Elevated serum IL-6 levels predict treatment interruption in patients with moderate to severe psoriasis: a 6-year real-world cohort study

Abstract Background: Real-world, primary data on the treatment of psoriasis are scarce, especially concerning the role of soluble biomarkers as outcome predictors. Objective: The authors evaluated the utility of Th1/Th17 serum cytokines along with clinical characteristics as predictors of drug survival in the treatment of psoriasis. Methods: The authors consecutively included participants with moderate to severe psoriasis who were followed up for 6 years. Baseline interferon-α, tumor necrosis factor-α, and inter-leukin (IL)-2, IL-4, IL-6, IL-10, and IL-17A were measured using a cytometric bead array; clinical data were assessed. The authors calculated hazard ratios (HRs) for drug survival using a Cox proportional hazards model. Results: The authors included 262 patients, most of whom used systemic immunosuppressants or biologics. In the multivariate model, poor quality of life measured by the Dermatology Life Quality Index (HR = 1.04; 95% CI 1.01-1.07; p = 0.012) and elevated baseline IL-6 (HR = 1.99; 95% CI 1.29-3.08; p = 0.002) were associated with treatment interruption. Study limitations: The main limitation of any cohort study is the presence of confounders that could not be detected in clinical evaluation. Conclusions: Poor quality of life and elevated baseline serum IL-6 level predicted treatment interruption in patients with moderate to severe psoriasis. Although IL-6 is not the most important mediator of the inflammatory pathway in the skin environment, it is an interesting biomarker candidate for predicting psoriasis treatment response.

Elevated serum IL-6 levels predict treatment interruption in patients with moderate to severe psoriasis: a 6-year real-world cohort study.

BACKGROUND: Real-world, primary data on the treatment of psoriasis are scarce, especially concerning the role of soluble biomarkers as outcome predictors. OBJECTIVE: The authors evaluated the utility of Th1/Th17 serum cytokines along with clinical characteristics as predictors of drug survival in the treatment of psoriasis. METHODS: The authors consecutively included participants with moderate to severe psoriasis who were followed up for 6 years. Baseline interferon-α, tumor necrosis factor-α, and interleukin (IL)-2, IL-4, IL-6, IL-10, and IL-17A were measured using a cytometric bead array; clinical data were assessed. The authors calculated hazard ratios (HRs) for drug survival using a Cox proportional hazards model. RESULTS: The authors included 262 patients, most of whom used systemic immunosuppressants or biologics. In the multivariate model, poor quality of life measured by the Dermatology Life Quality Index (HR = 1.04; 95% CI 1.01‒1.07; p = 0.012) and elevated baseline IL-6 (HR = 1.99; 95% CI 1.29‒3.08; p = 0.002) were associated with treatment interruption. STUDY LIMITATIONS: The main limitation of any cohort study is the presence of confounders that could not be detected in clinical evaluation. CONCLUSIONS: Poor quality of life and elevated baseline serum IL-6 level predicted treatment interruption in patients with moderate to severe psoriasis. Although IL-6 is not the most important mediator of the inflammatory pathway in the skin environment, it is an interesting biomarker candidate for predicting psoriasis treatment response.

Randomized Phase III Trial Evaluating Subcutaneous Rituximab for the First-Line Treatment of Low-Tumor Burden Follicular Lymphoma: Results of a LYSA Study.

PURPOSE: Rituximab improves progression-free survival (PFS) and time to next treatment (TTNT) when compared with the watch and wait strategy for patients with low-tumor burden follicular lymphoma (FL). Prolonged rituximab maintenance did not prolong TTNT, whereas it raises concerns about resources use and patient adhesion. Our aim was then to investigate the use of short rituximab maintenance using the subcutaneous (SC) route in patients with low-tumor burden FL. METHODS: Patients with histologically confirmed CD20+ low-tumor burden FL were randomly assigned to receive either rituximab, 375 mg/m2 once daily on D1, D8, D15, and D22, intravenous route (IV, control arm), or rituximab, 375 mg/m2, on day 1 (D1), IV followed by rituximab 1,400 mg total dose, SC once daily on D8, D15, and D22, with maintenance at months 3 (M3), M5, M7, and M9 (experimental arm). The primary end point was PFS. Secondary end points included safety, overall response rates, TTNT, and overall survival (OS). RESULTS: Two hundred two patients with low-tumor burden FL were randomly assigned to the experimental (n = 100) or control arm (n = 102). The primary end point was met: the 4-year PFS was 58.1% (95% CI, 47.5 to 67.4) and 41.2% (95% CI, 30.6 to 51.6) in experimental and control arms, respectively (hazard ratio, 0.585 [0.393 to 0.871]; P = .0076). Complete response (CR) rates were 59.0% (95% CI, 48.7 to 68.7) in the experimental arm and 36.3% (95% CI, 27.0 to 46.4) in the control arm (P = .001). TTNT and OS were not significantly different. CR was associated with longer PFS and TTNT. High rituximab exposure during the first three months was independently associated with higher CR, PFS, and TTNT. CONCLUSION: SC rituximab improves PFS for patients with low-tumor burden FL when used in induction followed by short maintenance. High rituximab exposure during the first 3 months after treatment initiation is, however, the only parameter influencing patient outcomes.

Pomalidomide and dexamethasone until progression after first salvage therapy in multiple myeloma.

