RESUMEN
BACKGROUND: Higher levels of inflammatory biomarkers are associated with an increased risk of perioperative atrial fibrillation and myocardial injury after non-cardiac surgery (MINS). Colchicine is an anti-inflammatory drug that might reduce the incidence of these complications. METHODS: COP-AF was a randomised trial conducted at 45 sites in 11 countries. Patients aged 55 years or older and undergoing major non-cardiac thoracic surgery were randomly assigned (1:1) to receive oral colchicine 0·5 mg twice daily or matching placebo, starting within 4 h before surgery and continuing for 10 days. Randomisation was done with use of a computerised, web-based system, and was stratified by centre. Health-care providers, patients, data collectors, and adjudicators were masked to treatment assignment. The coprimary outcomes were clinically important perioperative atrial fibrillation and MINS during 14 days of follow-up. The main safety outcomes were a composite of sepsis or infection, and non-infectious diarrhoea. The intention-to-treat principle was used for all analyses. This trial is registered with ClinicalTrials.gov, NCT03310125. FINDINGS: Between Feb 14, 2018, and June 27, 2023, we enrolled 3209 patients (mean age 68 years [SD 7], 1656 [51·6%] male). Clinically important atrial fibrillation occurred in 103 (6·4%) of 1608 patients assigned to colchicine, and 120 (7·5%) of 1601 patients assigned to placebo (hazard ratio [HR] 0·85, 95% CI 0·65 to 1·10; absolute risk reduction [ARR] 1·1%, 95% CI -0·7 to 2·8; p=0·22). MINS occurred in 295 (18·3%) patients assigned to colchicine and 325 (20·3%) patients assigned to placebo (HR 0·89, 0·76 to 1·05; ARR 2·0%, -0·8 to 4·7; p=0·16). The composite outcome of sepsis or infection occurred in 103 (6·4%) patients in the colchicine group and 83 (5·2%) patients in the placebo group (HR 1·24, 0·93-1·66). Non-infectious diarrhoea was more common in the colchicine group (134 [8·3%] events) than the placebo group (38 [2·4%]; HR 3·64, 2·54-5·22). INTERPRETATION: In patients undergoing major non-cardiac thoracic surgery, administration of colchicine did not significantly reduce the incidence of clinically important atrial fibrillation or MINS but increased the risk of mostly benign non-infectious diarrhoea. FUNDING: Canadian Institutes of Health Research, Accelerating Clinical Trials Consortium, Innovation Fund of the Alternative Funding Plan for the Academic Health Sciences Centres of Ontario, Population Health Research Institute, Hamilton Health Sciences, Division of Cardiology at McMaster University, Canada; Hanela Foundation, Switzerland; and General Research Fund, Research Grants Council, Hong Kong.
Asunto(s)
Fibrilación Atrial , Sepsis , Cirugía Torácica , Humanos , Masculino , Anciano , Femenino , Fibrilación Atrial/etiología , Fibrilación Atrial/prevención & control , Colchicina/efectos adversos , Sepsis/epidemiología , Sepsis/etiología , Sepsis/prevención & control , Diarrea/inducido químicamente , Ontario , Resultado del Tratamiento , Método Doble CiegoRESUMEN
BACKGROUND: Portal vein arterialization (PVA) has been used in liver transplantation (LT) to maximize oxygen delivery when arterial circulation is compromised or has been used as an alternative reperfusion technique for complex portal vein thrombosis (PVT). The effect of PVA on portal perfusion and primary graft dysfunction (PGD) has not been assessed. AIM: To examine the outcomes of patients who required PVA in correlation with their LT procedure. METHODS: All patients receiving PVA and LT at the Fundacion Santa Fe de Bogota between 2011 and 2022 were analyzed. To account for the time-sensitive effects of graft perfusion, patients were classified into two groups: prereperfusion (pre-PVA), if the arterioportal anastomosis was performed before graft revascularization, and postreperfusion (post-PVA), if PVA was performed afterward. The pre-PVA rationale contemplated poor portal hemodynamics, severe vascular steal, or PVT. Post-PVA was considered if graft hypoperfusion became evident. Conservative interventions were attempted before PVA. RESULTS: A total of 25 cases were identified: 15 before and 10 after graft reperfusion. Pre-PVA patients were more affected by diabetes, decompensated cirrhosis, impaired portal vein (PV) hemodynamics, and PVT. PGD was less common after pre-PVA (20.0% vs 60.0%) (P = 0.041). Those who developed PGD had a smaller increase in PV velocity (25.00 cm/s vs 73.42 cm/s) (P = 0.036) and flow (1.31 L/min vs 3.34 L/min) (P = 0.136) after arterialization. Nine patients required PVA closure (median time: 62 d). Pre-PVA and non-PGD cases had better survival rates than their counterparts (56.09 months vs 22.77 months and 54.15 months vs 31.91 months, respectively). CONCLUSION: This is the largest report presenting PVA in LT. Results suggest that pre-PVA provides better graft perfusion than post-PVA. Graft hyperperfusion could play a protective role against PGD.
