Search

Abstract Pulmonary arterial hypertension (PAH) is a disease characterized by pulmonary vascular remodeling. Since dephosphorylated-uncarboxylated Matrix Gla-Protein (dp-ucMGP) is associated with cardiovascular mortality in systemic sclerosis, a disease associated with PAH, and immune-system involvement in PAH is increasingly recognized, we investigated the relationship between dp-ucMGP, vascular remodeling and soluble immune-checkpoint proteins in PAH. This prospective cohort study included patients with idiopathic (I)PAH, connective tissue disease (CTD)-PAH, chronic thrombo-embolic PH (CTEPH) and CTD patients without PAH. Patients with IPAH and CTD-PAH were stratified by clinical signs of immune-mediated inflammatory disease (IMID). We measured dp-ucMGP plasma levels, soluble immune-checkpoint proteins (sICPs), and vascular smooth muscle cell (iVSMC) calcification. We found elevated dp-ucMGP levels in all PAH subtypes and CTD patients compared to healthy controls. PAH patients showed increased iVSMC calcification, but no direct correlation was found with dp-ucMGP. IMID-PAH patients had higher dp-ucMGP levels than non-IMID PAH patients. dp-ucMGP correlated with several sICPs in both IPAH and CTD patients; multiple sICPs were elevated in IMID PAH patients. High dp-ucMGP levels in IPAH patients were associated with worse survival. Our findings suggest dp-ucMGP as a potential biomarker of immune-mediated vascular remodeling in PAH. Hence, dp-ucMGP, could help identify PAH patients who might benefit from immunosuppressive therapies.

Objective: Systemic sclerosis (SSc) related mortality and morbidity remains high. Immunosuppressive therapy is considered most effective when immune activity and inflammation but not fibrosis still dominates the disease process. This study evaluated long-term intensified immunosuppression combined with therapeutic plasma exchange (TPE) in early-onset progressive SSc-related interstitial lung disease (ILD). Methods: The study cohort consisted of 161 SSc patients, with a median follow-up time of 8.9 years. The standardized mortality rate (SMR) and overall survival was calculated in patients with and without cardiopulmonary involvement. We used a standardized, pragmatic, non-randomized approach to treat 24 consecutive early progressive SSc-ILD patients with intensified immunosuppressive therapy, including plasma exchange. Outcome measurements were event-free survival (EFS), pulmonary function and safety profile. The outcome was compared with the analyzed data from the other SSc-ILD patients, who did not fulfill the inclusion criteria, and instead were treated with estimated optimal care (EOc). Results: The age-adjusted SMR of all 161 SSc patients was 3.0 (CI95%; 0.32–5.68). EFS at 10 years was 49.9% in the intensified treatment group and 43.3% in the EOc group (p = 0.106). Improvement of the percentage of predicted forced vital capacity (%pFVC) and percentage of predicted diffusing capacity for carbon monoxide (%pDLco) in the intensified treatment group was +10.1% respectively +3.6%, compared to a decrease of respectively 10.8% and 7% in the EOc (p

Starting antiretroviral therapy (ART) same-day, or as soon as possible after HIV diagnosis is advised in guidelines worldwide. Especially during acute HIV infection (AHI), rapid ART start may be more urgent because of a higher risk of transmission or symptoms of acute retroviral syndrome. During this phase, rapid ART start may have additional benefits for viral reservoir size and host immunity. We explored perceptions of rapid ART start among participants of The Netherlands Cohort Study on Acute HIV infection (NOVA study), who started ART rapidly after diagnosis of AHI. We conducted 20 in-depth qualitative interviews with NOVA study participants between October and December 2018. Data were analyzed thematically, using inductive and iterative coding techniques. Roughly half of the participants stated they felt well-informed about the importance of (rapid) ART. Starting ART rapidly was perceived positively by almost all participants, mostly because of the expected benefits on their health, and to prevent HIV transmission. Rapid ART start was seen as a way to cope with the diagnosis. However, a more negative perception was that rapid ART start confronted participants with their diagnosis, when they were still adjusting to a new situation. Our results show that among people diagnosed during AHI, rapid ART is well-accepted. These results should be encouraging to HIV care providers who encounter people with AHI in their clinical practice and to researchers who carry out cure-related studies, in which early ART is often included. The Clinical Trial Registration number is NCT05728996. [ABSTRACT FROM AUTHOR]

