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Large sets of radiocarbon dates are increasingly used as proxies for inferring past population dynamics and the last few years, in particular, saw an increase in the development of new statistical techniques to overcome some of the key challenges imposed by this kind of data. These include: 1) null hypothesis significance testing approaches based on Monte-Carlo simulations or mark permutations; 2) non-parametric Bayesian modelling approaches, and 3) the use of more traditional techniques such as correlation, regression, and AIC-based model comparison directly on the summed probability distribution of radiocarbon dates (SPD). While the range of opportunities offered by these solutions is unquestionably appealing, they often do not consider the uncertainty and the biases arising from calibration effects or sampling error. Here we introduce a novel Bayesian approach and nimbleCarbon, an R package that offers model fitting and comparison for population growth models based on the temporal frequency data of radiocarbon dates. We evaluate the robustness of the proposed approach on a range of simulated scenarios and illustrate its application on a case study focused on the demographic impact of the introduction of wet-rice farming in prehistoric Japan during the 1st millennium BCE.

This study aimed to analyze the anterior lens capsule specimens from both eyes of a patient with systemic sclerosis and compare them to the eyes of a control patient. No significant differences between systemic sclerosis and control eyes were observed in the results from the hematoxylin-eosin and picrosirius staining. In the samples obtained from both systemic sclerosis and control eyes, there were expressions of caspase, a molecule expressed in cell death by apoptosis. Heparanase was overexpressed in the systemic sclerosis sample compared to the control sample. Therefore, the anterior lens capsule of the patient with systemic sclerosis is probably affected by the disease since it showed marked expression of heparanase 1.

Defects of the Achilles tendon that include the surrounding soft tissue represent a challenge due to complex functionality and biomechanics. PURPOSE: The purpose of this study was to evaluate the functional and physical functioning score outcomes of patients following microsurgical reconstruction of the yarrow region, using a combination of objective, subjective, and semi-subjective measurements. METHODS: Between 2007 and 2018, 15 patients underwent delayed Achilles tendon region reconstruction with different anterolateral thigh flap types. Seven (7) patients underwent tendon and soft tissue reconstruction with a chimeric anterolateral thigh flap (ALT) and rolled-up fascia lata, and 8 patients underwent soft tissue reconstruction and only tendon coverage with fascia lata. Follow-up assessments included maximal range of motion (MROM) (plantarflexion and dorsiflexion), the American Orthopedic Foot and Ankle Society Ankle-Hindfoot Scale score, and the Medical Outcomes Study 36-item Short-Form Health Survey physical functioning subscore. RESULTS: A total of 15 patients (11 males and 4 females with a mean age of 39.86 years) were evaluated during a mean follow-up time of 23 months (SD = 7.12). The MROM for plantarflexion and dorsiflexion was 42.71 degrees (SD = 2.9) and 24.8 degrees (SD = 4.29), respectively, in patients who underwent composite ALT with a rolled-up fascia lata. The MROM for plantarflexion and dorsiflexion was 43 degrees (SD = 5.37) and 27.37 degrees (SD = 3.2), respectively, in patients who underwent fasciocutaneous ALT. The mean American Orthopaedic Foot and Ankle Society Ankle-Hindfoot Scale score was 82 for the first group and 86.87 for the second, whereas the mean Medical Outcomes Study 36-item Short-Form Health Survey scores were 82.57 and 81.5, respectively, for the 2 groups. Statistical analysis showed no significant difference between the 2 groups. CONCLUSIONS: The results of this case series suggest that the single-stage composite reconstruction with a fasciocutaneous flap with or without a strip of fascia lata is a safe and reliable strategy for composite reconstruction of the Achilles tendon region. Additional studies to evaluate these outcomes and instruments to evaluate functioning are necessary.

