ABSTRACT Background/Objective Patients with poor-grade subarachnoid bleed (pSAH, World Federation of Neurosurgeons grades 4-5) often improve their neurocognitive function months after their ictus. However, it is essential to explore the timing of intervention and its impact on long-term outcome. We compared the long-term outcomes between immediate management within 24 hours (IM) and delayed management after 24 hours (DM) in patients following pSAH. Methods This was a retrospective population-based study, including patients with pSAH who received definitive management between 1 st January 2011 and 31 st December 2016 in a large tertiary neurocritical care unit. The primary outcome was adjusted odds ratio (OR) of favourable outcome (Glasgow Outcome Scale (GOS) 4-5) for survivors at 12 months following discharge, as measured by the Glasgow Outcome Scale (GOS). The secondary outcomes included adjusted OR of a favourable outcome at discharge, three months and six months following discharge and survival rate at 28 days, three months, six months and 12 months following haemorrhage. Results 111 patients were included in this study: 53 (48%) received immediate management (IM) and 58 (41%) received delayed management (DM). The mean time delay from referral to intervention was 14.9±5.8 hours in IM patients, compared to 79.6±106.1 hours in DM patients. At 12 months following discharge, the adjusted OR for favourable outcome in IM versus DM patients was 0.96 (CI 0.17, 5.39; p=0.961). At hospital discharge, three months and six months, the adjusted OR for favourable outcome was 3.85 (CI 1.38, 10.73; p=0.010), 1.04 (CI 0.22, 5.00; p=0.956) and 0.98 (CI 0.21, 4.58; p=0.982), respectively. There were no differences in survival rate between the groups at 28 days, three months, six months and 12 months (71.7% in IM group vs 82.8% in DM group at 12 months, p=0.163). Conclusions IM and DM after pSAH are associated with similar morbidity and mortality at 12 months. Therefore, delaying intervention in poor-grade patients may be a reasonable approach, especially if time is needed to plan the procedure or stabilise the patient adequately.
Sepsis, a life-threatening organ dysfunction, is not caused by direct damage of pathogens and their toxins but by the host’s severe immune and metabolic dysfunction caused by the damage when the host confronts infection. Previous views focused on the damage-associated molecular patterns (DAMPs) and pathogen-associated molecular patterns (PAMPs), including metabolic proinflammatory factors in sepsis. Recently, new concepts have been proposed to group free fatty acids (FFAs), glucose, advanced glycation end products (AGEs), cholesterol, mitochondrial DNA (mtDNA), oxidized phospholipids (OxPLs), ceramides, and uric acid into metabolism-associated molecular patterns (MAMPs). The concept of MAMPs will bring new guidance to the research and potential treatments of sepsis. Nowadays, sepsis is regarded as closely related to metabolic disorders, and MAMPs play an important role in the pathogenesis and development of sepsis. According to this view, we have explained MAMPs and their possible roles in the pathogenesis of sepsis. Next, we have further explained the specific functions of different types of MAMPs in the metabolic process and their interactional relationship with sepsis. Finally, the therapeutic prospects of MAMPs in sepsis have been summarized.
Edema fluid resorption is critical for gas exchange, and both alveolar epithelial sodium channel (ENaC) and Na,K-ATPase are accredited with key roles in the resolution of pulmonary edema. Alveolar fluid clearance (AFC) was measured in in situ ventilated lungs by instilling isosmolar 5% BSA solution with Evans Blue-labeled albumin tracer (5 ml/kg) and measuring the change in Evans Blue-labeled albumin concentration over time. Treatment with lipoxin A4 and lipoxin receptor agonist (5(S), 6(R)-7-trihydroxymethyl 17 heptanoate) significantly stimulated AFC in oleic acid (OA)-induced lung injury, with the outcome of decreased pulmonary edema. Lipoxin A4 and 5(S), 6(R)-7-trihydroxymethyl 17 heptanoate not only up-regulated the ENaC α and ENaC γ subunits protein expression, but also increased Na,K-ATPase α1 subunit protein expression and Na,K-ATPase activity in lung tissues. There was no significant difference of intracellular cAMP level between the lipoxin A4 treatment and OA group. However, the intracellular cGMP level was significantly decreased after lipoxin A4 treatment. The beneficial effects of lipoxin A4 were abrogated by butoxycarbonyl-Phe-Leu-Phe-Leu-Ph (lipoxin A4 receptor antagonist) in OA-induced lung injury. In primary rat alveolar type II epithelial cells stimulated with LPS, lipoxin A4 increased ENaC α and ENaC γ subunits protein expression and Na,K-ATPase activity. Lipoxin A4 stimulated AFC through activation of alveolar epithelial ENaC and Na,K-ATPase.
