Combined 13-valent pneumococcal conjugate and 23-valent pneumococcal polysaccharide vaccine regimens for adults with systemic lupus erythematosus: Does the sequence of pneumococcal vaccination affect immunogenicity responses? A single-center cohort study in Brazil.

OBJECTIVE: A combination of 13-valent pneumococcal conjugate vaccine (PCV13) and 23-valent pneumococcal polysaccharide vaccine (PPSV23) is currently recommended for adults with systemic lupus erythematosus (SLE). However, data on the immunogenicity elicited by sequential pneumococcal vaccination in this patient population are scarce. In this study, we compared short-term antibody responses to both PCV13/PPSV23 (≥8-week interval) and PPSV23/PCV13 (≥12-month interval) vaccination strategies in pneumococcal vaccine-naive adults with SLE. METHODS: This longitudinal, open-label, quasi-randomized study was performed in a single-center cohort of adults (18 years or older) with SLE. In both vaccination groups, blood samples were collected immediately before administering the first dose of the pneumococcal vaccine (timepoint T0), 4-6 weeks after the priming dose (T1), and 4-6 weeks after the booster dose (T2). We focused on the 12 shared serotypes between PCV13 and PPSV23, and compared the following immunogenicity outcomes between the groups at T2: anti-pneumococcal antibody geometric mean concentration (ApAb GMC), fold increase in ApAb levels (FI-ApAb), overall seroprotection rate, and overall seroconversion rate. The protective level for each pneumococcal serotype was set at 1.3 µg/mL. We used the multi-analyte immunodetection method to determine serum levels of ApAbs. RESULTS: Thirty-four patients with SLE were screened between April 2019 and January 2020, and 16 of them (mean age: 39.4 years, 87.5% female, and 100% on immunosuppressants) had evaluable immunogenicity results at T2. The median time elapsed between the pneumococcal vaccinations was 56 days in the PCV13/PPSV23 group (n = 11 patients) and 16 months in the PPSV23/PCV13 group (n = 5 patients). Priming with PCV13 (PCV13/PPSV23 group), as opposed to PPSV23 (PPSV23/PCV13 group), yielded significantly better results regarding FI-ApAb, overall seroconversion rate, and overall seroprotection rate 4-6 weeks after each pneumococcal vaccination. A trend toward augmented ApAb GMC in the patients who received the PCV13/PPSV23 sequence was also observed. No relevant safety issues were identified with sequential pneumococcal vaccination. CONCLUSION: The PCV13-priming PPSV23-boost strategy in adults with SLE induced greater antibody responses for most immunogenicity outcomes than those elicited by the PPSV23/PCV13 strategy.

Safety of CoronaVac and ChAdOx1 vaccines against SARS-CoV-2 in patients with rheumatoid arthritis: data from the Brazilian multicentric study safer.

BACKGROUND: Patients with immune-mediated rheumatic diseases (IMRDs) have been prioritized for COVID-19 vaccination to mitigate the infection severity risks. Patients with rheumatoid arthritis (RA) are at a high risk of severe COVID-19 outcomes, especially those under immunosuppression or with associated comorbidities. However, few studies have assessed the safety of the COVID-19 vaccine in patients with RA. OBJECTIVE: To evaluate the safety of vaccines against SARS-CoV-2 in patients with RA. METHODS: This data are from the study "Safety and Efficacy on COVID-19 Vaccine in Rheumatic Diseases," a Brazilian multicentric prospective phase IV study to evaluate COVID-19 vaccine in IMRDs in Brazil. Adverse events (AEs) in patients with RA of all centers were assessed after two doses of ChAdOx1 (Oxford/AstraZeneca) or CoronaVac (Sinovac/Butantan). Stratification of postvaccination AEs was performed using a diary, filled out daily and returned at the end of 28 days for each dose. RESULTS: A total of 188 patients with RA were include, 90% female. CoronaVac was used in 109 patients and ChAdOx1 in 79. Only mild AEs were observed, mainly after the first dose. The most common AEs after the first dose were pain at the injection (46,7%), headache (39,4%), arthralgia (39,4%), myalgia (30,5%) and fatigue (26,6%), and ChAdOx1 had a higher frequency of pain at the injection (66% vs 32 %, p < 0.001) arthralgia (62% vs 22%, p < 0.001) and myalgia (45% vs 20%, p < 0.001) compared to CoronaVac. The more common AEs after the second dose were pain at the injection (37%), arthralgia (31%), myalgia (23%), headache (21%) and fatigue (18%). Arthralgia (41,4% vs 25%, p = 0.02) and pain at injection (51,4% vs 27%, p = 0.001) were more common with ChAdOx1. No serious AEs were related. With Regard to RA activity level, no significant difference was observed between the three time periods for both COVID-19 vaccines. CONCLUSION: In the comparison between the two immunizers in patients with RA, local reactions and musculoskeletal symptoms were more frequent with ChAdOx1 than with CoronaVac, especially after the first dose. In summary, the AE occurred mainly after the first dose, and were mild, like previous data from others immunizing agents in patients with rheumatoid arthritis. Vaccination did not worsen the degree of disease activity.

