Search

Osteosarcoma (OS) is a malignant bone tumor, with a peak of incidence in the second decade of life and possibly associated with the presence of germline mutations. Besides, clinicians have pointed to a second, rarer group of patients that develops OS before 10 years old. Here we access, through next-generation sequencing (NGS) strategy, the genetic alterations present in OS and blood samples from patients diagnosed before and during the second decade of life. A custom NGS panel, designed for the main alterations described in childhood and adolescence neoplasms, named Oncomine Childhood Cancer Research Assay (OCCRA©), was used. Of all 84 OS samples investigated, 42 (50%) presented some somatic variant, with TP53, MYC, CDK4, RB1 and PDGFRA genes harboring the most observed genetic variants. MYC CNVs were more frequent in tumors from patients diagnosed before 10 years old (X21= 5.18, p = 0.023). Additionally, patients diagnosed during the second decade of life presented a higher percentage of somatic and germline variants. Germline variants in TP53 and RB1 were found in 5 of the 11 (45.5%) patients analyzed. Clinical variables and tumor histopathological characteristics were also collected and correlated with our molecular findings.

BackgroundPublications suggest immunomodulation co-therapy improves responder rates in uncontrolled/refractory gout patients undergoing pegloticase treatment. The MIRROR open-label trial showed a 6-month pegloticase + methotrexate co-therapy responder rate of 79%, compared to an established 42% pegloticase monotherapy responder rate. Longer-term efficacy/safety data are presented here.MethodsUncontrolled gout patients (serum urate [SU] ≥ 6 mg/dL and SU ≥ 6 mg/dL despite urate-lowering therapy [ULT], ULT intolerance, or functionally-limiting tophi) were included. Patients with immunocompromised status, G6PD deficiency, severe kidney disease, or methotrexate contraindication were excluded. Oral methotrexate (15 mg/week) and folic acid (1 mg/day) were administered 4 weeks before and during pegloticase therapy. Twelve-month responder rate (SU ResultsFourteen patients were included (all male, 49.3 ± 8.7 years, 13.8 ± 7.4-year gout history, pre-therapy SU 9.2 ± 2.5 mg/dL). Three patients were non-responders and discontinued study treatment before 24 weeks, one patient exited the study per protocol at 24 weeks (enrolled prior to treatment extension amendment), and 10 remained in the study through week 52. Of the 10, 8 completed 52 weeks of pegloticase + methotrexate and were 12-month responders. The remaining two discontinued pegloticase + methotrexate at week 24 (met treatment goals) and stayed in the study under observation (allopurinol prescribed at physicians’ discretion); one remained a responder at 12 months. At 52 weeks, change from baseline in SU was − 8.2 ± 4.1 mg/dL (SU 1.1 ± 2.4 mg/dL,n = 10). Gout flares were common early in treatment but progressively decreased while on therapy (weeks 1–12, 13/14 [92.9%]; weeks 36–52, 2/8 [25.0%]). One patient recovered from sepsis (serious AE). Two non-responders developed high ADA titers; fewer patients had trough concentrations (Cmin) below the quantitation limit (BQL), and the medianCminwas higher (1.03 µg/mL vs. BQL) than pegloticase monotherapy trials.ConclusionsPegloticase + methotrexate co-therapy was well-tolerated over 12 months, with sustained SU lowering, progressive gout flare reduction, and no new safety concerns. Antibody/PK findings suggest methotrexate attenuates ADA formation, coincident with higher treatment response rates.Trial registrationClinicalTrials.gov,NCT03635957. Registered on 17 August 2018.

Infliximab and golimumab are intravenously (IV) administered tumor necrosis factor inhibitors approved to treat moderate-to-severe rheumatoid arthritis (RA) with concomitant methotrexate. Owing to differences in biologic construct, patients with IV-infliximab treatment failure may benefit from switching to IV-golimumab. Utilizing the ACR’s Rheumatology Informatics System for Effectiveness (RISE), a large electronic health records registry based in the USA, we assessed RA disease activity in patients switching from IV-infliximab to IV-golimumab. This retrospective, longitudinal, single-arm study included adults (≥ 18 years) with ≥ 1 RA diagnosis code between 2014 and 2018 and ≥ 1 IV-infliximab prescription within 6 months of a new IV-golimumab order (index date). Longitudinal assessments of disease activity using the Clinical Disease Activity Index (CDAI) were calculated in patients continuing IV-golimumab for 6–9- and 9–12-months post-switch. Paired t-tests evaluated significance of mean improvements during the follow-up periods. Most RA patients with disease activity assessments during the 6-month follow-up (N = 100; mean age: 65.3 years; 81% female; 74% white) demonstrated moderate-to-high disease activity (CDAI: 73% [38/52]) at enrollment. On average, patients showed significant improvement in disease activity within 6–9 months of switching; mean CDAI scores improved from 21.3 to 14.1 (p Key Points• This study used real-world data from the Rheumatology Informatics System for Effectiveness (RISE) registry to evaluate the efficacy of directly switching from intravenous (IV)-infliximab to IV-golimumab to control rheumatoid arthritis (RA) disease activity.• Most IV-infliximab patients had moderate-to-high disease activity at the time of the switch.• On average, IV-golimumab was effective in improving RA disease activity after switching from IV-infliximab as measured by the Clinical Disease Activity Index.• These data suggest that real-world RA patients with persistent symptoms despite treatment with IV-infliximab may realize improved disease control with a switch to IV-golimumab.

Background COPA syndrome is a rare hereditary inflammatory disease caused by mutations in the gene encoding the coatomer protein subunit alpha, causing excessive production of type I interferon. This case is a reminder for the general paediatrician, highlighting the relevance of the association between arthritis and lung involvement in toddlers. Case presentation We report the case of a 2-year-old girl with intermittent limping and joint pain. Her family history was relevant for a Still disease with lung involvement in the mother. Physical examination showed moderate wrist swelling. Laboratory findings on admission showed an increase in inflammatory markers, positive rheumatoid factor, antibodies antinuclear antibody (ANA) and cyclic citrullinated peptide (anti-CCP). Wrists’ ultrasound documented synovial thickening, and chest X-rays showed an unexpected severe interstitial pneumopathy. Genetic testing confirmed the diagnosis of a heterozygous mutation of the COPA gene in c.841C > T (p.R281W). Janus kinase treatment was started (baricitinib, 4 mg daily per os) with a remarkable improvement in limping and joint pain after two weeks. Conclusions In cases of recurrent arthritis with family history and multiple involvement organs, a genetic disorder should be suspected and genetic testing should be performed. Furthermore, this case suggests that therapy with jak inhibitors may be effective and safe in interferonopathies.

Introduction: Epithelial cells (ECs) are structures regularly observed during urine microscopy analysis. The correct identification of EC subtypes can be useful since renal tubular epithelial cells (RTECs) are clinically relevant. We investigate the urinary ECs report and the judgement of its clinical importance by Brazilian laboratories. Materials and methods: A survey with four questions was made available to participants of the Urinalysis External Quality Assessment Program (EQAP) from Controllab. Laboratories composed 3 groups: (1) differentiating ECs subtypes: "squamous", "transitional" and "RTECs" ; (2) differentiating ECs subtypes: "squamous" or "non- squamous" cells ; (3) without ECs subtype identification. Participants did not necessarily answer to all questions and the answers were evaluated both within the same laboratory's category and within different categories of laboratories. Results: A total of 1336 (94%) laboratories answered the survey ; Group 1, 119/140 (85%) reported that ECs differentiation is important to the physician and 62% want to be evaluated by EQAP, while in Group 3, 455/1110 (41%) reported it is useful to them, however only 25% want be evaluated by EQAP. Group 2 laboratories 37/51 (73%) reported that the information is important, but only 13/52 (25%) are interested in an EQAP with differentiation of the 3 ECs subtypes. Conclusion: Most of the laboratories do not differentiate ECs in the three subtypes, despite the clinical importance of RTECs. Education of laboratory staff about the clinical significance of urinary particles should be considered a key priority.

Aicardi–Goutières syndrome (AGS) is a rare genetic disease caused by mutations in nine genes that are all involved in nucleic acid metabolism or sensing.

