An altered expression of miR-376a-3p and miR-20a-5p in peripheral blood exosomes regulates the autophagy and inflammatory systemic substrates, and relates to the smoking habit and age in Crohn's disease.

miRNAs are short single-stranded noncoding RNAs that participate as epigenetic regulators in inflammatory bowel disease. Most miRNAs detectable in serum are concentrated in exosomes, with relevant cargo for immunobiological processes. We set to evaluate the exosomes miRNAs content in the serum of patients with Crohn's disease (CD) and run a prospective observational study on CD patients on biological monotherapy and healthy controls. miRNA cargo was evaluated in peripheral blood-derived exosomes. Serum autophagy and inflammatory substrates were measured. Patients were followed for 6 months. Patients (n = 28) showed an overexpression of miR-376a-3p and a downregulation of miR-20a-5p compared to controls (n = 10), without significant differences between patients according to biologics. Serum autophagy substrates ATG4C (r = .57; p = .001) and ACRV1C (r = .66; p = .001) inversely correlated with miR-376a-3p expression, whereas IGF1R correlated with miR-20a-5p expression (r = .42; p = .02). Th1-related cytokines correlated with miR-376a-3p expression, whereas the Th17-associated cytokines inversely correlated with miR-20a-5p expression. Smoking (ß = -2.301 CI 95% -3.790/-0.811, p = .004) remained as independent factor related to the overexpression of miR-376a-3p, whereas diagnosis before 16 years of age (ß = 2.044 CI 95% 0.934/3.154, p = .001) and a younger age of patients (ß = -.720 CI 95% -0.108/-0.035, p = .001) were related to decreased miR-20a-5p expression. Seven patients (25%) had a flare in the 6-month follow-up. Patients with overexpression of miR-376a-3p at the baseline showed an increased risk of flare during this period (OR 0.475 [0.237-0.950], p = .035). Finally, a comparative miRNA signature between biologic monotherapies was also explored. Targeting miR-376a-3p and miR-20a-5p epigenetic regulators may yield homeostatic effects on relevant biological processes related to disease progression in CD patients.

Telomerase Reverse Transcriptase-Promoter Mutation in Young Patients with Bladder Tumors.

The TERT (Telomerase Reverse Transcriptase) gene promoter mutation is one of the most prevalent mutations in urothelial bladder tumors and this mutation is related to bladder tumor progression. Our purpose was to evaluate the presence of this mutation in a population of patients who were first diagnosed at age ≤ 40 years and to examine its relationship with tumor characteristics and progression. A molecular study was performed to detect the two most prevalent mutations in the TERT promoter (C228T and C250T). The study included 29 patients, with a mean follow-up of 152 months. There were no statistically significant differences in the clinical or tumor characteristics according to the presence or absence of the mutation. Although the mutation group showed poorer recurrence-free survival (RFS), there was no statistically significant difference and there was no difference in progression-free survival by group (p > 0.05). The pTERT mutations in bladder tumor cells occurred less frequently in younger patients than in older patients, a finding that could indicate different mechanisms of carcinogenesis. The trend towards lower RFS in patients with mutated pTERT needs to be confirmed by further studies, given the small number of patients included in these studies due to the low incidence of bladder tumors in this age group.

Cirrhosis-downregulated LSECtin can be retrieved by cytokines, shifts the TLR-induced LSECs secretome and correlates with the hepatic Th response.

BACKGROUND AND AIMS: We evaluated tolerogenic C-type lectin LSECtin loss in cirrhosis and its potential regulation by cytokines. METHODS: Liver tissue from patients with cirrhosis and healthy controls, immortalised and generated LSECtin-CRISPR immortalised LSECs, and murine primary LSECs from the CCl4 model were handled. RESULTS: LSECtin expression was reduced in liver tissue from cirrhotic patients, and it decreased from compensated to decompensated disease. Increased phosphorylation of MAPK, Akt and NFkB was observed upon LSECtin stimulation in LSEC murine cell line, showing a pattern of inflammatory and chemotactic cytokines either restrained (IL-10, CCL4) or unrestrained (TNF-α, IL-1ß, IL-6, CCL2). CD44 attenuated whereas LAG-3 increased all substrates phosphorylation in combination with TLR4 and TLR2 ligands except for NFkB. TNF-α, IL-1 ß, IL-6 and CCL2 were restrained by LSECtin crosslinking on TLRs studied. Conversely, IL-10 and CCL4 were upregulated, suggesting a LSECtin-TLRs synergistic effect. Also, LSECtin was significantly induced after IL-13 stimulation or combined with anti-inflammatory cytokines in cirrhotic and immortalised LSECs. Th17 and regulatory T cells were progressively increased in the hepatic tissue from compensated to decompensated patients. A significant inverse correlation was present between gene expression levels of CLEC4G/LSECtin and RORγT and FOXP3 in liver tissues. CONCLUSION: LSECtin restrains TLR proinflammatory secretome induced on LSECs by interfering immune response control, survival and MAPKs signalling pathways. The cytokine-dependent induction of LSECtin and the association between LSECtin loss and Th17 cell subset expansion in the liver, provides a solid background for exploring LSECtin retrieval as a mechanism to reprogram LSEC homeostatic function hampered during cirrhosis.

