tbuckley/cabot-search huggingface dataset:
History, Indian Health
Authors: Everett R. Rhoades
Journal: JAMA (2005)

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
A prospective study assessing the value of geriatric assessment in elderly patients with stage III NSCLC for concurrent chemoradiation.
Authors: Maite Antonio Rebollo, Jenniffer Linares Aceituno, Juana Saldana, Arturo Navarro, Maria Dolores Arnaiz, Jose Carlos Ruffinelli, Ramon Palmero, Maria Plana, Isabel Brao, Susana Padrones, Valentín Navarro-Perez, Felipe Cardenal, Ernest Nadal-Alforja
Journal: Journal of Clinical Oncology (2016)

8509 Background: Concurrent chemoradiotherapy (cCRT) has proven to increase survival in elderly patients (p) with unresectable stage III NSCLC, but it is not yet accepted as standard of care. The geriatric assessment (GA) might help to characterize p who benefit from cCRT. Methods: Elderly p ( ≥ 74 years) with stage III NSCLC underwent GA, including validated instruments to assess comorbidity, polypharmacy, functional status, geriatric syndromes (GS), mood, cognition and Vulnerable Elders Survey (VES-13). P were classified according to the GA into fit and medium fit who were deemed candidates for antitumoral treatment and unfit patients received best supportive care. Clinical, GA and follow-up data were prospectively collected. Median overall survival (mOS) was calculated using Kaplan-Meier method. Results: From 07/2008 to 11/2015, 73 elderly p with unresectable stage III NSCLC were identified. Median age: 79.5 (74-86); gender (M/F): 88%/12%; histology (SCC/AD/NOS): 58%/22%/20%; stage (IIIA/IIIB): 67%/33%; median Karnofsky: 80% (60-100).GA groups (fit/medium fit/unfit): 38%/44%/18%; comorbidities ( ≥ 5/ < 5): 47%/53%; drugs ( ≥ 5/ < 5): 66%/34%; Barthel ( < 95/ ≥ 95): 21%/79%; Lawton-Brody ( < 4/ ≥ 4): 19%/81%; GS (yes/no): 10%/90%; Pfeiffer ( ≥ 3/ < 3): 5%/95%; Yesavage test ( ≥ 10/ < 10): 1%/99%; VES-13 ( ≥ 3/ < 3): 56%/44%; weight loss ( ≥ 5%/ < 5%): 20%/80%. Fit and medium fit p had significantly better mOS (21.1 and 11.6 m, respectively) as compared with unfit p (7.7 m, p = 0.041). Vulnerable p (VES-13 ≥ 3) had significantly shorter mOS (9.6 m) as compared to other p (22.6 m, p = 0.019). In the multivariate survival analysis, GA groups and VES-13 had independent prognostic value. Most fit and medium fit p received cCRT (73%) and had a mOS of 21.1 m (95% CI 12.8 – 29.4). Higher VES-13 ( ≥ 3) was associated with shorter mOS (p=0.037) and higher risk of G3-4 toxicity (p = 0.012). Adverse events (G3-4) ≥ 10%: neutropenia, 18%; respiratory infection, 13%; radiation pneumonitis, 15%. Conclusions: GA and VES-13 may help in the selection of elderly p for cCRT to avoid undertreatment of those p. VES-13 had independent prognostic value and was significantly associated with higher risk of toxicity.
Rare germline variants in ATM are associated with chronic lymphocytic leukemia
Authors: G Tiao, M R Improgo, S Kasar, W Poh, A Kamburov, D-A Landau, E Tausch, A Taylor-Weiner, C Cibulskis, S Bahl, S M Fernandes, K Hoang, E Rheinbay, H T Kim, J Bahlo, S Robrecht, K Fischer, M Hallek, S Gabriel, E S Lander, S Stilgenbauer, C J Wu, A Kiezun, G Getz, J R Brown
Journal: Leukemia (2017)
New Insights into Deregulated Gene Expression Pathways in MLL- and AF10-Rearranged T-Lineage Acute Lymphoblastic Leukemia
Authors: Huining Kang, Nitesh Sharma, Christian K Nickl, Scott Ness, Meenakshi Devidas, Brent L. Wood, Barbara L. Asselin, Elizabeth Raetz, William L. Carroll, Naomi Winick, Mignon L. Loh, Stephen P. Hunger, Nyla A. Heerema, Andrew J. Carroll, Kimberly P. Dunsmore, Richard S. Larson, Stuart S. Winter, Ksenia Matlawska-Wasowska
Journal: Blood (2016)
Prise en charge de l'hémorragie digestive liée l'hypertension portale au cours de la cirrhose: Evaluation de la conférence de consensus de Paris
Authors: C Charpignon, F Oberti, P Bernard, E Bartoli, A Pauwels, P Renard, JF Cadranel, B Bernard-Chabert, JC Barbare, I Ingrand, M Beauchant
Journal: Endoscopy (2006)

