Evaluating the efficacy of biologics with and without methotrexate in the treatment of psoriatic arthritis: a network meta-analysis.

INTRODUCTION: An important consideration in the treatment of patients with psoriatic arthritis (PsA) is whether the addition of methotrexate (MTX) to biologics has greater efficacy than biologic monotherapy with respect to efficacy outcomes in these patients. OBJECTIVES: To conduct a network meta-analysis (NMA) comparing biologics by treatment class with and without MTX for treatment of adults with active PsA. METHODS: A systematic literature review (SLR) identified randomised, double-blinded, controlled trials, and a Bayesian NMA compared biologics with and without MTX by treatment class (tumour necrosis factor inhibitors (TNFi), interleukin-23 inhibitors (IL-23i) and IL-17i). Efficacy outcomes included American College of Rheumatology 20%, 50% and 70% (ACR20, ACR50 and ACR70) improvement response. RESULTS: The SLR initially identified 31 studies, of which 17 met feasibility criteria for the NMA by containing the 'without MTX' subgroup. For ACR20 efficacy (the most robust assessment examined), all active treatments were significantly better than placebo. No statistically significant differences were demonstrated between biologic monotherapy (for all classes examined) and biologics in combination with MTX for ACR20/50. IL-17i were comparable to IL-23i, and IL-17i were significantly better than TNFi for ACR20. Although limited by fewer trials, TNFi, IL-23i and IL-17i were not statistically different for ACR50/70. CONCLUSIONS: Concomitant use of MTX and biologics did not improve ACR efficacy outcomes versus biologic monotherapy. MTX does not appear to be necessary as a background therapy when biologics are used for the achievement of ACR20/50 responses in patients with PsA.

Re-entry catheters in subintimal lower limb recanalization: up to date.

In their daily practice, vascular specialists face the challenge of treating peripheral artery disease (PAD) of the lower limbs. During the last decade, there has been an increasing adoption of endovascular techniques worldwide and a simultaneous expansion of the endovascular instrument portfolio to improve technical results during PAD treatment. The proper use of dedicated endovascular devices is essential to achieve technical success. To know indication, mechanism of action, and possible complications of different devices is of paramount importance to achieve immediate procedural success in the shortest time possible and long-term patency of the treated vessels. All the re-entry catheters on the market are presented with their own unique characteristics. The pros and cons of the use of these devices is also discussed and compared to other possible recanalization strategies. The re-entry devices have been demonstrated to be effective in increasing the procedural success rate, in limiting the dissection of distal healthy vessel segments and shortening the procedural time. They should therefore be considered part of essential tools in the treatment of lower limb chronic total occlusions especially for clinicians who do not feel comfortable in performing retrograde access.

Wedge fragment variations of tibial shaft fractures with intramedullary nailing / Fragmento em cunha das fraturas da diáfise da tíbia com haste intramedular

ABSTRACT Introduction: Tibial shaft fracture is the most common long-bone fracture, and the standard treatment is intramedullary (IM) nail fixation. Regardless of the development of this technique pseudoarthrosis remains prevalent. Objectives: Evaluate the correlation between wedge fragment size and displacement, displacement of the main fragments of the 42B2 type, and pseudoarthrosis incidence. Methods: We retrospectively assessed all patients with 42B2 type fracture treated with IM nailing between January, 2015 and December, 2019. Six radiographic parameters were defined for preoperative radiographs in the anteroposterior (AP) and lateral views. Another six parameters were defined for postoperative radiographs at three, six, and 12 months. The Radiographic Union Score for Tibial Fractures score was used to assess bone healing. Results: Of 355 patients with tibial shaft fractures, 51 were included in the study. There were 41 (82.0%) male patients, with a mean age of 36.7 years, 37 (72.5%) had open fractures, and 28 (54.9%) had associated injuries. After statistical analysis, the factors that correlated significantly with nonunion were wedge height > 18 mm, preoperative translational displacement of the fracture in the AP view > 18 mm, and final distance of the wedge in relation to its original anatomical position after IM nailing > 5 mm. Conclusion: Risk factors for nonunion related to the wedge and42B2 fracture are wedge height > 18 mm, initial translation in the AP view of the fracture > 18 mm, and distance > 5 mm of the wedge from its anatomical position after IM nailing. Evidence level III; Retrospective comparative study .

