Development and Validation of a Scoring System to Predict Response to Obeticholic Acid in Primary Biliary Cholangitis.

BACKGROUND & AIMS: Obeticholic acid (OCA) is the only licensed second-line therapy for primary biliary cholangitis (PBC). With novel therapeutics in advanced development, clinical tools are needed to tailor the treatment algorithm. We aimed to derive and externally validate the OCA response score (ORS) for predicting the response probability of individuals with PBC to OCA. METHODS: We used data from the Italian RECAPITULATE (N = 441) and the IBER-PBC (N = 244) OCA real-world prospective cohorts to derive/validate a score including widely available variables obtained either pre-treatment (ORS) or also after 6 months of treatment (ORS+). Multivariable Cox regressions with backward selection were applied to obtain parsimonious predictive models. The predicted outcomes were biochemical response according to POISE (alkaline phosphatase [ALP]/upper limit of normal [ULN]<1.67 with a reduction of at least 15%, and normal bilirubin), or ALP/ULN<1.67, or Normal range criteria (NR: normal ALP, alanine aminotransferase [ALT], and bilirubin) up to 24 months. RESULTS: Depending on the response criteria, ORS included age, pruritus, cirrhosis, ALP/ULN, ALT/ULN, GGT/ULN, and bilirubin. ORS+ also included ALP/ULN and bilirubin after 6 months of OCA therapy. Internally validated c-statistics for ORS were 0.75, 0.78, and 0.72 for POISE, ALP/ULN<1.67, and NR response, which raised to 0.83, 0.88, and 0.81 with ORS+, respectively. The respective performances in validation were 0.70, 0.72, and 0.71 for ORS and 0.80, 0.84, and 0.78 for ORS+. Results were consistent across groups with mild/severe disease. CONCLUSIONS: We developed and externally validated a scoring system capable to predict OCA response according to different criteria. This tool will enhance a stratified second-line therapy model to streamline standard care and trial delivery in PBC.

Long-term safety and efficacy results in hepatitis C virus genotype 1-infected patients receiving ombitasvir/paritaprevir/ritonavir + dasabuvir ± ribavirin in the TOPAZ-I and TOPAZ-II trials.

The 3-DAA regimen consisting of ombitasvir/paritaprevir/ritonavir plus dasabuvir (OBV/PTV/r + DSV) ± ribavirin (RBV) has shown high sustained virologic response rates (~95%) in phase 3 clinical trials including >2300 HCV genotype 1-infected patients. Real-world evidence studies have confirmed the effectiveness of OBV/PTV/r ± DSV ± RBV in patients with chronic HCV genotype 1 infection and are consistent with clinical trial results. TOPAZ-I and TOPAZ-II are ongoing phase 3b trials, assessing safety, efficacy and long-term progression of liver disease and clinical outcomes for up to 5 years post-treatment in patients treated with OBV/PTV/r + DSV ± RBV. High rates of sustained virologic response (SVR) were achieved regardless of presence or absence of cirrhosis.In this report, we assessed the long-term progression of liver disease and incidence of clinical outcomes up to 3 years of post-treatment follow-up in patients with chronic HCV GT1 infection who were treated with (OBV/PTV/r + DSV) ± RBV in the TOPAZ-I and TOPAZ-II studies. Improvements were observed in liver disease markers including FIB-4, METAVIR and Child-Pugh scores as well as platelet counts. Clinical outcomes related to long-term progression of liver disease such as liver decompensation were infrequent (<1%). Hepatocellular carcinoma (HCC) occurred in 1.4% of cirrhotic patients.

Prevalence and risk factors of fatty liver in Portuguese adults.

BACKGROUND: Prevalence of fatty liver (FL) and nonalcoholic fatty liver disease (NAFLD) depends mainly on obesity, diabetes and genetic factors. FL and NAFLD prevalence was evaluated in Portuguese adult population and correlated with several risk factors and related mortality data, within the same period. MATERIALS AND METHODS: A cross-sectional, population-based multicenter study, voluntary and randomly selected in 834 Portuguese adults (18-79 years). Participants were evaluated after 12-hour fasting. Anthropometric data, past history including alcohol consumption, and associated diseases were registered. Blood samples were collected for biochemical testing. Dietary intake was evaluated using a semi-quantitative food frequency questionnaire. Presence of FL was evaluated using ultrasound, and NAFLD was diagnosed after exclusion of other causes for liver disease. RESULTS: Adjusted prevalence of FL and NAFLD was 37.8% and 17.0%, respectively. FL individuals were older, more frequently males, with increased probability of having obesity, diabetes or harmful alcohol consumption (HAC). NAFLD individuals were also older, but had a similar sex distribution and an increased probability of obesity and diabetes. In both groups, no differences were found regarding dietary pattern or physical activity. During the same time period, nonalcoholic steatohepatitis (NASH) liver-related deaths in Portugal were 0.105/100 000, while alcohol-related liver disease mortality was 6.790/100 000. CONCLUSION: The large spectrum of FL was present in more than one third of the population, although only less than half could be classified as NAFLD. Other significant risk factors, such as HAC, are probably implicated in FL, explaining the low NASH-related mortality compared with the high alcohol-related mortality during the same time period.