Background This study evaluated the effect of treatment with TKI-258 on apoptosis, involving Rho GTPases and their effectors in SCC-4 cells of oral squamous cell carcinoma. Methods Markers of cell death and apoptosis were analyzed in control and TKI-258 treated SCC-4 cells by flow cytometry. The involvement of Rho GTPases and effectors in the induction of apoptosis by TKI-258 was evaluated by quantification of cleaved PARP. Also gene expression analysis of those proteins was performed. Results The treatment with TKI-258 led to a significant increase in cell death (7-AAD) and apoptosis (Annexin V and cleaved PARP). When Rho GTPases were stimulated with LPA and inhibited with Toxin A Clostridium difficile, the percentage of apoptotic cells increased and decreased, respectively. A similar effect was found when the treatment was with TKI-258 combined with LPA and Toxin A. Treatment with TKI-258 significantly increased RhoA gene expression, while RhoB, RhoC, Rac1 and Cdc42 decreased significantly. ROCKs inhibitors (Y-27632 and HA-1077) reduced apoptosis compared with control. TKI-258 combined with Y-27632 or HA-1077 led to an increase in apoptosis compared with inhibitors only. Treatment with TKI-258 led to an increase in ROCK1 and ROCK2 gene expression, and a decrease in PAK1 and PAK2 gene expression. Conclusions TKI-258 stimulates apoptosis in SCC-4 cells of oral squamous cell carcinoma. Possibly, RhoA GTPase and their effectors ROCKs participate in the signalling pathway inhibited by TKI-258. Clinical relevance Therapies with multi-target inhibitors, such as TKI-258, may be promising alternatives for the clinical treatment of oral squamous cell carcinoma.

Summary Objective Sprifermin (recombinant human fibroblast growth factor-18), a potential disease-modifying osteoarthritis (OA) drug, demonstrated dose-dependent effects on femorotibial cartilage thickness (by quantitative magnetic resonance imaging [MRI]) in the phase II FORWARD study. This post-hoc analysis evaluated the potential effects of sprifermin on several articular structures in the whole joint over 24 months using semi-quantitative MRI assessment. Design Patients aged 40–85 years with symptomatic radiographic knee OA, Kellgren–Lawrence grade 2 or 3, and medial minimum joint space width ≥2.5 mm in the target knee were randomized (1:1:1:1:1) to receive three double-blinded, once-weekly, intra-articular injections of sprifermin 30 μg or 100 μg or placebo every 6 (q6mo) or 12 months. 1.5- or 3 T MRIs were read using the Whole-Organ Magnetic Resonance Imaging Score (WORMS) system at baseline and 24 months. Change from baseline at 24 months on compartment and/or whole knee level was assessed for cartilage morphology, bone marrow lesions (BMLs), and osteophytes by delta-subregional and delta-sum (DSM) approaches. Menisci, Hoffa-synovitis, and effusion-synovitis were also evaluated for worsening. Results 549 patients were included. Dose-dependent treatment effects from baseline to 24 months were observed on cartilage morphology (sprifermin 100 μg q6mo vs placebo; mean DSM (95% confidence interval [CI]) −0.6 (−1.5, 0.2); less cartilage worsening) in the entire knee and BMLs sprifermin 100 μg q6mo vs placebo; mean DSM (95% CI) −0.2 (−0.5, 0.1) in the patellofemoral compartment. No effects over 24 months were observed on osteophytes, menisci, Hoffa-synovitis or effusion-synovitis. Conclusions Positive effects associated with sprifermin were observed for cartilage morphology changes, and BML improvement. There were no meaningful negative or positive effects associated with sprifermin in the other joint tissues examined.

Osteoarthritis (OA) is a highly prevalent chronic condition with marked implications for affected individuals and public health care. There are available treatments to manage pain and symptoms but no effective treatment for OA. In the past 10 years, joint imaging, particularly MRI, has evolved rapidly due to technical advances and their application to clinical research, which has led to abundant evidence regarding the natural history of the disease. Radiography remains the primary imaging modality in clinical practice for the diagnosis and follow-up of OA. The many developments in MRI techniques capable of assessing cartilage morphologic features and the methods for evaluating its biochemical composition will be discussed. Advances in quantitative morphologic cartilage assessment and semiquantitative whole-organ assessment will be reviewed, as will other modalities such as US, CT and CT arthrography, and nuclear medicine techniques that play a complementary role. Various therapeutic approaches and ongoing developments, including the impact of artificial intelligence on the field of OA imaging, will also be discussed.

