A propensity score-weighted comparison between adalimumab originator and its biosimilars, ABP501 and SB5, in inflammatory bowel disease: a multicenter Italian study

Background: Adalimumab is an effective and safe biological drug for the treatment of inflammatory bowel disease (IBD). Nowadays, several biosimilar agents are available, but data regarding their efficacy and safety in patients with IBD are still lacking. We aimed to compare the effectiveness and tolerability between adalimumab originator, ABP501 and SB5 biosimilars in patients with IBD in the short term (after induction and after 6 months of treatment) through a propensity score-weighted multicenter cohort study. Methods: We included 156 patients with IBD, 69 patients with ulcerative colitis and 87 patients with Crohn's disease (CD) receiving ABP501 or SB5 biosimilars from January 2019 to April 2020 for moderate-to-severe disease. For comparison, a group of age- and sex-matched patients treated with adalimumab originator was used. We collected clinical and biochemical data after induction and at 6 months of treatment. Endoscopic data were recorded only at baseline. Results: Overall, clinical benefit was achieved by 86.4% and 85.3% after induction and at 6 months, respectively, without a statistically significant difference between the three treatment groups (p = 0.68 and p = 0.46). However, after induction, we found significant differences between the two types of the disease (ulcerative colitis or CD, p = 0.004), with a greater clinical benefit achieved by patients with CD. Also, the therapeutic optimization rate between the three drugs was not statistically significant different (p = 0.30). All treatments showed a good safety profile, with only 10 patients who needed to stop therapy because of adverse events. Conclusion: Adalimumab biosimilars seem to be as effective and safe as the originator in patients with IBD. Surely, they represent a great opportunity to reduce the costs of biological therapies, however larger and longer real-life studies are necessary

Effectiveness, retrievability, and safety of celect vs. ALN inferior vena cava filters: a randomized prospective multicenter controlled study

The purpose of this study is to compare IVC Celect and ALN filters in regard to their efficacy, retrievability, and one-year follow-up after retrieval. Materials and Methods: This is a prospective randomized study, conducted in three centers between April 2020 and May 2021. A total of 115 participants were randomized, of which 15 participants were excluded for various reasons. Each group of 50 participants was finally assigned a type of filter (Celect n = 50 and ALN = 50). Tilt angles at placement and retrieval, rates of overall filter retrieval, complications, complex retrieval, and clinical follow-up at 12 months were compared. Results: One hundred participants (59 men and 41 women) were included. The mean age was 62.4 ± 13.3, with no significant differences between both groups (p 0.503). The mean of dwelling time was 44.7 ± 93 days. (p 0.520) Filter retrieval was successful in all participants (100%). The main complication in CT prior to removal was tilt >15° (31%) and filter tip embedment (16%). No significant differences were observed in the type of retrieval (standard or complex) between both filters (p 0.24); however, fluoroscopy time was significantly longer in the complex removal of the Celect filter: 29.1 ± 12 min vs. 17.5 ± 10.3 (p 0.005). After one year, no recurrent pulmonary embolism was observed in both types of filters. Conclusions: The ALN filter had a significantly lower rate of tip and filter tip embedding, with no differences in complexity or removal success rate. There were significant differences in the fluoroscopy time consumed for standard and complex retrievals between both filters, with less time for the ALN filter

A comparative study of a small series of patients (50 patients) with pelvic varicose veins treated with plugs alone or plugs and polidocanol

Level of Evidence: Level 2. Purpose: To compare the safety and efficacy of vascular plug (VP) and vascular plug and polidocanol foam (VPPF) treatments for embolization in pelvic congestion syndrome (PCS). Materials and methods: A comparative, prospective, two-center study enrolled 50 women with PCS from January 2019 to January 2020. The patients were divided into two groups, and embolization was performed with VP (n = 25) and VPPF (n = 25) treatments. The mean age of the patients was 45.6 years ± 6.9. Three clinical parameters were assessed: abdominal pain, dyspareunia, and lower limb pain. The primary outcome (clinical success at 1 yr using a VAS), number of devices, procedure and fluoroscopy times, radiation doses, costs, and complications were compared. The participants were followed-up at 1, 3, 6, and 12 months. Results: At the 1-year follow-up, clinical success did not significantly differ between the two groups (VP vs. VPPF) regarding the improvement of the symptoms analyzed (pelvic pain, dyspareunia, lower extremity pain, and other symptoms (p < 0.05)). The mean number of devices per case was 4 ± 1.1 for the VP group and 2 ± 0.31 for the VPPF group (p < 0.001). No major complications were recorded in either group. The VPPF group had a significantly longer fluoroscopy time (42.8 min ± 14.2 vs. 25.4 min ± 7) and longer radiation dose (VPPF air kerma 839.4 ± 513 vs. VP air kerma 658.4 mGy ± 355 (all p < 0.001)). Conclusions: Embolization for PCS resulted in pain relief in 90% of patients; the use of polidocanol did not demonstrate changes in the clinical outcome. The use of a VP alone was associated with decreased fluoroscopy time and radiation dose

Extracellular NK histones promote immune cell anti-tumor activity by inducing cell clusters through binding to CD138 receptor.