No Evidence for Lower Levels of Serum Vitamin D in the Presence of Hepatic Steatosis. A Study on the Portuguese General Population.

Introduction and aims: Nonalcoholic fatty liver disease (NAFLD) has become highly prevalent, paralleling the pandemic of obesity and diabetes, and represents an important burden. Nutrition knowledge is fundamental, in prevention, evolution and treatment of NAFLD. Association of low serum levels of vitamin D (VD) with several diseases, including NAFLD, has been emphasized in the last decade. We evaluated how serum levels of VD correlate with the presence of hepatic steatosis, and VD intake, in a random sample of the Portuguese adult population. Methods: Participants underwent a dietary intake inquiry, using a semi-quantitative food frequency questionnaire representative of the usual intake over the previous year. Anthropometric measures, blood tests and ultrasound were done. Hepatic steatosis was quantified according to Hamaguchi's ultrasonographic score (steatosis defined by a score ≥ 2). Results: We recruited 789 adult individuals, 416 males (52.7%), mean age of 49.9 ± 17.0 years (18-79). Prevalence of hepatic steatosis was 35.5%, and after exclusion of excessive alcohol consumption, 28.0%. Mean VD serum levels were 26.0 ± 9.8 ng/ml and 68.4% participants had serum VD levels below 30 ng/ml. Mean serum levels of VD were not significantly different between participants with steatosis vs. no steatosis: 25.2±8.7 vs. 26.4±10.3 ng/ml, respectively (p=0.071). There was no correlation between VD serum levels and VD intake, measured by the FFQ, r=0.075 (p= 0.383). Conclusions: In spite of a high prevalence rate, there was no evidence that decreased VD serum levels were associated with hepatic steatosis. No significant correlation was found between VD dietary ingestion and VD serum levels.

A New Paradigm in Gallstones Diseases and Marked Elevation of Transaminases: An Observational Study.

BACKGROUND: In clinical practice, it is assumed that a severe rise in transaminases is caused by ischemic, viral or toxic hepatitis. Nevertheless, cases of biliary obstruction have increasingly been associated with significant hypertransaminemia. With this study, we sought to determine the true etiology of marked rise in transaminases levels, in the context of an emergency department. MATERIAL AND METHODS: We retrospectively identified all patients admitted to the emergency unit at Centro Hospitalar e Universitário de Coimbra between 1st January 2010 and 31st December 2010, displaying an increase of at least one of the transaminases by more than 15 times. All patient records were analyzed in order to determine the cause of hypertransaminemia. RESULTS: We analyzed 273 patients - 146 males, mean age 65.1 ± 19.4 years. The most frequently etiology found for marked hypertransaminemia was pancreaticobiliary acute disease (n = 142;39.4%), mostly lithiasic (n = 113;79.6%), followed by malignancy (n = 74;20.6%), ischemic hepatitis (n = 61;17.0%), acute primary hepatocellular disease (n = 50;13.9%) and muscle damage (n = 23;6.4%). We were not able to determine a diagnosis for 10 cases. There were 27 cases of recurrence in the lithiasic pancreaticobiliary pathology group. Recurrence was more frequent in the group of patients who had not been submitted to early cholecystectomy after the first episode of biliary obstruction (p = 0.014). The etiology of hypertransaminemia varied according to age, cholestasis and glutamic-pyruvic transaminase values. CONCLUSION: Pancreaticobiliary lithiasis is the main cause of marked hypertransaminemia. Hence, it must be considered when dealing with such situations. Not performing cholecystectomy early on, after the first episode of biliary obstruction, may lead to recurrence.

Plasma osteopontin is a biomarker for the severity of alcoholic liver cirrhosis, not for hepatocellular carcinoma screening.

