PCOM Library / Hot Topics in Research / Archive for "Internal Medicine"

Category: Internal Medicine

Sexual Health in Women Affected by Cancer: Focus on Sexual Pain

katheride Hot Topics in Research, Oncology

Sexual Health in Women Affected by Cancer: Focus on Sexual Pain
As cancer therapies improve, the number of women surviving or living long lives with cancer continues to increase. Treatment modalities, including surgery, chemotherapy, radiotherapy, and hormonal therapy, affect sexual function and may cause sexual pain through a variety of mechanisms, depending on treatment type. Adverse sexual effects resulting from ovarian damage, anatomic alterations, and neurologic, myofascial, or pelvic organ injury may affect more than half of women affected by cancer. Despite the fact that no specialty is better qualified to render care for this consequence of cancer treatments, many obstetrician–gynecologists (ob-gyns) feel uncomfortable or ill-equipped to address sexual pain in women affected by cancer. Asking about sexual pain and dyspareunia and performing a thorough physical examination are essential steps to guide management, which must be tailored to individual patient goals. Understanding the cancer treatment-related pathophysiology of sexual pain aids in providing this care. Effective mechanism-based treatments for sexual pain and dyspareunia are available, and by using them, knowledgeable ob-gyns can enhance the quality of life of potentially millions of women affected by cancer.
 
Deborah Coady, MD, and Vanessa Kennedy, MD
Obstet Gynecol 2016;128:775–91    DOI: 10.1097/AOG.0000000000001621

Long-term benefits and risks of frontline nilotinib vs imatinib for chronic myeloid leukemia in chronic phase: 5-year update of the randomized ENESTnd trial

katheride Blood, Hot Topics in Research, Oncology

Long-term benefits and risks of frontline nilotinib vs imatinib for chronic myeloid leukemia in chronic phase: 5-year update of the randomized ENESTnd trial
In the phase 3 Evaluating Nilotinib Efficacy and Safety in Clinical Trials–Newly Diagnosed Patients (ENESTnd) study, nilotinib resulted in earlier and higher response rates and a lower risk of progression to accelerated phase/blast crisis (AP/BC) than imatinib in patients with newly diagnosed chronic myeloid leukemia in chronic phase (CML-CP). Here, patients’ long-term outcomes in ENESTnd are evaluated after a minimum follow-up of 5 years. By 5 years, more than half of all patients in each nilotinib arm (300 mg twice daily, 54%; 400 mg twice daily, 52%) achieved a molecular response 4.5 (MR4.5; BCR-ABL ⩽0.0032% on the International Scale) compared with 31% of patients in the imatinib arm. A benefit of nilotinib was observed across all Sokal risk groups. Overall, safety results remained consistent with those from previous reports. Numerically more cardiovascular events (CVEs) occurred in patients receiving nilotinib vs imatinib, and elevations in blood cholesterol and glucose levels were also more frequent with nilotinib. In contrast to the high mortality rate associated with CML progression, few deaths in any arm were associated with CVEs, infections or pulmonary diseases. These long-term results support the positive benefit-risk profile of frontline nilotinib 300 mg twice daily in patients with CML-CP.
A Hochhaus, G Saglio, TP Hughes, RA Larson, D-W Kim, S Issaragrisil, PD le Coutre, G Etienne , PE Dorlhiac-Llacer, RE Clark, IW Flinn, H Nakamae, B Donohue, W Deng, D Dalal, HD Menssen and HM Kantarjian
Leukemia (2016) 30, 1044–1054; doi:10.1038/leu.2016.5

Detyrosinated microtubules buckle and bear load in contracting cardiomyocytes

katheride Cardiology, Hot Topics in Research

Detyrosinated microtubules buckle and bear load in contracting cardiomyocytes
The microtubule (MT) cytoskeleton can transmit mechanical signals and resist compression in contracting cardiomyocytes. How MTs perform these roles remains unclear because of difficulties in observing MTs during the rapid contractile cycle. Here, we used high spatial and temporal resolution imaging to characterize MT behavior in beating mouse myocytes. MTs deformed under contractile load into sinusoidal buckles, a behavior dependent on posttranslational “detyrosination” of α-tubulin. Detyrosinated MTs associated with desmin at force-generating sarcomeres. When detyrosination was reduced, MTs uncoupled from sarcomeres and buckled less during contraction, which allowed sarcomeres to shorten and stretch with less resistance. Conversely, increased detyrosination promoted MT buckling, stiffened the myocyte, and correlated with impaired function in cardiomyopathy. Thus, detyrosinated MTs represent tunable, compression-resistant elements that may impair cardiac function in disease.