Evaluation of Genetic Variants Associated with the Risk of Thiopurine-Related Pancreatitis: A Case Control Study from ENEIDA Registry.

INTRODUCTION: Risk factors for developing pancreatitis due to thiopurines in patients with inflammatory bowel disease (IBD) are not clearly identified. Our aim was to evaluate the predictive pharmacogenetic risk of pancreatitis in IBD patients treated with thiopurines. METHODS: We conducted an observational pharmacogenetic study of acute pancreatitis events in a cohort study of IBD patients treated with thiopurines from the prospectively maintained ENEIDA registry biobank of GETECCU. Samples were obtained and the CASR, CEL, CFTR, CDLN2, CTRC, SPINK1, CPA1, and PRSS1 genes, selected based on their known association with pancreatitis, were fully sequenced. RESULTS: Ninety-five cases and 105 controls were enrolled; a total of 57% were women. Median age at pancreatitis diagnosis was 39 years. We identified 81 benign variants (50 in cases and 67 in controls) and a total of 35 distinct rare pathogenic and unknown significance variants (10 in CEL, 21 in CFTR, 1 in CDLN2, and 3 in CPA1). None of the cases or controls carried pancreatitis-predisposing variants within the CASR, CPA1, PRSS1, and SPINK1 genes, nor a pathogenic CFTR mutation. Four different variants of unknown significance were detected in the CDLN and CPA1 genes; one of them was in the CDLN gene in a single patient with pancreatitis and 3 in the CPA1 gene in 5 controls. After the analysis of the variants detected, no significant differences were observed between cases and controls. CONCLUSION: In patients with IBD, genes known to cause pancreatitis seem not to be involved in thiopurine-related pancreatitis onset.

Exploring the Relationship between Liver Disease, Bacterial Translocation, and Dysbiosis: Unveiling the Gut-Liver Axis.

Background: The global burden of liver disease and cirrhosis has been progressively increasing in the last decade. The interplay between gut microbiota and immune system and the bidirectional relationship with the liver, known as the gut-liver axis, has arisen as a fundamental aspect of liver disease. Summary: Alterations of the gut microbiome have been described and include both dysbiotic microbial signatures and intestinal bacterial overgrowth. The integrity of the intestinal epithelial barrier is essential for preventing the access of harmful substances and bacterial products into the host. Bacterial translocation due to altered host-microbiota interactions triggers local immune cell activation and facilitates a chronic inflammatory state that can ultimately lead to immune exhaustion, characteristic of cirrhosis. In cirrhosis, breakdown of the gut vascular barrier allows access of bacterial products to portal blood circulation and facilitates their influx into the liver, further contributing to disease progression. Key Messages: A better understanding of the contributing factors to pathological bacterial translocation and the impact of dysbiosis in liver disease will lead to achieve innovative therapeutic strategies in cirrhosis.

Peripheral blood regulatory T cells and disease activity, quality of life, and outcomes in children with juvenile idiopathic arthritis.

OBJECTIVES: To measure regulatory T cell (Treg) levels in the peripheral blood of children with juvenile idiopathic arthritis (JIA) and analyse the association of this measure with disease activity, quality of life, adjustment of treatment, and hospitalisation. METHODS: We conducted a two-phase study (cross-sectional and prospective), including consecutive children with a JIA diagnosis according to ILAR criteria. Our independent variables were Tregs, Th1, Th2, and cytokines in peripheral blood, and our dependent variables in the cross-sectional phase were arthritis category, JIA activity, and patient-reported outcomes. To test associations, we used Spearman's correlation coefficient and the Mann-Whitney U test. In the prospective phase, we explored the probability of treatment adjustment and hospitalisation for JIA during follow-up according to Tregs levels at baseline, using Cox proportional regression. RESULTS: Our sample included 87 participants (median age 11 years, 63.2% girls). Tregs were not associated with most variables of interest. However, we found that higher Tregs concentration was associated with lower erythrocyte sedimentation rate (ESR) and better subjective disease status and course, while higher IL-10 and TGF-ß levels were associated with lower ESR, less pain, and better subjective disease status We found no association between Tregs and treatment adjustments or hospitalisation. CONCLUSIONS: Higher baseline Treg levels in the peripheral blood of children with JIA may be associated with reduced disease activity and better quality of life, though were not informative on the inflammatory progression on the follow-up.

