Population-based evaluation of the impact of socioeconomic status on clinical outcomes in patients with heart failure in integrated care settings.

INTRODUCTION AND OBJECTIVES: Low socioeconomic status (SES) is associated with poor outcomes in patients with heart failure (HF). We aimed to examine the influence of SES on health outcomes after a quality of care improvement intervention for the management of HF integrating hospital and primary care resources in a health care area of 209 255 inhabitants. METHODS: We conducted a population-based pragmatic evaluation of the implementation of an integrated HF program by conducting a natural experiment using health care data. We included all individuals consecutively admitted to hospital with at least one ICD-9-CM code for HF as the primary diagnosis and discharged alive in Catalonia between January 1, 2015 and December 31, 2019. We compared outcomes between patients exposed to the new HF program and those in the remaining health care areas, globally and stratified by SES. RESULTS: A total of 77 554 patients were included in the study. Death occurred in 37 469 (48.3%), clinically-related hospitalization in 41 709 (53.8%) and HF readmission in 29 755 (38.4%). On multivariate analysis, low or very low SES was associated with an increased risk of all-cause death and clinically-related hospitalization (all Ps <.05). The multivariate models showed a significant reduction in the risk of all-cause death (HR, 0.812; 95%CI, 0.723-0.912), clinically-related hospitalization (HR, 0.886; 95%CI, 0.805-0.976) and HF hospitalization (HR, 0.838; 95%CI, 0.745-0.944) in patients exposed to the new HF program compared with patients exposed to the remaining health care areas and this effect was independent of SES. CONCLUSIONS: An intensive transitional HF management program improved clinical outcomes, both overall and across SES strata.

The Regulators of Peroxisomal Acyl-Carnitine Shuttle CROT and CRAT Promote Metastasis in Melanoma.

Circulating tumor cells are the key link between a primary tumor and distant metastases, but once in the bloodstream, loss of adhesion induces cell death. To identify the mechanisms relevant for melanoma circulating tumor cell survival, we performed RNA sequencing and discovered that detached melanoma cells and isolated melanoma circulating tumor cells rewire lipid metabolism by upregulating fatty acid (FA) transport and FA beta-oxidation‒related genes. In patients with melanoma, high expression of FA transporters and FA beta-oxidation enzymes significantly correlates with reduced progression-free and overall survival. Among the highest expressed regulators in melanoma circulating tumor cells were the carnitine transferases carnitine O-octanoyltransferase and carnitine acetyltransferase, which control the shuttle of peroxisome-derived medium-chain FAs toward mitochondria to fuel mitochondrial FA beta-oxidation. Knockdown of carnitine O-octanoyltransferase or carnitine acetyltransferase and short-term treatment with peroxisomal or mitochondrial FA beta-oxidation inhibitors thioridazine or ranolazine suppressed melanoma metastasis in mice. Carnitine O-octanoyltransferase and carnitine acetyltransferase depletion could be rescued by medium-chain FA supplementation, indicating that the peroxisomal supply of FAs is crucial for the survival of nonadherent melanoma cells. Our study identifies targeting the FA-based cross-talk between peroxisomes and mitochondria as a potential therapeutic opportunity to challenge melanoma progression. Moreover, the discovery of the antimetastatic activity of the Food and Drug Administration‒approved drug ranolazine carries translational potential.

Long-term docosahexaenoic acid (DHA) supplementation in cystic fibrosis patients: a randomized, multi-center, double-blind, placebo-controlled trial.