PATRICK ROBISON, MATTHEW A. CAPORIZZO, HOSSEIN AHMADZADEH, ALEXEY I. BOGUSH, CHRISTINA YINGXIAN CHEN, KENNETH B. MARGULIES, VIVEK B. SHENOY, BENJAMIN L. PROSSER

SCIENCE 

Dietary patterns and the risk of major adverse cardiovascular events in a global study of high-risk patients with stable coronary heart disease

katheride Cardiology, coronary artery disease, Hot Topics in Research

Dietary patterns and the risk of major adverse cardiovascular events in a global study of high-risk patients with stable coronary heart disease

Objectives To determine whether dietary pattern assessed by a simple self-administered food frequency questionnaire is associated with major adverse cardiovascular events (MACE) in high-risk patients with stable coronary artery disease.

Background A Mediterranean dietary pattern has been associated with lower cardiovascular (CV) mortality. It is less certain whether foods common in western diets are associated with CV risk.

Methods At baseline, 15 482 (97.8%) patients (mean age 67 ± 9 years) with stable coronary heart disease from 39 countries who participated in the Stabilisation of atherosclerotic plaque by initiation of darapladib therapy (STABILITY) trial completed a life style questionnaire which included questions on common foods. A Mediterranean diet score (MDS) was calculated for increasing consumption of whole grains, fruits, vegetables, legumes, fish, and alcohol, and for less meat, and a ‘Western diet score’ (WDS) for increasing consumption of refined grains, sweets and deserts, sugared drinks, and deep fried foods. A multi-variable Cox proportional hazards models assessed associations between MDS or WDS and MACE, defined as CV death, non-fatal myocardial infarction, or non-fatal stroke.

Results After a median follow-up of 3.7 years MACE occurred in 7.3% of 2885 subjects with an MDS ≥15, 10.5% of 4018 subjects with an MDS of 13–14, and 10.8% of 8579 subjects with an MDS ≤12. A one unit increase in MDS >12 was associated with lower MACE after adjusting for all covariates (+1 category HR 0.95, 95% CI 0.91, 0.98, P = 0.002). There was no association between WDS (adjusted model +1 category HR 0.99, 95% CI 0.97, 1.01) and MACE.

Conclusion Greater consumption of healthy foods may be more important for secondary prevention of coronary artery disease than avoidance of less healthy foods typical of Western diets.

 
 
Ralph A. H. Stewart1*, Lars Wallentin2, Jocelyne Benatar1, Nicolas Danchin3, Emil Hagstro¨m2, Claes Held2, Steen Husted4, Eva Lonn5, Amanda Stebbins6, Karen Chiswell6, Ola Vedin2, David Watson7, and Harvey D. White
European Heart Journal Apr 2016, DOI: 10.1093/eurheartj/ehw125

Pioglitazone after Ischemic Stroke or Transient Ischemic Attack

katheride Cardiology, Hot Topics in Research

Pioglitazone after Ischemic Stroke or Transient Ischemic Attack
BACKGROUND Patients with ischemic stroke or transient ischemic attack (TIA) are at increased risk for future cardiovascular events despite current preventive therapies. The identification of insulin resistance as a risk factor for stroke and myocardial infarction raised the possibility that pioglitazone, which improves insulin sensitivity, might benefit patients with cerebrovascular disease.
METHODS In this multicenter, double-blind trial, we randomly assigned 3876 patients who had had a recent ischemic stroke or TIA to receive either pioglitazone (target dose, 45 mg daily) or placebo. Eligible patients did not have diabetes but were found to have insulin resistance on the basis of a score of more than 3.0 on the homeostasis model assessment of insulin resistance (HOMA-IR) index. The primary outcome was fatal or nonfatal stroke or myocardial infarction.
RESULTS By 4.8 years, a primary outcome had occurred in 175 of 1939 patients (9.0%) in the pioglitazone group and in 228 of 1937 (11.8%) in the placebo group (hazard ratio in the pioglitazone group, 0.76; 95% confidence interval [CI], 0.62 to 0.93; P=0.007). Diabetes developed in 73 patients (3.8%) and 149 patients (7.7%), respectively (hazard ratio, 0.48; 95% CI, 0.33 to 0.69; P<0.001). There was no significant between-group difference in all-cause mortality (hazard ratio, 0.93; 95% CI, 0.73 to 1.17; P=0.52). Pioglitazone was associated with a greater frequency of weight gain exceeding 4.5 kg than was placebo (52.2% vs. 33.7%, P<0.001), edema (35.6% vs. 24.9%, P<0.001), and bone fracture requiring surgery or hospitalization (5.1% vs. 3.2%, P=0.003).
CONCLUSIONS In this trial involving patients without diabetes who had insulin resistance along with a recent history of ischemic stroke or TIA, the risk of stroke or myocardial infarction was lower among patients who received pioglitazone than among those who received placebo. Pioglitazone was also associated with a lower risk of diabetes but with higher risks of weight gain, edema, and fracture. (Funded by the National Institute of Neurological Disorders and Stroke; ClinicalTrials.gov number, NCT00091949.)
 