RESUMO Introdução: A fratura da diáfise da tíbia é a fratura mais comum dentre os ossos longos, sendo o tratamento padrão a fixação com haste intramedular (HIM). Independentemente do desenvolvimento da técnica cirúrgica, a pseudoartrose continua prevalente. Objetivo: Avaliar a associação entre o tamanho e o desvio da cunha, os desvios dos fragmentos principais do tipo 42B2 e a incidência de pseudoartrose. Métodos: Avaliamos, retrospectivamente, todos os pacientes com fraturas tipo 42B2 tratados com hastes intramedulares entre janeiro de 2015 e dezembro de 2019. Seis parâmetros radiográficos foram definidos para as radiografias pré-operatórias nas incidências anteroposterior (AP) e perfil. Outros seis parâmetros foram definidos para as radiografias pós-operatórias em 3, 6 e 12 meses de acompanhamento pós-operatório. O Escore Radiográfico de União para as Fraturas da Tíbia (RUST) foi o instrumento usado para avaliar a consolidação óssea. Resultados: Dos 355 pacientes com fraturas da diáfise da tíbia, 51 foram incluídos no estudo. Os pacientes incluídos foram 41 (82,0%) do sexo masculino, com idade média de 36,7 anos, 37 (72,5%) com fraturas expostas e 28 (54,9%) com lesões associadas. Após análise estatística, os fatores que se correlacionaram significativamente com a não consolidação foram a altura da cunha > 18 mm, o deslocamento translacional pré-operatório da fratura na incidência AP > 18 mm e a distância final da cunha em relação à sua posição anatômica original após a cravação do MI > 5 mm. Conclusão: Os fatores de risco para a pseudartrose relacionada com a fratura em cunha e42B2 são a altura da cunha > 18 mm, a translação inicial na vista AP da fratura > 18 mm e a distância > 5 mm da cunha em relação à sua posição anatómica após a fixação IM. Nível de evidência III; estudo comparativo retrospectivo. Nível de evidência III; Estudo retrospectivo comparativo .

Predictive factors of non-sentinel lymph node disease in breast cancer patients with positive sentinel lymph node.

INTRODUCTION: Management of positive sentinel lymph node biopsy (SLNB) in breast cancer remains a matter of debate. Our aim was to evaluate the incidence and identify predictive factors of non-sentinel lymph node metastases. METHODS: Retrospective review of all cN0 breast cancer patients treated between January 2013 and December 2017, with positive SLNB that were submitted to ALND. RESULTS: Of the 328 patients included, the majority of tumors were cT1 or cT2, with lymphovascular invasion in 58.4% of cases. The mean isolated nodes in SLNB was 2.7, with a mean of 1.6 positive nodes, 60.7% with extracapsular extension. Regarding ALND, a mean of 13.9 nodes were isolated, with a mean of 2.1 positive nodes. There was no residual disease in the ALND in 50.9% of patients, with 18.9% having ≥4 positive nodes. In the multivariate analysis, lymphovascular invasion, extracapsular extension in SLN, largest SLN metastases size (>10 mm) and ratio of positive SNL (>50%) were independent predictors of non-sentinel lymph node metastases. These four factors were used to build a non-pondered score to predict the probability of a positive ALND after a positive SLNB. The AUC of the model was 0.69 and 81% of patients with score = 0 and 65.6% with score = 1 had no additional disease in ALND. CONCLUSION: The absence of non-sentinel lymph node metastases in the majority of patients with 1-2 positive SLN with low risk score questions the need of ALND in this population. The identified predictive factors may help select patients in which ALND can be omitted.

Ru(II)/amino acid complexes inhibit the progression of breast cancer cells through multiple mechanism-induced apoptosis.

