Human IP3 receptor triple knockout stem cells remain pluripotent despite altered mitochondrial metabolism.

Inositol 1,4,5-trisphosphate receptors (IP3Rs) are ER Ca2+-release channels that control a broad set of cellular processes. Animal models lacking IP3Rs in different combinations display severe developmental phenotypes. Given the importance of IP3Rs in human diseases, we investigated their role in human induced pluripotent stem cells (hiPSC) by developing single IP3R and triple IP3R knockouts (TKO). Genome edited TKO-hiPSC lacking all three IP3R isoforms, IP3R1, IP3R2, IP3R3, failed to generate Ca2+ signals in response to agonists activating GPCRs, but retained stemness and pluripotency. Steady state metabolite profiling and flux analysis of TKO-hiPSC indicated distinct alterations in tricarboxylic acid cycle metabolites consistent with a deficiency in their pyruvate utilization via pyruvate dehydrogenase, shifting towards pyruvate carboxylase pathway. These results demonstrate that IP3Rs are not essential for hiPSC identity and pluripotency but regulate mitochondrial metabolism. This set of knockout hiPSC is a valuable resource for investigating IP3Rs in human cell types of interest.

Recomendaciones sobre reanimación cardiopulmonar en pacientes con sospecha o infección confirmada por SARS-CoV-2 (COVID-19). Resumen ejecutivo / Recommendations on cardiopulmonary resuscitation in patients with suspected or confirmed SARS-CoV-2 infection (COVID-19). Executive summary

La pandemia por SARS-CoV-2 ha generado nuevos escenarios que requieren modificaciones de los protocolos habituales de reanimación cardiopulmonar. Las guías clínicas vigentes sobre el manejo de la parada cardiorrespiratoria no incluyen recomendaciones para situaciones aplicables a este contexto. Por ello, el Plan Nacional de Reanimación Cardiopulmonar de la Sociedad Española de Medicina Intensiva, Crítica y Unidades Coronarias, en colaboración con el Grupo Español de RCP Pediátrica y Neonatal y con el programa de Enseñanza de Soporte Vital en Atención Primaria de la Sociedad Española de Medicina Familiar y Comunitaria, ha redactado las siguientes recomendaciones, que están divididas en 5 partes que tratan los principales aspectos para cada entorno asistencial. En este artículo se presenta un resumen ejecutivo de las mismas

The SARS-CoV-2 pandemic has created new scenarios that require modifications to the usual cardiopulmonary resuscitation protocols. The current clinical guidelines on the management of cardiorespiratory arrest do not include recommendations for situations that apply to this context. Therefore, the National Cardiopulmonary Resuscitation Plan of the Spanish Society of Intensive and Critical Care Medicine and Coronary Units (SEMICYUC), in collaboration with the Spanish Group of Pediatric and Neonatal CPR and with the Teaching Life Support in Primary Care program of the Spanish Society of Family and Community Medicine (SEMFyC), have written these recommendations, which are divided into 5 parts that address the main aspects for each healthcare setting. This article consists of an executive summary of them

[Recommendations on cardiopulmonary resuscitation in patients with suspected or confirmed SARS-CoV-2 infection (COVID-19). Executive summary]. / Recomendaciones sobre reanimación cardiopulmonar en pacientes con sospecha o infección confirmada por SARS-CoV-2 (COVID-19). Resumen ejecutivo.

The SARS-CoV-2 pandemic has created new scenarios that require modifications to the usual cardiopulmonary resuscitation protocols. The current clinical guidelines on the management of cardiorespiratory arrest do not include recommendations for situations that apply to this context. Therefore, the National Cardiopulmonary Resuscitation Plan of the Spanish Society of Intensive and Critical Care Medicine and Coronary Units (SEMICYUC), in collaboration with the Spanish Group of Pediatric and Neonatal CPR and with the Teaching Life Support in Primary Care program of the Spanish Society of Family and Community Medicine (SEMFyC), have written these recommendations, which are divided into 5 parts that address the main aspects for each healthcare setting. This article consists of an executive summary of them.

Role of Elevated Aminotransferases in ICU Patients with Rhabdomyolysis.

To evaluate whether patients with rhabdomyolysis and serum alanine aminotransferase (ALT) and/or aspartate aminotransferase (AST) higher than 1000 IU/L had higher mortality that patients with low aminotransferases. Retrospective analysis of intensive care unit patients with rhabdomyolysis [creatine kinase (CK) higher than 5000 IU/L]. Patients were classified in two groups: low aminotransferases group, when AST and ALT were equal or lower to 1000 IU/L, and elevated aminotransferases group, when AST or ALT was above 1000 IU/L. Forty-six out of 189 patients included in the analysis (24.3%) had elevated aminotransferases. The mortality of patients with rhabdomyolysis was 25.9 per cent, being higher in patients with elevated aminotransferases compared with patients with low aminotransferases (60.9% vs 14.7%; P < 0.001). Mortality stratified by quartiles of CK in patients with low aminotransferases was independent of the level of CK (P = 0.67). Logistic regression analysis showed that the independent variables associated with mortality were Simplified Acute Physiology Score II [1.11 (1.07-1.16) for each point of increase, P < 0.001], the international normalized ratio value [4.2 (1.6-10.7) for each point of increase, P = 0.003], and the need of renal replacement therapy [5.4 (1.7-17.2), P = 0.004]. Patients with rhabdomyolysis with elevated serum aminotransferases had higher mortality than patients with low serum aminotransferase levels.