L'évaluation des recommandations pour la prise en charge de l'hémorragie de l'hypertension portale de la cirrhose n'a fait l'objet que de rares travaux.Le but de cette enquête transversale a été d'évaluer le degré de conformité des pratiques et l'influence de la Conférence de consensus Française de Paris de décembre 2003.
Abstract 224: Primary Human Cells Isolated From Atria and Bone Marrow Exhibit Comparable Anti-fibrotic Cell Phenotypes Upon Transfection With MicroRNA-301a
Authors: Alison L Müller, Darren H Freed
Journal: Circulation Research (2015)

There are many cell types that can contribute to cardiac fibrosis including atrial fibroblasts (AFs) and bone marrow-derived progenitor cells (MPCs). We have previously shown that MPCs display a myofibroblast phenotype in vitro which is linked to altered microRNA(miR)-301a expression, a miR affiliated with maintaining proliferation in numerous cell types. We have also shown that miR-301a influences a dichotomous phenotype in primary human MPCs isolated from patients undergoing open heart surgery. As both MPCs and AFs display a dichotomous phenotype where each cell type displays a phenotype that pathologically contributes to fibrosis, we transfected both MPCs and AFs with miR-301a. AFs were also isolated from patients undergoing open heart surgery. We observed decreases in levels of both mRNA and protein of collagen I, non-muscle myosin IIA, and EDA-fibronectin. These proteins are expressed in myofibroblasts, the cell type predominantly responsible for causing cardiac fibrosis. In addition, transfection of miR301a caused both cell types to increase proliferation, which was analyzed using MTT proliferation assays. These results indicate that miR-301a could be influencing a non-fibrotic phenotype, which could prove useful in cell therapy trials where progenitor cells are injected into scar tissue in order to help heal patients who have suffered from a myocardial infarction. Over-expressing miR-301a in cells used could prevent them from differentiating into pro-fibrotic phenotypes and encourage their proliferation, thereby potentiating their efficacy.
<i>PALB2</i> mutation carriers: Are clinicians acting on the molecular diagnosis?
Authors: Virginia Speare, Emily Dalton, Holly Laduca, Courtney Grosvenor, Jane Z. Kuo, Erick Lin, Jill S Dolinsky
Journal: Journal of Clinical Oncology (2016)

e13121 Background: PALB2 is a frequently mutated hereditary breast and ovarian cancer gene. Recent studies have demonstrated up to a 58% lifetime risk for breast cancer with increased risks for pancreatic and other cancers. However, the precise risks and recommendations for management in PALB2 mutation carriers (PALB2+) are not well established. The National Comprehensive Cancer Network guidelines include breast MRI surveillance for female PALB2+, but comment on prophylactic surgeries is vague and other cancer screening is not mentioned. This study aimed to provide preliminary data on how clinicians manage cancer risks in PALB2+. Methods: 156 patients with a PALB2 mutation were identified from a clinical diagnostic laboratory from Aug 2012 to Sept 2015. Clinicians with ≥ 2 PALB2+ were invited to participate by completing a survey on the impact the molecular diagnosis had on management for their patient. Results: Of 19 females and 1 male, 70% (n = 14) had a history of breast cancer only and 15% (n = 3) had 2 cancers, including breast. The remaining cases (n = 3) included 2 ovarian cancers and 1 unaffected female. Additional breast MRI surveillance was recommended in 5 cases and 2 of these recommendations were based onthe PALB2 result without a contributory family history. After genetic testing, 3 prophylactic mastectomies were recommended and performed, 2 of which were based on the identification of a PALB2 mutation. Six of 11 at risk women were recommended to have risk reducing oophorectomy. The option for pancreatic cancer screening was discussed with half (10/19) at risk patients, although none had a family history of the disease. Conclusions: These data demonstrate that some clinicians find the risks for cancer sufficient in PALB2+ to warrant prophylactic surgery. The data also suggest that the risk for pancreatic cancer is concerning enough to warrant screening. This study is limited by small numbers and a lack of data concerning factors such as patient preference; however our survey of clinicians reveals that knowledge of carrier status is impacting risk management in some cases. Longitudinal studies measuring cancer incidence and survival are needed to evaluate the effectiveness of surveillance and preventative measures among PALB2+.
Abstract 288: Significantly Reduced Hepatic Microcirculatory Blood Flow After Resuscitation in a Rat Model of Cardiac Arrest
Authors: Jie Qian, Shen Zhao, Jiangang Wang, Ping Gong, Zhengfei Yang, Xiaobo Wu, Jena Cahoon, Wanchun Tang
Journal: Circulation (2014)

