Dermatological and environmental toxicological impact of the sunscreen ingredient oxybenzone/benzophenone-3

Summary

Oxybenzone (Benzophenone-3) is an emerging human and environmental contaminant used in sunscreens and personal care products to help minimize the damaging effects of ultraviolet radiation. The Center for Disease Control fourth national report on human exposure to environmental chemicals demonstrated that approximately 97% of the people tested have oxybenzone present in their urine, and independent scientists have reported various concentrations in waterways and fish worldwide. Oxybenzone can also react with chlorine, producing hazardous by-products that can concentrate in swimming pools and wastewater treatment plants. Moreover, adverse reactions could very well be increased by the closed loop of ingesting fish contaminated with oxybenzone and/or washing the ingredient off our bodies and having it return in drinking water as treatment plants do not effectively remove the chemical as part of their processing protocols. In humans, oxybenzone has been reported to produce contact and photocontact allergy reactions, implemented as a possible endocrine disruptor and has been linked to Hirschsprung's disease. Environmentally, oxybenzone has been shown to produce a variety of toxic reactions in coral and fish ranging from reef bleaching to mortality. Lastly, with the rise in skin cancer rates and the availability of more effective sunscreen actives such as micronized zinc oxide and titanium dioxide, serious doubts about the relative prevention benefit of personal care products containing oxybenzone must be raised and compared with the potential negative health and environmental effects caused by the accumulation of this and other chemicals in the ecosystem.

http://ift.tt/2z2pwvF

The pathogenesis of cutaneous squamous cell carcinoma in organ transplant recipients

Summary

The pathogenesis of keratinocyte carcinoma following organ transplantation is multifactorial, and recent evidence suggests a complex and often synergistic interplay between the carcinogenic effects of ultraviolet radiation, compromised immune surveillance, direct pro- and anticarcinogenic effects of drugs, oncogenic viruses (in particular, beta-genus human papillomaviruses) and host genetic susceptibility factors. We present an overview of those factors for which there is currently the most convincing evidence and highlight important gaps in our knowledge. In particular, a clear understanding of the interdependence and relative contributions of these co-factors is currently lacking, yet has important implications for rational development of clinically relevant biomarkers and targeted strategies for treatment and prevention of post-transplant keratinocyte cancers.

http://ift.tt/2z0OnAb

Research gaps in the management and prevention of cutaneous squamous cell carcinoma in organ transplant recipients

Summary

Although tremendous progress has been made in recent years in skin cancer care for organ transplant recipients, significant gaps remain in data-driven clinical guidelines, particularly for the treatment and prevention of cutaneous squamous cell carcinoma (cSCC), the most common malignancy among this population. In this review, we aim to summarize current knowledge around the management of cSCC and highlight the most significant gaps in knowledge that continue to pose challenges in the delivery of skin cancer care for organ transplant recipients. We suggest future directions for research that will bridge existing gaps and establish evidence-driven guidelines for primary prevention, screening and treatment of cSCC in this high-risk patient population.

http://ift.tt/2iMl549

Introduction to the 2017 Cardiovascular Surgery-Themed Issue of Circulation.

Author: Ruel, Marc MD, MPH; Gardner, Timothy J. MD

Page: 1675

http://ift.tt/2yfMeDD

Does Use of Bilateral Internal Mammary Artery Grafting Reduce Long-Term Risk of Repeat Coronary Revascularization?: A Multicenter Analysis.

Author: Iribarne, Alexander MD, MS; Schmoker, Joseph D. MD; Malenka, David J. MD; Leavitt, Bruce J. MD; McCullough, Jock N. MD; Weldner, Paul W. MD; DeSimone, Joseph P. MD; Westbrook, Benjamin M. MD; Quinn, Reed D. MD; Klemperer, John D. MD; Sardella, Gerald L. MD; Kramer, Robert S. MD; Olmstead, Elaine M. BA; DiScipio, Anthony W. MD; for The Northern New England Cardiovascular Disease Study Group

Page: 1676-1685

http://ift.tt/2lwWWj8

Bilateral Versus Single Internal Mammary Artery Bypass Grafting: Do We Have the Answer?.

Author: Sellke, Frank W. MD

Page: 1686-1687

http://ift.tt/2yfcmyd

Study Comparing Vein Integrity and Clinical Outcomes in Open Vein Harvesting and 2 Types of Endoscopic Vein Harvesting for Coronary Artery Bypass Grafting: The VICO Randomized Clinical Trial (Vein Integrity and Clinical Outcomes).

Author: Krishnamoorthy, Bhuvaneswari PhD; Critchley, William R. MRes; Thompson, Alexander J. MSc; Payne, Katherine PhD; Morris, Julie PhD; Venkateswaran, Rajamiyer V. MD; Caress, Ann L. PhD; Fildes, James E. PhD *; Yonan, Nizar MD *

Page: 1688-1702

http://ift.tt/2lukncF

Immediate and Midterm Cardiac Remodeling After Surgical Pulmonary Valve Replacement in Adults With Repaired Tetralogy of Fallot: A Prospective Cardiovascular Magnetic Resonance and Clinical Study.

Author: Heng, Ee Ling MBBS, BSc, MRCP, PhD; Gatzoulis, Michael A. MD, PhD, FESC; Uebing, Anselm MD, PhD; Sethia, Babulal FRCS; Uemura, Hideki MD, MPhil, FRCS; Smith, Gillian C. PhD; Diller, Gerhard-Paul MD, PhD; McCarthy, Karen P. BSc, PhD; Ho, Siew Yen PhD, FRCPath, FESC; Li, Wei MD, PhD; Wright, Piers BSc; Spadotto, Veronica MD; Kilner, Philip J MD, PhD; Oldershaw, Paul FRCP; Pennell, Dudley J. MD, FRCP, FESC; Shore, Darryl F. FRCS; Babu-Narayan, Sonya V. MB, BS, BSc, FRCP, PhD, FESC

Page: 1703-1713

http://ift.tt/2ygWhIf

Left Ventricular Assist Device Malfunctions: It Is More Than Just the Pump.

Author: Kormos, Robert L. MD; McCall, Michael MEng; Althouse, Andrew PhD; Lagazzi, Luigi MD; Schaub, Richard PhD; Kormos, Michael A. BME; Zaldonis, Jared A. BSCE; Sciortino, Christopher MD, PhD; Lockard, Kathleen RN; Kuntz, Nicole RN; Dunn, Elizabeth RN; Teuteberg, Jeffrey J. MD

Page: 1714-1725

http://ift.tt/2lujZLf

A Population-Based Study of Abdominal Aortic Aneurysm Treatment in Finland 2000 to 2014.