Paracetamol poisoning is the most common cause of acute liver failure (ALF) in Western Europe, Australia and USA. The N-acetyl derivative of the amino acid cysteine (NAC) serves as a precursor to the production of glutathione and is the treatment of choice in early paracetamol toxicity. Patients with hyperacute or acute liver failure often require significant volumes of fluid resuscitation. Patients with liver failure are prone to hypoglycaemia. Liver failure leads to a loss of synthetic function of hepatocytes and reduction of coagulation factors, and international normalized ratio (INR) is a very important prognostic factor. The complications of liver failure include hepatic encephalopathy, intracranial hypertension, renal failure and adrenal dysfunction. In a selected group of patients liver transplantation is the treatment of choice. Overall survival, without transplantation, is about 40% following the onset of ALF. Acute on chronic liver failure represents the decompensation of otherwise stable chronic liver disease.
Maresin1 (MaR1), a new anti-inflammatory and proresolving lipid mediator, has been proven to exert organ-protective effects in septic animal models. However, the potential mechanisms are still not fully elucidated. In this study, we sought to explore the impact of MaR1 on metabolic dysfunction in cecal ligation and puncture- (CLP-) induced septic mice. We found that MaR1 significantly increased the overall survival rate and attenuated lung and liver injuries in septic mice. In addition, MaR1 markedly reduced the levels of proinflammatory cytokines (TNF-α and IL-6) and alleviated mitochondrial damage. Based on a 1H NMR-based metabolomics analysis, CLP-induced septic mice had increased levels of acetate, pyruvate, and lactate in serum and decreased levels of alanine, aspartate, glutamate, and fumarate in lungs. However, these metabolic disorders, mainly involving energy and amino acid metabolism, can be recovered by MaR1 treatment. Therefore, our results suggest that the protective effects of MaR1 on sepsis could be related to the recovery of metabolic dysfunction and the alleviation of inflammation and mitochondrial damage.
INTRODUCTION: Gallstone diseases affect intestinal inflammation, bile flow, and gut microbiota, which in turn may increase the risk of inflammatory bowel disease (IBD). However, epidemiological studies exploring the associations between gallstone diseases and subsequent IBD risk have been limited. METHODS: This is a combined analysis of 3 prospective cohort studies (Nurses' Health Study, Nurses' Health Study II, and UK Biobank) and replicated in a case-control study (Chinese IBD Etiology Study). We evaluated the hazard ratios (HRs)/odds ratios (ORs) between gallstone diseases with IBD risk by Cox logistic regression or conditional logistic regression, adjusting for demographic characteristics, lifestyles, comorbidities, and medication usage. RESULTS: We identified 3,480 cases of IBD over 2,127,471 person-years of follow-up in the 3 cohort studies. The participants with gallstone disease had a 38% increase in the risk of IBD (HR 1.38, 95% confidence intervals [CI] 1.21–1.59), 68% increase in Crohn's disease (HR 1.68, 95% CI 1.38–2.06), and 24% increase in ulcerative colitis (HR 1.24, 95% CI 1.03–1.49). In Chinese IBD Etiology Study, we found even larger magnitude of effects between gallstone diseases and IBD risk (IBD: OR 3.03, 95% CI 2.32–3.97; Crohn's disease: OR 5.31; 95% CI 3.71–7.60; ulcerative colitis: OR 1.49; 95% CI 1.07–2.06). There were no major differences in the estimated associations between the presence of unremoved gallstones and prior cholecystectomy with IBD risk. DISCUSSION: Gallstone disease was linked to an increased risk of IBD and its subtypes, independent of traditional risk factors. Further research is needed to confirm these associations and clarify the underlying biological mechanisms.
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