Drug delivery systems based in microneedles for dermatological diseases and aesthetic enhancement.

Microneedle (MN) devices comprise of micron-sized structures that circumvent biological barriers in a minimally invasive manner. MN research continues to grow and evolve; the technology was recently identified as one of the top ten overall emerging technologies of 2020. There is a growing interest in using such devices in cosmetology and dermatological conditions where the MNs mechanically disrupt the outer skin barrier layer, creating transient pathways that allow the passage of materials to underlying skin layers. This review aims to appraise the application of microneedle technologies in skin science, provide information on potential clinical benefits, as well as indicate possible dermatological conditions that can benefit from this technology, including autoimmune-mediated inflammatory skin diseases, skin aging, hyperpigmentation, and skin tumors. A literature review was carried out to select studies that evaluated the use of microneedles as drug delivery enhancement for dermatologic purposes. MN patches create temporary pathways that allow the passage of material to deeper layers of the skin. Given their demonstrable promise in therapeutic applications, it will be essential for healthcare professionals to engage with these new delivery systems.

Guidelines on COVID-19 vaccination in patients with immune-mediated rheumatic diseases: a Brazilian Society of Rheumatology task force.

OBJECTIVE: To provide guidelines on the coronavirus disease 2019 (COVID-19) vaccination in patients with immune-mediated rheumatic diseases (IMRD) to rheumatologists considering specific scenarios of the daily practice based on the shared-making decision (SMD) process. METHODS: A task force was constituted by 24 rheumatologists (panel members), with clinical and research expertise in immunizations and infectious diseases in immunocompromised patients, endorsed by the Brazilian Society of Rheumatology (BSR), to develop guidelines for COVID-19 vaccination in patients with IMRD. A consensus was built through the Delphi method and involved four rounds of anonymous voting, where five options were used to determine the level of agreement (LOA), based on the Likert Scale: (1) strongly disagree; (2) disagree, (3) neither agree nor disagree (neutral); (4) agree; and (5) strongly agree. Nineteen questions were addressed and discussed via teleconference to formulate the answers. In order to identify the relevant data on COVID-19 vaccines, a search with standardized descriptors and synonyms was performed on September 10th, 2021, of the MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials, ClinicalTrials.gov, and LILACS to identify studies of interest. We used the Newcastle-Ottawa Scale to assess the quality of nonrandomized studies. RESULTS: All the nineteen questions-answers (Q&A) were approved by the BSR Task Force with more than 80% of panelists voting options 4-agree-and 5-strongly agree-, and a consensus was reached. These Guidelines were focused in SMD on the most appropriate timing for IMRD patients to get vaccinated to reach the adequate covid-19 vaccination response. CONCLUSION: These guidelines were developed by a BSR Task Force with a high LOA among panelists, based on the literature review of published studies and expert opinion for COVID-19 vaccination in IMRD patients. Noteworthy, in the pandemic period, up to the time of the review and the consensus process for this document, high-quality evidence was scarce. Thus, it is not a substitute for clinical judgment.

