Antiviral therapy in acute viral hepatitis B: why and when

Acute viral hepatitis B is cleared in more than 95% of patients, while the remainder ones may develop either chronic HBV infection or, rarely, fulminant hepatitis

Polymyxin B hemoperfusion therapy and extracorporeal CO2 removal in a patient with COVID-19: A case report

Introduction: In December 2019, an outbreak of pneumonia caused by a novel coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) quickly spread and the corona virus disease 2019 (COVID-19) became a pandemic. We report on a 54-year-old patient with SARS-CoV-2 infection suffering from septic shock due to nosocomial infection and pulmonary derangement caused by SARS-CoV-2. The patient was treated with polymyxin B hemoperfusion (PMX-HP), a blood purification therapy against septic shock, followed by continuous low flow extracorporeal CO2 removal therapy. Case Report: A 54-year-old man was hospitalized for coronavirus disease 2019 (COVID-19). Chest computed tomography (CCT) showed extensive non-segmental ground glass opacity. Despite the initiation of standard therapy, respiratory failure progressed. After two days of polymyxin B hemoperfusion therapy (PMX-HP) with adjunctive corticosteroid for multi-resistant Gram-negative infection (Acinetobacter) the patient's condition improved. In rapidly progressive COVID-19 cases with secondary infection, the early use of PMX-HP may avoid the need for mechanical ventilation by suppressing local inflammation of the lung. Conclusion: The concern of life-threatening bacterial infections in critically ill COVID-19 patients due to antibiotics resistance is high. Secondary bacterial infections may develop during or following COVID-19 infection. The use of PMX-HP in septic shock patients has resulted in decreased dependency on ventilators, which is a serious issue during this COVID-19 pandemic. Combined and less invasive approaches might be considered in COVID-19 patients with multiple organ failure (MOF)

MaTESe: Machine Translation Evaluation as a Sequence Tagging Problem

Starting from last year, WMT human evaluation has been performed within the Multidimensional Quality Metrics (MQM) framework, where human annotators are asked to identify error spans in translations, alongside an error category and a severity. In this paper, we describe our submission to the WMT 2022 Metrics Shared Task, where we propose using the same paradigm for automatic evaluation: we present the MATESE metrics, which reframe machine translation evaluation as a sequence tagging problem. Our submission also includes a reference-free metric, denominated MATESE-QE. Despite the paucity of the openly available MQM data, our metrics obtain promising results, showing high levels of correlation with human judgements, while also enabling an evaluation that is interpretable. Moreover, MATESE-QE can also be employed in settings where it is infeasible to curate reference translations manually

Invasive mould infections in solid organ transplant patients: modifiers and indicators of disease and treatment response

Invasive mould infections, in particular invasive aspergillosis (IA), are comparatively frequent complications of immunosuppression in patients undergoing solid organ transplantation (SOT). Guidelines provide recommendations as to the procedures to be carried out to diagnose and treat IA, but only limited advice for SOT recipients. Literature review and expert consensus summarising the existing evidence related to prophylaxis, diagnosis, treatment and assessment of response to IA and infections by Mucorales in SOT patients Response to therapy should be assessed early and at regular intervals. No indications of improvement should lead to a prompt change of the antifungal treatment, to account for possible infections by Mucorales or other moulds such as Scedosporium. Imaging techniques, especially CT scan and possibly angiography carried out at regular intervals during early and long-term follow-up and coupled with a careful clinical diagnostic workout, should be evaluated as diagnostic tools and outcome predictors, and standardised to improve therapy monitoring. The role of biomarkers such as the galactomannan test and PCR, as well as selected inflammation parameters, has not yet been definitively assessed in the SOT population and needs to be studied further. The therapeutic workup should consider a reduction of immunosuppressive therapy. The role of immunosuppression and immune tolerance mechanisms in the response to invasive fungal infection treatment is an important factor in the SOT population and should not be underestimated. The choice of the antifungal should consider not only their toxicity but also their effects on the immune system, two features that are intertwined

Capsaicin-induced corneal sensory denervation and healing impairment are reversed by NGF treatment.

PURPOSE. We aimed to evaluate the nerve growth factor (NGF) pathway and its influence on corneal healing mechanisms in normal conditions and in an animal model of corneal denervation induced by capsaicin. METHODS. Peripheral sensory damage was induced in rat pups by subcutaneous injection of capsaicin and the effects evaluated by hot-plate test, corneal nerve count, and tear secretion. Corneal damage was induced in capsaicin-treated and -untreated rats by epithelial scraping. Healing rate; NGF pathway (NGF, tyrosine kinase A [TrkA], p75); and the stem cell marker p63 were evaluated by RT-PCR, ELISA, Western blot, and immunohistochemistry. The effects of exogenous NGF administration as eye drop formulation were also tested. RESULTS. Capsaicin treatment induced a significant reduction of peripheral sensitivity, corneal innervation, tear secretion, and corneal healing rate. The ocular effects of capsaicin treatment were associated with an NGF pathway alteration. NGF eye drop treatment aided corneal healing mechanisms through a significant increase in the NGF receptors TrkA and p75, and in the stem cell marker p63. CONCLUSIONS. In this study, we show that an alteration in the NGF pathway is responsible for a delay in corneal healing in an animal model of sensory denervation. Moreover, we show that NGF eye drop administration modulates corneal innervation, epithelial cell healing, and corneal stem cells. These findings may trigger further research on the role of the NGF pathway in limbal stem cell deficiency. (Invest Ophthalmol Vis Sci. 2012; 53:8280‐8287) DOI:10.1167/iovs.12-1059

