tbuckley/cabot-search huggingface dataset:
Abstract P177: Urine Creatinine Based Estimates of Fat Free Mass: The Rancho Bernardo Study
Authors: Simerjot K Jassal, Christina L Wassel, Gail A Laughlin, Elizabeth Barrett-Connor, Dena E Rifkin, Joachim H Ix
Journal: Circulation (2012)

Background: Sarcopenia is difficult to identify without imaging. An accurate, easily obtainable screening tool would allow identification of older persons who might benefit from interventions to increase muscle mass. Urine creatinine excretion rate (CER) on 24-hour urine collections is highly correlated with muscle mass but collection is cumbersome. Spot urine creatinine (UCr) may also mark muscle mass, but is influenced by transient changes in urine tonicity. We previously developed a prediction equation to estimate CER (eCER) on 24-hour urine specimens. Whether this equation is associated with measures of muscle mass and whether spot UCr provides similar estimates to eCER is unknown. Methods: We measured spot UCr and fat free mass (FFM) by dual energy x-ray absorptiometry (DXA) among 1372 community-dwelling individuals. We used the equation developed in our prior study to estimate CER: eCER (mg/day) = 879.89 + 12.51*weight (kg) - 6.19*age + 34.51 if black - 379.42 if female. Spearman correlation coefficients and linear regression were used to determine strengths of association of eCER and spot UCr with FFM by DXA. Results: Mean (SD) age was 70 (11) years, 58% were women, and mean eGFR was 69 (15) ml/min/1.73m 2 . Mean values for FFM by DXA, eCER, and spot UCr were 47 (11) kg, 1107 (339) mg/day, and 94 (55) mg/dL, respectively. eCER was more strongly correlated with FFM by DXA (r = 0.93, p&lt;0.001) than spot UCr (r = 0.39, p&lt;0.001). Figure 1 shows the mean regression lines and 95% limits of agreement for the association of eCER (A) and spot UCr (B) with FFM; the 95% limits of agreement were narrower for eCER compared to spot UCr. The regression equations were: FFM (kg) = 13.21 + 0.03*eCER (mg/day) and FFM (kg) = 39.3 + 0.08* spot UCr (mg/dL). Conclusions: An equation incorporating age, weight, sex, and race to estimate CER was highly correlated with FFM by DXA and was more precise than spot UCr in community-dwelling older adults. Future studies should evaluate whether eCER provides a simple method to predict frailty and mortality in older persons.
What Metrics Accurately Reflect Surgical Quality?
Authors: Andrew M. Ibrahim, Justin B. Dimick
Journal: Annual Review of Medicine (2018)

Surgeons are increasingly under pressure to measure and improve their quality. While there is broad consensus that we ought to track surgical quality, there is far less agreement about which metrics matter most. This article reviews the important statistical concepts of case mix and chance as they apply to understanding the observed wide variation in surgical quality. We then discuss the benefits and drawbacks of current measurement strategies through the framework of structure, process, and outcomes approaches. Finally, we describe emerging new metrics, such as video evaluation and network optimization, that are likely to take on an increasingly important role in the future of measuring surgical quality.
The atypical receptor CCRL2 is required for CXCR2-dependent neutrophil recruitment and tissue damage
Authors: Annalisa Del Prete, Laura Martínez-Muñoz, Cristina Mazzon, Lara Toffali, Francesca Sozio, Lorena Za, Daniela Bosisio, Luisa Gazzurelli, Valentina Salvi, Laura Tiberio, Chiara Liberati, Eugenio Scanziani, Annunciata Vecchi, Carlo Laudanna, Mario Mellado, Alberto Mantovani, Silvano Sozzani
Journal: Blood (2017)
Smoking, telomere length and lung function decline: a longitudinal population-based study
Authors: Pascal Andujar, Dominique Courbon, Emilie Bizard, Elisabeth Marcos, Serge Adnot, Laurent Boyer, Pascal Demoly, Debbie Jarvis, Catherine Neukirch, Isabelle Pin, Gabriel Thabut, Jorge Boczkowski, Bénédicte Leynaert
Journal: Thorax (2017)