RESUMEN
Opioids are one of the most potent drugs for treating moderate to severe pain. Despite irrefutable clinical application in chronic pain management, the long-term use of opioids has been increasingly questioned due to undesired side effects that demand attention. Opioids such as morphine mediate clinically relevant effects primarily through the µ-opioid receptor that go beyond their classical role as analgesics, causing potentially fatal side effects such as tolerance, dependence, and addiction. Furthermore, there is growing evidence that opioids affect immune system function, cancer progression, metastasis, and recurrence. Though a biological plausibility, the clinical evidence for the action of opioids on cancer is mixed, revealing a more complex picture as researchers struggle to establish a vital link between opioid receptor agonists, cancer progression, and suppression, or both. Thus, in light of the uncertainty of opioid effects on cancer, in this review, a focused overview of the role of opioid receptors in modulating cancer progression, their underlying signaling mechanisms, and the biological activity of opioid receptor agonists and antagonists is provided.
Asunto(s)
Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos , Neoplasias , Humanos , Analgésicos Opioides/efectos adversos , Receptores Opioides/uso terapéutico , Dolor/inducido químicamente , Dolor/tratamiento farmacológico , Analgésicos/uso terapéutico , Neoplasias/tratamiento farmacológico , Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos/tratamiento farmacológicoRESUMEN
In addition to attaining complete or near complete cytoreduction, the instillation of select heated chemotherapeutic agents into the abdominal cavity has offered a chance for cure or longer survival inpatients with peritoneal surface malignancies. While the heating of chemotherapeutic agents enhances cytotoxicity, the resulting systemic hyperthermia has been associated with an increased risk of severe hyperthermia and its associated complications. Factors that have been associated with an increased risk of severe hyperthermia include intraoperative blood transfusions and longer perfusion duration. However, the development of severe hyperthermia still remains largely unpredictable. Thus, at several institutions, cooling protocols are employed during cytoreductive surgery with hyperthermic intraperitoneal chemotherapy (CRS-HIPEC). Cooling protocols for CRS-HIPEC are not standardized and may be associated with episodes of severe hyperthermia or alternatively hypothermia. In theory, excessive cooling could result in a decreased effectiveness of the intraperitoneal chemotherapeutic agents. This presumption has been supported by a recent study of 214 adults undergoing CRS-HIPEC, where failure to attain a temperature of 38° C at the end of chemo-perfusion was associated with worse survival. Although not statistically significant, failure to maintain a temperature of 38° C for at least 30 minutes was associated with worse survival. Although studies are limited in this regard, the importance of maintaining a steady state of temperature during the hyperthermic phase of intraperitoneal chemotherapy administration cannot be disregarded. The following article describes the processes and physiological mechanisms responsible for hyperthermia during CRS-HIPEC. The challenges associated with temperature management during CRS-HIPEC and methods to avoid severe hypothermia and hyperthermia are also described.