Dynamic versus standard bougies for tracheal intubation with direct or indirect laryngoscopy in simulated or real scenarios: a systematic review and meta-analysis.

INTRODUCTION: This systematic review and meta-analysis aimed to compare the efficacy of dynamic versus standard bougies to achieve tracheal intubation. METHODS: We searched MEDLINE, Embase, CENTRAL, Web of Science, Scopus and Google Scholar on 10 October 2023. We included clinical trials comparing both devices. The primary outcome was the first-attempt intubation success rate. The secondary outcome was the time required for tracheal intubation. RESULTS: Eighteen studies were included. Dynamic bougies do not increase first-attempt success rate (RR 1.11; p = 0.06) or shorten tracheal intubation time (MD -0.30 sec; p = 0.84) in clinical trials in humans. In difficult airways, first-attempt success intubation rate was greater for dynamic bougies (RR 1.17; p = 0.002); Additionally, they reduced the time required for intubation (MD -4.80 sec; p = 0.001). First-attempt intubation success rate was higher (RR 1.15; p = 0.01) and time to achieve intubation was shorter when using Macintosh blades combined with dynamic bougies (MD -5.38 sec; p < 0.00001). Heterogeneity was high. CONCLUSION: Dynamic bougies do not increase the overall first-pass success rate or shorten tracheal intubation time. However, dynamic bougies seem to improve first-attempt tracheal intubation rate in patients with difficult airways and in those intubated with a Macintosh blade. Further research is needed for definitive conclusions. REGISTRATION OF PROSPERO: CRD42023472122.

Prevalence of crystal deposits in asymptomatic hyperuricemia according to different scanning definitions: A comparative study.

BACKGROUND/AIM: The appropriate sonographic protocol for assessing urate crystal deposits in asymptomatic hyperuricemia (AH) is undefined, as well as how the choice would impact on deposit rates and accompanying sonographic, clinical and laboratory features. METHODS: Patients with AH (serum urate ≥7 mg/dL) underwent musculoskeletal ultrasound of 10 locations for OMERACT elementary gout lesions (double contour [DC] signs, tophi, aggregates). Different definitions for AH with deposits were applied, varying according to deposits (any deposits; only DC and/or tophi); gradation (any grade; only grade 2-3 deposits), location (10 locations; 4-joint scheme including knees and 1MTPs; >1 location with deposits), or pre-defined definitions (DC sign in femoral condyles/1MTP and/or tophi in 1MTP). We evaluated crystal deposits rates and compared between other sonographic features, clinical and laboratory variables. RESULTS: Seventy-seven participants with AH showed a median 1 location (IQR 0-2) with tophi, 1 (IQR 1-2) with aggregates, and 0 locations (IQR 0-1) with DC sign. The deposition rate ranged from 23.4% (in >1 location with grade 2-3 DC or tophi) to 87.0% (in any deposit in all 10 locations). Accompanying inflammation - assessed by a positive power-Doppler (PD) signal - and erosions were found in 19.5% and 28.4% of participants, respectively. Positive PD signal was better discriminated by criteria requiring grade 2-3 or >1 location with lesions. Erosions and the different clinical and laboratory variables were similar among protocols. CONCLUSION: Rates of sonographic deposition in AH varied dramatically among studied protocols, while some could discriminate accompanying inflammation, all highlighting the need for a validated, consensus-based definition.

Clinical, Pathological Characteristics and Progression of Urothelial Bladder Cancer in Young Adult Patients. Our Experience and Literature Review.