Introduction:  Multiple organ dysfunction following successful resuscitation from cardiac arrest is associated with a low survival. Hepatic injuries are common clinical findings following resuscitation. In the present study, we investigated post-resuscitation hepatic microcirculatory changes in a rat model of cardiac arrest and resuscitation.   Methods:  A total of 15 Sprague-Dawley rats (450-550g) were randomized into two groups: 1) CPR group: 8 mins of untreated ventricular fibrillation (VF) followed by 8 mins of cardiopulmonary resuscitation and defibrillation (n=10); 2) sham control: animals underwent the same surgical procedure only VF and cardiopulmonary resuscitation were not performed (n=5). An upper midline laparotomy was performed to visualize the right lobe of the liver. Ten-second clips of the hepatic microcirculation were captured with the sidestream dark field video microscope at three locations at baseline, 1, 2, 4 and 8 hrs after the return of spontaneous circulation. Mean diameter of sinusoids and sinusoidal blood flow velocity were quantified off-line by using an automated vascular analysis (AVA 3.0) software.   Results:  Following resuscitation, both sinusoidal diameter (baseline: 10.9±0.7μm, PR 8 hrs: 7.7±0.9μm/s) and sinusoidal blood flow velocity (baseline: 341±58μm/s, PR 8 hrs: 88±19μm/s) decreased significantly when compared with the sham control group (both p   Conclusion:  Significant reduction in hepatic microcirculatory blood flow was observed following successful resuscitation from cardiac arrest.
Reproduction number of Ebola falls below critical threshold in Liberia
Authors: T. Nyenswah, D. Cummings, J. Read, J. Lessler, I. Rodriguez-Barraquer, L. Bawo, M. Mulbah, F. Kateh, M. Massaquaoi, C. Rivers, B. Lewis, N. Glass, Rudolf Knippenberg, Joshua Epstein, N. Hynes, T. Ahmed, Kirsch T, T. Perl, D. Peter
Journal: New England Journal of Medicine (2014)
Outcome disparities by age and 21-gene recurrence score (RS) in hormone receptor positive (HR+) breast cancer (BC).
Authors: Valentina I. Petkov, Dave P. Miller, Nadia Howlader, Nathan Gliner, Will Howe, Nicola C. Schussler, Kathleen Cronin, Frederick L. Baehner, Lynne Penberthy, Steven Shak
Journal: Journal of Clinical Oncology (2016)

574 Background: BC diagnoses in older patients (pts) are rising as population demographics change and life expectancy increases. The TEAM study (N = 9,766) reported worse outcomes for older pts with HR+ BC (JAMA. 2012;307:590). To confirm this finding and to examine the role of tumor biology, SEER and Genomic Health, Inc. collaborated to electronically supplement SEER registries with RS results and evaluate BC-specific mortality (BCSM). Methods: Oncotype DX RS results were provided to SEER, per registry linkage methods. Eligible pts were diagnosed (Jan 2004 – Dec 2011) with N0 HR+ BC, and had no prior malignancy or multiple tumors. BCSM, defined previously (JNCI. 2010;102:1584), was analyzed separately for pts < 70 y and ≥70 y. Mortality estimates were compared using a log-rank test. Results: Of 184,190 eligible pts, 70%/30% were < 70 y/≥70 y. 35,487 of 128,712 pts < 70 y (28%) had RS results (median age 55 y; 29%/54% grade 1/2; 26%/54% ≤1 cm/ > 1-2 cm). 4,647 of 55,478 pts ≥70 y (8%) had RS results (median age 73 y; 25%/55% grade 1/2; 20%/48% ≤1 cm/ > 1-2 cm). Reported CT use and 5-y BCSM are shown in Table. CT use was lower for pts ≥70 y (p < 0.001). Continuous RS result was associated with BCSM for pts both < 70 y and ≥70 y (p < 0.001). As expected, 5-y other-cause mortality was higher in pts ≥70 y (11%) than in pts < 70 y (4%), but was not associated with RS results (p = 0.92). 5-y BCSM was worse for pts ≥70 y, particularly for those with RS ≥18 (p < 0.001). For pts ≥70 y with no RS assay (50,422 pts; 4% CT use), 5-y BCSM was 5.4% (95%CI, 5.2%-5.6%). Conclusions: This large population-based observational study of N0 HR+ BC indicates that unacceptably high BCSM persists in US clinical practice for pts ≥70 y with either no 21-gene RS assay done or an RS ≥18 (but not RS < 18). Further research and actions are urgently needed to understand and address the factors behind this outcome disparity. RS < 18 RS 18-30 RS ≥31 N CT (% of N) 5-y BCSM (95% CI) N CT (% of N) 5-y BCSM (95% CI) N CT (% of N) 5-y BCSM (95% CI) All pts 21760 7% 0.4 (0.3,0.5) 15152 35% 1.4 (1.1,1.7) 3222 70% 4.5 (3.5,5.8) < 70 y 19137 8% 0.3 (0.2,0.4) 13549 37% 1.2 (0.9,1.5) 2801 72% 3.7 (2.8,4.9) ≥70 y 2623 2% 1.2 (0.6,2.2) 1603 15% 2.8 (1.9,4.2) 421 53% 11.7 (7.1,18.9)
Assessment of microRNA regulation of INCENP, KRT14, and KRT16 in lung cancer
Authors: Vincent Paulino, Lynne Bemis, Nhan Tran, Wilbur Franklin, Michio Sugita, Jennifer Caputo, Jerry Haney, Paul Bunn, Glen Weiss
Journal: Cancer Research (2008)

