tbuckley/cabot-search huggingface dataset:
Annals Consult Guys - Antibiotic Prophylaxis and Aspirin Before Dental Procedures: What's Needed?
Authors: Geno J. Merli, Howard H. Weitz
Journal: Annals of Internal Medicine (2019)

Web Exclusives19 March 2019Annals Consult Guys - Antibiotic Prophylaxis and Aspirin Before Dental Procedures: What's Needed?FREEGeno J. Merli, MD and Howard H. Weitz, MDGeno J. Merli, MDThomas Jefferson University, Philadelphia, Pennsylvania (G.J.M., H.H.W.)Search for more papers by this author and Howard H. Weitz, MDThomas Jefferson University, Philadelphia, Pennsylvania (G.J.M., H.H.W.)Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/W18-0042 SectionsSupplemental MaterialAboutVisual Abstract ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail Annals Consult Guys brings a new perspective to the art and science of medicine with lively discussion and analysis of real-world cases and situations. They address medically relevant topics—whether they be poignant, thought-provoking, or just plain entertaining.For more videos from and information on Annals Consult Guys, visit go.annals.org/ConsultGuys. Comments0 CommentsSign In to Submit A Comment Author, Article, and Disclosure InformationAffiliations: Thomas Jefferson University, Philadelphia, Pennsylvania (G.J.M., H.H.W.)Disclosures: Geno J. Merli, MD, reports the following: Research grants/contracts: Bristol-Myers Squibb. Howard H. Weitz, MD, reports that he has no financial relationships or interests to disclose.Editors' Disclosures: Christine Laine, MD, MPH, Editor in Chief, reports that her spouse has stock options/holdings with Targeted Diagnostics and Therapeutics. Darren B. Taichman, MD, PhD, Executive Editor, reports that he has no financial relationships or interests to disclose. Cynthia D. Mulrow, MD, MSc, Senior Deputy Editor, reports that she has no relationships or interests to disclose. Jaya K. Rao, MD, MHS, Deputy Editor, reports that she has stock holdings/options in Eli Lilly and Pfizer. Catharine B. Stack, PhD, MS, Deputy Editor, Statistics, reports that she has stock holdings in Pfizer, Johnson & Johnson, and Colgate-Palmolive. Christina C. Wee, MD, MPH, Deputy Editor, reports employment with Beth Israel Deaconess Medical Center. Sankey V. Williams, MD, Deputy Editor, reports that he has no financial relationships or interests to disclose. Yu-Xiao Yang, MD, MSCE, Deputy Editor, reports that he has no financial relationships or interest to disclose. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 19 March 2019Volume 170, Issue 6Page: CG1KeywordsAntibiotic prophylaxisDiagnostic techniquesDisclosureResearch grantsResearch reporting guidelines ePublished: 19 March 2019 Issue Published: 19 March 2019 Copyright & PermissionsCopyright © 2019 by American College of Physicians. All Rights Reserved.Loading ...