W.N. Kernan, C.M. Viscoli, K.L. Furie, L.H. Young, S.E. Inzucchi, M. Gorman, P.D. Guarino, A.M. Lovejoy, P.N. Peduzzi, R. Conwit, L.M. Brass,* G.G. Schwartz, H.P. Adams, Jr., L. Berger, A. Carolei, W. Clark, B. Coull, G.A. Ford, D. Kleindorfer, J.R. O’Leary, M.W. Parsons, P. Ringleb, S. Sen, J.D. Spence, D. Tanne, D. Wang, and T.R. Winder
 
N Engl J Med 2016;374:1321-31. DOI: 10.1056/NEJMoa1506930 Copyright © 2016 Massachusetts Medical Society

Low-Dose Acetylsalicylic Acid Treatment and Impact on Short-Term Mortality in Staphylococcus aureus Bloodstream Infection: A Propensity Score–Matched Cohort Study

katheride Cardiology, Hot Topics in Research

Low-Dose Acetylsalicylic Acid Treatment and Impact on Short-Term Mortality in Staphylococcus aureus Bloodstream Infection: A Propensity Score–Matched Cohort Study
Abstract
Objectives: Staphylococcus aureus bloodstream infection is associated with considerable mortality. Experimental models suggest a direct antistaphylococcal effect of acetylsalicylic acid, but evidence from human studies is scarce. We aimed to estimate the effect of low-dose acetylsalicylic acid therapy on mortality in bloodstream infections caused by S. aureus compared with Escherichia coli.
Design: Retrospective cohort study based on observational data from 838 and 602 episodes of S. aureus and E. coli bloodstream infection, respectively. Setting: Swiss tertiary referral center. Patients: Adult patients with S. aureus and E. coli bloodstream infection, respectively, categorized according to low-dose acetylsalicylic acid therapy as outpatient or inpatient before bacteremia.
Interventions: None.
Measurements and Main Results: Thirty-day all-cause mortality was analyzed in a total of 314 propensity score-matched S. aureus bloodstream infection and in 268 E. coli bloodstream infection patients, respectively (1:1 match of low-dose acetylsalicylic acid users and nonusers). S. aureus bloodstream infection cases and controls were equally matched for relevant confounders except treatment with statins, which was strongly associated with a low-dose acetylsalicylic acid use (p < 0.001). At day 30, 12.1% of cases and 27.4% of controls had died (hazard ratio, 0.40; p < 0.001). Low-dose acetylsalicylic acid use was associated with a reduced 30-day all-cause mortality in multivariate analysis (hazard ratio, 0.38; 95% CI, 0.21-0.69; p = 0.001) of matched patients and also of the entire cohort (n = 689) after adjustment for the propensity score (hazard ratio, 0.58, 95% CI, 0.34-0.98; p = 0.04). In contrast, low-dose acetylsalicylic acid use was not associated with the primary endpoint in patients with E. coli bloodstream infection (hazard ratio, 0.78; 95% CI, 0.40-1.55; p = 0.8).
Conclusions: Low-dose acetylsalicylic acid at the time of bloodstream infection was strongly associated with a reduced short-term mortality in patients with S. aureus bloodstream infection. Future studies are required to investigate if early low-dose acetylsalicylic acid is a suitable treatment in patients with S. aureus bloodstream infection.
Osthoff, Michael MD; Sidler, Jan A. MD; Lakatos, Botond MD; Frei, Reno MD; Dangel, Marc MPH; Weisser, Maja MD; Battegay, Manuel MD; Widmer, Andreas F. MD, MS
Copyright (C) by 2016 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. All Rights Reserved.