5036    Background:  MicroRNAs (miR) have been shown to play a role in regulation of genes important in carcinogenesis. INCENP plays an essential role for proper chromosome segregation and cytokinesis. KRT14 and KRT16 are overexpressed in some cancers, but not by microarray in lung cancer lines. Here we assess regulation of INCENP, KRT14, and KRT16 by miR-520e at the protein level in lung cancer lines.     Methods:  Baseline microarray gene expression and miR-520e expression guided cell line selection for validation experiments. Cells were transfected with miR-520e mimic and inhibitor. Western blotting (WB) for INCENP, KRT14, and KRT16 was performed. Immunohistochemistry (IHC) was scored using H-scoring (scale 0-300; over 100 is expressed). Correct defines decrease in protein by mimic or increase in protein by inhibitor transfection; incorrect is the opposite result from that hypothesized; while  change defines no protein alteration.   Results:  By microarray, INCENP is 1 of the highest expressed genes, while KRT14 and KRT16 are 2 of the lowest expressed genes from 30 lung cancer lines. Baseline protein expression correlated with high or low microarray level, respectively, in 9 of 15 IHC stains and 11 of 15 WB. H157, Colo699, and H69 had low miR-520e levels, while H2122 and H358 had normal and high levels, respectively (Table). After mimic or inhibitor transfections, IHC staining was “correct” 5 of 30, “incorrect” 5 of 30, and “no change” in 20 of 30 possibilities. After mimic or inhibitor transfections in 23 available possibilities, WB was “correct” 8 of 23 and “no change” in 15 of 23 possibilities.   Conclusions:  WB appears to correlate better than IHC with microarray expression levels. For hypothesized miR regulation of protein, WB appears to correlate better than IHC. Imperfect results may be due to varying transfection efficiency and heterogeneity between cell lines. MiR-520e may play a role in lung cancer proliferation. Examination of clinically annotated patient samples may further define this miR’s role.
Abstract 19779: Nod2 Knock Down Improves Left Ventricular Function and Attenuates Pathophysiological Key Mechanisms in Experimental Coxsackievirus B3-induced Myocarditis
Authors: Carsten Tschöpe, Irene Müller, Yu Xia, Christin Zietsch, Kostas Savvatis, Dirk Lassner, Uwe Kühl, Heinz-Peter Schultheiss, Burkert Pieske, Sophie Van Linthout
Journal: Circulation (2015)