Abstract MP34: Associations Muscle Quality, Muscle Strength, and Muscle Mass With All-Cause Mortality in Elderly Men and Women
Authors: Chong-Do Lee, Samuel Lee
Journal: Circulation (2019)

Although muscle mass, muscle strength, and muscle quality are important risk factors for disability and mortality in elderly men and women, the associations of these variables with all-cause mortality remain less explored. PURPOSE: We investigated the associations of muscle quality, muscle strength, and muscle mass with all-cause mortality in elderly US men and women. We also compared the strength of these associations with all-cause mortality. Methods: Cox proportional hazards regression was used to examine the associations of muscle quality, muscle strength, and muscle mass with all-cause mortality. We followed 1,361 men and women, aged 60 to 85 years, who participated in the National Health and Nutrition Examination Survey 1999-2002. All participants completed baseline lifestyle factors, and muscle strength and muscle mass measurements. Body composition was estimated by Dual-energy X-ray absorptiometry. Appendicular skeletal muscle mass (SMS) was computed by combining lean tissues in both arms and legs, and relative muscle mass was computed as SMS divided by height in meters squared (AMS). Leg muscle strength (MST) was estimated using the Kin Com MP dynamometer. Leg muscle quality (MQI) was computed as the peak force (Newton) divided by lean mass in the right leg. We further categorized AMS, MST, and MQI as sex-specific quartile categories. The significance of AMS, MST, and MQI with all-cause mortality was also tested by the Cox hazards models with the likelihood ratio statistics with and without adjustment for multiple risk factors. Results: During an average of 9.8 years of follow-up (9,4687 person-years), there were a total of 372 all-cause deaths (85 CVD, 202 chronic diseases). After adjustment for multiple risk factors, the risks of all-cause mortality across MQI quartile categories were (95% CI) 1.00 (Q1, referent), 0.72 (0.55, 0.95), 0.66 (0.49, 0.90), and 0.50 (0.31, 0.80) (P for trend &lt;0.001). The risks of all-cause mortality across MST categories were (95% CI) 1.00 (Q1, referent), 0.85 (0.59, 1.21), 0.50 (0.33, 0.75), and 0.46 (0.31, 0.67) (P for trend &lt;0.001). The risks of all-cause mortality across AMS categories were (95% CI) 1.00 (Q1, referent), 0.77 (0.56, 1.07), 0.75 (0.52, 1.10), and 0.65 (0.47, 0.90) (P for trend = 0.01). As a single measure, after adjustment for multiple risk factors, the hazards for all-cause mortality across MQI, MST, and AMS were 0.97 (p&lt;0.001), 0.99 (p&lt;0.001), and 0.84 (p = 0.001), respectively. When we included all these variables in the fully-adjusted model, only MQI (p = 0.03) was a strong risk factor for all-cause mortality, but not for MST (p = 0.84) and AMS (p = 0.05). Conclusion: Muscle quality was a strong risk factor for all-cause mortality in elderly men and women when compared with muscle strength or relative muscle mass. The American Heart Association should emphasize the importance of improving muscle quality in this geriatric population.
Late administration of luteinizing hormone-releasing hormone (LHRH) agonists and the impact on testosterone suppression in the real-world management of prostate cancer.
Authors: Przemyslaw Twardowski, A. Oliver Sartor, John A. McLane, Debbie Boldt-Houle, Stuart Atkinson, Scott T. Tagawa
Journal: Journal of Clinical Oncology (2019)

149 Background: LHRH agonists are standard for androgen deprivation therapy (ADT) for advanced prostate cancer (PCa). Increasing evidence suggests maintaining very low testosterone (T) levels is desirable and correlate with disease-specific survival. However, T levels may rise above castrate level between administrations, especially if the next dose is delayed. A previous publication showed that subcutaneously-administered leuprolide acetate (LA) provided a longer duration of action than intramuscularly-administered LA past the dosing interval. This study evaluated the timeliness of LHRH agonist administrations and subsequent rate of T breakthroughs in PCa patients. Methods: A retrospective review of electronic medical records from 1/1/07-6/30/16 of 85,030 LHRH agonist administrations for PCa treatment was conducted to evaluate the percentage of late subsequent administrations and T tests with T &gt; 50 ng/dL. A late administration was defined as occurring on or after day 33 (1 mo formulation), 98 (3 mo), 129 (4 mo), or 195 (6 mo). Descriptive statistics were used. Results: 26.9% of all subsequent LHRH agonist administrations were late: 14.4% were ≤ 1 week late, 3.1% were between 1 and 2 weeks late, and 9.4% were &gt; 2 weeks late. 21% of T tests demonstrated T &gt; 50 ng/dL when administrations were late, in contrast to only 4% of measured T levels exceeded 50 ng/dL when LHRH agonists were administered early or on time. Conclusions: Across LHRH agonists, greater than a quarter of subsequent administrations were defined as late. Among late administrations, about half were &gt; 1 week late, and more than a third were &gt; 2 weeks late. Late administrations were correlated with inadequate castration over 20% of the time. Considering the clinical benefits of maintaining effective T suppression during ADT, clinicians should administer treatments within approved dosing instructions, include routine monitoring of T levels, and consider prescribing treatments with proven prolonged effect through the dosing period to achieve T suppression to castrate levels.