To estimate prevalence of unprotected sexual activity and associated factors in the Brazilian population.This was a cross-sectional study with 61,523 adults aged 18 years or older who took part in the 2019 National Health Survey. We estimated prevalence of unprotected sexual activity in the last year. We analyzed association of socioeconomic and demographic variables with the outcome using Poisson regression, estimating prevalence ratios (PR) and 95% confidence intervals (95%CI).Prevalence of unprotected sexual activity was 76.9% (95%CI 76.3;77.6), being higher in all the country's regions in comparison to the Northern region, as well as being higher among people living in rural areas (PR = 1.04; 95%CI 1.03;1.06), females (PR = 1.06; 95%CI 1.05;1.08), participants aged 60 years or older (PR = 1.33; 95%CI 1.27;1.38), married individuals (PR = 1.25; 95%CI 1.23;1.27) and those with less education (PR = 1.05; 95%CI 1.03;1.06).Strategies aimed at groups with higher prevalence of unprotected sexual activity are necessary.Estimar a prevalência e fatores associados à atividade sexual desprotegida na população brasileira.Estudo transversal com 61.523 adultos, na idade de 18 anos ou mais, participantes da Pesquisa Nacional de Saúde 2019. Foram estimadas as prevalências de atividade sexual desprotegida no último ano. A associação das variáveis socioeconômicas e demográficas com o desfecho foi analisada pela regressão de Poisson, com estimação das razões de prevalência (RPs) e intervalo de confiança de 95% (IC95%).A prevalência de atividade sexual desprotegida foi de 76,9% (IC95% 76,3;77,6), maior em todas as macrorregiões nacionais quando comparadas à região Norte, em moradores da zona rural (RP = 1,04; IC95% 1,03;1,06), sexo feminino (RP = 1,06; IC95% 1,05;1,08), idade de 60 anos ou mais (RP = 1,33; IC95% 1,27;1,38), casados (RP = 1,25; IC95% 1,23;1,27) e menos escolarizados (RP = 1,05; IC95% 1,03;1,06).Estratégias direcionadas aos grupos com maior prevalência de atividade sexual desprotegida são necessárias.Estimar la prevalencia y los factores asociados a la actividad sexual sin protección en la población brasileña.Estudio transversal con 61.523 adultos mayores de 18 años participantes de la Encuesta Nacional de Salud 2019. Se estimó la prevalencia de actividad sexual sin protección en el último año. La asociación de variables socioeconómicas y demográficas con el desenlace se analizó mediante regresión de Poisson, con estimación de razones de prevalencia (RP) e IC95%.La prevalencia de actividad sexual sin protección fue del 76,9% (IC95% 76,3;77,6), siendo mayor en todas las regiones en comparación con el Norte, residentes rurales (RP = 1,04; IC95% 1,03;1,06), sexo femenino (RP = 1,06; IC95% 1,05;1,08), mayores de 60 años (RP = 1,33; IC95% 1,27;1,38), casados (RP = 1,25; IC95% 1,23;1,27) y menos educados (RP = 1,05; IC95% 1,03;1,06).Se necesitan estrategias dirigidas a los grupos con mayor prevalencia de actividad sexual sin protección.

Background: An introductory acupuncture course has been offered to primary health care physicians and family medicine residents in southern Brazil since 2011. Objective: To analyze the profile of acupuncture utilization of primary care physicians who completed an introductory course of acupuncture between 2011 and 2018. Method: A survey using an electronic questionnaire was sent to all 119 physicians who completed the course. Results: Fifty-five physicians answered the questionnaire. The majority of them reported continuation of the practice of acupuncture in scheduled appointments and on spontaneous demand. The most commonly used principles of point selection were traditional acupuncture point function, myofascial trigger point needling and point protocols. As barriers to the practice of acupuncture, time limitation and inadequate physical space were predominant. The participants described the problem-solving potential of the procedure and good patient acceptance as facilitators. The most common problems treated with acupuncture were musculoskeletal pain, and mood and anxiety disorders. A reduction in referrals to specialists and reduced prescription of pain medications were also reported. Most physicians answered that they often combined acupuncture with other medications or associated acupuncture with other complementary practices. The main adverse events reported by the participants were vascular trauma and fainting. Conclusion: Most primary care physicians who completed the introductory course and answered the survey still used acupuncture in their routine, primarily for the management of musculoskeletal conditions and mental health conditions. These physicians reported reductions in specialist referrals and prescription of pain medication after integrating basic acupuncture skills into primary care practice.

Introduction/objective Tofacitinib is an oral Janus kinase inhibitor for the treatment of rheumatoid arthritis (RA). This post-hoc analysis evaluated the effect of temporary discontinuation and reinitiation of tofacitinib on disease control in patients with RA in the vaccine sub-study of the long-term extension (LTE) study ORAL Sequel (NCT00413699). Methods The sub-study of ORAL Sequel was a randomized, parallel-group, open-label study. Patients who received tofacitinib 10 mg twice daily for ≥ 3 months in ORAL Sequel were randomized to receive continuous (tofacitinib monotherapy/with methotrexate) or interrupted (tofacitinib withdrawn for 2 weeks post-randomization then reinitiated as monotherapy/with methotrexate) treatment. Efficacy assessments included ACR20/50/70 response rates, change from baseline (∆) in C-reactive protein (CRP), Health Assessment Questionnaire-Disability Index (HAQ-DI), Disease Activity Score in 28 joints, erythrocyte sedimentation rate (DAS28-4 [ESR]), Clinical Disease Activity Index (CDAI), Patient Global Assessment of arthritis (PtGA), Pain (Visual Analog Scale [VAS]), and Physician Global Assessment of arthritis (PGA). Safety was assessed throughout. Results The sub-study included 99 patients each in the continuous and interrupted treatment groups. ACR20/50 response rates, ∆CRP, ∆HAQ-DI (day 15), ∆DAS28-4 (ESR), ∆CDAI, ∆PtGA, ∆Pain (VAS), and ∆PGA were significantly worse in interrupted vs continuous patients during dose interruption, but were generally similar to pre-interruption/continuous treatment levels 28 days post-reinitiation. A numerically higher proportion of interrupted patients reported adverse events (49.5%) vs continuous patients (35.4%). Conclusions Tofacitinib efficacy can be re-established after temporary withdrawal and reinitiation. The safety profile of patients who temporarily discontinued tofacitinib in the sub-study was consistent with previous tofacitinib LTE studies over 9 years. Clinical trial registration number NCT00413699 Key Points• In this sub-study of the long-term extension (LTE) study, ORAL Sequel, the efficacy of tofacitinib was re-established after temporary withdrawal (2 weeks) and reinitation of treatment in patients with RA.• Patients with RA who temporarily discontinued tofacitinib had similar safety events to those reported in previous LTE studies.• The results of this sub-study were consistent with a post-hoc analysis of pooled data from two LTE studies, ORAL Sequel and A3921041, which assessed the efficacy of tofacitinib following a treatment discontinuation period of 14–30 days.

ObjectivesTo evaluate the efficacy through 52 weeks of guselkumab, an interleukin 23-p19 subunit inhibitor, in subgroups of pooled psoriatic arthritis (PsA) patients from the DISCOVER-1 and DISCOVER-2 trials defined by baseline patient characteristics.MethodsAdults with active PsA despite standard therapies were enrolled in DISCOVER-1 (≥3 swollen and ≥3 tender joints, C reactive protein (CRP) level ≥0.3 mg/dL) and DISCOVER-2 (≥5 swollen and ≥5 tender joints, CRP ≥0.6 mg/dL, biological-naïve). Randomised patients received 100 mg guselkumab at weeks 0, 4, and then every 4 or 8 weeks (Q4W/Q8W) or placebo. Guselkumab effects on joint (ACR20/50/70), skin (IGA 0/1, IGA 0), patient-reported outcome (Health Assessment Questionnaire Disability Index/Functional Assessment of Chronic Illness Therapy-Fatigue) and disease severity (minimal disease activity/PsA Disease Activity Score low disease activity) endpoints were evaluated by patient sex, body mass index, PsA duration, swollen/tender joint counts, CRP level, percent body surface area with psoriasis, Psoriasis Area and Severity Index score, and conventional synthetic disease-modifying antirheumatic drug use at baseline.ResultsBaseline patients characteristics in DISCOVER-1 (N=381) and DISCOVER-2 (N=739) were well balanced across randomised groups. At week 24, 62% (232/373) and 60% (225/375), respectively, of guselkumab Q4W-treated and Q8W-treated patients pooled across DISCOVER-1 and DISCOVER-2 achieved the primary endpoint of ACR20 response versus 29% (109/372) of placebo-treated patients. Guselkumab treatment effect at week 24 was observed across patient subgroups. Within each patient subgroup, response rates across all disease domains were sustained or increased at week 52 with both guselkumab regimens.ConclusionsGuselkumab Q4W and Q8W resulted in robust and sustained improvements in PsA signs and symptoms consistently in subgroups of patients defined by diverse baseline characteristics.Trial registration numbersNCT03162796, NCT03158285.

Cytoplasmic nucleic acids sensing through cGAS-STING-TBK1 pathway is crucial for the production of antiviral interferons (IFNs). IFN production can also be induced by lipopolysaccharide (LPS) stimulation through Toll-like receptor 4 (TLR4) in appropriate conditions. Of note, both IFN production and dysregulated LPS-response could play a role in the pathogenesis of Systemic Lupus Erythematosus (SLE). Indeed, LPS can trigger SLE in lupus-prone mice and bacterial infections can induce disease flares in human SLE. However, the interactions between cGAS and TLR4 pathways to IFNs have been poorly investigated. To address this issue, we studied LPS-stimulation in cellular models with a primed cGAS-STING-TBK1 pathway. cGAS-stimulation was naturally sustained by undigested self-nucleic acids in fibroblasts from DNase2-deficiency interferonopathy, whilst it was pharmacologically obtained by cGAMP-stimulation in THP1 cells and murine bone marrow-derived dendritic cells. We showed that cells with a primed cGAS-STING-TBK1 pathway displayed enhanced IFNs production after TLR4-challenge. STING-inhibition did not affect IFN production after LPS alone, but prevented the amplified IFN production in cGAMP-primed cells, suggesting that functional STING is required for priming-dependent enhancement. Furthermore, we speculated that an increased PIK3AP1 expression in DNase2-deficient fibroblasts may link cGAMP-priming with increased LPS-induced IFN production. We showed that both the hyper-expression of PIK3API and the enhanced LPS-induced IFN production can be contrasted by STING inhibitors. Our results may explain how bacterial LPS can synergize with cGAS-pathway in promoting the development of SLE-like autoimmunity.