Lenalidomide maintenance in myeloma is well established. Nevertheless, pomalidomide could provide an alternative. Myeloma patients in first relapse, initially treated in the Intergroupe Francophone du Myélome (IFM) 2009 trial, and subsequently in the IFM 2013-01 phase 2 trial, received four cycles of salvage therapy with pomalidomide plus cyclophosphamide plus dexamethasone (PCD) with transplantation plus 2 PCD consolidation or without transplantation but with 5 PCD and for all patients pomalidomide plus dexamethasone maintenance therapy. This consisted of 28-day cycles of pomalidomide 4 mg daily on days 1-21 and dexamethasone 20 mg weekly until progression. The primary endpoint was an improved response to treatment. A total of 75/100 patients reached therapy. The median follow-up time was 73 months. The median duration of treatment was 23.7 months. One third of patients improved their response from the initiation of treatment: 11%, 19% and 4% to a very good partial response, complete response or stringent complete response respectively. The median progression-free survival time was 33.2 months and the median overall survival time was not reached. Among the 75 patients, the reasons for pomalidomide discontinuation were progressive disease (54%), adverse events (AEs) (30%), investigator discretion (11%) and consent withdrawal (5%). Grade (G) 3/4 haematological AEs included neutropenia (51%) and lymphopenia (35%); G3/4 drug-related non-haematological AEs (>5%) comprised 13% infections. Long-term administration of pomalidomide and dexamethasone is feasible and one third of the patients improved their response.

Twenty years of real-world data to estimate chronic kidney disease prevalence and staging in an unselected population.

Chronic kidney disease (CKD) represents a global public health burden, but its true prevalence is not fully characterized in the majority of countries. We studied the CKD prevalence in adult users of the primary, secondary and tertiary healthcare units of an integrated health region in northern Portugal (n = 136 993; representing ∼90% of the region's adult population). Of these, 45 983 (33.6%) had at least two estimated glomerular filtration rate (eGFR) assessments and 30 534 (22.2%) had at least two urinary albumin:creatinine ratio (UACR) assessments separated by at least 3 months. CKD was defined according to the Kidney Disease: Improving Global Outcomes (KDIGO) guidelines as a persistent decrease in eGFR (<60 ml/min/1.73 m2) and/or an increase in UACR (≥30 mg/g). The estimated overall prevalence of CKD was 9.8% and was higher in females (5.5%) than males (4.2%). From these, it was possible to stratify 4.7% according to KDIGO guidelines. The prevalence of CKD was higher in older patients (especially in patients >70 years old) and in patients with comorbidities. This is the first real-world-based study to characterize CKD prevalence in a large, unselected Portuguese population. It probably provides the nearest estimate of the true CKD prevalence and may help healthcare providers to guide CKD-related policies and strategies focused on prevention and on the improvement of cardiovascular disease and other outcomes.

Heterogeneity in long-term outcomes for patients with Revised International Staging System stage II, newly diagnosed multiple myeloma.

In the era of personalized treatment in multiple myeloma, high-risk patients must be accurately identified. The International Myeloma Working Group recommends using the Revised International Staging System (R-ISS) to pick out high-risk patients. The main purpose of our work was to explore the heterogeneity of outcome among R-ISS stage II patients assessing the impact of International Staging System (ISS) stage, chromosomal abnormalities and lactate dehydrogenase level in this subgroup. Data were collected from 1,343 patients up to 65 years old with newly diagnosed myeloma, enrolled in three clinical trials implemented by the Intergroupe Francophone du Myélome. All patients were eligible for intensive treatment. Patients in R-ISS stage II but ISS stage I had 1.6 times higher risk of death than patients in R-ISS stage I (adjusted hazard ratio=1.6; 95% confidence interval: 1.1-2.2; P=0.01) and patients in R-ISS stage II but with ISS stage III had a better overall survival than patients in R-ISS stage III (adjusted hazard ratio=0.7; 95% confidence interval: 0.4-0.9, P=0.02). However, among patients classified in R-ISS II, ISS stage and chromosomal abnormalities (del[17p] and t[4;14]) were still relevant prognostic factors for death. Dividing R-ISS stage II into three subgroups: ISS I with standard-risk chromosomal abnormalities, ISS II or III with standard-risk chromosomal abnormalities and patients with high-risk chromosomal abnormalities, median overall survival times were, respectively, not reached, 112 months and 71 months (P<0.001). In conclusion, stratification of patients in the R-ISS stage II group can be improved by taking into account chromosomal abnormalities and ISS. However, this does not improve predictive performance of survival models.

Bortezomib and high-dose melphalan conditioning regimen in frontline multiple myeloma: an IFM randomized phase 3 study.

High-dose melphalan (HDM) and transplantation are recommended for eligible patients with multiple myeloma. No other conditioning regimen has proven to be more effective and/or safer. We previously reported in a phase 2 study that bortezomib can safely and effectively be combined with HDM (Bor-HDM), with a 32% complete response (CR) rate after transplantation. These data supported a randomized phase 3 trial. Randomization was stratified according to risk and response to induction: 300 patients were enrolled, and 154 were allocated to the experimental arm (ie, arm A) with bortezomib (1 mg/m2 intravenously [IV]) on days -6, -3, +1, and +4 and melphalan (200 mg/m2 IV) on day -2. The control arm (ie, arm B) consisted of HDM alone (200 mg/m2 IV). There were no differences in stringent CR + CR rates at day 60 posttransplant (primary end point): 22.1% in arm A vs 20.5% in arm B (P = .844). There were also no differences in undetectable minimum residual disease rates: 41.3% vs 39.4% (P = .864). Median progression-free survival was 34.0 months for arm A vs 29.6 months for arm B (adjusted HR, 0.82; 95% CI, 0.61-1.13; P = .244). The estimated 3-year overall survival was 89.5% in both arms (hazard ratio, 1.28; 95% CI, 0.62-2.64; P = .374). Sixty-nine serious adverse events occurred in 18.7% of Bor-HDM-treated patients (vs 13.1% in HDM-treated patients). The proportion of grade 3/4 AEs was similar within the 2 groups (72.0% vs 73.1%), mainly (as expected) blood and gastrointestinal disorders; 4% of patients reported grade 3/4 or painful peripheral neuropathy in arm A (vs 1.5% in arm B). In this randomized phase 3 study, a conditioning regimen with Bor-HDM did not improve efficacy end points or outcomes compared with HDM alone. The original trial was registered at www.clinicaltrials.gov as #NCT02197221.

