Real-World Effectiveness and Safety of Glecaprevir/Pibrentasvir for the Treatment of Chronic Hepatitis C: A Prospective Cohort Study in Portugal.

INTRODUCTION: Information about pan-genotypic treatments for hepatitis in Portugal is scarce. We aimed to evaluate the effectiveness and safety of glecaprevir plus pibrentasvir (GLE/PIB) treatment for hepatitis C virus (HCV) infection in real-world clinical practice. METHODS: An observational prospective study was implemented in six hospitals with 121 adult HCV patients who initiated treatment with GLE/PIB between October 2018 and April 2019, according to clinical practice. Eligible patients had confirmed HCV infection genotype (GT) 1 to 6 and were either treatment-naïve or had experience with interferon-, ribavirin- or sofosbuvir-based regimens, with or without compensated cirrhosis. Baseline sociodemographic and safety data are described for the total population (N = 115). Effectiveness [sustained virologic response 12 weeks after treatment (SVR12)] and patient-reported outcomes are presented for the core population with sufficient follow-up data (n = 97). RESULTS: Most patients were male (83.5%), aged < 65 years (94.8%), with current or former alcohol consumption (77.3%), illicit drug use (72.6%), and HCV acquisition through intravenous drug use (62.0%). HIV co-infection occurred in 22.6% of patients. The prevalence of each GT was: GT1 51.3%, GT2 1.7%, GT3 30.4%, GT4 16.5%, and GT5.6 0%. Most patients were non-cirrhotic (80.9%) and treatment-naïve (93.8%). The SVR12 rates were 97.9% (95% CI: 92.8 - 99.4), and > 95% across cirrhosis status, GT, illicit drug use, alcohol consumption, and HCV treatment experience. The adverse event rate was 2.6%, and no patient discontinued treatment due to adverse events related to GLE/PIB. CONCLUSION: Consistent with other real-world studies and clinical trials, treatment with GLE/PIB showed high effectiveness and tolerability overall and in difficult-to-treat subgroups (ClinicalTrials.gov: NCT03303599).

Dor e articulação do punho na artrite reumatoide: O impacto na capacidade funcional / Pain and wrist joint in rheumatoid arthritis: The impact on functional capacity / Dolor y articulación de la muñeca en la artritis reumatoide: El impacto en la capacidad funcional

Resumo Enquadramento: Artrite reumatoide (AR), doença autoimune, inflamatória e crónica. Caracteriza-se por poliartrite, dor crónica e dificuldade em mobilizar as articulações, que levam à incapacidade funcional dos doentes. Objetivos: Avaliar a influência da mobilidade articular do punho e da dor, na capacidade funcional de doentes com AR. Metodologia: Estudo quantitativo, descritivo e correlacional, constituído por uma amostra de 105 doentes, com aplicação do Índice de Incapacidade - Questionário Avaliação de Saúde (HAQ-DI); Escala Visual Analógica da Dor (EVA) e medição da amplitude articular do punho, com goniómetro. Resultados: A mobilidade articular do punho é representativa na funcionalidade (p < 0,05), no entanto, a sua extensão e flexão, não influenciam diretamente a dor (p > 0,05). Observou-se que a dor é impactante na capacidade funcional dos doentes (p = 0,010). Conclusão: A mobilidade articular do punho e a dor afetam as atividades diárias dos doentes com AR, expressas através da capacidade funcional de avaliação de saúde.

Abstract Background: Rheumatoid arthritis (RA) is a chronic, autoimmune, and inflammatory disease. Symptoms include polyarthritis, chronic pain, and difficulty in joint mobilization, which lead to functional disability in patients. Objectives: To assess the influence of wrist joint mobility and pain on the functional capacity of patients with RA. Methodology: Quantitative, descriptive, and correlational study in a sample of 105 patients. Health Assessment Questionnaire - Disability Index (HAQ-DI) and Visual Analog Pain Scale (VAS) were applied, and the wrist joint range of motion was measured with a goniometer. Results: Joint wrist mobility is representative of functionality (p < 0.05). However, wrist joint extension and flexion do not directly influence pain (p > 0.05). Pain was observed to impact the functional capacity in patients (p = 0.010). Conclusion: Joint wrist mobility and pain affect the daily activities of patients with RA, expressed through the functional capacity for health assessment.

