SUMMARY The past 2 decades have seen a revolution in our approach to therapeutic immunosuppression. We have moved from relying on broadly active traditional medications, such as prednisolone or methotrexate, toward more specific agents that often target a single receptor, cytokine, or cell type, using monoclonal antibodies, fusion proteins, or targeted small molecules. This change has transformed the treatment of many conditions, including rheumatoid arthritis, cancers, asthma, and inflammatory bowel disease, but along with the benefits have come risks. Contrary to the hope that these more specific agents would have minimal and predictable infectious sequelae, infectious complications have emerged as a major stumbling block for many of these agents. Furthermore, the growing number and complexity of available biologic agents makes it difficult for clinicians to maintain current knowledge, and most review articles focus on a particular target disease or class of agent. In this article, we review the current state of knowledge about infectious complications of biologic and small molecule immunomodulatory agents, aiming to create a single resource relevant to a broad range of clinicians and researchers. For each of 19 classes of agent, we discuss the mechanism of action, the risk and types of infectious complications, and recommendations for prevention of infection.

Summary Since coronavirus disease 2019 ( COVID ‐19) emerged in Wuhan, China in December 2019 and spread around the world, over 1100 clinical studies have been registered globally on clinical trials registries, including over 500 randomised controlled trials. Such rapid development and launch of clinical trials is impressive but presents challenges, including the potential for duplication and competition. There is currently no known effective treatment for COVID ‐19. In order to focus on those studies most likely to influence clinical practice, we summarise the 31 currently registered randomised trials with a target sample size of at least 1000 participants. We have grouped these trials into four categories: prophylaxis; treatment of outpatients with mild COVID ‐19; treatment of hospitalised patients with moderate COVID ‐19; and treatment of hospitalised patients with moderate or severe disease. The most common therapeutic agent being trialled currently is hydroxychloroquine (24 trials with potential sample size of over 25 000 participants), followed by lopinavir–ritonavir (seven trials) and remdesevir (five trials) There are many candidate drugs in pre‐clinical and early phase development, and these form a pipeline for future large clinical trials if current candidate therapies prove ineffective or unsafe.

A set of 44 Zinc-ligand bond-lengths and of 60 ligand-metal-ligand bond angles from 10 diverse transition-metal complexes, representative of the coordination spheres of typical biological Zn systems, were used to evaluate the performance of a total of 18 commonly available density functionals in geometry determination. Five different basis sets were considered for each density functional, namely two all-electron basis sets (a double-zeta and triple-zeta formulation) and three basis sets including popular types of effective-core potentials: Los Alamos, Steven-Basch-Krauss, and Stuttgart-Dresden. The results show that there are presently several better alternatives to the popular B3LYP density functional for the determination of Zn-ligand bond-lengths and angles. BB1K, MPWB1K, MPW1K, B97-2 and TPSS are suggested as the strongest alternatives for this effect presently available in most computational chemistry software packages. In addition, the results show that the use of effective-core potentials (in particular Stuttgart-Dresden) has a very limited impact, in terms of accuracy, in the determination of metal-ligand bond-lengths and angles in Zinc-complexes, and is a good and safe alternative to the use of an all-electron basis set such as 6-31G(d) or 6-311G(d,p).