Teste de Progresso para estudantes de Medicina: experiência de um consórcio na Região Nordeste do Brasil / Progress Test for medical students: experience of a consortium in Northeastern Brazil

Resumo: Introdução: A colaboração entre escolas médicas para a realização do Teste de Progresso (TP) vem sendo ampliada com o propósito de tornar-se um modelo de prática educacional. Relato de experiência: O núcleo de escolas médicas CIN1 foi instituído no ano de 2013, tendo na sua organização um coordenador-geral e coordenadores de cada escola participante. Realiza dois testes ao ano, variando o número de escolas participantes. O teste possui 120 questões distribuídas nas seis áreas (ciências básicas aplicada, saúde coletiva, pediatria, clínica médica, cirurgia/urgência e emergência, e ginecologia e obstetrícia) e tem seu blueprint baseado em matriz previamente validada. O teste é aplicado a todos os estudantes das escolas participantes, no mesmo dia e com duração de quatro horas. Aconteceu on-line em 2020 e 2021, por causa da pandemia da Covid-19. A pontuação total do estudante é calculada pelo número de questões corretas, sem a opção "não sei", nem penalidades para incorretas. A análise é realizada por meio da teoria clássica do item. Os estudantes recebem a análise do desempenho comparativamente com a média obtida pelos discentes no mesmo ano e a progressão em relação ao teste anterior. As escolas recebem o desempenho dos respectivos estudantes, a análise da dificuldade e discriminação geral dos itens, e uma avaliação global do teste. Discussão: A implantação do CIN1 representou um grande avanço para as escolas envolvidas. A colaboração não se deu apenas sobre o teste, mas também para o desenvolvimento docente de forma conjunta. Impedimentos de regimento interno e custos podem justificar a variação na participação das escolas. Conclusão: A organização de um núcleo de escolas para o TP traz benefícios e muitos desafios. O aperfeiçoamento dos critérios de análises e feedback e a inclusão de estudantes na avaliação de questões são etapas a serem discutidas e implantadas. A utilização do ambiente virtual, de mais baixo custo, pode ser um facilitador para ampliar a participação das escolas.

Abstract: Introduction: Collaboration between medical schools to hold the PT has expanded, constituting a model of educational practice. Experience report: The CIN 1 group of medical schools was established in 2013, organized with a general coordinator and coordinators from each participating school. It holds two tests a year, with a varying number of participant schools. The test has 120 questions distributed in 6 areas (Applied Basic Sciences, Public Health, Pediatrics, Internal Medicine, Surgery/Urgent and Emergency, Gynecology and Obstetrics) and its blueprint is based on a previously validated Matrix. The 4-hour test is applied to all students from participating schools, on the same day and at the same time. It was administered online in 2020 and 2021 due to the COVID-19 pandemic. The student's total score is calculated by the number of correct questions, excluding the "don't know" option, or penalties for incorrect ones, and is analyzed by classical item theory. Students receive performance analysis compared to the average attained by students in the same year, and the progression in relation to the previous test. The schools receive the performance of the respective students and analysis of the difficulty and general breakdown of the items and an overall evaluation of the test. Discussion: The implementation of CIN 1 represented a great advance for the schools involved. The collaboration was not only about the test, but also for the teacher development in a joint way. Bylaw impediments and costs may justify the variation in school participation. Conclusion: The organization of a group of schools for the TP brings benefits and many challenges. Improving analysis and feedback criteria and including students in the assessment of questions are steps to be discussed and implemented. The use of the lower cost virtual environment may facilitate increased participation of schools.

Avaliação do conhecimento dos profissionais de Enfermagem na prevenção da lesão por pressão na terapia intensiva / Evaluación del conocimiento de los profesionales de Enfermería en la prevención de lesiones por presión en cuidados intensivos / Evaluation of the knowledge of nursing professionals in the prevention of pressure ulcer in intensive care

RESUMO Objetivo analisar o conhecimento dos profissionais de Enfermagem sobre a avaliação, prevenção e classificação das lesões por pressão na terapia intensiva antes e após a realização de um treinamento. Método trata-se de um estudo comparativo, tipo antes e depois, transversal, com delineamento prospectivo, que utilizou o instrumento Teste de Conhecimento sobre Lesão por Pressão de Caliri-Pieper (TCLP CALIRI-PIEPER) aplicado antes e após a realização de um treinamento com 55 e 50 profissionais da Enfermagem, respectivamente. A média de acerto aceitável foi de acima de 90%. Resultados do total de 41 itens do instrumento, 14 (34%) não obtiveram pontuação média acima de 90% de acerto, sendo os técnicos de Enfermagem inseridos neste contingente. Evidenciou-se que o efeito do treinamento na amostra total obteve, em média, um acréscimo de 3,5 pontos no nível de conhecimento. A diferença média entre a pontuação obtida no pré e pós-teste foi estatisticamente significativa (p<0,001). Conclusões e implicações para a prática os participantes avaliados demonstraram níveis de conhecimento eficaz e baixa divergência entre as categorias, evidenciando que os profissionais estão capacitados e preparados, possuindo domínio nos fatores relacionados à avaliação, prevenção e classificação das lesões por pressão na terapia intensiva após a realização de um treinamento.