Objective: This study evaluated the involvement of Rho GTPases proteins in the regulation of cytodifferentiation of the SCC-4 human oral squamous cell carcinoma cell line. Methods: Cytokeratin and vimentin immunofluorescence and F-actin staining, assays were performed with control cells and Clostridium difficile 1, 2 and 4 μg/mL Toxin A (Rho GTPases inhibitor) treated SCC-4 cells on three-dimensional MatrigelTM for 24 h. Samples were analyzed by using confocal laser microscopy. Significances were p

OBJECTIVE: Eligibility for clinical trials in osteoarthritis (OA) is usually limited to Kellgren-Lawrence (KL) grades 2 and 3 knees. Our aim was to describe the prevalence and severity of cartilage damage in KL 2 and 3 knees by compartment and articular subregion. DESIGN: The Multicenter Osteoarthritis (MOST) study is a cohort study of individuals with or at risk for knee OA. All baseline MRIs with radiographic disease severity KL2 and 3 were included. Knee MRIs were read for cartilage damage in 14 subregions. We determined the frequencies of no, any and widespread full-thickness cartilage damage by knee compartment, and the prevalence of any cartilage damage in 14 articular subregions. RESULTS: 665 knees from 665 participants were included (mean age 63.8 ± 7.9 years, 66.5% women). 372 knees were KL2 and 293 knees were KL3. There was no cartilage damage in 78 (21.0%) medial tibio-femoral joint (TFJ), 157 (42.2%) lateral TFJ and 62 (16.7%) patello-femoral joint (PFJ) compartments of KL2 knees, and 17 (5.8%), 115 (39.3%) and 35 (12.0%) compartments, respectively, of KL3 knees. There was widespread full-thickness damage in 94 (25.3%) medial TFJ, 36 (9.7%) lateral TFJ and 176 (47.3%) PFJ compartments of KL2 knees, and 217 (74.1%), 70 (23.9%) and 104 (35.5%) compartments, respectively, of KL3 knees. The subregions most likely to have any damage were central medial femur (80.5%), medial patella (69.8%) and central medial tibia (69.9). CONCLUSIONS: KL2 and KL3 knees vary greatly in cartilage morphology. Heterogeneity in the prevalence, severity and location of cartilage damage in in KL2 and 3 knees should be considered when planning disease modifying trials for knee OA.

ObjectiveHerpes zoster virus can cause inflammatory neuropathy of the facial nerve. However, studies evaluating the prevalence of this agent in peripheral facial palsy are heterogeneous regarding sample group selection, laboratory analysis method and variables studied. In addition, there are a lack of epidemiological data in the Brazilian population on this serological phenomenon in peripheral facial palsy. This study estimated herpes zoster reactivation prevalence in serological samples through chemiluminescence immunoassay for quantitative determination of specific antibodies directed against the virus.MethodsThis cross-sectional study sought to determine the prevalence of viral reactivation by herpes zoster in subjects with idiopathic peripheral facial palsy through analysis of serological samples over a year.ResultsForty-seven patients (32 females and 15 males) participated. Severe paralysis was more common in older patients (p = 0.017). Facial pain (p = 0.02) and vertigo (p = 0.001) were related to a worse evolution of facial palsy. The rate of serological reactivation of the virus was 12.76 per cent.ConclusionThe rate of serological reactivation of herpes virus in idiopathic peripheral facial palsy in our population is similar to foreign literature data, suggesting similar aetiological mechanisms in the genesis of this morbidity.

