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.

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.

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.

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.

Multiresistent Cupriavidus pauculus infection in an immunocompromised elderly patient.

Cupriavidus pauculus is a gram-negative bacillus aerobic bacteria widely distributed in nature that can cause, in rare cases, serious infections both in immunocompromised and immunocompetent patients. We describe a case of an elderly patient admitted in emergency room with septic shock and diagnosed with a urinary tract infection. During his hospital stay, his clinical and analytical conditions have deteriorated. Blood cultures were positive for C. pauculus only sensitive to minocycline. Despite every effort, due to multiple comorbidities and a nosocomial pneumonia, the patient ends up dying.

A Case of Liver Injury after Exposure to Isopropanol: A Challenging Diagnosis.

Drug-induced liver injury is hardly diagnosed, considering not only the wide range of hepatotoxic substances but also the diversity of associated phenotypes and the absence of specific biomarkers. Symptom chronology, drug or toxic exposure, and temporal association help to establish the diagnosis. Exposure to isopropanol has known but rare toxic effects. We report the clinical case of a 33-year-old female hairdresser admitted to the hospital with fatigue, epigastric pain, and jaundice. She presented the following values: aspartate aminotransferase, 485 U/L; alanine transaminase, 908 U/L; ALP, 240 U/L; GGT, 370 U/L; total bilirubin, 3.5 mg/dL; and direct bilirubin, 2.1 mg/dL. Albumin, platelet, and INR values were normal. Structural, infectious, immune, and vascular causes were excluded. Liver biopsy was suggestive of toxic hepatitis. A possible association with ibuprofen intake was considered. The patient resumed professional activity, with fatigue and jaundice relapse, as well as a new liver enzyme increase, despite ibuprofen withdrawal. It was concluded that a new hair product containing isopropanol had recently been introduced. As soon as its professional use was discontinued, there was no recurrence of the symptoms. Given the temporal association between the development of acute hepatitis and the use of an isopropanol-containing product, liver toxicity by exposure to isopropanol was assumed. This substance is metabolized in the liver and toxicity may occur by ingestion, skin exposure, or inhalation, and it is described in cases of occupational or accidental exposure. The treatment is symptomatic and comprises toxic suspension.

A lesão hepática induzida por tóxicos é um dos distúrbios de mais difícil diagnóstico, quer pela existência de múltiplos hepatotóxicos, quer pela diversidade de fenótipos associados e ausência de biomarcadores específicos. A cronologia dos sintomas, exposição a fármacos ou tóxicos e associação temporal auxilia o diagnóstico. A exposição a isopropanol tem efeitos tóxicos conhecidos e raros. Descrevemos o caso clínico de uma mulher de 33 anos, cabeleireira, admitida por fadiga, epigastralgias e icterícia. Apresentava AST 485 U/L, ALT 908 U/L, FA 240 U/L, GGT 370 U/L, bilirrubina total 3,5 mg/dL e bilirrubina direta 2,1 mg/dL; o doseamento sérico de albumina, plaquetas e o valor de INR eram normais. Foram excluídas lesões estruturais, causas infeciosas, imunes e vasculares. Biópsia hepática sugestiva de hepatite tóxica. Considerada possível associação a toma de ibuprofeno. Retomou atividade profissional, com recorrência de fadiga e icterícia, bem como elevação das enzimas hepáticas novamente, apesar de suspensão de ibuprofeno. Apurada exposição a tóxicos profissionais, percebendo-se que o quadro coincidiu com início da utilização de novo produto capilar contendo isopropanol. A doente retomou atividade profissional, não utilizando o produto, sem recorrência. Dada a relação temporal entre o desenvolvimento de hepatite aguda e a utilização de produtos contendo isopropanol, assumiu-se hepatotoxicidade por exposição profissional ao isopropanol. Esta substância é metabolizada no fígado e a toxicidade pode ocorrer por ingestão, exposição cutânea ou inalação, estando descrita em casos de exposição ocupacional ou acidental. O tratamento é sintomático e inclui a suspensão do tóxico.