Author: Laine, Matti T. MD; Laukontaus, Sani J. MD, PhD; Sund, Reijo PhD; Aho, Pekka S. MD, PhD; Kantonen, Ilkka MD, PhD; Alback, Anders MD, PhD; Venermo, Maarit MD, PhD

Page: 1726-1734

http://ift.tt/2yhdb9X

Opportunities for Improving Population-Based Management of Abdominal Aortic Aneurysms.

Author: Mell, Matthew W. MD, MS

Page: 1735-1736

http://ift.tt/2lu9Yhg

The Optimal Timing of Stage 2 Palliation for Hypoplastic Left Heart Syndrome: An Analysis of the Pediatric Heart Network Single Ventricle Reconstruction Trial Public Data Set.

Author: Meza, James M. MD; Hickey, Edward J. MD; Blackstone, Eugene H. MD; Jaquiss, Robert D.B. MD; Anderson, Brett R. MD, MBA; Williams, William G. MD; Cai, Sally MSc; Van Arsdell, Glen S. MD; Karamlou, Tara MD, MSc; McCrindle, Brian W. MD, MPH

Page: 1737-1748

http://ift.tt/2yfXT56

Mechanisms, Consequences, and Prevention of Coronary Graft Failure.

Author: Gaudino, Mario MD; Antoniades, Charalambos MD; Benedetto, Umberto MD; Deb, Saswata MD; Di Franco, Antonino MD; Di Giammarco, Gabriele MD; Fremes, Stephen MD; Glineur, David MD; Grau, Juan MD; He, Guo-Wei MD; Marinelli, Daniele MD; Ohmes, Lucas B. MD; Patrono, Carlo MD; Puskas, John MD; Tranbaugh, Robert MD; Girardi, Leonard N. MD; Taggart, David P. MD; The ATLANTIC (Arterial Grafting International Consortium) Alliance; Ruel, Marc MD; Bakaeen, Faisal G. MD

Page: 1749-1764

http://ift.tt/2lvaqfb

Interventions and Outcomes in Children With Hypoplastic Left Heart Syndrome Born in England and Wales Between 2000 and 2015 Based on the National Congenital Heart Disease Audit.

Author: Rogers, Libby MMath; Pagel, Christina PhD; Sullivan, Ian D. MD, FRCP; Mustafa, Muhammed MD; Tsang, Victor MS, FRCS; Utley, Martin PhD; Bull, Catherine MRCP; Franklin, Rodney C. MD, FRCP; Brown, Katherine L. MPH, MD

Page: 1765-1767

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Ousting RAGE in melanoma: A viable therapeutic target?

Publication date: Available online 24 October 2017
Source:Seminars in Cancer Biology
Author(s): Deeba N. Syed, Ahmed Aljohani, Durdana Waseem, Hasan Mukhtar
Melanoma remains an important health concern, given the steady increase in incidence and acquisition of resistance to systemic therapies. The receptor for advanced glycation end products (RAGE) initially identified for its binding to advanced glycation end products was subsequently acknowledged as a pattern recognition receptor given its ability to recognize similar structural elements within numerous ligands. Recent studies have elucidated a plausible role of RAGE in melanoma progression through modulation of inflammatory, proliferative and invasive cellular responses. Several of its ligands including the S100 proteins and HMGB1 are being investigated for their involvement in melanoma metastasis and as potential biomarkers of the disease. Targeting RAGE signaling represents a viable therapeutic strategy which remains underexplored in cutaneous malignancies. Here we have summarized current knowledge on the functionality of RAGE with special focus on specific ligands enumerated in various in vitro and in vivo melanoma models.



http://ift.tt/2zkapkc

Epigenetics of Malignant Melanoma

Publication date: Available online 23 October 2017
Source:Seminars in Cancer Biology
Author(s): Bruce Moran, Romina Silva, Antoinette S. Perry, William M. Gallagher
Patients with malignant melanoma generally have a good prognosis if the disease presents prior to metastasis. Due to progress with targeted and immunotherapies, the median survival of metastatic melanoma patients is now over 2 years. The disease is characterised by one of the highest somatic mutation rates observed amongst cancer types, with a specific mutational signature based on UV radiation damage evident. Highly prevalent mutations, such as the BRAF^V600E, in the MAPK cascade indicate truncal involvement of this pathway in the earliest stage of melanoma. The molecular sub-classification of melanoma based on genetic alterations is now well established. This has paved the way for researchers in epigenetics to investigate specific pathways of known importance, and the involvement of the diverse range of epigenetic mechanisms. Herein, we review the literature to highlight that epigenetic alterations are integrally involved in this malignancy. We focus on the most current evidence around the epigenetic mechanisms: DNA methylation and demethylation including 5-hydroxy-methylcytosine; histone post-translational modifications including variant histones; chromatin remodelling complexes and in particular the polycomb-repressive complex PRC2 and its histone methyltransferase subunit EZH2; and non-coding RNAs. Each mechanism is described generally, studies involving melanoma are assessed and clinical relevance is highlighted where possible.



http://ift.tt/2iOTzml

Oxidation, glycation and glycoxidation—The vicious cycle and lung cancer

Publication date: Available online 19 October 2017
Source:Seminars in Cancer Biology
Author(s): Saheem Ahmad, Mohd Yasir Khan, Zeeshan Rafi, Hamda Khan, Zeba Siddiqui, Shahnawaz Rehman, Uzma Shahab, Mohd Sajid Khan, Mohd Saeed, Sultan Alouffi, Mohd Shahnawaz Khan
The combine effect of oxidative and glycative stress predisposed to glycoxidation, and their outcomes that play critical role in lung cancer have been examined in different ways. The therapeutic approaches for lung cancer are still unsatisfactory. We observe some unclear and decisive pathways which might play an important role in targeting lung cancer. The roadmap of signaling pathway includes p38 MAPK, NF-ƙB, TNF-α and AGE-RAGE binding affinity play role in the cell growth, proliferation, apoptosis inhibition and metastasis. The goal of this review is to achieve a new signaling map inside the lung cancer which is mediated by glycoxidative products mainly reactive dicarbonyls and advanced glycation end products (AGEs). Additionally, AGE-RAGE binding critically regulates the suppression and promotion of lung cancer via inhibition and activation of different signaling pathways. Hence, this review suggests the role of oxidation, glycation, and glycoxidation in lung cancer.



