Sickle Cell/β0-Thalassemia Associated With the 1393 bp Deletion Can be Associated With a Severe Phenotype

In patients who have inherited both the sickle cell gene and the β-thalassemia (β-thal) gene, the nature of the β-thal mutation will impact on the disease phenotype. The β-thal mutation caused by the 1393 bp deletion has previously been described as having a mild clinical phenotype when inherited with the sickle gene. We describe three members of a family with this deletion who present with a more severe phenotype. The severity cannot be explained by their Hb F levels, or the XmnI-HBG2 polymorphism. This deletion cannot be presumed to be associated with a mild disease phenotype and we recommend that patients with Hb S/β⁰-thal are screened for this deletion.     

Where Do We Stand With the Genetics of Psoriatic Arthritis?

Psoriasis and psoriatic arthritis (PsA) are interrelated heritable diseases. Polymorphisms in the genes encoded in the major histocompatibility complex region have consistently been associated with psoriasis and PsA and account for about 30% of the genetic risk. Recently, the results of multiple well-powered genome-wide association studies have identified several additional loci outside the major histocompatibility complex region associated with psoriasis risk, including three genes involved in interleukin (IL)-23 signaling (IL-23R, IL-23A, IL-12B), two genes that regulate nuclear factor-κB signaling (TNIP1, TNFAIP3), and two genes involved in the modulation of T-helper type 2 immune responses (IL-4, IL-13). These initial findings are beginning to illuminate the molecular pathways implicated in the pathogenesis of psoriasis and suggest priority targets for study in PsA cohorts. Of course, the next step will be to identify genetic risk factors specifically associated with PsA, and indeed, a formal genome-wide association study on PsA is being undertaken.     

Has the Time Come to Be More Aggressive With Bariatric Surgery in Obese Patients With Chronic Systolic Heart Failure?

Purpose of Review

Obesity is a strong risk factor for the development of heart failure (HF). Diet, exercise, and weight-loss pharmacotherapies have limited potential to achieve significant and sustainable weight loss, especially in patients with symptomatic systolic HF. This review seeks to determine the role of bariatric surgery for patients with systolic HF and obesity.

Recent Findings

Bariatric surgeries such as the laparoscopic sleeve gastrectomy (LSG) and Roux-en-Y gastric bypass (RYGB) represent the most successful long-term strategy for achieving weight loss and diabetes and hypertension remission in the general obese population. These benefits translate to reductions in cardiovascular events and mortality, as well as improvements in myocardial structure and function. There is also now data supporting the safety of LSG or RYGB in patients with systolic dysfunction and a reduction in HF admissions post-operatively.

Summary

Current literature and clinical experience suggest that the most appropriate bariatric surgery candidates with HF are patients aged <?50–60 years, with severely depressed systolic function and NYHA II-III symptoms, who have failed non-surgical strategies and have a high likelihood of future cardiac transplantation candidacy after weight loss. This review seeks to determine the role of bariatric surgery for patients with systolic HF and obesity.

     

Addition of Digoxin Improves Cardiac Function in Children With the Dilated Cardiomyopathy With Ataxia Syndrome: A Mitochondrial Cardiomyopathy

Background

The dilated cardiomyopathy with ataxia syndrome (DCMA) is a rare mitochondrial disorder characterized by progressive cardiomyopathy, prolonged QT interval and early death in childhood related to intractable heart failure. We present a case series of 9 children with DCMA who demonstrated functional improvement and favourable left ventricular remodeling only after digoxin was added to their medical therapy.

The Association of Frailty With In-Hospital Bleeding Among Older Adults With Acute Myocardial Infarction: Insights From the ACTION Registry

Objectives

The aim of this study was to determine whether frailty is associated with increased bleeding risk in the setting of acute myocardial infarction (AMI).

Increased Expression of the Autocrine Motility Factor is Associated With Poor Prognosis in Patients With Clear Cell–Renal Cell Carcinoma

Glucose-6-phosphate isomerase (GPI), also known as phosphoglucose isomerase, was initially identified as the second glycolytic enzyme that catalyzes the interconversion of glucose-6-phosphate to fructose-6-phosphate. Later studies demonstrated that GPI was the same as the autocrine motility factor (AMF), and that it mediates its biological effects through the interaction with its surface receptor (AMFR/gp78). In this study, we assessed the role of GPI/AMF as a prognostic factor for clear cell renal cell carcinoma (ccRCC) cancer-specific (CSS) and progression-free survival (PFS). In addition, we evaluated the expression and localization of GPI/AMF and AMFR, using tissue microarray-based immunohistochemistry (TMA-IHC), indirect immunofluorescence (IF), and confocal microscopy analysis.Primary renal tumor and nonneoplastic tissues were collected from 180 patients who underwent nephrectomy for ccRCC. TMA-IHC and IF staining showed an increased signal for both GPI and AMFR in cancer cells, and their colocalization on plasma membrane. Kaplan–Meier curves showed significant differences in CSS and PFS among groups of patients with high versus low GPI expression. In particular, patients with high tissue levels of GPI had a 5-year survival rate of 58.8%, as compared to 92.1% for subjects with low levels (P < 0.0001). Similar findings were observed for PFS (56.8% vs 93.3% at 5 years). At multivariate analysis, GPI was an independent adverse prognostic factor for CSS (HR = 1.26; P = 0.001), and PFS (HR = 1.16; P = 0.01).In conclusion, our data suggest that GPI could serve as a marker of ccRCC aggressiveness and a prognostic factor for CSS and PFS.     

