Pulmonary interstitial emphysema and spontaneous pneumomediastinum are more prevalent in sighthounds than other dog breeds undergoing thoracic CT.

Spontaneous pneumomediastinum is an uncommon condition described in veterinary medicine with concurrent respiratory disease. It can be caused by the Macklin effect, which is when gas leaks from the alveoli into the surrounding interstitial lung tissue. Pulmonary interstitial emphysema (PIE) is the presence of gas within the pulmonary vascular sheaths and indicates the presence of the Macklin effect. In the authors' experience, spontaneous pneumomediastinum and PIE are more prevalent in sighthound dogs than in other breeds and are often considered incidental findings. This retrospective, observational, cross-sectional study compared the prevalence of PIE and subsequent pneumomediastinum in sighthound with other purebred dogs. It characterized the appearance of PIE in CT and analyzed a possible association with concomitant pulmonary pathologies or with the use of general anesthesia. Medical records and thoracic CTs of sighthounds and nonsighthound dogs from two institutions were reviewed. A total of 256 dogs, comprising 127 sighthounds and 129 other purebred dogs, were included. The prevalence of PIE and pneumomediastinum was statistically higher in sighthound (14.2%) compared with other nonsighthound dogs (2.2%). There was no statistical association between the presence of PIE and pneumomediastinum with different age and weight groups or with sex. There was no statistical difference in the prevalence of PIE and pneumomediastinum between dogs with and without pulmonary pathology or in dogs undergoing CT with sedation or general anesthesia. Spontaneous pneumomediastinum in sighthounds is more prevalent than in other breeds, and its prevalence is not associated with the presence of pulmonary pathology or the use of general anesthesia.

Clinical, experimental and pathophysiological effects of Yaq-001: a non-absorbab le, gut-restricted adsorbent in models and patients with cirrhosis.

OBJECTIVE: Targeting bacterial translocation in cirrhosis is limited to antibiotics with risk of antimicrobial resistance. This study explored the therapeutic potential of a non-absorbable, gut-restricted, engineered carbon bead adsorbent, Yaq-001 in models of cirrhosis and acute-on-chronic liver failure (ACLF) and, its safety and tolerability in a clinical trial in cirrhosis. DESIGN: Performance of Yaq-001 was evaluated in vitro. Two-rat models of cirrhosis and ACLF, (4 weeks, bile duct ligation with or without lipopolysaccharide), receiving Yaq-001 for 2 weeks; and two-mouse models of cirrhosis (6-week and 12-week carbon tetrachloride (CCl4)) receiving Yaq-001 for 6 weeks were studied. Organ and immune function, gut permeability, transcriptomics, microbiome composition and metabolomics were analysed. The effect of faecal water on gut permeability from animal models was evaluated on intestinal organoids. A multicentre, double-blind, randomised, placebo-controlled clinical trial in 28 patients with cirrhosis, administered 4 gr/day Yaq-001 for 3 months was performed. RESULTS: Yaq-001 exhibited rapid adsorption kinetics for endotoxin. In vivo, Yaq-001 reduced liver injury, progression of fibrosis, portal hypertension, renal dysfunction and mortality of ACLF animals significantly. Significant impact on severity of endotoxaemia, hyperammonaemia, liver cell death, systemic inflammation and organ transcriptomics with variable modulation of inflammation, cell death and senescence in the liver, kidneys, brain and colon was observed. Yaq-001 reduced gut permeability in the organoids and impacted positively on the microbiome composition and metabolism. Yaq-001 regulated as a device met its primary endpoint of safety and tolerability in the clinical trial. CONCLUSIONS: This study provides strong preclinical rationale and safety in patients with cirrhosis to allow clinical translation. TRIAL REGISTRATION NUMBER: NCT03202498.

Identification of injured elements in computational models of spinal cord injury using machine learning.