Impact of Bortezomib- or Lenalidomide-Based Induction Treatment on High Risk Cytogenetic Transplant-Ineligible Patients with Newly Diagnosed Multiple Myeloma Enrolled in the Gimema-MM-03-05 and EMN01 Trials
Authors: Alessandra Larocca, Massimo Offidani, Pellegrino Musto, Francesca Patriarca, Lorenzo De Paoli, Paolo Corradini, Marco Salvini, Clotilde Cangialosi, Tommasina Guglielmelli, Giovannino Ciccone, Fausto Dore, Angelo Belotti, Mattia D'Agostino, Felicetto Ferrara, Daniela Oddolo, Riccardo Centurioni, Fabrizio Ciambelli, Stefano Spada, Donatella Iolanda Vincelli, Michele Cavo, Nicola Giuliani, Alberto Bosi, Concetta Conticello, Roberto Ria, Maria Teresa Petrucci, Mario Boccadoro
Journal: Blood (2017)
Abstract 20137: Comparison of Fractional Myocardial Mass, a Vessel-specific Myocardial Mass-at-risk, With Coronary Angiographic Scoring Systems for Predicting Percutaneous Revascularization
Authors: Hyung Yoon Kim, Jin-Ho Choi
Journal: Circulation (2017)

Introduction: The burden of coronary artery disease has been assessed by various semi-quantitative angiographic scores, which are frequently distinct. A non-invasive and quantitative modality may s...
A phase II study of bexarotene + GM-CSF in refractory AML and high risk MDS.
Authors: Kelly J. Norsworthy, Richard J. Jones, Erica D. Warlick, Eunpi Cho, William H. Matsui, B. Douglas Smith
Journal: Journal of Clinical Oncology (2015)

e13542 Background: Retinoids are known to cause terminal differentiation and apoptosis in non-APL AML cell lines, but have not proven clinically effective in patients (pts) with MDS or AML. Bexarotene (bex) is a retinoid that selectively binds RXR and mediates expression of genes that control differentiation and inhibits tumor cell growth in vitro. It is FDA approved for cutaneous T cell lymphoma. GM-CSF enhances the differentiation potential of bex in leukemia cells in vitro and we hypothesized the combination may have clinical activity in AML/MDS. Methods: A Phase II trial to assess safety and efficacy of bex + GM-CSF in pts with high-risk MDS or relapsed/refractory AML was performed. GM-CSF at 125 µg/m2/d SQ and oral bex at 300 mg/m2/d were given for 28 d cycles (cy) for a total of 6 planned cy. Clinical responses were assessed using IWG criteria in subjects receiving at least 2 cy. Results: 26 pts with AML or MDS met the eligibility criteria. Median age was 72 (range, 49-89) years. Of 16 AML pts, 13 had AML out of MDS, 2 had therapy-related AML and 1 had refractory disease; the other 10 had MDS. 17 pts (65%) had an abnormal karyotype. Median prior regimens was 2 (range, 0-5) and median ECOG PS 1 (range 0-2). 45 total cy of therapy were given with 13 pts (50%) completing 2 or more cy. After 2 cy, 1 pt with AML had a PR and 4 had HI-N (1 AML, 3 MDS), for an ORR of 38%; 4 had SD (2 AML, 2 MDS) and 4 had PD (3 AML, 1 MDS). 2 MDS pts remained with SD after 6 cy. Overall, there was a trend towards improved neutrophil count with mean ANC 639 at baseline and 1396 after 2 cy (p = 0.13), with no increase in marrow blasts (p = 0.57). All cy (n = 53) were analyzed for Grade 3 / 4 toxicities, which included neutropenic fever (n = 4), neutropenic infection (n = 2), bone pain (n = 1), fatigue (n = 2), edema (n = 1), weakness (n = 2), hypertriglyceridemia (n = 2), and elevated LFTs (n = 4). Conclusions: Bex/GM-CSF did not result in CRs in pts with poor risk myeloid malignancies; however, there was a trend towards higher ANCs without an increase in blasts, suggesting an impact on cellular differentiation. ORR was 38% and over 2/3 of pts who received 2 cy achieved at least SD; 2 pts maintained SD after 6 cy. These findings support further studies assessing the role of longer term maintenance therapy in less refractory pts. Clinical trial information: NCT00425477.