Interferonopathies are rare genetic conditions defined by systemic inflammatory episodes caused by innate immune system activation in the absence of pathogens. Currently, no targeted drugs are authorized for clinical use in these diseases. In this work, we studied the contribution of sulforaphane (SFN), a cruciferous-derived bioactive molecule, in the modulation of interferon-driven inflammation in an immortalized human hepatocytes (IHH) line and in two healthy volunteers, focusing on STING, a key-component player in interferon pathway, interferon signature modulation, and GSTM1 expression and genotype, which contributes to SFN metabolism and excretion. In vitro, SFN exposure reduced STING expression as well as interferon signature in the presence of the pro-inflammatory stimulus cGAMP (cGAMP 3 h vs. SFN+cGAMP 3 h p value &lt, 0.0001, cGAMP 6 h vs. SFN+cGAMP 6 h p &lt, 0.001, one way ANOVA), restoring STING expression to the level of unstimulated cells. In preliminary experiments on healthy volunteers, no appreciable variations in interferon signature were identified after SFN assumption, while only in one of them, presenting the GSTM1 wild type genotype related to reduced SFN excretion, could a downregulation of STING be recorded. This study confirmed that SFN inhibits STING-mediated inflammation and interferon-stimulated genes expression in vitro. However, only a trend towards the downregulation of STING could be reproduced in vivo. Results obtained have to be confirmed in a larger group of healthy individuals and in patients with type I interferonopathies to define if the assumption of SFN could be useful as supportive therapy.

Background Recurrent aphthous stomatitis with systemic signs of inflammation can be encountered in inflammatory bowel disease, Behçet’s disease (BD), Systemic Lupus Erythematosus (SLE). In addition, it has been proposed that cases with very early onset in childhood can be underpinned by rare monogenic defects of immunity, which may require targeted treatments. Thus, subjects with early onset recurrent aphthous stomatitis receiving a clinical diagnosis of BD-like or SLE-like disease may deserve a further diagnostic workout, including immunologic and genetic investigations. Objective To investigate how an immunologic, genetic and transcriptomics assessment of interferon inflammation may improve diagnosis and care in children with recurrent aphthous stomatitis with systemic inflammation. Methods Subjects referred to the pediatric rheumatologist for recurrent aphthous stomatitis associated with signs of systemic inflammation from January 2015 to January 2020 were enrolled in the study and underwent analysis of peripheral lymphocyte subsets, sequencing of a 17-genes panel and measure of interferon score. Results We enrolled 15 subjects (12 females, median age at disease onset 4 years). The clinical diagnosis was BD in 8, incomplete BD in 5, BD/SLE overlap in 1, SLE in 1. Pathogenic genetic variants were detected in 3 patients, respectively 2 STAT1 gain of function variants in two patients classified as BD/SLE overlap and SLE, and 1 TNFAIP3 mutation (A20 haploinsufficiency) in patients with BD. Moreover 2 likely pathogenic variants were identified in DNASE1L3 and PTPN22, both in patients with incomplete BD. Interferon score was high in the two patients with STAT1 GOF mutations, in the patient with TNFAIP3 mutation, and in 3 genetic-negative subjects. In two patients, the treatment was modified based on genetic results. Conclusions Although recurrent aphthous stomatitis associated with systemic inflammation may lead to a clinical diagnosis of BD or SLE, subjects with early disease onset in childhood deserve genetic investigation for rare monogenic disorders. A wider genetic panel may help disclosing the genetic background in the subset of children with increased interferon score, who tested negative in this study.

Background Systemic lupus erythematosus (SLE) is a complex multi-system disease, characterized by both autoimmune and autoinflammatory clinical and laboratory features. The role of type I interferon (IFN) in SLE has been demonstrated from the 2000s, by gene expression analyses showing significant over-expression of genes related to type I IFN signalling pathway (IFN signature). However, several studies questioned the role of measuring the intensity of IFN signature (IFN score) to chase SLE activity. We would assess if the IFN signature can help the clinical and therapeutic stratification of patients with pediatric SLE. Methods We measured the IFN score in peripheral whole blood from a series of subjects with childhood-onset SLE and correlated the results with clinical and laboratory parameters. Results Thirty-one subjects were included in the study, among which the 87% displayed a positive IFN score. The only significant relation was found for high IFN score in subjects with normocomplementemia. No correlation was observed between IFN score and SLEDAI-2K, BILAG-2004 and SLICC. Patients with high IFN score and normal complement levels also presented lower anti-dsDNA antibodies. Conclusions The integration between IFN signature analysis and complement levels may easily distinguish two groups of subjects, in which the autoimmune or autoinflammatory component of the disease seems to be prevalent.

The dynamics of a population expanding into unoccupied habitat has been primarily studied for situations in which growth and dispersal parameters are uniform in space or vary in one dimension. Here we study the influence of finite-sized individual inhomogeneities and their collective effect on front speed if randomly placed in a two-dimensional habitat. We use an individual-based model to investigate the front dynamics for a region in which dispersal or growth of individuals is reduced to zero (obstacles) or increased above the background (hotspots), respectively. In a regime where front dynamics is determined by a local front speed only, a principle of least time can be employed to predict front speed and shape. The resulting analytical solutions motivate an event-based algorithm illustrating the effects of several obstacles or hotspots. We finally apply the principle of least time to large heterogeneous environments by solving the Eikonal equation numerically. Obstacles lead to a slow-down that is dominated by the number density and width of obstacles, but not by their precise shape. Hotspots result in a speedup, which we characterise as function of hotspot strength and density. Our findings emphasise the importance of taking the dimensionality of the environment into account., Comment: Authors Wolfram M\"obius and Francesca Tesser contributed equally

Gliomas represent the most frequent central nervous system (CNS) tumors in children and adolescents. However, therapeutic strategies for these patients, based on tumor molecular profile, are still limited compared to the wide range of treatment options for the adult population. We investigated molecular alterations, with a potential prognostic marker and therapeutic target in gliomas of childhood and adolescence using the next-generation sequencing (NGS) strategy. We selected 95 samples with initial diagnosis of glioma from patients treated at Pediatric Oncology Institute-GRAACC/UNIFESP. All samples were categorized according to the 2021 World Health Organization Classification of Tumors of the CNS, which included 39 low-grade gliomas (LGGs) and 56 high-grade gliomas (HGGs). Four HGG samples were classified as congenital glioblastoma (cGBM). NGS was performed to identify somatic genetic variants in tumor samples using the Oncomine Childhood Cancer Research Assay® (OCCRA®) panel, from Thermo Fisher Scientific®. Genetic variants were identified in 76 of 95 (80%) tumors. In HGGs, the most common molecular alteration detected was H3F3A c.83A > T variant (H3.3 K27M) and co‐occurring mutations in ATRX, TP53, PDGFRA, MET, and MYC genes were also frequently observed. One HGG sample was reclassified as supratentorial ependymoma ZFTA-fusion positive after NGS was performed. In LGGs, four KIAA1549–BRAF fusion transcripts were detected and this alteration was the most recurrent genetic event and favorable prognostic factor identified. Additionally, genetic variants in ALK and NTRK genes, which provide potential targets for therapy with Food and Drug Administration-approved drugs, were identified in two different cases of cGBM that were classified as infant-type hemispheric glioma, a newly recognized subgroup of pediatric HGG. Molecular profiling by the OCCRA® panel comprehensively addressed the most relevant genetic variants in gliomas of childhood and adolescence, as these tumors have specific patterns of molecular alterations, outcomes, and effectiveness to therapies.

Aims Acute and chronic kidney dysfunction is common in patients with end-stage liver disease. Differentiation between acute kidney injury (AKI) due to hepatorenal syndrome (HRS) or acute tubular necrosis (ATN) remains difficult, however urine cast scoring systems using renal tubular epithelial cells (RTECs) and granular casts (GCs) can help to identify intrinsic kidney diseases. The objective of this study was to evaluate the urine sediment profile of patients with liver disease and hyperbilirubinemia/hyperbilirubinuria and the use of a urine sediment scoring system to identify the most common score in AKI patients and high urine bilirubin concentrations. Materials and methods A retrospective study in the database of a large laboratory that assists a hospital-complex in Brazil was performed. Results Urinary casts, in particular GCs, as well as RTECs were observed more frequently in patients with hyperbilirubinemia/hyperbilirubinuria, while hyaline casts were observed in patients without hyperbilirubinemia/hyperbilirubinuria. Regardless of the AKI or non-AKI condition, the relative risk for scores 2 or 3 (sediment consistent with tubular damage, with GCs and/or RTECs in different quantities) in group 4 was 3.61 times higher compared to patients in group 1. Conclusion In patients with higher urinary bilirubin levels, the urine sediment had greater numbers of GCs and RTECs and higher urine sediment scores (scores 2 or 3). The presence of a larger number of urine particles (RTECs and GCs) originating in the kidneys in the groups with higher levels of urinary bilirubin suggests an association between hyperbilirubinemia/hyperbilirubinuria and tubular injury independent of AKI or non-AKI.