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A doença de Gaucher (DG) foi a primeira doença de armazenamento lisossomal descrita e a mais encontrada. Caracteriza-se pela deficiência hereditária da atividade da enzima lisossomal glucocerebrosidase, que bloqueia o metabolismo do glicocerebrosídeo. A proposta deste trabalho foi estudar as características clínicas, laboratoriais e radiológicas, as principais mutações encontradas, relacionando-as com as formas clínicas e avaliar a resposta à terapia de reposição enzimática (TRE) nos pacientes com DG em Santa Catarina. Foram estudados dez pacientes com DG no Hospital Universitário, no período entre 1998 e 2003, após confirmação diagnóstica da doença pela dosagem da enzima beta-glicosidase em leucócitos. Pesquisa das mutações foi realizada em amostras de sangue e de mucosa oral. A média de idade ao diagnóstico foi de 19,6 anos. A DG tipo 1 foi diagnosticada em 80% dos casos, e a tipo 2 em 20%. Quatro pacientes tiveram história familiar de DG. Hepatoesplenomegalia foi a manifestação clínica mais comum. Anemia e trombocitopenia ocorreram em 100% dos casos. Dores ósseas foram relatadas por 75% dos pacientes. Os alelos mutantes encontrados foram N370S e L444P. Houve elevação dos níveis de hemoglobina em todos os pacientes com DG tipo 1. Concluímos que a DG tipo 1 é a forma clínica mais comum. Anemia, trombocitopenia, hepatoesplenomegalia e osteopenia são as características mais freqüentes dos pacientes com DG. O alelo N370S é o mais freqüente, estando relacionado com o tipo 1. O alelo L444P em homozigose sugere letalidade precoce. A TRE é segura e efetiva para a DG tipo 1. Rev. bras. hematol. hemoter. IntroduçãoA doença de Gaucher (DG) foi a primeira doença de armazenamento lisossomal descrita e é a lipidose mais freqüentemente encontrada. É caracterizada pela deficiência hereditária da atividade da enzima lisossomal glucocerebrosidase (ou beta-glicosidase), que hidrolisa o glicocerebrosídeo glucosilceramida em glicose e ceramida. Tal deficiência induz ao acúmulo deste glicolipídio, levando às altera-ções histológicas, que são especialmente evidenciadas nos órgãos ricos em elementos do sistema imunológico monocítico-fagocitário (fígado, baço, linfonodos e medula óssea). 1,2 Foi classificada em três tipos (1, 2 e 3), tendo como base a presença e a gravidade de envolvimento neurológico. O tipo 1 ou não neuropático (adulto) é a forma mais comum da doença, correspondendo a 99% dos casos. É especialmente prevalente entre os judeus Ashkenazi com uma incidência de cerca de 1:450 indivíduos e de 1:40.000 na população Artigo / Article

Streptococcus oralis is part of the normal flora of the oropharyngeal, nasal, gastrointestinal and genitourinary tracts. Classically, it shows low pathogenicity and virulence, but can very rarely cause meningitis in patients who have undergone dental procedures and have poor oral hygiene. The purpose of this report is to highlight the importance of considering S. oralis as a cause of meningitis in patients with poor oral hygiene. A 53-year-old man was admitted to the emergency department with high fever (39.4°C), headache and drowsiness. His mouth was unhygienic. He was diagnosed with meningitis and empiric antibiotics (ceftriaxone plus ampicillin) and dexamethasone were started. S. oralis was isolated from cerebrospinal fluid. Ampicillin and dexamethasone were stopped, while ceftriaxone was continued with full recovery of the patient.

Aim To compare the performance of the Nanra and Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation for estimating glomerular filtration rate in pregnancy against the 24 h urine creatinine clearance. Methods Pregnant women had 24 h urine collections with simultaneous serum creatinine levels. Measured 24 h urine creatinine clearance was compared to two equations: Nanra and CKD-EPI. Level of concordance was measured, with an a priori bias acceptance of ±15 ml/min/1.73 m2. Results A total of 53 synchronous urine and serum creatinine samples were analysed. The Nanra equation had a bias of −13.4 ml/min/1.73 m2 while the CKD-EPI equation had bias of 14.2 ml/min/1.73 m2. Both equations showed a high degree of proportional error and had poor agreement with 24 h urine creatinine clearance. Conclusions None of the equations were shown to reliably measure the estimated glomerular filtration rate in pregnant women. A valid serum creatinine-based estimated glomerular filtration rate equation in pregnancy is yet to be established.

The incremental cost-effectiveness ratio for patient treated at F2F3 ranged from 3 000 € / QALY to 20 000 € / QALY for 8 and 12 weeks treatment duration. The sensitivity analyses carried out confirmed the robustness of this result. ConClusions: Sofosbuvir-ledipasvir association is a cost-effective treatment option for patients with hepatitis C in most clinical contexts.