http://ift.tt/2zkfFEz

KRAS, YAP, and obesity in pancreatic cancer: a signaling network with multiple loops

Publication date: Available online 24 October 2017
Source:Seminars in Cancer Biology
Author(s): Guido Eibl, Enrique Rozengurt
Pancreatic ductal adenocarcinoma (PDAC) continues to be a lethal disease with no efficacious treatment modalities. The incidence of PDAC is expected to increase, at least partially because of the obesity epidemic. Increased efforts to prevent or intercept this disease are clearly needed. Mutations in KRAS are initiating events in pancreatic carcinogenesis supported by genetically engineered mouse models of the disease. However, oncogenic KRAS is not entirely sufficient for the development of fully invasive PDAC. Additional genetic mutations and/or environmental, nutritional, and metabolic stressors, e.g. inflammation and obesity, are required for efficient PDAC formation with activation of KRAS downstream effectors. Multiple factors "upstream" of KRAS associated with obesity, including insulin resistance, inflammation, changes in gut microbiota and GI peptides, can enhance/modulate downstream signals. Multiple signaling networks and feedback loops "downstream" of KRAS have been described that respond to obesogenic diets. We propose that KRAS mutations potentiate a signaling network that is promoted by environmental factors. Specifically, we envisage that KRAS mutations increase the intensity and duration of the growth-promoting signaling network. As the transcriptional activator YAP plays a critical role in the network, we conclude that the rationale for targeting the network (at different points), e.g. with FDA approved drugs such as statins and metformin, is therefore compelling.



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Editorial Board & Publication Information

Publication date: October 2017
Source:Seminars in Cancer Biology, Volume 46





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THE ROLE OF DIETARY PATTERN, FOODS, NUTRIENTS AND NUTRACEUTICALS IN SUPPORTING CANCER PREVENTION AND TREATMENT

Publication date: October 2017
Source:Seminars in Cancer Biology, Volume 46





http://ift.tt/2zkfER1

The Rural Plastic Surgery Residency Rotation: Rising to Meet a National Crisis

No abstract available

http://ift.tt/2z58IGn

Plastic Surgery 2017: The Abstract Supplement

No abstract available

http://ift.tt/2A23byg

Cultivating Skills for Success in Learning Health Systems: Learning to Lead

http://ift.tt/2gUS4Te

JACC Instructions for Authors

http://ift.tt/2gWKIhZ

Outcomes With Transcatheter Mitral Valve Repair in the United States: An STS/ACC TVT Registry Report

AbstractBackground

Post-market surveillance is needed to evaluate the real-world clinical effectiveness and safety of U.S. Food and Drug Administration–approved devices.

Objectives

The authors examined the commercial experience with transcatheter mitral valve repair for the treatment of mitral regurgitation.

Methods

Data from the Society of Thoracic Surgery/American College of Cardiology Transcatheter Valve Therapy Registry on patients commercially treated with transcatheter mitral valve repair were analyzed. The study population consisted of 2,952 patients treated at 145 hospitals between November 2013 and September 2015. In 1,867 patients, data were linked to patient-specific Centers for Medicare and Medicaid Services administrative claims for analyses.

Results

The median age was 82 years (55.8% men), with a median Society of Thoracic Surgery predicted risk of mortality of 6.1% (interquartile range: 3.7% to 9.9%) and 9.2% (interquartile range: 6.0% to 14.1%) for mitral repair and replacement, respectively. Overall, in-hospital mortality was 2.7%. Acute procedure success occurred in 91.8%. Among the patients with Centers for Medicare and Medicaid Services linkage data, the mortality at 30 days and at 1 year was 5.2% and 25.8%, respectively, and repeat hospitalization for heart failure at 1 year occurred in 20.2%. Variables associated with mortality or rehospitalization for heart failure after multivariate adjustment were increasing age, lower baseline left ventricular ejection fraction, worse post-procedural mitral regurgitation, moderate or severe lung disease, dialysis, and severe tricuspid regurgitation.

Conclusions

Our findings demonstrate that commercial transcatheter mitral valve repair is being performed in the United States with acute effectiveness and safety. Our findings may help determine which patients have favorable long-term outcomes with this therapy.

http://ift.tt/2yXzIbl

Reply: Heart Failure With Preserved Ejection Fraction: A Late Stage of Hypertensive Heart Disease

http://ift.tt/2gUS1H2

First TMVR Enters U.S. Market as a Therapy, and a Gateway

http://ift.tt/2gWSMzA

A Test in Context: D-Dimer

Abstract

D-dimer is a soluble fibrin degradation product that results from ordered breakdown of thrombi by the fibrinolytic system. Numerous studies have shown that D-dimer serves as a valuable marker of activation of coagulation and fibrinolysis. Consequently, D-dimer has been extensively investigated for the diagnosis of venous thromboembolism (VTE) and is used routinely for this indication. In addition, D-dimer has been evaluated for determining the optimal duration of anticoagulation in VTE patients, for diagnosing and monitoring disseminated intravascular coagulation, and as an aid in the identification of medical patients at high risk for VTE. Thus, quantification of D-dimer levels serves an important role in guiding therapy. This review: 1) describes how D-dimer is generated; 2) reviews the assays used for its detection; and 3) discusses the role of D-dimer determination in these various conditions.

http://ift.tt/2gWSF78

Mechanisms of Very Late Bioresorbable Scaffold Thrombosis: The INVEST Registry

AbstractBackground

Very late scaffold thrombosis (VLScT) occurs more frequently after bioresorbable scaffold (Absorb BVS 1.1, Abbott Vascular, Santa Clara, California) implantation than with metallic everolimus-eluting stents.

Objectives

The purpose of this study was to elucidate mechanisms underlying VLScT as assessed by optical coherence tomography (OCT).

Methods

The INVEST (Independent OCT Registry on Very Late Bioresorbable Scaffold Thrombosis) registry is an international consortium of investigators who used OCT to examine patients with VLScT.