BACKGROUND: Bladder cancer is highly prevalent even though its incidence is considerably lower in patients younger than 40 years, thus raising the issue of the influence of age at diagnosis on the natural history of this disease. This study aimed to evaluate the characteristics and progression of young patients with urothelial bladder carcinoma with at least 10 years of follow-up and to compare the results with those of previously reported studies. MATERIAL AND METHODS: A retrospective study between 1990 and 2007 was conducted. The medical records and tissue samples of patients with urothelial bladder tumours were reviewed, and patients with a first diagnosis of urothelial carcinoma of the bladder at age 40 years or younger were selected. Their clinical and pathological data and disease-free survival were analysed. RESULTS: This study included 43 patients, with a median follow-up of 152 months (interquartile range (IQR): 96-222) and a mean age at diagnosis of 34 years (SD: 4.6). Thirty-five patients (81.4%) had non-muscle invasive tumours at diagnosis, and 53.5%, 27.9% and 18.6% had tumour grades of G1, G2 and G3, respectively. Fifteen patients (34.9%) experienced recurrence, and eight (18.6%) progressed. At 24 and 60 months, the recurrence-free survival rates were 84.8% (95% confidence interval (CI): 69.2%-92.9%) and 68.9% (95% CI: 51.7%-81%), respectively, and the progression-free survival rates were 94.9% (95% CI: 81%-98.7%) and 92.2% (95% CI: 77.8%-97.4%), respectively. CONCLUSIONS: Bladder cancer is an uncommon disease in young patients. In most cases, it consists of non-muscle-invasive tumours, with a low rate of recurrence and progression. The prognosis is based on the tumour's characteristics and not on the patient's age.

The biochemical pattern defines MASLD phenotypes linked to distinct histology and prognosis.

BACKGROUND: MASLD can manifest as hepatocellular damage, which can result in mild elevation of aminotransferases. However, in some patients, MASLD presents with cholestatic pattern. OBJECTIVE: To assess the impact of the biochemical pattern on the natural course of MASLD, including liver damage in histology, the accuracy of non-invasive tests(NITs), and prognosis. METHODS: Multicenter study enrolling 2156 patients with biopsy-proven MASLD, who were classified based on their[ALT/ULN)]/[(ALP/ULN)] levels at the time of biopsy: (a) hepatocellular pattern(H), > 5; (b) mixed pattern(M),2-5; (c) cholestatic pattern(C), < 2. OUTCOMES: (a) histological evaluation of the single components of NAS, MASH, and fibrosis; (b) NITs and transient elastography assessing advanced fibrosis; (c) prognosis determined by the appearance of decompensated cirrhosis and death. RESULTS: Out of the 2156 patients, 22.9% exhibited the H-pattern, whilst 31.7% exhibited the C-pattern. Severe steatosis, ballooning, lobular inflammation, and MASH (56.4% H vs. 41.9% M vs. 31.9% C) were more common in H-pattern (p = 0.0001),whilst C-pattern was linked to cirrhosis (5.8% H vs. 5.6% M vs. 10.9% C; p = 0.0001). FIB-4(0.74(95% CI 0.69-0.79) vs. 0.83 (95% CI 0.80-0.85); p = 0.005) and Hepamet Fibrosis Score(0.77 (95% CI 0.69-0.85) vs. 0.84 (95% CI 0.80-0.87); p = 0.044)exhibited lower AUROCs in the H-pattern. The C-pattern[HR 2.37 (95% CI 1.12-5.02); p = 0.024], along with age, diabetes, and cirrhosis were independently associated with mortality. Most patients maintained their initial biochemical pattern during the second evaluation. CONCLUSIONS: The H-pattern exhibited greater necro-inflammation in the histology than the C-pattern, whereas the latter showed more cirrhosis. The accuracy of NITs in detecting fibrosis was decreased in H-pattern. The occurrence of decompensated events and mortality was predominant in C-pattern. Therefore, identifying MASLD phenotypes based on the biochemical presentation could be relevant for clinical practice.

Executive Summary of the Spanish Society of Anesthesiology, Reanimation and Pain Therapy (SEDAR) Spanish Society of Emergency and Emergency Medicine (SEMES) and Spanish Society of Otolaryngology, Head and Neck Surgery (SEORL-CCC) Guideline for difficult airway management.

The Airway section of the Spanish Society of Anesthesiology, Reanimation and Pain Therapy (SEDAR), Spanish Society of Emergency and Emergency Medicine (SEMES) and Spanish Society of Otolaryngology, Head and Neck Surgery (SEORL-CCC) present the Guidelines for the integral management of difficult airway in adult patients. This document provides recommendations based on current scientific evidence, theoretical-educational tools and implementation tools, mainly cognitive aids, applicable to the treatment of the airway in the field of anesthesiology, critical care, emergencies and prehospital medicine. Its principles are focused on the human factors, cognitive processes for decision-making in critical situations and optimization in the progression of the application of strategies to preserve adequate alveolar oxygenation in order to improve safety and quality of care.

