tbuckley/cabot-search huggingface dataset:
Abstract 15465: Precision Medicine Approach to Resistant Hypertension: Genetic Markers of Resistant Hypertension Through a Genome-wide Association Study (GWAS) in the Secondary Prevention of Subcortical Strokes (SPS3)
Authors: Nihal El Rouby, Caitrin W McDonough, Yan Gong, Leslie A McClure, Braxton D Mitchell, Richard B Horenstein, Robert L Talbert, Atsushi Takahashi, Toshihiro Tanaka, Michiaki Kubo, Carl Pepine, Rhonda M Cooper-DeHoff, Oscar Benavente, Alan R Shuldiner, Julie A Johnson
Journal: Circulation (2015)

Introduction: Resistant hypertension (RHTN), a blood pressure (BP) ≥140/90 mm Hg despite ≥ 3 antihypertensive drugs or BP &lt; 140/90 mm Hg using ≥ 4 drugs, is associated with increased incidence of adverse cardiovascular outcomes, especially stroke. Hypothesis and objective: We hypothesize common variants exist in the genes regulating BP response and may lead to RHTN in some patients. Methods: A discovery cohort of hypertensive participants were included as cases (as defined above) or controls (N=719; 263 whites, 322 Hispanics, and 134 African Americans) from SPS3-GENES. They were genotyped on the Illumina Omni 5 Exome chip. Multiple logistic regression analysis was conducted separately in each race using an additive genetic model, adjusting for predictors for RHTN, principle components for ancestry and BP target treatment arms. Results from the 3 racial groups were combined using meta-analysis with inverse-variance weighting, with the hypothesis that functional variants are consistent across races. The associations of seven SNPs that met the suggestive level of association (p &lt;1 x10-5) in the SPS3 meta-analysis were tested for replication in 1,194 participants (657 whites, and 537 Hispanics) from the INternational VErapamil-SR trandolapril STudy GENEtic Substudy (INVEST-GENES). Bonferroni adjusted p was set at 0.007 to correct for multiple comparisons. Combined meta-analysis between INVEST and SPS3 was conducted for replicated SNPs or SNPs that had consistent association in the two cohorts with a nominal significance. Results: A missense SNP (rs3766160; Asp114Asn) in CELA2B was associated with increased risk of RHTN in SPS3 (Combined OR=1.8, p=6x10-6)). The same SNP replicated in INVEST (Combined OR=1.3, p=0.004; INVEST/SPS3 meta-p=4.5x10-7). An intronic SNP rs3789592 in strong linkage disequilibrium (r2=0.98) with a missense SNP (rs1049434; Asp490Glu) in SLC16A1 was associated with RHTN in SPS3 (Combined OR=2.0, p=7.6x10-7) and had a consistent association in INVEST (Combined OR=1.2, p=0.048; INVEST/SPS3 meta-p=7.6x10-7). Conclusion: Genetic loci in CELA2B, SLC16A1 were identified and confirmed for association in two cohorts. These associations, if further validated may help identify those patients at risk for RHTN.
Improving Health Care Value by Considering Cost-effectiveness—Reply
Authors: Ankur Pandya
Journal: JAMA (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 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
Prognostic value of patient-reported outcomes (PROs) in advanced cancer.
Authors: Shiven B. Patel, Wallace L. Akerley, Dominik Ose, Tyler Haydell, Jim Martineau, William A. Dunson, Anna Weinberg Chalmers, Laura Cannon, Neal J. Meropol, Ben Haaland
Journal: Journal of Clinical Oncology (2018)