The purpose of this study was to use machine learning (ML) algorithms to identify tissue damage based on the mechanical outputs of computational models of spinal cord injury (SCI). Three datasets corresponding to gray matter, white matter, and the combination of gray and white matter tissues were used to train the models. These datasets were built from the comparison of histological images taken from SCI experiments in non-human primates and corresponding subject-specific finite element (FE) models. Four ML algorithms were evaluated and compared using cross-validation and the area under the receiver operating characteristic curve (AUC). After hyperparameter tuning, the AUC mean values for the algorithms ranged between 0.79 and 0.82, with a standard deviation no greater than 0.02. The findings of this study also showed that k-nearest neighbors and logistic regression algorithms were better at identifying injured elements than support vector machines and decision trees. Additionally, depending on the evaluated dataset, the mean values of other performance metrics, such as precision and recall, varied between algorithms. These initial results suggest that different algorithms might be more sensitive to the skewed distribution of classes in the studied datasets, and that identifying damage independently or simultaneously in the gray and white matter tissues might require a better definition of relevant features and the use of different ML algorithms. These approaches will contribute to improving the current understanding of the relationship between mechanical loading and tissue damage during SCI and will have implications for the development of prevention strategies for this condition.Clinical Relevance- Linking FE model predictions of mechanical loading to tissue damage is an essential step for FE models to provide clinically relevant information. Combined with imaging technologies, these models can provide useful insights to predict the extent of damage in animal subjects and guide the decision-making process during treatment planning.

Novel prognostic biomarkers in decompensated cirrhosis: a systematic review and meta-analysis.

BACKGROUND: Patients with decompensated cirrhosis experience high mortality rates. Current prognostic scores, including the model for end-stage liver disease (MELD), may underperform in settings other than in those they were initially developed. Novel biomarkers have been proposed to improve prognostication accuracy and even to predict development of complications. METHODS: We performed a systematic review and meta-analysis on novel urine and blood biomarkers and their ability to predict 90-day mortality in patients with decompensated cirrhosis. Secondary outcomes included 28-day and 1-year mortality, and development of acute-on-chronic liver failure, acute kidney injury and other complications. To overcome differences in units, temporal changes in assays and reporting heterogeneity, we used the ratio of means (RoM) as measure of association for assessing strength in predicting outcomes. An RoM>1 implies that the mean biomarker level is higher in those that develop the outcome than in those that do not. RESULTS: Of 6629 unique references, 103 were included, reporting on 29 different biomarkers, with a total of 31 362 biomarker patients. Most studies were prospective cohorts of hospitalised patients (median Child-Pugh-Turcotte score of 9 and MELD score of 18). The pooled 90-day mortality rate was 0.27 (95% CI 0.24 to 0.29). The RoM for predicting 90-day mortality was highest for interleukin 6 (IL-6) (2.56, 95% CI 2.39 to 2.74), followed by urinary neutrophil gelatinase-associated lipocalin (uNGAL) (2.42, 95% CI 2.20 to 2.66) and copeptin (2.33, 95% CI 2.17 to 2.50). These RoMs were all higher than for MELD (1.44, 95% CI 1.42 to 1.46). CONCLUSION: Novel biomarkers, including IL-6, uNGAL and copeptin, can probably improve prognostication of patients with decompensated cirrhosis compared with MELD alone.

Bilateral renal histiocytic sarcoma with disseminated lung involvement in a Siberian Forest Cat.

Case summary: A 5-year-old female neutered Siberian Forest Cat presented with a 7-day history of lethargy, hyporexia and weight loss. Abdominal ultrasonography revealed bilateral renal changes suggestive of neoplasia. Thoracic radiography documented diffuse pulmonary nodules. The cat was euthanased during diagnostic investigations. Histopathological assessment and immunohistochemical staining of post-mortem renal biopsies were consistent with a histiocytic lesion, most likely histiocytic sarcoma (HS). The lung lesions were suspected of representing disseminated disease. Relevance and novel information: HS is considered a rare neoplastic process in cats. This report describes a case of feline bilateral renal HS with suspected concomitant pulmonary involvement. A primary renal origin was suspected, with the lung lesions being a result of disseminated disease. Renal HS should be included as a differential diagnosis when renal ultrasonography reveals changes suggestive of neoplasia.

