Low exercise blood pressure and risk of cardiovascular events and all-cause mortality: Systematic review and meta-analysis

Objective

The independent prognostic significance of abnormally low systolic blood pressure (SBP) during exercise stress testing (LowExBP) across different clinical and exercise conditions is unknown. We sought by systematic review and meta-analysis to determine the association between cardiovascular/all-cause outcomes and LowExBP across different patient clinical presentations, exercise modes, exercise intensities and categories of LowExBP.

Methods

Seven online databases were searched for longitudinal studies reporting the association of LowExBP with risk of fatal and non-fatal cardiovascular events and/or all-cause mortality. LowExBP was defined as either: SBP drop below baseline; failure to increase >10 mmHg from baseline or; lowest SBP quantile among reporting studies.

Results

After review of 13,257 studies, 19 that adjusted for resting SBP were included in the meta-analysis, with a total of 45,895 participants (average follow-up, 4.4 ± 3.0 years). For the whole population, LowExBP was associated with increased risk for fatal and non-fatal cardiovascular events and all-cause mortality (hazard ratio [HR]: 2.01, 95% confidence interval [CI]: 1.59–2.53, p < 0.001). In continuous analyses, a 10 mmHg decrease in exercise SBP was associated with higher risk (n = 9 HR: 1.13, 95% CI: 1.06–1.20, p < 0.001). LowExBP was associated with increased risk regardless of clinical presentation (coronary artery disease, heart failure, hypertrophic cardiomyopathy or peripheral artery disease), exercise mode (treadmill or bike), exercise intensity (moderate or maximal), or LowExBP category (all p < 0.05). However, bias toward positive results was apparent (Eggers test p < 0.001 and p = 0.009).

Conclusion

Our data show that irrespective of clinical or exercise conditions, LowExBP independently predicts fatal and non-fatal cardiovascular events and all-cause mortality.     

Preictal Dynamics of EEG Complexity in Intracranially Recorded Epileptic Seizure: A Case Report

Recent findings suggest that neural complexity reflecting a number of independent processes in the brain may characterize typical changes during epileptic seizures and may enable to describe preictal dynamics. With respect to previously reported findings suggesting specific changes in neural complexity during preictal period, we have used measure of pointwise correlation dimension (PD2) as a sensitive indicator of nonstationary changes in complexity of the electroencephalogram (EEG) signal. Although this measure of complexity in epileptic patients was previously reported by Feucht et al (Applications of correlation dimension and pointwise dimension for non-linear topographical analysis of focal onset seizures. Med Biol Comput. 1999;37:208–217), it was not used to study changes in preictal dynamics. With this aim to study preictal changes of EEG complexity, we have examined signals from 11 multicontact depth (intracerebral) EEG electrodes located in 108 cortical and subcortical brain sites, and from 3 scalp EEG electrodes in a patient with intractable epilepsy, who underwent preoperative evaluation before epilepsy surgery. From those 108 EEG contacts, records related to 44 electrode contacts implanted into lesional structures and white matter were not included into the experimental analysis.The results show that in comparison to interictal period (at about 8–6 minutes before seizure onset), there was a statistically significant decrease in PD2 complexity in the preictal period at about 2 minutes before seizure onset in all 64 intracranial channels localized in various brain sites that were included into the analysis and in 3 scalp EEG channels as well. Presented results suggest that using PD2 in EEG analysis may have significant implications for research of preictal dynamics and prediction of epileptic seizures.     

Arylazopyrazole AAP1742 Inhibits CDKs and Induces Apoptosis in Multiple Myeloma Cells via Mcl‐1 Downregulation

Inhibitors of cyclin‐dependent kinases 9 have been developed as potential anticancer drugs for the treatment of multiple myeloma. We have previously prepared a library of arylazo‐3,5‐diaminopyrazole inhibitors of CDKs. Here, we describe a novel member, AAP1742 (CDK9 inhibition with IC₅₀ = 0.28 μm ), that reduces the viability of multiple myeloma cell lines in low micromolar concentrations. Consistent with inhibition of CDK9, AAP1742 decreases the phosphorylation of RNA polymerase II and inhibits mRNA synthesis of anti‐apoptotic proteins Mcl‐1, Bcl‐2, and XIAP, followed by apoptosis in the RPMI‐8226 cell line in a dose‐ and a time‐dependent manner. These results are consistent with the biochemical profile of AAP1742 and further suggest cellular inhibition of CDK9 as a possible target for anticancer drugs.     

Adherence to osteoporosis guideline: survey among Czech general practitioners

Rationale and objectives

General practitioners (GPs) play an important role in management of patients at risk of osteoporosis (OP). The objectives were to assess (1) knowledge about OP and use of OP clinical guideline in comparison with other information sources and (2) association between the use of individual information sources and knowledge and self-reported quality of care among GPs.

