Added value of lymphocyte subpopulations in the classification of Sjögren's syndrome.

Sjögren's Syndrome (SjS) is a chronic systemic immune-mediated inflammatory disease characterized by lymphocytic infiltration and consequent lesion of exocrine glands. SjS diagnosis and classification remains a challenge, especially at SjS onset, when patients may have milder phenotypes of the disease or uncommon presentations. New biomarkers are needed for the classification of SjS, thus, we aimed to evaluate the added-value of lymphocyte subpopulations in discriminating SjS and non-Sjögren Sicca patients. Lymphocyte subsets from 62 SjS and 63 Sicca patients were characterized by flow cytometry. The 2002 AECG and the 2016 ACR/EULAR SjS classification criteria were compared with clinical diagnosis. The added discriminative ability of joining lymphocytic populations to classification criteria was assessed by the area under the Receiver-Operating-Characteristic Curve (AUC). Considering clinical diagnosis as the gold-standard, we obtained an AUC = 0.952 (95% CI: 0.916-0.989) for AECG and an AUC = 0.921 (95% CI: 0.875-0.966) for ACR/EULAR criteria. Adding Tfh and Bm1 subsets to AECG criteria, performance increased, attaining an AUC = 0.985 (95% CI: 0.968-1.000) (p = 0.021). Th1/Breg-like CD24hiCD27+ and switched-memory B-cells maximized the AUC of ACR/EULAR criteria to 0.953 (95% CI: 0.916-0.990) (p = 0.043). Our exploratory study supports the potential use of lymphocyte subpopulations, such as unswitched memory B cells, to improve the performance of classification criteria, since their discriminative ability increases when specific subsets are added to the criteria.

The Baumann Angle: An Analysis from Theory to Practice.

Objective To analyze how the Baumann angle (BA) is affected by inadequate radiographic inclinations. Methods The study was performed from radiographs of the distal humerus of children aged 3 to 10 years. The BA measurements performed by five observers were compared, and each radiograph was evaluated for its quality as "adequate" or "inadequate." The correlation between radiographic quality and the normality of the angles was evaluated. Results Sample was composed of 141 patients, 44% between 3 and 6 years of age and 56% between 7 and 10. We observed the BA between 52.01 and 89.82 degrees, with about 16% of the measurements outside the normal limits of the literature. A total of 33.3% of the evaluated radiographs were classified as "inadequate". On the BA measurements outside the normality parameter, we observed that its proportion was higher among images with inadequate radiographic quality (31.1 vs. 6.2%), and this difference was significant ( p < 0.001). Conclusions The BA is a very variable measurement and, alone, it is unreliable for the evaluation of angular deformities of the pediatric elbow, with radiographic quality proven to be an important causal factor of this variability.

The Baumann Angle: An Analysis from Theory to Practice / O ângulo de Baumann: Uma análise da teoria à prática

Abstract Objective To analyze how the Baumann angle (BA) is affected by inadequate radiographic inclinations. Methods The study was performed from radiographs of the distal humerus of children aged 3 to 10 years. The BA measurements performed by five observers were compared, and each radiograph was evaluated for its quality as "adequate" or "inadequate." The correlation between radiographic quality and the normality of the angles was evaluated. Results Sample was composed of 141 patients, 44% between 3 and 6 years of age and 56% between 7 and 10. We observed the BA between 52.01 and 89.82 degrees, with about 16% of the measurements outside the normal limits of the literature. A total of 33.3% of the evaluated radiographs were classified as "inadequate". On the BA measurements outside the normality parameter, we observed that its proportion was higher among images with inadequate radiographic quality (31.1 vs. 6.2%), and this difference was significant (p< 0.001). Conclusions The BA is a very variable measurement and, alone, it is unreliable for the evaluation of angular deformities of the pediatric elbow, with radiographic quality proven to be an important causal factor of this variability.