8 Background: Performance status, which is prognostic of survival, is a physician’s interpretation of PROs. This retrospective study evaluated prognosis of PROs, independent of physician assessment, with overall survival (OS) and hospitalization-free survival (HFS). Methods: Patients (pts) at HCI were assessed using the NCI PROMIS-Ca bank from May 2016. Physical function (PF), fatigue, depression, anxiety, and pain scores were collected via iPad in pts with metastatic cancers. A single PRO score collected within 6 months of metastatic diagnosis for each pt was merged with outcome data using the Flatiron Health database. Associations between PROs, gender, cancer type, OS and HFS were assessed. Results: 287 complete sets of pt data were available. The PRO domains were interrelated with moderate-strong correlations (0.40-0.79). Cancer types differed by OS and HFS (p’s &lt; 0.001). PF scores were worse for NSCLC than other cancers (p &lt; 0.001). Individual PRO scores were worse for women than men, HFS was better for women and survival was not different. All individual PRO domains were strongly associated with HFS and OS. After correction for gender, cancer type, and individual PROs, only PF remained significant among individual PROs. Conclusions: PROs, especially PF, are prognostic of OS and HFS without physician interpretation. Gender difference may influence PROs. [Table: see text]
CDKN2A germline mutations are not associated with poor survival in an Italian cohort of melanoma patients
Authors: Bruna Dalmasso, Lorenza Pastorino, Giulia Ciccarese, Virginia Andreotti, Federica Grillo, Luca Mastracci, Francesco Spagnolo, Alberto Ballestrero, Paola Queirolo, William Bruno, Paola Ghiorzo
Journal: Journal of the American Academy of Dermatology (2018)
Induction of resistance to chimeric antigen receptor T cell therapy by transduction of a single leukemic B cell
Authors: Marco Ruella, Jun Xu, David M. Barrett, Joseph A. Fraietta, Tyler J. Reich, David E. Ambrose, Michael Klichinsky, Olga Shestova, Prachi R. Patel, Irina Kulikovskaya, Farzana Nazimuddin, Vijay G. Bhoj, Elena J. Orlando, Terry J. Fry, Hans Bitter, Shannon L. Maude, Bruce L. Levine, Christopher L. Nobles, Frederic D. Bushman, Regina M. Young, John Scholler, Saar I. Gill, Carl H. June, Stephan A. Grupp, Simon F. Lacey, J. Joseph Melenhorst
Journal: Nature Medicine (2018)
Abstract 20295: Endothelial ERK5 Signaling is Critical for Cardiovascular Homeostasis
Authors: Irinna Papangeli, Saejeong Park, Takaomi Adachi, Hyung J Chun
Journal: Circulation (2017)

Introduction: ERK5 is a member of the MAPK protein family involved in several crucial cellular functions, including cell proliferation, differentiation, and migration. Unlike the rest of the MAPK f...
Ongoing professional practice evaluation: An infrastructure for accountability.
Authors: Diane Denny, DBA, Danielle Gross, Gary Bernstein
Journal: Journal of Clinical Oncology (2018)

239 Background: As a national network of five hospitals treating patients fighting complex cancers, continuous monitoring of clinical staff competence is a priority. Recognizing an opportunity for an enhanced structure for ongoing professional practice evaluation (OPPE), a process mandated by The Joint Commission, the network set out to create heightened accountability, reliability and understanding of the review of performance data. Methods: Two work groups were established. The first was charged with the selection of meaningful specialty specific measures applicable to the oncology patient population. The second tasked to leverage resources expended using existing software and limiting the need for manual intervention. This group was responsible for creation and implementation of a consistent workflow with defined roles for physicians, medical staff operations and quality reviewers. Results: Over 50 subspecialties were mapped to over 250 selected metrics, with overlap when applicable to more than one specialty. A standard network-wide policy was approved by each center’s medical executive team. A workflow was clearly defined to include responsibilities associated with (pre-review) analyst role, service chief and credential committee. The use of the network’s reporting tool was standardized for OPPE as well as additional sources of quality data identified outside of the tool as needed, specifically for low volume and non-patient facing providers. A review calendar was created to guide the process on a rolling basis. Lastly, an OPPE Toolkit was created to govern and educate on the process that includes a pocket guide, Q&amp;A, and on-boarding materials for physicians to understand their data relevant to metrics for which they are accountable. Conclusions: This systemic and timely evaluation of practitioner specific data supports improvement of practitioner performance and provides objective information for credentialing and privileging decisions across the network. Physicians’ visibility into their own data has increased. Automating the majority of efforts associated with OPPE has reduced the time associated with fulfilling this external requirement and resulted in full compliance.
Hospitalization and hospital discharge destinations after chemotherapy: Using the Oncology Care Model (OCM) methodology in 2012–2015 Medicare data.
Authors: Yi Peng, Jiannong Liu, Leon Raskin, Michael Anthony Kelsh, Rebecca Zaha, Rohini K. Hernandez, David Henry, Gary H. Lyman
Journal: Journal of Clinical Oncology (2018)