BACKGROUND: Implementation of surveillance programs for at-risk populations and identification of biomarkers for early hepatocellular carcinoma (HCC) detection are a major public health goal. Recently, osteopontin (OPN) has attracted attention as a promising biomarker, with some potential advantages compared to alpha-fetoprotein (AFP), but its role in the context of alcoholic cirrhosis has never been assessed. The aims of this study are to assess the utility of plasma OPN in the diagnosis of HCC in alcoholic cirrhotic patients and to investigate whether increased values are due to the tumor or underlying liver disease severity. METHODS: A total of 90 consecutively alcoholic cirrhosis patients, observed between Jun 2013 and May 2014 at a Liver Disease Unit, were included and divided into two groups: 45 without (group I) and 45 with HCC (group II). Plasma levels of OPN (ELISA, Immuno-Biological Laboratories, Gunma, Japan) and AFP (IMMULITE® 2000 AFP, Siemens Healthcare Diagnostics, Tarrytown, New York) were assessed. The diagnostic accuracy of each marker was evaluated using Receiver-Operating Characteristic (ROC) curve analysis (AUC) and its 95 % Confidence Interval (CI). RESULTS: Plasma OPN levels in group I patients (1176.28 +/-744.59 ng/mL) weren't significantly different from those of group II (1210.75 +/-800.60 ng/mL) (p = 0.826). OPN levels significantly increased with advancing BCLC tumor stage and with advancing Child-Pugh class, in both groups. Comparing the two groups, AUC for OPN and AFP were 0.51 (95 % CI: 0.39-0.63) and 0.79 (95 % CI: 0.70-0.89), respectively. Based on the ROC analysis, there were no satisfactory cut-off values for OPN that would distinguish patients with from those without tumour. CONCLUSIONS: Despite having a correlation with BCLC stage, the same was observed with progressive deterioration of underlying liver function in terms of Child-Pugh class and MELD score, and isn't a useful diagnostic biomarker for HCC in alcoholic cirrhotic patients, particularly in the early stages. AFP confirms the performance evidenced in other studies, being superior to OPN. Searching more specific biomarkers for early diagnosis of HCC in alcoholic cirrhosis is still warranted.

A new cluster-based oversampling method for improving survival prediction of hepatocellular carcinoma patients.

Liver cancer is the sixth most frequently diagnosed cancer and, particularly, Hepatocellular Carcinoma (HCC) represents more than 90% of primary liver cancers. Clinicians assess each patient's treatment on the basis of evidence-based medicine, which may not always apply to a specific patient, given the biological variability among individuals. Over the years, and for the particular case of Hepatocellular Carcinoma, some research studies have been developing strategies for assisting clinicians in decision making, using computational methods (e.g. machine learning techniques) to extract knowledge from the clinical data. However, these studies have some limitations that have not yet been addressed: some do not focus entirely on Hepatocellular Carcinoma patients, others have strict application boundaries, and none considers the heterogeneity between patients nor the presence of missing data, a common drawback in healthcare contexts. In this work, a real complex Hepatocellular Carcinoma database composed of heterogeneous clinical features is studied. We propose a new cluster-based oversampling approach robust to small and imbalanced datasets, which accounts for the heterogeneity of patients with Hepatocellular Carcinoma. The preprocessing procedures of this work are based on data imputation considering appropriate distance metrics for both heterogeneous and missing data (HEOM) and clustering studies to assess the underlying patient groups in the studied dataset (K-means). The final approach is applied in order to diminish the impact of underlying patient profiles with reduced sizes on survival prediction. It is based on K-means clustering and the SMOTE algorithm to build a representative dataset and use it as training example for different machine learning procedures (logistic regression and neural networks). The results are evaluated in terms of survival prediction and compared across baseline approaches that do not consider clustering and/or oversampling using the Friedman rank test. Our proposed methodology coupled with neural networks outperformed all others, suggesting an improvement over the classical approaches currently used in Hepatocellular Carcinoma prediction models.

Chest pain in the emergency department: risk stratification with Manchester triage system and HEART score.

BACKGROUND: Fast and accurate chest pain risk stratification in the emergency department (ED) is critical. The HEART score predicts the short-term incidence of major adverse cardiac events (MACE) in this population, dividing it in three risk categories. We aimed to describe the population with chest pain, to characterize the subgroup of patients with acute coronary syndrome (ACS) and to assess the prognostic value of Manchester triage system and of HEART score. METHODS: Retrospective observational study including patients admitted to the ED of a tertiary hospital with chest pain as the presenting symptom. The primary outcome was a composite of all-cause mortality, myocardial infarction or unscheduled revascularization at 6 weeks. RESULTS: We enrolled 233 patients (age 58 ± 19; 55.4 % males). The most common final diagnosis was non-specific chest pain (n = 86, 36.9 %), followed by ACS (n = 22, 9.4 %). Male gender, smoking and chronic kidney disease were associated with higher risk of ACS. According to Manchester triage system, chest pain patients stratified with red or orange priority had a higher incidence of ACS (16.5 % vs. 3.8 %, p = 0.006). The application of HEART score showed that most patients were in low risk category (56.3 %). The six-week incidence of MACE in each category was 2 %, 15.6 % and 76.9 % (p < 0.001). HEART score accurately predicted the short-term incidence of MACE in chest pain patients (c-statistic 0.880; 95 % CI, 0.807-0.950, p < 0.001). CONCLUSIONS: Chest pain patients have very different levels of severity and the discriminatory power of Manchester triage system should be used in the assessment of this population. The HEART score seems to be an effective tool for risk stratification in the ED.