Telomere shortening is associated with COPD and impaired lung function in cross-sectional studies, but there is no longitudinal study. We used data from 448 participants recruited as part of the French follow-up of the European Community Respiratory Health Survey. We found no relationship between telomere length at baseline and FEV1 decline after 11 years of follow-up. However, heavy smoking was associated with an accelerated FEV1 decline in individuals with short telomeres, but not in subjects with longer telomeres (p for interaction p=0.08). Our findings suggest that short telomere length in peripheral leucocytes might be a marker for increased susceptibility to the effect of smoking.
Adjuvant versus neoadjuvant chemotherapy for muscle-invasive bladder cancer (MIBC): Analysis of the National Cancer Database (NCDB).
Authors: Guru Sonpavde, Rebecca A. Nelson, Quoc-Dien Trinh, Neeraj Agarwal, Jeffrey Nix, Steven Kardos, Joaquim Bellmunt, Toni K. Choueiri, Sumanta K. Pal
Journal: Journal of Clinical Oncology (2016)

4524 Background: Neoadjuvant chemotherapy (NC) preceding radical cystectomy (RC) is the standard for muscle invasive bladder cancer (MIBC). The efficacy of post-RC adjuvant chemotherapy (AC) is unproven, although meta-analyses and retrospective analyses support its efficacy. We conducted a retrospective analysis of the NCDB to compare the overall survival (OS) with NC vs. AC. Methods: The NCDB was employed including patients (pts) with new diagnoses of urothelial carcinoma of bladder in the US from 2004-2013. Pts with clinical stage T2-T4aN0 who underwent RC were included. Those with prior malignancy and prior radiotherapy were excluded. Multivariate analyses were conducted to determine whether NC conferred differential impact on OS compared with AC after controlling for baseline clinical stage, age, race, year of diagnosis, Charlson Comorbidity Index (CCI), number of lymph nodes examined at RC and gender. Owing to suboptimal durations between RC and chemotherapy and significant discord between clinical and pathologic staging in cT2N0 pts, sub-analyses were conducted in such pts with time from first chemotherapy to RC < 6 months (mo) in the NC group, and time from RC to first chemotherapy < 4 mo in the AC group. Results: A total of 7704 pts were eligible for analysis, of whom 1624 received NC, 839 received AC and 5241 underwent RC alone. On multivariate analysis, NC was associated with significantly longer OS compared to AC (HR = 1.19 [95% CI: 1.05-1.36], p = 0.008). Sub-analyses comparing the cT2N0 group that received NC followed by RC within 6 mo vs. the modeled and congruent AC group that received RC followed by AC within 4 mo showed no significant OS difference (HR = 0.93 [95% CI: 0.64-1.36]). Limitations of a retrospective analysis apply. Conclusions: Overall, NC conferred better OS than AC in MIBC patients with cT2-T4aN0, although OS appeared similar in modeled pts receiving more optimal NC and AC. These data suggest caution in interpreting results from meta-analyses and retrospective analyses supporting AC as an alternative to NC, and suggest that NC should remain the preferred standard for MIBC. A trial comparing NC vs. AC should be considered.
Health services must encourage pragmatic research
Authors: Peter Bergin
Journal: BMJ (2017)

Surely the most interesting finding in the debate among Campbell, Weijer, and colleagues is that the authors all agree on the benefits of doctors participating in pragmatic research.1 Even those who don’t think that doctors should be forced to participate agree that participation benefits society.

The issue of “duty” or “obligation” misses the point: we need a …
Frailty and cancer: Implications for oncology surgery, medical oncology, and radiation oncology
Authors: Cecilia G. Ethun, Mehmet A. Bilen, Ashesh B. Jani, Shishir K. Maithel, Kenneth Ogan, Viraj A. Master
Journal: CA A Cancer Journal for Clinicians (2017)