Apoptosis in epithelial cells and its correlation with leukocyte accumulation in lamellar tissue from horses subjected to experimental sepsis-associated laminitis.

Inflammation and apoptosis in the hoof lamellar interface both contribute to the early stages of sepsis-associated laminitis, but it is not clear whether apoptosis is occurring before the onset of inflammation or is being provoked by inflammation. Apoptosis and inflammation were therefore measured in lamellar tissues obtained at different time points throughout the early stages of experimentally induced laminitis. Apoptotic cells and leukocyte were enumerated in archived paraffin embedded lamellar tissue samples from previous experiments in which acute laminitis was induced using Black Walnut Extract (BWE) or starch (CHO). BWE-derived samples from 20 horses were allocated into four groups: Control (CON = 5); Early Time Point (ETP, 1.5 h after induction, n = 5); Developmental Time Point (DTP, 3-4 h after induction, n = 5); Obel Grade 1 (OG1, Onset of Lameness, n = 5). CHO-derived samples from 25 horses were allocated into four groups: CON (n = 8); DTP (10-12 h after induction, n = 6); OG 1 (n = 6); Obel 3 (OG3, lameness progression, n = 5). Apoptotic cells were enumerated using a horse validated TUNEL technique. Compared to controls, significant increases in apoptotic cell counts were not detected in lamellar epithelial cells during the developmental phase or at the onset of lameness during laminitis induction. A negative correlation between apoptosis and leukocyte infiltration was detected in the BWE model (P < 0.05). In conclusion, apoptosis does not play an important role in the initial stages of sepsis-related laminitis.

Changes in metabolic and physiological biomarkers in Mangalarga Marchador horses with induced obesity.

This study aimed to characterize and correlate physiological and metabolic changes in horses fed a hypercaloric diet (HD). Nine mature horses with a mean initial body condition score of 2.9 ± 1 (scale, 1-9) were fed a high-calorie diet for 5 months. Fasting blood samples were collected before the study and biweekly for the duration of the project to determine the concentrations of cholesterol (CHOL), very low (VLDL), low (LDL) and high-density (HDL) lipoproteins, triglycerides, non-esterified fatty acids, and fructosamine. A low-dose oral glucose tolerance test (LGTT) was conducted before, 75 and 150 days after HD introduction. Mean arterial blood pressure was measured monthly. Following HD introduction, CHOL, LDL, HDL, and fructosamine blood concentrations increased (P < 0.001). These four variables were also positively and significantly correlated with the blood insulin response to LGTT. These findings confirm the occurrence of hypercholesterolemia concomitantly with insulin dysregulation development in horses exposed to HD.

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.

Incidence of Antibiotic Treatment Failure in Patients with Nursing Home-Acquired Pneumonia and Community Acquired Pneumonia.

PURPOSE: Nursing home-acquired pneumonia (NHAP) patients are at higher risk of multi-drug resistant infection (MDR) than those with community-acquired pneumonia (CAP). Recent evidence suggests a single risk factor for MDR does not accurately predict the need for broad-spectrum antibiotics. The goal of this study was to compare the rate antibiotic failure between NHAP and CAP patients. METHODS: Demographic characteristics, co-morbidities, clinical and laboratory variables, antibiotic therapy, and mortality data were collected retrospectively for all patients with pneumonia admitted to an Internal Medicine Service between April 2017 and April 2018. RESULTS: In total, 313 of 556 patients had CAP and 243 had NHAP. NHAP patients were older, and were more likely to be dependent, to have recent antibiotic use, and to experience treatment failure (odds ratio (OR) 1.583; 95% CI 1.102-2.276; p = 0.013). In multivariate analysis, patient's origin did not predict treatment failure (OR 1.083; 95% CI 0.726-1.616; p = 0.696). DISCUSSION: Higher rates of antibiotic failure and mortality in NHAP patients were explained by the presence of other risk factors such as comorbidities, more severe presentation, and age. Admission from a nursing home is not a sufficient condition to start broader-spectrum antibiotics.