Autoimmune Hepatitis on a Living Liver Donor: An Unexpected Long-Term Complication.

In Western countries, deceased donor liver transplantation remains the standard of care for patients with end-stage liver disease. Living donor liver transplantation is a viable and feasible strategy for patients with end-stage liver disease designed to mitigate the deceased organ shortage. Donor safety is the primary concern because liver donors, ideally, should not have any complication. We report a case of middle-aged woman without a history of chronic liver disease who developed autoimmune hepatitis more than 20 years after live liver donation. Changes in these patients' liver enzymes should prompt swift referral to an hepatologist for initial liver disease work-up.

The Detection of Thoracolumbar Spine Injuries in Horses with Chronic Laminitis Using a Novel Clinical-Assessment Protocol and Ultrasonographic Examination.

Postural adaptation is a prominent feature in horses affected by laminitis. Laminitis induces intense pain, especially in the forelimbs, prompting affected horses to assume a caudally displaced trunk posture, resulting in the hyperflexion of the thoracolumbar spine. This study assessed the nature and prevalence of thoracolumbar injuries in horses with chronic laminitis compared to horses without it. Sixty horses were used (thirty laminitic and thirty non-laminitic) of different athletic purposes and ages (2-20 years). The experimental protocol entailed a single assessment of horses' thoracolumbar spines, utilizing physical examination by MACCTORE, a scoring system developed specifically for this study. Additional evaluations included the Grimace Equine Pain Scale (HGS) and ultrasound exams. Statistical tests were used to compare values (Mann-Whitney or t-test) and lesions prevalences (Fisher) between groups (p < 0.05). The results showed a higher pain manifestation (HGS and heart rate, p < 0.0001) and thoracolumbar-spine-injury levels in chronic laminitis horses, both in MACCTORE clinical examinations (11.7 ± 4.8 vs. 4.2 ± 3.3, p < 0.0001) and general ultrasonographic indices (39.6 ± 12.0 vs. 20.7 ± 7.1, p < 0.0001), including specific examination approaches for various spinal elements. Horses with laminitis presented with a 14-fold higher prevalence of ultrasound-relevant lesions in the thoracolumbar spine (CI: 4.4 to 50.6, p < 0.0001) compared to controls. These findings constitute new evidence of an association between chronic laminitis and the presence of thoracolumbar spine injuries in horses, which may be confirmed by more sophisticated study designs.

Iron stores assessment in alcoholic liver disease.

BACKGROUND: The relation between alcoholic liver disease (ALD) and iron overload is well known. Liver biopsy is the gold standard for assessing iron stores. MRI is also validated for liver iron concentration (LIC) assessment. We aimed to assess the effect of active drinking in liver iron stores and the practicability of measuring LIC by MRI in ALD patients. MATERIALS AND METHODS: We measured LIC by MRI in 58 ALD patients. We divided patients into two groups - with and without active alcoholism - and we compared several variables between them. We evaluated MRI-LIC, liver iron stores grade, ferritin and necroinflammatory activity grade for significant correlations. RESULTS: Significant necroinflammation (40.0% vs. 4.3%), LIC (40.1 vs. 24.3 µmol/g), and ferritin (1259.7 vs. 568.7 pmol/L) were significantly higher in drinkers. LIC values had a strong association with iron stores grade (r s = 0.706). Ferritin correlated with LIC (r s = 0.615), iron stores grade (r s = 0.546), and necroinflammation (r s = 0.313). The odds ratio for elevated serum ferritin when actively drinking was 7.32. CONCLUSION: Active alcoholism is associated with increased ALD activity. It is also the key factor in iron overload. Scheuers' semiquantitative score with Perls' staining gives a fairly accurate picture of liver iron overload. Serum ferritin also shows a good correlation with LIC values and biopsy iron stores grade. As most patients present only with mild iron overload, serum ferritin measurement and semiquantitative evaluation of iron stores are adequate, considering MRI high cost. However, if MRI is required to evaluate liver structure, LIC assessment could be performed without added cost.