Results

Between June 2013 and May 2017, 36 patients with 38 lesions who had VLScT underwent OCT at 19 centers. VLScT occurred at a median of 20 months (interquartile range: 16 to 27 months) after implantation. At the time of VLScT, 83% of patients received aspirin monotherapy and 17% received dual-antiplatelet therapy. The mechanisms underlying VLScT were (in descending order) scaffold discontinuity (42.1%), malapposition (18.4%), neoatherosclerosis (18.4%), underexpansion or scaffold recoil (10.5%), uncovered struts (5.3%), and edge-related disease progression (2.6%). Discontinuity (odds ratio [OR]: 110; 95% confidence interval [CI]: 73.5 to 173; p < 0.001), malapposed struts (OR: 17.0; 95% CI: 14.8 to 19.7; p < 0.001), and uncovered struts (OR: 7.3; 95% CI: 6.2 to 8.8; p < 0.001) were more frequent in the thrombosed than the nonthrombosed scaffold regions. In 2 of 16 patients with scaffold discontinuity, intercurrent OCT before VLScT provided evidence of circularly apposed scaffold struts with minimal tissue coverage.

Conclusions

The leading mechanism underlying VLScT was scaffold discontinuity, which suggests an unfavorable resorption-related process, followed by malapposition and neoatherosclerosis. It remains to be determined whether modifications in scaffold design and optimized implantation can mitigate the risk of VLScT. (Independent OCT Registry on Very Late Bioresorbable Scaffold Thrombosis [INVEST]; NCT03180931)

http://ift.tt/2yXzJfp

Tubular Bioprosthetic Tricuspid Valve Implant Demonstrates Chordae Formation and No Calcification: Long-Term Follow-Up

http://ift.tt/2gUS3i8

Discontinuity: Is it a Major Cause of Scaffold Thrombosis?

http://ift.tt/2yZ02C1

Reply: Left Main Extrinsic Compression in Pulmonary Arterial Hypertension: From Identification to Percutaneous Coronary Intervention Optimization

http://ift.tt/2gUS05W

Sex-Related Differences in Vasomotor Function in Patients With Angina and Unobstructed Coronary Arteries

AbstractBackground

Coronary vasomotor dysfunction is an important mechanism for angina in patients with unobstructed coronary arteries.

Objectives

The purpose of this study was to determine sex differences in the prevalence and clinical presentation of vasomotor dysfunction in a European population and to examine sex differences in the dose of acetylcholine leading to a positive acetylcholine provocation test (ACH test).

Methods

Between 2007 and 2014, we included 1,379 consecutive patients with stable angina, unobstructed coronaries and ACH test performed for epicardial vasospasm or coronary microvascular dysfunction (CMD) due to microvascular spasm. The predictive value of sex, risk factors, symptoms, and noninvasive test results was analyzed by means of logistic regression.

Results

The mean patient age was 62 years, and 42% were male. There were 813 patients (59%) with a pathological ACH test, 33% for CMD and 26% for epicardial vasospasm. A pathological test was more common in females (70% vs. 43%; p < 0.001). In a multivariable logistic regression model the sex difference was statistically significant with a female–male odds ratio for CMD and epicardial vasospasm of 4.2 (95% confidence interval: 3.1 to 5.5; p < 0.001) and 2.3 (95% confidence interval: 1.7 to 3.1; p < 0.001), respectively. Effort-related symptoms, but neither risk factors nor noninvasive stress tests, contributed to predicting a pathological test. Female patients were more sensitive to acetylcholine with vasomotor dysfunction occurring at lower ACH doses compared with male patients.

Conclusions

Vasomotor dysfunction is frequent in patients with angina and unobstructed coronaries in a European population. Female patients have a higher prevalence of vasomotor dysfunction (especially CMD) compared with male patients. A pathological ACH test was observed at lower ACH doses in women compared with men.

http://ift.tt/2gUS8Cm

The Role of Nitroglycerin and Other Nitrogen Oxides in Cardiovascular Therapeutics

Abstract

The use of nitroglycerin in the treatment of angina pectoris began not long after its original synthesis in 1847. Since then, the discovery of nitric oxide as a biological effector and better understanding of its roles in vasodilation, cell permeability, platelet function, inflammation, and other vascular processes have advanced our knowledge of the hemodynamic (mostly mediated through vasodilation of capacitance and conductance arteries) and nonhemodynamic effects of organic nitrate therapy, via both nitric oxide–dependent and –independent mechanisms. Nitrates are rapidly absorbed from mucous membranes, the gastrointestinal tract, and the skin; thus, nitroglycerin is available in a number of preparations for delivery via several routes: oral tablets, sublingual tablets, buccal tablets, sublingual spray, transdermal ointment, and transdermal patch, as well as intravenous formulations. Organic nitrates are commonly used in the treatment of cardiovascular disease, but clinical data limit their use mostly to the treatment of angina. They are also used in the treatment of subsets of patients with heart failure and pulmonary hypertension. One major limitation of the use of nitrates is the development of tolerance. Although several agents have been studied for use in the prevention of nitrate tolerance, none are currently recommended owing to a paucity of supportive clinical data. Only 1 method of preventing nitrate tolerance remains widely accepted: the use of a dosing strategy that provides an interval of no or low nitrate exposure during each 24-h period. Nitric oxide's important role in several cardiovascular disease mechanisms continues to drive research toward finding novel ways to affect both endogenous and exogenous sources of this key molecular mediator.

http://ift.tt/2yZ2fgE

A Short History of Vasospastic Angina

http://ift.tt/2yXrtMv

2017 ACC Expert Consensus Decision Pathway on the Management of Mitral Regurgitation: A Report of the American College of Cardiology Task Force on Expert Consensus Decision Pathways

Abstract

Mitral regurgitation (MR) is a complex valve lesion that can pose significant management challenges for the cardiovascular clinician. This Expert Consensus Document emphasizes that recognition of MR should prompt an assessment of its etiology, mechanism, and severity, as well as indications for treatment. A structured approach to evaluation based on clinical findings, precise echocardiographic imaging, and when necessary, adjunctive testing, can help clarify decision making. Treatment goals include timely intervention by an experienced heart team to prevent left ventricular dysfunction, heart failure, reduced quality of life, and premature death.

http://ift.tt/2yXdc2f

Eosinophilic Myocarditis: Characteristics, Treatment, and Outcomes

AbstractBackground

Eosinophilic myocarditis (EM) is an acute life-threatening inflammatory disease of the heart. Neither large case series nor clinical trials on this specific myocarditis have been reported.