Implementation of an ERAS program in patients undergoing thoracic surgery at a third-level university hospital: an ambispective cohort study

Abstract Objective To analyze the effects of an ERAS program on complication rates, readmission, and length of stay in patients undergoing pulmonary resection in a tertiary university hospital. Methods Ambispective cohort study with a prospective arm of 50 patients undergoing thoracic surgery within an ERAS program (ERAS group) versus a retrospective arm of 50 patients undergoing surgery before the protocol was implemented (Standard group). The primary outcome was the number of patients with 30-day surgical complications. Secondary outcomes included ERAS adherence, non-surgical complications, mortality, readmission, reintervention rate, pain, and hospital length of stay. We performed a multivariate logistic analysis to study the correlation between outcomes and ERAS adherence. Results In the univariate analysis, we found no difference between the two groups in terms of surgical complications (Standard 18 [36%] vs. ERAS 12 [24%], p = 0.19). In the ERAS group, only the readmission rate was significantly lower (Standard 15 [30%] vs. ERAS 6 [12%], p = 0.03). In the multivariate analysis, ERAS adherence was the only factor associated with a reduction in surgical complications (OR [95% CI] = 0.02 [0.00, 0.59], p = 0.03) and length of stay (HR [95% CI] = 18.5 [4.39, 78.4], p < 0.001). Conclusions The ERAS program significantly reduced the readmission rate at our hospital. Adherence to the ERAS protocol reduced surgical complications and length of stay.

Enhanced recovery after surgery protocol versus conventional perioperative care in colorectal surgery: a single center cohort study / Aceleração da recuperação após protocolo cirúrgico versus cuidados perioperatórios convencionais em cirurgia colorretal: um estudo de coorte em centro único

Abstract Background Enhanced recovery after surgery (ERAS) protocols consist of a set of perioperative measures aimed at improving patient recovery and decreasing length of stay and postoperative complications. We assess the implementation and outcomes of an ERAS program for colorectal surgery. Methods Single center observational study. Data were collected from consecutive patients undergoing open or laparoscopic colorectal surgery during 2 time periods, 3 years before (Pre-ERAS) and 2 years after (Post-ERAS) the implementation of an ERAS protocol. Baseline characteristics of both groups were compared. The primary outcome was the number of patients with 180 days follow-up with moderate or severe complications; secondary outcomes were postoperative length of stay, and specific complications. Data were extracted from patient records. Results There were 360 patients in the Pre-ERAS group and 319 patients in the Post-ERAS Group. 214 (59.8%) patients developed at least one complication in the pre ERAS group, versus 163 patients in the Post-ERAS group (51.10%). More patients in the Pre-ERAS group developed moderate or severe complications (31.9% vs. 22.26%, p = 0.009); and severe complications (15.5% vs. 5.3%; p < 0.0001). The median length of stay was 13 (17) days in Pre-ERAS Group and 11 (10) days in the Post-ERAS Group (p = 0.034). No differences were found on mortality rates (4.7% vs. 2.5%; p = 0.154), or readmission (6.39% vs. 4.39%; p = 0.31). Overall ERAS protocol compliance in the Post-ERAS cohort was 88%. Conclusions The implementation of ERAS protocol for colorectal surgery was associated with a significantly reduction of postoperative complications and length of stay.

Resumo Justificativa O protocolo ERAS - do Inglês Enhanced Recovery After Surgery - consiste em um conjunto de medidas perioperatórias destinadas a melhorar a recuperação do paciente e diminuir o tempo de internação e as complicações pós-operatórias. Avaliamos a implantação e os resultados de um protocolo ERAS para cirurgia colorretal. Métodos Estudo observacional em centro único. Os dados foram coletados de pacientes consecutivos submetidos à cirurgia colorretal aberta ou laparoscópica durante dois períodos: três anos antes (pré-ERAS) e dois anos após (pós-ERAS) a implantação de um protocolo ERAS. As características basais de ambos os grupos foram comparadas. O desfecho primário foi o número de pacientes com 180 dias de acompanhamento com complicações moderadas ou graves. Os desfechos secundários foram tempo de internação pós-cirurgia e complicações específicas. Os dados foram extraídos de prontuários dos pacientes. Resultados O grupo pré-ERAS foi composto por 360 pacientes e o grupo pós-ERAS por 319. No grupo pré ERAS, 214 pacientes (59,8%) desenvolveram pelo menos uma complicação versus 163 (51,10%) no grupo pós-ERAS. Um número maior de pacientes do grupo pré-ERAS desenvolveu complicações moderadas ou graves (31,9% vs. 22,26%, p = 0,009); e complicações graves (15,5% vs. 5,3%; p < 0,0001). A mediana do tempo de internação foi de 13 (17) dias no grupo pré-ERAS e de 11 (10) dias no grupo pós-ERAS (p = 0,034). Não houve diferença nas taxas de mortalidade (4,7% vs. 2,5%; p = 0,1554) ou de reinternação (6,39% vs. 4,39%; p = 0,31). A conformidade geral do protocolo ERAS na coorte pós-ERAS foi de 88%. Conclusões A implantação do protocolo ERAS para cirurgia colorretal foi associada a uma redução significativa das complicações pós-operatórias e do tempo de internação.

