Cutting Edge Issues in the Churg–Strauss Syndrome

Churg–Strauss syndrome (CSS) is a rare systemic small-vessel vasculitis that develops in the background of bronchial asthma, which is characterized by eosinophilia and eosinophilic infiltration of various tissues. It belongs to the group of antineutrophil cytoplasmic autoantibody (ANCA)-associated vasculitides. The triggering factors and pathogenesis of CSS are still unknown. The possible role of eotaxin-3 and CCR4-related chemokines in selective recruitment of eosinophils to the target tissues in CSS has been recently suggested, but the role of eosinophilic inflammation in the development of vasculitic lesions is not completely understood. From the clinical view, two distinct phenotypes of the disease are slowly emerging depending on the ANCA-positivity status. Glucocorticoids are still the mainstay of treatment; however, data are accumulating regarding the beneficial role of novel immunosuppressants and biologic compounds, especially in patients with poorer prognosis.     

Predictors of Coronary and Carotid Atherosclerosis in Patients with Severe Degenerative Aortic Stenosis

Background. Patients with degenerative aortic stenosis (AS) exhibit elevated prevalence of coronary artery disease (CAD) and internal carotid artery stenosis (ICAS). Our aim was to investigate prevalence of significant CAD and ICAS in relation to demographic and cardiovascular risk profile among patients with severe degenerative AS.Methods. We studied 145 consecutive patients (77 men and 68 women) aged 49-91 years (median, 76) with severe degenerative AS who underwent coronary angiography and carotid ultrasonography in our tertiary care center. The patients were divided into two groups according to the presence of either significant CAD (n=86) or ICAS (n=22).Results. The prevalence of significant CAD or ICAS was higher with increasing number of traditional risk factors (hypertension, hypercholesterolemia, diabetes, smoking habit) and decreasing renal function. We found interactions between age and gender in terms of CAD (p=0.01) and ICAS (p=0.06), which was confirmed by multivariate approach. With the reference to men with a below-median age, the prevalence of CAD or ICAS increased in men aged >76 years (89% vs. 55% and 28% vs. 14%, respectively), whereas the respective percentages were lower in older vs. younger women (48% vs. 54% and 7% vs. 17%).Conclusions. In severe degenerative AS gender modulates the association of age with coronary and carotid atherosclerosis with its lower prevalence in women aged >76 years compared to their younger counterparts. This may result from a hypothetical “survival bias”, i.e., an excessive risk of death in very elderly women with severe AS and coexisting relevant coronary or carotid atherosclerosis.     

Integration of light scattering with machine learning for label free cell detection

Light scattering has been used for label-free cell detection. The angular light scattering patterns from the cells are unique to them based on the cell size, nucleus size, number of mitochondria, and cell surface roughness. The patterns collected from the cells can then be classified based on different image characteristics. We have also developed a machine learning (ML) method to classify these cell light scattering patterns. As a case study we have used this light scattering technique integrated with the machine learning to analyze staurosporine-treated SH-SY5Y neuroblastoma cells and compare them to non-treated control cells. Experimental results show that the ML technique can provide a classification accuracy (treated versus non-treated) of over 90%. The predicted percentage of the treated cells in a mixed solution is within 5% of the reference (ground-truth) value and the technique has the potential to be a viable method for real-time detection and diagnosis.     

Non‐invasive left ventricular myocardial work indices in healthy adolescents at rest

Global myocardial work (GMW) provides a metric of left ventricular (LV) function and energy consumption. Its non-invasive assessment by echocardiography correlates with invasive measures and normal values have been reported in healthy adults. We aimed to establish normal values in a healthy adolescent population. Fifty-two healthy adolescents (mean age?=?14.5?±?2.0 years, range 11–19 years, 62% male) with normal echocardiograms were included. Brachial cuff blood pressure was obtained immediately following apical imaging in the supine position. Post-processing of echocardiograms for speckle tracking strain measurement and derivation of global myocardial work indices from LV pressure–strain loops was performed. The mean global work index (GWI) was 1802.0?±?264.4 mmHg% with mean global work efficiency of 95.5?±?1.1%. The mean global constructive work (GCW) was 2054.5?±?297.3 mmHg%, and the mean global wasted work 83.8?±?28.1 mmHg%. On multivariable analysis, there were significant associations between both GWI and GCW with systolic blood pressure (β coefficient?=?0.57, p?<?0.001; β coefficient?=?0.67, p?<?0.001 respectively) and LV global longitudinal strain (GLS) (β coefficient = ? 0.56, p?<?0.001; β coefficient = ? 0.52, p?<?0.001 respectively). There were no associations with any of the work indices with age, sex, body surface area, heart rate or LV ejection fraction. This study provides echocardiographic reference ranges for non-invasive indices of GMW in normal adolescents.

     

Effect of specific surface area on syngas production performance of pure ceria in high-temperature thermochemical redox cycling coupled to methane partial oxidation

Specific surface area is a key parameter determining the rates of thermochemical redox reactions in metal oxides. We have experimentally investigated the effect of specific surface area on syngas production of pure ceria powders under two experiments such as a heating experiment without syngas production and an isothermal thermochemical redox cycling experiment using carbon dioxide splitting and methane partial oxidation. The specific surface area of ceria powders decreased relatively slowly during 50 hours of ceria powder heating without syngas production due to a combination of oriented attachment and grain-boundary diffusion. When cycled thermochemically, the specific surface area of ceria powders rapidly decreased only in the initial 10 minutes of reduction in the 1st cycle due to evaporation and condensation. A significant decrease of specific surface area during the initial stage of thermochemical ceria powder cycling is unavoidable even if temperatures as low as T = 1173 K are used in the reduction reaction coupled to methane partial oxidation.