T-helper 17 lymphocytes in ocular cicatricial pemphigoid

T-helper 17 lymphocytes (Th17) were identified in the healthy conjunctiva and in patients with ocular cicatricial pemphigoid (OCP), a disease characterized by chronic ocular surface inflammation

Relationship between physical growth, motor performance, biological maturation and chronological age in boys

Os objetivos desse estudo foram: a) comparar o desempenho motor e características antropométricas de jovens em diferentes estágios maturacionais em faixas etárias específicas (10-11, 12, 13, 14, 15-16 anos de idade); b) na faixa etária de 10 a 16 anos, verificar a contribuição relativa conjunta de caracter ísticas antropométricas, das idades cronológica e biológica (estágio de pilosidade) e de medidas de desempenho motor, nos resultados dos testes de SEMO (agilidade), salto horizontal e corrida de 30 m (velocidade). A amostra foi composta por 268 jovens do sexo masculino entre 10 e 16 anos de idade(M = 13,6; DP = 1,5) freqüentadores de um programa de iniciação esportiva. O conhecimento do estágio maturacional em que o jovem se encontrava não contribuiu na explicação da variabilidade dos resultados em nenhuma das medidas de desempenho motor realizadas. Concluiu-se que, em jovens de faixa etária semelhante, aqueles em estágios maturacionais mais adiantados tenderam a apresentar uma maior massa corporal e estatura, mas não apresentaram diferenças significantes na maioria das compara ções entre as variáveis de desempenho motor nos diferentes grupos considerados.The purposes of this study were: a) to compare the motor performance and anthropometric characteristics of youngsters with different maturation stages in specific age ranges (10-11, 12, 13, 14, 15-16 years); b) in the age range of 10 to 16 years, to verify the relative grouped contribution of anthropometric characteristics, biological age (pubic hair stage), chronological age and motor performance measures, in the results of the SEMO's test (agility), standing long jump and 30 m run (velocity). The sample was composed of 268 boys participants of a sport initiation program, with ages between 10 to 16 years (M = 13,6; SD = 1,53). The knowledge of the youth's maturacional status had no interference on performance variability explanation in the motor tests. In conclusion, boys with similar age range and advanced maturation status, showed a tendency to have a bigger body mass and to be higher than their peers, but significant differences were not found in most comparisons of motor performance variables in the different groups considered

Risk of Hepatocellular Carcinoma after HCV Clearance by Direct-Acting Antivirals Treatment. Predictive Factors and Role of Epigenetics

Abstract: Direct-acting antivirals (DAAs) induce a rapid virologic response (SVR) in up to 99% of chronic hepatitis C patients. The role of SVR by DAAs on the incidence or recurrence of carcinoma (HCC) is still a matter of debate, although it is known that SVR does not eliminate the risk of HCC. In this review, we made an updated analysis of the literature data on the impact of SVR by DAAs on the risk of HCC as well as an assessment of risk factors and the role of epigenetics. Data showed that SVR has no impact on the occurrence of HCC in the short–medium term but reduces the risk of HCC in the medium–long term. A direct role of DAAs in the development of HCC has not been demonstrated, while the hypothesis of a reduction in immune surveillance in response to the rapid clearance of HCV and changes in the cytokine pattern influencing early carcinogenesis remains to be further elucidated. HCV induces epigenetic alterations such as modifications of the histone tail and DNA methylation, which are risk factors for HCC, and such changes are maintained after HCV clearance. Future epigenetic studies could lead to identify useful biomarkers and therapeutic targets. Cirrhosis has been identified as a risk factor for HCC, particularly if associated with high liver stiffness and α-fetoprotein values, diabetes and the male sex. Currently, considering the high number and health cost to follow subjects’ post-HCV clearance by DAAs, it is mandatory to identify those at high risk of HCC to optimize management

Nattokinase historical sketch on experimental and clinical evidence

Nattokinase (NK) is a protease derived from food used mainly in the Japanese diet that has several properties. The main activity is related to improving fibrinolytic activities. Other activities have been demonstrated in the regulation of blood pressure by the action toward angiotensin proteases and in the antiplatelet activities. NK can be given orally and reaches its maximal concentration after 12 hours. In addition, an antithrombotic activity based on various NK activities has been proposed. First, increased fibrinolytic activity increases thrombus dissolution and/or the formation of atherosclerotic plaques; second, its enhanced antiplatelet action adds to clot dissolution. All activities have been studied in animals and humans in vitro and in vivo. Relevant adverse effects of NK therapy have not been described, however clinical experience is restricted to case series and volunteers and is not based on clinical studies, thus clinical trials are required to confirm

Carriers of ADAMTS13 Rare Variants Are at High Risk of Life-Threatening COVID-19

Thrombosis of small and large vessels is reported as a key player in COVID-19 severity. However, host genetic determinants of this susceptibility are still unclear. Congenital Thrombotic Thrombocytopenic Purpura is a severe autosomal recessive disorder characterized by uncleaved ultra-large vWF and thrombotic microangiopathy, frequently triggered by infections. Carriers are reported to be asymptomatic. Exome analysis of about 3000 SARS-CoV-2 infected subjects of different severities, belonging to the GEN-COVID cohort, revealed the specific role of vWF cleaving enzyme ADAMTS13 (A disintegrin-like and metalloprotease with thrombospondin type 1 motif, 13). We report here that ultra-rare variants in a heterozygous state lead to a rare form of COVID-19 characterized by hyper-inflammation signs, which segregates in families as an autosomal dominant disorder conditioned by SARS-CoV-2 infection, sex, and age. This has clinical relevance due to the availability of drugs such as Caplacizumab, which inhibits vWF-platelet interaction, and Crizanlizumab, which, by inhibiting P-selectin binding to its ligands, prevents leukocyte recruitment and platelet aggregation at the site of vascular damage