For some cancer subtypes, such as triple-negative breast cancer, there are no specific therapies, which leads to a poor prognosis associated with invasion and metastases. Ruthenium complexes have been developed to act in all steps of tumor growth and its progression. In this study, we investigated the effects of Ruthenium (II) complexes coupled to the amino acids methionine (RuMet) and tryptophan (RuTrp) on the induction of cell death, clonogenic survival ability, inhibition of angiogenesis, and migration of MDA-MB-231 cells (human triple-negative breast cancer). The study also demonstrated that the RuMet and RuTrp complexes induce cell cycle blockage and apoptosis of MDA-MB-231 cells, as evidenced by an increase in the number of Annexin V-positive cells, p53 phosphorylation, caspase 3 activation, and poly(ADP-ribose) polymerase cleavage. Moreover, morphological changes and loss of mitochondrial membrane potential were detected. The RuMet and RuTrp complexes induced DNA damage probably due to reactive oxygen species production related to mitochondrial membrane depolarization. Therefore, the RuMet and RuTrp complexes acted directly on breast tumor cells, leading to cell death and inhibiting their metastatic potential; this reveals the potential therapeutic action of these drugs.

Radiological results of severe scfe treatment at iot-fmusp from 2012 to 2018 / Resultados radiológicos do tratamento de epifisiolistese grave no iot-fmusp entre 2012-2018

ABSTRACT Objective: To assess the complications in patients with severe slipped capital femoral epiphysis treated with the Dunn or modified Dunn procedure from 2012 to 2018 at the Institute of Orthopedics and Traumatology, Medical School, Universidade de São Paulo. Methods: Analysis of medical records, preoperative and postoperative radiographs with at least one year of radiographic follow-up of patients with severe slipped capital femoral epiphysis. Results: We reviewed the complications in 19 operated cases from 2012 to 2018, out of which 36.8% had osteonecrosis of the femoral head, one patient had chondrolysis, and another had postoperative infection. Conclusion: The osteonecrosis rate observed in this series of cases is similar to that described in other orthopedic facilities. We assessed factors that could potentially influence this outcome, including other characteristics of the patient (obesity, endocrine diseases, and history of sports activities) and of the health system. Level of Evidence III, Restropective Case Series.

RESUMO Objetivo: Avaliar as complicações apresentadas nos pacientes com epifisiolistese grave tratados por meio do procedimento de Dunn ou Dunn Modificado entre 2012 e 2018 no IOT-FMUSP. Métodos: Análise de prontuários, radiografias pré-operatórias e radiografias pós-operatórias com pelo menos 1 ano de seguimento radiográfico dos pacientes com epifisiolistese grave. Resultados: Analisou-se a presença de complicações em 19 casos operados de 2012 a 2018. Desses pacientes, 36,8% apresentaram osteonecrose da cabeça femoral, oi observada condrólise em 1 paciente e infecção pós-operatória em 1 paciente. Conclusão: A taxa de osteonecrose observada nesta série de casos está próxima à descrita em outros serviços. Alguns fatores que potencialmente influenciariam neste desfecho poderiam ter sido avaliados, como outras características do paciente (obesidade, doenças endócrinas e atividade esportiva) e do sistema de saúde. Nível de Evidência III, Série Retrospectiva de Casos .

Dataset of the vascular e-Learning during the COVID-19 pandemic (EL-COVID) survey.

This dataset supports the findings of the vascular e-Learning during the COVID-19 pandemic survey (the EL-COVID survey). The General Data Protection Regulation (GDPR) of the European Union was taken into consideration in all steps of data handling. The survey was approved by the institutional ethics committee of the Primary Investigator and an online English survey consisting of 18 questions was developed ad-hoc. A bilingual English-Mandarin version of the questionnaire was developed according to the instructions of the Chinese Medical Association in order to be used in mainland People's Republic of China. Differences between the two questionnaires were minor and did affect the process of data collection. Both questionnaires were hosted online. The EL-COVID survey was advertised through major social media. All national and regional contributors contacted their respective colleagues through direct messaging on social media or by email. Eight national societies or groups supported the dissemination of the EL-COVID survey. The data provided demographics information of the EL-COVID participants and an insight on the level of difficulty in accessing or citing previously attended online activities and whether participants were keen on citing these activities in their Curricula Vitae. A categorization of additional comments made by the participants are also based on the data. The survey responses were filtered, anonymized and submitted to descriptive analysis of percentage.

Efficacy and safety of baricitinib for the treatment of hospitalised adults with COVID-19 (COV-BARRIER): a randomised, double-blind, parallel-group, placebo-controlled phase 3 trial.

