Increased expression of fatty-acid and calcium metabolism genes in failing human heart

Background: Heart failure (HF) involves alterations in metabolism, but little is known about cardiomyopathy-(CM)-specific or diabetes-independent alterations in gene expression of proteins involved in fatty-acid (FA) uptake and oxidation or in calcium-(Ca(2+))-handling in the human heart. Methods: RT-qPCR was used to quantify mRNA expression and immunoblotting to confirm protein expression in left-ventricular myocardium from patients with HF (n = 36) without diabetes mellitus of ischaemic (ICM, n = 16) or dilated (DCM, n = 20) cardiomyopathy aetiology, and non-diseased donors (CTL, n = 6). Results: Significant increases in mRNA of genes regulating FA uptake (CD36) and intracellular transport (Heart-FA-Binding Protein (HFABP)) were observed in HF patients vs CTL. Significance was maintained in DCM and confirmed at protein level, but not in ICM. mRNA was higher in DCM than ICM for peroxisome-proliferator-activated-receptor-alpha (PPARA), PPAR-gamma coactivator-1-alpha (PGC1A) and CD36, and confirmed at the protein level for PPARA and CD36. Transcript and protein expression of Ca(2+)-handling genes (Two-Pore-Channel 1 (TPCN1), Two-Pore-Channel 2 (TPCN2), and Inositol 1,4,5-triphosphate Receptor type-1 (IP3R1)) increased in HF patients relative to CTL. Increases remained significant for TPCN2 in all groups but for TPCN1 only in DCM. There were correlations between FA metabolism and Ca(2+)-handling genes expression. In ICM there were six correlations, all distinct from those found in CTL. In DCM there were also six (all also different from those found in CTL): three were common to and three distinct from ICM. Conclusion: DCM-specific increases were found in expression of several genes that regulate FA metabolism, which might help in the design of aetiology-specific metabolic therapies in HF. Ca(2+)-handling genes TPCN1 and TPCN2 also showed increased expression in HF, while HF- and CM-specific positive correlations were found among several FA and Ca(2+)-handling genes

Nesfatin-1 in human and murine cardiomyocytes: synthesis, secretion, and mobilization of GLUT-4

Nesfatin-1, a satiety-inducing peptide identified in hypothalamic regions that regulate energy balance, is an integral regulator of energy homeostasis and a putative glucose-dependent insulin coadjuvant. We investigated its production by human cardiomyocytes and its effects on glucose uptake, in the main cardiac glucose transporter GLUT-4 and in intracellular signaling. Quantitative RT-PCR, Western blots, confocal immunofluorescence microscopy, and ELISA of human and murine cardiomyocytes and/or cardiac tissue showed that cardiomyocytes can synthesize and secrete nesfatin-1. Confocal microscopy of cultured cardiomyocytes after GLUT-4 labeling showed that nesfatin-1 mobilizes this glucose transporter to cell peripherals. The rate of 2-deoxy-D-[(3)H]glucose incorporation demonstrated that nesfatin-1 induces glucose uptake by HL-1 cells and cultured cardiomyocytes. Nesfatin-1 induced dose- and time-dependent increases in the phosphorylation of ERK1/2, AKT, and AS160. In murine and human cardiac tissue, nesfatin-1 levels varied with diet and coronary health. In conclusion, human and murine cardiomyocytes can synthesize and secrete nesfatin-1, which is able to induce glucose uptake and the mobilization of the glucose transporter GLUT-4 in these cells. Nesfatin-1 cardiac levels are regulated by diet and coronary health

Retroperitoneal non-functional paraganglioma: Report of a case from the Cardioinfantil Foundation, Bogotá, Colombia = Paraganglioma retroperitoneal no funcional: reporte de un caso en la Fundación Cardioinfantil, Bogotá, Colombia

Paragangliomas are tumors that derive from chromaffin cells, which originate in the neural crest. This gives them the ability to secrete catecholamines, hormones and peptides. They form extra-adrenal tumors of the central nervous system and can be found in the skull base, neck, chest and abdomen. Depending on their characterization they are usually classified into functioning and non-functioning. The patient initially presented to us with unspecified pain in the right hypochondrium. The presence of a neuroblastoma was suspected after initial imaging studies; however, due to similarities with other pathologies it was not possible to differentiate it from paraganglioma, ganglioneuroblastoma or neurofibroblastoma. Once the decision was made to conduct surgery, the pathology report showed extensive hemorrhagic areas compatible with non-functioning extra-adrenal paraganglioma. Non-functioning extra-adrenal paragangliomas are uncommon tumors of diverse location and difficult surgical treatment

Tumores estromales gastrointestinales: enfoque actual Presentación de seis casos Gastrointestinal stromal tumors: current management and report of six cases