RESUMEN Objetivo analizar los conocimientos de los profesionales de Enfermería sobre la evaluación, prevención y clasificación de las lesiones por presión en cuidados intensivos antes y después de la realización de una formación. Método se trata de un estudio comparativo, antes y después, transversal con un diseño prospectivo que utilizó el instrumento Caliri-Pieper Pressure Injury Knowledge Test (CALIRI-PIEPER TCLP) aplicado antes y después del entrenamiento con 55 y 50 profesionales de Enfermería, respectivamente. La media aceptable de derecho a golpe fue superior al 90%. Resultados del total de 41 ítems del instrumento, 14 (34%) no obtuvieron un puntaje promedio superior al 90% de acierto, con los técnicos de Enfermería incluidos en este contingente. Se evidenció que el efecto formación en la muestra total obtuvo, en promedio, un incremento de 3,5 puntos en el nivel de conocimientos. La diferencia promedio entre las puntuaciones previas y posteriores a la prueba fue estadísticamente significativa (p <0,001). Conclusiones e implicaciones para la práctica los participantes evaluados demostraron niveles de conocimiento efectivo y baja divergencia entre las categorías, evidenciando que los profesionales están capacitados y preparados, teniendo dominio de los factores relacionados con la evaluación, prevención y clasificación de lesiones por presión en cuidados intensivos después del entrenamiento.

ABSTRACT Objective to analyze the knowledge of Nursing professionals on the assessment, prevention and classification of pressure ulcers in intensive care before and after a training course. Method this is a comparative, before-and-after, cross-sectional, prospective study that used the Caliri-Pieper Pressure Ulcer Knowledge Test (CALIRI-PIEPER PUKT) applied before and after training with 55 and 50 nursing professionals, respectively. The acceptable mean score was above 90%. Results of the total of 41 items of the instrument, 14 (34%) did not obtain an average score above 90% of correct answers, and the nursing technicians were included in this contingent. It was evident that the effect of the training on the total sample obtained, on average, a 3.5 point increase in the level of knowledge. The mean difference between the scores obtained in the pre- and post-test was statistically significant (p<0.001). Conclusions and implications for the practice the participants evaluated demonstrated effective levels of knowledge and low divergence between the categories, showing that the professionals are trained and prepared, having domain in the factors related to the evaluation, prevention and classification of pressure ulcers in intensive care after training.

Ultrasound-guided percutaneous renal biopsy at a university hospital: retrospective analysis of success and complication rates.

OBJECTIVE: To evaluate the success and complication rates of ultrasound-guided renal biopsy at a tertiary care hospital. MATERIALS AND METHODS: This was a retrospective analysis of 97 ultrasound-guided renal biopsies, all performed by the same radiologist, between 1 March, 2017 and 31 October, 2019. RESULTS: Of the 97 biopsies evaluated, 87 had a definitive pathological diagnosis. In five cases (5.4%), the biopsy results were inconclusive and a second procedure was required. In seven procedures (7.6%), there were complications, all of which were properly resolved. CONCLUSION: Ultrasound-guided renal biopsy has proven to be a safe, effective method for the diagnosis of nephropathies, with high success rates.

OBJETIVO: Avaliar taxas de sucesso e de complicações de biópsias renais guiadas por ultrassonografia em um hospital terciário. MATERIAIS E MÉTODOS: Análise retrospectiva de 97 biópsias renais realizadas entre 1º de março de 2017 e 31 de outubro de 2019, guiadas por ultrassonografia e executadas por um único médico radiologista. RESULTADOS: Oitenta e sete biópsias apresentaram diagnóstico anatomopatológico definitivo. Cinco biópsias foram inconclusivas (5,4%) e precisaram de um segundo procedimento. Houve complicações em sete procedimentos (7,6%), todas devidamente solucionadas. CONCLUSÃO: A biópsia renal guiada por ultrassonografia demonstrou ser um método efetivo e seguro para o diagnóstico de nefropatias, com elevada taxa de sucesso em sua execução.

Ultrasound-guided percutaneous renal biopsy at a university hospital: retrospective analysis of success and complication rates / Biópsia renal percutânea guiada por ultrassonografia: análise retrospectiva de sucesso e complicações em um hospital universitário

Abstract Objective: To evaluate the success and complication rates of ultrasound-guided renal biopsy at a tertiary care hospital. Materials and Methods: This was a retrospective analysis of 97 ultrasound-guided renal biopsies, all performed by the same radiologist, between 1 March, 2017 and 31 October, 2019. Results: Of the 97 biopsies evaluated, 87 had a definitive pathological diagnosis. In five cases (5.4%), the biopsy results were inconclusive and a second procedure was required. In seven procedures (7.6%), there were complications, all of which were properly resolved. Conclusion: Ultrasound-guided renal biopsy has proven to be a safe, effective method for the diagnosis of nephropathies, with high success rates.

Resumo Objetivo: Avaliar taxas de sucesso e de complicações de biópsias renais guiadas por ultrassonografia em um hospital terciário. Materiais e Métodos: Análise retrospectiva de 97 biópsias renais realizadas entre 1º de março de 2017 e 31 de outubro de 2019, guiadas por ultrassonografia e executadas por um único médico radiologista. Resultados: Oitenta e sete biópsias apresentaram diagnóstico anatomopatológico definitivo. Cinco biópsias foram inconclusivas (5,4%) e precisaram de um segundo procedimento. Houve complicações em sete procedimentos (7,6%), todas devidamente solucionadas. Conclusão: A biópsia renal guiada por ultrassonografia demonstrou ser um método efetivo e seguro para o diagnóstico de nefropatias, com elevada taxa de sucesso em sua execução.