Abstract Answer questions and earn CME/CNE The concept of frailty has become increasingly recognized as one of the most important issues in health care and health outcomes and is of particular importance in patients with cancer who are receiving treatment with surgery, chemotherapy, and radiotherapy. Because both cancer itself, as well as the therapies offered, can be significant additional stressors that challenge a patient's physiologic reserve, the incidence of frailty in older patients with cancer is especially high—it is estimated that over one‐half of older patients with cancer have frailty or prefrailty. Defining frailty can be challenging, however. Put simply, frailty is a state of extreme vulnerability to stressors that leads to adverse health outcomes. In reality, frailty is a complex, multidimensional, and cyclical state of diminished physiologic reserve that results in decreased resiliency and adaptive capacity and increased vulnerability to stressors. In addition, over 70 different measures of frailty have been proposed. Still, it has been demonstrated that frail patients are at increased risk of postoperative complications, chemotherapy intolerance, disease progression, and death. Although international standardization of frailty cutoff points are needed, continued efforts by oncology physicians and surgeons to identify frailty and promote multidisciplinary decision making will help to develop more individualized management strategies and optimize care for patients with cancer. CA Cancer J Clin 2017;67:362–377. © 2017 American Cancer Society.
Prevalence of clinic-defined food allergy in early adolescence: The SchoolNuts study
Authors: Mari Sasaki, Jennifer J. Koplin, Shyamali C. Dharmage, Michael J. Field, Susan M. Sawyer, Vicki McWilliam, Rachel L. Peters, Lyle C. Gurrin, Peter J. Vuillermin, Jo Douglass, Angela Pezic, Maia Brewerton, Mimi L.K. Tang, George C. Patton, Katrina J. Allen
Journal: Journal of Allergy and Clinical Immunology (2017)
Genetic Predisposition to Breast Cancer Due to Mutations Other Than <i>BRCA1</i> and <i>BRCA2</i> Founder Alleles Among Ashkenazi Jewish Women
Authors: Tom Walsh, Jessica B. Mandell, Barbara M. Norquist, Silvia Casadei, Suleyman Gulsuner, Ming K. Lee, Mary-Claire King
Journal: JAMA Oncology (2017)

<h3>Importance</h3> Among Ashkenazi Jewish women, 3 mutations in<i>BRCA1</i>and<i>BRCA2</i>severely increase the risk of breast and ovarian cancer. However, among Ashkenazi Jewish patients with breast cancer who do not carry one of these founder mutations, the likelihood of carrying another pathogenic mutation in<i>BRCA1</i>or<i>BRCA2</i>or another breast cancer gene is not known. This information would be valuable to the patient and family for cancer prevention and treatment. <h3>Objective</h3> To determine the frequency of cancer-predisposing mutations other than the<i>BRCA1</i>and<i>BRCA2</i>founder alleles among patients of Ashkenazi Jewish ancestry with breast cancer. <h3>Design, Setting, and Participants</h3> In this cohort study, genomic DNA of women from 12 major cancer centers with a first diagnosis of invasive breast cancer who identified themselves and all 4 grandparents as Ashkenazi Jewish and participated in the New York Breast Cancer Study (NYBCS) from 1996 to 2000 was sequenced for known and candidate breast cancer genes. Data analysis was performed from July 10, 2014, to March 10, 2017. <h3>Main Outcomes and Measures</h3> Genomic DNA from all 1007 NYBCS probands was sequenced for 23 known and candidate breast cancer genes using BROCA, a targeted multiplexed gene panel. <h3>Results</h3> Of the 1007 probands in the study, 903 probands had no founder mutations in<i>BRCA1</i>or<i>BRCA2</i>; of these probands, 7 (0.8%) carried another pathogenic mutation in<i>BRCA1</i>or<i>BRCA2</i>, and 31 (3.4%) carried a pathogenic mutation in another breast cancer gene (29 in<i>CHEK2</i>, and 1 each in<i>BRIP1</i>and<i>NBN</i>). Of all inherited predispositions to breast cancer in the NYBCS, 73.8% (104 of 142) were due to a<i>BRCA1</i>or<i>BRCA2</i>founder allele, 4.9% (7 of 142) to another<i>BRCA1</i>or<i>BRCA2</i>mutation, and 21.8% (31 of 142) to a mutation in another gene. Overall, 14.1% (142 of 1007) of Ashkenazi Jewish patients with breast cancer in the NYBCS carried a germline mutation responsible for their disease: 11.0% (111 of 1007) in<i>BRCA1</i>or<i>BRCA2</i>, and 3.1% (31 of 1007) in<i>CHEK2</i>or another breast cancer gene. Of the 111 patients with<i>BRCA1</i>or<i>BRCA2</i>mutations, 57 (51.4%) had a mother or sister with breast or ovarian cancer and 54 patients (48.6%) did not. <h3>Conclusions and Relevance</h3> Comprehensive sequencing would provide complete relevant genetic information for Ashkenazi Jewish patients with breast cancer.
Differences Between CEBPA bZIP and TAD Mutations and Their Effect on Outcome-an Analysis in 4578 Patients with Acute Myeloid Leukemia
Authors: Julia-Annabell Georgi, Franziska Taube, Michael Kramer, Sylvia Herold, Kerstin Schaefer-Eckart, Norbert Schmitz, Christian Eberlein, Sebastian Stasik, Walter E Aulitzky, Alwin Kraemer, Wolf Roesler, Mathias Haenel, Hermann Einsele, Claudia D. Baldus, Jan Moritz Middeke, Uwe Platzbecker, Christoph Roellig, Hubert Serve, Wolfgang E Berdel, Gerhard Ehninger, Martin Bornhaeuser, Johannes Schetelig, Christian Thiede
Journal: Blood (2016)
Critical roles of IL-12/23 from tumor-infiltrating dendritic cells and Type-1 cytokine responses in the anti-tumor immunity induced by vaccination with interleukin-4 transfected tumors
Authors: Junichi Eguchi, Naruo Kuwashima, Manabu Hatano, Fumihiko Nishimura, Jill E. Dusak, Walter J. Storkus, Hideho Okada
Journal: Cancer Research (2005)

