No abstract

PurposeTo evaluate the influence of riociguat on World Health Organization functional class (WHO FC), 6-min walk distance (6MWD), right heart remodeling, and right ventricular–pulmonary arterial (RV–PA) coupling in patients with idiopathic pulmonary arterial hypertension (IPAH) who are treatment-naïve or who have failed to achieve treatment goals with sildenafil therapy.MethodsTwenty patients with IPAH were enrolled: 12 had not previously received PAH-targeted therapy (treatment-naïve subgroup) and 8 had been receiving sildenafil therapy but failed to achieve treatment goals; on entering this pilot study these 8 patients were switched from sildenafil to riociguat therapy (treatment-switch subgroup). Patients received riociguat individually dose-adjusted up to a maximum of 2.5 mg three times daily. After 12 weeks, patients were assessed for WHO FC, 6MWD, right heart remodeling, and RV–PA coupling.ResultsRiociguat significantly improved WHO FC in treatment-naïve patients (from 0/4/8/0 patients in WHO I/II/III/IV at baseline to 1/6/5/0 at week 12) and in treatment-switch patients (from 0/4/4/0 patients in WHO I/II/III/IV at baseline to 1/4/3/0 at week 12). Additionally, treatment-naïve and treatment-switch patients showed significant improvements at week 12 versus baseline in 6MWD (increases of + 76.8 m and + 71.6 m, respectively), RV systolic function, and RV–PA coupling.ConclusionThese results support the proven efficacy of riociguat in patients with IPAH, including treatment-naïve patients and those switching to riociguat following failure to achieve treatment goals with sildenafil, and suggest that it may be possible to delay disease progression in this patient group.Electronic supplementary materialThe online version of this article (10.1007/s00408-018-0160-4) contains supplementary material, which is available to authorized users.

No abstract

Nowadays, there is an interest in biomedical and nanobiotechnological studies, such as studies on carotenoids as antioxidants and studies on molecular markers for cardiovascular, endocrine, and oncological diseases. Moreover, interest in industrial production of microalgal biomass for biofuels and bioproducts has stimulated studies on microalgal physiology and mechanisms of synthesis and accumulation of valuable biomolecules in algal cells. Biomolecules such as neutral lipids and carotenoids are being actively explored by the biotechnology community. Raman spectroscopy (RS) has become an important tool for researchers to understand biological processes at the cellular level in medicine and biotechnology. This review provides a brief analysis of existing studies on the application of RS for investigation of biological, medical, analytical, photosynthetic, and algal research, particularly to understand how the technique can be used for lipids, carotenoids, and cellular research. First, the review article shows the main applications of the modified Raman spectroscopy in medicine and biotechnology. Research works in the field of medicine and biotechnology are analysed in terms of showing the common connections of some studies as caretenoids and lipids. Second, this article summarises some of the recent advances in Raman microspectroscopy applications in areas related to microalgal detection. Strategies based on Raman spectroscopy provide potential for biochemical-composition analysis and imaging of living microalgal cells, in situ and in vivo. Finally, current approaches used in the papers presented show the advantages, perspectives, and other essential specifics of the method applied to plants and other species/objects.