Stress hyperglycaemia in critically ill patients: potential role of incretin hormones; a preliminary study.

BACKGROUND: Stress hyperglycaemia is common in the intensive care unit (ICU) setting and has been related to a worst outcome. OBJECTIVE: The objective was to characterize the association of glucoregulatory hormones, mainly incretins, with the levels of glycaemia, and its relationship with outcome in ICU patients. METHODS: We prospectively studied 60 patients. Stress hyperglycaemia was diagnosed when glycaemia was < 115 mg/dL. At ICU admission we determined glycaemia, insulin, glucagon, cortisol, glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) plasma levels. Groups were compared using Kruskal-Wallis test. The association between glycaemia levels and glucoregulatory hormones was evaluated using linear regression. RESULTS: Forty-five patients (75%) had hyperglycaemia. We observed no differences in glucoregulatory hormones levels between normo- and hyper- glycaemia groups. Glycaemia levels were not significantly correlated with insulin, glucagon, cortisol or GIP levels, but were correlated with GLP-1 (p = 0.04). GLP-1 was also correlated with cortisol (p = 0.01), but failed to show a significant correlation with insulin, glucagon or GIP levels. Lower levels of plasma GLP-1 were found in patients with stress hyperglycaemia requiring vasoactive support (p = 0.02). CONCLUSIONS: Glycaemia levels were correlated with GLP-1 levels in ICU patients. GLP-1 levels were also associated with cortisol. Patients with stress hyperglycaemia who required vasoactive support had lower incretin levels compared with those patients with stress hyperglycaemia who were hemodynamically stables. (ClinicalTrials.gov Identifier: NCT01087372).

Stress hyperglycaemia in critically ill patients; Potential role of incretinhormones; a preliminary study / Hiperglucemia de estrés en el paciente crítico; papel potencial de las incretinas; estudio preliminar

Background: Stress hyperglycaemia is common in the intensive care unit (ICU) setting and has been related to a worst outcome. Objective: The objective was to characterize the association of glucoregulatory hormones, mainly incretins, with the levels of glycaemia, and its relationship with outcome in ICU patients. Methods: We prospectively studied 60 patients. Stress hyperglycaemia was diagnosed when glycaemia was > 115 mg/dL. At ICU admission we determined glycaemia, insulin, glucagon, cortisol, glucose-dependent insulino -tropic polypeptide (GIP) and glucagon-like peptide-1(GLP-1) plasma levels. Groups were compared using Kruskal-Wallis test. The association between glycaemia levels and glucoregulatory hormones was evaluated using linear regression. Results: Forty-five patients (75%) had hyperglycaemia.We observed no differences in glucoregulatory hormones levels between normo- and hyper- glycaemia groups. Glycaemia levels were not significantly correlated with insulin, glucagon, cortisol or GIP levels, but were correlated withGLP-1 (p = 0.04). GLP-1 was also correlated with cortisol (p = 0.01), but failed to show a significant correlation withinsulin, glucagon or GIP levels. Lower levels of plasmaGLP-1 were found in patients with stress hyperglycaemia requiring vasoactive support (p = 0.02).Conclusions: Glycaemia levels were correlated withGLP-1 levels in ICU patients. GLP-1 levels were also associated with cortisol. Patients with stress hyperglycaemia who required vasoactive support had lower incretin levels compared with those patients with stress hyperglycaemia who were hemodynamically stables.(ClinicalTrials.gov Identifier: NCT01087372) (AU)

Antecedentes: La hiperglucemia de estrés es habitual en el contexto de la Unidad de cuidados intensivos (UCI) y se ha relacionado con un peor pronóstico. Objetivo: el objetivo fue caracterizar la asociación de hormonas glucorreguladoras, principalmente las incretinas, con las glucemias y su relación con el pronóstico de los pacientes de UCI. Métodos: Estudiamos de forma prospectiva a 60pacientes. La hiperglucemia de estrés se diagnosticaba cuando la glucemia era > 115 mg/dl. En el ingreso en la UCI, determinamos la glucemia y las concentraciones plasmáticas de insulina, glucagón, cortisol, polipéptidoinsulinotropo dependiente de glucosa (GIP) y péptido-1de tipo glucagón (GLP-1). Se compararon los grupos mediante la prueba de Kruskal-Wallis. La asociación entre las glucemias y las hormonas contrarreguladoras se evaluó mediante regresión linear. Resultados: 45 pacientes (75%) tenían hiperglucemia.No observamos diferencias en las concentraciones de hormonas glucorreguladoras entre los grupos de normo ehiperglucemia. Las glucemias no se correlacionaron de forma significativa con las concentraciones de insulina,glucagón, cortisol o GIP, pero sí con el GLP-1 (p = 0,04).El GLP-1 también se correlacionó con el cortisol (p =0,01), pero no consiguió mostrar una correlación significativa con las concentraciones de insulina, glucagón o GIP. Se encontraron menores concentraciones plasmáticas de GLP-1 en los pacientes con hiperglucemia de estrés que requerían soporte vasoactivo (p = 0,02). Conclusiones: las glucemias se correlacionaron con las concentraciones de GLP-1 en los pacientes en UCI . Las concentraciones de GLP-1 también se asociaron con el cortisol. Los pacientes con hiperglucemia de estrés que necesitaron soporte vasoactivo tenían menores concentraciones de incretina en comparación con aquellos con hiperglucemia de estrés con estabilidad hemodinámica(ClinicalTrials.gov Identifier: NCT01087372) (AU)