Sex differences in heart failure patients assessed by combined echocardiographic and cardiopulmonary exercise testing

BackgroundWe aimed to test the differences in peak VO2 between males and females in patients diagnosed with heart failure (HF), using combined stress echocardiography (SE) and cardiopulmonary exercise testing (CPET).MethodsPatients who underwent CPET and SE for evaluation of dyspnea or exertional intolerance at our institution, between January 2013 and December 2017, were included and retrospectively assessed. Patients were divided into three groups: HF with preserved ejection fraction (HFpEF), HF with mildly reduced or reduced ejection fraction (HFmrEF/HFrEF), and patients without HF (control). These groups were further stratified by sex.ResultsOne hundred seventy-eight patients underwent CPET-SE testing, of which 40% were females. Females diagnosed with HFpEF showed attenuated increases in end diastolic volume index (P = 0.040 for sex × time interaction), significantly elevated E/e' (P < 0.001), significantly decreased left ventricle (LV) end diastolic volume:E/e ratio (P = 0.040 for sex × time interaction), and lesser increases in A-VO2 difference (P = 0.003 for sex × time interaction), comparing to males with HFpEF. Females diagnosed with HFmrEF/HFrEF showed diminished increases in end diastolic volume index (P = 0.050 for sex × time interaction), mostly after anaerobic threshold was met, comparing to males with HFmrEF/HFrEF. This resulted in reduced increases in peak stroke volume index (P = 0.010 for sex × time interaction) and cardiac output (P = 0.050 for sex × time interaction).ConclusionsCombined CPET-SE testing allows for individualized non-invasive evaluation of exercise physiology stratified by sex. Female patients with HF have lower exercise capacity compared to men with HF. For females diagnosed with HFpEF, this was due to poorer LV compliance and attenuated peripheral oxygen extraction, while for females diagnosed with HFmrEF/HFrEF, this was due to attenuated increase in peak stroke volume and cardiac output. As past studies have shown differences in clinical outcomes between females and males, this study provides an essential understanding of the differences in exercise physiology in HF patients, which may improve patient selection for targeted therapeutics

Vascular Behcet and Mutations in Thrombogenic Genes: Methylene Tetrahydrofolate Reductase, Factor V, and Prothrombin

Vasculitis, thrombophlebitis, arterial aneurysms, and occlusions occur in about 25% of patients with Behcet's disease (BD). The common inherited gene defects, factor V (FV) 1691A (Leiden), methylene tetrahydrofolate reductase (MTHFR) 677T, and prothrombin 20210A, are known risk factors for thrombosis. The aim of the study was to evaluate the contribution of these mutations to thrombosis in Israeli patients with BD. Fifty-four patients with BD (n = 54; 27 men and 27 women) underwent clinical and genetic evaluation. Most patients (n = 43; 79.6%) were of Arab descent (31 sporadic and 12 familial cases from 4 families), and 11 patients (20.4%) were of Jewish descent (all sporadic cases). The FV Leiden mutation was identified in five patients (9.2%), and eight patients were MTHFR 677TT homozygotes (14.8%). None had the 20210A mutant prothrombin allele. No statistical differences between carriers and noncarriers with regards to demographic and disease manifestations were calculated. Arabs were diagnosed earlier than Jewish patients (25.8 +/- 11.6 compared with 37.2 +/- 10.7, p = 0.01, respectively), but Jewish patients had, respectively, more events of deep vein thrombosis (DVT) compared with Arabs (3 of 11, 27.3% and 3 of 43, 7%, p = 0.09). Thrombotic events in our patients with BD were not associated with variations in thrombophilic genes

Radionuclide Methods in the Diagnosis of Sacroiliitis in Patients with Spondyloarthritis: An Update