Effectiveness and safety of obeticholic acid in a Southern European multicentre cohort of patients with primary biliary cholangitis and suboptimal response to ursodeoxycholic acid.

BACKGROUND: Obeticholic acid (OCA) was recently approved as the only on-label alternative for patients with primary biliary cholangitis (PBC) with intolerance or suboptimal response to ursodeoxycholic acid (UDCA). However, few data are available outside clinical trials. AIM: To assess the effectiveness and safety of OCA in a real-world cohort of patients with non-effective UDCA therapy. METHODS: Open-label, prospective, real-world, multicentre study, enrolling consecutive patients who did not meet Paris II criteria, from 18 institutions in Spain and Portugal. Effectiveness was assessed by the changes in GLOBE and UK-PBC scores from baseline. POISE and Paris II criteria were evaluated after 12 months of OCA . Liver fibrosis was evaluated by FIB-4 and AST to platelet ratio index (APRI). RESULTS: One hundred and twenty patients were eligible, median time since PBC diagnosis 9.3 (4.0-13.8) years, 21.7% had cirrhosis, and 26.7% received had previous or concomitant treatment with fibrates. Seventy-eight patients completed at least 1 year of OCA. The Globe-PBC score decreased to 0.17 (95% CI 0.05 to 0.28; P = 0.005) and the UK-PBC score decreased to 0.81 (95% CI -0.19 to 1.80; P = 0.11). There was a significant decrease in alkaline phosphatase of 81.3 U/L (95% CI 42.5 to 120; P < 0.001), ALT 22.1 U/L (95% CI 10.4 to 33.8; P < 0.001) and bilirubin 0.12 mg/dL (95% CI 0 to 0.24; P = 0.044). FIB-4 and APRI remained stable. According to the POISE criteria, 29.5% (23 out of 78) achieved response. The adverse events rate was 35%; 11.67% discontinued (8.3% due to pruritus). CONCLUSIONS: This study supports data from phase III trials with significant improvement of PBC-Globe continuous prognostic marker score among OCA-treated patients with good tolerability.

Clostridioides (Clostridium) difficile-associated diarrhea in equine in Minas Gerais, Brazil: clinical and microbiological characterization of six cases / Diarreia por Clostridioides (Clostridium) difficile em equinos em Minas Gerais, Brasil: caracterização clínica e microbiológica de seis casos

ABSTRACT: Clostridioides (Clostridium) difficile is the main causative agent of antimicrobial-related diarrhea in humans and a major pathogen-associated enteric disorder in foals and adult horses. Moreover, studies have suggested that animals are a possible reservoir of toxigenic C. difficile strains for humans. Despite this known importance, the epidemiology of C. difficile infection (CDI) in equine is still largely unknown. Therefore, this study described six cases of equine CDI occurring in Minas Gerais, Brazil, including the characterization of the isolates. All but one equine included in this research developed CDI after antimicrobial therapy, three of which occurred during hospitalization. Coinfection with Salmonella Heidelberg and S. Infantis was detected in three cases, making the antimicrobial treatment challenging. All animals recovered after metronidazole administration. All C. difficile isolates were susceptible to metronidazole and vancomycin, while three were resistant to moxifloxacin and two were resistant to clindamycin. The isolates were classified as RT126 (n = 4), RT078 (n = 1), and RT014/020 (n = 1), all previously reported infecting humans and animals worldwide.