Management of Mechanical Prosthetic Heart Valve Thrombosis: JACC Review Topic of the Week.

Mechanical prosthetic heart valves, though more durable than bioprostheses, are more thrombogenic and require lifelong anticoagulation. Mechanical valve dysfunction can be caused by 4 main phenomena: 1) thrombosis; 2) fibrotic pannus ingrowth; 3) degeneration; and 4) endocarditis. Mechanical valve thrombosis (MVT) is a known complication with clinical presentation ranging from incidental imaging finding to cardiogenic shock. Thus, a high index of suspicion and expedited evaluation are essential. Multimodality imaging, including echocardiography, cine-fluoroscopy, and computed tomography, is commonly used to diagnose MVT and follow treatment response. Although surgery is oftentimes required for obstructive MVT, other guideline-recommended therapies include parenteral anticoagulation and thrombolysis. Transcatheter manipulation of stuck mechanical valve leaflet is another treatment option for those with contraindications to thrombolytic therapy or prohibitive surgical risk or as a bridge to surgery. The optimal strategy depends on degree of valve obstruction and the patient's comorbidities and hemodynamic status on presentation.

Sympathetic nervous activation, mitochondrial dysfunction and outcome in acutely decompensated cirrhosis: the metabolomic prognostic models (CLIF-C MET).

BACKGROUND AND AIMS: Current prognostic scores of patients with acutely decompensated cirrhosis (AD), particularly those with acute-on-chronic liver failure (ACLF), underestimate the risk of mortality. This is probably because systemic inflammation (SI), the major driver of AD/ACLF, is not reflected in the scores. SI induces metabolic changes, which impair delivery of the necessary energy for the immune reaction. This investigation aimed to identify metabolites associated with short-term (28-day) death and to design metabolomic prognostic models. METHODS: Two prospective multicentre large cohorts from Europe for investigating ACLF and development of ACLF, CANONIC (discovery, n=831) and PREDICT (validation, n=851), were explored by untargeted serum metabolomics to identify and validate metabolites which could allow improved prognostic modelling. RESULTS: Three prognostic metabolites strongly associated with death were selected to build the models. 4-Hydroxy-3-methoxyphenylglycol sulfate is a norepinephrine derivative, which may be derived from the brainstem response to SI. Additionally, galacturonic acid and hexanoylcarnitine are associated with mitochondrial dysfunction. Model 1 included only these three prognostic metabolites and age. Model 2 was built around 4-hydroxy-3-methoxyphenylglycol sulfate, hexanoylcarnitine, bilirubin, international normalised ratio (INR) and age. In the discovery cohort, both models were more accurate in predicting death within 7, 14 and 28 days after admission compared with MELDNa score (C-index: 0.9267, 0.9002 and 0.8424, and 0.9369, 0.9206 and 0.8529, with model 1 and model 2, respectively). Similar results were found in the validation cohort (C-index: 0.940, 0.834 and 0.791, and 0.947, 0.857 and 0.810, with model 1 and model 2, respectively). Also, in ACLF, model 1 and model 2 outperformed MELDNa 7, 14 and 28 days after admission for prediction of mortality. CONCLUSIONS: Models including metabolites (CLIF-C MET) reflecting SI, mitochondrial dysfunction and sympathetic system activation are better predictors of short-term mortality than scores based only on organ dysfunction (eg, MELDNa), especially in patients with ACLF.