Association Between Treatment at a High-Volume Facility and Improved Survival for Radiation-Treated Men With High-Risk Prostate Cancer

katheride Hot Topics in Research, Oncology, Prostate

Association Between Treatment at a High-Volume Facility and Improved Survival for Radiation-Treated Men With High-Risk Prostate Cancer
Purpose: Although the association between higher hospital volume and improved outcomes has been well-documented in surgery, there is little data about whether this effect exists for radiation-treated patients. We investigated whether treatment at a radiation facility that treats a high volume of prostate cancer patients is associated with improved survival for men with high-risk prostate cancer. Methods and Materials: We used the National Cancer Database (NCDB) to identity patients diagnosed with prostate cancer from 2004 to 2006. The radiation case volume (RCV) of each hospital was based on its number of radiation-treated prostate cancer patients. We used propensity-score based analysis to compare the overall survival (OS) of high-risk prostate cancer patients in high versus low RCV hospitals. Primary endpoint is overall survival. Covariates adjusted for were tumor characteristics, sociodemographic factors, radiation type, and use of androgen deprivation therapy (ADT). Results: A total of 19,565 radiation-treated high-risk patients were identified. Median follow-up was 81.0 months (range: 1-108 months). When RCV was coded as a continuous variable, each increment of 100 radiation-managed patients was associated with improved OS (adjusted hazard ratio [AHR]: 0.97; 95% confidence interval [CI]: 0.95- 0.98; P<.0001) after adjusting for known confounders. For illustrative purposes, when RCV was dichotomized at the 80th percentile (43 patients/year), high RCV was associated with improved OS (7-year overall survival 76% vs 74%, log-rank test PZ.0005; AHR: 0.91, 95% CI: 0.86-0.96, PZ.0005). This association remained significant when RCV was dichotomized at 75th (37 patients/year), 90th (60 patients/year), and 95th (84 patients/year) percentiles but not the 50th (19 patients/year). Conclusions: Our results suggest that treatment at centers with higher prostate cancer radiation case volume is associated with improved OS for radiation-treated men with high-risk prostate cancer. 
Int J Radiation Oncol Biol Phys, Vol. 94, No. 4, pp. 683e690, 2016
Copyright: 2016 The Authors
Yu-Wei Chen, MD, MS, Brandon A. Mahal, MD, Vinayak Muralidhar, MSc, Michelle Nezolosky, BA, Clair J. Beard, MD, Robert B. Den, MD, Felix Y. Feng, MD,Karen E. Hoffman, MD, MPH, MHSc, Neil E. Martin, MD, MPH, Peter F. Orio, DO, MS, and Paul L. Nguyen, MD

Visualization of regional tau deposits using 3H-THK5117 in Alzheimer brain tissue

katheride Alzheimer Disease, Hot Topics in Research

Visualization of regional tau deposits using 3H-THK5117 in Alzheimer brain tissue

Abstract

 The accumulation of neurofibrillary tangles, composed of aggregated hyperphosphorylated tau protein, starts spreading early in specific regions in the course of Alzheimer’s disease (AD), correlating with the progression of memory dysfunction. The non-invasive imaging of tau could therefore facilitate the early diagnosis of AD, differentiate it from other dementing disorders and allow evaluation of tau immunization therapy outcomes. In this study we characterized the in vitro binding properties of THK5117, a tentative radiotracer for positron emission tomography (PET) imaging of tau brain deposits.

Results

Saturation and competition binding studies of 3H-THK5117 in post-mortem AD brain tissue showed the presence of multiple binding sites. THK5117 binding was significantly higher in hippocampal (p < 0.001) and temporal (p < 0.01) tissue homogenates in AD compared to controls. Autoradiography studies with 3H-THK5117 was performed on large frozen brain sections from three AD cases who had been followed clinically and earlier undergone in vivo 18F-FDG PET investigations. The three AD cases showed distinct differences in regional THK5117 binding that were also observed in tau immunohistopathology as well as in clinical presentation. A negative correlation between in vivo 18F-FDG PET and in vitro 3H-THK5117 autoradiography was observed in two of the three AD cases.

Conclusions

This study supports that new tau PET tracers will provide further understanding on the role of tau pathology in the diversity of the clinical presentation in AD.