BACKGROUND: Natural killer (NK) cells are important anti-tumor cells of our innate immune system. Their anti-cancer activity is mediated through interaction of a wide array of activating and inhibitory receptors with their ligands on tumor cells. After activation, NK cells also secrete a variety of pro-inflammatory molecules that contribute to the final immune response by modulating other innate and adaptive immune cells. In this regard, external proteins from NK cell secretome and the mechanisms by which they mediate these responses are poorly defined. METHODS: TRANS-stable-isotope labeling of amino acids in cell culture (TRANS-SILAC) combined with proteomic was undertaken to identify early materials transferred between cord blood-derived NK cells (CB-NK) and multiple myeloma (MM) cells. Further in vitro and in vivo studies with knock-down of histones and CD138, overexpression of histones and addition of exogenous histones were undertaken to confirm TRANS-SILAC results and to determine functional roles of this material transferred. RESULTS: We describe a novel mechanism by which histones are actively released by NK cells early after contact with MM cells. We show that extracellular histones bind to the heparan sulfate proteoglycan CD138 on the surface of MM cells to promote the creation of immune-tumor cell clusters bringing immune and MM cells into close proximity, and thus facilitating not only NK but also T lymphocyte anti-MM activity. CONCLUSION: This study demonstrates a novel immunoregulatory role of NK cells against MM cells mediated by histones, and an additional role of NK cells modulating T lymphocytes activity that will open up new avenues to design future immunotherapy clinical strategies

Significant Clinical Activity of Olaparib in a Somatic BRCA1-Mutated Triple-Negative Breast Cancer With Brain Metastasis

Breast cancer is a biologically and clinically heterogeneous disease, and patients with similar clinical stage have markedly different outcomes. Triple-negative breast cancer (TNBC) is defined by the lack of expression of estrogen receptor (ER), progesterone receptor, and human epidermal growth factor receptor 2 (HER2).1,2 This subtype represents 15% to 20% of all breast cancers and is associated with the worst outcome of all subtypes, with greater tendency to distant recurrence in general and visceral metastasis in particular, including brain metastasis.3,4 To date, chemotherapy remains the standard of care for TNB

Reabilitação respiratória em pessoas com doença pulmonar obstrutiva crónica – Protocolo de estudo