Aim. To study demographic and clinical characteristics and to give a comparative description of the functional and hemodynamic status, profile of concomitant pathology in patients with various forms of pulmonary arterial hypertension (PAH), and chronic thromboembolic pulmonary hypertension (CTEPH) according to the Russian National Registry. Methods. During the period from January 01, 2012, till January 01, 2019, 1105 patients aged >18 years with verified diagnosis of PAH and CTEPH, who were subsequently observed at 15 PH expert centers of the Russian Federation in the 52 provinces, are included in the Russian registry on the basis of the Federal State Budgetary Institution of Cardiology of the Ministry of Healthcare of Russia. All newly diagnosed patients (n=727) were entered into the registry database (NCT03707561). A comparative analysis of demographic and clinical characteristics, profile of concomitant pathology, and parameters of a comprehensive examination of patients was performed. Results. Among newly diagnosed patients, 67% had PAH and 28.3% had CTEPH. In the PAH group, 40.9% of patients had idiopathic arterial PAH (IPAH), 36.6% had PAH associated with simple congenital heart disease (PAH-CHD), 19.3% had PAH associated with systemic connective tissue disease (PAH-CTD), 1.8% had portal pulmonary hypertension (PoPH), 0.6% had PAH associated with HIV infection (PAH-HIV), 0.4% had heritable PAH (HPAH), and 0.4% had drug/toxin-induced PAH. At the time of diagnosis, PAH patients were younger than patients with CTEPH (45.2±14.9; 52.6±15.3 years, respectively) (p<0.05). At the time of diagnosis, 71% PAH and 77% CTEPH patients had WHO FC III/IV. Mean (±SD) 6MWD was significantly less in CTEPH vs. the PAH group 331.3±110.3 vs. 361.8±135.7 m (p=0.0006). Echo data showed a comparable sPAP between groups; CTEPH population had a more pronounced increase in the area of the right atrium (SRA) (24 [20; 32] cm2 and 19 [15; 26] cm2, respectively), and a significant decrease in FAC (24.7 [22, 4; 29.0] and 29.0 [23.0; 31.0] %, respectively) as compared to the PAH group. RHC showed a comparable increase of sPAP and mPAP in PAH and CTEPH groups. 15.2% of patients with IPAH and HPAH demonstrated positive results in the acute vasoreactivity testing. CTEPH patients were more often obese and suffered from arterial hypertension and right heart failure. Deep venous thrombosis was significantly more often observed in patients with CTEPH (53%). The most common concomitant pathology was erosive-ulcerative lesion of the stomach/duodenum, less often of the esophagus (23.5% and 44.5%, respectively). Conclusion. According to the Russian registry in patients with PAH and IPAH, the diagnosis is established at a younger age in comparison with the European registries. CTEPH patients are characterized by more severe functional status, pronounced signs of right heart failure taking into account the older age and the spectrum of comorbid pathology, which limits the possibility of surgical treatment. An increase in the number of expert centers participating in the registry is the key to improving early diagnosis of PH and optimal follow-up according to common standards in order to timely optimize therapy and reduce mortality of patients.

This is a PDF file of an article that has undergone enhancements after acceptance, such as the addition of a cover page and metadata, and formatting for readability, but it is not yet the definitive version of record. This version will undergo additional copyediting, typesetting and review before it is published in its final form, but we are providing this version to give early visibility of the article. Please note that, during the production process, errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.

No abstract

Aim. Assess the prevalence, clinical course, current therapy, and mortality in patients with pulmonary arterial hypertension (PAH) in the National Registry. Materials and methods. In the prospective study we included patients over 18 years of age with diagnosed PAH [idiopathic PAH (IPAH); Drug - and Toxin-Induced Pulmonary Hypertension; inherited PAH; PAH associated with congenital heart disease (PAH-CHD); PAH associated with systemic connective tissue disease (PAH-CTD); PAH associated with HIV infection (PAH-HIV); with portal pulmonary hypertension (portoPAH)]. The observation was carried out in 15 expert centers of Russia from 01.01.2012 to 31.12.2017. Results. Our registry included 470 patients with PAH: IPAH - 41.5%, PAH-CHD - 36%, PAH-CTD - 19.5%, inherited PAH - 0.4%, portoPAH - 1.9%, PAH-HIV - 0.4%, Drug - and Toxin-Induced PAH - 0.4%. The prevalence among women was 84%. The mean age at the time of patient enrollment in the registry for the overall group of PAH was 42.7±15.3 years. The distance in the 6-minute walking test was 361.3±129.3 m. Among all patients with PAH, 65% had functional class (FC) III/IV at the time of diagnosis, among IPAH - 62%. 69.9% received PAH-specific therapy, of which 62.1% - monotherapy, 32.7% - dual combination therapy, and 5.2% triple therapy. Sildenafil is the most commonly prescribed drug in the regimen of monotherapy. 31.6% of patients were treated with bosentan, 6.4% - riociguat, 3.4% - ambrisentan, 2.1% - macitentan and 2.0% iloprost. Survival of patients with PAH was 98.9% at 1 year of follow-up, 94.1% at 3 years and 86.0% at 5 years. Conclusion. The registry data indirectly indicates the need to increase efforts aimed at improving the diagnosis of systemic connective tissue diseases in adults, as well as congenital heart defects in children for timely surgical treatment. In recent years, PAH-specific drugs of the new generation have been introduced into clinical practice, but currently in Russia there are no parenteral prostanoids, which are recommended for the most severe patients.