Twenty-eight-day prophylaxis with apixaban after radical cystectomy: Early results in safety.
Authors: Taha Anwar, Johar Raza, Naveen Pokala, Zachary Hamilton, Katie Murray
Journal: Journal of Clinical Oncology (2019)

488 Background: Venous thromboembolism (VTE) after oncologic surgery is a known risk and therefore guidelines recommend extended VTE prophylaxis up to 4 weeks for these populations. This prophylaxis is often costly and cumbersome to patients, as it requires self-injections with enoxaparin. The FDA has extended the indication for apixaban to include deep venous thrombosis (DVT) and pulmonary embolism (PE) prophylaxis in adults who have undergone hip or knee replacement surgery. The objective of this study was to identify safety concerns with using this prophylaxis for an extended time after radical cystectomy for bladder cancer. Methods: Patients from two institutions who underwent radical cystectomy for bladder cancer were retrospectively reviewed. Patients were included if they were discharged from the hospital with at least 28 days of prophylactic apixaban 2.5 mg BID. Descriptive statistics are used to show patient and outcome characteristics. Results: As of October 2018, 12 patients met inclusion criteria for this study. The median age was 69.5 years (interquartile range: 64.75 to 74 years) and 11 (91.7%) of the patients were male. 3 (25%), 1 (8.3%), 2 (16.7%), 1 (8.3%) and 5 (41.7%) of the patients were pathologic stage T0, Tis, T1, T2, T3/4, respectively, and 2 (16.7%) had node positive disease. Seven (58.3%) of the patients received neoadjuvant chemotherapy prior to radical cystectomy. No patients were identified with a symptomatic or asymptomatic VTE during pre-operative work up or during post-operative stay. No major bleeding events or complications related to the anticoagulant were identified in any patient, and no patient has developed a post-operative VTE including DVT or PE to date. Conclusions: Apixaban is approved for prophylaxis in preventing VTE after major surgery in other surgical specialties. This report shows that in the early stages of investigation of post-discharge use of apixaban, no increase in complications or readmissions have been identified in patients who have undergone radical cystectomy for bladder cancer. This safety, efficacy, and potential superiority needs further investigation.
Limitations of fibrosis grade as diagnostic criteria for post polycythemia vera and essential thrombocytosis myelofibrosis.