Occult hepatitis C infection identified in injection drug users with direct antiviral agents therapy and spontaneous resolution of hepatitis C virus infection.

BACKGROUND: Occult hepatitis C infection (OCI) is characterized by the detection of hepatitis C virus (HCV) RNA in hepatocytes and in peripheral blood mononuclear cells (PBMCs) without detection in serum. We aimed to evaluate OCI in drug and no drug users who achieved sustained virological response (SVR) after therapy with direct-acting antivirals (DAAs) and with HCV spontaneous resolution. METHODS: Twenty-four patients in the AVP group (who achieved a SVR after DAAs therapy), 13 in the NAVP group (with HCV spontaneous resolution) and 7 HCV-RNA positive patients (CPP, control positive group) were included in the study. HCV/OCI-RNA was screened in serum and PBMCs samples of the patients by ddPCR for OCI patients' identification. Plasma and red blood cells (RBCs) samples of the patients were also evaluated for HCV/OCI-RNA detection by ddPCR. RESULTS: OCI was presented in injection drug users (IDUs) in the AVP (20.8%) and NAVP (23.1%) groups by ddPCR with a higher statistically significant percentage detected in RBCs samples of the patients in the AVP group comparatively to NAVP (p<0.01) and CPP (p < 0.05) groups. CONCLUSION: OCI was identified in IDUs patients of the AVP and NAVP groups by ddPCR. These results suggest that OCI patients in the AVP group might not be entirely cured, and that OCI patients in the NAVP group were not identified at clinical evaluation time when just serum samples were analysed. A higher percentage of HCV/OCI-RNA was detected in RBCs samples. Overall results recommends that HCV/OCI identification in patients with DAAs therapy and spontaneous resolution of HCV infection should be studied more accurately in future and in larger patient groups if possible. Additionally, suggest also PBMCs and RBCs samples as predictors for HCV/OCI diagnosis and management.

Comparison Between the Direct Method and Friedewald's Formula for the Determination of Low-Density Lipoprotein Cholesterol Serum Levels in Horses.

This study aimed to compare the use of enzymatic colorimetry and Friedewald's formula for the determination of LDL in horses. A total of 260 samples were used. Direct analysis was performed to determine low-density lipoprotein (LDL), high-density lipoprotein (HDL) cholesterol, triglycerides (TG), and total cholesterol (TC). The LDL level was calculated using the Friedewald equation (LDL= TC-HDL-TG/5). The correlations between the direct LDL analysis and the LDL calculated using the Friedewald formula were determined by Pearson's tests, and the coefficient of determination was also obtained by linear regression using SAS software (P<.05) and the kappa value. The mean value (± standard deviation) of the LDL was 22.12 (±10.34) mg/dL, and that of the result obtained by the Friedewald formula was 19.94 (±19.13) mg/dL. The correlation between the two variants analyzed in this experiment was significant, with a value of P < .001, and values of r = 0.688 and R2 = 0.4893. These results are relevant, given that recent studies have demonstrated a correlation between LDL plasma values and equine metabolic syndrome. Previous studies have reported discrepancies between the data obtained using Friedewald's method and the LDL-c values directly determined in humans and animals. The results of the present study suggest that the Friedewald method can be used to estimate the LDL plasma concentration in horses. Nevertheless, the coefficient of determination was not found to be adequate to recommend the Friedewald formula as a replacement for the enzymatic colorimetric method in determining LDL in horses.

Histological comparison of the lamellar tissue of Iberian origin breed horses created in semi-feral conditions or in an intensive system.

Although the external conformation of wild horse hooves has been proposed as an ideal model for domesticated modern horses, histological signs of laminitis have been reported among them. With the hypothesis that the lamellar tissue of horses of Iberian origin raised in semi-feral is healthier than those raised in an intensive management system (stall confinement and high-calorie diet intake), the objective was to compare their lamellar tissues. Lamellar tissue samples were taken from the forelimb hoof of eight domesticated Mangalarga Marchador (MM) horses and from six semi-feral Marajoara (MJ) and Puruca (MP) horses. Primary epidermal lamella (PEL) and secondary epidermal lamella (SEL) were measured (length and width) in several regions, and their shapes were morphologically classified into different types. Breed groups were compared using analysis of variance, followed by Tukey or Dunn tests (P<0.05). Early signs of laminitis such as abnormal keratinization of the abaxial primary dermal lamella, tapered tips of the axial PELs, pointed tips of the SEL, nuclei condensation, and abnormal spatial orientation of the secondary epidermal basal cells (SELBC), were seen only in MM horses. MP horses had a greater interface of epidermis/dermis contact than MJ horses and more rounded nuclei in the round SELBC than MM horses. In agreement with the study hypothesis, semi-feral MJ and MP horses' lamellae were classified as healthier than MM horses, which showed early signs of endocrinopathic laminitis.