Objective To evaluate the safety and efficacy of intravenous golimumab + methotrexate (MTX) in patients with active rheumatoid arthritis (RA) aged

Ependymoma (EPN) accounts for approximately 10% of all primary central nervous system (CNS) tumors in children and in most cases, chemotherapy is ineffective and treatment remains challenging. We investigated molecular alterations, with a potential prognostic marker and therapeutic target in EPNs of childhood and adolescence, using a next-generation sequencing (NGS) panel specific for pediatric neoplasms. We selected 61 samples with initial diagnosis of EPN from patients treated at Pediatric Oncology Institute-GRAACC/UNIFESP. All samples were divided according to the anatomical compartment of the CNS - 42 posterior fossa (PF), 14 supratentorial (ST), and five spinal (SP). NGS was performed to identify somatic genetic variants in tumor samples using the Oncomine Childhood Cancer Research Assay® (OCCRA®) panel, from Thermo Fisher Scientific®. Genetic variants were identified in 24 of 61 (39.3%) tumors and over 90% of all variants were pathogenic or likely pathogenic. The most commonly variants detected were in CIC, ASXL1, and JAK2 genes and have not been reported in EPN yet. MN1-BEND2 fusion, alteration recently described in a new CNS tumor type, was identified in one ST sample that was reclassified as astroblastoma. Additionally, YAP1‐MAMLD1 fusion, a rare event associated with good outcome in ST-EPN, was observed in two patients diagnosed under 2 years old. Molecular profiling by the OCCRA® panel showed novel alterations in pediatric and adolescent EPNs, which highlights the clinical importance in identifying genetic variants for patients’ prognosis and therapeutic orientation.

Mitoquinone (MitoQ) is a mitochondrial reactive oxygen species scavenger that is characterized by high bioavailability. Prior studies have demonstrated its neuroprotective potential. Indeed, the release of reactive oxygen species due to damage to mitochondrial components plays a pivotal role in the pathogenesis of several neurodegenerative diseases. The present study aimed to examine the impact of the inflammation platform activation on the neuronal cell line (DAOY) treated with specific inflammatory stimuli and whether MitoQ addition can modulate these deregulations. DAOY cells were pre-treated with MitoQ and then stimulated by a blockade of the cholesterol pathway, also called mevalonate pathway, using a statin, mimicking cholesterol deregulation, a common parameter present in some neurodegenerative and autoinflammatory diseases. To verify the role played by MitoQ, we examined the expression of genes involved in the inflammation mechanism and the mitochondrial activity at different time points. In this experimental design, MitoQ showed a protective effect against the blockade of the mevalonate pathway in a short period (12 h) but did not persist for a long time (24 and 48 h). The results obtained highlight the anti-inflammatory properties of MitoQ and open the question about its application as an effective adjuvant for the treatment of the autoinflammatory disease characterized by a cholesterol deregulation pathway that involves mitochondrial homeostasis.

Off-label use of medications is still a common practice in pediatric rheumatology. JAK inhibitors are authorized in adults in the treatment of rheumatoid arthritis, psoriatic arthritis and ulcerative colitis. Although their use is not authorized yet in children, JAK inhibitors, based on their mechanism of action and on clinical experiences in small series, have been suggested to be useful in the treatment of pediatric interferon-mediated inflammation. Accordingly, an increased interferon score may help to identify those patients who might benefit of JAK inhibitors. We describe the clinical experience with JAK inhibitors in seven children affected with severe inflammatory conditions and we discuss the correlation between clinical features and transcriptomic data. Clinical improvements were recorded in all cases. A reduction of interferon signaling was recorded in three out of seven subjects at last follow-up, irrespectively from clinical improvements. Other signal pathways with significant differences between patients and controls included upregulation of DNA repair pathway and downregulation of extracellular collagen homeostasis. Two patients developed drug-related adverse events, which were considered serious in one case. In conclusion, JAK inhibitors may offer a valuable option for children with severe interferon-mediated inflammatory disorders reducing the interferon score as well as influencing other signal pathways that deserve future studies.

In the light of the comparative analysis of health systems, we discuss three strategic phenomena for the SUS universalization, as follows: a) health tax expenditures; b) State funding of private plans for public servants; and c) trade union's demand for private health plans. Among the ideal types of health systems, SUS is universal in law, but hybrid in practice: Beveridgian in primary health care (PHC) and mixed in specialized/hospital care; without really being universal (public spending is only 43% of total health expenditure). There is a massive state subsidy to the private sector, through health tax expenditures (30% of the federal health budget) and financing of private plans for public servants, which generates incoherence, segmentation of the health system and inequities. Despite the general support to the SUS, the union movements have been using private health plans in collective recruitment (76% of them), reinforcing the private sector. Reducing health tax expenditures - including state funding of servants' private plans - would significantly increase the SUS budget and facilitate articulation between health workers and trade unionists, bringing the high strength of unions closer to the long struggle for the universality of the SUS and PHC.

Aquaporin-4 antibody (AQP4-IgG) neuromyelitis optica spectrum disorders (NMOSD) are rare idiopathic autoimmune diseases, presenting with optic neuritis (ON), longitudinally extensive transverse myelitis (LETM), and brainstem syndromes and a prevalence range between 0.5 and 4/100,000. Only 3% to 25% of NMOSD have been described as a paraneoplastic (PN) syndrome (PNNMOSD). Both idiopathic NMOSD (INMOSD) and PNNMOSD cases mostly affect females, but PNNMOSD usually presents with a spinal cord or brainstem involvement in elderly patients. Few cases of both malignancies (for the majority breast or lung cancer) and benign tumors (monoclonal gammopathy) were previously reported. Currently, there is no consensus on treatment approach for PNNMOSD (only surgical removal or surgery combined with chronic immunosuppression). Here, we present a series of three newly diagnosed PNNMOSD cases, who differ from each other for demographic and clinical features, tumor association, long-term treatment, and outcome. We propose that a PN etiology should be considered always whenever a new diagnosis of NMOSD is made, not only in patients over 50 years old or in spinal cord/brainstem lesions presentations. Our findings add to existing evidence and raise awareness on PNNMOSD. We enhance the importance for the clinicians of recognizing tumor symptoms and signs whenever a NMOSD is newly diagnosed.

ObjectiveTo examine the efficacy and safety of pegloticase in combination with methotrexate (MTX) in patients with uncontrolled gout in an exploratory, open-label clinical trial (ClinicalTrials.gov: NCT03635957) prior to a randomized, controlled trial.MethodsA multicenter, open-label efficacy and safety study of pegloticase with MTX co-treatment was conducted in patients with uncontrolled gout. Patients were administered oral MTX (15 mg/week) and folic acid (1 mg/day) 4 weeks prior to and throughout pegloticase treatment. The primary study outcome was the proportion of responders, defined as serum uric acid (sUA) < 6 mg/dL for ≥ 80% of the time during Month 6 (Weeks 20, 22, and 24). All analyses were performed on a modified intent-to-treat population, defined as patients who received ≥ 1 pegloticase infusion.ResultsSeventeen patients were screened and 14 patients (all men, average age 49.3 ± 8.7 years) were enrolled. On Day 1, mean sUA was 9.2 ± 2.5 mg/dL, and 12 of the 14 patients had visible tophi. At the 6-month timepoint, 11/14 (78.6%, 95% CI 49.2–95.3%) met the responder definition, with 3 patients discontinuing after meeting protocol-defined treatment discontinuation rules (preinfusion sUA values > 6 mg/dL at 2 consecutive scheduled visits). All patients tolerated MTX. No new safety concerns were identified.ConclusionIn this study, an increased proportion of patients maintained therapeutic response at 6 months when treated concomitantly with MTX and pegloticase as compared to the previously reported 42% using pegloticase alone. These results support the need for a randomized study of MTX or placebo with pegloticase to validate these open-label findings.

A 32 year-old woman presented to the emergency department with symptoms of urinary tract infection. Over the past 2 days, she reported the use of a medication whose active compounds were methenamine (120 mg) + methylthioninium chloride (20 mg). A collected urine sample had a strong blue-green discoloration. Uroculture was negative and dipstick urinalysis revealed the following results: SG 1.015, pH 7, Albumin 3+, Bilirubin 2+ and Haemoglobin 2+. Urine microscopic analysis revealed 5–6 squamous epithelial cells/high power field (HPF), 5–6 leukocytes/HPF and 7–8 erythrocytes/HPF. No bacteria, cellular casts, or renal tubular epithelial cells were present in the urine sample. The most remarkable feature of the urine sediment was that some cells (squamous epithelial cells, macrophages, leukocytes and erythrocytes) were strongly stained in blue. The albuminuria measured by dipstick shows 3+ (300 mg/dL), but in turbidimetric method the urine protein concentration was 18 mg/dL, showing an important interference of methylene blue on the dipstick albumin area.