Introduction: Nucleotide binding oligomerization domain 2 (NOD2) is a cytoplasmatic pattern recognition receptor belonging to the NOD-like receptor family, which is part of the innate immune system. Hypothesis: Since NOD2 recognises ssRNA and Coxsackievirus B3 (CVB3) is a ssRNA virus, we hypothesised that NOD2 regulates cardiac inflammatory signaling in CVB3-induced myocarditis. Methods: Gene expression was analyzed on endomyocardial biopsies (EMBs) taken from ejection fraction- and age-matched CVB3+ (n=10) and CVB3- control (n=7) patients and on EMBs from CVB3+patients who spontaneously eliminated CVB3 (n=6). NOD2 -/- mice and wild-type (wt) C57BL/6 mice were i.p. infected with 5 x 105 p.f.u. of CVB3. Seven days after infection, mice were hemodynamically characterized, and left ventricles (LV) were isolated. Results: NOD2 mRNA expression was 3.7-fold (p&lt;0.05) increased in CVB3+ vs CVB3- control patients. Interestingly, NOD2 and Nrlp3 mRNA expression significantly dropped in EMBs of CVB3+ patients who spontaneously eliminated CVB3. In addition, LV NOD2 mRNA expession was increased in CVB3 vs wt mice. NOD2-/- CVB3 mice showed an improved LV function compared to CVB3 wt mice. In parallel, infiltration of CD4-, CD8-, CD11b- and CD68-positive cells was less pronounced in CVB3-infected NOD2-/- mice compared to CVB3 wt mice. Concomitantly, LV mRNA levels for TNF-alpha, IL-1ß, IFN-gamma, IFN-ß, TLR4, and MyD88 were 3.9-fold, 2.9-fold, 5.3-fold, 8.0-fold, 1.4-fold and 2.0-fold reduced in CVB3 NOD2-/- vs CVB3 wt mice, respectively (p&lt;0.05). LV viral copy number was lower in CVB3 NOD2-/- vs CVB3 wt mice. CVB3-infected NOD2-/- mice exhibited less pronounced cardiac fibrosis, as indicated by lower collagen I and III mRNA expression and a 2.7-fold (p&lt;0.0005) lower collagen I/III protein ratio. NOD2 knockdown in HL-1 cardiomyocytes was associated with a decreased inflammatory response, a 1.4-fold (p&lt;0.05) lower CVB3 copy number, and a 3.4-fold (p&lt;0.005) reduced TLR4 protein expression and underlying signaling. Conclusions: NOD2 knock down improves LV function and attenuates pathophysiological key mechanisms in acute CVB3-induced myocarditis mice. Modulation of NOD2 might represent a promising therapeutic strategy to treat viral myocarditis.
Liver transplantion for young adult hepatocellular carcinoma.
Authors: Stefanie Thomas, Diana Moke, Rocio Lopez, Naim Alkhouri
Journal: Journal of Clinical Oncology (2016)

e13082 Background: Liver transplantation (LT) is curative for hepatocellular carcinoma (HCC). HCC is typically a disease of older adults; therefore the characteristics and outcomes of LT for young adults (YA, ages 18-40) are not well described. The objective of this study is to assess the characteristics and outcomes of YAs with HCC receiving LT and compare these to older subjects > 40 years. Methods: YAs with HCC who had their first LT from the UNOS database were included in this study. A sub-group of subjects after implementation of the Model for End-Stage Liver Disease (MELD) score were evaluated separately. As a control group, patients 40 or older with a diagnosis of HCC (post-MELD) were matched 4:1 to the young adult HCC group based on gender and MELD score (±1). Descriptive statistics describing demographics and co-morbidities including other liver diseases were generated. Kaplan-Meier product limit estimates were used to assess patient and graft survival. Conditional logistic regression and Cox proportional hazards frailty models were used to compare the groups. Results: A total of 464 subjects were included in the study group, with an increase (n = 320) post-MELD; 1280 subjects served as the control. Co-morbid obesity and diabetes were more frequent in the older group (p < 0.001). Underlying liver disease differed between the two groups with autoimmune/cholestatic disease and hepatitis B being more frequent in the younger population and hepatitis C, alcoholic liver disease, and nonalcoholic steatohepatitis more common in the older group (all p < 0.001). Post-transplant 5-year survival for the entire study group was 58.8% and 73.1% post-MELD with a re-transplantation rate of 9.7% and 7.8% respectively. In the older group, survival and re-transplantation rates were lower (68.6% p = 0.093; 4.3% p = 0.001). Conclusions: Although HCC is typically a disease of older adults, 464 YAs with HCC received LT in the UNOS database. Compared to the older population, survival and re-transplantation rate was higher. Hepatitis B, a vaccine preventable illness, was more frequently associate with HCC in younger patients. The MELD-exception for HCC has allowed an increased number of YAs with HCC to receive LT who would have otherwise had little hope for long-term survival.
Human Papillomavirus Triage of Women With Atypical Squamous Cells of Undetermined Significance—Reduction of Overtreatment Needed
Authors: Chris J. L. M. Meijer, Peter J. F. Snijders
Journal: JAMA Oncology (2017)

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