Índice de vulnerabilidade à COVID-19: uma aplicação para a cidade de Fortaleza (CE), Brasil / Vulnerability index to COVID-19: Fortaleza, Brazil study case

RESUMO O estudo propôs a elaboração de um índice de vulnerabilidade à propagação da COVID-19 utilizando análise multivariada associada à análise geoespacial. O método empregado considerou a vulnerabilidade como uma combinação de três fatores: exposição, susceptibilidade e capacidade de resposta. A metodologia foi composta de seis etapas: seleção e agrupamento de variáveis; definição dos indicadores; normalização; atribuição de pesos via análise dos componentes principais; estimativa e normalização do índice; e classificação por meio das técnicas Jenks, Kmeans, quantis e clusterização hierárquica (Hclust). Foi realizada uma caracterização da exposição da cidade de Fortaleza, Brasil, à COVID-19 por meio da densidade populacional, da quantidade de habitações subnormais e precárias, da porcentagem de idosos por residência e da proximidade a terminais de ônibus. O estudo procurou sobrepor fatores socioeconômicos e índices de abastecimento público e de esgotamento sanitário, para a classificação de setores censitários em cinco níveis de vulnerabilidade. Estes apresentaram, em sua maioria, classe de alta (Jenks e quantis) e moderada (K-means e Hclust) vulnerabilidade. As regiões de maior vulnerabilidade estão localizadas no sul e no oeste da cidade, onde há maior concentração de aglomerados subnormais. Os resultados podem auxiliar no desenvolvimento de estratégias de enfrentamento direcionadas para os grupos mais expostos aos riscos associados à COVID-19, assim como na preparação para futuras crises de saúde pública. A metodologia pode ser replicada para outras cidades e serve como ferramenta para os gestores públicos.

ABSTRACT The study proposes an index of vulnerability to the spread of COVID-19 using multivariate and geospatial analyses. Vulnerability was considered as a combination of exposure, susceptibility, and responsiveness of the population. The methodology consisted of six steps: selection and grouping of variables; definition of indicators; normalization of the variables; weight calculation using principal component analysis; index calculation and normalization; and classification using Jenks, Kmeans, Quantile, and Hclust techniques. The exposure of Fortaleza, Brazil, to COVID-19 was assessed by means of population density, number of subnormal and precarious housing, percentage of aged people per residence and proximity to bus terminals. The study integrates factors related to socioeconomic characteristics, public water supply and sanitation for the classification of census tracts in five levels of vulnerability. Most of them present high (Jenks and Quantile) and moderate (K-means and Hclust) vulnerability. The most vulnerable regions are in the South and West Zones of the city, where many subnormal agglomerates are located. The results can assist the development of coping strategies for the groups most exposed to the risks associated with COVID-19, as well as in the preparation for future public health crises. The methodology can be replicated in other cities and can be useful for public managers.

Mapping Salivary Proteases in Sjögren's Syndrome Patients Reveals Overexpression of Dipeptidyl Peptidase-4/CD26.

Sjögren's Syndrome (SS) is an autoimmune exocrinopathy characterized by the progressive damage of salivary and lacrimal glands associated with lymphocytic infiltration. Identifying new non-invasive biomarkers for SS diagnosis remains a challenge, and alterations in saliva composition reported in patients turn this fluid into a source of potential biomarkers. Among these, proteases are promising candidates since they are involved in several key physio-pathological processes. This study evaluated differentially expressed proteases in SS individuals' saliva using synthetic fluorogenic substrates, zymography, ELISA, and proteomic approaches. Here we reported, for the first time, increased activity of the serine protease dipeptidyl peptidase-4/CD26 (DPP4/CD26) in pSS saliva, the expression level of which was corroborated by ELISA assay. Gelatin zymograms showed that metalloproteinase proteolytic band profiles differed significantly in intensity between control and SS groups. Focusing on matrix metalloproteinase-9 (MMP9) expression, an increased tendency in pSS saliva (p = 0.0527) was observed compared to the control group. Samples of control, pSS, and sSS were analyzed by mass spectrometry to reveal a general panorama of proteases in saliva. Forty-eight protein groups of proteases were identified, among which were the serine proteases cathepsin G (CTSG), neutrophil elastase (ELANE), myeloblastin (PRTN3), MMP9 and several protease inhibitors. This work paves the way for proteases to be explored in the future as biomarkers, emphasizing DPP4 by its association in several autoimmune and inflammatory diseases. Besides its proteolytic role, DPP4/CD26 acts as a cell surface receptor, signal transduction mediator, adhesion and costimulatory protein involved in T lymphocytes activation.

Enhanced IL-6 and IL-12B Gene Expression After SARS-CoV-2 Infection in Leprosy Patients May Increase the Risk of Neural Damage.

