Comparison of Side Effects with Extended Release Epidural Morphine and Other Analgesic Modalities

Opioids are the mainstay of post-operative pain management and may produce side effects that impact patient recovery. Use of Extended Release Epidural Morphine (EREM) has been shown to result in significantly less average morphine usage and to have superior analgesic efficacy than other modes of postoperative pain management. The purpose of this retrospective review was to compare the incidence and onset of side effects of ERE and other post-operative Analgesic regiments

Microbial Preparations (Probiotics) for the Prevention of Clostridium difficile Infection in Adults and Children: An Individual Patient Data Meta-analysis of 6,851 Participants.

OBJECTIVETo determine whether probiotic prophylaxes reduce the odds of Clostridium difficile infection (CDI) in adults and children.DESIGNIndividual participant data (IPD) meta-analysis of randomized controlled trials (RCTs), adjusting for risk factors.METHODSWe searched 6 databases and 11 grey literature sources from inception to April 2016. We identified 32 RCTs (n=8,713); among them, 18 RCTs provided IPD (n=6,851 participants) comparing probiotic prophylaxis to placebo or no treatment (standard care). One reviewer prepared the IPD, and 2 reviewers extracted data, rated study quality, and graded evidence quality.RESULTSProbiotics reduced CDI odds in the unadjusted model (n=6,645; odds ratio [OR] 0.37; 95% confidence interval [CI], 0.25-0.55) and the adjusted model (n=5,074; OR, 0.35; 95% CI, 0.23-0.55). Using 2 or more antibiotics increased the odds of CDI (OR, 2.20; 95% CI, 1.11-4.37), whereas age, sex, hospitalization status, and high-risk antibiotic exposure did not. Adjusted subgroup analyses suggested that, compared to no probiotics, multispecies probiotics were more beneficial than single-species probiotics, as was using probiotics in clinical settings where the CDI risk is ≥5%. Of 18 studies, 14 reported adverse events. In 11 of these 14 studies, the adverse events were retained in the adjusted model. Odds for serious adverse events were similar for both groups in the unadjusted analyses (n=4,990; OR, 1.06; 95% CI, 0.89-1.26) and adjusted analyses (n=4,718; OR, 1.06; 95% CI, 0.89-1.28). Missing outcome data for CDI ranged from 0% to 25.8%. Our analyses were robust to a sensitivity analysis for missingness.CONCLUSIONSModerate quality (ie, certainty) evidence suggests that probiotic prophylaxis may be a useful and safe CDI prevention strategy, particularly among participants taking 2 or more antibiotics and in hospital settings where the risk of CDI is ≥5%.TRIAL REGISTRATIONPROSPERO 2015 identifier: CRD42015015701Infect Control Hosp Epidemiol 2018;771-781

Genome-wide association study identifies multiple risk loci for renal cell carcinoma

Previous genome-wide association studies (GWAS) have identified six risk loci for renal cell carcinoma (RCC). We conducted a meta-analysis of two new scans of 5,198 cases and 7,331 controls together with four existing scans, totalling 10,784 cases and 20,406 controls of European ancestry. Twenty-four loci were tested in an additional 3,182 cases and 6,301 controls. We confirm the six known RCC risk loci and identify seven new loci at 1p32.3 (rs4381241, P=3.1 × 10−10), 3p22.1 (rs67311347, P=2.5 × 10−8), 3q26.2 (rs10936602, P=8.8 × 10−9), 8p21.3 (rs2241261, P=5.8 × 10−9), 10q24.33-q25.1 (rs11813268, P=3.9 × 10−8), 11q22.3 (rs74911261, P=2.1 × 10−10) and 14q24.2 (rs4903064, P=2.2 × 10−24). Expression quantitative trait analyses suggest plausible candidate genes at these regions that may contribute to RCC susceptibility

Purinergic signalling and immune cells

This review article provides a historical perspective on the role of purinergic signalling in the regulation of various subsets of immune cells from early discoveries to current understanding. It is now recognised that adenosine 5'-triphosphate (ATP) and other nucleotides are released from cells following stress or injury. They can act on virtually all subsets of immune cells through a spectrum of P2X ligand-gated ion channels and G protein-coupled P2Y receptors. Furthermore, ATP is rapidly degraded into adenosine by ectonucleotidases such as CD39 and CD73, and adenosine exerts additional regulatory effects through its own receptors. The resulting effect ranges from stimulation to tolerance depending on the amount and time courses of nucleotides released, and the balance between ATP and adenosine. This review identifies the various receptors involved in the different subsets of immune cells and their effects on the function of these cells