BACKGROUND: Cystic fibrosis (CF) patients have an alteration in fatty acid (FA) metabolism, associated with increased omega-6 and low omega-3 FA. Previous studies on supplementation with omega-3 FA in CF had contradictory results, and to date there is no evidence to recommend routine use of omega-3 supplements in CF patients. We hypothesized that long-term supplementation with docosahexaenoic acid (DHA) will have beneficial effects in these patients, by reducing pulmonary, systemic and intestinal inflammation. METHODS: This was a randomized, double-blind, parallel, placebo-controlled trial. CF patients (age >2 months) were randomized to receive a seaweed DHA oil solution (50 mg/Kg/day) or matching placebo for 48 weeks. Primary outcomes were pulmonary (interleukin [IL]-8), systemic (IL-8) and intestinal (calprotectin) inflammatory biomarkers. Secondary outcomes included other pulmonary (IL-1ß, IL-6, neutrophil elastase, lactate and calprotectin) and systemic (serum-IL-1ß, IL-6) inflammatory biomarkers, as well as clinical outcomes (FEV1, pulmonary exacerbations, antibiotic use, nutritional status and quality of life). RESULTS: Ninety six CF patients, 44 female, age 14.6±11.9 years (48 DHA and 48 placebo) were included. At trial completion, there were no differences in all primary outcomes [serum-IL-8 (p=0.909), respiratory-IL-8 (p=0.384) or fecal calprotectin (p=0.948)], all secondary inflammatory biomarkers, or in any of the clinical outcomes evaluated. There were few adverse events, with similar incidence in both study groups. CONCLUSION: In this study, long-term DHA supplementation in CF patients was safe, but did not offer any benefit on inflammatory biomarkers, or in clinical outcomes compared with placebo. (NCT01783613).

A phase II trial of gemcitabine and weekly high-dose 5-fluorouracil in a 48-hour continuous-infusion schedule in patients with advanced pancreatic carcinoma. A study of the Spanish Cooperative Group for Gastrointestinal Tumour Therapy (TTD).

AIM: A multi-centred, open-labelled, phase 11 study containing 46 patients was conducted to evaluate the clinical benefit of gemcitabine (1,400 mg/m(2)) combined with 5-FU (3 g/m(2)) in a 48 h continuous infusion (CI). METHODS: Both drugs were administered on days 1, 8 and 15 of every 4 week cycle in chemotherapy-naïve patients with locally advanced unresectable metastatic pancreatic carcinoma. The minimum follow-up was 6 months. RESULTS: Clinical benefit response was the primary endpoint and this was achieved by 24.4% of the patients. Quality of life (QoL) improved in 16.6% of patients. Objective response was observed in 7% of the patients. The median progression-free survival (PFS) was 14.4 weeks and the median overall survival (OS) time was 22.7 weeks. One-year survival was 25%. The most frequent grade 3-4 toxicities were neutropenia (45%), mucositis (7.5%) and hyperbilirubinaemia (10.5%). CONCLUSIONS: This schedule was not superior in terms of clinical benefit, response rate, PFS and OS than standard gemcitabine treatment

A phase II trial of gemcitabine and weekly high-dose 5-fluorouracil in a 48-hour continuous-infusion schedule in patients with advanced pancreatic carcinoma. A study of the Spanish Cooperative Group for Gastrointestinal Tumour Therapy (TTD)

Aim. A multi-centred, open-labelled, phase II study containing 46 patients was conducted to evaluate the clinical benefit of gemcitabine (1,400 mg/m2) combined with 5-FU (3 g/m2) in a 48h continuous infusion (CI). Methods. Both drugs were administered on days 1, 8 and 15 of every 4 week cycle in chemotherapy-naïve patients with locally advanced un-resectable metastatic pancreatic carcinoma. The minimum follow-up was 6 months. Results. Clinical benefit response was the primary endpoint and this was achieved by 24.4% of the patients. Quality of life (QoL) improved in 16.6% of patients. Objective response was observed in 7% of the patients. The median progression-free survival (PFS) was 14.4 weeks and the median overall survival (OS) time was 22.7 weeks. One-year survival was 25%. The most frequent grade 3-4 toxicities were neutropenia (45%), mucositis (7.5%) and hyperbilirubinaemia (10.5%). Conclusions. This schedule was not superior in terms of clinical benefit, response rate, PFS and OS than standard gemcitabine treatment