Se presentan seis pacientes con diagnóstico inmuno-histoquímico de tumores estromales gastrointestinales y extragastrointestinales localizados en diferentes órganos del tracto digestivo y otras áreas, estudiados e intervenidos en nuestra institución a partir del año 2000, con seguimiento en su evolución clínica hasta la fecha por los servicios de hemato- oncología y cirugía; a excepción de una paciente. En su mayoría sin diagnóstico claro en su preoperatorio o con alta sospecha de presentar tumores mesenquimales complicados por masa compresiva, oclusión intestinal o sangrado. Se plantean de manera concreta los aspectos relevantes en su diagnóstico y clasificación patológica, manejo quirúrgico y tratamiento en relación a la literatura actual, exponiendo algunas de las controversias existentes. Además de fijar nuestra posición como grupo terapéutico frente a esta neoplasia, con base en la revisión realizada y nuestra limitada experiencia.We hereby report six patients with inmunohistochemical diagnosis of GIST located in different organs of the gastrointestinal tract and other areas, who were managed at our institution, except one case, starting in 2000 and followed until now in the services of hemato-oncology and surgery. The majority of these patients did not have a clear preoperative diagnosis or presented with high suspicion of a mesenchyunal tumor, complicate by a compressing mass, intestinal obstruction, or bleeding. We describe the most relevant aspects pertinent to diagnosis and pathologic classification, surgical management in the context of current literature reports, with emphasis on the ongoing controversies. Furthermore, we define our policy as a group on the basis of the literature review and the careful analysis of our limited experience

Antitumor activity of lurbinectedin in second-line small cell lung cancer patients who are candidates for re-challenge with the first-line treatment

Introduction: The National Comprehensive Cancer Network guidelines recommend re-challenge with the first-line treatment for relapsed small cell lung cancer (SCLC) with chemotherapy-free interval (CTFI)≥180 days. A phase II study (NCT02454972) showed remarkable antitumor activity in SCLC patients treated with lurbinectedin 3.2 mg/m2 1 -h intravenous infusion every 3 weeks as second-line therapy. We report results for the pre-planned subset of patients with CTFI ≥ 180 days. Material and Methods: Twenty patients aged ≥18 years with pathologically proven SCLC diagnosis, pretreated with only one prior platinum-containing line, no CNS metastases, and with CTFI ≥ 180 days were evaluated. The primary efficacy endpoint was the overall response rate (ORR) assessed by the Investigators according to RECIST v1.1. Results: ORR was 60.0 % (95 %CI, 36.1−86.9), with a median duration of response of 5.5 months (95 %CI, 2.9−11.2) and disease control rate of 95.0 % (95 %CI, 75.1−99.9). Median progression-free survival was 4.6 months (95 %CI, 2.6−7.3). With a censoring of 55.0 %, the median overall survival was 16.2 months (95 %CI, 9.6-upper level not reached). Of note, 60.9 % and 27.1 % of patients were alive at 1 and 2 years, respectively. The most common grade 3/4 adverse events and laboratory abnormalities were hematological disorders (neutropenia, 55.0 %; anemia; 10.0 % thrombocytopenia, 10.0 %), fatigue (10.0 %) and increased liver function tests (GGT, 10 %; ALT and AP, 5.0 % each). No febrile neutropenia was reported. Conclusion: Lurbinectedin is an effective treatment for platinum-sensitive relapsed SCLC, especially in patients with CTFI ≥ 180 days, with acceptable safety and tolerability. These encouraging results suggest that lurbinectedin can be another valuable therapeutic option rather than platinum re-challenge.SCOPUS: ar.jinfo:eu-repo/semantics/publishe

Colombian surgical outcomes study insights on perioperative mortality rate, a main indicator of the lancet commission on global surgery – a prospective cohort studyResearch in context

Summary: Background: Surgical care holds significant importance in healthcare, especially in low and middle-income countries, as at least 50% of the 4.2 million deaths within the initial 30 days following surgery take place in these countries. The Lancet Commission on Global Surgery proposed six indicators to enhance surgical care. In Colombia, studies have been made using secondary data. However, strategies to reduce perioperative mortality have not been implemented. This study aims to describe the fourth indicator, perioperative mortality rate (POMR), with primary data in Colombia. Methods: A multicentre prospective cohort study was conducted across 54 centres (hospitals) in Colombia. Each centre selected a 7-day recruitment period between 05/2022 and 01/2023. Inclusion criteria involved patients over 18 years of age undergoing surgical procedures in operating rooms. Data quality was ensured through a verification guideline and statistical analysis using mixed-effects multilevel modelling with a case mix analysis of mortality by procedure-related, patient-related, and hospital-related conditions. Findings: 3807 patients were included with a median age of 48 (IQR 32–64), 80.3% were classified as ASA I or II, and 27% of the procedures had a low-surgical complexity. Leading procedures were Orthopedics (19.2%) and Gynaecology/Obstetrics (17.7%). According to the Clavien–Dindo scale, postoperative complications were distributed in major complications (11.7%, 10.68–12.76) and any complication (31.6%, 30.09–33.07). POMR stood at 1.9% (1.48–2.37), with elective and emergency surgery mortalities at 0.7% (0.40–1.23) and 3% (2.3–3.89) respectively. Interpretation: The POMR was higher than the ratio reported in previous national studies, even when patients had a low–risk profile and low-complexity procedures. The present research represents significant public health progress with valuable insights for national decision-makers to improve the quality of surgical care. Funding: This work was supported by Universidad del Rosario and Fundación Cardioinfantil-Instituto de Cardiología grant number CTO-057-2021, project-ID IV-FGV017