Specific surface area is a key parameter determining the rates of thermochemical redox reactions in metal oxides.     

Adverse events related to topical drug treatments for acne vulgaris

ABSTRACT

Introduction: Acne vulgaris is a widespread skin disease. Topical therapy is a standard treatment for mild to moderate acne. Given the complex pathophysiology of acne, various agents with complementary action are nowadays frequently combined to increase the efficacy of therapy.

Area covered: This review focus on safety profile of topical agents used for the treatment of acne vulgaris, including topical retinoids, benzyl peroxide, azelaic acid, topical antibiotic, and combined agents. Data from clinical trials but also metanalyses, systematic reviews, and other secondary analyses are presented.

Expert opinion: In general, topical agents used for acne vulgaris have a favorable safety profile. The most commonly reported AEs were associated with local skin irritation, usually mild to moderate in intensity, intermittent, and rarely led to the cessation of therapy. Irritative potential seems to be highest for BPO and topical retinoids. Due to the possibility of development of Cutibacterium acnes resistance, topical antibiotics should not be used in monotherapy but as a part of combination therapy. In female adolescent and adults of childbearing potential, topical retinoids should be used with caution, because they are contraindicated in pregnant females (FDA Pregnancy category) C (adapalene, tretinoin) and X (tazarotene).     

Phosphate Kinetics During Weekly Cycle of Hemodialysis Sessions: Application of Mathematical Modeling

Both hyperphosphatemia and hypophosphatemia are associated with increased morbidity and mortality among patients on dialysis. The control of serum phosphate concentration is a considerable clinical problem. Our study aimed to improve understanding of phosphate kinetics in patients on dialysis using mathematical modeling. Three consecutive hemodialysis sessions with breaks of 2–2–3 days were monitored in 25 patients. Phosphate concentration was measured every hour and 45 min after the end of dialysis in blood serum and every 30 min in dialysate during each session. Volume of fluid compartments and body composition were assessed by bioimpedance. The pseudo one‐compartment model was applied to describe the profile of phosphate in blood serum during intra‐ and interdialytic periods of 1‐week cycle of three hemodialysis sessions. Model parameters, such as phosphate internal clearance (K_M) and the rate of phosphate mobilization (R_M), were correlated with the reduction of serum phosphate concentration during dialysis (C_post/C_pre) and with equivalent continuous clearance (ECC) for phosphate. K_M correlated negatively with predialysis serum phosphate concentration. There was significant positive correlation between R_M and age. Postdialysis volume of phosphate central compartment was lower than, but correlated to, extracellular water volume. Parameters of the pseudo one‐compartment model, phosphate internal clearance, and the rate of phosphate inflow to the central compartment (the one accessible for dialysis) from other phosphate body reservoirs correlated with the indices of dialysis adequacy, such as reduction of serum phosphate and ECC. The pseudo one‐compartment model can be successfully extended from a single hemodialysis to the standard weekly cycle of sessions and the model parameters strongly correlate with the adequacy parameters of dialytic removal of phosphate.     

Pulmonary embolism in a patient with unstable angina treated with surgical revascularisation--a case report

A case of a 58-year-old female patient with unstable angina is presented. Two weeks earlier the patient suffered from acute myocardial infarction treated with thrombolysis. The patient underwent surgical revascularisation which was complicated by acute pulmonary embolism. Repeated surgery and inspection of pulmonary arteries revealed the presence of thrombus which was successfully removed. The post-operative course was uneventful. The causes and treatment of pulmonary embolism complicating coronary artery by-pass grafting are discussed.     

Clinical aspects of the three major genetic forms of long QT syndrome (LQT1, LQT2, LQT3)

Background

A comprehensive report on the clinical course of the three major genotypes of the long QT syndrome (LQTS) in a large U.S. patient cohort is lacking.

Methods

Our study consisted of 1,923 U.S. subjects from the Rochester‐based LQTS Registry with genotype‐positive LQT1 (n = 879), LQT2 (n = 807), and LQT3 (n = 237). We evaluated the risk of a first cardiac event (syncope, aborted cardiac arrest, or sudden cardiac death, whichever occurred first) from birth through age 50 years. Cox proportional hazards regression models incorporating clinical covariates were used to assess genotype‐specific risk of cardiac events.

Results

For all three genotypes, the cumulative probability of a first cardiac event increased most markedly during adolescence. Multivariate analysis identified proband status and QTc > 500 ms as predictors of cardiac events in all three genotypes, and males <14 years and females >14 years as predictors of cardiac events in LQT1 and LQT2 only. Beta‐blockers significantly reduced the risk of cardiac events in LQT1 (HR: 0.49, p = .002) and LQT2 patients (HR: 0.48, p = .001). A trend toward beta‐blocker benefit in reducing cardiac events was found in LQT3 females (HR: 0.32, p = .078), but not in LQT3 males (HR: 1.37, p = .611).

Conclusion

Risk factors and outcomes in LQTS patients varied by genotype. In all three genotypes, proband status and prolonged QTc were risk factors for cardiac events. Younger males and older females experienced increased risk in LQT1 and LQT2 only. Beta‐blockers were most effective in reducing cardiac events in LQT1 and LQT2, with a potential benefit in LQT3 females.