Severe Ascites in Common Variable Immunodeficiency.

Liver disease is one of the possible clinical manifestations of common variable immunodeficiency and can range from mild hepatomegaly and persistent elevation of liver enzymes to cirrhosis, portal hypertension, and nodular regenerative hyperplasia. The last one is the most common histologic presentation of liver involvement by common variable immunodeficiency and its clinical spectrum can range from asymptomatic to cholestasis, liver cirrhosis, or idiopathic non-cirrhotic portal hypertension, with the severe manifestations being less recognised. We present a case of a 48-year-old woman who was referred for an internal medicine consultation for evaluation of rapidly progressing (span of three months) large-volume ascites and marked asthenia. The patient had a past medical history of common variable immunodeficiency and a recent episode of severe haemolytic anaemia. Peritoneal fluid analyses identified portal hypertension as the cause of the ascites. Abdominal Doppler ultrasound and contrasted abdominal computed tomography confirmed the presence of permeable hepatic and portal veins. Liver biopsy revealed regenerative nodular hyperplasia without cirrhosis. A diagnosis of idiopathic non-cirrhotic portal hypertension secondary to common variable immunodeficiency was made. Treatment was adjusted with considerable improvement in ascites. In conclusion, idiopathic non-cirrhotic portal hypertension is a possible and often overlooked complication in patients with common variable immunodeficiency and is an exclusion diagnosis that requires a high level of suspicion, especially in patients with ascites.

Spontaneous Bacterial Peritonitis in Cirrhotic Patients: A Shift in the Microbial Pattern? A Retrospective Analysis.

Introduction: Over the last decade, a shift in the spontaneous bacterial peritonitis (SBP) microbial pattern toward an increasing incidence of gram-positive and multidrug-resistant (MDR) bacteria has been reported. Systematic surveillance of the local microbiological scenario and antibiotic resistance is crucial to SBP treatment success. The main objective of this study was to evaluate the microbiological profile and bacterial resistance of SBP pathogens in a Portuguese cohort to allow selection of the most appropriate empirical antibiotics. Methods: This is a single-center retrospective study including 63 adult cirrhotic patients with culture-positive SBP. Patients were identified using a hospital general diagnostic database and searching for all SBP events (neutrophil count in ascitic fluid ≥250/mm3) from January 1, 2012, to December 31, 2017. Patients were excluded if they had culture-negative SBP, secondary peritonitis, peritoneal dialysis, a liver transplant, or immunodeficiency. The site of SBP acquisition was classified as nosocomial if it was diagnosed 48 h or longer after hospitalization or as nonnosocomial if it was diagnosed within the first 48 h. MDR bacteria were those with an acquired resistance to at least 1 agent in 3 or more antimicrobial categories. All statistical analyses were carried out using IBM SPSS Statistics software version 22 (IBM, New York, USA). Results: The study cohort comprised 53 (84.1%) men. The mean age of the patients was 60.6 ± 11.2 years. Alcohol was the most common etiology (88.9%) and most patients had advanced liver cirrhosis (87.1%, Child C). Gram-negative bacteria were slightly more frequent than gram-positive bacteria (56.9 vs. 43.1%). Escherichia coli was the most common pathogen (33.8%). Nineteen (31.7%) bacteria were classified as MDR. Resistance to third-generation cephalosporins, quinolones, piperacillin-tazobactam, and carbapenems was found in 31.7, 35, 26.7, and 18.3% of the cases, respectively. The rates of gram-positive bacteria were similar between nosocomial and nonnosocomial episodes (45 vs. 42.2%; p = 0.835). MDR bacteria were more common in the nosocomial group (50 vs. 23.8%; p = 0.046). Resistance to third-generation cephalosporins (50 vs. 23.8%; p = 0.046), piperacillin-tazobactam (44.4 vs. 19.1%; p = 0.041), and carbapenems (33.3 vs. 11.9%; p = 0.049) occurred more frequently in nosocomial episodes. Resistance to first-line antibiotic occurred in 29.3% of the patients, being more common in the nosocomial group (44.4 vs. 22.5%; p = 0.089). Conclusion: Although gram-negative bacteria remain the most common causative microorganisms, our results emphasize the shift in SBP microbiological etiology, as almost half of the isolated microorganisms were gram positive. The emergence of bacteria resistant to traditionally recommended empirical antibiotics underlines the importance of basing this choice on local flora and antibiotic susceptibility data, allowing a more rational and successful use of antibiotics.