Authors: Krisstina L. Gowin, Srdan Verstovsek, Naval Guastad Daver, Naveen Pemmaraju, Ricardo Valdez, Heidi Kosiorek, Amylou C. Dueck, Ruben A. Mesa
Journal: Journal of Clinical Oncology (2015)

e18078 Background: The clinical phenotype of patients with myeloproliferative neoplasms (MPNs) including primary myelofibrosis (PMF), polycythemia vera (PV), and essential thrombocytosis (ET) who manifest WHO grade 1 fibrosis is poorly defined. We observed patients with existing PV and ET who manifest clinical progression towards a post PV/ET phenotype yet fail to meet IWG-MRT criteria due to subtheshold fibrosis. Methods: We retrospectively analyzed the clinical characteristics of 91 MPN patients with 1+ fibrosis. Descriptive statistics were used to summarize the two groups, PMF and PV/ET. IWG-MRT criteria applied for post-PV/ET MF with fibrosis component omitted and evaluated for percentage of criteria fulfillment. Results: 91 MPN pts with WHO grade 1 fibrosis were identified. Clinical characteristics and statistical comparison reported in table 1. When IWG-MRT criteria were applied to the PV/ET group, 38/58 (66%) of patients fulfilled criteria for diagnosis of post-PV/ET myelofibrosis (2+fibrosis requirement). Conclusions: PV/ET patients with WHO grade 1 fibrosis manifest a phenotype that suggests progression to post-PV/ET MF; however, these patients currently fail to meet 2008 IWG-MRT diagnostic criteria for this diagnosis on basis of sub-threshold fibrosis. MPN progression represents a biological spectrum and definitions of progression in ET/PV may benefit from other criteria not restricted by degree of fibrosis. Comparison of PMF and early fibrosis PV/ET. PMF (N:33) PV/ET (N:58) Total (N:91) P value Median age (yrs) 63 55 59 0.005 Male Female 25 (76%) 8 (24%) 32 (55%) 26 (45%) 57 (63%) 34 (37%) 0.05 JAK V617F + 16/33: (49%) 40/58: (69%) 56/91: (62%) 0.02 Median Hgb (g/dL) 11.1 (7.9-16.4) 12.8 (8.0-19.8) 12.2 (7.9-19.8) 0.24 Median WBC (X10 (9)) 26.9 (1.3-188) 8.9 (3.5-51.3) 10.8 (1.3-188) 0.02 Median Platelet (X10 (9)) 179 (18.0-1194) 505 (67-2286) 370 (18-2286) <0.001 Leukoerythroblastic Blood Smear 15/33 (45%) PV: 17 ET: 5 Total: 22/58 (38%) 37/91 (41%) 0.48 Splenomegaly (cm BCM) 18/33: (55%) 25/58: (43%) 43/91(48%) 0.29 Transfusion dependence 6/33: (18%) 2/58: (4%) 8/91: (9%) 0.02 Presence Of ≥ 1 symptom 17/33: (52%) 33/58: (57%) 50/91: (55%) 0.62
Glepaglutide, a novel long-acting glucagon-like peptide-2 analogue, for patients with short bowel syndrome: a randomised phase 2 trial
Authors: Rahim M Naimi, Mark Hvistendahl, Lotte H Enevoldsen, Jan L Madsen, Stefan Fuglsang, Steen S Poulsen, Hannelouise Kissow, Jens Pedersen, Nikolaj Nerup, Rikard Ambrus, Michael P Achiam, Lars B Svendsen, Jens J Holst, Bolette Hartmann, Svend H Hansen, Lars O Dragsted, Adam Steensberg, Ulrik Mouritzen, Mark B Hansen, Palle B Jeppesen
Journal: The Lancet. Gastroenterology & hepatology (2019)
A PDE3A Promoter Polymorphism Regulates cAMP-Induced Transcriptional Activity in Failing Human Myocardium
Authors: Carmen C. Sucharov, Stephanie J. Nakano, Dobromir Slavov, Jessica A. Schwisow, Erin Rodriguez, Karin Nunley, Allen Medway, Natalie Stafford, Penny Nelson, Timothy A. McKinsey, Matthew Movsesian, Wayne Minobe, Ian A. Carroll, Matthew R.G. Taylor, Michael R. Bristow
Journal: Journal of the American College of Cardiology (2019)
The role of biomarkers in improving clinical trial success: A study of 1,079 oncology drugs.