Tratamiento endovascular con técnica de chimenea para patologías del arco aórtico / Endovascular management with chimney technique for pathologies ofthe aortic arch

Introducción. La patología del arco aórtico se ha tratado principalmente con cirugía por vía abierta, pero con una alta morbimortalidad. Las técnicas endovasculares híbridas y las reconstrucciones en "chimenea" son una técnica válida y segura para disminuir el riesgo y la mortalidad. Métodos. Se presentan dos pacientes con patología del arco aórtico y contraindicación de manejo quirúrgico abierto, atendidos en el Servicio de Cirugía Vascular, Hospital Universitario Clínica de San Rafael, Bogotá, D.C., Colombia. Resultados. Se realizaron dos procedimientos endovasculares del arco aórtico para tratar un aneurisma torácico roto y una úlcera aórtica sintomática, con cubrimiento de los troncos supra aórticos con una endoprótesis y canalización de los vasos supra aórticos con prótesis cubiertas y uso de la "técnica de chimenea", de manera exitosa. Discusión. La patología del arco aórtico es de alta complejidad y se asocia con una morbimortalidad elevada por lo que, en los últimos 20 años se han desarrollado diferentes técnicas utilizando procedimientos percutáneos. Conclusión. La "técnica de chimenea" se puede realizar de una manera mínimamente invasiva en pacientes con patología del arco aórtico, no candidatos para cirugía abierta, con resultados exitosos.

Introduction. Aortic arch pathology has been treated mainly by open surgery, but with high morbidity and mortality. Hybrid endovascular techniques and "chimney" reconstructions are a valid and safe techniques to reduce risk and mortality. Method. Two patients with pathology of the aortic arch and contraindication for open surgical management, treated at the Vascular Surgery Service, Hospital Universitario Clínica de San Rafael, Bogotá, Colombia, are presented. Results. Two endovascular aortic procedures were performed successfully to treat a ruptured thoracic aneurysm and a symptomatic aortic ulcer, with coverage of the supra-aortic trunks with an endoprosthesis and cannulation of the supra-aortic vessels with covered prostheses and use of the "chimney technique". Discussion. The pathology of the aortic arch is highly complex and is associated with high morbidity and mortality, being the reason that during the last 20 years, different techniques have been developed using percutaneous procedures. Conclusions. The "chimney technique" can be performed with successful results in a minimally invasive manner in patients with pathology of the aortic arch, who are not candidates for open surgery

Severity of gastrointestinal bleeding is similar between patients receiving direct oral anticoagulants or vitamin K antagonists

Background: gastrointestinal bleeding (GIB) is a commonadverse event related to anticoagulation therapy. However,evidence comparing the severity, etiology and outcome ofGIB in patients taking direct oral anticoagulants (DOAC) vs.vitamin K antagonists (VKA) is scarce.Aim: to evaluate the severity, etiology and outcomes of GIBin patients under DOACs compared to VKA.Methods: patients under oral anticoagulant therapy admitted to the emergency department with acute GIB wereprospectively recruited from July 2016 to January 2018 ata tertiary referral hospital. Demographic and clinical out comes were obtained from medical records. GIB severitywas classified as mild, major, or severe according to theclinical presentation and type of support needed. Etiologyand location of bleeding, number of packed red blood cells(PRBC) transfused, and length of hospital stay were recorded until discharge or in-hospital death.Results: a total of 208 patients with acute GIB under oralanticoagulant treatment were recruited: 119 patients wereon VKA and 89 patients on DOAC, with similar characteristics. Thirty-one patients had severe GIB; 134 had major and43 had mild GIB, with no differences in severity, numberof PRBC, and length of hospital stay between the groups.Peptic disease was the most frequent etiology of GIB inpatients on VKA (20.2 % vs. 13.6 %, p = 0.20). Diverticularbleeding was the most frequent adverse event in patientson DOAC (14.3 % vs. 24.8 %, p = 0.056).Conclusions: severity and clinical outcomes of GIB aresimilar between patients on DOAC and patients on VKA,regardless of GIB etiology. (AU)

Lifetime management of patients with symptomatic severe aortic stenosis: a computed tomography simulation study.