Resumo Objetivo Analisar como o ângulo de Baumann (AB) é afetado por inclinações radiográficas inadequadas. Métodos Estudo realizado a partir de radiografias do úmero distal de crianças de 3 a 10 anos. Foram comparadas as aferições do AB realizadas por cinco observadores, e cada radiografia foi avaliada quanto à sua qualidade em "adequada" ou "inadequada". A correlação entre a qualidade radiográfica e a normalidade dos ângulos foi avaliada. Resultados Amostra composta por 141 pacientes, 44% entre 3 e 6 anos e 56% entre 7 e 10. Observamos AB entre 52,01 e 89,82 graus, tendo cerca de 16% das medidas fora dos limites de normalidade da literatura. Um total de 33,3% das radiografias avaliadas foram classificadas como "inadequadas". Sobre as medidas do AB fora do parâmetro da normalidade, observamos que sua proporção foi maior entre as imagens com qualidade radiográfica inadequada (31,1% vs. 6,2%), tendo essa diferença se mostrado significativa (p< 0,001). Conclusões O AB é uma medida muito variável e, isoladamente, pouco confiável para a avaliação de deformidades angulares do cotovelo pediátrico, tendo a qualidade radiográfica se mostrado um fator causal importante dessa variabilidade.

The trochlear physeal line angle: a novel method to assess coronal plane alignment of the paediatric distal humerus.

Supracondylar humeral fractures account for 60% of elbow fractures in childhood, with cubitus varus being its most common complication. It can be avoided by accurate assessment of distal humeral alignment after fracture reduction, and the Baumann angle is the usual measurement for this purpose. However, several reports demonstrate an inconsistency of this angle, and our hypothesis is that reliability could be improved with angles drawn between the trochlear physeal line and the humeral longitudinal axis. The aim of the study was to compare intra- and interobserver reliability between the Baumann angle and angles drawn between the trochlear physeal line and (1) humeral longitudinal axis (X-angle), (2) humeral lateral cortex line (Y-angle), (3) humeral medial cortex line (Z-angle). Angle measurements were performed on 141 distal humerus' radiographs of children aged 3-10 years by five observers in a tertiary hospital. The measurements were compared for their intra- and interobserver agreement. All measurements showed good or excellent intraobserver agreement levels, with the highest for Z-angle [intraclass correlation coefficient (ICC) = 0.906] and the lowest for Baumann angle. There were also excellent interobserver agreement levels for all angles, the highest for Z-angle (ICC = 0.885). There are indications that Z-angle had higher agreement levels when compared to the others (ICC = 0.954; 0.936-0.969) in the group aged 7-10 years. The angle drawn between the humeral medial cortex and trochlear physeal line showed greater agreement than the other angles analysed, becoming a potentially useful tool for evaluation of children with supracondylar humeral fractures in daily practice.

Measuring quality of life of patients with axial spondyloarthritis for economic evaluation.

OBJECTIVES: To estimate the relationship between EQ5D (three levels, UK version) and the Ankylosing Spondylitis Disease Activity Score (ASDAS) for use in the economic evaluation of health technologies for people with axial spondyloarthritis (axSpA). To compare against the relationship with the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI). METHODS: An electronic, prospective, Portuguese, nationwide, rheumatic disease register (Reuma.pt) provided data on 1140 patients (5483 observations) with a confirmed diagnosis of axSpA. We estimated models of EQ5D as a function of ASDAS, alone or in combination with measures of functional impairment, using bespoke mixture models which reflect the complex distributional features of EQ5D. The SPondyloArthritis Caught Early cohort provided data from 344 patients (1405 observations) in four European countries and was used for validation. A previously published model of BASDAI/Bath Ankylosing Spondylitis Functional Index (BASFI) was also used to generate predicted EQ5D scores and model performance compared. RESULTS: A non-linear relationship exists between EQ5D from ASDAS. The final model included ASDAS, ASDAS squared, age and age squared and demonstrated close fit in both datasets except where data were sparse for patients with very high levels of disease activity (ASDAS >4). This finding held in the validation dataset. Models that included BASFI improved model fit. The ASDAS based models fit the data marginally less well than models using BASDAI. CONCLUSIONS: Mapping models linking ASDAS to EQ5D allow results from clinical studies to be used in economic evaluation of health technologies with confidence. There is some loss of information compared with BASDAI but this has only a marginal impact.

Safety and efficacy of subcutaneous ianalumab (VAY736) in patients with primary Sjögren's syndrome: a randomised, double-blind, placebo-controlled, phase 2b dose-finding trial.

