance of this inhibitory axis in the suppression of human tumor-specific T cell responses. In spite of the key role of PD-L1 expression by cells within the tumor microenvironment, our understanding of the regulation of the PD-L1 protein is limited. Using a haploid genetic screen, we here identify CMTM6, a poorly described type 3 transmembrane protein of previously unknown function, as a regulator of the PD-L1 protein. Interference with CMTM6 expression results in impaired PD-L1 protein expression in all tumor cell types tested and also in primary human dendritic cells. Furthermore, through both a haploid genetic modifier screen in CMTM6 deficient cells and genetic complementation experiments, we demonstrate that this function is shared by its closest family member CMTM4, but not by all other CMTM members tested. Notably, CMTM6 increases the PD-L1 protein pool without affecting PD-L1 transcript levels. Rather, we demonstrate that CMTM6 is present at the cell surface, associates with PD-L1 protein, and increases PD-L1 protein half-life. Consistent with this role, T cell inhibitory capacity of PD-L1 expressing tumor cells is enhanced by CMTM6. Collectively, our data reveal that PD-L1 relies on CMTM6/4 to efficiently carry out its inhibitory function, and suggest potential new avenues to block this pathway. [C.S., R.M., and L.T.J. contributed equally to this work. T.R.B. and T.N.M.S. are both corresponding authors.] Citation Format: Chong Sun, Riccardo Mezzadra, Lucas T. Jae, Raquel Gomez-Eerland, Evert de Vries, Wei Wu, Yanling Xiao, Albert J. Heck, Jannie Borst, Thijn R. Brummelkamp, Ton N. Schumacher. Identification of CMTM6 and CMTM4 as PD-L1 protein regulators [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr LB-291. doi:10.1158/1538-7445.AM2017-LB-291
LSD1 Inhibitor T-3775440 Inhibits SCLC Cell Proliferation by Disrupting LSD1 Interactions with SNAG Domain Proteins INSM1 and GFI1B
Authors: Shinji Takagi, Yoshinori Ishikawa, Akio Mizutani, Shinji Iwasaki, Satoru Matsumoto, Yusuke Kamada, Toshiyuki Nomura, Kazuhide Nakamura
Journal: Cancer Research (2017)

T-3775440 is an irreversible inhibitor of the chromatin demethylase LSD1, which exerts antiproliferative effects by disrupting the interaction between LSD1 and GFI1B, a SNAG domain transcription factor, inducing leukemia cell transdifferentiation. Here, we describe the anticancer effects and mechanism of action of T-3775440 in small-cell lung cancer (SCLC). T-3775440 inhibited proliferation of SCLC cells in vitro and retarded SCLC tumor growth in vivo T-3775440 disrupted the interaction between LSD1 and the transcriptional repressor INSM1, thereby inhibiting expression of neuroendocrine-associated genes, such as ASCL1 INSM1 silencing phenocopied the effects of T-3775440 on gene expression and cell proliferation, consistent with the likelihood T-3775440 mediated its effects in SCLC by inhibiting INSM1. T-3775440 also inhibited proliferation of an SCLC cell line that overexpressed GFI1B, rather than INSM1, by disrupting the interaction between LSD1 and GFI1B. Taken together, our results argue that LSD1 plays an important role in neuroendocrine-associated transcription and cell proliferation of SCLC via interactions with the SNAG domain proteins INSM1 and GFI1B. Targeting these critical interactions with LSD1 inhibitors offers a novel rational strategy to therapeutically manage SCLC. Cancer Res; 77(17); 4652-62. ©2017 AACR.
Safety, Phamacokinetics (PK), Pharmacodynamics (PD) and Preliminary Activity in Acute Leukemia of Ory-1001, a First-in-Class Inhibitor of Lysine-Specific Histone Demethylase 1A (LSD1/KDM1A): Initial Results from a First-in-Human Phase 1 Study
Authors: Tim Somervaille, Olga Salamero, Pau Montesinos, Christophe Willekens, Jose Antonio Perez Simon, Arnaud Pigneux, Christian Recher, Rakesh Popat, Cesar Molinero, Christina Mascaro, Tamara Maes, Francesc Bosch
Journal: Blood (2016)
Multistate Outbreak of <i>Salmonella</i> Anatum Infections Linked to Imported Hot Peppers — United States, May–July 2016
Authors: Rashida Hassan, Joshua Rounds, Alida Sorenson, Greg Leos, Jeniffer Concepción-Acevedo, Taylor Griswold, Adiam Tesfai, Tyann Blessington, Cerise Hardy, Colin Basler
Journal: MMWR Morbidity and Mortality Weekly Report (2017)