BACKGROUND: Given enough time, transcatheter heart valves (THVs) will degenerate and may require reintervention. Redo transcatheter aortic valve implantation (TAVI) is an attractive strategy but carries a risk of coronary obstruction. AIMS: We sought to predict how many TAVIs patients could undergo in their lifetime using computed tomography (CT) simulation. METHODS: We analysed paired CT scans (baseline and 30 days post-TAVI) from patients in the LRT trial and EPROMPT registry. We implanted virtual THVs on baseline CTs, comparing predicted valve-to-coronary (VTC) distances to 30-day CT VTC distances to evaluate the accuracy of CT simulation. We then simulated implantation of a second virtual THV within the first to estimate the risk of coronary obstruction due to sinus sequestration and the need for leaflet modification. RESULTS: We included 213 patients with evaluable paired CTs. There was good agreement between virtual (baseline) and actual (30 days) CT measurements. CT simulation of TAVI followed by redo TAVI predicted low coronary obstruction risk in 25.4% of patients and high risk, likely necessitating leaflet modification, in 27.7%, regardless of THV type. The remaining 46.9% could undergo redo TAVI so long as the first THV was balloon-expandable but would likely require leaflet modification if the first THV was self-expanding. CONCLUSIONS: Using cardiac CT simulation, it is possible to predict whether a patient can undergo multiple TAVI procedures in their lifetime. Those who cannot may prefer to undergo surgery first. CT simulation could provide a personalised lifetime management strategy for younger patients with symptomatic severe aortic stenosis and inform decision-making. CLINICALTRIALS: gov: NCT02628899; ClinicalTrials.gov: NCT03557242; ClinicalTrials.gov: NCT03423459.

Effect of rifaximin on infections, acute-on-chronic liver failure and mortality in alcoholic hepatitis: A pilot study (RIFA-AH).

BACKGROUND & AIMS: Alcoholic hepatitis (AH) is associated with a high incidence of infection and mortality. Rifaximin reduces bacterial overgrowth and translocation. We aimed to study whether the administration of rifaximin as an adjuvant treatment to corticosteroids decreases the number of bacterial infections at 90 days in patients with severe AH compared to a control cohort. METHODS: This was a multicentre, open, comparative pilot study of the addition of rifaximin (1200 mg/day/90 days) to the standard treatment for severe AH. The results were compared with a carefully matched historical cohort of patients treated with standard therapy and matching by age and model of end-stage liver disease (MELD). We evaluated bacterial infections, liver-related complications, mortality and liver function tests after 90 days. RESULTS: Twenty-one and 42 patients were included in the rifaximin and control groups respectively. No significant baseline differences were found between groups. The mean number of infections per patient was 0.29 and 0.62 in the rifaximin and control groups, respectively (p = .049), with a lower incidence of acute-on-chronic liver failure (ACLF) linked to infections within the treatment group. Liver-related complications were lower within the rifaximin group (0.43 vs. 1.26 complications/patient respectively) (p = .01). Mortality was lower in the treated versus the control groups (14.2% vs. 30.9, p = .15) without significant differences. No serious adverse events were associated with rifaximin treatment. CONCLUSIONS: Rifaximin is safe in severe AH with a significant reduction in clinical complications. A lower number of infections and a trend towards a lower ACLF and mortality favours its use in these patients.

Severity of gastrointestinal bleeding is similar between patients receiving direct oral anticoagulants or vitamin K antagonists.

BACKGROUND: Gastrointestinal bleeding (GIB) is a common adverse event related to anticoagulation therapy. However, evidence comparing the severity, etiology and outcome of GIB in patients taking direct oral anticoagulants (DOAC) vs. vitamin K antagonists (VKA) is scarce. AIMS: To evaluate the severity, etiology and outcomes of GIB in patients under DOACs compared to VKA. METHODS: Patients under oral anticoagulant therapy admitted to the emergency department with acute GIB were prospectively recruited from July 2016 to January 2018 at a tertiary referral hospital. Demographic and clinical outcome were obtained from medical records. Severity of the GIB event was classified as mild, major or severe according to clinical presentation and the type of support needed. Etiology and location of bleeding, number of packed red blood cells transfused (PRBC) and length of hospital stay were recorded until discharge or in-hospital death. RESULTS: A total of 208 patients with acute GIB under oral anticoagulant treatment were recruited: 119 patients were on VKA and 89 patients on DOAC with similar characteristics. Thirty-one patients had severe GIB; 134 major and 43 mild, with no differences in severity, number of PRBC and length of hospital stay between the groups. Peptic disease was the most frequent etiology of GIB in patients on VKA (20.2 % vs. 13.6%, p=0.20). Diverticular bleeding was the most frequent adverse event in patients on DOAC (14.3% vs. 24.8%, p= 0.056). CONCLUSIONS: Severity and clinical outcomes of GIB are similar between patients on DOAC and patients on VKA, regardless of etiology of GIB.