Experts have called attention to the possible negative impact of the coronavirus disease 2019 (COVID-19)-related cytokine storm syndrome on the progression of leprosy-related disabilities. We assessed the frequency of reactional states in patients co-infected with Mycobacterium leprae and severe acute respiratory syndrome (SARS) coronavirus (CoV) 2 (SARS-CoV-2). We consecutively included patients during the first peak of the COVID-19 epidemic in Brazil and analyzed the expressions of genes encoding interleukin (IL)-1ß, IL-6, IL-8, IL-10, IL-12A, IL-12B, and tumor necrosis factor-α in peripheral blood mononuclear cells. We included 64 leprosy patients and 50 controls. Twelve of the leprosy patients and 14 of the controls had been diagnosed with COVID-19. Co-infection was associated with increased IL-6 (P = 0.043) and IL-12B (P = 0.017) expression. The median disability grades were higher for leprosy/COVID-19 patients; however, the difference was not significant (P = 0.194). Patients co-infected with M. leprae and SARS-CoV-2 may experience a higher-grade proinflammatory state.

Análise das práticas assistenciais para prevenção das infecções primárias da corrente sanguínea / Análisis de las prácticas asistenciales para la prevención de las infecciones primarias de la circulación sanguínea / Analysis of healthcare practices for prevention of primary bloodstream infections

RESUMO Objetivo: analisar as práticas assistenciais no uso do cateter venoso central para a prevenção das Infecções Primárias da Corrente Sanguínea em uma Unidade de Terapia Intensiva. Método: estudo transversal realizado em um Hospital Universitário entre março e junho de 2018 com profissionais de uma Unidade de Terapia Intensiva. Utilizaram-se questionário estruturado e observação não participante dos procedimentos inserção, preparo e administração de medicação e troca de curativos de cateter central. Os dados foram analisados por meio da estatística descritiva com aplicação do Teste Qui-quadrado e exato de Fisher. Resultados: participaram 83 profissionais de enfermagem e 25 médicos. Foram observadas 260 administrações de medicações, 32 inserções de cateter e 29 trocas de curativos. Houve inadequação da prática de higienização das mãos nos procedimentos de manutenção, principalmente entre os técnicos de enfermagem. Os melhores resultados foram preparo da pele (94%), secagem espontânea do antisséptico antes das punções (96,87%) e respeito às trocas dos equipos de infusão contínua e intermitente (93,42%). Conclusão: o seguimento dasmedidas preventivas estava comprometido em oportunidades importantes para evitar Infecções Primárias da Corrente Sanguínea, sendo necessário reforçar a educação permanente e a implementação de protocolos assistenciais.

RESUMEN Objetivo: analizar las prácticas asistenciales en el uso del catéter venoso central para la prevención de las Infecciones Primarias de la Circulación Sanguínea en una Unidad de Cuidados Intensivos. Método: estudio transversal realizado en un Hospital Universitario entre marzo y junio de 2018 con profesionales de una Unidad de Cuidados Intensivos. Se utilizaron cuestionario estructurado y observación no participante de los procedimientos inserción, preparación y administración de medicación y cambio de vendajes de catéter central. Los datos fueron analizados por medio de la estadística descriptiva con aplicación delaPrueba Chi-cuadrado y exacta de Fisher. Resultados: participaron 83 profesionales de enfermería y 25 médicos. Se observaron 260 administraciones de medicamentos, 32 inserciones de catéter y 29 intercambios de vendajes. Hubo inadecuación de la práctica de higienización de las manos en los procedimientos de mantenimiento, principalmente entre los técnicos de enfermería. Los mejores resultados fueron preparación de la piel (94%), secado espontáneo del antiséptico antes de las punciones (96,87%) y respeto a los cambios de los equipos de infusión continua e intermitente (93,42%). Conclusión: el seguimiento de las medidas preventivas estaba comprometido en oportunidades importantes para evitar Infecciones Primarias de la Circulación Sanguínea, siendo necesario reforzar la educación permanente y la implementación de protocolos asistenciales.

ABSTRACT Objective: to analyze healthcare practices in the use of central venous catheters for the prevention of Primary Bloodstream Infections in an Intensive Care Unit. Method: cross-sectional study conducted in a University Hospital between March and June 2018 with professionals working in an Intensive Care Unit. A structured questionnaire and non-participant observation of the procedures related to insertion, preparation and administration of drugs and change of central catheter dressings were used. The data were analyzed using descriptive statistics and applying the Chi-square and Fisher's exact tests. Results: a total of 83 nursing professionals and 25 physicians participated. There were 260 drug administrations, 32 catheter insertions and 29 dressing changes. There was inadequacy of the hand hygiene practice in maintenance procedures, especially among nursing technicians. The best results were: skin preparation (94%), spontaneous drying of the antiseptic before punctures (96.87%) and respect for the changes of continuous and intermittent infusion sets (93.42%). Conclusion: the follow-up of preventive measures was undermined in important opportunities to avoid Primary Bloodstream Infections, being necessary to reinforce continuing education and implementation of healthcare protocols.

Medical education in times of COVID - 19: an experience at Faculdade Pernambucana da Saúde / Educação médica em tempos de COVID - 19: a experiência da Faculdade Pernambucana da Saúde

Abstract Objectives: to describe and discuss interventions and strategies carried out at Faculdade Pernambucana de Saúde (FPS) during the COVID-19 pandemic to mitigate impairment in learning and preserve students, tutors, and staff's health. Experience report: the teaching methodology used by FPS is problem-based learning, which greatly facilitated the non-discontinuity of theoretical activities carried out in-person in tutorial sessions involving a tutor and 10 to 12 students. This format was transferred to Webex Meetings rooms and held remotely. Practical laboratory activities were suspended and resumed when allowed in July. The teaching outpatient activities (third and fourth year) were suspended and resumed in August. Two years of internship were interrupted for 30 days (fifth year) and for 15 days (sixth year). External activities of practices in primary care were also suspended and resumed gradually. All assessments and activities that required face-to-face meetings, integrations, scientific initiation program orientations, collegiate meetings, meetings of the self-assessment committee were and are being carried out remotely. Conclusions: we believe that we were able to mitigate impairment in students' learning without compromising the conclusion of the school year that was facilitated by Problem Based Learning method.