Microbioma y traslocación bacteriana en la cirrosis / Microbiome and bacterial translocation in cirrhosis

Los cambios cualitativos y cuantitativos en la microbiota intestinal juegan un papel muy importante en la cirrosis. El ser humano alberga cerca de 100 trillones de bacterias intestinales, representando así alrededor de 10 veces más células microbianas que eucariotas. El tracto gastrointestinal es el área de superficie más grande del cuerpo y se encuentra en constante exposición a estos microorganismos vivos. La simbiosis existente, demostrada por la falta de respuesta proinflamatoria contra bacterias comensales, implica la presencia de líneas de comunicación claramente definidas que contribuyen al mantenimiento de la homeostasis del hospedador. Así, las alteraciones en la flora intestinal parecen tener un papel en la patogénesis y la progresión de varias enfermedades hepáticas y gastrointestinales. Esto ha convertido su modificación selectiva en un área de interés terapéutico. La traslocación bacteriana se define como el paso de bacterias y/o sus productos desde el intestino a los ganglios linfáticos mesentéricos. Por tanto, las alteraciones en la microbiota intestinal han mostrado su importancia, al menos parcialmente, en la patogénesis de varias complicaciones que surgen en la enfermedad hepática en fase terminal, tales como la encefalopatía hepática, la hipertensión portal y la peritonitis bacteriana espontánea. En esta revisión se resume, por un lado, cómo la enfermedad hepática puede alterar la composición habitual de la microbiota intestinal, y por otro, cómo esta alteración contribuye al desarrollo de complicaciones en la cirrosis

Qualitative and quantitative changes in gut microbiota play a very important role in cirrhosis. Humans harbour around 100 quintillion gut bacteria, thus representing around 10 times more microbial cells than eukaryotic ones. The gastrointestinal tract is the largest surface area in the body and it is subject to constant exposure to these living microorganisms. The existing symbiosis, proven by the lack of proinflammatory response against commensal bacteria, implies the presence of clearly defined communication lines that contribute to the maintenance of homeostasis of the host. Therefore, alterations of gut flora seem to play a role in the pathogenesis and progress of multiple liver and gastrointestinal diseases. This has made its selective modification into an area of high therapeutic interest. Bacterial translocation is defined as the migration of bacteria or bacterial products from the intestines to the mesenteric lymph nodes. It follows that alteration in gut microbiota have shown importance, at least to some extent, in the pathogenesis of several complications arising from terminal liver disease, such as hepatic encephalopathy, portal hypertension and spontaneous bacterial peritonitis. This review sums up, firstly, how liver disease can alter the common composition of gut microbiota, and secondly, how this alteration contributes to the development of complications in cirrhosis

Intraoperative goal directed hemodynamic therapy in noncardiac surgery: a systematic review and meta-analysis / Terapia hemodinâmica alvo-dirigida no intraoperatório de cirurgia não cardíaca: revisão sistemática e meta-análise

Abstract Background: The goal directed hemodynamic therapy is an approach focused on the use of cardiac output and related parameters as end-points for fluids and drugs to optimize tissue perfusion and oxygen delivery. Primary aim: To determine the effects of intraoperative goal directed hemodynamic therapy on postoperative complications rates. Methods: A meta-analysis was carried out of the effects of goal directed hemodynamic therapy in adult noncardiac surgery on postoperative complications and mortality using Preferred Reporting Items for Systematic Reviews and Meta-Analyses methodology. A systematic search was performed in Medline PubMed, Embase, and the Cochrane Library (last update, October 2014). Inclusion criteria were randomized clinical trials in which intraoperative goal directed hemodynamic therapy was compared to conventional fluid management in noncardiac surgery. Exclusion criteria were trauma and pediatric surgery studies and that using pulmonary artery catheter. End-points were postoperative complications (primary) and mortality (secondary). Those studies that fulfilled the entry criteria were examined in full and subjected to quantifiable analysis, predefined subgroup analysis (stratified by type of monitor, therapy, and hemodynamic goal), and predefined sensitivity analysis. Results: 51 RCTs were initially identified, 24 fulfilling the inclusion criteria. 5 randomized clinical trials were added by manual search, resulting in 29 randomized clinical trials in the final analysis, including 2654 patients. A significant reduction in complications for goal directed hemodynamic therapy was observed (RR: 0.70, 95% CI: 0.62-0.79, p < 0.001). No significant decrease in mortality was achieved (RR: 0.76, 95% CI: 0.45-1.28, p = 0.30). Quality sensitive analyses confirmed the main overall results. Conclusions: Intraoperative goal directed hemodynamic therapy with minimally invasive monitoring decreases postoperative complications in noncardiac surgery, although it was not able to show a significant decrease in mortality rate.

