Pre-Menopausal Breast Fat Density Might Predict MACE During 10 Years of Follow-Up: The BRECARD Study

ObjectivesThis study sought to determine whether the breast gland adipose tissue is associated with different rates of major adverse cardiac events (MACEs) in pre-menopausal women.BackgroundTo our knowledge, no study investigated the impact of breast adipose tissue infiltration on MACEs in pre-menopausal women.MethodsProspective multicenter cohort study conducted on pre-menopausal women >40 years of age without cardiovascular disease and breast cancer at enrollment. The study started in January 2000 and ended in January 2009, and the end of the follow-up for the evaluation of MACEs was in January 2019. Participants underwent mammography to evaluate breast density and were divided into 4 groups according to their breast density. The primary endpoint was the probability of a MACE at 10 years of follow-up in patients staged for different breast deposition/adipose tissue deposition.ResultsThe propensity score matching divided the baseline population of 16,763 pre-menopausal women, leaving 3,272 women according to the category of breast density from A to D. These women were assigned to 4 groups of the study according to baseline breast density. At 10 years of follow-up, we had 160 MACEs in group 1, 62 MACEs in group 2, 27 MACEs in group 3, and 16 MACEs in group 4. MACEs were predicted by the initial diagnosis of lowest breast density (hazard ratio: 3.483; 95% confidence interval: 1.476 to 8.257). Further randomized clinical trials are needed to translate the results of the present study into clinical practice. The loss of ex vivo breast density models to study the cellular/molecular pathways implied in MACE is another study limitation.ConclusionsAmong pre-menopausal women, a higher evidence of adipose tissue at the level of breast gland (lowest breast density, category A) versus higher breast density shows higher rates of MACEs. Therefore, the screening mammography could be proposed in overweight women to stage breast density and to predict MACEs. (Breast Density in Pre-menopausal Women Is Predictive of Cardiovascular Outcomes at 10 Years of Follow-Up [BRECARD]; NCT03779217)     

HCV chronic hepatitis in patients with HIV: clinical management issues

HIV-hepatitis C virus (HCV) coinfection is common and affects more than one-third of all HIV infected persons worldwide. Prevalence among risk categories varies according to shared risk factors for transmission, mainly intravenous drug use (IDU) and hemophiliacs. Chronic HCV infection seems to accelerate the course of HIV disease, resulting in a worsened clinical and immunological progression. At the same time, several studies suggest that HIV disease modifies the natural history of HCV infection, leading to a faster course of progression from active hepatitis to cirrhosis, to end stage liver disease and death. HCV infection mimics opportunistic diseases because its natural history is significantly accelerated in HIV patients. Since highly active antiretroviral therapy (HAART) has slowed the progression of HIV disease and decreased the rate of HIV associated mortality, the prognosis of HIV disease has been modified, and the need to treat HCV coinfection become a significant issue. Because of the poor response rate obtained by either interferon alone or interferon thrice weekly plus ribavirin, the combination of pegylated interferon and ribavirin will probably become the standard of care, although the clinicians should be aware of the overlapping toxicity of nucleoside analogues and ribavirin. Many selected categories of patients pose particular challenges to physicians treating HCV infection: nonresponders to interferon, cirrhotic patients, and patients infected with both HCV and HBV. Liver transplantation in HIV patients is currently under evaluation, but should become the rescue therapy for HIV patients with end stage liver disease.     

<Emphasis Type="Italic">Acinetobacter</Emphasis> Infections in Neonates

Purpose of Review

MDR-Gram-negative bacteria are a great concern in the neonatal population, with a worldwide rise in the reported incidence and with very limited therapeutic options. Acinetobacter baumannii is responsible for many infections in neonates and outbreaks in neonatal intensive care unit (NICU); also, outbreaks caused by other Acinetobacter species have been reported. The aim of this review is to document the epidemiology of Acinetobacter spp. infections in neonates and risk factors for acquisition of Acinetobacter spp. in the NICU using data from published studies.

Recent Findings

Acinetobacter spp. infections are increasing in neonates in NICU. Outbreak caused by multidrug resistant (MDR) or extensively drug resistant (XDR) A. baumannii but also outbreak caused by susceptible A. soli and A. septicus sp. nov., were reported in neonates. Acinetobacter spp. were responsible for bloodstream infections and respiratory tract infections in neonates. Risk factors for A. baumannii acquisition in neonates were low birthweight, length of NICU stay, umbilical catheterization, central-venous catheterization, assisted ventilation, and prior antibiotic use.