BACKGROUND: Baricitinib is an oral selective Janus kinase 1/2 inhibitor with known anti-inflammatory properties. This study evaluates the efficacy and safety of baricitinib in combination with standard of care for the treatment of hospitalised adults with COVID-19. METHODS: In this phase 3, double-blind, randomised, placebo-controlled trial, participants were enrolled from 101 centres across 12 countries in Asia, Europe, North America, and South America. Hospitalised adults with COVID-19 receiving standard of care were randomly assigned (1:1) to receive once-daily baricitinib (4 mg) or matched placebo for up to 14 days. Standard of care included systemic corticosteroids, such as dexamethasone, and antivirals, including remdesivir. The composite primary endpoint was the proportion who progressed to high-flow oxygen, non-invasive ventilation, invasive mechanical ventilation, or death by day 28, assessed in the intention-to-treat population. All-cause mortality by day 28 was a key secondary endpoint, and all-cause mortality by day 60 was an exploratory endpoint; both were assessed in the intention-to-treat population. Safety analyses were done in the safety population defined as all randomly allocated participants who received at least one dose of study drug and who were not lost to follow-up before the first post-baseline visit. This study is registered with ClinicalTrials.gov, NCT04421027. FINDINGS: Between June 11, 2020, and Jan 15, 2021, 1525 participants were randomly assigned to the baricitinib group (n=764) or the placebo group (n=761). 1204 (79·3%) of 1518 participants with available data were receiving systemic corticosteroids at baseline, of whom 1099 (91·3%) were on dexamethasone; 287 (18·9%) participants were receiving remdesivir. Overall, 27·8% of participants receiving baricitinib and 30·5% receiving placebo progressed to meet the primary endpoint (odds ratio 0·85 [95% CI 0·67 to 1·08], p=0·18), with an absolute risk difference of -2·7 percentage points (95% CI -7·3 to 1·9). The 28-day all-cause mortality was 8% (n=62) for baricitinib and 13% (n=100) for placebo (hazard ratio [HR] 0·57 [95% CI 0·41-0·78]; nominal p=0·0018), a 38·2% relative reduction in mortality; one additional death was prevented per 20 baricitinib-treated participants. The 60-day all-cause mortality was 10% (n=79) for baricitinib and 15% (n=116) for placebo (HR 0·62 [95% CI 0·47-0·83]; p=0·0050). The frequencies of serious adverse events (110 [15%] of 750 in the baricitinib group vs 135 [18%] of 752 in the placebo group), serious infections (64 [9%] vs 74 [10%]), and venous thromboembolic events (20 [3%] vs 19 [3%]) were similar between the two groups. INTERPRETATION: Although there was no significant reduction in the frequency of disease progression overall, treatment with baricitinib in addition to standard of care (including dexamethasone) had a similar safety profile to that of standard of care alone, and was associated with reduced mortality in hospitalised adults with COVID-19. FUNDING: Eli Lilly and Company. TRANSLATIONS: For the French, Japanese, Portuguese, Russian and Spanish translations of the abstract see Supplementary Materials section.

Vascular e-Learning During the COVID-19 Pandemic: The EL-COVID Survey.

BACKGROUND: The corona virus disease (COVID-19) pandemic has radically changed the possibilities for vascular surgeons and trainees to exchange knowledge and experience. The aim of the present survey is to inventorize the e-learning needs of vascular surgeons and trainees as well as the strengths and weaknesses of vascular e-Learning. METHODS: An online survey consisting of 18 questions was created in English, with a separate bilingual English-Mandarin version. The survey was dispersed to vascular surgeons and trainees worldwide through social media and via direct messaging from June 15, 2020 to October 15, 2020. RESULTS: Eight hundred and fifty-six records from 84 different countries could be included. Most participants attended several online activities (>4: n = 461, 54%; 2-4: n = 300, 35%; 1: n = 95, 11%) and evaluated online activities as positive or very positive (84.7%). In deciding upon participation, the topic of the activity was most important (n = 440, 51.4%), followed by the reputation of the presenter or the panel (n = 178, 20.8%), but not necessarily receiving accreditation or certification (n = 52, 6.1%). The survey identified several shortcomings in vascular e-Learning during the pandemic: limited possibility to attend due to lack of time and increased workload (n = 432, 50.5%), no protected/allocated time (n = 488, 57%) and no accreditation or certification, while technical shortcomings were only a minor problem (n = 25, 2.9%). CONCLUSIONS: During the COVID-19 pandemic vascular e-Learning has been used frequently and was appreciated by vascular professionals from around the globe. The survey identified strengths and weaknesses in current e-Learning that can be used to further improve online learning in vascular surgery.