Análise da respiração mitocondrial em tecido cerebral de gato após isquemia e reperfusão Analysis of mitochondrial respiration in brain cerebral tissue of cats after ischemia and reperfusion

INTRODUÇÃO: A isquemia cerebral é uma doença freqüente e de difícil tratamento médico. De particular interesse neurocirúrgico são as situações de vasoespasmo após hemorragia subaracnóidea, de oclusão temporária de vasos nas neurocirurgias e de tromboses de artérias intracranianas. A lesão cerebral resultante da isquemia depende da sua duração e pode ser agravada pela reperfusão do território isquêmico. Vários estudos clínicos e experimentais têm sido realizados para melhor entender esses fenômenos. OBJETIVO: Este trabalho visou a avaliação precoce dos efeitos da isquemia focal seguida da reperfusão no cérebro de gatos. MÉTODOS: A isquemia cerebral foi provocada por clipagem temporária da artéria cerebral média por tempos determinados com reperfusão durante 10 minutos, e avaliação foi efetuada através da análise da respiração mitocondrial no tecido isquemiado. Resultados - Houve redução significativa no consumo de O2 nas amostras de tecido cerebral isquemiado por 60 minutos, seguidos de 10 minutos de reperfusão, quando comparadas ao tecido cerebral contralateral (não isquemiado). CONCLUSÕES: Com base nos resultados obtidos, pode-se concluir que o tempo de duração da isquemia foi um fator determinante na alteração da respiração mitocondrial de gatos submetidos à isquemia e reperfusão de curta duração (alterações significativas apenas após 60 minutos de isquemia seguidos de 10 de reperfusão).<br>OBJECTIVE: Brain ischemia is considered a disease difficult to be treated. Despite many other clinical situations, of particular interest for neurosurgery is its occurrence in cerebral vasoespam following subarachnoid hemorrhage, in temporary occlusion of intracranial vessels during neurosurgeries and, in intracranial arterial thrombosis. The cerebral lesion caused by isquemia is time-related and it can aggravated by the reperfusion of the ischemic site. Many clinical and experimental studies have been perfomed aiming the better understanding of these phenomena. This study aimed to analyse the precocious effects of focal isquemia and reperfusion uppon the brain of cats. METHODS: Focal brain ischemia was performed by temporary clipping of the middle cerebral artery for determined times followed by reperfusion during 10 minutes. The effects of isquemia were assessed through mitochondrial respiration analysis in the ischemic tissue. RESULTS: The results showed a significant decrease in O2 consumption in samples of brain tissue submitted to 60 minutes of ischemia and 10 minutes of reperfusion when compared with not ischemic brain tissue, indicating compromising of the mitocondrial function. CONCLUSION: Based on the results we can conclude that time of ischemia was a determinant factor in the mitochondrial respiration alterations in brain tissue of cats submitted to ischemia and reperfusion of short duration (significant alterations observed only after 60 minutes of ischemia followed by 10 minutes of reperfusion)

Regulation of Aryl Hydrocarbon Receptor Interacting Protein (AIP) Protein Expression by MiR-34a in Sporadic Somatotropinomas

Patients with germline AIP mutations or low AIP protein expression have large, invasive somatotroph adenomas and poor response to somatostatin analogues (SSA).To study the mechanism of low AIP protein expression 31 sporadic somatotropinomas with low (n = 13) or high (n = 18) AIP protein expression were analyzed for expression of AIP messenger RNA (mRNA) and 11 microRNAs (miRNAs) predicted to bind the 3'UTR of AIP. Luciferase reporter assays of wild-type and deletion constructs of AIP-3'UTR were used to study the effect of the selected miRNAs in GH3 cells. Endogenous AIP protein and mRNA levels were measured after miRNA over- and underexpression in HEK293 and GH3 cells.No significant difference was observed in AIP mRNA expression between tumors with low or high AIP protein expression suggesting post-transcriptional regulation. miR-34a was highly expressed in low AIP protein samples compared high AIP protein adenomas and miR-34a levels were inversely correlated with response to SSA therapy. miR-34a inhibited the luciferase-AIP-3'UTR construct, suggesting that miR-34a binds to AIP-3'UTR. Deletion mutants of the 3 different predicted binding sites in AIP-3'UTR identified the c.*6-30 site to be involved in miR-34a's activity. miR-34a overexpression in HEK293 and GH3 cells resulted in inhibition of endogenous AIP protein expression.Low AIP protein expression is associated with high miR-34a expression. miR-34a can down-regulate AIP-protein but not RNA expression in vitro. miR-34a is a negative regulator of AIP-protein expression and could be responsible for the low AIP expression observed in somatotropinomas with an invasive phenotype and resistance to SSA