Infected pancreatic necrosis: outcomes and clinical predictors of mortality. A post hoc analysis of the MANCTRA-1 international study

: The identification of high-risk patients in the early stages of infected pancreatic necrosis (IPN) is critical, because it could help the clinicians to adopt more effective management strategies. We conducted a post hoc analysis of the MANCTRA-1 international study to assess the association between clinical risk factors and mortality among adult patients with IPN. Univariable and multivariable logistic regression models were used to identify prognostic factors of mortality. We identified 247 consecutive patients with IPN hospitalised between January 2019 and December 2020. History of uncontrolled arterial hypertension (p = 0.032; 95% CI 1.135-15.882; aOR 4.245), qSOFA (p = 0.005; 95% CI 1.359-5.879; aOR 2.828), renal failure (p = 0.022; 95% CI 1.138-5.442; aOR 2.489), and haemodynamic failure (p = 0.018; 95% CI 1.184-5.978; aOR 2.661), were identified as independent predictors of mortality in IPN patients. Cholangitis (p = 0.003; 95% CI 1.598-9.930; aOR 3.983), abdominal compartment syndrome (p = 0.032; 95% CI 1.090-6.967; aOR 2.735), and gastrointestinal/intra-abdominal bleeding (p = 0.009; 95% CI 1.286-5.712; aOR 2.710) were independently associated with the risk of mortality. Upfront open surgical necrosectomy was strongly associated with the risk of mortality (p < 0.001; 95% CI 1.912-7.442; aOR 3.772), whereas endoscopic drainage of pancreatic necrosis (p = 0.018; 95% CI 0.138-0.834; aOR 0.339) and enteral nutrition (p = 0.003; 95% CI 0.143-0.716; aOR 0.320) were found as protective factors. Organ failure, acute cholangitis, and upfront open surgical necrosectomy were the most significant predictors of mortality. Our study confirmed that, even in a subgroup of particularly ill patients such as those with IPN, upfront open surgery should be avoided as much as possible. Study protocol registered in ClinicalTrials.Gov (I.D. Number NCT04747990)

Unidad Hospitalaria de Patología Dual Grave: un año de experiencia

This is an observational, descriptive, cross-sectional study on patients admitted for one year to the inpatient unit of a Severe Dual Diagnosis Program (SDDP). Socio- demographic, clinical and pharmacological information was obtained using data collection forms designed for this purpose. The sample size was of 82 inpatients, whose profile was that of males with a mean age of 36.7 years, referred from the outpatient clinic of the SDDP. Admission was mainly involuntary. The main psychiatric diagnosis was psychotic disorder, especially paranoid schizophrenia, and the most prevalent substances consumed were alcohol (33%), cocaine (26%) and cannabis (20%). Among the psychotherapeutic techniques worthy of mention, there was a Brief Motivational Psycho-educational Therapy-Dual (BMPT-D) with a group format, in which around two thirds of the patients participated. The most widely-used group of drugs was antipsychotics, specifically quetiapine [60%] and the long-term action injectable risperidone (LAIR, 51%). In the group of patients with alcohol abuse or dependence, the most commonly prescribed antipsychotics were quetiapine and tiapride (both 43%). Antidepressants were used in 37% of cases, especially duloxetine. In the group with cocaine abuse or dependence, schizophrenia was the most prevalent co-morbid disorder (75%) and the most widely-prescribed drugs were antipsychotics, especially LAIR (91%). Opioid and cocaine dependence was the most common association within the multi-dependent patients (56%) and schizophrenia the most frequent co-morbid diagnosis in this group.Se trata de un estudio observacional, descriptivo, transversal en el que se incluyeron los pacientes ingresados en la Unidad de Hospitalización del Programa de Patología Dual Grave (UHPPDG) durante un año. Los datos sociodemográficos, clínicos y farmacológicos se obtuvieron mediante hojas de recogida de datos diseñadas al efecto. El total de pacientes ingresados fue de 82 en cuyo perfil prevalecen los varones con una edad media de 36,7 años, derivados del subprograma ambulatorio del propio Programa de Patología Dual Grave (PPDG) y con ingreso de tipo involuntario. El diagnóstico psiquiátrico más frecuente fue el trastorno psicótico, especialmente la Esquizofrenia Paranoide. Las sustancias tóxicas más consumidas fueron: alcohol (33 %), cocaína (26 %) y el cannabis (20 %). Dentro de las técnicas psicoterápicas destaca la Terapia Psicoeducativa Motivacional Breve-Dual (TPMB-D), de formato grupal, en la que participaron alrededor de 2/3 de los pacientes. El grupo de fármacos más utilizados fueron los antipsicóticos (quetiapina [60%] y la risperidona inyectable de larga duración (RILD). En el grupo de pacientes con Dependencia/Abuso de Alcohol, los antipsicóticos más utilizados fueron la quetiapina y la tiaprida (43%). Los antidepresivos se utilizaron en el 37% de los casos, especialmente la duloxetina. En el grupo con Dependencia/ Abuso de Cocaína, la Esquizofrenia es el trastorno comórbido más prevalente (75%), y los antipsicóticos el grupo farmacológico más prescrito, en especial la RILD (91%). Entre los pacientes multidependientes la asociación más frecuente fue la Dependencia de Opiáceos y Cocaína (56%). El diagnóstico comórbido más frecuente en este grupo fue la Esquizofrenia