Objectives

Based on a systematic revision of all published histologically proven cases, this study aimed to describe the clinical presentation, treatment, and outcome of EM.

Methods

The study screened 443 manuscripts in MEDLINE and EMBASE on cases of EM published until June 2017. The authors identified 264 patients and included in the main analysis 179 patients admitted to hospital with histologically proven EM.

Results

Median age was 41 years (interquartile range: 27 to 53 years) with similar prevalence in both sexes; pediatric cases (≤16 years of age) accounted for 10.1%. The main symptom at presentation was dyspnea (59.4%), with peripheral eosinophilia observed in 75.9%. Median left ventricular ejection fraction at presentation was 35% (interquartile range: 25% to 50%). The disorders most frequently associated with EM were hypersensitivity and eosinophilic granulomatosis with polyangiitis, which accounted for 34.1% and 12.8% of cases, respectively, whereas idiopathic or undefined forms accounted for 35.7% of cases. Steroids were administered in 77.7% of patients. A temporary mechanical circulatory support (n = 30) was instituted in 16.8% of patients. In-hospital death was 22.3% (n = 40), with the highest occurrence in the hypersensitivity form (36.1%; p = 0.026).

Conclusions

EM has a poor prognosis during the acute phase, despite a publication bias that could have led to an overestimation of mortality. Associated conditions are identified in approximately 65% of cases. Specific trials and multicenter registries are needed to provide evidence-based treatments to improve in-hospital outcome.

http://ift.tt/2gWTP26

Myocardial Iron Deficiency in Hemodialysis-Dependent End-Stage Renal Disease Patients Undergoing Oral Iron Therapy

http://ift.tt/2yZ02lv

Eosinophilic Myocarditis as a Cause of Acute Cardiac Syndromes: The Importance of Awareness

http://ift.tt/2yZIoxE

Heart Failure With Preserved Ejection Fraction: A Late Stage of Hypertensive Heart Disease

http://ift.tt/2yXifQa

Prognostic Value of Serial ST2 Measurements in Patients With Acute Heart Failure

AbstractBackground

Several clinical studies have evaluated the association between ST2 and outcome in patients with heart failure (HF). However, little is known about the predictive value of frequently measured ST2 levels in patients with acute HF.

Objectives

This study sought to describe the prognostic value of baseline and repeated ST2 measurements in patients with acute HF.

Methods

In the TRIUMPH (Translational Initiative on Unique and novel strategies for Management of Patients with Heart failure) clinical cohort study, 496 patients with acute HF were enrolled in 14 hospitals in the Netherlands between 2009 and 2014. Repeated blood samples (7) were drawn during 1-year follow-up. ST2 and N-terminal pro–B-type natriuretic peptide (NT-proBNP) levels were measured in a central laboratory. The primary endpoint was the composite of all-cause mortality and HF rehospitalization. Associations between repeated biomarker measurements and the primary endpoint were assessed using a joint model.

Results

Median age was 74 years, and 37% of patients were women. The primary endpoint was reached in 188 patients (40%) during a median follow-up of 325 days (interquartile range: 85 to 401). The median baseline ST2 level was 71 ng/ml (interquartile range: 46 to 102). After adjustment for clinical factors and NT-proBNP, baseline ST2 was associated with an increased risk of the primary endpoint, and the hazard ratio per 1 SD increase of the baseline ST2 level (on the log₂ scale) was 1.30 (95% confidence interval: 1.08 to 1.56; p = 0.005). When repeated measurements were taken into account, the adjusted hazard ratio per 1 SD increase of the ST2 level (on the log₂ scale) during follow-up increased to 1.85 (95% confidence interval: 1.02 to 3.33; p = 0.044), adjusted for clinical factors and repeated measurements of NT-proBNP. Furthermore, ST2 levels appeared to elevate several weeks before the time of the primary endpoint.

Conclusions

Repeated ST2 measurements appeared to be a strong predictor of outcome in patients with acute HF, independent of repeatedly measured NT-proBNP. Hence ST2 may be helpful in clinical practice for prognostication and treatment monitoring. (TRanslational Initiative on Unique and novel strategies for Management of Patients with Heart failure [TRIUMPH]; NTR1893)

http://ift.tt/2gWnY1S

Left Main Extrinsic Compression in Pulmonary Arterial Hypertension: From Identification to Percutaneous Coronary Intervention Optimization

http://ift.tt/2yYlSVY

Neoadjuvant Pembrolizumab + Epacadostat Prior to Curative Surgical Care for Squamous Cell Carcinoma of the Head and Neck

Condition:   Squamous Cell Carcinoma of the Head and Neck
Interventions:   Drug: Pembrolizumab;   Drug: Epacadostat
Sponsor:   University of Chicago
Not yet recruiting

http://ift.tt/2hpI15Q

Serum Immunological Profiles in Head and Neck Cancer Patients Receiving Curative Radiotherapy

Condition:   Head and Neck Cancers Patients
Intervention:   Diagnostic Test: Serum levels of immunologic profiles
Sponsor:   National Taiwan University Hospital
Recruiting

http://ift.tt/2zSmf11

Views of Dermatopathologists about Clonality Assays in the Diagnosis of Cutaneous T cell and B cell Lymphoproliferative Disorders

Background

Appropriate use criteria have been developed for many tests using expert judgment, evidence-based practice, and clinical experience. In this context, the opinions of practitioners about clonality assays in various clinical scenarios where cutaneous lymphoma is suspected are reported.

Methods

An Appropriate Use Criteria Task Force sponsored by the American Society of Dermatopathology (ASDP) synthesized clinical scenarios for cutaneous lymphoproliferative disorders (LPD). We conducted, summarized, and presented a relevant literature search to an audience of 144 dermatopathologists with a variety of practice experiences at the 53^rd Annual Meeting of the ASDP in Chicago, IL.

Results

27 clinical scenarios for lymphoproliferative disorders (13 T cell and 14 B cell) were defined. 40 relevant studies for T-cell receptor gene clonality assays and 20 relevant studies for IgH/IgK clonality assays were identified. Audience response data from participating dermatopathologists reflected a wide variety of approaches to the application of clonality assays in the evaluation of LPDs, based on practice setting, personal experience and test availability.