Introdução: Na última década assistiu-se a uma mudança no padrão microbiológico da peritonite bacteriana espontânea (PBE), com aumento da incidência de bactérias gram-positivas e multirresistentes. Uma vigilância sistemática do cenário microbiológico e da resistência antibiótica é crucial para o sucesso do tratamento da PBE. O principal objetivo deste estudo foi avaliar o perfil microbiológico e os padrões de resistência antibiótica dos agentes bacterianos responsáveis pelos casos de PBE numa coorte portuguesa de doentes cirróticos, de modo a permitir uma seleção mais apropriada da antibioterapia empírica. Métodos: Estudo retrospetivo unicêntrico, que incluiu 63 doentes adultos cirróticos com PBE culturapositiva. A identificação dos doentes foi efetuada a partir da base de dados eletrónica do centro hospitalar, pesquisando todos os internamentos por PBE (contagem de neutrófilos no líquido ascítico ≥250/mm3) entre 1 janeiro de 2012 e 31 de dezembro de 2017. Foram aplicados como critérios de exclusão: cultura de líquido ascítico negativa, peritonite secundária, diálise peritoneal, transplante hepático ou imunodeficiência. O local de aquisição da PBE foi classificado como nosocomial se diagnóstico após as primeiras 48 horas de hospitalização, e não-nosocomial se diagnóstico nas primeiras 48 horas. Multirresistência foi definida como resistência adquirida a pelo menos um agente em três ou mais categorias antimicrobianas. A análise estatística foi efetuada com recurso ao software IBM SPSS Statistics versão 22 (IBM, New York, USA). Resultados: A coorte incluiu 53 (84.1%) doentes cirróticos do género masculino. A idade média dos doentes foi de 60.6 ± 11.2 anos. O álcool constituiu a etiologia mais comum (88.9%) e a maioria dos doentes apresentava uma cirrose em estadio avançado (87.1%, Child-C). As bactérias gram-negativas revelaram-se ligeiramente mais frequentes que as gram-positivas (56.9 vs. 43.1%). Escherichia coli foi o microrganismo mais frequente (33.8%). Dezanove (31.7%) das bactérias isoladas foram classificadas como multirresistentes. As resistências às cefalosporinas de terceira-geração, às quinolonas, à piperacilina-tazobactam e aos carbapenemes foram de 31.7, 35, 26.7 e 18.3%, respetivamente. A taxa de bactérias gram-positivas foi similar entre PBE nosocomial e não-nosocomial (45 vs. 42.2%; p = 0.835). As bactérias multirresistentes foram mais frequentes no grupo nosocomial (50 vs. 23.8%; p = 0.046). A resistência às cefalosporinas de terceira-geração (50 vs. 23.8%; p = 0.046), à piperacilina-tazobactam (44.4 vs. 19.1%; p = 0.041) e aos carbapenemes (33.3 vs. 11.9%; p = 0.049) foi significativamente superior nas infeções nosocomiais. A resistência à antibioterapia empírica de primeira linha ocorreu em 29.3% dos doentes, sendo mais frequente no grupo nosocomial (44.4 vs. 22.5%; p = 0.089). Conclusão: Apesar de as bactérias gram-negativas constituírem, nesta coorte, a maioria dos microrganismos responsáveis pela PBE, os nossos resultados enfatizam a mudança na etiologia microbiológica da PBE, na medida em que, quase metade dos microrganismos isolados foram gram-positivos. A emergência de bactérias resistentes aos antibióticos empíricos tradicionalmente recomendados sublinha a importância de basear esta escolha nos dados locais sobre flora bacteriana e susceptibilidade antibiótica, permitindo uma escolha mais racional e um uso bem-sucedido dos antibióticos.

Mechanical nociceptive assessment of the equine hoof after navicular bursa anesthetic infiltration validated by bursography.

The analgesic specificity of navicular bursa (NB) anesthetic infiltration is still questionable. The study aimed to determine the mechanical nociceptive threshold of non-specific analgesia in the dorsal lamellar stratum, as well as in the sole, coronary band, and heel bulbs of the hoof, after navicular bursa anesthetic infiltration. Six healthy horses with no clinical or radiographic changes of the digits and no communication between the NB and the distal interphalangeal joint, were used. After random selection, the NB of one of the forelimbs was infiltrated with 2% lidocaine and the contralateral one with lactated ringer's solution. Contrast was added to confirm radiographic infiltration. The mechanical nociceptive threshold was determined using a portable pressure dynamometer, before and at various times after the infiltration, in 10 points of the hoof. The effects of time and treatment were verified by ANOVA (P<0.05). There was no statistical difference in the values of the mechanical nociceptive threshold (P>0.05) in all regions evaluated. However, in one of the six hooves that receives lidocaine, complete absence of response to the painful stimulus (maximum force of 6 Kg over an area of 38.46 mm2, for a maximum of 4 seconds) was observed in the dorsal lamellae between 30 and 60 min after infiltration. In conclusion, lidocaine infiltration of NB did not promote significant increases in the nociceptive threshold of the sole, coronary band, bulbs of the heel and dorsal lamellae clinically healthy horses. However, the occurrence of analgesia in one of the six hooves subjected to NB anesthesia indicates that the technique may not be fully specific in few horses.

