Chronic Chagas disease cardiomyopathy (CCC) is the most important clinical manifestation of infection with Trypanosma cruzi (T. cruzi) due to its frequency and effects on morbidity and mortality. Peripheral blood mononuclear cells (PBMC) infiltrate the tissue and differentiate into inflammatory macrophages. Advances in pathophysiology show that myeloid cell subpopulations contribute to cardiac homeostasis, emerging as possible therapeutic targets. We previously demonstrated that fenofibrate, PPARα agonist, controls inflammation, prevents fibrosis and improves cardiac function in a murine infection model. In this work we investigated the spontaneous release of inflammatory cytokines and chemokines, changes in the frequencies of monocyte subsets, and fenofibrate effects on PBMC of seropositive patients with different clinical stages of Chagas disease. The results show that PBMC from Chagas disease patients display higher levels of IL-12, TGF-β, IL-6, MCP1, and CCR2 than cells from uninfected individuals (HI), irrespectively of the clinical stage, asymptomatic (Asy) or with Chagas heart disease (CHD). Fenofibrate reduces the levels of pro-inflammatory mediators and CCR2 in both Asy and CHD patients. We found that CHD patients display a significantly higher percentage of classical monocytes in comparison with Asy patients and HI. Besides, Asy patients have a significantly higher percentage of non-classical monocytes than CHD patients or HI. However, no difference in the intermediate monocyte subpopulation was found between groups. Moreover, monocytes from Asy or CHD patients exhibit different responses upon stimulation in vitro with T. cruzi lysates and fenofibrate treatment. Stimulation with T. cruzi significantly increases the percentage of classical monocytes in the Asy group whereas the percentage of intermediate monocytes decreases. Besides, there are no changes in their frequencies in CHD or HI. Notably, stimulation with T. cruzi did not modify the frequency of the non-classical monocytes subpopulation in any of the groups studied. Moreover, fenofibrate treatment of T. cruzi-stimulated cells, increased the frequency of the non-classical subpopulation in Asy patients. Interestingly, fenofibrate restores CCR2 levels but does not modify HLA-DR expression in any groups. In conclusion, our results emphasize a potential role for fenofibrate as a modulator of monocyte subpopulations towards an anti-inflammatory and healing profile in different stages of chronic Chagas disease.
BackgroundSingle and multi-center studies have described substantial changes in the landscape of health care in cardiac intensive care units (CICU). Few reports have quantitatively characterized current diagnoses in a contemporary CICU in Latin America. This study aims to describe demographics, diagnoses, care patterns, and outcomes in patients admitted to a CICU in a high-volume center in South America. Methods A total of 1629 consecutive patients admitted to CICU from December 2017 to April 2020 were included in a prospective registry. The variables analyzed included demographic data, admission and final diagnoses, management, and outcomes. Results Among 1629 participants, 32.4% were women, and the median age was 62 years (53-71). Admissions were due to primary cardiac causes in 1335 (81.9%), postsurgical care in 13.3%, and a combination of general and cardiac diagnoses in 4.8% of patients. The most frequent diagnosis on admission was acute coronary syndrome (ACS) (35.7%). Primary reasons for CICU admission were postprocedural observation (PPO) (31.8%), diagnosed or suspected ACS (31.7%), heart failure (10.1%), postsurgical management after cardiovascular surgery (8.9%), arrhythmia (5.8%), shock (4.5%) and cardiac arrest (CA) (1.2%). Advanced CICU therapy requirements were ventilatory assistance (19.3%) and vasoactive or inotropic drug use (19.6%). The overall mortality rate was 6.4%. Admission diagnoses associated with the highest mortality rates were CA (52.6%), noncardiogenic shock (39.5%), and cardiogenic shock (32.3%). Notably, patients admitted solely for PPO had a mortality rate of 0.8%. ConclusionsIn a contemporary CICU from a high-volume reference center in South America, the most frequent diagnosis was an ACS, although it represented only one-third of the admissions. One-fifth of admissions required advanced CICU therapies. CA and shock on admission carried a poor prognosis. We identified PPO as a substantially low-risk population.
Background Idiopathic pulmonary arterial hypertension is associated with high morbidity and mortality. In recent years, the use of targeted therapies has led to an improvement in prognosis. Prostacyclin analogues treprostinil and epoprostenol require continuous subcutaneous or intravenous infusion and are generally administered in a stepwise approach. However, there are no clear recommendations for transition in high-risk patients requiring high doses of prostacyclin analogues. Case summary In this report, we describe the case of a 20-year-old woman under combined treatment with sildenafil, macitentan, and treprostinil who required transition from subcutaneous treprostinil therapy to intravenous epoprostenol due to erratic drug absorption and functional class progression. The transition was performed over 48 h in a stepwise approach reducing treprostinil dose 4 ng/kg/min every 3 h while increasing epoprostenol infusion 2 ng/kg/min until achieving a maintenance dose of 32 ng/kg/min. There were no side effects requiring changes in the infusion rate. Discussion Patients with advanced pulmonary arterial hypertension may necessitate switching from subcutaneous treprostinil to epoprostenol. Although many protocols have been used to date, there are no guidelines to direct this process safely. This 48-h scheme based on the pharmacokinetic properties of each drug was successful and well-tolerated.
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