Conclusions

Our clinical scenario analysis and literature review revealed well supported clinical scenarios and identified opportunities for additional research to further define the utility of clonality assays in some clinical scenarios.

http://ift.tt/2iMeHtA

Risk Factors stratifying malignancy of nodules in contralateral thyroid lobe in patients with preoperative ultrasound indicated unilateral papillary thyroid carcinoma: A retrospective analysis from single center

Summary

Objective

Papillary thyroid carcinoma (PTC) is the most common thyroid carcinoma with a favorable clinical outcome. For unilateral PTC patients with thyroid nodules in the contralateral lobes, the necessity of total thyroidectomy (TT) is still in doubt. In this study, we aimed to define clinical factors that could be indicators for malignancy in nodules in the contralateral thyroid lobe, which could aid the clinician in selecting the appropriate operation approach.

Design, Patients and Measurements

This is a retrospective study from Jan 2014 to Dec 2016 conducted in Shanghai Ruijin Hospital. 1442 cases with unilateral PTC and ultrasonographically benign nodules in the contralateral lobe who underwent TT at a single institution were enrolled. All patients underwent preoperative ultrasonography (US) and all the cases were confirmed by board-certified pathologists. Clinicopathological features such as age, gender, tumor location, tumor size, TgAb and TPOAb levels, capsular invasion, multifocality, central lymph node metastases and BRAF mutation were examined to evaluate the rate of malignancy in the contralateral thyroid nodules.

Results

In total, 47% of patients (677 cases)were confirmed to have malignancy in the contralateral lobe. Univariant analysis indicated that capsular invasion, Hashimoto's thyroiditis, multifocal loci, central lymph node metastases as well as BRAF mutation predicted a high incidence of occult contralateral carcinoma. Multivariant analysis showed capsular invasion, multifocal ipsilateral thyroid lobe, central lymph node metastases as well as BRAF mutation can serve as independent predictors for malignancy in the contralateral thyroid lobe.

Conclusions

Malignancy in the contralateral lobe was found in 47% of patients. This finding was associated with multifocal primary carcinomas involvement, capsular invasion, Hashimoto's thyroiditis history, central lymph node metastases and BRAF mutation, which should therefore be taken into consideration when planning therapeutic strategy for the patients.

This article is protected by copyright. All rights reserved.

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Cosmetics, Vol. 4, Pages 45: Non-Targeted Secondary Metabolite Profile Study for Deciphering the Cosmeceutical Potential of Red Marine Macro Alga Jania rubens—An LCMS-Based Approach

Cosmetics, Vol. 4, Pages 45: Non-Targeted Secondary Metabolite Profile Study for Deciphering the Cosmeceutical Potential of Red Marine Macro Alga Jania rubens—An LCMS-Based Approach

Cosmetics doi: 10.3390/cosmetics4040045

Authors: Dhara Dixit C. R. K. Reddy

This study aims to unveil the cosmeceutical traits of Jania rubens by highlighting its mineral composition, antioxidant potential, and presence of bioactive molecules using non-targeted metabolite profiling. This study showed that among minerals, (macro), Ca (14790.33 + 1.46 mg/100 g dry weight (DW)) and in (micro) Fe (84.93 + 0.89 mg/100 g DW) was the highest. A total of 23 putative metabolites in the +ESI (Electrospray Ionization) mode of LCMS-TOF (Liquid Chromatography Mass Spectrometry-Time of Flight) were detected. Two anthocyanins—malonylshisonin and 4′′′-demalonylsalvianin (m/z 825.19; anti-aging, antioxidant, anticancer properties) were detected. Two flavonoids, viz, medicocarpin and agecorynin C, 4′-O-methylglucoliquiritigenin—a flavonoid-7-O-glycoside, and 5,6,7,8,3′,4′,5′-heptamethoxyflavone, a polymethoxygenated flavone (m/z 415.15), were detected. Maclurin 3-C-(2″,3″,6″-trigalloylglucoside) (m/z 863.15) (antioxidant, antimicrobial and anticancer traits) and theaflavonin (m/z 919.18), belonging to the class of theaflavins (whitening and anti-wrinkle agent), were obtained. Pharmacologically active metabolites like berberrubin (m/z 305.1; antitumor activity), icaceine (m/z 358.24; anticonvulsant properties), agnuside (m/z 449.15; constituent for treatment of premenstrual syndrome), γ-coniceine (m/z 108.12; formulations to treat breast cancer), eremopetasitenin B2, and eremosulphoxinolide A (m/z 447.18; therapeutic effect of allergy and asthma) were observed. 6-O-Methylarmillaridin (m/z 445.18) (antimicrobial and antifungal) and simmondsin 2-ferulate, (m/z 534.21) (insecticidal, antifungal and antifeedant) were detected. Aromatic lignans, viz, 8-Acetoxy-4′-methoxypinoresinol, sesartemin, and cubebinone (m/z 413.16), in addition to an aromatic terpene glycoside, tsangane L3 glucoside (m/z 357.23), were detected. Zizybeoside I, benzyl gentiobioside, and trichocarposide were also detected. The determination of antioxidant potential was performed through assays such as like DPPH (2,2-diphenyl-1-picrylhydrazyl), FRAP (Ferric Ion Reducing Antioxidant Power), ABTS (2,2′-azino-bis(3-ethylbenz-thiazoline-6-sulfonic acid)), and total antioxidants. Therefore, this study progresses the probability for the inclusion of J. rubens as an ingredient in modern day cosmetic formulations.

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A novel technique for clinical examination of buried head and neck free flaps

Abstract

Monitoring buried flaps within the head and neck presents a unique challenge to the microsurgeon. We conducted an independent review of the literature using Medline, PubMed and Q Read performed up to February 2017. This showed that head and neck free flaps have contemporary success rates of between 92 and 98%, which is similar to rates reported for all types of flaps (90–98%). Studies looking specifically at buried free flaps were scarce, with success rates (90–98%) precisely mirroring those of studies looking at all flaps. In studies in which both buried and non-buried flaps were stratified, buried flaps did have lower rates of success (93.5 vs. 98.2% and 93 vs. 98%). While overall success rates may have been similar, lower rates of salvage were clearly shown for buried flaps. Salvage rates ranged from 0 to 75%. The highest rate was achieved using implantable Doppler, which has been shown to increase salvage rates by up to 21%. However, this technique is associated with significant rates of false positives, which have been shown to be between 8 and 40.4% Another monitoring technique in use for buried flaps was externalised monitoring segments, which has been associated with higher rates of pharyngeal fistula in head and neck reconstruction. In this article, we present a variation of the Acland's empty-and-refill test which may be used to monitor buried flaps that have a venous anastomosis in an end-to-end fashion to the external jugular vein.