Discovery of Potent Dual PPARα Agonists/CB1 Ligands

This letter describes the synthesis and in vitro and in vivo evaluation of dual ligands targeting the cannabinoid and peroxisome proliferator-activated receptors (PPAR). These compounds were obtained from fusing the pharmacophores of fibrates and the diarylpyrazole rimonabant, a cannabinoid receptor antagonist. They are the first examples of dual compounds with nanomolar affinity for both PPARα and cannabinoid receptors. Besides, lead compound <b>2</b> proved to be CB1 selective. Unexpectedly, the phenol intermediates tested were equipotent (compound <b>1</b> as compared to <b>2</b>) or even more potent (compound <b>3</b> as compared with <b>4</b>). This discovery opens the way to design new dual ligands

Individualised, perioperative open-lung ventilation strategy during one-lung ventilation (iPROVE-OLV): a multicentre, randomised, controlled clinical trial

Background: It is uncertain whether individualisation of the perioperative open-lung approach (OLA) to ventilation reduces postoperative pulmonary complications in patients undergoing lung resection. We compared a perioperative individualised OLA (iOLA) ventilation strategy with standard lung-protective ventilation in patients undergoing thoracic surgery with one-lung ventilation. Methods: This multicentre, randomised controlled trial enrolled patients scheduled for open or video-assisted thoracic surgery using one-lung ventilation in 25 participating hospitals in Spain, Italy, Turkey, Egypt, and Ecuador. Eligible adult patients (age ≥18 years) were randomly assigned to receive iOLA or standard lung-protective ventilation. Eligible patients (stratified by centre) were randomly assigned online by local principal investigators, with an allocation ratio of 1:1. Treatment with iOLA included an alveolar recruitment manoeuvre to 40 cm H2O of end-inspiratory pressure followed by individualised positive end-expiratory pressure (PEEP) titrated to best respiratory system compliance, and individualised postoperative respiratory support with high-flow oxygen therapy. Participants allocated to standard lung-protective ventilation received combined intraoperative 4 cm H2O of PEEP and postoperative conventional oxygen therapy. The primary outcome was a composite of severe postoperative pulmonary complications within the first 7 postoperative days, including atelectasis requiring bronchoscopy, severe respiratory failure, contralateral pneumothorax, early extubation failure (rescue with continuous positive airway pressure, non-invasive ventilation, invasive mechanical ventilation, or reintubation), acute respiratory distress syndrome, pulmonary infection, bronchopleural fistula, and pleural empyema. Due to trial setting, data obtained in the operating and postoperative rooms for routine monitoring were not blinded. At 24 h, data were acquired by an investigator blinded to group allocation. All analyses were performed on an intention-to-treat basis. This trial is registered with ClinicalTrials.gov, NCT03182062, and is complete. Findings: Between Sept 11, 2018, and June 14, 2022, we enrolled 1380 patients, of whom 1308 eligible patients (670 [434 male, 233 female, and three with missing data] assigned to iOLA and 638 [395 male, 237 female, and six with missing data] to standard lung-protective ventilation) were included in the final analysis. The proportion of patients with the composite outcome of severe postoperative pulmonary complications within the first 7 postoperative days was lower in the iOLA group compared with the standard lung-protective ventilation group (40 [6%] vs 97 [15%], relative risk 0·39 [95% CI 0·28 to 0·56]), with an absolute risk difference of -9·23 (95% CI -12·55 to -5·92). Recruitment manoeuvre-related adverse events were reported in five patients. Interpretation: Among patients subjected to lung resection under one-lung ventilation, iOLA was associated with a reduced risk of severe postoperative pulmonary complications when compared with conventional lung-protective ventilation. Funding: Instituto de Salud Carlos III and the European Regional Development Funds