Cell spheroids as a versatile research platform: formation mechanisms, high throughput production, characterization and applications.

Three-dimensional (3D) cell culture has tremendous advantages to closely mimic thein vivoarchitecture and microenvironment of healthy tissue and organs, as well as of solid tumors. Spheroids are currently the most attractive 3D model to produce uniform reproducible cell structures as well as a potential basis for engineering large tissues and complex organs. In this review we discuss, from an engineering perspective, processes to obtain uniform 3D cell spheroids, comparing dynamic and static cultures and considering aspects such as mass transfer and shear stress. In addition, computational and mathematical modeling of complex cell spheroid systems are discussed. The non-cell-adhesive hydrogel-based method and dynamic cell culture in bioreactors are focused in detail and the myriad of developed spheroid characterization techniques is presented. The main bottlenecks and weaknesses are discussed, especially regarding the analysis of morphological parameters, cell quantification and viability, gene expression profiles, metabolic behavior and high-content analysis. Finally, a vast set of applications of spheroids as tools forin vitrostudy model systems is examined, including drug screening, tissue formation, pathologies development, tissue engineering and biofabrication, 3D bioprinting and microfluidics, together with their use in high-throughput platforms.

Characteristics associated with COVID-19 vaccine hesitancy: A nationwide survey of 1000 patients with immune-mediated inflammatory diseases.

OBJECTIVES: To identify potential predictors of COVID-19 vaccine hesitancy (C19-VH) in adults with immune-mediated inflammatory diseases (IMID). METHODS: A total of 1000 IMID patients were enrolled in this web-based cross-sectional study. A standardised and self-administered survey was designed by members of the Brazilian Society of Rheumatology Steering Committee for Infectious and Endemic diseases and distributed to IMID patients spread across Brazil. RESULTS: Of the 908 (90.8%) respondents eligible for analysis, 744 (81.9%) were willing to get vaccinated against COVID-19. In our multivariable logistic regression model, concurrent malignancy, fibromyalgia, hydroxychloroquine use, and recent corticosteroid pulse therapy were independently associated with higher odds of C19-VH. The short duration of COVID-19 vaccine clinical trials was the main reason for C19-VH. CONCLUSION: We identified novel characteristics potentially associated with C19-VH among adults with IMID. Greater awareness on the safety and efficacy of COVID-19 vaccines is needed for both IMID patients and attending physicians.

Correction to: Mortality burden associated with all-cause pneumonia among adults with autoimmune inflammatory rheumatic diseases, human immunodeficiency virus infection, and malignancies: a population-based comparative study for informed decision-making in public health policies.

The Table 2 in the original version of the above article was incorrectly presented. The data where misaligned during publication process.].

An imaging flow cytometry-based technique to quantify erythrocyte nuclear alterations.

Morphological nuclear alterations are indicative of DNA damage and have been considered excellent markers of exposure to several pollutants in aquatic environments. Flow cytometry is a powerful technique for measuring cell phenotypes in large numbers of cells in a short period of time. This technique is suited to the study of cell populations and subset identification as a function of its high-throughput and multi-parameter characteristics. We used the quantification of erythrocyte nuclear alterations to compare the techniques of imaging flow cytometry and light microscopy. The comparison used blood samples of the fish Oreochromis niloticus assayed using cadmium as a nuclear alteration-inducing agent. The results showed that imaging flow cytometry has higher sensitivity than light microscopy for detecting and quantifying erythrocytic nuclear alterations. We conclude that imaging flow cytometry can produce fast and reliable results and could potentially be useful in studies involving fish erythrocytes under normal and impacted environmental conditions.

Distinct mortality profile in systemic sclerosis: a death certificate study in Rio de Janeiro, Brazil (2006-2015) using a multiple causes of death analysis.