Introduction: Chronic Obstructive Pulmonary Disease is one of the main causes of morbidity and mortality worldwide, with an important and growing economic and social burden. The benefits of Pulmonary Rehabilitation (PR) include better control of dyspnoea and major improvements in exercise capacity and health-related quality of life. The general objective of this study is to evaluate the impact of implementing a Pulmonary Rehabilitation program in Outpatients with COPD and with Follow-up at Home.Methodology: A quasi-experimental single-group, descriptive and correlational study. Participants will be subject to PR sessions 3 times a week in a total of 36 sessions, in the Health Center of the area of residence and teleconsultation, in a previously defined scheme. Evaluations will be carried out at the beginning of the intervention, at the 18th and 36th sessions and 6 and 12 weeks after the 36th session. Throughout the PR sessions, physical exercise plans will be developed, education about exacerbating factors and control of risk factors, respiratory functional re-education techniques and inhalotherapy training. Participants will be provided with a customized plan to be implemented at their home, with teleconsultation monitoring after the end of the PR program (12th week).Expected results: The aim is to achieve clinical and statistically significant improvements in the ability to perform ADL, in the quality of life, in the management of symptoms and the therapeutic regimen, in the ability to walk and in the reduction of costs associated with exacerbations. It is also intended to verify whether there are significant differences between the two modalities of implementation of the program.Conclusion: Through the planned intervention, it is expected to reach the end of 2023 with data that allow to optimize the response to the needs of people with COPD in the district of Bragança and highlight the value of the specialized intervention in Rehabilitation Nursing in Primary Health Care.Introducción: La Enfermedad Pulmonar Obstructiva Crónica (EPOC) es una de las principales causas de morbilidad y mortalidad a nivel mundial, con una importante carga económica y social. Los beneficios de la Rehabilitación Respiratoria (RR) incluyen un mejor control de la disnea y mejoras importantes en la capacidad de ejercicio y la calidad de vida relacionada con la salud. El objetivo general de este estudio es evaluar el impacto de la implementación de un programa de rehabilitación respiratoria en pacientes con EPOC en ambulatorio y seguimiento a domicilio. Metodología: Estudio cuasi-experimental de grupo único, de carácter descriptivo y correlacional. Los participantes serán objeto de sesiones de RR 3 veces por semana en un total de 36 sesiones, en el Centro de Salud del área de residencia y en teleconsulta, en esquema previamente definido. Se realizarán evaluaciones al comienzo de la intervención, a la 18ª y a la 36ª sesiones y 6 y 12 semanas después de la 36ª sesión. A lo largo de las sesiones de RR se desarrollarán planes de ejercicio físico, enseñanza sobre factores exacerbantes y control de los factores de riesgo, técnicas de reeducación funcional respiratoria y entrenamiento de inaloterapia. Se proporcionará a los participantes un plan personalizado para ser implementado en su domicilio, con monitoreo por teleconsulta después del término del programa de RR (12ª semana). Resultados esperados: Se pretende lograr mejoras clínicas y estadísticamente significativas en la capacidad para el desempeño de las AVD, en la calidad de vida, en la gestión de los síntomas y del régimen terapéutico, en la capacidad para la marcha y en la reducción de los costes asociados a las exacerbaciones. También se pretende comprobar si existen diferencias significativas entre las dos modalidades de aplicación del programa. Conclusión: A través de la intervención planeada, se prevé llegar al final de 2023 con datos que permitan optimizar la respuesta a las necesidades de las personas con EPOC en el distrito de Braganza y evidenciar la másvalía de la intervención especializada en Enfermería de Rehabilitación en los Cuidados de Salud Primarios.Introdução: A Doença Pulmonar Obstrutiva Crónica é uma das principais causas de morbilidade e mortalidade em todo o mundo, com peso económico e social importante e crescente. Os benefícios da Reabilitação Respiratória (RR) incluem um melhor controlo de dispneia e melhorias importantes na capacidade de exercício e qualidade de vida relacionada com a saúde. O objetivo geral deste estudo é avaliar o impacto da implementação de um programa de Reabilitação Respiratória em pessoas com DPOC em Ambulatório e com Follow-up no Domicílio. Metodologia: Estudo quasi-experimental de grupo único, de caráter descritivo e correlacional. Os participantes serão alvo de sessões de RR 3 vezes por semana num total de 36 sessões, no Centro de Saúde da área de residência e em teleconsulta, em esquema previamente definido. Serão efetuadas avaliações no início da intervenção, à 18ª e à 36ª sessões e 6 e 12 semanas depois da 36ª sessão. Ao longo das sessões de RR serão desenvolvidos planos de exercício físico, ensino sobre fatores exacerbantes e controlo dos fatores de risco, técnicas de reeducação funcional respiratória e treino de inaloterapia. Será fornecido aos participantes um plano personalizado para ser implementado no seu domicílio, com monitorização por teleconsulta após o término do programa de RR (12ª semana). Resultados esperados: Pretende-se obter melhorias clínica e estatisticamente significativas na capacidade para o desempenho das AVD, na qualidade de vida, na gestão dos sintomas e do regime terapêutico, na capacidade para a marcha e na redução dos custos associados às exacerbações. Pretende-se, ainda, verificar se existem diferenças significativas entre as duas modalidades de implementação do programa. Conclusão: Através da intervenção planeada, prevê-se chegar ao final de 2023 com dados que permitam otimizar a resposta às necessidades das pessoas com DPOC no distrito de Bragança e evidenciar a mais-valia da intervenção especializada em Enfermagem de Reabilitação nos Cuidados de Saúde Primários

Hepatitis A and E seroprevalence and associated risk factors: a community-based cross-sectional survey in rural Amazonia