6018   Although interleukin (IL)-4 is often regarded as a Type-2 response inducer, recent studies have demonstrated that local IL-4 delivery at the site of vaccination activates local antigen-presenting cells (APC) and promote Type-1 T cell responses. We have demonstrated IL-4 gene transfected glioma cell vaccines induce effective therapeutic immunity in preclinical glioma models, and initiated phase I trials in patients with malignant gliomas. To determine the critical mediators of the IL-4-transfected tumor vaccines, we employed MCA205 and CMS-4 sarcoma models and syngeneic animals. Although wild type, IL-12/23p40 -/-  and interferon(IFN)-γ -/-  mice rejected initial inoculation of IL-4 transfected tumors, IL-12/23p40 -/-  and IFN-γ -/-  mice as well as athymic mice failed to mount a sustained systemic response against rechallenge with parental tumor cells. Ectopic IL-4 expression at the vaccine site enhanced the number of tumor infiltrating dendritic cells (TIDC) and their expression of IL-12p70. Adoptive transfer of wild type-TIDCs obtained from IL-4 expressing tumor, but not IL-12/23p40 -/- -TIDC, elicited a tumor specific CTL response in the recipient animals, suggesting that IL-12/23 expression by TIDCs play a critical role in IL-4 transfected tumor vaccines. To further delineate the roles of Type-1 and -2 cytokine responses in the IL-4 gene therapy, we employed STAT4 -/-  and STAT6 -/-  mice. Interestingly, both STAT4 -/-  and STAT6 -/-  mice failed to suppress the growth of IL-4 expressing syngeneic tumors. TIDCs from STAT6 -/-  mice failed to enhance the expression of IL-12p70, and cell surface expression of MHC Class II and CD86 were lower than the wild-type mice-derived TIDCs, suggesting that STAT6 plays a critical role in the maturation of TIDC. Nevertheless, splenocytes from STAT6 -/-  mice immunized with IL-4 transfected tumors, but not STAT4 -/-  mice, mounted a tumor specific CTL response against parental tumor cells even though its level was lower than that in the wild-type mice. Furthermore, splenocytes from STAT4 -/-  mice immunized with IL-4 transfected tumors failed to produce IFN-γ. These results demonstrate critical roles of host-Type-1 cytokine responses in IL-4 transfected tumor vaccines. As cancer patients often display impaired Type-1 cytokine response, it may be of importance to correlate host-Type-1 cytokine status and the response to IL-4 gene transfected tumor cell vaccines.
ANGPTL3 Inhibition in Homozygous Familial Hypercholesterolemia
Authors: Daniel Gaudet, Daniel A Gipe, Robert Pordy, Zahid Ahmad, Marina Cuchel, Prediman K Shah, Kuang-Yuh Chyu, William J Sasiela, Kuo-Chen Chan, Diane Brisson, Etienne Khoury, Poulabi Banerjee, Viktoria Gusarova, Jesper Gromada, Neil Stahl, George D Yancopoulos, G Kees Hovingh
Journal: New England Journal of Medicine (2017)

Evinacumab, a monoclonal antibody that blocks ANGPTL3, was administered to nine adults with homozygous familial hypercholesterolemia. At 4 weeks, LDL cholesterol was reduced by a mean of 49%, with a mean absolute change from baseline of −157 mg per deciliter.
The 1999 ASCI Presidential Address
Authors: Ajit Varki
Journal: Journal of Clinical Investigation (1999)