Histone deacetylate inhibitors (HDACi), as valproic acid (VA), have been reported to enhance efficacy and to prevent drug resistance in some tumors, including medulloblastoma (MB). In the present study, we investigated VA role, combined to cisplatin (CDDP) in cell viability and gene expression of MB cell lines. Dose-response curve determined IC50 values for each treatment: (1) VA single, (2) CDDP single, and (3) VA and CDDP combined. Cytotoxicity and flow cytometry evaluated cell viability after exposure to treatments. Quantitative PCR evaluated gene expression levels of AKT, CTNNB1, GLI1, KDM6A, KDM6B, NOTCH2, PTCH1, and TERT, before and after treatment. Besides, we performed next-generation sequencing (NGS) for PTCH1, TERT, and TP53 genes. The most effective treatment to reduce viability was combined for D283MED and ONS-76; and CDDP single for DAOY cells (p

Malnutrition is the most frequent nutritional disorder in patients with gastrointestinal cancer and is associated with cachexia syndrome, worsening of prognosis, and shortened survival rate. Early nutrition screening, assessment, and intervention are able to favorably modify the clinical evolution of affected patients. The adequate provision of nutritional requirements has been associated with improvement of immunologic status, and avoidance of further complications related to poor nutritional status, surgical treatment, and anticancer therapy. In malnourished patients, the supplementation of perioperative immunonutrition might contribute to fewer infectious and noninfectious complications, shorter length of hospitalization, and improved wound healing.

// Alini Trujillo-Paolillo 1, 2 , Francine Tesser-Gamba 1 , Antonio Sergio Petrilli 3 , Maria Teresa de Seixas Alves 4 , Reynaldo Jesus Garcia Filho 5 , Renato de Oliveira 6 and Silvia Regina Caminada de Toledo 1, 2, 7 1 Genetics Laboratory, Pediatric Oncology Institute (IOP/GRAACC), Federal University of Sao Paulo, Rua Botucatu, Vila Clementino, Sao Paulo SP, 04023-062, Brazil 2 Department of Clinical and Experimental Oncology, Federal University of Sao Paulo, Rua Dr. Diogo de Faria, Vila Clementino, Sao Paulo SP, 04037-003, Brazil 3 Pediatric Oncology Institute (IOP/GRAACC), Department of Pediatrics, Federal University of Sao Paulo, Rua Botucatu, Vila Clementino, Sao Paulo SP, 04023-062, Brazil 4 Department of Pathology, Federal University of Sao Paulo, Rua Botucatu, Vila Clementino, Sao Paulo SP, 04023-062, Brazil 5 Department of Orthopedic Surgery and Traumatology, Federal University of Sao Paulo, Rua Borges Lagoa, Vila Clementino, Sao Paulo SP, 04038-031, Brazil 6 Department of Thoracic Surgery, Federal University of Sao Paulo, Rua Napoleao de Barros, Vila Clementino SP, 04024-002, Brazil 7 Department of Morphology and Genetics, Federal University of Sao Paulo, Rua Botucatu, Vila Clementino, Sao Paulo SP, 04023-062, Brazil Correspondence to: Silvia Regina Caminada de Toledo, email: silviatoledo@graacc.org.br Keywords: osteosarcoma, cytochrome P-450, osteosarcoma cell line, tumor microenvironment, treatment response Received: March 22, 2016 Accepted: January 06, 2017 Published: March 03, 2017 ABSTRACT Osteosarcoma (OS) is the most common malignant bone tumor in children and adolescents. The present study investigated the expression of Cytochrome P-450 ( CYP ) genes: CYP1A2 , CYP3A4 and CYP3A5 by qRT-PCR in 135 specimens obtained from OS patients, including biopsy (pre-chemotherapy), tumor resected in surgery (post-chemotherapy), adjacent bone to tumor (nonmalignant tissue), pulmonary metastasis and adjacent lung to metastasis (nonmalignant tissue). Normal bone and normal lung tissues were used as control. We also investigated in five OS cell lines the modulation of CYPs expression by cisplatin, doxorubicin and methotrexate. As result, the adjacent lung specimens presented CYP1A2 overexpression compared to the normal lung (p=0.0256). Biopsy specimens presented lower CYP3A4 expression than normal bone (p=0.0314). The overexpression of both CYP1A2 and CYP3A4 in post-chemotherapy specimens were correlated with better event free-survival (p=0.0244) and good response (p=0.0484), respectively. Furthermore, in vitro assays revealed that CYP1A2 was upregulated by doxorubicin (p=0.0034); CYP3A4 was upregulated by cisplatin, doxorubicin and methotrexate (p=0.0004, p=0.0024, p

Complementary and Alternative Medicine (CAM) need to be increasingly understood in the academic and research setting, given their growing inclusion in health institutions and scientific studies. However, vague definitions or broad generalizations are common in the Brazilian scientific literature, an example of which is the relationship between CAM and social medicalization. This study aims to discuss the medicalizing and de-medicalizing potential of the use of CAM, especially in primary healthcare (PHC). This essay summarizes the underlying lack of definition concerning the medicalizing and de-medicalizing potential of various CAM, based on the selected literature, which reports theoretical and empirical convergences. The exercise of CAM in the clinical context has a medicalizing potential, due to its positive, expanded, and holistic conception of health and its etiological multidimensionality, potentially generating so-called "holistic illness", which has been reported theoretically and empirically. CAM also have de-medicalizing potential, depending on the practitioner, due to greater interpretative flexibility, contextualization, singularization, users' participation in the care, closer clinical relationship, the values and traditions of some CAM, diversity of interventions, and the potential for enrichment of self-care. The medicalizing or de-medicalizing potential of various CAM is activated by their practitioners, and the context of PHC tends to favors the de-medicalizing potential.As Práticas Integrativas e Complementares em Saúde (PICS) deveriam estar cada vez mais compreendidas no ambiente acadêmico e de pesquisa, dada sua crescente inserção nas instituições de saúde e em pesquisas científicas. Entretanto, comumente há conceituações ou generalizações temerárias na literatura científica brasileira, sendo exemplo a relação das PICS com a medicalização social. O objetivo deste trabalho é discutir o potencial medicalizante e desmedicalizante do uso de PICS, especialmente na atenção primária à saúde (APS). Trata-se de ensaio que sintetiza a indefinição referente ao potencial simultaneamente medicalizante e desmedicalizante de várias PICS, baseado em literatura selecionada, que registra convergências teóricas e empíricas. O exercício de PICS em contexto clínico tem potencial medicalizante, devido ao seu conceito positivo, ampliado e holístico de saúde e sua multidimensionalidade etiológica, podendo gerar o chamado “adoecimento holístico”, observado teórica e empiricamente. Tal exercício apresenta também potencial desmedicalizante, dependente do praticante, devido a maior flexibilidade interpretativa, contextualização, singularização e participação do usuário no cuidado, relação clínica mais próxima, valores e tradições de algumas PICS, diversidade de intervenções e seu potencial de enriquecimento do autocuidado. O potencial medicalizante ou desmedicalizante de várias PICS é ativado por seus praticantes, e o contexto da APS é favorável ao segundo.Las Medicina Complementaria y Alternativa (MCA) deberían estar cada vez más comprendidas en el ambiente académico y de investigación, dada su creciente inserción en las instituciones de salud y en investigaciones científicas. No obstante, comúnmente existen conceptualizaciones o generalizaciones temerarias en la literatura científica brasileña, siendo un ejemplo la relación de las MCA con la medicalización social. El objetivo de este trabajo es discutir el potencial medicalizante y desmedicalizante del uso de MCA, especialmente en la atención primaria en salud (APS). Se trata de un ensayo que sintetiza la indefinición referente al potencial simultáneamente medicalizante y desmedicalizante de varias MCA; basado en literatura seleccionada, que registra convergencias teóricas y empíricas. El ejercicio de MCA en un contexto clínico tiene potencial medicalizante, debido a su concepto positivo, ampliado y holístico de salud y su multidimensionalidad etiológica, pudiendo generar el denominado “padecimiento holístico”, observado teórica y empíricamente. Tal ejercicio presenta también potencial desmedicalizante, dependiente del practicante, debido a una mayor flexibilidad interpretativa, contextualización, singularización, así como la participación del usuario en el cuidado, una relación clínica más cercana, valores y tradiciones de algunas MCA, diversidad de intervenciones y su potencial de enriquecimiento con el autocuidado. El potencial medicalizante o desmedicalizante de varias MCA se activa mediante sus practicantes y el contexto de la APS es favorable al segundo.