Summary

This review highlights the importance of surveillance of risk factors for healthcare-associated infections in NICU to control MDR and XDR A. baumannii infections in neonates.

     

Left ventricular performance and autonomic dysfunction in patients with long-term insulin-dependent diabetes mellitus

Cardiac autonomic neuropathy (CAN) is a very frequent complication of insulin-dependent mellitus type 1, affecting the sympathetic or parasympathetic sections or both. The different impairment in the two sections might modify left ventricular function early. To evaluate this relationship, we studied 61 patients (mean age 39.6±7 years) with type 1 diabetes for more than 10 years, without coronary artery disease (CAD; negative ergometric stress test) and without other pathologies that could interfere with ventricular function. All patients underwent MONO-, 2-dimensional and Doppler echocardiographic examination and radionuclide angiography with⁹⁹Tc (RNA). According to the outcome of the Ewing tests, patients were divided into two groups: group A with two or more tests altered (26 patients with CAN) and group B with one or no tests altered (35 patients without CAN). No significant differences between the two groups were found in the systolic function parameters with either technique. In contrast, a pattern of abnormal relaxation was found for the diastolic function parameters: in group A a decrease in E-wave velocity and its time-velocity integral and an increase in A-wave and its time-velocity integral were detected with echocardiography. Moreover, RNA showed a reduced peak filling rate and an increased isovolumic relaxation time. When compared with normal values, an abnormal diastolic filling, defined as two independent echocardiography plus one RNA variable impairment, was found in 15 patients (57.6%) in group A and in only 4 patients (11.4%) in group B (P<0.001). Our findings suggest an early involvement of diastolic function in patients with CAN.     

Step‐down approach using either cyclosporin A or methotrexate as maintenance therapy in early rheumatoid arthritis

Objective

To evaluate the feasibility and outcome of the step‐down approach using either cyclosporin A (CSA) or methotrexate (MTX) as maintenance therapy following 6 months treatment with these 2 agents in combination in early, nonerosive rheumatoid arthritis (RA).

Methods

Fifty‐seven patients younger than 65 years with early, nonerosive RA were first treated with CSA and MTX in combination for 6 months. They were then randomly stepped down to single‐agent maintenance treatment for another 18 months. Safety, clinical efficacy, survival on treatment, and radiographic progression were evaluated.

Results

When being treated with combination therapy, 7 of the 57 patients (12.3%) withdrew because of adverse events. Of the remaining 50 patients, 42 (84.0%) were American College of Rheumatology (ACR) 20% responders, 30 (60.0%) were ACR 50% responders, and 23 (46.0%) were ACR 70% responders. At month 6, 22 patients were randomized to CSA and 27 to MTX. During this trial period, the treatment was discontinued by 16 patients taking CSA (mainly because of loss of efficacy) and by 4 taking MTX. At month 24, the probability (± SEM) of survival on treatment was 0.273 ± 0.09 for CSA and 0.852 ± 0.07 for MTX. Of the 6 CSA patients who completed the trial, 4 (66.7%) were ACR 20% responders, and 3 (50%) were both ACR 50% and ACR 70% responders. Of the 23 completers in the MTX arm, 21 (91.3%) were ACR 20% responders, 18 (78.3%) were ACR 50%, and 10 (43.5%) were ACR 70% responders. The treatment was not responsible for severe adverse events. Radiography showed a slow progression in the damage score and number of eroded joints in both treatment groups.

Conclusion

Stepping down to single agent maintenance therapy following 6 months of combination treatment with CSA and MTX in early RA was only successful with MTX. Because this treatment did not prevent some radiographic progression, other approaches (e.g., step‐up approach) may be more appropriate in early RA.

     

Evaluation of the effects of catheter sampling for the study of platelet behavior in the pulmonary and coronary circulation