The objective of this study was to assess the mortality profile related to SSc in the state of Rio de Janeiro, Brazil. We retrospectively examined all registered deaths in the region (2006-2015 period) in which the diagnosis of SSc was mentioned on any line of the death certificates (underlying cause of death [UCD], n = 223; non-UCD, n = 151). Besides the analysis of gender, age, and the causes of death, we also compared the mortality from UCDs between individuals whose death causes included SSc (cases) and those whose death causes did not include SSc (deceased controls). For the latter comparison, we used the mortality odds ratio to approximate the cause-specific standardized mortality ratio. We identified 1495 death causes among the 374 SSc cases. The mean age at death of the SSc cases (85% women) was significantly lower than that of the controls (n = 1,294,117) (58.7 vs. 65.5 years, respectively). The main death causes were circulatory system diseases, infections, and respiratory diseases (36%, 34%, and 21% of SSc cases, respectively). Compared to the deceased controls, there were proportionally more deaths among the SSc cases from pulmonary arterial hypertension, lung fibrosis, septicemia, gastrointestinal hemorrhage, other systemic connective tissue diseases, and heart failure (for death age < 50 years). We confirmed the high burden of cardiovascular, respiratory, and infectious causes in this predominantly non-Caucasian sample of SSc patients. Of interest, the percentage of infection-related deaths in our report was about three times higher than that in SSc studies with predominantly Caucasian populations.

[Preliminary results of Artisan phakic intraocular lens implantation to correct myopia]. / Resultados preliminares do implante de lente intra-ocular fácica Artisan para correção de miopia.

PURPOSE: To observe the preliminary results based on the efficacy, stability and safety of Artisan anterior chamber intra-ocular lens for the correction of myopia in the first 6 months. METHODS: A retrospective study of 18 patients (34 eyes) that received the implantation of Artisan anterior chamber intraocular lens for the correction of myopia was conducted. Best visual preoperative acuity, best visual postoperative acuity, dynamic preoperative and postoperative refraction, loss and improvement of lines of vision and complications were evaluated. RESULTS: Eighteen patients (34 eyes) were included in this study. Fourteen patients were females (77.8%) and 4 were males. The mean age was 30 years (SD +/- 7.3), range from 21 to 46 years. They were followed up for an average of 8.5 months (SD +/- 3.6). The mean endothelial cell loss was 4.75% at 6 months follow-up. The average preoperative uncorrected visual acuity was 0.02 (20/800) range from 0.01 to 0.13. The average preoperative spherical equivalent was -13.25 D, range from -5.75 D to -19,75 D. On the last follow-up, uncorrected visual acuity was 0.64 (20/32), range from 0.33 to 1.00; the average spherical equivalent was -1.18 D (DP +/- 0.92) range from +0.25 to -3.0. Complications were observed in 1 case (3.4%) of our study, in one patient who had a dislocation of the lens after an ocular trauma. CONCLUSION: The use of Artisan anterior chamber intraocular lens in phakic eyes for the correction of myopia was safe, effective and predictable. However, a larger prospective study with a higher number of cases and longer follow-up is necessary to determine long-term safety of the lens.

Guidelines on COVID-19 vaccination in patients with immune-mediated rheumatic diseases: a Brazilian Society of Rheumatology task force