113 Background: The Medicare OCM gives financial incentives for efficient, high-quality care. Hospitalizations of cancer patients receiving chemotherapy substantially increases costs. We assessed reasons for hospitalization and hospitalization discharge destinations after chemotherapy in cancer patients. Methods: We applied OCM methodology in a Medicare fee-for-service 20% sample data to estimate 6-month patient episodes triggered by chemotherapy from 2012 to 2015. We summarized the most frequent reasons for hospitalization (using ICD-9-CM codes in the first 5 positions of hospital claims) and the discharge destinations among all episodes and by cancer type. Results: Of 485,186 6-month episodes in 255,229 patients, 121,886 (25%) episodes had ≥1 hospitalization. The most frequent reasons for hospitalization were infection (13%), anemia (7%), dehydration (5%), and congestive heart failure (CHF; 3%; Table). Most hospitalized patients were discharged to home (71%) or a skilled nursing facility (SNF; 13%); some died in the hospital (6%) or went to hospice (5%). Reasons for hospitalization and discharge destination varied by cancer type. Patients with lung cancer had the highest rates of infection and anemia and higher proportions of death and hospice discharge compared with other cancers. Conclusions: Among Medicare beneficiaries receiving chemotherapy, hospitalizations most often occurred as a result of infection or anemia. Patients were most often discharged to home or SNF. Variations across cancer types in the reasons for hospitalization, as well as discharge destinations, should be considered when evaluating OCM practice performance. [Table: see text]
The Effect of Cancer Treatments on Telomere Length: A Systematic Review of the Literature
Authors: Lisa Gallicchio, Shahinaz M Gadalla, John D Murphy, Naoko I Simonds
Journal: JNCI Journal of the National Cancer Institute (2018)

It has been hypothesized that cancer treatments cause accelerated aging through a mechanism involving the shortening of telomeres. However, the effect of cancer treatments on telomere length is unclear.We systematically reviewed the epidemiological evidence evaluating the associations between cancer treatment and changes in telomere length. Searches were performed in PubMed for the period of January 1966 through November 2016 using the following search strategy: telomere AND (cancer OR tumor OR carcinoma OR neoplasm) AND (survivor OR patient). Data were extracted and the quality of studies was assessed.A total of 25 studies were included in this review. Ten were solid cancer studies, 11 were hematological malignancy studies, and 4 included a mixed sample of both solid and hematological cancers. Three of the 10 solid tumor studies reported a statistically significant association between cancer treatment and telomere length shortening, and one reported longer telomere length after treatment. Among the hematological cancer studies, three showed statistically significant decreases in telomere length with treatment, and two showed elongation. When these studies were rated using quality criteria, most of the studies were judged to be of moderate quality.The findings from this review indicate that the effect of cancer treatment on telomere length may differ by cancer type and treatment as well as other factors. Definitive conclusions cannot be made based on the published literature, because sample sizes tended to be small; treatments, cancer types, and biospecimens were heterogenous; and the length of follow-up times differed greatly.
Radioguided Surgery With Gallium for Neuroendocrine Tumors
Authors: James R. Howe
Journal: JAMA Surgery (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 Surgery 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 Surgery journal
<i>Notes from the Field:</i>Blastomycosis Cases Occurring Outside of Regions with Known Endemicity — New York, 2007–2017
Authors: Robert McDonald, Elizabeth Dufort, Brendan R. Jackson, Ellis H. Tobin, Alexandra Newman, Kaitlin Benedict, Debra Blog
Journal: MMWR Morbidity and Mortality Weekly Report (2018)

In October 2017, the New York State Department of Health was alerted by Albany-area infectious disease physicians about local cases of blastomycosis that included multiple severe infections in the state health department's Capital District, an area where Blastomyces spp. fungi are not considered endemic.
Transition of dose-adjusted EPOCH therapy into the outpatient healthcare setting: Quality and cost considerations for outpatient treatment.
Authors: Ali McBride, Kelly Yiu, Emad Elquza, Daniel Oscar Persky, Abhijeet Kumar
Journal: Journal of Clinical Oncology (2018)

110 Background: Dose-adjusted etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin (EPOCH)-containing regimens are frequently utilized in lymphoma, however, outpatient EPOCH or modified inpatient/outpatient EPOCH has not been described extensively. We transitioned inpatient EPOCH to the outpatient setting and modified EPCOH to be given in the inpatient setting with rituximab outpatient to improve quality of care and access to patient assistance programs. We describe our institutional experiences with inpatient and modified EPOCH to the outpatient setting. Methods: A single-center, institutional review board-approved retrospective study was conducted for adults receiving EPOCH-based regimens. Clinical and financial data were collected by chart review for each patient. Descriptive statistics were utilized for analysis. Results: A total of 31 patients received 116 cycles of an EPOCH-containing regimen (11 [9.5%] inpatient), 54 [46.5%] outpatient, and 51 [44.0%] hybrid inpatient and outpatient). Nine outpatient cycles, 9 (17.6%) hybrid cycles and no inpatient cycles resulted in admissions for FN. Two inpatient cycles were delayed (18.2%) due to disease-related procedures and one (9.1%) was delayed due to low blood counts. Five (9.2%) outpatient cycles were delayed due to logistics (i.e. insurance delays, scheduling errors) and two (3.7%) outpatient cycles were delayed due to disease-related adverse events (bowel obstruction, chest pain). Transitioning EPOCH to the outpatient setting decreased overall costs for hospital stays on average by $19,792 per cycle with an overall approximate cost savings to the health-system of 1,114,992 dollars with 432 bed days saved. Costs savings to patients with medications assistance programs is pending final analysis. Conclusions: EPOCH-containing regimens can be safely transitioned into the outpatient setting, side effects can be monitored and outcomes optimized, to better adapt treatment strategies for individualized patient therapies. As new healthcare payment models are developed, outpatient treatments allow for adaptive financial options both for the health-system and the patient.
Emerging Biomarkers, Tools, and Treatments for Diabetic Polyneuropathy
Authors: Gidon J Bönhof, Christian Herder, Alexander Strom, Nikolaos Papanas, Michael Roden, Dan Ziegler
Journal: Endocrine Reviews (2018)