Abstract\ud \ud Background\ud Hepatitis A virus (HAV) and hepatitis E virus (HEV) are both transmitted by the faecal-oral route, and represent common causes of acute hepatitis in developing countries. The endemicity of HAV infection has shifted from high to moderate in Brazil. Human cases of HEV infection seem to be rare, although the virus has been detected in swine livestock and effluents of slaughterhouses. This study was to determine the epidemiology of hepatitis A and E in one of the largest agricultural settlements in the Amazon Basin of Brazil.\ud \ud \ud Methods\ud Serum samples collected from 397 individuals aged between 5 and 90 years during a population-based cross-sectional survey were tested for anti-HAV and anti-HEV antibodies. Associated risk factors and spatial clustering of HAV and HEV seropositivity were also analyzed.\ud \ud \ud Results\ud The overall rate of HAV seropositivity was 82.9% (95% confidence interval (CI), 79.2-86.6%). Multilevel logistic regression analysis identified increasing age (in years; odds ratio (OR), 1.097; 95% CI, 1.050-1.147; P < 0.001) and crowding (OR, 1.603; 95% CI, 1.054-2.440; P = 0.028) as significant risk factors for HAV seropositivity. Anti-HEV IgG was detected in 50/388 settlers (12.9%, 95% CI, 9.5-16.2%). Anti-HEV IgM was detected in 7/43 (16.3%) anti-IgG positive samples, and 4 of them had a confirmed result by immunoblot. Increasing age was the only significant determinant of HEV seropositivity (OR, 1.033; 95% CI, 1.016-1.050; P < 0.001). No significant spatial clustering of HAV and HEV seropositivity was detected in the area.\ud \ud \ud Conclusions\ud Both HAV and HEV are endemic, with differing rates of infection in children and adults in this rural setting of the Brazilian Amazon. Anti-HEV prevalence was considerably higher than those previously reported in Brazil. The detection of HEV- specific IgM antibodies in four asymptomatic individuals is highly suggestive of the circulation of HEV in this rural population.This work was supported by grants from the Fundação de Amparo à\ud Pesquisa do Estado do Rio de Janeiro (FAPERJ E-26/ 110.278/2012 - APQ1)\ud and Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP,\ud 05/51988-0). MdSN was supported by a PhD scholarship from FAPESP, RCCP\ud was supported by a CNPq scholarship. MUF, MAP, and AMCG receive sênior\ud research scholarships from the Conselho Nacional de Desenvolvimento\ud Científico e Tecnológico (CNPq), Brazil.\ud Vitral et al. BMC Infectious Diseases 2014, 14:458 Page 7 of 9\ud http://www.biomedcentral.com/1471-2334/14/458\ud We would like to thank the inhabitants of Ramal do Granada for their\ud enthusiastic participation in the study; Adamílson L. de Souza for their help in\ud fieldwork, and Estéfano A. de Souza and Bruna A. Luz for data management

Quality in Emergency Departments: a study on 3,285,440 admissions

INTRODUCTION: A multi-centre study has been conducted, during 2005, by means of a questionnaire posted on the Italian Society of Emergency Medicine (SIMEU) web page. Our intention was to carry out an organisational and functional analysis of Italian Emergency Departments (ED) in order to pick out some macro-indicators of the activities performed. Participation was good, in that 69 ED (3,285,440 admissions to emergency services) responded to the questionnaire. METHODS: The study was based on 18 questions: 3 regarding the personnel of the ED, 2 regarding organisational and functional aspects, 5 on the activity of the ED, 7 on triage and 1 on the assessment of the quality perceived by the users of the ED. RESULTS AND CONCLUSION: The replies revealed that 91.30% of the ED were equipped with data-processing software, which, in 96.83% of cases, tracked the entire itinerary of the patient. About 48,000 patients/year used the ED: 76.72% were discharged and 18.31% were hospitalised. Observation Units were active in 81.16% of the ED examined. Triage programmes were in place in 92.75% of ED: in 75.81% of these, triage was performed throughout the entire itinerary of the patient; in 16.13% it was performed only symptom-based, and in 8.06% only on-call. Of the patients arriving at the ED, 24.19% were assigned a non-urgent triage code, 60.01% a urgent code, 14.30% a emergent code and 1.49% a life-threatening code. Waiting times were: 52.39 min for non-urgent patients, 40.26 min for urgent, 12.08 for emergent, and 1.19 for life-threatening patients

NÍVEIS DE ZINCO NA DIETA DE LEITÕES RECÉM-DESMAMADOS SOBRE O PERFIL DE PARÂMETROS SANGÜÍNEOS

adição de diferentes níveis (0, 1.500, 3.000 e 4.500 ppm) de zinco (utilizando como fonte o ZnO) na dieta de leitões influencia o perfil de parâmetros sangüíneos (cálcio, cobre, ferro, zinco, hemoglobina (Hb)), hematócrito (Ht), proteínas séricas totais (PST), albumina (ALB), globulina (GLOB) e atividade enzimática sérica de fosfatase alcalina (FA), aspartato aminotransferase (ASP), alanina aminotransferase (ALT) e gama glutamil transferase (GGT)). Utilizaram-se sessenta leitões machos castrados, mestiços, desmamados aos 21 dias de idade, procedentes de sistema de criação em sítios separados, dentro dos períodos: Período 1 (P1), do desmame (dia zero) até 14 dias pós-desmame; Período 2 (P2), de 15 a 42 dias pós-desmame e Período Total (PT), do desmame aos 42 dias pós-desmame. As coletas de sangue foram efetuadas aos 0, 7, 14, 21 e 42 dias pós-desmame. Utilizou-se o DIC, num esquema em parcelas subdivididas, tendo como parcelas os quatro níveis de Zn nas rações, e como subparcelas os dias de coleta. Concluiu-se que a adição de 4.500 ppm de Zn por duas semanas pós-desmame pode elevar o nível sérico de Zn. Os parâmetros sangüíneos sofreram efeito do dia de coleta. PALAVRAS-CHAVES: Leitões desmamados, óxido de zinco, suínos