Level of Evidence: Level IV, diagnostic study.

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Evaluation of the effect of new formulation, food, or a proton pump inhibitor on the relative bioavailability of the smoothened inhibitor glasdegib (PF-04449913) in healthy volunteers

Abstract

Purpose

This phase I open-label study investigated the oral bioavailability of two novel maleate salt-based glasdegib (PF-04449913) tablet formulations (small- and large-particle size) relative to the current clinical formulation (diHCl salt-based). In addition, the effect of a gastric pH-altering agent (rabeprazole) and food on the pharmacokinetics of the large-particle size formulation of glasdegib were evaluated. The pharmacokinetics of glasdegib oral solution was also assessed.

Methods

Thirty-four healthy subjects received glasdegib 100 mg as three different formulations in the fasted state (diHCl salt or small- or large-particle size maleate formulation); 13 received the large-particle maleate formulation (fed), and 14 concurrently with rabeprazole (fasted); six subjects received glasdegib 50 mg oral solution (fasted).

Results

For both new tablet formulations of glasdegib, ratios (Test:Reference) of adjusted geometric means (90% confidence interval) of area under the concentration–time curve from 0 to infinity and maximum plasma concentration were within 80–125% compared with the diHCl formulation (fasted). For the large-particle size formulation (fed), these ratios were 86.3% (81.0–92.0%) and 75.7% (65.3–87.7%), respectively, compared with fasted. When the large-particle maleate formulation was administered concurrently with rabeprazole versus alone (fasted), these ratios were 111.9% (102.8–121.9%) and 87.2% (75.9–100.3%), respectively. The pharmacokinetics of oral solution was similar to the tablet.

Conclusions

The maleate salt-based tablet formulations were bioequivalent to the diHCl tablet formulation. The extent of the observed effect of a high-fat, high-calorie meal or concurrent rabeprazole treatment on glasdegib exposure is not considered clinically meaningful.

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Correction to: Innovative intraoral cooling device better tolerated and equally effective as ice cooling

Unfortunately, the online published article has error in Table 1. The correct Table 1 is given in the following page.

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Therapeutic potential of the metabolic modulator Metformin on osteosarcoma cancer stem-like cells

Abstract

Purpose

Osteosarcoma is the most common primary bone tumour appearing in children and adolescents. Recent studies demonstrate that osteosarcoma possesses a stem-like cell subset, so-called cancer stem-like cells, refractory to conventional chemotherapeutics and pointed out as responsible for relapses frequently observed in osteosarcoma patients. Here, we explored the therapeutic potential of Metformin on osteosarcoma stem-like cells, alone and as a chemosensitizer of doxorubicin.

Methods

Stem-like cells were isolated from human osteosarcoma cell lines, MNNG/HOS and MG-63, using the sphere-forming assay. Metformin cytotoxicity alone and combined with doxorubicin were evaluated using MTT/BrdU assays. Protein levels of AMPK and AKT were evaluated by Western Blot. Cellular metabolic status was assessed based on [¹⁸F]-FDG uptake and lactate production measurements. Sphere-forming efficiency and expression of pluripotency transcription factors analysed by qRT-PCR were tested as readout of Metformin effects on stemness features.

Results

Metformin induced a concentration-dependent decrease in the metabolic activity and proliferation of sphere-forming cells and improved doxorubicin-induced cytotoxicity. This drug also down-regulated the expression of master regulators of pluripotency (OCT4, SOX2, NANOG), and decreased spheres' self-renewal ability. Metformin effects on mitochondria led to the activation and phosphorylation of the energetic sensor AMPK along with an upregulation of the pro-survival AKT pathway in both cell populations. Furthermore, Metformin-induced mitochondrial stress increased [¹⁸F]-FDG uptake and lactate production in parental cells but not in the quiescent stem-like cells, suggesting the inability of the latter to cope with the energy crisis induced by metformin.

Conclusions

This preclinical study suggests that Metformin may be a potentially useful therapeutic agent and chemosensitizer of osteosarcoma stem-like cells to doxorubicin.

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Massive adrenal incidentalomas and late diagnosis of congenital adrenal hyperplasia in prostate cancer

Summary

In a 61-year-old Caucasian male with prostate cancer, leuprolide and bicalutamide failed to suppress the androgens. He presented to endocrinology with persistently normal testosterone and incidental massive (up to 18 cm) bilateral adrenal myelolipomas on CT scan. Blood test did not reveal metanephrine excess. The patient was noted to have short stature (151 cm) and primary infertility. Elementary school photographs demonstrated precocious puberty. Physical examination revealed palpable abdominal (adrenal) masses. Abiraterone and glucocorticoid treatment was commenced with excellent suppression of testosterone. Genetic testing revealed a mutation in CYP21A2 confirming 21-hydroxylase-deficient congenital adrenal hyperplasia (CAH). Association of large myelolipomas with CAH has been reported in the literature. Our case highlights the importance of considering CAH in patients with non-suppressed testosterone despite androgen deprivation therapy. Large myelolipomas should raise the suspicion of congenital adrenal hyperplasia.

Learning points:

Adrenal myelolipomas are rare benign lesions that are more common in patients with longstanding untreated congenital adrenal hyperplasia thought to be due to ACTH stimulation.

Consider undiagnosed congenital adrenal hyperplasia in patients with adrenal myelolipoma.

Glucocorticoid replacement may be an efficacious treatment for patients with prostate cancer and CAH. Abiraterone therapy has a risk of adrenal crisis if glucocorticoids are not replaced.

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Atypical manifestation of parathyroid carcinoma with late-onset distant metastases

Summary

Parathyroid carcinoma is an extremely rare endocrine malignancy that accounts for less than 1% of cases of primary hyperparathyroidism. We report a 44-year-old woman who presented with fatigue and diffuse bone pain. Laboratory findings revealed highly elevated serum calcium and parathyroid hormone (PTH) levels and a 4.5 × 3 × 2.5 cm cystic lesion in the lower pole of the right thyroid lobe that was shown histologically to be a parathyroid carcinoma. Ten years later, the patient developed brain and pulmonary metastases and recurrence of PTH-related hypercalcemia. Treatment of hypercalcemia along with localized radiotherapy and various chemotherapy regimens failed to induce a biochemical or radiological response. In conclusion, parathyroid carcinoma is a rare neoplasia that may develop metastases even after prolonged follow-up, for which there is no evidence-based treatment besides surgery. Different chemotherapeutic schemes did not prove to be of any benefit in our case highlighting the need for registering such patients to better understand tumor biology and develop specific treatment.