Sacroiliitis, inflammation of the sacroiliac joint (SIJ), is the hallmark of ankylosing spondylitis and spondyloarthritis (SpA) in general. The arsenal of recommended diagnostic modalities for imaging of the SIJ is scanty and, in practice, includes only conventional X-rays and magnetic resonance imaging (MRI). This review suggests that bone scintigraphy, particularly single-photon emission computed tomography (SPECT) with calculation of indices, or SPECT in combination with low-dose computed tomography (CT) can be a sensitive and specific tool for the diagnosis of sacroiliitis and can be used as part of the individualized approach to the diagnosis of axial SpA. In addition, [18F]fluoride positron emission tomography (PET)/CT imaging and immunoscintigraphy, using labeled monoclonal anti-cytokine antibodies, are promising methods of current scientific interest in this field

Giant Cell Arteritis: State of the Art in Diagnosis, Monitoring, and Treatment

Giant cell arteritis (GCA) is the most prevalent subtype of vasculitis in adults. In recent years, there has been substantial improvement in the diagnosis and treatment of GCA, mainly attributed to the introduction of highly sensitive diagnostic tools, incorporation of modern imaging modalities for diagnosis and monitoring of large-vessel vasculitis, and introduction of highly effective novel biological therapies that have revolutionized the field of GCA. This article reviews state-of-the-art approaches for the diagnosis, monitoring, and treatment options of GCA

Penetration and Accumulation of Dendrons with Different Peripheral Composition in Pseudomonas aeruginosa Biofilms

Multi-drug resistant bacterial infections threaten to become the number one cause of death by the year 2050. Development of antimicrobial dendritic polymers is considered promising as an alternative infection control strategy. For antimicrobial dendritic polymers to effectively kill bacteria residing in infectious biofilms, they have to penetrate and accumulate deep into biofilms. Biofilms are often recalcitrant to antimicrobial penetration and accumulation. Therefore, this work aims to determine the role of compact dendrons with different peripheral composition in their penetration into Pseudomonas aeruginosa biofilms. Red-fluorescently labeled dendrons with pH-responsive NH3+ peripheral groups initially penetrated faster from a buffer suspension at pH 7.0 into the acidic environment of P. aeruginosa biofilms than dendrons with OH or COO- groups at their periphery. In addition, dendrons with NH3+ peripheral groups accumulated near the top of the biofilm, due to electrostatic double-layer attraction with negatively-charged biofilm components. However, accumulation of dendrons with OH and COO- peripheral groups was more evenly distributed across the depth of the biofilms than NH3+ composed dendrons and exceeded accumulation of NH3+ composed dendrons after 10 min exposure. Unlike dendrons with NH3+ groups at their periphery, dendrons with OH or COO- peripheral groups, lacking strong electrostatic double-layer attraction with biofilm components, were largely washed-out during exposure to PBS without dendrons. Thus, penetration and accumulation of dendrons into biofilms is controlled by their peripheral composition through electrostatic double-layer interactions, which is an important finding for the further development of new antimicrobial or antimicrobial-carrying dendritic polymers

Evidence-based recommendations for the practical management of Familial Mediterranean Fever

International audienceAim: Familial Mediterranean Fever (FMF) is the most common recurrent autoinflammatory fever syndrome. Still, many issues-e.g.: colchicine dosage adjustment, maximum dosage of colchicine in children and adults, definition of colchicine resistance, alternative treatment solutions in colchicine-resistant patients, and genetic screening for asymptomatic siblings-have not yet been standardized. The current paper aims at summarizing consensus recommendations to approach these issues.Methods: A literature review concerning these practical management questions was performed through PubMed. On the basis of this analysis, expert recommendations were developed during a consensus meeting of caregivers from France and Israel.Results: A patient experiencing more than four FMF attacks a year needs colchicine dose adjustment. In case of persistent attacks (≥6 per year) in patients with maximum doses of colchicine (2 mg in children; 3 mg in adults), alternative treatment to colchicine with IL1 inhibitors should be considered. Routine genetic testing for MEFV mutations in asymptomatic siblings of an index case is not recommended.Conclusion: This is a first attempt to resolve practical questions in the daily management of FMF patients