The missing link in the history of the locked intramedullary nail / O elo perdido na história da haste intramedular bloqueada

ABSTRACT Femoral Shaft intramedullary nails were first described by the Aztecs in 16th century, but the modern use of intramedullary nails as the gold standard treatment for femoral shaft fractures began with Gerald Kuntcher in 1939. From the first Kuntcher's study in 1939, to the creation of interlocking nail, a long and some minor developments were described around the world. However, a major development is missing: the first nail to have a rotational and vertical stability locking system was described by Flavio Godoy Moreira, but was never published on an indexed journal for the correct historical reference. Level of Evidence V, Therapeutics Studies, Expert Opinion.

RESUMO A história da haste intramedular bloqueada nas fraturas do fêmur se inicia com os Astecas no século 16, mas o uso moderno que a tornou o padrão ouro no tratamento destas fraturas se inicia com Gerald Kuntcher em 1939. Do estudo inicial de Kutcher até o desenvolvimento da haste bloqueada muitos pequenos desenvolvimentos foram descritos ao redor do mundo. Dentro deste desenvolvimento, a primeira haste a ter um controle vertical e rotacional foi descrito por Flavio Pires de Camargo, e nunca foi publicado em um jornal indexado que permita sua correta referência histórica. Nível de Evidência V, Estudos Terapêuticos, Opinião de especialista.

Effect of Friction Stir Welding Techniques and Parameters on Polymers Joint Efficiency-A Critical Review.

The objective of current work is to analyse the influence of different welding techniques and welding parameters on the morphology and mechanical strength of friction stir welds (FSW) in polymers, based on data collected in the literature. In the current work, only articles that provide data on the joint efficiency, or sufficient information to estimate it are considered. The process using conventional tool is presented and compared with new procedures developed for FSW of polymers, such as those using tools with heated stationary shoulder, preheating of the polymer or double-side passage of the tool. The influence of tool rotational speed (w), welding speed (v), tilt angle and geometry of the pin are discussed. This work focuses on the polymers most studied in the literature, polyethylene (PE) and polypropylene (PP). The use of external heating and tools with stationary shoulder proved to be of great importance in improving the surface finish, reducing defects, and increasing the mechanical strength of the welds. The increase in the w/v ratio increased the joint efficiency, especially when using conventional tools on PE. A trend was obtained for conventional FSW, but it was difficult to establish mathematical relationships, because of the variability of welding conditions.

Compreendendo o GRADE: PICO e qualidade dos estudos / Understanding GRADE system: PICO and study quality

A saúde baseada em evidências se refere ao uso criterioso do conhecimento científico existente, oriundo de pesquisas clínicas, utilizando metodologias específicas que garantam solidez e clareza nas informações a serem aplicadas na tomada de decisão clínica. Dessa forma, reduzem-se as incertezas no julgamento clínico. O objetivo deste artigo foi descrever a metodologia PICO e a qualidade dos estudos com base no sistema GRADE. (AU)

Evidence-based health refers to the judicious use of existing scientific knowledge from clinical research, using specific methodologies that ensure solidity and clarity to the information to be applied in clinical decision-making, thus reducing uncertainties in clinical judgment. The objective of this article is to describe PICO methodology and the quality of studies in the GRADE system. (AU)

Olive Stones as Filler for Polymer-Based Composites: A Review.