BACKGROUND: Sjögren's syndrome is an autoimmune disease characterised by dry eyes and mouth, systemic features, and reduced quality of life. There are no disease-modifying treatments. A new biologic, ianalumab (VAY736), with two modes of suppressing B cells, has previously shown preliminary efficacy. This dose-finding trial aimed to assess the safety and efficacy of different subcutaneous doses of ianalumab in patients with moderate to severe primary Sjögren's syndrome. METHODS: VAY736A2201 was a randomised, parallel, double-blind, placebo-controlled, phase 2b dose-finding study done in 56 centres in 19 countries. Patients aged 18-75 years with primary Sjögren's syndrome with moderate to severe disease activity (European Alliance of Associations for Rheumatology [EULAR] Sjögren's Syndrome Disease Activity Index [ESSDAI] score ≥6) and symptom severity (EULAR Sjögren's Syndrome Patient Reported Index score ≥5) were eligible. Participants were randomly assigned (1:1:1:1) to receive subcutaneous placebo or ianalumab (5 mg, 50 mg, or 300 mg) every 4 weeks for 24 weeks using a secure, online randomisation system. Randomisation was stratified by the ESSDAI score at baseline (≥10 or <10). Study personnel and patients were masked to treatment assignment. The primary outcome was the change in ESSDAI score from baseline to 24 weeks in all randomly assigned patients. Dose-related change in disease activity (ESSDAI) from baseline at week 24 was assessed by multiple comparison procedure with modelling analysis. Safety was measured in all patients who received at least one dose of study drug. This trial is registered with ClinicalTrials.gov, NCT02962895. FINDINGS: Between June 27, 2017, and Dec 06, 2018, 293 patients were screened, 190 of whom were randomly assigned (placebo n=49, ianalumab 5 mg n=47, ianalumab 50 mg n=47, ianalumab 300 mg n=47). Statistically significant dose-responses were seen for overall disease activity (ESSDAI score) in four of the five dose-response models tested (p<0·025 in four models, p=0·060 in one model). The ESSDAI score decreased from baseline in all ianalumab groups, with the maximal ESSDAI score change from baseline observed in the ianalumab 300 mg group: placebo-adjusted least-squares mean change from baseline -1·92 points (95% CI -4·15 to 0·32; p=0·092). There were four serious adverse events in three patients considered treatment-related (pneumonia [n=1] and gastroenteritis [n=1] in the placebo group; appendicitis plus tubo-ovarian abscess in the same patient in the ianalumab 50 mg group). INTERPRETATION: The study met its primary objective, showing a dose-related decrease in disease activity as measured by ESSDAI at week 24. Overall, ianalumab was well tolerated and safe, with no increase in infections. To our knowledge, this is the first large, randomised, controlled trial in primary Sjögren's syndrome that met its primary endpoint, and its results mean there is potential for more studies of this mechanism in the future. FUNDING: Novartis.

Corneal sub-basal nerve plexus assessment and its association with phenotypic features and lymphocyte subsets in Sjögren's Syndrome.

PURPOSE: To assess and compare corneal sub-basal nerve plexus morphology with circulating lymphocyte subsets, immunologic status and disease activity in Sjögren syndrome (SjS) patients. METHODS: Fifty-five SjS patients, 63 Sicca patients (not fulfilling SjS criteria), 18 rheumatoid arthritis (RA) patients and 20 healthy controls (HC) were included. Systemic disease activity in SjS was assessed with the ESSDAI score. Lymphocyte subpopulations were studied with flow cytometry. Corneal confocal microscopy and ImageJ software were used to characterize corneal sub-basal nerve plexus in terms of nerve density (CNFD), length (CNFL) and tortuosity (CNFT). Conventional dry eye tests were also performed. RESULTS: CNFL and CNFD were lower in SjS, Sicca and RA groups, compared to HC (p < 0.001 for both SjS and Sicca); CNFL p = 0.005, CNFD p = 0.018 in RA). CNFT was higher in SjS, followed by Sicca, RA and HC. A negative correlation was found between ESSDAI score and CNFL (r=-0.735, p = 0.012). CNFL correlated negatively with IL21+ CD8+ T cells (r=-0.279, p = 0.039) and a positively with total memory (r = 0.299, p = 0.027), unswitched memory (r = 0.281, p = 0.038) and CD24Hi CD27+ (r = 0.278, p = 0.040) B cells. CNFD showed a tendency to significance in its negative correlation with ESSDAI (r=-0.592, p = 0.071) and in its positive correlation with switched memory B cells (r = 0.644, p = 0.068). CONCLUSIONS: This is the first study aiming to correlate ocular findings with lymphocyte subsets in SjS. The associations founded between CNFL and CNFD and disease activity, IL21+ follicular T cells and some B-cell subsets suggest that corneal nerve damage may parallel systemic disease activity and inflammatory cells' dynamics.