Resumen Marco contextual: Artritis reumatoide (AR), una enfermedad autoinmune, inflamatoria y crónica. Se caracteriza por la poliartritis, el dolor crónico y la dificultad para movilizar las articulaciones, lo que provoca la incapacidad funcional de los pacientes. Objetivos: Evaluar la influencia de la movilidad articular de la muñeca y el dolor en la capacidad funcional de los pacientes con AR. Metodología: Estudio cuantitativo, descriptivo y correlacional, compuesto por una muestra de 105 pacientes, en el que se aplicó el Índice de Discapacidad - Cuestionario de Evaluación de la Salud (HAQ-DI); la Escala Visual Analógica del Dolor (EVA) y la medición de la amplitud articular de la muñeca, con un goniómetro. Resultados: La movilidad articular de la muñeca es representativa en la funcionalidad (p < 0,05), sin embargo, la extensión y la flexión no influyen directamente en el dolor (p > 0,05). Se observó que el dolor tiene un impacto en la capacidad funcional de los pacientes (p = 0,010). Conclusión: La movilidad articular de la muñeca y el dolor afectan las actividades diarias de los pacientes con AR, expresadas a través de la capacidad funcional de evaluación de la salud.

Clinical and Epidemiological Features of Hospitalized and Ambulatory Patients with Human Monkeypox Infection: A Retrospective Observational Study in Portugal.

Monkeypox, a neglected and re-emergent zoonotic disease caused by monkeypox virus (MPXV) infection, has been endemic in Central and Western Africa for decades. More recently, an outbreak has spread to a global level, occurring in sites with no previous reported cases and being clustered among men who have sex with men, suggesting new modes of transmission. There is an urgent need for research for a better understanding of the genomic evolution and changing epidemiology of the Orthopoxvirus group. Our work aimed to characterize the clinical and epidemiological features of a cohort of patients with MPXV infection in a Portuguese hospital, admitted between 5 May and 26 July 2022. In this retrospective observational study, aggregate data of a case series on the presentation, clinical course, and outcomes of confirmed MPXV infections are reported. The study included 40 men and 1 woman, with a mean age of 37.2 years old; 92.7% identified as men who have sex with men, 90.2% had unprotected sex or sex with multiple or anonymous partners in the previous month, and 39.0% reported to have had sex with an MPXV-confirmed case; 59.5% had previously known human immunodeficiency virus (HIV) infection, all of whom were under antiretroviral therapy, and no patients had acquired immunodeficiency syndrome (AIDS) criteria. About a quarter of patients were observed only a week after symptom onset. All patients had skin or mucosal lesions and the anogenital region was the most frequent lesion site. There were no statistically significant clinical differences between HIV-positive and negative individuals. Four patients were admitted to the inpatient clinic, two of whom had proctitis with difficult-to-manage anal pain. There were no reported deaths. Our findings suggest the sexual route as a relevant mode of transmission of MPXV and confirm the mostly benign presentation of this disease.

Roles of Calcium Signaling in Gene Expression and Photosynthetic Acclimatization of Solanum lycopersicum Micro-Tom (MT) after Mechanical Damage.