Methods

Survey among random sample of Czech GPs was performed to find out their attitudes and role in OP management. The return rate of the postal questionnaire was 38% (525 respondents). Quality of care was assessed using three indicators: suspicion on OP, referral to the specialist and initial check-up.

Results

Respondents (median age 52 years, 59% women) had a very good knowledge of several risk factors, while others, namely low body mass index, history of hip fracture in mother and smoking were perceived as risk factors by only 40%, 45% and 55% of respondents, respectively. 10% of GPs stated the correct answer regarding daily calcium intake recommended for postmenopausal women. The OP guideline was considered accessible by 83% of respondents and used repeatedly by 54%. Use of the guideline correlated positively with knowledge score (P < 0.001), while use of each individual other source of information did not. Use of the guideline correlated with all three indicators of quality of care. Use of each other information source correlated only with a maximum of two indicators.

Conclusion

We identified areas of insufficient knowledge that should be targeted in educational activities for GPs. It is recommended to further motivate GPs to use their clinical guidelines regularly.     

Rapid Detection and Identification of Mucormycetes in Bronchoalveolar Lavage Samples from Immunocompromised Patients with Pulmonary Infiltrates by Use of High-Resolution Melt Analysis

Rapid differential diagnostics of pulmonary infiltrates suspected of invasive fungal disease in an immunocompromised host and early initiation of effective antifungal therapy are crucial for patient outcomes. There are no serological tests available to detect mucormycetes; therefore, PCR-based methods are highly suitable. We validated our previously published PCR followed by high-resolution melt analysis (PCR/HRMA) to detect Rhizopus spp., Rhizomucor pusillus, Lichtheimia corymbifera, and Mucor spp. in bronchoalveolar lavage (BAL) samples from immunocompromised patients who were at risk of invasive fungal disease. All PCR/HRMA-positive samples were retested using novel real-time quantitative PCR (RQ PCR) assays specific to the species identified. In total, between January 2009 and December 2012 we analyzed 99 BAL samples from 86 patients with pulmonary abnormalities using PCR/HRMA. Ninety (91%) BAL samples were negative, and 9 (9%) samples were positive. The sensitivity and specificity of PCR/HRMA were 100% and 93%, respectively. By combining the positive results of PCR/HRMA with positive RQ PCR results, the specificity was raised to 98%. PCR/HRMA, due to its high negative predictive value (99%), represents a fast and reliable tool for routine BAL sample screening for the differential diagnosis of pulmonary infiltrates in immunocompromised patients for the four most clinically important mucormycetes.     

Structure Refinement and Fragmentation of Precipitates under Severe Plastic Deformation: A Review

During severe plastic deformation (SPD), the processes of lattice defect formation as well as their relaxation (annihilation) compete with each other. As a result, a dynamic equilibrium is established, and a steady state is reached after a certain strain value. Simultaneously, other kinetic processes act in opposite directions and also compete with each other during SPD, such as grain refinement/growth, mechanical strengthening/softening, formation/decomposition of solid solution, etc. These competing processes also lead to dynamic equilibrium and result in a steady state (saturation), albeit after different strains. Among these steady-state phenomena, particle fragmentation during the second phase of SPD has received little attention. Available data indicate that precipitate fragmentation slows down with increasing strain, though saturation is achieved at higher strains than in the case of hardness or grain size. Moreover, one can consider the SPD-driven nanocrystallization in the amorphous phase as a process that is opposite to the fragmentation of precipitates. The size of these crystalline nanoprecipitates also saturates after a certain strain. The fragmentation of precipitates during SPD is the topic of this review.     

Substantial Improvement of High Temperature Strength of New-Generation Nano-Oxide-Strengthened Alloys by Addition of Metallic Yttrium

Oxide-dispersion-strengthened (ODS) Fe-Al-Y₂O₃-based alloys (denoted as FeAlOY) containing 5 vol. % of nano-oxides have a potential to become top oxidation and creep-resistant alloys for applications at temperatures of 1100–1300 °C. Oxide dispersoids cause nearly perfect strengthening of grains; thus, grain boundaries with limited cohesive strength become the weak link in FeAlOY in this temperature range. One of the possibilities for significantly improving the strength of FeAlOY is alloying with appropriate elements and increasing the cohesive strength of grain boundaries. Nearly 20 metallic elements have been tested with the aim to increase cohesive strength in the frame of preliminary tests. A positive influence is revealed for Al, Cr, and Y, whereby the influence of Y is enormous (addition of 1% of metallic Y increases strength by a factor of 2), as it is presented in this paper.