Association between EBV serological patterns and lymphocytic profile of SjS patients support a virally triggered autoimmune epithelitis.

Sjögren's syndrome (SjS) is characterized by lymphocytic infiltration of exocrine glands, i.e. autoimmune epithelitis. Lymphocytes are central in SjS pathogenesis, with B-cell hyperactivity mediated by T-cells. B-cells are main targets of Epstein-Barr virus (EBV) infection, a frequently-suggested trigger for SjS. We aimed to evaluate how the EBV infection modulates B and T-cell subsets in SjS, including as controls Rheumatoid arthritis patients (RA) and healthy participants (HC). SjS patients presented decreased CXCR5+T-cells, although IL21-secreting Tfh and Tfc cells were increased. Tfc were positively correlated with ESSDAI scores, suggesting their relevant role in SjS pathogenesis. As previously described, SjS patients showed expanded circulating naïve B-cell compartments. SjS patients had a higher incidence of EBV-EA-D-IgG+ antibodies, characteristic of recent EBV-infection/reactivation. SjS patients with past infection or recent infection/reactivation showed increased CXCR3+Th1 and CXCR3+Tfh1 cells compared to those without active infection. SjS patients with a recent infection/reactivation profile presented increased transitional B-cells compared to patients with past infection and increased plasmablasts, compared to those without infection. Our results suggest EBV-infection contributes to B and T-cell differentiation towards the effector phenotypes typical of SjS. Local lymphocyte activation at ectopic germinal centres, mediated by Tfh and Tfc, can be EBV-driven, perpetuating autoimmune epithelitis, which leads to gland destruction in SjS.

Lymphocyte subpopulations in Sjögren's syndrome are distinct in anti-SSA-positive patients and related to disease activity.

OBJECTIVES: Sjögren's syndrome (SjS) patients exhibit great phenotypical heterogeneity, reinforced by the positiveness of anti-SSA antibody. We aimed to evaluate lymphocyte subpopulations in SSA-positive (SSA+SjS) and SSA-negative (SSA-SjS) SjS patients, Sicca patients, and healthy controls (HC), and to investigate associations between lymphocyte subpopulations and disease activity in SjS. METHODS: According to the fulfilment of the ACR/EULAR 2016 classification criteria, patients were included as SjS or as Sicca. HC were selected from the Ophthalmology outpatient clinic. Lymphocyte subpopulations were characterized by flow cytometry. Statistical analysis was performed with GraphPad PrismTM, with statistical significance concluded if p < 0.05. RESULTS: We included 53 SjS patients (38 SSA+ and 15 SSA-), 72 Sicca, and 24 HC. SSA+SjS patients presented increased IL-21+CD4+ and CD8+ T cells compared to Sicca and HC, whereas compared to SSA-SjS patients, only IL-21+CD4+ T cell percentages were increased and Tfh17 percentages and numbers were decreased. Compared to Sicca and HC, SSA+SjS patients had higher levels of CD24HiCD38Hi B cells, naïve B cells, and IgM-/+CD38++ plasmablasts, and lower levels of memory B cells, including CD24HiCD27+ B cells. SSA+SjS patients with clinically active disease had positive correlations between ESSDAI and IL-21+CD4+ (p = 0.038, r = 0.456) and IL-21+CD8+ T cells (p = 0.046, r = 0.451). CONCLUSIONS: In SjS, a distinct lymphocyte subset distribution profile seems to be associated with positive anti-SSA. Moreover, the association between ESSDAI and IL-21+CD4+ and IL-21+CD8+ (follicular) T cells in SSA+SjS patients suggests the involvement of these cells in disease pathogenesis and activity, and possibly their utility for the prognosis and assessment of response to therapy. Key Points • SSA+SjS patients have a pronounced naïve/memory B cell imbalance. • SSA+SjS patients have more active disease associated with IL-21+CD4+ and IL-21+CD8+ follicular T cell expansion. • IL-21+CD4+ and IL-21+CD8+ T cell quantification may be useful for the prognosis and assessment of response to therapy.