A momentary increase in cytoplasmic Ca2+ generates an oscillation responsible for the activation of proteins, such as calmodulin and kinases, which interact with reactive oxygen species (ROS) for the transmission of a stress signal. This study investigated the influence of variations in calcium concentrations on plant defense signaling and photosynthetic acclimatization after mechanical damage. Solanum lycopersicum Micro-Tom was grown with 0, 2 and 4 mM Ca2+, with and without mechanical damage. The expression of stress genes was evaluated, along with levels of antioxidant enzymes, hydrogen peroxide, lipid peroxidation, histochemistry, photosynthesis and dry mass of organs. The ROS production generated by mechanical damage was further enhanced by calcium-free conditions due to the inactivation of the oxygen evolution complex, contributing to an increase in reactive species. The results indicated that ROS affected mechanical damage signaling because calcium-free plants exhibited high levels of H2O2 and enhanced expression of kinase and RBOH1 genes, necessary conditions for an efficient response to stress. We conclude that the plants without calcium supply recognized mechanical damage but did not survive. The highest expression of the RBOH1 gene and the accumulation of H2O2 in these plants signaled cell death. Plants grown in the presence of calcium showed higher expression of SlCaM2 and control of H2O2 concentration, thus overcoming the stress caused by mechanical damage, with photosynthetic acclimatization and without damage to dry mass production.

Rare Case of Rickettsiosis Caused by Rickettsia monacensis, Portugal, 2021.

We report a case of rickettsiosis caused by Rickettsia monacensis in an immunocompetent 67-year-old man in Portugal who had eschar, erythematous rash, and an attached Ixodes ricinus tick. Seroconversion and eschar biopsy led to confirmed diagnosis by PCR. Physicians should be aware of this rare rickettsiosis, especially in geographic regions with the vector.

A Rare Form of Metastatic Melanoma in an HIV-Infected Patient - A Diagnosis to Remember.

Malignant melanoma (MM), which is amongst the rarest skin cancers, still remains one of the deadliest and most likely to spread, and, in human immunodeficiency virus (HIV)-infected patients, generally has a more aggressive behaviour. Although gastrointestinal (GI) tract metastases are frequent, secondary symptomatic colonic disease is rare. We present the case of a 76-year-old HIV-infected patient, with a 15-month history of GI and constitutional symptoms and a previous diagnosis of malignant melanoma. Diagnostic workup revealed metastatic involvement of the cecum. This case highlights the need to bear in mind the metastatic involvement of the GI tract by MM, and MM itself, especially in HIV-infected patients.

Mediterranean spotted fever: case series of 24 years (1989-2012).

PURPOSE: Mediterranean spotted fever (MSF) is the most prevalent zoonosis in Portugal. To characterize it's evolution between 1989 and 2012, the authors reviewed the cases diagnosed at their unit during this period. METHODS: Review of clinical records of patients with MSF diagnosis, between 1989 and 2012. RESULTS: Data from 250 patients was included, 54% male. Mean age at diagnosis was 58 years (11-92). Mean annual incidence was 10 cases, with clear summer predominance. Most patients, 78% lived in rural areas, 34% had contact with dogs and 10% noticed the tick bite. Most common symptoms were: fever (98%), myo-arthralgia (64%) and headache (48%). Maculopapular rash was noticed in 87%, affecting palms in 77% and soles in 69%. Inoculation eschar was found in 60%, mostly located on the trunk. Treatment included doxycycline in 86% and chloramphenicol in 12%, with a mean duration of 8 days. Most frequent blood test abnormalities were C-reactive protein, lactate dehydrogenase, aspartate aminotransferase and alanine transaminase elevations and thrombocytopenia. First serologic evaluation was positive in 37% (78/212), having seroconversion been documented in 85% (72/85). Most frequent complication was acute renal injury. ICU admission occurred in 5%. Average length of hospital stay was 11.2 days (1-106), with a mortality of 3.6%. CONCLUSIONS: In our series, there was clear summer predominance of MSF, which had rural origin in 78%. Most common symptoms were fever, myo-arthralgia and headache. Maculopapular rash was noticed in 87% of cases and inoculation eschar in 60%. Most cases had favourable outcome, having 5% been admitted to ICU. Mortality was 3.6%.