Resumo Objetivo: descrever e discutir intervenções e estratégias realizadas pela Faculdade Pernambucana de Saúde (FPS) durante a pandemia de COVID-19 para atenuar prejuízos no aprendizado e preservar a saúde de estudantes, docentes e funcionários. Relato de experiência: a metodologia de ensino usada pela FPS é a aprendizagem baseada em problemas, que facilitou a não descontinuidade das atividades teóricas realizadas presencialmente em sessões tutoriais que envolvem um docente e dez a 12 estudantes, que foram transferidas para salas de Webex Meetings de forma remota. As atividades de laboratórios práticas foram suspensas e retomadas quando permitido no mês de julho. As atividades de ambulatório de ensino (terceiro e quarto ano) foram suspensas e retomadas em agosto. Os dois anos de internato sofreram interrupção de 30 dias (quinto ano) e 15 dias (sexto ano). As atividades externas de práticas em atenção primária também foram suspensas e retomadas gradativamente. Todas as avaliações e atividades que necessitavam reuniões presenciais: integrações, orientações de programa de iniciação científica, reuniões colegiadas, reuniões da comissão própria de autoavaliação foram e estão sendo realizadas de forma remota. Conclusões: acreditamos que conseguimos minimizar os prejuízos no aprendizado dos estudantes sem comprometimento de conclusão do ano letivo que foi facilitado pela metodologia de aprendizagem baseada em problemas.

Atuação da gestão institucional na prevenção das infecções primárias da corrente sanguínea

RESUMO Objetivo: Analisar a atuação da gestão institucional na prevenção das Infecções Primárias da Corrente Sanguínea. Material e Método: Estudo descritivo exploratório de abordagem qualitativa, realizado com profissionais de Unidade de Terapia Intensiva adulto e gestores hospitalares, em um Hospital Universitário de uma capital do nordeste brasileiro no período de março a dezembro de 2018. Na primeira etapa a amostra foi composta por 25 médicos e 83 profissionais de enfermagem, sendo 19 enfermeiros e 64 técnicos de enfermagem, totalizando 108 participantes. Foram aplicados questionários com perguntas abertas sobre o sentimento de apoio institucional e motivação à cultura de segurança. A taxa de resposta dos questionários foi de 96,43%. Na segunda etapa os achados foram discutidos com sete representantes da gestão em um grupo focal. Realizou-se análise de conteúdo com Atlas ti® versão 8.3.20. Resultados: Foram elucidadas as seguintes categorias: 1) dificuldades no cuidado seguro aos pacientes com cateter venoso central; 2) práticas resolutivas para enfrentamento das dificuldades; 3) fatores organizacionais e educacionais relacionados à ocorrência das infecções e 4) propostas dos gestores para alcançar bons resultados. Conclusões: Para prevenção das infecções, evidenciou-se a necessidade de participação das equipes assistenciais na construção de protocolos, organização tecnológica interna, controle do desabastecimento, padronização do acesso à unidade e aumento da periodicidade das capacitações com uso do ensino à distância, utilizando metodologias ativas

ABSTRACT Objective: To analyze the institutional management performance in the prevention of primary bloodstream infections. Material and Method: Descriptive exploratory study with a qualitative approach, conducted with professionals of an adult Intensive Care Unit and hospital managers in a university hospital in a city of the Brazilian Northeast, between March and December 2018. In the first stage, the sample consisted of 25 physicians and 83 nursing professionals, 19 nurses and 64 nursing technicians, totaling 108 participants. Questionnaires with open-ended questions about the feeling of institutional support and motivation towards safety culture were applied. The response rate of the questionnaires was 96.43%. In the second stage, the findings were discussed with seven managers within a focus group. Content analysis was carried out using Atlas.ti® version 8.3.20. Results: The following categories emerged: 1) difficulties regarding safe care for patients with central venous catheters; 2) resolutive practices to face difficulties; 3) organizational and educational factors related to the occurrence of infections and 4) managers' proposals to achieve good results. Conclusions: In order to prevent infections it is necessary to encourage the participations of care teams in the elaboration of protocols, internal technological organization, control of shortages, standardization of access by professionals in the unit, increased frequency of training using distance learning platforms and implementation of active methodologies

RESUMEN Objetivo: Analizar el desempeño del manejo institucional en la prevención de infecciones primarias del torrente sanguíneo. Material y Método: Estudio exploratorio descriptivo con abordaje cualitativo, realizado con profesionales de una Unidad de Cuidados Intensivos para adultos y gestores hospitalarios en un hospital universitario de una capital del nordeste brasileiro, en el período de marzo a diciembre de 2018. En la primera etapa la muestra estuvo compuesta por 25 médicos y 83 profesionales de enfermería, 19 enfermeros y 64 técnicos de enfermería, totalizando 108 participantes. Fueron aplicados cuestionarios com preguntas abiertas sobre el sentimento de apoyo institucional y motivación hacia la cultura de seguridad. La taza de respuesta de los cuestionarios fue de 96,43%. En la segunda etapa los hallazgos fueron discutidos con siete representantes de la gerencia en un grupo focal. El análisis de contenido se realizó con Atlas ti® versión 8.3.20. Resultados: Se definieron las siguientes categorías: 1) dificultades en la atención segura de pacientes con catéteres venosos centrales; 2) prácticas resolutivas para enfrentar dificultades; 3) factores organizativos y educativos relacionados con la ocurrencia de infecciones y 4) propuestas de los gerentes para lograr buenos resultados. Conclusiones: Para prevenir infecciones, se observó la necesidad de participación de los equipos de atención en la construcción de protocolos, organización tecnológica interna, control de la escasez, estandarización del acceso por parte de los profesionales de la unidad, mayor frecuencia de capacitación por plataformas de aprendizaje a distancia y uso de metodologías activas