Patient-related outcomes in Sjögren syndrome treated with stimulants of salivary secretion: Randomized clinical trial.

OBJECTIVES: To investigate the impact of gustatory stimulants of salivary secretion (GSSS) on Sjögren's syndrome patients' self-perception of xerostomia, oral health-related quality of life (OHRQoL) and salivary secretion. METHODS: A total of 110 Sjögren's syndrome patients were randomly allocated to be treated with either a malic acid lozenge or a citric acid mouthwash and then crossed over. Before and after the interventions, the Xerostomia Inventory 5 (SXI-5-PL) and the Oral Health Impact Profile (OHIP-14-PT) questionnaires (both in the Portuguese language) were administered to patients. Unstimulated, mechanical and gustatory-stimulated salivary flows were determined. Repeated measures and between-subject analyses were performed. Statistical significance was set at 5%. RESULTS: After the intervention and within each group, both GSSS elicited a reduction in the SXI-5-PL and OHIP-14-PT scores and an increase in salivary output, significant in the malic acid lozenge group. The malic acid treatment resulted in a greater effect size and percentage improvement than citric acid mouthwash. The malic acid lozenge also produced a significant greater salivary output than the citric acid rising solution. CONCLUSIONS: In Sjögren's syndrome patients, lozenges containing malic acid increased saliva production and xerostomia relief, resulting in improved quality of life.

Tear Meniscus and Corneal Sub-basal Nerve Plexus Assessment in Primary Sjögren Syndrome and Sicca Syndrome Patients.

PURPOSE: To evaluate lower tear meniscus and corneal sub-basal nerve plexus in primary Sjögren's syndrome (pSS) and Sicca syndrome patients. METHODS: Cross-sectional study of 116 patients with Sicca syndrome associated with pSS and not associated with Sjögren's syndrome (non-SS Sicca) and 20 normal control subjects. Tear meniscus height and area were measured using anterior segment optical coherence tomography; corneal sub-basal nerve plexus density, length, and tortuosity were evaluated using in vivo confocal microscopy. Data analysis was performed using IBM-SPSS Statistics 24.0. RESULTS: Corneal sub-basal nerve plexus density and length were significantly lower, and tortuosity was significantly higher in pSS and non-SS Sicca groups than in normal control subjects (P < 0.001; P = 0.018, respectively). Corneal sub-basal nerve plexus presented a strong association with Schirmer test I and tear breakup time. Cutoff values of sub-basal nerve plexus density (36.5 nerve/mm) and length (12.5 mm/mm) presented 80.2% to 81.9% sensitivity and 85% specificity for detecting Sicca syndrome patients. No significant differences were found between the 3 groups regarding tear meniscus height and area. CONCLUSIONS: Corneal sub-basal nerve plexus in vivo confocal microscopy may be a useful tool in the assessment of dry eye disease in Sicca syndrome, complementing the information provided by the conventional modalities used in dry eye disease evaluation.

Validation of Oral Health Impact Profile-14 and its association with Hypossialia in a Sjögren Syndrome Portuguese Population.

AIMS: The objective of this study was to perform the Portuguese transcultural adaptation of the original Brazilian version of the Oral Health Impact Profile-14 (OHIP-14) while evaluating the association between hyposalivation and quality of life in a Sjögren´s Syndrome population. METHODS: The original Brazilian version of the Oral Health Impact Profile-14 was culturally adapted following the guidelines for cross-cultural adaptation of health-related quality of life measures. The questionnaires were administered by trained and calibrated dental doctors to 86 patients with Sjögren´s Syndrome. Oral Health Impact Profile-14 properties were examined including reliability, internal consistency and test-retest reliability, using Cronbach's alpha, total and inter-item correlation, and intra-class correlation coefficients, respectively. Whole saliva secretion rates and hyposalivation-related variables were collected and statistically analyzed. Spearman´s rho correlations were obtained between salivary flows and OHIP -14 domains and total score. Alpha was set at 0.05. Informed consents and local ethical committee clearance were obtained. RESULTS: Each question of the questionnaire performed adequately. Cronbach alpha values for the 14 questions were 0.89 for both test administrations and were lower if item removed. Scores for both questionnaire administration and ICC results presented good to excellent reliability with ICC ranging from 84% to 92%. Mean salivary flow rate was 0.05 (SD: 0.03) ml/min and mean stimulated salivary flow was 0.57 (SD: 0.44) ml/min, which are within expected values in a population with hyposalivation. The results describe a negative and significant correlation between total OHIP-14-PT score, physical pain, physical disability domain and stimulated and differential salivary flows. There was a negative and significant correlation between unstimulated salivary flow with physical pain. CONCLUSION: Within the limitations of this study, the OHIP-14-PT seems to be a valid and reliable instrument for measuring oral health related quality of life in patients with Sjögren´s Syndrome. Both differential and stimulated salivary flows seem to correlate negatively with age and the quality of life is significantly diminished by lower stimulated salivary flow rates.