Foodborne salmonellosis causes an estimated 1 million illnesses and 400 deaths annually in the United States (1). Salmonella Anatum is one of the top 20 Salmonella serotypes in the United States. During 2013-2015 there were approximately 300-350 annual illnesses reported to PulseNet, the national molecular subtyping network for foodborne disease surveillance. In June 2016, PulseNet identified a cluster of 16 Salmonella Anatum infections with an indistinguishable pulsed-field gel electrophoresis (PFGE) pattern from four states.* In April 2016, the same PFGE pattern had been uploaded to PulseNet from an isolate obtained from an Anaheim pepper, a mild to medium hot pepper. Hot peppers include many pepper varieties, such as Anaheim, jalapeño, poblano, and serrano, which can vary in heat level from mild to very hot depending on the variety and preparation. This rare PFGE pattern had been seen only 24 times previously in the PulseNet database, compared with common PFGE patterns for this serotype which have been seen in the database hundreds of times. Local and state health departments, CDC, and the Food and Drug Administration (FDA) investigated to determine the cause of the outbreak. Thirty-two patients in nine states were identified with illness onsets from May 6-July 9, 2016. Whole-genome sequencing (WGS) was performed to characterize clinical isolates and the Anaheim pepper isolate further. The combined evidence indicated that fresh hot peppers were the likely source of infection; however, a single pepper type or source farm was not identified. This outbreak highlights challenges in reconciling epidemiologic and WGS data, and the difficulties of identifying ingredient-level exposures through epidemiologic investigations alone.
Phase Ib/2 study of venetoclax with low-dose cytarabine in treatment-naive patients age ≥ 65 with acute myelogenous leukemia.
Authors: Tara L. Lin, Stephen Anthony Strickland, Walter Fiedler, Roland B. Walter, Jing-Zhou Hou, Gail J. Roboz, Anoop Enjeti, Kaffa Mussumeh Fakhoui, David E Darden, Martin Dunbar, Ming Zhu, John W. Hayslip, Andrew H. Wei
Journal: Journal of Clinical Oncology (2016)

7007 Background: Treatment options for older patients (pts) with acute myelogenous leukemia (AML) unfit for intensive chemotherapy are limited. Expected complete remission rates for low-dose cytarabine (LDAC) are about 10% in this population. Targeting the pro-survival molecule BCL-2 has demonstrated clinical efficacy as a therapeutic strategy in various hematologic malignancies. Venetoclax (VEN), a selective BCL-2 inhibitor, shows synergy with cytarabine in several AML cell lines and primary samples. Methods: This is a non-randomized, open-label phase 1/2 dose-escalation/expansion study of VEN + LDAC, in treatment-naïve AML pts ≥ 65 years not eligible for intensive chemotherapy. Pts receive oral VEN once daily (QD) on days 1‒28 and subcutaneous LDAC 20 mg/m2 QD on days 1‒10 of each 28-day cycle. VEN dose escalation follows a 3 + 3 design; dose-limiting toxicities (DLTs: grade 4 toxicity, platelet count < 25,000/μL, or absolute neutrophil count < 500/μL within 14 days of last VEN dose) areassessed during cycle 1, up to day 42. Primary objectives include safety and preliminary efficacy evaluations. Results: As of Oct 1 2015, 18 pts (66.7% male; median age 74 years) have received LDAC + VEN in the phase 1 portion (VEN 600 mg target dose [n = 8]; VEN 800 mg target dose [n = 10]). Median time on study is 127.5 (range 30‒272) days; 9 pts (50%) remain on study. DLTs of Grade 4 thrombocytopenia lasting > 42 days without evidence of residual leukemia occurred in 2 pts in the VEN 800 mg dose group. The recommended phase 2 dose is 600 mg. Adverse events (AEs; ≥ 30% prevalence) were nausea (77.8%), anemia (55.6%), febrile neutropenia, neutropenia, fatigue (each 38.9%), vomiting, diarrhea and hypokalemia (each 33.3%). The most common serious AE was febrile neutropenia (33.3%). No clinically significant tumor lysis syndrome was observed. The overall response rate in phase 1 was 44% (complete remission, n = 4; complete remission without complete marrow recovery, n = 4; resistant disease, n = 8; death before evaluation, n = 2). Conclusions: Initial findings suggest that VEN + LDAC has acceptable tolerability and promising clinical activity in older, treatment-naïve AML pts. Available phase 2 updates will be presented. Clinical trial information: NCT02287233.
Abstract P103: Effect of Agents Specific to Triglyceride Lowering, Statins Alone, or a Combination of Both Among Patients with Diabetes and Very High Triglycerides
Authors: Gregory A Nichols, Kristi Reynolds, Teresa M Kimes, Tope Olufade, Deborah Anzalone, Stephen P Fortmann
Journal: Circulation (2016)