Impact of COVID-19 Pandemic on In-Hospital Mortality in Patients Without SARS-CoV-2 Infection in an Internal Medicine Ward of a Tertiary Care Hospital in Portugal.

INTRODUCTION: Despite the emergence of a new worldwide cause of death related to COVID-19, several studies have hypothesized that the international mortality rate attributed to non-COVID-19 causes was significantly higher during the COVID pandemic, questioning whether this excess in mortality is related only to COVID-19 or to the difficulties that the healthcare systems faced during the pandemic. Therefore, understanding the impact of the COVID-19 pandemic on the prognosis of patients without severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is a major unmet need as this was overshadowed by the overwhelming number of patients with SARS-CoV-2. METHODS: This is a retrospective, cross-sectional, observational study in the internal medicine non-COVID-19 wards of a tertiary care hospital in Portugal. A total of 2021 patients without SARS-CoV-2 infection admitted between March and May of 2019 and 2020 were included. For each patient, we collected information regarding demographic characteristics, emergency department admission information, hospitalization information, date of discharge or death, health comorbidities, and current medication. RESULTS: Data from 1013 patients in 2019 and 1008 patients in 2020 was analyzed. The patients' demographic characteristics, health comorbidities, and current medications were distributed in similar patterns in the two studied periods. There was a statistically significant difference in the in-hospital mortality in patients without SARS-CoV-2 infection between 2019 and 2020 (12% vs 17%, p-value < 0.001) and in admission severity in hospitalized patients without SARS-CoV-2 infection between 2019 and 2020 (0.9 vs 0.6, p-value < 0.001). CONCLUSION: Our work showed a statistically significant increase in in-hospital mortality during the COVID-19 pandemic in patients without SARS-CoV-2 infection, which was not apparently explained by differences in the characteristics of hospitalized patients. As this is one of the first works describing the silent impact of the COVID-19 pandemic in Portugal, we believe it holds an important value in the provision of bases for building up future health policies in case of new COVID-19 outbreaks or other medical emergencies.

Chronic hepatitis C treated with peginterferon alfa plus ribavirin in clinical practice.

BACKGROUND/AIMS: The role of genotype and viremia were retrospectively evaluated on sustained virological response (SVR) rates in routine clinical practice. METHODOLOGY: From 1907 patients with chronic hepatitis C proposed for treatment, we analysed 1380 (1124 naive and 256 treatment-experienced) with complete follow-up. Genotype and HCV RNA quantification were assayed by commercial tests. Viremia was considered high if >800,000IU/mL, and low if <400,000IU/mL. Liver fibrosis was staged in 614 patients. RESULTS: Genotype 1 was the most frequent (60%), followed by 3 (25%), 4 (9%) and 2 (2%); 3.2% had other or unclassified genotype. Genotype 1 was more prevalent in central Portugal and genotype 4 in the south. Viremia was =800,000IU/mL in 54.6% and <400,000IU/mL in 34.6% of the patients, particularly in genotype 2 (p<0.03) and 4 (p<0.001). Genotype non-1 had a significantly lower viral load (p=0.004). Mild or moderate fibrosis was present in 71.7% and bridging fibrosis or cirrhosis in 28.3%, with no differences among genotypes. Treatment was discontinued in 19.8%. SVR was achieved in 55.3% of naive and 36.3% of re-treated patients. CONCLUSIONS: Standard treatment of chronic hepatitis C in real-life achieves similar results obtained in clinical trials, despite differences of demographic and viral parameters.

Depression preceding the diagnosis of pancreatic cancer.

Pancreatic cancer is the tumour related to higher rates of depression. Several papers have validated the association between pancreatic cancer and depression. It was noticed that in some cases the psychiatric symptoms precede the somatic ones. We present a case of a progressive and incapacitating diffuse abdominal pain, initially attributed to psychosomatic disorder. This hindered a timely correct diagnosis leading to a poor outcome. A pancreatic adenocarcinoma in an unresectable stage was confirmed by histopathology. The patient underwent chemotherapy.