Acta Neuropathologica Communications20153:40, DOI: 10.1186/s40478-015-0220-4; Lemoine et al. 2015; Received: 14 June 2015; Accepted: 15 June 2015; Published: 2 July 2015

Antithrombotic Therapy for VTE Disease: CHEST Guideline and Expert Panel Report

katheride Blood, Hot Topics in Research, Lung, Research Commentary

Antithrombotic Therapy for VTE Disease: CHEST Guideline and Expert Panel Report
BACKGROUND: We update recommendations on 12 topics that were in the 9th edition of these guidelines, and address 3 new topics.
METHODS: We generate strong (Grade 1) and weak (Grade 2) recommendations based on high- (Grade A), moderate- (Grade B), and low- (Grade C) quality evidence.
RESULTS: For VTE and no cancer, as long-term anticoagulant therapy, we suggest dabigatran (Grade 2B), rivaroxaban (Grade 2B), apixaban (Grade 2B), or edoxaban (Grade 2B) over vitamin K antagonist (VKA) therapy, and suggest VKA therapy over low-molecular-weight heparin (LMWH; Grade 2C). For VTE and cancer, we suggest LMWH over VKA (Grade 2B), dabigatran (Grade 2C), rivaroxaban (Grade 2C), apixaban (Grade 2C), or edoxaban (Grade 2C). We have not changed recommendations for who should stop anticoagulation at 3 months or receive extended therapy. For VTE treated with anticoagulants, we recommend against an inferior vena cava filter (Grade 1B). For DVT, we suggest not using compression stockings routinely to prevent PTS (Grade 2B). For subsegmental pulmonary embolism and no proximal DVT, we suggest clinical surveillance over anticoagulation with a low risk of recurrent VTE (Grade 2C), and anticoagulation over clinical surveillance with a high risk (Grade 2C). We suggest thrombolytic therapy for pulmonary embolism with hypotension (Grade 2B), and systemic therapy over catheter-directed thrombolysis (Grade 2C). For recurrent VTE on a non-LMWH anticoagulant, we suggest LMWH (Grade 2C); for recurrent VTE on LMWH, we suggest increasing the LMWH dose (Grade 2C).
CONCLUSIONS: Of 54 recommendations included in the 30 statements, 20 were strong and none was based on high-quality evidence, highlighting the need for further research.
 
CHEST 2016; 149(2):315-352
Clive Kearon, MD, PhD; Elie A. Akl, MD, MPH, PhD; Joseph Ornelas, PhD; Allen Blaivas, DO, FCCP; David Jimenez, MD, PhD, FCCP; Henri Bounameaux, MD; Menno Huisman, MD, PhD; Christopher S. King, MD, FCCP; Timothy A. Morris, MD, FCCP; Namita Sood, MD, FCCP; Scott M. Stevens, MD; Janine R. E. Vintch, MD, FCCP; Philip Wells, MD; Scott C. Woller, MD; and COL Lisa Moores, MD, FCCP

Atrial fibrillation as risk factor for cardiovascular disease and death in women compared with men: systematic review and meta-analysis of cohort studies

katheride Atrial Fibrillation, Cardiology, Hot Topics in Research

Atrial fibrillation as risk factor for cardiovascular disease and death in women compared with men: systematic review and meta-analysis of cohort studies
Abstract

Objective To determine whether atrial fibrillation is a stronger risk factor for cardiovascular disease and death in women compared with men.

Design Meta-analysis of cohort studies.

Data sources Studies published between January 1966 and March 2015, identified through a systematic search of Medline and Embase and review of references.

Eligibility for selecting studies Cohort studies with a minimum of 50 participants with and 50 without atrial fibrillation that reported sex specific associations between atrial fibrillation and all cause mortality, cardiovascular mortality, stroke, cardiac events (cardiac death and non-fatal myocardial infarction), and heart failure.

Data extraction Two independent reviewers extracted study characteristics and maximally adjusted sex specific relative risks. Inverse variance weighted random effects meta-analysis was used to pool sex specific relative risks and their ratio.

Results 30 studies with 4 371 714 participants were identified. Atrial fibrillation was associated with a higher risk of all cause mortality in women (ratio of relative risks for women compared with men 1.12, 95% confidence interval 1.07 to 1.17) and a significantly stronger risk of stroke (1.99, 1.46 to 2.71), cardiovascular mortality (1.93, 1.44 to 2.60), cardiac events (1.55, 1.15 to 2.08), and heart failure (1.16, 1.07 to 1.27). Results were broadly consistent in sensitivity analyses.

Conclusion Atrial fibrillation is a stronger risk factor for cardiovascular disease and death in women compared with men, though further research would be needed to determine any causality.

 
Connor A Emdin, DPhil; Christopher X Wong; Allan J Hsiao; Douglas G Altman; Sanne AE Peters; Mark Woodward; Ayodele A Odutayo
BMJ 2016; 352 doi: http://dx.doi.org/10.1136/bmj.h7013 (Published 19 January 2016)