An asymptomatic respiratory viral infection during cardiac surgery could lead to pulmonary complications and increased mortality. For elective surgery, testing for respiratory viral infection before surgery or vaccination could reduce the number of these pulmonary complications. The aim of this study was to investigate the association between influenzalike illness (ILI) seasons and prolonged mechanical ventilation and inhospital mortality in a Dutch cohort of adult elective cardiac surgery patients. Cardiac surgery patients who were admitted to the intensive care unit between January 1, 2014, and February 1, 2020, were included. The primary endpoint was the duration of invasive mechanical ventilation in the ILI season compared with baseline season. Secondary endpoints were the median Pa o 2 to fraction of inspired oxygen ratio on days 1, 3, and 7 and postoperative inhospital mortality. A total of 42,277 patients underwent cardiac surgery, 12,994 (30.7%) in the ILI season, 15,843 (37.5%) in the intermediate season, and 13,440 (31.8%) in the baseline season. No hazard rates indicative of a longer duration of invasive mechanical ventilation during the ILI season were found. No differences were found for the median Pa o 2 to fraction of inspired oxygen ratio between seasons. However, inhospital mortality was higher in the ILI season compared with baseline season (odds ratio 1.67; 95% CI, 1.14-2.46). Patients undergoing cardiac surgery during the ILI season were at increased risk of inhospital mortality compared with patients in the baseline season. No evidence was found that this difference is caused by direct postoperative pulmonary complications. [Display omitted] [ABSTRACT FROM AUTHOR]

Purpose: This article explores the views of Smallholder Marketing Cooperatives' (SMCs) leaders and staff, to gain insight about the particular roles SMCs play in facilitating smallholders' market access. Design/methodology/approach: The authors conceptualized and executed two international workshops in which participants from 42 SMCs from 24 countries deliberated their lessons learned from real-life experiences. Findings: Participants defined three core issues to be tackled by SMCs to play their role related to facilitating their members' market access: good FO governance and management; access to capital and networking. They highlighted that smallholders' market access improves not only as a result of SMCs networking and negotiation with key actors in the public and private sectors, but also due to improved interrelationships among SMCs and other types of Farmers' Organizations (FOs). Peer-to-peer relationships with other SMCs are critical for mutual learning, collaboration and collective action. Practical implications: Peer-to-peer relationships among SMCs are crucial for them to overcome the internal and external social dilemmas SMCs are bound to face while improving smallholders' market access. This goes beyond the three kinds of relationships that scholars have pointed out thus far needed for effective FO development (relationships with members; the public sector and civil society; and with market players). This can be promoted and supported by development programmes. Originality/value: Most SMC studies concentrate primarily on their efficiency in production and marketing activities. This research proposes looking beyond this perspective, using a qualitative approach to explore the real-life experiences and views of actors involved. (Contains 3 tables, 4 figures and 1 note.)

Although stakeholder participation is expected to promote equitable and sustainable natural resource management, lessons from the past tell us that more careful attention needs to be paid to achieving equitable impacts. Now the question is how to address social inequities and power asymmetries. Some authors emphasize the need for more dialogue, while others prefer a critical perspective, arguing that dialogue might not be sufficient to avert the risk of a process deepening existing social inequities. This article aims to enrich this debate and question the practical implications of the critical perspective through an in-depth analysis of power games in a participatory process. A Companion Modelling (ComMod) process was conducted in an Akha community of Northern Thailand with a critical perspective, i.e. with a concern for the less influent stakeholders. Simulation tools such as role-playing games were used to mediate a cross-cultural learning process among researchers, farmers and administrators about a local irrigation water management problem. The detailed analysis of power games in this learning and negotiation process reveals that in spite of initial power asymmetries, the poorest farmers of the community started to voice and assert their interests. This was very much due to the role of a Western researcher who put the equity issue on the public agenda and to the strategic support of a charismatic Christian leader. We identify a set of practical facilitation methods that helped to manage power asymmetries and to level the playing field, but we also discuss the main limits of our cultural-embedded methodological choices. Acknowledging that "the facilitators' neutrality" is an illusion, this study allows us to raise the question of their social legitimacy. We suggest that they should systematically make explicit and reflect on their cultural-ideological background and methodological hypothesis and choices and their effects on the socio-political context. This article is an original attempt to accept this challenge. (Contains 2 tables and 3 figures.)