Parir e nascer em casa: vivências de enfermeiras obstétricas na assistência ao parto domiciliar planejado / Giving birth and born at home: experiences of obstetric nurses in care during the home birth

Objetivo: discutir a vivência de enfermeiras que atuam na assistência ao parto domiciliar planejado, evidenciando práticas obstétricas, desafios e obstáculos. Método: estudo qualitativo, realizado no período de agosto de 2019 a março de 2020, com nove enfermeiras obstétricas atuante no cenário de parto domiciliar. Os dados foram coletados através de entrevista em profundidade, e analisados pela análise temática, considerando o método de narrativa de vida proposto por Daniel Bertaux. Resultados: emergiram três temas: A opção pelo parto domiciliar: perfil de mulheres e escolhas; O resgate do processo fisiológico e o cuidado da enfermeira obstétrica no parto domiciliar planejado; O parto domiciliar no Brasil: obstáculos e desafios para a atuação da enfermagem obstétrica. Conclusões: Através deste estudo, constatou-se que a enfermagem obstétrica no parto domiciliar planejado apresenta-se como uma opção para o resgate do parto fisiológico. A vivência das enfermeiras obstétricas evidencia que ainda há inúmeros obstáculos no cenário do PDP, mas, ainda sim, a enfermagem obstétrica tem conseguido se fortalecer como um dos pilares no processo de humanização do parto. (AU)

Objective: Discuss the experience of nurses who work in care during the home birth, evidencing obstetric practices, challenges and obstacles. Methods: Qualitative study carried out from August 2019 to March 2020 with nine Obstetric Nurses who work in home birth. Data were collected through an in-depth interview, and analyzed by thematic analysis, considering the life narrative method proposed by Daniel Bertaux. Results: Three themes emerged: The option for home birth: profile of women and choices; The rescue of the physiological process, and the care of the obstetric nurse in home birth; Home birth in Brazil: obstacles and challenges for the performance of obstetric nursing. Conclusions: Through this study, it was found that obstetric nursing in planned home birth is presented as an option for the rescue of physiological childbirth. The experience of obstetric nurses shows that there are still numerous obstacles in the PDP scenario, but even so, obstetric nursing has managed to strengthen itself as one of the pillars in the humanization process of childbirth. (AU)

Objetivo: Discutir la experiencia de las enfermeras que trabajan en la asistencia al parto en casa, mostrando prácticas obstétricas, desafíos y obstáculos. Métodos: Studio cualitativo, realizado desde agosto de 2019 hasta marzo de 2020, con nueve enfermeras obstétricas trabajando en el escenario de parto en casa. Los datos fueron recolectados a través de una entrevista en profundidad, y analizado por análisis temático, considerando el método narrativo de la vida propuesto por Daniel Bertaux. Resultados: Surgieron tres temas: La opción para el parto en casa: perfil de mujeres y opciones; El rescate del proceso fisiológico y el cuidado de la enfermera obstétrica en el parto en casa; Parto en casa en Brasil: obstáculos y desafíos para el desempeño de la enfermería obstétrica. Conclusiones: El estudio muestra que, aunque el parto en casa ha sufrido ataques de algunos profesionales, todavía está consagrado como una alternativa al parto institucional, sin embargo, el gran desafío hoy es expandir este servicio a todos los estratos sociales. Mediante este estudio se encontró que la enfermería obstétrica en el parto domiciliario planificado se presenta como una opción para el rescate del parto fisiológico. La experiencia de las enfermeras obstétricas muestra que aún existen numerosos obstáculos en el escenario de la PDP, pero aún así, la enfermería obstétrica ha logrado fortalecerse como uno de los pilares en el proceso de humanización del parto. (AU)

Long-term efficacy and safety of 2CdA (cladribine) in extra-pulmonary adult-onset Langerhans cell histiocytosis: analysis of 23 cases from the French Histiocytosis Group and systematic literature review.

Langerhans cell histiocytosis (LCH) is a rare protean disease that usually affects children. Few data are available for management of adult-onset cases. A complete picture of the efficacy and safety of 2CdA (2-chlorodeoxyadenosine, cladribine) is lacking. We report a retrospective multicentre study of 23 adult LCH (a-LCH) patients who received single-agent 2CdA and a systematic literature review. All had previously received systemic therapy (vinblastine, n = 19). Response to 2CdA was evaluable in 22 cases. Overall response rate (ORR) was 91%. Complete response (CR) occurred in 11 cases (50%). Nine patients (39%) developed grade 3-4 neutropenia and/or severe infection. A literature review yielded 48 additional cases. A pooled analysis confirmed our findings (ORR: 88%, CR: 49%). CRs were rare with cumulative dose <50 mg/m2 . Disease progression rates were 20% and 30% at two and five years, respectively. Partial response (PR) to 2CdA was predictive of disease progression. Among eight re-treated patients, five went into CR, two in PR, and one died. Single-agent 2CdA is effective in reactivated a-LCH, including at intermediate doses. Toxicity, significant but acceptable, warrants infectious prophylaxis. Complete responders may enter prolonged remission. Further studies are needed to determine 2CdA sequencing with other agents (vinblastine, cytarabine).