Authors: Gilberto Lopes, Jayson L. Parker, Andrew Willan, Syed Shah, Ashini Weerasinghe, Daniel Rubinger, Adam Falconi
Journal: Journal of Clinical Oncology (2015)

e17804 Background: Despite many recent successes in oncology, a large number of drugs still fail during clinical trial testing. It is widely believed that biomarkers are an important tool to improve the chances of a compound moving forward in drug development, but there is a dearth of data available to support this assertion. In this study we conducted the most rigorous analysis of biomarker impact in cancer drug testing to date. Methods: We obtained data from the National Institutes of Health Clinical Trials database (ClinicalTrials.gov) and other publicly available sources from January 1, 1998 until July 1, 2013, pooled across four indications: breast, lung, and colorrectal cancer and melanoma. We examined how far drugs made through clinical trial testing based on the presence or absence of biomarker use. Records were assessed for eligibility by two independent investigators. Disagreements between reviewers regarding study inclusion were resolved through consensus within the group. The clinical trial success rate was calculated by determining the percentage of unique drugs that successfully completed a phase of development out of the total number of drugs tested in a particular phase of development, as demonstrated using the following equation: Success rate for Phase x = (# of drugs that passed to Phase x+1)/((# of drugs that passed to Phase x+1) + (# drugs that failed at Phase x)). An overall statistical model (Kaplan-Meier log rank test) was run that combined all indications, before interrogating each indication separately. Results: Over 10,000 studies were screened and yielded 1,079 drugs that met our inclusion criteria, pooled across all four indications. The overall model revealed a strong effect of biomarker use in improving clinical trial outcomes. Succes rates for drugs developed with a biomarker was 24% versus 6% for compounds developed without biomarkers, a four-fold increase (p = 0.026). For each specific disease these results were most marked for phase III clinical trials. Conclusions: Biomarkers improve the chances of clinical trial success for cancer drugs. Investigators should prioritize study accrual to those trials that include biomarkers.
Relative copy number variation of genes in malignant gastric tissues.
Authors: Denis S. Kutilin, Dmitry I. Vodolazhsky, Dmitry S. Trifanov, Yury Valentinovich Przhedetsky
Journal: Journal of Clinical Oncology (2015)

e15033 Background: Gene copy number variation (CNV) is one of the mechanisms controlling gene expression. Identification of the number of copies of genes is important for the detection of predictive markers of malignancy. The purpose of our study was to investigate CNV genes responsible for apoptosis, oncogenesis, proliferation and oxidative phosphorylation. Methods: Tissues of 29 patients in Southern Russia with histologically confirmed diagnosis of gastric cancer: adenocarcinoma of G1-G2 and G3, signet ring cell and mixed carcinomas were studied. Determination of CNV of 19 genetic loci (BAX, GSTP1, CASP3, CASP8, HIF1A, OCT4, C-MYC, SOX2, BCL2, CASP8/FADD, NANOG, P53, CASP9, IL10, NFKB1, HV2, ACTB) was performed by RT-qPCR. Primers were designed using reference DNA sequences of NCBI GenBank. RT-qPCR was conducted using Thermal Cycler Bio-Rad CFX96 (Bio-Rad, USA). Locus B2M was used as a reference. Results: The study of patients with adenocarcinoma of the stomach (stage G1-2) showed significant (p < 0.05) decline in the relative copy number of gene 3 (OCT4, SOX2 and ACTB) and increase in MKI67 copy number in gastric tumor tissue compared with normal tissue. Statistically significant decrease in copy number of 12 genetic loci (BAX, CASP3, CASP8, OCT4, C-MYC, SOX2, BCL2, NANOG, CASP9, NFKB1, HV2 mtDNA and ACTB) was found in patients with gastric adenocarcinoma (stage G3). Patients with mixed types of cancer (G3 adenocarcinoma + signet ring cell carcinoma) showed a decrease in copy number of genes BAX, CASP8, CASP9, IL10 and HV2 and increased copy number of the GSTP1 gene. A decrease in the relative copy number of the P53 gene and an increase in copy number of GSTP1 and BCL2 genes were found in patients with signet ring cell type gastric cancer. Conclusions: Changes in CNV pattern are specific to a particular histological type of cancer, and also depend on the stage of tumor cell differentiation.