Abstract Objective: To provide guidelines on the coronavirus disease 2019 (COVID-19) vaccination in patients with immune-mediated rheumatic diseases (IMRD) to rheumatologists considering specific scenarios of the daily practice based on the shared-making decision (SMD) process. Methods: A task force was constituted by 24 rheumatologists (panel members), with clinical and research expertise in immunizations and infectious diseases in immunocompromised patients, endorsed by the Brazilian Society of Rheumatology (BSR), to develop guidelines for COVID-19 vaccination in patients with IMRD. A consensus was built through the Delphi method and involved four rounds of anonymous voting, where five options were used to determine the level of agreement (LOA), based on the Likert Scale: (1) strongly disagree; (2) disagree, (3) neither agree nor disagree (neutral); (4) agree; and (5) strongly agree. Nineteen questions were addressed and discussed via teleconference to formulate the answers. In order to identify the relevant data on COVID-19 vaccines, a search with standardized descriptors and synonyms was performed on September 10th, 2021, of the MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials, ClinicalTrials.gov, and LILACS to identify studies of interest. We used the Newcastle-Ottawa Scale to assess the quality of nonrandomized studies. Results: All the nineteen questions-answers (Q&A) were approved by the BSR Task Force with more than 80% of panelists voting options 4—agree—and 5—strongly agree—, and a consensus was reached. These Guidelines were focused in SMD on the most appropriate timing for IMRD patients to get vaccinated to reach the adequate covid-19 vaccination response. Conclusion: These guidelines were developed by a BSR Task Force with a high LOA among panelists, based on the literature review of published studies and expert opinion for COVID-19 vaccination in IMRD patients. Noteworthy, in the pandemic period, up to the time of the review and the consensus process for this document, high-quality evidence was scarce. Thus, it is not a substitute for clinical judgment.

3D-printed PCL scaffolds for the cultivation of mesenchymal stem cells.

INTRODUCTION: Tissue engineering is a field which is currently under a great deal of investigation for the development and/or restoration of tissue and organs, through the combination of cell therapy with biomaterials. Rapid prototyping or additive manufacturing is a versatile technology which makes possible the fabrication of three dimensional (3D) structures from a wide range of materials with complex geometry and accuracy, such as scaffolds. AIM: The aim of this study has been to investigate the interaction between mesenchymal stem cells with poly (ε-caprolactone) (PCL) biomaterials used for obtaining scaffolds through additive manufacturing. MATERIALS AND METHODS: Scanning electron microscopy, confocal microscopy and biological assays were performed to analyse the successful interaction between the cells and the biomaterials. RESULTS: As a result, the number of viable cells attached to the scaffolds was lower when compared to the control group; however, it was possible to observe cells in the scaffolds since day 1 of analysis, with regions of confluence after 21 days of seeding. CONCLUSIONS: To conclude, these biomaterials are interesting if used as medical artifacts, principally in tissue with prolonged regeneration time and which requires 3D supports with good mechanical properties.

Delivery of Human Adipose Stem Cells Spheroids into Lockyballs.

Adipose stem cells (ASCs) spheroids show enhanced regenerative effects compared to single cells. Also, spheroids have been recently introduced as building blocks in directed self-assembly strategy. Recent efforts aim to improve long-term cell retention and integration by the use of microencapsulation delivery systems that can rapidly integrate in the implantation site. Interlockable solid synthetic microscaffolds, so called lockyballs, were recently designed with hooks and loops to enhance cell retention and integration at the implantation site as well as to support spheroids aggregation after transplantation. Here we present an efficient methodology for human ASCs spheroids biofabrication and lockyballs cellularization using micro-molded non-adhesive agarose hydrogel. Lockyballs were produced using two-photon polymerization with an estimated mechanical strength. The Young's modulus was calculated at level 0.1362 +/-0.009 MPa. Interlocking in vitro test demonstrates high level of loading induced interlockability of fabricated lockyballs. Diameter measurements and elongation coefficient calculation revealed that human ASCs spheroids biofabricated in resections of micro-molded non-adhesive hydrogel had a more regular size distribution and shape than spheroids biofabricated in hanging drops. Cellularization of lockyballs using human ASCs spheroids did not alter the level of cells viability (p > 0,999) and gene fold expression for SOX-9 and RUNX2 (p > 0,195). The biofabrication of ASCs spheroids into lockyballs represents an innovative strategy in regenerative medicine, which combines solid scaffold-based and directed self-assembly approaches, fostering opportunities for rapid in situ biofabrication of 3D building-blocks.

Bone mineral density evaluation among patients with neuromuscular scoliosis secondary to cerebral palsy.