Background: Severe hypertriglyceridemia is an often-neglected risk factor that is associated with increased risk of cardiovascular disease, pancreatitis and mortality, especially when other comorbidities are present. We investigated the association between triglyceride (TG)-lowering therapy and subsequent reduction in TG levels in patients with diabetes and very high triglycerides (VHTG). Methods: We combined data from the Southern California and Northwest regions of Kaiser Permanente to identify patients with diabetes and a TG measurement &gt; 500 mg/dL with a follow-up measure 6-15 months later. Patients were stratified by whether they received no treatment, pharmacotherapy specific to TG lowering (fibrates, niacin, omega-3 products) only, a statin only or a combination of both between the two TG measures. We compared the characteristics of the four groups of patients and constructed a multivariable logistic regression model to determine the probability of achieving TG &lt;500 mg/dL following therapy, controlling for other characteristics. Results: Of the 3,188 diabetic patients with VHTG, 23% received no therapy, 8% received a TG-specific drug only (72% fibrates, 27% niacin, 1% omega-3), 55% received a statin only, and 14% received both. Compared with no treatment, those receiving a TG-specific agent were not significantly more likely to attain TG &lt;500 mg/dL. However, patients receiving a statin only were more likely to do so (OR 1.79, 95% CI 1.42-2.25), as were patients receiving both a statin and TG-specific agent (1.77, 1.29-2.43). In addition to higher initial TG level, non-Hispanic blacks (1.81, 1.07-3.05), Hispanics (1.26, 1.03-1.54), and men (1.43, 1.16-1.75) were more likely to attain TG level &lt;500 mg/dL. Lower A1C (0.91, 0.87-0.96), systolic blood pressure (0.98, 0.97-0.99), and higher HDL-C (1.02, 1.01-1.04) were also associated with attaining TG &lt;500 mg/dL. Conclusion: Our results suggest that pharmacotherapy is essential for the attainment of TG levels &lt;500 mg/dL in patients with diabetes and VHTG. Because better control of other risk factors was also associated with TG improvement, uncontrolled VHTG may represent an important marker or additional risk factor for diabetes complications that deserves consideration.
RAS Pathway Mutations Are Associated with Proliferative Features and Frequently Co-Occur with TET2 mutationsin Philadelphia Negative MPN Subtypes
Authors: Bartlomiej M Getta, Emily C Zabor, Sean Devlin, Kristina Marie Knapp, Minal Patel, Abhinita Mohanty, Marcel van den Brink, Maria Arcila, Ross L. Levine, Rapaport Franck, Raajit K. Rampal
Journal: Blood (2016)
Diabetes in a Large Dementia Cohort: Clinical Characteristics and Treatment From the Swedish Dementia Registry
Authors: Juraj Secnik, Pavla Cermakova, Seyed-Mohammad Fereshtehnejad, Pontus Dannberg, Kristina Johnell, Johan Fastbom, Bengt Winblad, Maria Eriksdotter, Dorota Religa
Journal: Diabetes Care (2017)

OBJECTIVE We aimed to investigate the differences in clinical characteristics and pharmacological treatment associated with the presence of diabetes in a large cohort of patients with dementia. RESEARCH DESIGN AND METHODS A cross-sectional registry-based study was conducted using data from the Swedish Dementia Registry (SveDem). Data on dementia diagnosis, dementia type, and demographic determinants were extracted from SveDem. Data from the Swedish Patient Register and Prescribed Drug Register were combined for the diagnosis of diabetes. Data on antidiabetic, dementia, cardiovascular, and psychotropic medications were extracted from the Swedish Prescribed Drug Register. Logistic regression was used to determine whether the variables were associated with diabetes after adjustment for confounders. In total, 29,630 patients were included in the study, and 4,881 (16.5%) of them received a diagnosis of diabetes. RESULTS In the fully adjusted model, diabetes was associated with lower age at dementia diagnosis (odds ratio [OR] 0.97 [99% CI 0.97–0.98]), male sex (1.41 [1.27–1.55]), vascular dementia (1.17 [1.01–1.36]), and mixed dementia (1.21 [1.06–1.39]). Dementia with Lewy bodies (0.64 [0.44–0.94]), Parkinson disease dementia (0.46 [0.28–0.75]), and treatment with antidepressants (0.85 [0.77–0.95]) were less common among patients with diabetes. Patients with diabetes who had Alzheimer disease obtained significantly less treatment with cholinesterase inhibitors (0.78 [0.63–0.95]) and memantine (0.68 [0.54–0.85]). CONCLUSIONS Patients with diabetes were younger at dementia diagnosis and obtained less dementia medication for Alzheimer disease, suggesting less optimal dementia treatment. Future research should evaluate survival and differences in metabolic profile in patients with diabetes and different dementia disorders.