[Acute bacterial meningitis as an occupational disease]. / Meningite bacteriana aguda como doença ocupacional.

Streptococcus suis is a zoonotic pathogen with worldwide distribution, responsible for more than 700 human cases globally reported. This infection affects mostly men, exposed to pig or pork, which leads to its usual classification as an occupational disease. We report a case of acute bacterial meningitis in a 44 years old male. According to his past medical history, the patient had chronic alcoholism and worked in a restaurant as a piglet roaster. Microbiological examination of blood and CSF revealed S. suis. After 14 days of ceftriaxone the patient fully recovered. The authors review the clinical reports previously described in Portugal. In all of them was possible to identify risk exposition to pork. We alert to this microorganism's importance in Portugal where it is probably underdiagnosed.

Streptococcus suis é um agente zoonótico com distribuição mundial, atualmente responsável por mais de 700 casos reportados em humanos. Atinge quase em exclusivo indivíduos do sexo masculino com exposição a suínos ou à sua carne, classificando-se neste contexto como uma doença ocupacional. Os autores apresentam um caso de meningite bacteriana aguda por este agente infeccioso, num homem de 44 anos com antecedentes de etilismo crónico cuja atividade profissional consistia em assar leitões num restaurante. A análise microbiológica do sangue e do LCR revelou S. suis, agente etiológico desta infecção. Foi tratado empiricamente com ceftriaxona, completando 14 dias de antibioterapia com resolução total do quadro. Reveem-se os casos previamente descritos em Portugal. Em todos foi possível identificar exposição a carne de porco crua. Alerta-se para a importância deste agente infeccioso em Portugal, onde possivelmente se encontrará sub-diagnosticado.

[Brucellar spondylodiscitis: case series of the last 25 years]. / Espondilodiscite Brucélica: Casuística dos Últimos 25 Anos.

INTRODUCTION: Brucellosis is an endemic zoonosis in Portugal. Brucellar spondylodiscitis is one of the most frequent focal manifestations which may cause severe sequelae despite appropriate therapy. MATERIAL AND METHODS: Retrospective study of patients with diagnosis of brucellar spondylodiscitis admitted to the Infectious Diseases Department of Centro Hospitalar e Universitário de Coimbra, over a 25-year period (1988-2012). RESULTS: We identified 54 patients, 55.6% male, mean age of 54.8 years. In 81.5% an epidemiological context was identified, mostly contact with sheep and goats. The duration of symptoms prior to diagnosis was 5.5 months. The most common signs and symptoms were pain (98.1%), fever (46.3%) and neurological deficits (25.9%). Spinal magnetic resonance imaging was the most used imaging method (77.8%) showing abscesses in 29.6% of patients. Lumbar location predominated (77.7%). Diagnosis was attained in 47 patients (87.0%): positive blood cultures (3 patients), positive serology (32 patients) or by both methods (12 patients). Combined regimens of doxycycline and rifampicin (64.8%), or streptomycin (24.1%) were most used, for an average duration of 4.4 months. A patient was referred for surgery for abscess drainage. Evolution was mostly favorable (92.6%), no deaths occurring. DISCUSSION: Research of the epidemiologic context turned out to be a major key leading to the diagnosis. Treatment of osteoarticular brucellosis is still controversial. CONCLUSIONS: Brucellar spondylodiscitis should be considered in the differential diagnosis of patients with low back pain, even in the absence of fever, particularly in regions where the disease is endemic. Antibiotic regimen, its' duration and the need for surgery should be individualized to achieve a better prognosis. Cases have declined over the years, a fact related to better control of animal endemic.