Introduction: Acute kidney injury (AKI) occurs in about 22% of the patients undergoing cardiac surgery and 2.3% requires renal replacement therapy (RRT). The current diagnostic criteria for AKI by increased serum creatinine levels have limitations and new biomarkers are being tested. Urine sediment may be considered a biomarker and it can help to differentiate pre-renal (functional) from renal (intrinsic) AKI. Aims: To investigate the microscopic urinalysis in the AKI diagnosis in patients undergoing cardiac surgery with cardiopulmonary bypass. Methods: One hundred and fourteen patients, mean age 62.3 years, 67.5 % male, with creatinine 0.91 mg/dL (SD 0.22) had a urine sample examined in the first 24 h after the surgery. We looked for renal tubular epithelial cells (RTEC) and granular casts (GC) and associated the results with AKI development as defined by KDIGO criteria. Results: Twenty three patients (20.17 %) developed AKI according to the serum creatinine criterion and 76 (66.67 %) by the urine output criterion. Four patients required RRT. Mortality was 3.51 %. The use of urine creatinine criterion to predict AKI showed a sensitivity of 34.78 % and specificity of 86.81 %, positive likelihood ratio of 2.64 and negative likelihood ratio of 0.75, AUC-ROC of 0.584 (95%CI: 0.445-0.723). For the urine output criterion sensitivity was 23.68 % and specificity 92.11 %, AUC-ROC was 0.573 (95%CI: 0.465-0.680). Conclusion: RTEC and GC in urine sample detected by microscopy is a highly specific biomarker for early AKI diagnosis after cardiac surgery. Resumo Introdução: Lesão renal aguda (LRA) ocorre em cerca de 22% dos pacientes submetidos a cirurgia cardíaca e 2,3% necessitam de terapia renal substitutiva (TRS). Os atuais critérios diagnósticos para LRA fundamentados no aumento dos níveis de creatinina sérica apresentam limitações e novos biomarcadores estão sendo testados. O sedimento urinário é um biomarcador que pode ajudar a diferenciar a LRA pré-renal (funcional) da LRA renal (intrínseca). Objetivos: Investigar a urinálise microscópica no diagnóstico de LRA em pacientes submetidos a cirurgia cardíaca com circulação extracorpórea. Métodos: Um total de 114 pacientes com idade média de 62,3 anos, 67,5% do sexo masculino e níveis médios de creatinina de 0,91 mg/dL (DP 0,22) tiveram amostras de urina examinadas nas primeiras 24 horas após a cirurgia. A identificação de células epiteliais tubulares renais (CETR) e cilindros granulares (CG) foi associada a desfechos de desenvolvimento de LRA conforme os critérios do KDIGO. Resultados: Vinte e três pacientes (20,17%) desenvolveram LRA pelo critério de creatinina sérica e 76 (66,67%) pelo critério de diurese. Quatro pacientes necessitaram de TRS. A mortalidade foi de 3,51%. O uso da creatinina urinária como critério preditivo para LRA mostrou sensibilidade de 34,78% e especificidade de 86,81%; razão de verossimilhança positiva de 2,64 e razão de verossimilhança negativa de 0,75; e ASC-COR de 0,584 (IC 95%: 0,445-0,723). Para o critério de diurese, a sensibilidade foi de 23,68% e a especificidade 92,11%; a ASC-COR foi 0,573 (IC 95%: 0,465-0,680). Conclusão: A identificação de CETR e CG em amostras de urina por microscopia representa um biomarcador altamente específico para o diagnóstico precoce de LRA após cirurgia cardíaca.

Strongyloides stercoralis (SS) hyperinfection is a well-documented condition. However, SS eggs in stool samples are not commonly observed during routine analysis. Here, we report a case on SS hyperinfection where both larvae and eggs were observed in the stool sample of an immunossupressed liver allograft transplanted patient.

Introduction Somali-born women comprise a large group of immigrant women of childbearing age in Sweden, with increased risks for perinatal morbidity and mortality and poor experiences of care, despite the goal of providing equitable healthcare for the entire population. Rethinking how care is provided may help to improve outcomes. Overall aim To develop and test the acceptability, feasibility and immediate impacts of group antenatal care for Somali-born immigrant women, in an effort to improve experiences of antenatal care, knowledge about childbearing and the Swedish healthcare system, emotional well-being and ultimately, pregnancy outcomes. This protocol describes the rationale, planning and development of the study. Methods and analysis An intervention development and feasibility study. Phase I includes needs assessment and development of contextual understanding using focus group discussions. In phase II, the intervention and evaluation tools, based on core values for quality care and person-centred care, are developed. Phase III includes the historically controlled evaluation in which relevant outcome measures are compared for women receiving individual care (2016–2018) and women receiving group antenatal care (2018–2019): care satisfaction (Migrant Friendly Maternity Care Questionnaire), emotional well-being (Edinburgh Postnatal Depression Scale), social support, childbirth fear, knowledge of Swedish maternity care, delivery outcomes. Phase IV includes the process evaluation, investigate process, feasibility and mechanisms of impact using field notes, observations, interviews and questionnaires. All phases are conducted in collaboration with a stakeholder reference group. Ethics and dissemination The study is approved by the Regional Ethical Review Board, Stockholm, Sweden. Participants receive information about the study and their right to decline/withdraw without consequences. Consent is given prior to enrolment. Findings will be disseminated at antenatal care units, national/international conferences, through publications in peer-reviewed journals, seminars involving stakeholders, practitioners, community and via the project website. Participating women will receive a summary of results in their language.

In the light of the comparative analysis of health systems, we discuss three strategic phenomena for the SUS universalization, as follows: a) health tax expenditures; b) State funding of private plans for public servants; and c) trade union's demand for private health plans. Among the ideal types of health systems, SUS is universal in law, but hybrid in practice: Beveridgian in primary health care (PHC) and mixed in specialized/hospital care; without really being universal (public spending is only 43% of total health expenditure). There is a massive state subsidy to the private sector, through health tax expenditures (30% of the federal health budget) and financing of private plans for public servants, which generates incoherence, segmentation of the health system and inequities. Despite the general support to the SUS, the union movements have been using private health plans in collective recruitment (76% of them), reinforcing the private sector. Reducing health tax expenditures - including state funding of servants' private plans - would significantly increase the SUS budget and facilitate articulation between health workers and trade unionists, bringing the high strength of unions closer to the long struggle for the universality of the SUS and PHC.À luz da análise comparada de sistemas de saúde (SS), discutimos três fenômenos estratégicos para a universalização do SUS: a) os gastos tributários em saúde; b) o financiamento estatal de planos privados de servidores públicos; c) a demanda sindical por planos privados. Dentre os tipos-ideais de SS, o SUS é universal na lei, mas híbrido na prática: beveridgeano na atenção primária à saúde (APS) e misto no cuidado especializado/hospitalar; sem ser universal na realidade (gastos públicos são só 43% dos gastos totais em saúde). Há grande subsídio estatal ao setor privado, via gastos tributários em saúde (30% do orçamento federal na saúde) e financiamento de planos privados para servidores públicos, o que gera incoerência, segmentação do sistema de saúde e iniquidades. Apesar do apoio genérico ao SUS, os movimentos sindicais vem usando planos de saúde na contratação coletiva (76% deles), reforçando o setor privado. A redução dos gastos tributários em saúde - incluindo o financiamento estatal dos planos privados de servidores - aumentaria significativamente o orçamento do SUS e facilitaria a articulação entre sanitaristas e sindicalistas, aproximando a grande força dos sindicatos da longa luta pela universalidade do SUS e da APS.

(1) Background: To limit the COVID-19 outbreak, the Italian government implemented social restrictions that may have had psychological and cognitive repercussions on people with dementia. We aimed to analyze cognitive decline during the pandemic year in people evaluated in a memory clinic in northern Italy, the epicenter of COVID-19 spread. (2) Methods: A single-center retrospective study was carried out, including individuals with annual follow-up evaluated in three different years (2020-GROUP, 2019-GROUP, 2018-GROUP). We performed an intergroup comparison of cognitive decline over a one-year follow-up, and an intragroup comparison in the 2020-GROUP to analyze the five-year cognitive decline trajectory, as measured by the MMSE. (3) Results: The 2020-GROUP showed a significant loss of MMSE points per year in the considered follow-up period compared with the 2019-GROUP and 2018-GROUP (p = 0.021). Demographics, clinical features, and the other analyzed variables, including rate of diagnosis, therapy, and comorbidities, did not significantly differ between groups. The five-year cognitive decline trajectory confirmed a significant worsening of cognitive decline between 2019 and 2020 (p < 0.001), while the decrease in MMSE scores was not statistically significant between previous time points. (4) Conclusions: COVID-19 pandemic measures have induced a significant worsening of cognitive decline in people with dementia, needing more careful assistance to minimize the adverse effects of social isolation in case of future lockdowns.

Microbial nucleic acid recognition serves as the major stimulus to an antiviral response, implying a requirement to limit the misrepresentation of self nucleic acids as non-self and the induction of autoinflammation. By systematic screening using a panel of interferon-stimulated genes we identify two siblings and a singleton variably demonstrating severe neonatal anemia, membranoproliferative glomerulonephritis, liver fibrosis, deforming arthropathy and increased anti-DNA antibodies. In both families we identify biallelic mutations in DNASE2, associated with a loss of DNase II endonuclease activity. We record increased interferon alpha protein levels using digital ELISA, enhanced interferon signaling by RNA-Seq analysis and constitutive upregulation of phosphorylated STAT1 and STAT3 in patient lymphocytes and monocytes. A hematological disease transcriptomic signature and increased numbers of erythroblasts are recorded in patient peripheral blood, suggesting that interferon might have a particular effect on hematopoiesis. These data define a type I interferonopathy due to DNase II deficiency in humans., Nucleic acid sensing is important to ensure that an innate immune response is only mounted against microbial nucleic acid. Here, the authors identify loss-of-function mutations in the DNASE2 gene that cause type I interferon-mediated autoinflammation due to enhanced systemic interferon signaling.