Association between memory B-cells and clinical and immunological features of primary Sjögren's syndrome and Sicca patients.

B-cells play a pivotal role in primary Sjögren's syndrome (pSS) pathogenesis. We aim to (1) evaluate the distribution of B-lymphocyte subpopulations in pSS and Sicca patients, (2) establish cut-off points that discriminate pSS from controls, (3) evaluate the association between memory B-cells and phenotypic features in pSS. We included 57 pSS patients, 68 Sicca and 24 healthy controls. Circulating B-cells were characterized by flow cytometry as naïve and memory subsets and classified from Bm1 to Bm5. Compared to controls, pSS patients had lower percentages (29.5 vs 44.4%) and absolute numbers (47 vs 106 cells/µl) of memory B-cells. Through ROC curves, a cut-off of ≤ 58 total memory B-cells/µl yielded a specificity of 0.88 and a sensitivity of 0.60 for pSS, and was met by 59.6% of pSS patients, 38.8% of Sicca and 12.5% of controls. A cut-off of < 23.5 Switched-memory B-cells/µl yielded a specificity of 0.88 and a sensitivity of 0.54 and was met by 54.4% of pSS patients, 37.3% of Sicca and 12.5% of controls. In pSS, lower total memory B-cells count was associated with longer disease duration (14.3 vs 8.1 years, p = 0.006) and more active disease profile, as evaluated by the European League Against Rheumatism (EULAR) Sjögren's Syndrome Disease Activity Index (ESSDAI) (3.1 vs 1.4, p = 0.043). Decreased numbers of memory B-cells clearly discriminated pSS from controls and can also have prognostic value. It remains to be clarified whether Sicca patients with decreased memory B-cells represent pSS and if B-cell profiling could help in the diagnosis of pSS.

Portuguese recommendations for the use of methotrexate in rheumatic diseases - 2016 update.

BACKGROUND: Methotrexate (MTX) is the first-line drug in the treatment of rheumatoid arthritis (RA) and the most commonly prescribed disease modifying anti-rheumatic drug. Moreover, it is also used as an adjuvant drug in patients under biologic therapies, enhancing the efficacy of biologic agents. OBJECTIVES: To review the literature and update the Portuguese recommendations for the use of MTX in rheumatic diseases first published in 2009. METHODS: The first Portuguese guidelines for the use of MTX in rheumatic diseases were published in 2009 and were integrated in the multinational 3E Initiative (Evidence Expertise Exchange) project. The Portuguese rheumatologists based on literature evidence and consensus opinion formulated 13 recommendations. At a national meeting, the recommendations included in this document were further discussed and updated. The document resulting from this meeting circulated to all Portuguese rheumatologists, who anonymously voted online on the level of agreement with the updated recommendations. RESULTS: Results presented in this article are mainly in accordance with previous guidelines, with some new information regarding hepatitis B infection during MTX treatment, pulmonary toxicity monitoring, hepatotoxicity management, association with hematologic neoplasms, combination therapy and tuberculosis screening during treatment. CONCLUSION: The present recommendations combine scientific evidence with expert opinion and attained desirable agreement among Portuguese rheumatologists. The regular update of these recommendations is essential in order to keep them a valid and useful tool in daily practice.