Resumo Justificativa: A terapia hemodinâmica alvo-dirigida (THAD) é uma abordagem focada no uso do débito cardíaco (DC) e parâmetros relacionados, como desfechos para fluidos e medicamentos para aprimorar a perfusão tecidual e o fornecimento de oxigênio. Objetivo primário: determinar os efeitos da THAD sobre as taxas de complicações no pós-operatório. Métodos: Metanálise dos efeitos da THAD em cirurgias não cardíacas de adultos sobre as complicações pós-operatórias e mortalidade, com a metodologia PRISMA. Uma busca sistemática foi feita no Medline PubMed, Embase e Biblioteca Cochrane (última atualização, outubro de 2014). Os critérios de inclusão foram estudos clínicos randômicos (ECRs) nos quais a THAD no intraoperatório foi comparada com a terapia convencional de reposição de líquidos em cirurgia não cardíaca. Os critérios de exclusão foram traumatismo e estudos de cirurgia pediátrica e aqueles que usaram cateter de artéria pulmonar. Os desfechos, primário e secundário, foram complicações pós-operatórias e mortalidade, respectivamente. Os estudos que atenderam aos critérios de inclusão foram examinados na íntegra e submetidos à análise quantitativa, análise de subgrupo pré-definido (estratificada por tipo de monitor, terapia e objetivo hemodinâmico) e análise de sensibilidade pré-definida. Resultados: 51 ECRs foram identificados inicialmente, 24 atenderam aos critérios de inclusão. Cinco ECRs foram adicionados por busca manual, resultando em 29 ECRs para análise final, incluindo 2.654 pacientes. Uma redução significativa das complicações para a THAD (RR: 0,70, IC de 95%: 0,62-0,79, p < 0,001). Nenhuma diminuição significativa na mortalidade foi observada (RR: 0,76, IC de 95%: 0,45-1,28, p = 0,30). Análises de sensibilidade qualitativa confirmaram os principais resultados gerais. Conclusões: THAD no intraoperatório com monitoração minimamente invasiva diminui as complicações no pós-operatório de cirurgia não cardíaca, embora não tenha mostrado uma redução significativa da taxa de mortalidade.

Asociación entre marcadores inflamatorios y traslocación bacteriana en pacientes con infección por el virus de la inmunodeficiencia humana en tratamiento antirretroviral / Association between inflammatory markers and microbial translocation in patients with human immunodeficiency virus infection taking antiretroviral treatment

Fundamento y objetivo: Ciertos marcadores inflamatorios están elevados en pacientes con infección por el virus de la inmunodeficiencia humana (VIH). El tratamiento antirretroviral (TAR) mejora algunos de estos parámetros, pero no suele normalizarlos. El objetivo de este estudio es determinar los factores, incluida la traslocación bacteriana, asociados a una mayor actividad inflamatoria en pacientes con infección por VIH en tratamiento. Pacientes y métodos: Estudio observacional transversal. Se incluyeron pacientes con infección por VIH que recibían TAR y tenían carga viral plasmática del VIH (CVP-VIH) < 400 copias/ml. Se seleccionaron pacientes consecutivos entre noviembre de 2011 y enero de 2012. Las variables de resultado fueron los valores séricos de interleucina 6 (IL-6) y de tumour necrosis factor α (TNF-α, «factor de necrosis tumoral α»). La variable explicativa principal fueron los marcadores de traslocación bacteriana (ADN ribosomal 16S y sCD14). Los pacientes con valores de IL-6 o TNF-α por encima del percentil 75 (grupo 1) se compararon con el resto de pacientes (grupo 2), y se calcularon las odds ratio (OR) brutas y ajustadas (análisis multivariante). Resultados: Se incluyeron 81 pacientes (73% varones, edad mediana 45 años, 48% en estadio C). El 26% tenía hepatitis crónica C. La mediana de linfocitos CD4 era de 493 cél/mm3 y el 30% tenía CVP-VIH detectable. Se detectó ADN ribosomal en el 21% de los pacientes. Los integrantes del grupo 1 presentaron con mayor frecuencia ADN ribosomal (OR 77, p < 0,0001), valores altos de sCD14 (p < 0,0001) y antecedentes de enfermedad cardiovascular (OR 15, p < 0,01). En el análisis multivariante la asociación se mantuvo para la presencia de ADN ribosomal (OR 62, p < 0,0001) y antecedentes cardiovasculares (OR 25, p < 0,01). Conclusiones: En pacientes con infección por VIH en tratamiento, los mayores valores de marcadores inflamatorios se observan en aquellos casos con traslocación bacteriana y antecedentes de enfermedad cardiovascular (AU)