To study the effects of sampling through cardiac catheters on indices of platelet function, we measured the levels of platelet factor 4 (PF₄), beta thromboglobulin (BTG), and platelet aggregate ratio (PAR) in 10 patients with atrioventricular accessory pathway (AVNAP), six patients with primary pulmonary hypertension (PPH), and six patients with critical narrowing of the left anterior descending artery (LAD). In AVNAP and LAD patients samples were drawn simultaneously from a peripheral vein, coronary sinus, and brachial artery; in AVNAP patients samples were also obtained from the axillary vein before the coronary sinus was entered. In PPH patients samples were drawn from pulmonary artery, aorta, and a peripheral vein; in these patients the effects of an intravenous infusion of prostacyclin (PGl₂) (2 to 8 ng/kg/min) on PF₄, BTG, and PAR were also studied at all sampling sites. In all patients arterial, coronary sinus, pulmonary arterial, and axillary venous levels of PF₄, BTG, and PAR significantly exceeded those measured in the peripheral vein. PGl₂ infusion resulted in a significant decrease of PF₄ at all sampling sites, while no consistent BTG changes were observed and PAR levels did not decrease in the peripheral vein. Although a considerable interpatient variability in PF₄ levels was observed, a significant (r = 0.91) correlation was found in patients with AVNAP between simultaneous coronary sinus and arterial PF₄ levels. The value of PF₄ coronary sinus-arterial difference in LAD patients was consistently higher than that calculated in AVNAP patients (54.5 ± 28.9 vs 4.2 ± 3.8 ng/ml). In conclusion: (1) a considerable and variable degree of platelet activation occurs with catheter sampling, preventing the measurement of absolute levels of platelet metabolites; (2) among the indices examined PF₄ appears the most sensitive for detecting changes in platelet activity; and (3) the measurement of coronary sinus-arterial PF₄ differences may provide information on directional changes in transcardiac platelet behavior.     

Early and long-term outcome of mitral valve repair with a Cosgrove band combined with coronary revascularization in patients with ischemic cardiomyopathy and moderate-severe mitral regurgitation

BACKGROUND AND AIM OF THE STUDY: Clinical and echocardiographic results were investigated to evaluate mitral valve repair in patients undergoing coronary artery bypass grafting (CABG) for ischemic cardiomyopathy (ICM) with moderately severe mitral regurgitation (MR). METHODS: A total of 78 patients (21 women, 57 men; mean age 69.5 +/- 7.8 years) with ischemic mitral regurgitation underwent mitral valve repair and CABG. The mean left ventricular ejection fraction (LVEF) was 42.4 +/- 12.4%. Among the patients, 19 (24.4%) had preoperative congestive heart failure (CHF). This surgery constituted a second such operation in five patients (6.4%). The MR was grade 3+ in 28 patients (35.9%) and 4+ in 50 (64.1%). The mean number of grafts was 3.6 per patient. RESULTS: Hospital mortality was 11.5% (n = 9). Risk factors for early mortality were preoperative NYHA class > or = III (p = 0.014), preoperative heart failure (p <0.001) and reoperation (p = 0.002). The five-year survival was 82.6 +/- 5.9%, and freedom from grade > or =2+ MR was 93.1 +/- 4.1%. Postoperatively, 66 patients (89.6%) were in NYHA class I and seven (9.4%) in class II, demonstrating a statistically significant improvement (p = 0.03). Late echocardiography showed a significant improvement in LVEF (from 42.4 +/- 12.4% to 51.7 +/- 10.9%; p = 0.01) and a reduction in pulmonary artery pressure (from 37.6 +/- 11.9 mmHg to 29.3 +/- 7.4 mmHg; p = 0.004). CONCLUSION: It is concluded that in patients with ICM, mitral valve repair combined with CABG provides a dramatic improvement in ejection fraction and in CHF, with excellent long-term survival, even in patients with a low LVEF.     

Androgen receptor gene and sex-specific Alzheimer's disease

Women are at a 2-fold risk of developing late-onset Alzheimer's disease (AD) (onset at 65 years of age or older) compared with men. During perimenopausal years, women undergo hormonal changes that are accompanied by metabolic, cardiovascular, and inflammatory changes. These all together have been suggested as risk factors for late-onset AD. However, not all perimenopausal women develop AD; we hypothesize that certain genetic factors might underlie the increased susceptibility for developing AD in postmenopausal women. We investigated the Androgen Receptor gene (AR) in a clinical cohort of male and female AD patients and normal control subjects by sequencing all coding exons and evaluating the length and distribution of the CAG repeat in exon 1. We could not establish a correlation between the repeat length, sex, and the disease status, nor did we identify possible pathogenic variants. AR is located on the X chromosome; to assess its role in AD, X-inactivation patterns will need to be studied to directly correlate the actual expressed repeat length to a possible sex-specific phenotypic effect.     

Early outcomes of migraine after erenumab discontinuation: data from a real-life setting

Neurological Sciences - Monoclonal antibodies targeting the calcitonin gene-related peptide, including erenumab, are migraine-specific preventive treatments, whose long-term effectiveness has still...