Treatment With Simvastatin and Rifaximin Restores the Plasma Metabolomic Profile in Patients With Decompensated Cirrhosis.

Patients with decompensated cirrhosis, particularly those with acute-on-chronic liver failure (ACLF), show profound alterations in plasma metabolomics. The aim of this study was to investigate the effect of treatment with simvastatin and rifaximin on plasma metabolites of patients with decompensated cirrhosis, specifically on compounds characteristic of the ACLF plasma metabolomic profile. Two cohorts of patients were investigated. The first was a descriptive cohort of patients with decompensated cirrhosis (n = 42), with and without ACLF. The second was an intervention cohort from the LIVERHOPE-SAFETY randomized, double-blind, placebo-controlled trial treated with simvastatin 20 mg/day plus rifaximin 1,200 mg/day (n = 12) or matching placebo (n = 13) for 3 months. Plasma samples were analyzed using ultrahigh performance liquid chromatography-tandem mass spectroscopy for plasma metabolomics characterization. ACLF was characterized by intense proteolysis and lipid alterations, specifically in pathways associated with inflammation and mitochondrial dysfunction, such as the tryptophan-kynurenine and carnitine beta-oxidation pathways. An ACLF-specific signature was identified. Treatment with simvastatin and rifaximin was associated with changes in 161 of 985 metabolites in comparison to treatment with placebo. A remarkable reduction in levels of metabolites from the tryptophan-kynurenine and carnitine pathways was found. Notably, 18 of the 32 metabolites of the ACLF signature were affected by the treatment. Conclusion: Treatment with simvastatin and rifaximin modulates some of the pathways that appear to be key in ACLF development. This study unveils some of the mechanisms involved in the effects of treatment with simvastatin and rifaximin in decompensated cirrhosis and sets the stage for the use of metabolomics to investigate new targeted therapies in cirrhosis to prevent ACLF development.

Controlled simultaneous iontophoresis of buflomedil hydrochloride and dexamethasone sodium phosphate to the mucosa for oral submucous fibrosis.

A novel concentric experimental set-up was used to investigate short-duration topical co-iontophoresis of cationic buflomedil hydrochloride (BUF) and anionic dexamethasone phosphate (DEX-P) to the oral mucosa. A constant current of 3.0 mA (0.6 mA/cm2 for BUF and 1.95 mA/cm2 for DEX-P) was applied to porcine esophageal mucosa for 5, 10 and 20 min. Iontophoresis for only 5 min increased total delivery of BUF from 29.8 ± 5.1 nmol/cm2 to 194.3 ± 23.8 nmol/cm2 and DEX-P from 29.4 ± 1.2 nmol/cm2 to 193.3 ± 19.8 nmol/cm2 as compared to passive controls. Quantification of drug between the electrode compartments reported on lateral ion migration. In the absence of current, DEX-P did not migrate laterally; however, iontophoresis for 5 min increased DEX-P delivery >5-fold under the cathodal compartment (its application area) and >8-fold in the adjacent "inter-electrode" area. Similarly, delivery of BUF increased ~6.8-fold under the anodal compartment and ~12.8-fold under the cathode. The results showed that co-iontophoresis enabled the controlled simultaneous delivery of BUF and DEX-P achieving therapeutically relevant concentrations after current application for only 5 min. Short duration topical co-iontophoresis of single or multiple therapeutics to the mucosa increases local bioavailability and presents a patient-friendly treatment for diseases of the oral cavity.