Diabetic neuropathy, with its major clinical sequels, notably neuropathic pain, foot ulcers, and autonomic dysfunction, is associated with substantial morbidity, increased risk of mortality, and reduced quality of life. Despite its major clinical impact, diabetic neuropathy remains underdiagnosed and undertreated. Moreover, the evidence supporting a benefit for causal treatment is weak at least in patients with type 2 diabetes, and current pharmacotherapy is largely limited to symptomatic treatment options. Thus, a better understanding of the underlying pathophysiology is mandatory for translation into new diagnostic and treatment approaches. Improved knowledge about pathogenic pathways implicated in the development of diabetic neuropathy could lead to novel diagnostic techniques that have the potential of improving the early detection of neuropathy in diabetes and prediabetes to eventually embark on new treatment strategies. In this review, we first provide an overview on the current clinical aspects and illustrate the pathogenetic concepts of (pre)diabetic neuropathy. We then describe the biomarkers emerging from these concepts and novel diagnostic tools and appraise their utility in the early detection and prediction of predominantly distal sensorimotor polyneuropathy. Finally, we discuss the evidence for and limitations of the current and novel therapy options with particular emphasis on lifestyle modification and pathogenesis-derived treatment approaches. Altogether, recent years have brought forth a multitude of emerging biomarkers reflecting different pathogenic pathways such as oxidative stress and inflammation and diagnostic tools for an early detection and prediction of (pre)diabetic neuropathy. Ultimately, these insights should culminate in improving our therapeutic armamentarium against this common and debilitating or even life-threatening condition.
Learning-Related Plasticity in Dendrite-Targeting Layer 1 Interneurons
Authors: Elisabeth Abs, Rogier B. Poorthuis, Daniella Apelblat, Karzan Muhammad, M. Belen Pardi, Leona Enke, Dahlia Kushinsky, De-Lin Pu, Max Ferdinand Eizinger, Karl-Klaus Conzelmann, Ivo Spiegel, Johannes J. Letzkus
Journal: Neuron (2018)
Role of apurinic/apyrimidinic nucleases in the regulation of homologous recombination in myeloma: mechanisms and translational significance
Authors: Subodh Kumar, Srikanth Talluri, Jagannath Pal, Xiaoli Yuan, Renquan Lu, Puru Nanjappa, Mehmet K. Samur, Nikhil C. Munshi, Masood A. Shammas
Journal: Blood Cancer Journal (2018)

We have previously reported that homologous recombination (HR) is dysregulated in multiple myeloma (MM) and contributes to genomic instability and development of drug resistance. We now demonstrate that base excision repair (BER) associated apurinic/apyrimidinic (AP) nucleases (APEX1 and APEX2) contribute to regulation of HR in MM cells. Transgenic as well as chemical inhibition of APEX1 and/or APEX2 inhibits HR activity in MM cells, whereas the overexpression of either nuclease in normal human cells, increases HR activity. Regulation of HR by AP nucleases could be attributed, at least in part, to their ability to regulate recombinase (RAD51) expression. We also show that both nucleases interact with major HR regulators and that APEX1 is involved in P73-mediated regulation of RAD51 expression in MM cells. Consistent with the role in HR, we also show that AP-knockdown or treatment with inhibitor of AP nuclease activity increases sensitivity of MM cells to melphalan and PARP inhibitor. Importantly, although inhibition of AP nuclease activity increases cytotoxicity, it reduces genomic instability caused by melphalan. In summary, we show that APEX1 and APEX2, major BER proteins, also contribute to regulation of HR in MM. These data provide basis for potential use of AP nuclease inhibitors in combination with chemotherapeutics such as melphalan for synergistic cytotoxicity in MM.