Olives' consumption produces copious agricultural byproducts that have accompanied humanity for millennia, but the increasing worldwide production complicates its management. Most wastes are generated during olive oil production in form of olive stones and other lignocellulosic derivatives. Industrial processes of chemical or physical nature to recover economically compounds from biomass residues are costly, difficult, and non-environmentally friendly. Cellulose, hemicellulose, and lignin biopolymers are the principal components of olive stones, which present interesting qualities as lignocellulosic fillers in polymeric composites. This review will summarize examples of composites based on thermoplastic polymers, such as polystyrene (PS), polylactide (PLA), polyvinyl chloride (PVC), polypropylene (PP), and polycaprolactone (PCL); thermosetting resins (phenol-formaldehyde, unsaturated polyesters, and epoxy) and acrylonitrile butadiene rubber/devulcanized waste rubber (NBR/DWR) blends focusing on the fabrication procedures, characterization, and possible applications. Finally, thanks to the wide disparity in polymer matrix types, the variability in applications is important, from adsorption to mechanical enhancement, showing the easiness and benefit of olive stone integration in many materials.

LONG TERM FOLLOW-UP IN SURGICAL STAGE I NON-SMALL CELL LUNG CANCER - A SINGLE CENTER EXPERIENCE.

INTRODUCTION: Lung cancer has a high mortality rate with an overall survival of 18% at 5 years. Surgical treatment is the gold standard for early stages and is associated with high rates of resolution with a 5-year survival of 80% reported in large studies. PURPOSE: To determinethe survival of patients with non-small cell lung cancer (NSCLC) in stage IA (T1N0M0) undergoing surgical treatment with curative intent in our center. METHODS: We performed a retrospective review of the clinical records of all patients with pathological stage T1a-c N0 (stage I) who underwent thoracic surgery with curative intent from 2010 and 2017 in our center. Overall survival and lung cancer-specific survival was estimated by the Kaplan-Meier method. RESULTS: 87 patients (54 men and 33 women) with a median age of 66 years (range 36 to 83 years) were included. Lobectomy with systematic lymph node dissection was performed in 67 patients (77%). Adenocarcinoma was the predominant histological subtype (n=69; 79%). Overall survival at 5th years was 86,7%. Patients submitted to limited resection (segmentectomy or wedge resection) had lower overall survival compared to those submitted to lobectomy (66,4% vs 88,7%; p=0.008). CONCLUSIONS: Our results show a high 5-year overall survival rate, in agreement with results from larger series studies. Lung cancer screening, although not yet widely implemented, has been shown to reduce mortality associated with lung cancer. These results reinforce the importance of screening programs for specific populations in order to identify patients in early stages and improve overall survival.

Endovascular treatment of wide-neck saccular renal artery aneurysm with waffle-cone technique / Tratamento endovascular de aneurisma renal sacular com colo largo com técnica do waffle-cone

Abstract In the past, treatment of visceral artery aneurysms (VAAs) was exclusively surgical. These aneurysms were rarely diagnosed in elective or emergency cases. Development of imaging techniques and endovascular procedures has changed the history of the therapeutic options for this pathology. Endovascular management of VAAs has arisen to advances in endovascular techniques and has achieved high efficacy.

Resumo No passado, o tratamento de aneurismas da artéria visceral (VAAs) era exclusivamente cirúrgico e raramente diagnosticado em casos eletivos ou de emergência. O desenvolvimento de técnicas de imagem e procedimentos endovasculares mudou a história das opções terapêuticas dessa patologia. O manejo endovascular de VAAs surgiu devido ao avanço das técnicas endovasculares, o qual apresentou uma alta eficácia.

Predictive factors of non-sentinel lymph node disease in breast cancer patients with positive sentinel lymph node. / Factores predictivos de metástasis en ganglios no centinela en el cáncer de mama con ganglio centinela positivo.

INTRODUCTION: Management of positive sentinel lymph node biopsy (SLNB) in breast cancer remains a matter of debate. Our aim was to evaluate the incidence and identify predictive factors of non-sentinel lymph node metastases. METHODS: Retrospective review of all cN0 breast cancer patients treated between January 2013 and December 2017, with positive SLNB that were submitted to ALND. RESULTS: Of the 328 patients included, the majority of tumors were cT1 or cT2, with lymphovascular invasion in 58.4% of cases. The mean isolated nodes in SLNB was 2.7, with a mean of 1.6 positive nodes, 60.7% with extracapsular extension. Regarding ALND, a mean of 13.9 nodes were isolated, with a mean of 2.1 positive nodes. There was no residual disease in the ALND in 50.9% of patients, with 18.9% having ≥ four positive nodes. In the multivariate analysis, lymphovascular invasion, extracapsular extension in SLN, largest SLN metastases size (>10 mm) and ratio of positive SNL (> 50%) were independent predictors of non-sentinel lymph node metastases. These four factors were used to build a non-pondered score to predict the probability of a positive ALND after a positive SLNB. The AUC of the model was 0.69 and 81% of patients with score = 0 and 65.6% with score = 1 had no additional disease in ALND. CONCLUSION: The absence of non-sentinel lymph node metastases in the majority of patients with 1-2 positive SLN with low risk score questions the need of ALND in this population. The identified predictive factors may help select patients in which ALND can be omitted.