Tratamento cirúrgico de fratura cominutiva da tíbia com utilização de duas placas com áreas de trabalho consecutivas e sobrepostas / Treatment of tibial cominutive fracture using two plates with consecutive and overlay work areas: case report

Objetivo: Relatar um caso no qual foi realizado tratamento cirúrgico de fratura cominutiva da tíbia de um homem de 26 anos, com utilização de duas placas com áreas de trabalho consecutivas e sobrepostas no Serviço de Ortopedia e Traumatologia do Hospital Galba Velloso, de Belo Horizonte, Minas Gerais. Métodos: Realizou-se extensa revisão bibliográfica em revistas, periódicos e literatura especializada, bem como foi acompanhado o pré e pós-operatório de um caso de fratura cominutiva de tíbia no qual foram utilizadas placas duplas no mesmo osso. Conclusão: A osteossíntese com sistema de duas placas com áreas de trabalho consecutivas e sobrepostas, apresentada no caso relatado, se mostrou estável e eficaz. (AU)

Objective: To report a case of comminuted tibial fracture surgical treatment in a 26 year old man, using two plates with consecutive and overlapping Working area in the Orthopedics and Traumatology Hospital Galba Velloso in Belo Horizonte, Minas Gerais. Methods: We performed extensive bibliographic review in journals, periodicals and specialized Literature and a preoperative and postoperative case of a comminuted tíbia fracture in which double plates were used in the same bone was accompanied. Conclusion: Osteosynthesis with two-plate system with consecutive and overlapping work areas, presented in the case reported, was shown to be stable and efficient. (AU)

IL10 low-frequency variants in Behçet's disease patients.

AIM: To explain the missing heritability after the genome-wide association studies era, sequencing studies allow the identification of low-frequency variants with a stronger effect on disease risk. Common variants in the interleukin 10 gene (IL10) have been consistently associated with Behçet's disease (BD) and the goal of this study is to investigate the role of low-frequency IL10 variants in BD susceptibility. METHODS: To identify IL10 low-frequency variants, a discovery group of 50 Portuguese BD patients were Sanger-sequenced in a 7.7 kb genomic region encompassing the complete IL10 gene, 0.9 kb upstream and 2 kb downstream, and two conserved regions in the putative promoter. To assess if the novel variants are BD- and/or Portuguese-specific, they were assayed in an additional group of BD patients (26 Portuguese and 964 Iranian) and controls (104 Portuguese and 823 Iranian). RESULTS: Rare IL10 coding variants were not detected in BD patients, but we identified 28 known single nucleotide polymorphisms with minor allele frequencies ranging from 0.010 to 0.390, and five novel non-coding variants in five heterozygous cases. ss836185595, located in the IL10 3' untranslated region, was also detected in one Iranian control individual and therefore is not specific to BD. The remaining novel IL10 variants (ss836185596 and ss836185602 in intron 3, ss836185598 and ss836185604 in the putative promoter region) were not found in the replication dataset. CONCLUSION: This study highlights the importance of screening the whole gene and regulatory regions when searching for novel variants associated with complex diseases, and the need to develop bioinformatics tools to predict the functional impact of non-coding variants and statistical tests which incorporate these predictions.

Análise anatômica da abdominoplastia / Anatomical analysis of abdominoplasty

A abdominoplastia está entre os procedimentos cirúrgicos mais realizados na cirurgia plástica, de forma que muitas variações técnicas têm sido criadas com o objetivo de se reduzirem as complicações e para se obter melhores resultados no contorno abdominal. Nesse contexto, a anatomia da parede abdominal ganha papel de destaque, uma vez que as justificavas em defesa de técnicas, como a abdominoplastia clássica e lipoabdominoplastia, estão atreladas a princípios anatômicos. Isso evidencia a necessidade do domínio da anatomia da região pelo cirurgião plástico, pois, além de entender os motivos de se adotar determinados procedimentos cirúrgicos, o torna mais capacitado de adaptá-los às características anatômicas de cada paciente, além de compreender as alterações morfofuncionais provocadas pela cirurgia. Diante disso, esse trabalho teve o objetivo de buscar na literatura estudos que enfocassem a descrição anatômica da abdominoplastia, tanto clássica quanto de outras variantes, como a lipoabdominoplastia, bem como as explicações anatomofisiopatológicas das principais complicações operatórias inerentes.

