Anxiety,Depression, and Health-Related QOL in Patients Diagnosed with PAH or CTEPH

Background

Pulmonary arterial hypertension (PAH) and chronic thromboembolic pulmonary hypertension (CTEPH) are life-threatening diseases with a high burden of symptoms. Although depression, anxiety, and reduced health related quality of life (HRQOL) have also been reported, a comparative analysis which explores these traits and their underlying factors was lacking.

Methods

A retrospective analysis of depression, anxiety, and health related QOL was conducted using a Hospital anxiety and depression scale (HADS) as well as the SF-36 HRQOL questionnaire. Results from these tools were compared with haemodynamic and functional parameters in 70 PAH and 23 CTEPH outpatients from a German tertiary care center specializing in pulmonary hypertension.

Results

Although HRQOL was reduced in both cohorts of patients, individuals diagnosed with CTEPH scored lower in nearly all SF-36 parameters. Significance was noted in both “mental health” (p = 0.01) and “mental component summary score” (MCS) (p = 0.02). Depression was also more frequent in patients with CTEPH (56%) than in patients with PAH (30%), (p = 0.03). Overall, depression and anxiety correlated with most SF-36 scales in both PAH and CTEPH. In CTEPH, depression also correlated with the Borg Dyspnea Scale (r = 0.44, p = 0.01). These patients also had significantly lower pCO₂ levels than the PAH cohort reflecting more severe ventilation/perfusion mismatch. All other haemodynamic and functional parameters did not differ across the groups.

Conclusion

While both cohorts of patients suffer from a reduced HRQOL as well as depression and anxiety, decreases in mental health parameters are more pronounced in the CTEPH cohort. This suggests a strong effort to improve early detection, especially in dyspneic patients with classical risk factors for CTEPH and PAH and argues for mental illness interventions alongside routine clinical care provided to patients diagnosed with PAH or CTEPH.

     

Neonatal encephalocardiomyopathy caused by mutations in VARS2

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Impact of non-transferrin-bound iron (NTBI) in comparison to serum ferritin on outcome after allogeneic stem cell transplantation (ASCT)

The optimal parameters and time points for the measurement of iron overload (IO) in allogeneic stem cell transplantation (ASCT) patients are still under discussion. Hyperferritinemia and IO are poor prognostic factors in ASCT. We hypothesize that non-transferrin-bound iron (NBTI) is possibly a better marker to predict the effect of IO on the outcome than serum ferritin (SF), which however is not specific for IO. The aim of this prospective observational trial was to evaluate the influence of NBTI in comparison to SF on the outcome of ASCT patients [overall survival, bloodstream infections (BSIs), and invasive fungal infections (IFIs)]. We analyzed daily transferrin saturation (TSAT), SF, and NTBI (if TSAT exceeded 70%) in 100 patients who received ASCT during conditioning, and on day 0, +7, and +14 post-ASCT. After a median NTBI level of 0 μmol/l at baseline, the median of the area under the curve (AUC) of NTBI between conditioning and ASCT (d0) increased to 17 μmol*d/l, and between ASCT and day +14 to 56.3 μmol*d/l. Higher NTBI-AUC d0 resulted in a higher risk of BSI (HR 1.042, p = 0.009) and IFI (HR 1.070, p = 0.001) and showed a trend of inferior 1-year survival (65 vs. 76%, p = 0.09). Baseline SF did not influence BSI, but higher levels resulted in more IFI (HR 1.26, p < 0.001). In conclusion, NTBI possibly better predict for a higher risk of bloodstream infections than SF and needs further investigation.     

Why meta-analyses are important for complementary and alternative medicine research

Complementary and alternative medicine (CAM) is defined as a group of interventions that are not generally considered part of conventional medicine. This definition already implies that CAM interventions are often not systematically studied; and the research evidence from single trials on CAM is often limited by small sample sizes, unclear methodology, and inadequate statistics. As a result, both, significant and insignificant results are often hard to interpret based on single trials. Summarizing the evidence from single CAM trials, qualitative systematic reviews still have to deal with the same problems as individual trials as they can only rely on the original reports. Thus, effects of CAM interventions are often underestimated or overestimated based on single trials or qualitative systematic reviews. While meta-analyses still are limited by the methodological shortcomings of the included studies, a well-conducted meta-analysis can deal with two common problems of CAM trials: inadequate statistics that rely on within-group comparisons and small underpowered sample sizes. Although large and high quality trials are urgently needed for most CAM interventions, funding often is limited. Until higher quality research is available, meta-analyses provide a useful tool to investigate the actual level of evidence of currently published CAM trials. This editorial presents examples of meta-analyses in the field of CAM and discusses how they contribute to the consolidation of evidence.     

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The discovery of the histamine H(4) receptor has added a new chapter to the century of extensive biogenic amine research. The human histamine H(4) receptor is mainly expressed in cells of the human immune system (e.g. mast cells, eosinophils, monocytes, dendritic cells, T cells) and mediates several effects on chemotaxis with numerous cell types. The distinct expression pattern and the immunomodulatory role highlight its physiological relevance in inflammatory and immunological processes. Inflammatory conditions, e.g. allergy, asthma and autoimmune diseases, were for a long time thought to be mainly mediated by activation of the histamine H(1) receptor subtype. However, in the treatment of diseases as chronic pruritus, asthma and allergic rhinitis the use of histamine H(1) receptor antagonists is unsatisfying. Selective H(4) receptor ligands and/or synergism of histamine H(1) and H(4) receptor modulation may be more effective in such pathophysiological conditions. Promising preclinical studies underline its role as an attractive target in the treatment of inflammatory and autoimmune disorders. Meanwhile, first histamine H(4) receptor antagonist has reached clinical phases for the treatment of respiratory diseases.     

Internalization of biotinylated compounds into cancer cells is promoted by a molecular Trojan horse based upon core streptavidin and clostridial C2 toxin

The C2 toxin produced by Clostridium botulinum is a binary AB-type exotoxin composed of the enzyme subunit C2I and the binding/translocation moiety C2II. After proteolytic activation, C2IIa mediates the subsequent internalization of C2I into the cytosol of mammalian target cells. The N-terminal domain of C2I (C2IN) is necessary for C2IIa-dependent uptake, but lacks the enzyme domain that is responsible for cytotoxicity. In the present study, we generated a delivery system building on C2IN and a truncated core streptavidin (Stv13) with enhanced solubility for the C2IIa-dependent internalization of biotinylated cargo molecules into mammalian cells. C2IN–Stv13 fusion protein expressed in Escherichia coli was obtained in high yields and purity. The affinity-purified protein formed tetramers and a defined higher order species in solution as shown by gel filtration and retained its biotin-binding properties, however with an obvious reduction in affinity. Uptake of C2IN–Stv13 into the cytosol of HeLa and other cancer cell lines was observed by immunoblot analysis, which was corroborated by confocal microscopy. In addition, the fusion protein was not cytotoxic and did not inhibit cell proliferation as determined by MTS assay. Finally, we demonstrated the C2IN–Stv13/C2IIa-mediated uptake of biocytin–Alexa 488 as cargo into HeLa cells, underscoring the functionality of the generated transport system.