Background and objective: Inflammatory biomarkers are increased in patients with human immunodeficiency virus (HIV) infection. Antiretroviral treatment (ART) improves some parameters but do not normalize them. The aim of this study is to determine those factors (including microbial translocation) associated with higher inflammation in HIV treated patients. Patients and methods: Transversal observational study. Inclusion criteria: HIV patients receiving ART with an HIV viral load (VL) < 400 copies/mL. Selection of patients: consecutively between November 2011 and January 2012. Main variable: plasma levels of interleukin 6 (IL-6) and tumour necrosis factor α (TNF-α). Main explanatory variable: microbial translocation markers (16S ribosomal DNA and sCD14). Patients with IL-6 or TNF-α levels above percentile 75 (group 1) were compared with the rest of patients (group 2). Odds ratio (OR) were determined. Results: Eighty-one patients were included (73% male, median age 45 years, 48% stage C). Twenty-six percent had chronic hepatitis C. Median CD4 cell was 493/mm3 and 30% had detectable HIV VL. 16S ribosomal DNA was detected in 21% of patients. Factors associated with the higher levels of inflammatory markers were 16S ribosomal DNA (OR 77, P < .0001), sCD14 levels (P < .0001) and history of cardiovascular disease (OR 15, P < .01). In multivariate analysis, associations remained for 16S ribosomal DNA (OR 62, P < .0001) and previous cardiovascular disease (OR 25, P < .01). Conclusions: In patients with HIV infection receiving treatment, the higher levels of inflammatory markers are associated with microbial translocation and past cardiovascular events (AU)

Translocación de productos de origen bacteriano en la cirrosis / Bacterial translocation in cirrhosis

La translocación bacteriana (TB) se define como el paso debacterias viables a través de la barrera intestinal hacia losganglios linfáticos mesentéricos, con la posibilidad que desdeallí puedan diseminarse hacia otros sistemas. La patogeniade la TB en la cirrosis se asienta en tres pilares: sobrecrecimientobacteriano, aumento de permeabilidadintestinal y alteraciones del sistema inmunológico. Recienteshallazgos indican que el concepto de TB podría ampliarsepara incluir la presencia de productos bacterianos (ADNbacteriano y endotoxina) en los ganglios linfáticos mesentéricosy en otros territorios. Tanto el ADN bacteriano comola endotoxina provocan una activación sostenida del sistemainmune, con liberación de citocinas proinflamatorias y efectores,como el óxido nítrico, que agravan las alteraciones hemodinámicaspresentes en pacientes con cirrosis. Este capítulodescribe con mayor detalle las anomalías presentes enpacientes con cirrosis que permiten la existencia de TB y lasconsecuencias inmunes y clínicas de este fenómeno

Bacterial translocation (BT) is defined as the passage of viablebacteria through the intestinal barrier toward the mesentericlymph nodes, where they may disseminate towardother systems. The pathogenesis of BT in cirrhosis involvesthree main factors: bacterial overgrowth, increased intestinalpermeability, and immune system alterations. Recentfindings indicate that the concept of BT could be broadenedto include the presence of bacterial products (bacterial DNAand endotoxin) in mesenteric lymph nodes and other territories.Both bacterial DNA and endotoxin provoke sustainedactivation of the immune system with release of proinflammatorycytokines and effectors such as nitric oxide, whichaggravate the hemodynamic alterations present in patientswith cirrhosis. This article provides a detailed description ofthe abnormalities present in patients with cirrhosis thatallow the existence of TB and the immune and clinical repercussionsof this phenomenon