Abdominoplasty is a common surgical procedure in plastic surgery. Consequently, several technical variations have been created with the aim of reducing complications and obtaining better results in the abdominal contour. The anatomy of the abdominal region plays an important role in this procedure, since arguments in favor of techniques, such as classic abdominoplasty and lipoabdominoplasty are linked to anatomical principles. This highlights the plastic surgeon's need to have a good knowledge of the anatomy of this region. Not only will this knowledge enable plastic surgeons to understand the reasons for adopting certain surgical procedures, but it will also enable them adapt these procedures to the anatomical characteristics of each patient. In addition, this knowledge will help determine the morphological changes caused by surgery. Therefore, this study aimed to identify studies in the literature focusing on the anatomical description of both classical abdominoplasty and other variants, such as lipoabdominoplasty. It also aimed to discover the anatomical and physiopathological explanations for the major inherent surgical complications.

Validation of Portuguese-translated computer touch-screen questionnaires in patients with rheumatoid arthritis and spondyloarthritis, compared with paper formats.

The aim of this paper was to assess the validity and reliability of the touch-screen standard Portuguese version of the following patient-reported outcomes (PROs), compared with paper format, in patients with rheumatoid arthritis (RA) and spondyloarthritis: Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), Bath Ankylosing Spondylitis Functional Index (BASFI), Ankylosing Spondylitis Quality of Life scale (ASQoL), Short-Form 36 (SF-36), Health Assessment Questionnaire (HAQ) and visual analogue scales (VAS) measuring pain and burden of disease. Adult patients with RA and spondyloarthritis attending the Portuguese Institute of Rheumatology were recruited from March 2013 to January 2014. Patients filled the paper and touch-screen formats of the standard Portuguese versions of the PROs. Two groups of VAS were used, RA and psoriatic arthritis (Global VAS) and another specific for spondyloarthrites (Spa-VAS). Paper questionnaires were filled 15 min before touch-screen formats. Agreement between formats (validity) was assessed by intraclass correlation coefficient (ICC), while internal consistency of scales (reliability) was assessed by Cronbach's alpha. Overall, 134 patients were included with a mean age of 51 years, 74.6 % female and 57.5 % presenting RA. BASDAI, BASFI, HAQ and ASQoL showed high ICC between paper and touch-screen formats (0.977, 0.958, 0.974 and 0.940, respectively). ICC for Global VAS ranged from 0.906 to 0.921, while Spa-VAS ranged from 0.867 to 0.943. The mean ICC for all SF-36 domains was 0.889 (ICC for each domain ranged from 0.781 to 0.944). Touch-screen standard Portuguese formats of these PROs may be valid and reliable tools for PRO measurement in rheumatology.

Comparative Effectiveness of Tocilizumab and TNF Inhibitors in Rheumatoid Arthritis Patients: Data from the Rheumatic Diseases Portuguese Register, Reuma.pt.

OBJECTIVES: To compare the effectiveness of TNF inhibitors (TNFi) and tocilizumab in rheumatoid arthritis (RA) treatment, according to different response criteria. METHODS: We included RA patients registered in the Rheumatic Diseases Portuguese Register treated with TNFi or tocilizumab for at least 6 months, between January 2008 and July 2013. We assessed remission/low disease activity (LDA) at 6 months according to DAS28, CDAI, and SDAI, as well as Boolean ACR/EULAR remission and EULAR response rate, adjusting for measured confounders. RESULTS: Tocilizumab-treated patients (n = 95) presented higher baseline disease activity and were less frequently naïve to biologics compared to TNFi users (n = 429). Multivariate logistic regression analysis including the propensity score for receiving tocilizumab showed that patients treated with tocilizumab were more likely to achieve remission or LDA according to DAS28 (OR = 11.0/6.2, 95% CI 5.6-21.6/3.2-12.0), CDAI (OR = 2.8/2.6, 95% CI 1.2-6.5/1.3-5.5), or SDAI (OR = 3.6/2.5, 95% CI 1.5-8.7/1.1-5.5), as well as a good EULAR response (OR = 6.4, 95% CI 3.4-12.0). However, both groups did not differ in Boolean remission (OR = 1.9, 95% CI 0.8-4.8) or good/moderate EULAR response (OR = 1.8, 95% CI 0.8-4.5). CONCLUSIONS: Compared with TNFi, tocilizumab was associated with greater likelihood of achieving DAS28, CDAI, and SDAI remission/LDA and EULAR good response. Boolean remission and EULAR good/moderate response did not differ significantly between groups.