Should Hypertension Guidelines Be Changed for Hypertensive Patients With the Metabolic Syndrome?

The authors analyzed the impact of present guidelines for hypertension management on cardiovascular (CV) risk factors in hypertensive patients with and without the metabolic syndrome (MS). Results in 549 nondiabetic hypertensive patients with a mean follow-up of 3.8+/-1.2 years on usual recommended care were reviewed. At baseline, 231 (42.1%) patients had MS and, per the definition, showed significantly higher values of traditional CV risk factors than non-MS patients. At the end of follow-up, blood pressure levels were similar in both groups; the lipid profile tended to improve in MS patients. Eighteen MS patients (7.8%) and 7 non-MS patients (2.2%) developed diabetes (P<.001). Prevalence of microalbuminuria was reduced in both groups, but it remained significantly higher in MS patients. Usual care of hypertensive patients achieved similar blood pressure and low-density lipoprotein cholesterol goals, both in MS and non-MS patients. Global CV risk, however, remained higher in MS patients, as suggested by a 3-fold higher incidence of new-onset diabetes (absolute increase of 5.6%) and a 2-fold increase in microalbuminuria.     

Absence of the α2c-Adrenoceptor Del322–325 Allele is Associated With Increased Mortality in Patients With Chronic Systolic Heart Failure

ObjectiveThe Del322–325 polymorphism of the α_2c-adrenoceptor is considered to be a possible risk factor for heart failure (HF). We investigated the possible clinical association between the presence or absence of the deletion allele and mortality.Methods and ResultsOf 261 chronic systolic HF patients evaluated, 216 (83%) carried no α_2c-adrenoceptor Del322–325 alleles (designated II); 28 patients (11%) were heterozygous (ID) and 17 patients (6%) homozygous (DD) for the deletion. Similar genetic distribution of α_2c-adrenoceptor Del322–325 subgroups was found in a control group of 96 healthy individuals. Mortality was significantly higher in HF patients in whom the deletion allele was absent than in HF patients who carried it: 67 (31%) patients in the II subgroup died compared with 7 (15.5%) in the ID/DD subgroup (P = .01). The odds ratio for death in HF patients who carried no α_2c-adrenoceptor Del322–325 alleles compared with HF patients with ≥1 allele was 2.45 (95% confidence interval 1.04?5.74). There were no differences in other relevant clinical parameters between the 2 subgroups of HF patients.ConclusionsThe mortality rate of chronic systolic HF patients carrying no α_2c-adrenoceptor Del322–325 alleles was significantly higher (almost 2.5-fold) than that of HF patients carrying ≥1 allele.     

Liver Function,In-Hospital,and Post-Discharge Clinical Outcome in Patients With Acute Heart Failure—Results From the Relaxin for the Treatment of Patients With Acute Heart Failure Study

BackgroundElevated plasma concentrations of liver function tests are prevalent in patients with chronic heart failure (HF). Little is known about liver function in patients with acute HF. We aimed to assess the prevalence and prognostic value of serial measurements of liver function tests in patients admitted with acute decompensated HF.MethodsWe investigated liver function tests from all 234 patients from the Relaxin for the Treatment of Patients With Acute Heart Failure study at baseline and during hospitalization. The end points were worsening HF through day 5, 60-day mortality or rehospitalization, and 180-day mortality.ResultsMean age was 70 ± 10 years, 56% were male, and most patients were in New York Heart Association functional class III/IV (73%). Abnormal liver function tests were frequently found for alanine transaminase (ALT; 12%), aspartate transaminase (AST; 21%), alkaline phosphatase (12%), and total bilirubin (19%), and serum albumin (25%) and total protein (9%) were decreased. In-hospital changes were very small. On a continuous scale, baseline ALT and AST were associated with 180-day mortality (hazard ratios [HRs; per doubling] 1.52 [P = .030] and 1.97 [P = .013], respectively) and worsening HF through day 5 (HRs [per doubling] 1.72 [P = .005] and 1.95 [P = .008], respectively). Albumin was associated with 180-day mortality (HR 0.86; P = .001) but not with worsening HF (HR 0.95; P = .248). Total protein was associated with only worsening HF (HR 0.91; P = .004).ConclusionsAbnormal liver function tests are often present in patients with acute HF and are associated with an increased risk for mortality, rehospitalization, and in-hospital worsening HF.