The story of antimalarials as antinflammatory drugs dates back several centuries. Chinin, the extract of the Cinchona bark, has been exploited since the 18th century for its antimalarial and antifebrile properties. Later, during the Second World War, the broad use of antimalarials allowed arguing their antirheumatic effect on soldiers. Since then, these drugs have been broadly used to treat Systemic Lupus Erythematosus, but, only recently, have the molecular mechanisms of action been partly clarified. Inhibitory action on vacuole function and trafficking has been considered for decades the main mechanism of the action of antimalarials, affecting the activation of phagocytes and dendritic cells. In addition, chloroquine is also known as a potent inhibitor of autophagy, providing another possible explanation of its antinflammatory action. However, much attention has been recently devoted to the action of antimalarials on the so-called cGASSTING pathway leading from the sensing of cytoplasmic nucleic acids to the production of type I interferons. This pathway is a fundamental mechanism of host defence, since it is able to detect microbial DNA and induce the type I interferon-mediated immune response. Of note, genetic defects in the degradation of nucleic acids lead to inappropriate cGAS-STING activation and inflammation. These disorders, called type I interferonopathies, represent a valuable model to study the antinflammatory potential of antimalarials. We will discuss possible development of antimalarials to improve the treatment of type I interferonopathies and likely multifactorial disorders characterised by interferon inflammation, such as Systemic Lupus Erythematosus.

Objective Primary health care (PHC) is the main entry point and the first level of contact for individuals, families and communities within the Brazilian public health system. Considering that few studies have investigated the use of acupuncture in PHC, this article presents our experience in the city of Florianópolis when integrating acupuncture into PHC using an educational programme developed to teach acupuncture to primary care physicians (PCPs). Methods The course programme was designed using the WHO standards for acupuncture training and discussed at three consensus meetings. Between 2011 and 2014 three iterations of an introductory acupuncture course for PCPs were offered. During this period 53 physicians finished the programme. Results The number of acupuncture sessions in PHC rose from 1349 in 2011 to 6488 in 2015. It was observed in 2015 that 81% of the course participants working in PHC were regularly using acupuncture in their daily practice, with a mean number of sessions of 11.35 sessions per month. Moreover, collaborative work, which started during the course between the PCPs and the acupuncture specialists in secondary and tertiary public health care, helped to increase the quality of acupuncture referrals and facilitate clinical case discussions. Conclusions Our experience in the city of Florianópolis shows that teaching acupuncture to PCPs is a sustainable model that can help introduce acupuncture into PHC. Furthermore it can expand access to acupuncture treatment for the population and increase the communication between PCPs and acupuncture specialists.

This bibliometric study was designed to evaluate the scientific output of Brazilian acupuncture publications and compare that output to the global trends in the same area.The analyzed data were retrieved from the online version of Science Citation Index Expanded (SCI-E) database and covered the period from 2000 to 2014. The documents were searched by using the topic filter to find acupuncture-related documents (ARDs) and the title filter for acupuncture-specific documents (ASDs). The analyzed categories included number of publications, type of documents, number of citations, universities/institutions, research areas, and journals.A total of 9301 ARDs and 5974 ASDs were published in the past 15 years worldwide. The global average number of citations per document was 10.61 for ARDs and 9.24 for ASDs. Brazil has published 252 ARDs and 169 ASDs, which corresponds to the tenth and ninth positions on the global correspondent rankings. The United States is the most productive country, with 2503 ARD publications, followed by China with 2143 and South Korea with 925. Norway is in the first position for the ARD citation rank, with 25.77 citations per document; Switzerland is in the first position for the ASD citation rank, with 26.66. Brazil has 4.19 citations per document, which corresponds to the 20th position in the ASD citation rankings. Evidence-Based Complementary Medicine, Acupuncture in Medicine, and The Journal of Alternative and Complementary Medicine are the leading journals in terms of numbers of ARDs and ASDs in Brazil and globally.The bibliometric analysis of the SCI-E database shows that global numbers of ARDs and ASDs and citations have constantly increased from 2000 to 2014. Brazil is among the top 10 most productive countries in the world in terms of number of acupuncture publications. However, the number of citations of Brazilian documents is below the global average.

Dieting and excessive fear of eating coexist in vulnerable individuals, which may progress to anorexia nervosa [AN], but there is no objective measure of this fear. Therefore, we adapted a computer program that was previously developed to measure the satiating effects of foods in order to explore the potential of food to induce anxiety and fear of eating in adolescent girls. Twenty four adolescents (AN) and ten healthy controls without eating disorders rated pictures of different types of foods in varying sized portions as too large or too small and rated the expected anxiety of five different portions (20-320 kcal). Two low energy dense (potatoes and rice) and two high energy dense (pizza and M&Ms) foods were used. The regression coefficient of line lengths (0-100 mm) marked from "No anxiety" to "this would give me a panic attack", regressed from portions shown, was the measure of "expected anxiety" for a given food. The maximum tolerated portion size [kcal] (MTPS), computed by method of constant stimulus from portions shown, was significantly smaller for high energy dense foods, whereas the expected anxiety response was greater, for all foods, for patients compared to controls. For both groups, expected anxiety responses were steeper, and maximum tolerated portion sizes were larger, for low, than high, energy dense foods. Both maximum tolerated portion size and expected anxiety response were significantly predicted by severity of illness for the patients. Those who had larger maximum tolerated portion sizes had smaller anticipated anxiety to increasing portion sizes. Visual size had a greater influence than energy content for these responses. This method could be used to quantify the anxiety inducing potential of foods and for studies with neuro-imaging and phenotypic clarifications.

A 64-year-old man who presented with photopsia was found to have elevated intraocular pressure in one eye and optic disc swelling in the other eye. He was initially diagnosed with neurocysticercosis and later metastatic lung adenocarcinoma. The purpose of this paper is to report a rare case of bilateral glare as the first sign of diffusely metastatic cancer and to raise clinical suspicion for systemic malignancy in the presence of multiple ocular manifestations.

Osteosarcoma (OS) is a class of cancer originating from the bone, affecting mainly children and young adults. Our previous study showed that MAPK7 gene overexpression was significantly associated with tumor progression, poor treatment response, and worse overall survival, suggesting that MAPK7 could play an important role in OS tumorigenesis. We have investigated if MAPK7 overexpression was a result of any genomic changes in OS tumor specimens. We identified five SNPs (Single Nucleotide Polymorphism) previously described in databases, dbSNP and COSMIC, and identified two single nucleotide substitution not yet described. We found, in prechemotherapy specimens, a significant association of MAPK7 rs2233072G allele variant with metastasis at diagnosis and relapse (0.0909 and 0.0455, respectively). In post-chemotherapy, rs1054206GG specimen's genotype was associated with osteoblastic histological type (P= 0.0249) and presented decreased MAPK7 gene expression when compared with pre-chemotherapy specimens of same patients (P = 0.0095). Interestingly, it was observed some SNPs genotype exchange after chemotherapy. Our data indicated that MAPK7 gene expression associated with genotype exchange after chemotherapy, and these SNPs associated with important clinical parameters might be a valuable indicator for predicting in OS.

Summary Background UK NICE guidelines, state that patients attending an outpatient clinic for the first time, should be screened for malnutrition. Aims To determine the prevalence of malnutrition in the medical and surgical gastroenterology outpatient department (OPD) using body mass index (BMI) and % weight loss (%WL) and to assess the physicians'/surgeons' response to malnutrition being detected. Methods The BMI and the %WL were determined for every patient over a 2 week period before the clinician saw the patient. The BMI and %WL were scored as in the Malnutrition Universal Screening Tool (MUST). Results 605 patients (316 females) of mean age 54 years were included. 150 (25%) were new patients. 519 (86%) had a normal BMI and %WL. 86 (14%) had a BMI Conclusions The prevalence of malnutrition in medical and surgical gastrointestinal outpatients was 14%. IBD and cancer patients had the highest prevalence. Most patients with malnutrition (52, 61%) were not being seen by a dietitian.

Made available in DSpace on 2019-10-04T12:14:04Z (GMT). No. of bitstreams: 0 Previous issue date: 2019-01-01. Added 1 bitstream(s) on 2019-10-09T18:33:27Z : No. of bitstreams: 1 S0034-89102019000100233.pdf: 241973 bytes, checksum: 00221ad17b7a809f24d6a29f4defe35a (MD5) OBJECTIVE: To evaluate whether the scheduling model influences the perception of the user about the quality of primary health care centers. METHODS: This is a cross-sectional and population-based study that measured the quality of centers by the Primary Care Assessment Tool (PCATool-Brazil), applied to adult users (n = 409) from 11 health centers in FlorianOpolis, state of Santa Catarina. Multilevel analysis was used to verify the relationship between the score of general quality of the primary health care and the scheduling model. The independent variables (age, skin color, scheduling model, panel size by primary health team, poverty ratio as income proxy, number of health teams, presence of economically interest areas, number of medical appointments in one year per primary health team, number of people treated in one year per health team), with p < 0.20 were selected for the multilevel model, which was adjusted with aggregates of information from users and health centers. RESULTS: The health center that used advanced access had a general score of 7.04, while those using a weekly carve-out had a score of 6.26; the carve-out every 15 days, score of 5.87; and the traditional carve-out, score of 6.29. CONCLUSIONS: The scheduling model of advanced access had a positive effect on the quality of primary health care, in the perception of users. Univ Fed Santa Catarina, Programa Posgrad Saude Colet, Florianopolis, SC, Brazil Univ Estadual Paulista, Programa Posgrad SaUde Colet, Sao Paulo, SP, Brazil Univ Fed Rio Grande do Sul, Fac Med, Programa Posgrad Epidemiol, Porto Alegre, RS, Brazil Univ Fed Rio Grande do Sul, Programa Posgrad Epidemiol, Porto Alegre, RS, Brazil Univ Estadual Paulista, Programa Posgrad SaUde Colet, Sao Paulo, SP, Brazil