RESUMO: Clostridioides (Clostridium) difficile é o principal agente envolvido em diarreias associadas ao uso de antimicrobianos em seres humanos e um enteropatógeno de grande relevância em quadros de diarreia em potros e equinos adultos. Em adição, estudos tem sugerido que animais são possíveis reservatórios de estirpes toxigênicas de C. difficile para humanos. Apesar da importância na saúde animal e humana, a epidemiologia da infecção por C. difficile (ICD) é ainda pouco conhecida. Dessa forma, o presente estudo tem como objetivo caracterizar seis casos de diarreia por C. difficile ocorridos em Minas Gerais, Brasil. Com exceção de um animal, todos os equinos incluídos no presente estudo desenvolveram ICD após antibioticoterapia, três dos quais durante a hospitalização. Coinfecção por Salmonella Heidelberg e S. Infantis foi detectada em três casos, tornando o tratamento antimicrobiano desafiador. Todos os animais recuperaram após administração de metronidazol. Os isolados obtidos no presente estudo foram sensíveis a metronidazol e vancomicina, porém três estirpes foram resistentes a moxifloxacina e duas a clindamicina. Os isolados foram classificados como ribotipos 126 (n=4), 078 (n=1) e 014/020 (n=1), todos previamente relatados em seres humanos com ICD no Brasil e em outros países.

Mechanical nociceptive assessment of the equine hoof following distal interphalangeal joint intra-articular anesthesia.

BACKGROUND: With the hypothesis that equine dorsal lamellar tissue can be desensitized by anesthesia injection into distal interphalangeal joint (DIPJ), the objective was to assess the mechanical nociceptive threshold of hoof dorsal lamellae following intra-articular (IA) administration of lidocaine into this joint. METHODS: The DIPJ of the forelimbs of six adult healthy horses were injected with either 5 mL of lidocaine, or 5 mL of lactated Ringer's solution. Treatments were randomly distributed, with each forelimb undergoing a single treatment. The hooves were evaluated pre- and post-injection at pre-selected times over 4 h, using a pressure algometry model. Mechanical nociceptive thresholds (MNTs) were recorded for the sole (dorsal, palmarolateral, and palmaromedial regions), coronary band (medial, lateral, and dorsal regions), heel bulbs (medial and lateral), and dorsal lamellar region (2 cm and 4 cm distal to the coronary band). The MNT means were compared over time using the Friedman test and between treatments using the Wilcoxon signed-rank test, with values of P < 0.05 considered statistically significant. RESULTS: There were no differences between treatments for any region of the hoof during the evaluation period. However, MNT values indicating analgesia were recorded in the dorsal lamellar region in 50% of hooves following adminstration of lidocaine into the DIPJ. CONCLUSION: The administration of 5 mL of lidocaine into the DIPJ does not significantly increase the mechanical nociceptive threshold of the equine hoof.

Novel anticoagulants in an older and frail population with atrial fibrillation: the effect of inappropriate dosing on clinical outcomes.

PURPOSE: An individualized approach should be taken regarding the use of novel oral anticoagulants (NOAC) in frail and older patients with atrial fibrillation (AF). We hypothesized that there would be a high proportion of underdosed patients among an older and frail population, where bleeding risk is higher. METHODS: We retrospectively analyzed patients admitted to an Internal Medicine ward with a previous diagnosis of AF and discharged with a NOAC (n = 327). We compared survival and incidence of dosing-related events (stroke, systemic embolism, and major bleeding) at 1-year between inappropriately underdosed patients (dose reduction without a formal indication) and the rest of the population. RESULTS: A total of 167 patients (51%) received a reduced dose despite lacking formal criteria for dose reduction. Before adjustment, underdosed patients, in comparison with non-underdosed patients, had a higher mortality at 1 year (HR = 1.6, 95% CI 1.2-2.1, p = 0.003) and a higher combined stroke, systemic embolism, and major bleeding event rate at 1-year (HR = 3.2, 95% CI 1.3-8.0, p = 0.015). After adjustment, combined stroke, systemic embolism, and major bleeding event rate was higher in underdosed patients (HR 3.7, 95% CI 1.1-12.3, p = 0.030), but survival was not different in the adjusted model (HR 1.4, 95% CI 0.9-2.1, p = 0.110). CONCLUSIONS: Underdosed patients have a significant survival disadvantage and this may be due to clinician prescription bias, since this difference does not remain after adjusting for confounders. Combined stroke, systemic embolism, and major bleeding event rate was higher in underdosed 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.