Learning points:

Metastases can develop many years after parathyroid cancer diagnosis.

Surgery is the only curative treatment for parathyroid carcinoma.

Chemotherapy and radiotherapy prove to be ineffective in parathyroid cancer treatment.

Patient registering is required in order to delineate underlining pathology and offer specific treatment.

http://ift.tt/2yWZvO9

Massive adrenal incidentalomas and late diagnosis of congenital adrenal hyperplasia in prostate cancer

Summary

In a 61-year-old Caucasian male with prostate cancer, leuprolide and bicalutamide failed to suppress the androgens. He presented to endocrinology with persistently normal testosterone and incidental massive (up to 18 cm) bilateral adrenal myelolipomas on CT scan. Blood test did not reveal metanephrine excess. The patient was noted to have short stature (151 cm) and primary infertility. Elementary school photographs demonstrated precocious puberty. Physical examination revealed palpable abdominal (adrenal) masses. Abiraterone and glucocorticoid treatment was commenced with excellent suppression of testosterone. Genetic testing revealed a mutation in CYP21A2 confirming 21-hydroxylase-deficient congenital adrenal hyperplasia (CAH). Association of large myelolipomas with CAH has been reported in the literature. Our case highlights the importance of considering CAH in patients with non-suppressed testosterone despite androgen deprivation therapy. Large myelolipomas should raise the suspicion of congenital adrenal hyperplasia.

Learning points:

Adrenal myelolipomas are rare benign lesions that are more common in patients with longstanding untreated congenital adrenal hyperplasia thought to be due to ACTH stimulation.

Consider undiagnosed congenital adrenal hyperplasia in patients with adrenal myelolipoma.

Glucocorticoid replacement may be an efficacious treatment for patients with prostate cancer and CAH. Abiraterone therapy has a risk of adrenal crisis if glucocorticoids are not replaced.

http://ift.tt/2gVLA6v

Outcome and prognostic factors in single brain metastases from small-cell lung cancer

Abstract

Purpose

Whole brain radiation therapy (WBRT) is historically the standard of care for patients with brain metastases (BM) from small-cell lung cancer (SCLC), although locally ablative treatments are the standard of care for patients with 1–4 BM from other solid tumors. The objective of this analysis was to find prognostic factors influencing overall survival (OS) and intracranial progression-free survival (iPFS) in SCLC patients with single BM (SBM) treated with WBRT.

Methods

A total of 52 patients were identified in the authors' cancer center database with histologically confirmed SCLC and contrast-enhanced magnet resonance imaging (MRI) or computed tomography (CT), which confirmed SBM between 2006 and 2015 and were therefore treated with WBRT. A Kaplan-Meier survival analysis was performed for OS analyses. The log-rank (Mantel-Cox) test was used to compare survival curves. Univariate Cox proportional-hazards ratios (HRs) were used to assess the influence of cofactors on OS and iPFS.

Results

The median OS after WBRT was 5 months and the median iPFS after WBRT 16 months. Patients that received surgery prior to WBRT had a significantly longer median OS of 19 months compared to 5 months in the group receiving only WBRT (p = 0.03; HR 2.24; 95% confidence interval [CI] 1.06–4.73). Patients with synchronous disease had a significantly longer OS compared to patients with metachronous BM (6 months vs. 3 months, p = 0.005; HR 0.27; 95% CI 0.11–0.68). Univariate analysis for OS revealed a statistically significant effect for metachronous disease (HR 2.25; 95% CI 1.14–4.46; p = 0.019), initial response to first-line chemotherapy (HR 0.58; 95% CI 0.35–0.97; p = 0.04), and surgical resection (HR 0.36; 95% CI 0.15–0.88; p = 0.026). OS was significantly affected by metachronous disease in multivariate analysis (HR 2.20; 95% CI 1.09–4.45; p = 0.028).

Conclusions

Univariate analysis revealed that surgery followed by WBRT can improve OS in patients with SBM in SCLC. Furthermore, synchronous disease and response to initial chemotherapy appeared to be major prognostic factors. Multivariate analysis revealed metachronous disease as a significantly negative prognostic factor on OS. The value of WBRT, stereotactic radiosurgery (SRS), or surgery alone or in combination for patients with a limited number of BM in SCLC should be evaluated in further prospective clinical trials.

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Corrected and Republished: Misaligned pCONus Device: Case Report of a Unique Complication

Journal of Clinical Imaging Science 2017 7(1):41-41



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Scholar : These new articles for Critical Discourse Studies are available online

The online platform for Taylor & Francis Online content New for Critical Discourse Studies and online now on Taylor & Francis Online: Corrigenda Corrigendum Pages: 1-1 | DOI: 10.1080/17405904.2017.1397348 To update which email alerts you receive, manage your alerts within the My Account area. You can also unsubscribe from this alert with one click. If you need any further help, please contact us at support@tandfonline.com Please do not reply to this email. To ensure that you receive your alerts and information from Taylor & Francis Online, please add "alerts@tandfonline.com" and "info@tandfonline.com" to your safe senders list. Taylor & Francis, an Informa business. Taylor & Francis is a trading name of Informa UK Limited, registered in England under no. 1072954. Registered office: 5 Howick Place, London, SW1P 1WG.

How to get thicker hair

Many people want to help their hair look thick and full without chemical treatments. We look at several natural hair treatments, from eggs to castor oil.

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Abstract: 3D Domestic Printer Use in Rhinoplasty

No abstract available

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A sporadic case of granulomatous disease negative for NOD2 mutations and mimicking Blau syndrome

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Cutaneous manifestations of phosphate solution extravasation

Summary

Extravasation injuries are common in patients receiving multiple intravenous infusions. Although such injuries are closely associated with the infusion of cytotoxic chemotherapy, they have also been been associated with extravasation of noncytotoxic drugs. Extravasation injuries can lead to skin ulceration and nerve and tendon damage, and therefore to permanent disability. We report three cases of phosphate solution extravasation leading to unusual cutaneous manifestations.

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