Case Answer A 15-year-old woman presented to a hospital with malaise and visible pallor that had lasted for 2 weeks. The patient was treated with ferrous iron and discharged home. Following discharge, the patient’s symptoms did not improve and she subsequently developed dark urine. As a result, the family decided to seek care at a larger center. When the patient arrived to our center, urinalysis was obtained in view of the reported symptoms. Dipstick urinalysis revealed pH 7.0, specific gravity 1.015, protein 3+, hemoglobin 3+, urobilinogen excess, and bilirubin 1+. Examination of the spun urine sediment revealed numerous renal tubular epithelial cells (RTECs) (>50/high power field), red blood cells (1–2/high …

This paper presents partial results of a research-intervention, through training of PHC work teams. Initial consultation was made in a group by HC professionals, and the osteopath then performed the consultation. The socialization and training of practical knowledge and techniques of the osteopathic approach was done between consultations. Multiprofessional teams from three health centers from Florianópolis, southern Brazil, participated in the training, and the process was audio and videorecorded, along with a final interview. Data was analyzed using the Grounded Theory. Apprehending the osteopathic knowledge was a triggering tool for reflective processes about care. Faced with the efficiency and resolution of this approach in practice, participants showed a willingness to transform their acts of care of patients and also their self-care. The professionals argue that the common understanding about self-regulating mechanisms and the inclusion of the tissue mobility in their anamnesis, including the stimulation of endogenous mechanisms, contributed to less protocol-based care, more appropriate care for each case, better multidisciplinary team work, the rational use of additional tests, medication, and surgical procedures.Este artigo apresenta resultados parciais de uma pesquisa-intervenção, por meio de capacitação, relativas à socialização de saberes/técnicas da abordagem osteopática para profissionais da Atenção Primária à Saúde (APS), na sua confrontação com os processos de trabalho e cuidado na APS, conforme a lógica da educação permanente em saúde. Participaram das capacitações, equipes multiprofissionais de três centros de saúde de Florianópolis, região sul do Brasil, sendo o processo registrado em áudio e vídeo e acrescido de uma entrevista final. A análise dos dados foi feita por meio da Grounded Theory. A aprendizagem de saberes osteopáticos mostrou-se como instrumento disparador de processos reflexivos acerca do cuidado. Confrontados com a eficácia e resolubilidade percebidas desta abordagem na prática, os participantes demonstraram disposição para transformar seus atos de cuidado consigo mesmo e dentro do seu processo de trabalho. Segundo os profissionais, o entendimento comum sobre os mecanismos de autorregulação e a inclusão do estudo da mobilidade tecidual em sua anamnese contribuíram para o trabalho em equipe envolvendo um cuidado menos protocolar, mais adequado à cada caso, que inclui o estímulo de mecanismos endógenos, o uso racional de exames complementares, medicação e procedimentos cirúrgicos.

The article analyzes the supply of Integrative and Complementary Health Practices in the Family Health Strategy (FHS), based on the agreement between answers by administrators and health professionals. This was a quantitative descriptive-exploratory study using two databases, the National Survey on Integrative and Complementary Practices in Health in the Unified National Health System (SUS) and the National Program for Improvement of Access and Quality of Basic Care (PMAQ). According to the administrators, the supply of Integrative and Complementary Health Practices was present in the FHS in 26.7% of the municipalities participating in the National Survey, compared to 25.5% of the municipalities according to the health professionals in the PMAQ. Of the 1,478 municipalities that participated in both surveys, in 8.6% there was an agreement of answers on the supply of Integrative and Complementary Health Practices in the FHS. The municipalities with the greatest agreement in the supply were those with small populations and greater coverage of basic care. The small proportion of municipalities with this supply according to both administrators and health professionals supports the hypothesis that the health professionals are the main force responsible for the expansion of Integrative and Complementary Health Practices in the SUS, as compared to initiatives by administrators. This scenario reflects the need for administrators to take greater stock of what is developed in the FHS to strengthen Integrative and Complementary Health Practices and to mobilize the institutional resources for their maintenance and expansion.O artigo apresenta análise da oferta das Práticas Integrativas e Complementares em Saúde (PICS) na Estratégia Saúde da Família (ESF), a partir da convergência da resposta de gestores e profissionais. Trata-se de uma pesquisa quantitativa descritivo-exploratória, utilizando dois bancos de dados: o Inquérito Nacional de Práticas Integrativas e Complementares em Saúde no SUS e o Programa Nacional de Melhoria do Acesso e da Qualidade da Atenção Básica (PMAQ). De acordo com os gestores, a oferta de PICS esteve presente na ESF de 26,7% dos municípios participantes do Inquérito e em 25,5% dos municípios do PMAQ, segundo os profissionais. Dos 1.478 municípios que participaram das duas pesquisas, em 8,6% deles houve convergência da oferta de PICS na ESF. Os municípios com maior convergência na oferta são de pequeno porte populacional e com maior cobertura de atenção básica. A pequena quantidade de municípios com oferta reconhecida por gestores e profissionais reforça o pressuposto de que são os profissionais os principais responsáveis pela expansão das PICS no SUS, em detrimento de iniciativas da gestão. Esse cenário caracteriza a necessidade de apropriação por parte dos gestores do que é desenvolvido na ESF, para o fortalecimento das PICS e a mobilização de recursos institucionais para sua manutenção e ampliação.El artículo presenta un análisis de la oferta de Prácticas Integradoras y Complementarias en Salud (PICS), dentro la Estrategia Salud de la Familia (ESF), a partir de la convergencia en la respuesta de gestores y profesionales. Se trata de una investigación cuantitativa descriptiva-exploratoria, utilizando dos bancos de datos: la Encuesta Nacional de Prácticas Integradoras y Complementarias de Salud en el SUS y el Programa Nacional de Mejora de Acceso y Calidad de la Atención Básica (PMAQ). De acuerdo con los gestores, la oferta de PICS estuvo presente en la ESF de un 26,7% de los municipios participantes en la Encuesta Nacional y en un 25,5% de los municipios del PMAQ, según los profesionales. De los 1.478 municipios que participaron en las dos investigaciones, en un 8,6% de ellos hubo convergencia de la oferta de PICS en la ESF. Los municipios con mayor convergencia en la oferta son de pequeño porte poblacional y con mayor cobertura de atención básica. La pequeña cantidad de municipios con oferta reconocida por gestores y profesionales refuerza la presuposición de que son los profesionales los principales responsables de la expansión de las PICS en el SUS, en detrimento de iniciativas de la gestión. Este escenario caracteriza la necesidad de apropiación por parte de los gestores de lo que se desarrolla en la ESF, para el fortalecimiento de las PICS y la movilización de recursos institucionales para su mantenimiento y ampliación.

The scope of this article is to interpret ethical values and principles of the yoga tradition and discuss them with a view to possible contributions to psychosocial care in Primary Health Care (PHC). A theoretical-hermeneutic study was conducted, in which concepts contained in the Yoga Sutras of Patañjali were interpreted from the standpoint of mental health. It was revealed that the values found in the texts can enrich the existing practices of yoga for PHC users (who suffer from afflictions inherent to life) by providing ideas and guidelines that promote a sense of liberation from suffering. Such values and ethical principles can be incorporated into the discussions in PHC and psychosocial care, such as the reduction of iatrogenic disorders and unnecessary medication (quaternary prevention). It can also contribute to the relativization of biomedical power, stimulation of empathy and participation of users in care, with their subjective repositioning, multiplying autonomous ways of managing suffering and building networks of psychosocial support. The conclusion drawn was that the values of the Yoga Sutras may be present in various domains of PHC, which might provide a broader understanding of what 'the practice of yoga' means.O presente artigo tem como objetivo interpretar valores e princípios éticos da tradição do yoga e discuti-los visando possíveis contribuições para a atenção psicossocial na Atenção Primária à Saúde (APS). Foi realizado um estudo teórico-hermenêutico, em que conceitos presentes na escritura Yoga Sutra de Patañjali foram interpretados sob o enquadramento da saúde mental. Constatou-se que os valores encontrados na escritura podem enriquecer as práticas de yoga atualmente existentes voltadas para os usuários da APS (que sofrem com aflições inerentes à vida) ao fornecerem ideias e diretrizes que favorecem um sentido de libertação do sofrimento. Tais valores e princípios éticos podem ser incorporados às discussões presentes na APS e na atenção psicossocial, como redução da iatrogenia e da medicalização desnecessária (prevenção quaternária), relativização do poder biomédico, estímulo ao exercício da empatia e da participação dos usuários nos cuidados, com seu reposicionamento subjetivo, pluralizando formas autônomas de manejo do sofrimento e construindo redes de apoio psicossocial. Concluiu-se que os valores do Yoga Sutra podem estar presentes em diversos âmbitos da APS, o que daria um entendimento expandido sobre o que significa uma “prática de yoga”.