Charge to the Commission"To evaluate and explicate the decline in preeminence of American medical schools over the last several decades, and the resulting flight of the best students and scientists to medical schools in Southeast Asia and elsewhere." PreambleAmerican medical schools in the year 2049 primarily consist of 2 types of faculty (Exhibit A, top).The first category includes full-time, practicing clinician-teachers who deliver excellent medical care, teach medical students to do the same, and conduct contracted clinical research for pharmaceutical companies.The second category is composed of basic scientist-teachers, whose primary function is to deliver preclinical teaching to medical students and who commit a limited amount of time to perform bench research.In contrast, the American medical schools of 50 years ago had 2 other kinds of faculty (Exhibit A, bottom).First, there were PhD scientists whose primary activity was basic research, who had a somewhat limited teaching role other than supervision of thesis projects by graduate and medical students.Second was the now-defunct category of biomedical researchers once called the "physician-scientist," who conducted varying combinations of patient-and disease-oriented research, or basic research, while also participating to some extent in teaching.After reviewing all available data, this commission concludes that the single major factor responsible for the decline of American medical schools is the disappearance of the physician-scientist, with the flight of basic researchers to nonmedical institutions and to other countries being a secondary consequence.
TREATMENT OF POST-PARTUM HÆMORRHAGE.
Journal: JAMA (1890)

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
At Our Fingertips
Authors: Ian Wicks
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
Intra-patient escalation dosing strategy with IMCgp100 results in mitigation of T-cell based toxicity and preliminary efficacy in advanced uveal melanoma.
Authors: Takami Sato, Paul D. Nathan, Leonel Fernando Hernandez-Aya, Joseph J Sacco, Marlana M. Orloff, Jessica Truscello, Cheryl McAlpine, Ann-Marie Hulstine, Mark C. Lanasa, Christina Marie Coughlin, Richard D. Carvajal
Journal: Journal of Clinical Oncology (2017)

9531 Background: IMCgp100 is a bispecific biologic capable of redirecting T cells against the melanocyte-associated antigen gp100. In the first-in-human (FIH) clinical trial, preliminary efficacy of IMCgp100 in advanced uveal melanoma (UM) was observed; however, cases of severe T cell-mediated toxicities with the first 2 doses limited dosing to 50 mcg QW. This phase 1 study was designed to implement intra-patient escalation to mitigate toxicity and maximize exposure of IMCgp100. Methods: Using a 3+3 design, HLA-A2+ pts with metastatic UM were treated with low weekly (QW) dosing of IMCgp100 iv at Cycle 1, Day 1 (C1D1) (20 mcg) and C1D8 (30 mcg), followed by the escalated cohort dose administered at C1D15 and beyond. Results: Nineteen metastatic UM pts with a median of 3 prior lines of therapy (range 0 - 8) were treated across 4 target dose cohorts (60, 70, 80, and 75 mcg). Fifteen of 19 pts remain on treatment at the data cutoff (25Nov16). Enrollment completed 15Sep16. DLT was observed in 1 of 6 pts in the 70-mcg cohort (LFT elevation), and 2 of 4 pts treated at 80 mcg QW (LFT and bilirubin elevation). The 80 mcg dose level was not tolerated and a 75 mcg cohort was enrolled. Six pts were treated at 75 mcg without DLT; this dose was identified as the MTD and RP2D. All 3 DLT resolved without corticosteroids and all pts resumed IMCgp100. Frequent related AE included pruritus (84%), pyrexia (84%), fatigue (74%), hypotension (74%) and peripheral edema (63%). Gr 3/4 drug-related AE include AST increased (15%), erythema (15%) and hypotension (15%). Preliminary efficacy data (RECIST v1.1) from 17 evaluable pts (2 pts had insufficient follow-up) showed no objective responses; 12 pts had a BOR of SD (63%) including 4 pts (24%) with a ≥10% reduction in target lesions. With median follow-up of 1.8 mo, the disease control rate (16 wks) was 32%. Conclusions: The intra-patient escalation regimen of IMCgp100 results in a 50% increase in dose above the FIH Phase 1, acceptable safety profile, and preliminary efficacy in UM pts. Considering the dismal prognosis of metastatic UM, the PFS observed in this study is encouraging. A Phase 2 expansion cohort and separate pivotal trial of IMCgp100 in advanced UM are ongoing. Clinical trial information: NCT02570308.