Efficacy and Safety of Ixekizumab with or Without Methotrexate in Biologic-Naïve Patients with Psoriatic Arthritis: 52-Week Results from SPIRIT-H2H Study.

INTRODUCTION: In the SPIRIT-H2H (ClinicalTrials.gov: NCT03151551) trial in biologic-naïve patients with active psoriatic arthritis (PsA), ixekizumab (IXE) was superior to adalimumab (ADA) at week 24 in terms of achieving a combined endpoint of ≥ 50% improved response in the American College of Rheumatology scale score (ACR50) and 100% improvement in the Psoriasis Areas and Severity Index (PASI100), and was non-inferior in terms of achieving ACR50. IXE resulted in similar improvements of PsA manifestations irrespective of the use of concomitant conventional synthetic disease-modifying anti-rheumatic drugs (csDMARDs), while ADA response was higher with concomitant csDMARD use. The aim of this study was to determine the efficacy and safety of treatment with IXE and ADA with or without methotrexate (MTX), the most commonly use csDMARD, through week 52 in patients with PsA. METHODS: In the open-label, rater-blinded, head-to-head SPIRIT-H2H trial, randomization of patients was stratified by concomitant use of csDMARD and moderate-to-severe plaque psoriasis involvement. In the post-hoc subgroup analysis presented here, subgroups were defined as with/without concomitant MTX use at baseline. Treatment group effects within subgroups were tested using Fisher's exact test. Missing data were imputed using non-responder imputation. RESULTS: By week 52, IXE provided similar improvements in the combined ACR50 and PASI100 endpoint, ACR50, and other PsA-related domains regardless of whether IXE was used with or without MTX, while ADA efficacy appeared to be improved with concomitant MTX use. When used without concomitant MTX, IXE resulted in significantly higher response versus ADA in terms of the combined ACR50 and PASI100 (p = 0.002) endpoint, minimal disease activity (p = 0.016), and very low disease activity (p = 0.037). The safety of both agents was consistent with their known safety profiles regardless of concomitant MTX use. CONCLUSION: In PsA patients with inadequate control of the disease, IXE delivers consistent efficacy in several clinical domains of the disease regardless of concomitant MTX use. The efficacy of ADA is increased by the concomitant use of MTX. These findings can inform treatment decisions when considering the need for concomitant MTX use with IXE or ADA at initiation or for long-term maintenance.

Hancornia speciosa serum fraction latex stimulates the angiogenesis and extracellular matrix remodeling processes.

The Hancornia speciosa latex reveals angiogenic, osteogenic, and anti-inflammatory properties, which present its potential for developing of wound healing drugs; however, the latex compounds responsible for angiogenesis remain unknown. One strategy to screen these active compounds is evaluation of latex fractions. This study aimed to obtain different fractions of latex and evaluate its angiogenic activity separately using the chick chorioallantoic membrane (CAM) assay. The serum (SE) fraction was responsible for angiogenesis, which was subject to biochemical characterization and computational simulations in order to understand the contribution of H. speciosa latex in wound healing process. Our results revealed weak antioxidant potential and absence of antimicrobial activity in the SE fraction. Phytochemical analysis identified chlorogenic acids (CGA) as the main compound of SE fraction. CGA bioactivity predictions identify different molecules associated with extracellular matrix (ECM) remodeling, such as metalloproteinases, which also are overexpressed in our CAM assay experiment. Docking simulations revealed the interactions between CGA and matrix metalloproteinase 2. In conclusion, SE latex fraction stimulates angiogenesis and may influence ECM remodeling. These properties may contribute to the wound healing process, and also confirm the widespread use of this plant.