Introdução: A brucelose é uma zoonose endémica em Portugal, sendo a espondilodiscite brucélica uma das manifestações focaismais frequentes. Pode provocar sequelas graves, apesar da terapêutica dirigida.Material e Métodos: Estudo retrospectivo dos processos dos doentes com espondilodiscite brucélica, internados no Serviço de Doenças Infecciosas do Centro Hospitalar e Universitário de Coimbra, num período de 25 anos (1988-2012).Resultados: Foram identificados 54 doentes, 55,6% do sexo masculino, com idade média de 54,8 anos. Em 81,5% identificou-se contexto epidemiológico, maioritariamente contacto com gado ovino e caprino. A duração da sintomatologia prévia ao diagnóstico foi de 5,5 meses. Os sinais e sintomas mais frequentes foram: dor (98,1%), febre (46,3%) e défices neurológicos (25,9%). A ressonância magnética nuclear da coluna foi o exame imagiológico mais usado (77,8%) evidenciando abcessos em 29,6% dos doentes. A localizaçãolombar predominou (77,7%). O diagnóstico etiológico foi confirmado em 47 doentes (87,0%): microbiologicamente (3 doentes), serologicamente (32 doentes) ou por ambos (12 doentes). As associações de doxiciclina com rifampicina (64,8%), ou estreptomicina (24,1%) foram as mais utilizadas, com duração média de 4,4 meses de tratamento. Um doente teve indicação cirúrgica para drenar abcesso. A evolução foi maioritariamente favorável (92,6%), sem óbitos.Discussão: A investigação de contexto epidemiológico revelou ser uma peça importante na suspeita do diagnóstico. O tratamento da brucelose osteoarticular ainda é controverso.Conclusões: A espondilodiscite brucélica deve ser considerada no diagnóstico diferencial dos doentes com lombalgia, mesmo naausência de febre, particularmente em regiões onde a doença é endémica. O esquema antibiótico, sua duração e a necessidade de cirurgia deverão ser individualizados, com vista a um melhor prognóstico. O número de casos tem diminuído ao longo dos anos, facto relacionado com melhor controlo da endemia animal.

Plasmodium falciparum malaria, bilateral sixth cranial nerve palsy and delayed cerebellar ataxia.

We describe the case of a 14-year-old Caucasian male, a resident in the Democratic Republic of the Congo, who was observed in Portugal with severe Plasmodium falciparum malaria with high-level parasitemia and severe thrombocytopenia. The course was complicated by bilateral sixth cranial nerve palsy during acute malaria, followed by the appearance of delayed cerebellar ataxia during the recovery phase. This occurred after successful treatment with quinine plus doxycycline over seven days. Different levels of thrombocytopenia and C-reactive protein were observed during both neurologic events in the presence of HRP-2 positive tests for Plasmodium falciparum antigen. The patient recovered completely after three months.

First report of acute autochthonous hepatitis E in Portugal.

Hepatitis E infection is usually a self-limiting disease. In industrialized countries, sporadic cases of acute hepatitis E virus (HEV) infections have been described; their number seems to be increasing in European countries. We report the first human case of autochthonous acute hepatitis E confirmed in Portugal. Patients with acute non-A-C hepatitis should be tested for HEV in Portugal and hepatitis E infection should be considered in the differential diagnosis of unexplained hepatitis cases.

Mediterranean spotted fever and encephalitis: a case report and review of the literature.

Mediterranean spotted fever (MSF) is a disease caused by Rickettsia conorii and transmitted by the brown dog tick Rhipicephalus sanguineus. It is widely distributed through southern Europe, Africa, and the Middle East. It is an emerging or a reemerging disease in some regions. Countries of the Mediterranean basin, such as Portugal, have noticed an increased incidence of MSF over the past 10 years. It was believed that MSF was a benign disease associated with a mortality rate of 1-3% before the antimicrobial drug era. It was called benign summer typhus. Severe forms were described in 1981, and the mortality rate reached 32% in Portugal in 1997. However, neurological manifestations associated with brain lesions are a rare event. We describe the case of a man with fever, maculopapular rash, a black spot, and hemisensory loss including the face on the left side of the body with brain lesions in the imaging studies.