The role of liver steatosis as measured with transient elastography and transaminases on hard clinical outcomes in patients with COVID-19.

Liver injury has been widely described in patients with Coronavirus disease 2019 (COVID-19). We aimed to study the effect of liver biochemistry alterations, previous liver disease, and the value of liver elastography on hard clinical outcomes in COVID-19 patients. We conducted a single-center prospective observational study in 370 consecutive patients admitted for polymerase chain reaction (PCR)-confirmed COVID-19 pneumonia. Clinical and laboratory data were collected at baseline and liver parameters and clinical events recorded during follow-up. Transient elastography [with Controlled Attenuation Parameter (CAP) measurements] was performed at admission in 98 patients. All patients were followed up until day 28 or death. The two main outcomes of the study were 28-day mortality and the occurrence of the composite endpoint intensive care unit (ICU) admission and/or death. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels were elevated at admission in 130 patients (35%) and 167 (45%) patients, respectively. Overall, 14.6% of patients presented the composite endpoint ICU and/or death. Neither ALT elevations, prior liver disease, liver stiffness nor liver steatosis (assessed with CAP) had any effect on outcomes. However, patients with abnormal baseline AST had a higher occurrence of the composite ICU/death (21% versus 9.5%, p = 0.002). Patients ⩾65 years and with an AST level > 50 U/ml at admission had a significantly higher risk of ICU and/or death than those with AST ⩽ 50 U/ml (50% versus 13.3%, p < 0.001). In conclusion, mild liver damage is prevalent in COVID-19 patients, but neither ALT elevation nor liver steatosis influenced hard clinical outcomes. Elevated baseline AST is a strong predictor of hard outcomes, especially in patients ⩾65 years.

Trombosis venosa portal extrahepática, manejo quirúrgico con derivación meso-Rex. Serie de 3 casos / Extrahepatic portal vein thrombosis, surgical management with meso-Rex shunt. Series of 3 cases

La vena porta es un conducto que drena el flujo esplácnico al hígado y se puede ocluir por diferentes patologías, variando su presentación clínica de acuerdo con la causa de la obstrucción. Es muy importante diferenciar la trombosis portal asociada o no a la cirrosis, ya que su tratamiento y pronóstico es diferente. La trombosis venosa portal extrahepática es una condición netamente de origen vascular, y es la principal causa de trombosis portal en niños y adultos. Presentamos tres casos tratados con derivación meso-Rex, con seguimiento a 6 meses

The portal vein is a conduit that drains splanchnic flow to the liver, it can be occluded by different pathologies and its clinical presentation varies according to the cause of the obstruction. It is very important to differentiate portal thrombosis associated or not with cirrhosis, since its treatment and prognosis is different. Extrahepatic portal vein thrombosis (PEVT) is a condition of purely vascular origin, being the main cause of portal thrombosis in children and adults. We present three cases with meso-Rex shunt, with a 6-month follow-up

PREDICT identifies precipitating events associated with the clinical course of acutely decompensated cirrhosis.