OBJECTIVE: To evaluate bone mineral density among patients with neuromuscular scoliosis secondary to quadriplegic cerebral palsy. METHODS: This was a descriptive prospective study in which both bone densitometric and anthropometric data were evaluated. The inclusion criteria used were that the patients should present quadriplegic cerebral palsy, be confined to a wheelchair, be between 10 and 20 years of age and present neuromuscular scoliosis. RESULTS: We evaluated 31 patients (20 females) with a mean age of 14.2 years. Their mean biceps circumference, calf circumference and body mass index were 19.4 cm, 18.6 cm and 16.9 kg/m(2), respectively. The mean standard deviation from bone densitometry was -3.2 (z-score), which characterizes osteoporosis. CONCLUSION: There is high incidence of osteoporosis in patients with neuromuscular scoliosis secondary to quadriplegic cerebral palsy.

OBJETIVO: avaliar a densidade mineral óssea em pacientes portadores de escoliose neuromuscular secundária à paralisia cerebral tetraespástica. MÉTODOS: estudo prospectivo, descritivo, em que se avaliaram, além da densitometria óssea, dados antropométricos. Como critério de inclusão, adotamos pacientes com paralisia cerebral tetraespástica, cadeirantes, entre 10 e 20 anos e com escoliose neuromuscular. RESULTADOS: avaliamos 31 pacientes, 20 do sexo feminino, cuja média de idade foi de 14,2 anos. A média da circunferência bicipital, da panturrilha e do IMC foi de 19,4 cm, 18,6 cm e 16,9 Kg/m2, respectivamente. O desvio padrão médio encontrado na densitometria óssea foi de ­3,2 (z-score), o que caracteriza osteoporose. CONCLUSÃO: existe elevada incidência de osteoporose em pacientes portadores de escoliose neuromuscular secundária à paralisia cerebral tetraespástica.

Comparison of the efficacy of transforaminal and interlaminar radicular block techniques for treating lumbar disk hernia.

OBJECTIVE: To compare the interlaminar and transforaminal block techniques with regard to the state of pain and presence or absence of complications. METHOD: This was a randomized double-blind prospective study of descriptive and comparative nature, on 40 patients of both sexes who presented lumbar sciatic pain due to central-lateral or foraminal disk hernias. The patients had failed to respond to 20 physiotherapy sessions, but did not present instability, as diagnosed in dynamic radiographic examinations. The type of block to be used was determined by means of a draw: transforaminal (group 1; 20 patients) or interlaminar (group 2; 20 patients). RESULTS: Forty patients were evaluated (17 males), with a mean age of 49 years. There was a significant improvement in the state of pain in all patients who underwent radicular block using both techniques, although the transforaminal technique presented better results than the interlaminar technique. CONCLUSION: Both techniques were effective for pain relief and presented low complication rates, but the transforaminal technique was more effective than the interlaminar technique.

OBJETIVO: Comparar a técnica de bloqueio interlaminar com a de bloqueio transforaminal, quanto ao quadro álgico e à presença ou não de complicações. MÉTODO: Estudo prospectivo, de caráter descritivo e comparativo, duplo-cego e randomizado, em que são sujeitos 40 pacientes, de ambos os sexos, portadores de lombociatalgia por hérnia de disco, do tipo centro-lateral ou foraminal, sem resposta a 20 sessões de fisioterapia e sem instabilidade, diagnosticada em exame de radiografia dinâmica. O tipo de bloqueio, transforaminal (grupo 1) ou interlaminar (grupo 2), a ser feito foi determinado por meio de sorteio e constituiu 20 pacientes do grupo 1 e 20 do grupo 2. RESULTADOS: Foram avaliados 40 pacientes, 17 do sexo masculino, média de 49 anos, nos quais houve melhoria significativa do quadro álgico em todos os submetidos ao bloqueio radicular em ambas as técnicas, embora a técnica transforaminal apresentasse melhores resultados quando comparada com a interlaminar. CONCLUSÃO: Ambas as técnicas são eficazes no alívio da dor e apresentam baixa taxa de complicação, mas a transforaminal foi mais eficaz do que a interlaminar.