BACKGROUND & AIMS: Acute decompensation (AD) of cirrhosis may present without acute-on-chronic liver failure (ACLF) (AD-No ACLF), or with ACLF (AD-ACLF), defined by organ failure(s). Herein, we aimed to analyze and characterize the precipitants leading to both of these AD phenotypes. METHODS: The multicenter, prospective, observational PREDICT study (NCT03056612) included 1,273 non-electively hospitalized patients with AD (No ACLF = 1,071; ACLF = 202). Medical history, clinical data and laboratory data were collected at enrolment and during 90-day follow-up, with particular attention given to the following characteristics of precipitants: induction of organ dysfunction or failure, systemic inflammation, chronology, intensity, and relationship to outcome. RESULTS: Among various clinical events, 4 distinct events were precipitants consistently related to AD: proven bacterial infections, severe alcoholic hepatitis, gastrointestinal bleeding with shock and toxic encephalopathy. Among patients with precipitants in the AD-No ACLF cohort and the AD-ACLF cohort (38% and 71%, respectively), almost all (96% and 97%, respectively) showed proven bacterial infection and severe alcoholic hepatitis, either alone or in combination with other events. Survival was similar in patients with proven bacterial infections or severe alcoholic hepatitis in both AD phenotypes. The number of precipitants was associated with significantly increased 90-day mortality and was paralleled by increasing levels of surrogates for systemic inflammation. Importantly, adequate first-line antibiotic treatment of proven bacterial infections was associated with a lower ACLF development rate and lower 90-day mortality. CONCLUSIONS: This study identified precipitants that are significantly associated with a distinct clinical course and prognosis in patients with AD. Specific preventive and therapeutic strategies targeting these events may improve outcomes in patients with decompensated cirrhosis. LAY SUMMARY: Acute decompensation (AD) of cirrhosis is characterized by a rapid deterioration in patient health. Herein, we aimed to analyze the precipitating events that cause AD in patients with cirrhosis. Proven bacterial infections and severe alcoholic hepatitis, either alone or in combination, accounted for almost all (96-97%) cases of AD and acute-on-chronic liver failure. Whilst the type of precipitant was not associated with mortality, the number of precipitant(s) was. This study identified precipitants that are significantly associated with a distinct clinical course and prognosis of patients with AD. Specific preventive and therapeutic strategies targeting these events may improve patient outcomes.

The PREDICT study uncovers three clinical courses of acutely decompensated cirrhosis that have distinct pathophysiology.

BACKGROUND & AIMS: Acute decompensation (AD) of cirrhosis is defined as the acute development of ascites, gastrointestinal hemorrhage, hepatic encephalopathy, infection or any combination thereof, requiring hospitalization. The presence of organ failure(s) in patients with AD defines acute-on-chronic liver failure (ACLF). The PREDICT study is a European, prospective, observational study, designed to characterize the clinical course of AD and to identify predictors of ACLF. METHODS: A total of 1,071 patients with AD were enrolled. We collected detailed pre-specified information on the 3-month period prior to enrollment, and clinical and laboratory data at enrollment. Patients were then closely followed up for 3 months. Outcomes (liver transplantation and death) at 1 year were also recorded. RESULTS: Three groups of patients were identified. Pre-ACLF patients (n = 218) developed ACLF and had 3-month and 1-year mortality rates of 53.7% and 67.4%, respectively. Unstable decompensated cirrhosis (UDC) patients (n = 233) required ≥1 readmission but did not develop ACLF and had mortality rates of 21.0% and 35.6%, respectively. Stable decompensated cirrhosis (SDC) patients (n = 620) were not readmitted, did not develop ACLF and had a 1-year mortality rate of only 9.5%. The 3 groups differed significantly regarding the grade and course of systemic inflammation (high-grade at enrollment with aggravation during follow-up in pre-ACLF; low-grade at enrollment with subsequent steady-course in UDC; and low-grade at enrollment with subsequent improvement in SDC) and the prevalence of surrogates of severe portal hypertension throughout the study (high in UDC vs. low in pre-ACLF and SDC). CONCLUSIONS: Acute decompensation without ACLF is a heterogeneous condition with 3 different clinical courses and 2 major pathophysiological mechanisms: systemic inflammation and portal hypertension. Predicting the development of ACLF remains a major future challenge. CLINICALTRIALS. GOV NUMBER: NCT03056612. LAY SUMMARY: Herein, we describe, for the first time, 3 different clinical courses of acute decompensation (AD) of cirrhosis after hospital admission. The first clinical course includes patients who develop acute-on-chronic liver failure (ACLF) and have a high short-term risk of death - termed pre-ACLF. The second clinical course (unstable decompensated cirrhosis) includes patients requiring frequent hospitalizations unrelated to ACLF and is associated with a lower mortality risk than pre-ACLF. Finally, the third clinical course (stable decompensated cirrhosis), includes two-thirds of all patients admitted to hospital with AD - patients in this group rarely require hospital admission and have a much lower 1-year mortality risk.