Minimally invasive surgery represented a significant milestone in modern surgery; however, continuous innovation and the emergence of new technologies pose new challenges in terms of surgical learning curves since new interventions are associated with increased surgical complexity and a higher risk of complications. For this reason, surgeons are aware of the beneficial effects of “learning before doing” and the importance of safely implementing new surgical procedures in order to obtain better patient outcomes. Considered the largest Latin American training center in minimally invasive surgery, IRCAD Barretos, São Paulo, Brazil, makes it possible to acquire surgical skills through training in different and the most complex areas of medicine, providing the experience of real and simulated situations, with focus on innovation. The center possesses state-of-the-art infrastructure and technology, with a very high-level teaching staff and an affectionate and hospitable reception. Since its inauguration, in 2011, the center has already qualified numerous professionals and has placed the country in a privileged position in terms of surgical knowledge. The present article describes the activities developed over these ten years of the institute in Brazil as the largest training center for surgeons of the continent in order to address the importance of surgical skills training.

The commensal microbiota plays a fundamental role in maintaining host gut homeostasis by controlling several metabolic, neuronal and immune functions. Conversely, changes in the gut microenvironment may alter the saprophytic microbial community and function, hampering the positive relationship with the host. In this bidirectional interplay between the gut microbiota and the host, hyaluronan (HA), an unbranched glycosaminoglycan component of the extracellular matrix, has a multifaceted role. HA is fundamental for bacterial metabolism and influences bacterial adhesiveness to the mucosal layer and diffusion across the epithelial barrier. In the host, HA may be produced and distributed in different cellular components within the gut microenvironment, playing a role in the modulation of immune and neuronal responses. This review covers the more recent studies highlighting the relevance of HA as a putative modulator of the communication between luminal bacteria and the host gut neuro-immune axis both in health and disease conditions, such as inflammatory bowel disease and ischemia/reperfusion injury.

The aim of the present study was to analyze the association between parental eating behavior and untreated early childhood caries (ECC). A cross-sectional study was conducted with a representative sample of 432 parent-child dyads with children aged 18 to 36 months, at Municipal Child Education Centers in São José dos Pinhais, Brazil. The parents answered a questionnaire addressing demographic and socioeconomic characteristics, and the children were examined for dental caries (modified dmft index) by a single examiner (kappa = 0.80). A six-item questionnaire was administered addressing parental food consumption, parental control of the child’s food consumption, and parental offering of foods to the child. Three items were considered indicative of positive behavior, and three, of negative behavior. Univariate and multivariate Poisson regression analyses with robust variance were used for the data analysis (α = 0.05). The prevalence of untreated ECC was 20.3% (95%CI: 16.7–24.4). In the multiple regression model adjusted for the child’s age and the parent’s schooling, negative parental behavior was associated with a greater frequency of untreated ECC (PRa = 1.213; 95%CI:1.032–1.427, p = 0.019), but lost its significance when adjusted by positive parental behavior (PRa = 1.156; 95%CI: 0.983–1.358, p = 0.079). Based on the present findings, positive parental eating behaviors are capable of minimizing the impact of negative parental behaviors on the prevalence of untreated early childhood caries.

Made available in DSpace on 2022-04-29T08:35:38Z (GMT). No. of bitstreams: 0 Previous issue date: 2022-01-01 Background: Chagasic megaesophagus (CM) as well as the presence of human papillomavirus (HPV) has been reported as etiological factors for esophageal squamous cell carcinoma (ESCC). Objective: We assessed the prevalence of HPV DNA in a series of ESCCs associated or not with CM. Data obtained were further correlated to the pathological and clinical data of affected individuals. Methods: A retrospective study was performed on 92 formalin-fixed and paraffin-embedded tissues collected from patients referred to 3 different hospitals in São Paulo, Brazil: Barretos Cancer Hospital, Barretos, São Paulo; Federal University of Triângulo Mineiro, Uberaba, Minas Gerais; and São Paulo State University, Botucatu, São Paulo. Cases were divided into 3 groups: (i) 24 patients with CM associated with ESCC (CM/ESCC); (ii) 37 patients with ESCC without CM (ESCC); and (iii) 31 patients with CM without ESCC (CM). Detection of HPV DNA was assessed in all samples by a genotyping assay combining multiplex polymerase chain reaction and bead-based Luminex technology. Results: We identified a high prevalence of high-risk HPV in patients in the CM group (12/31, 38.8%) and CM/ESCC (8/24, 33.3%), compared to individuals in the ESCC group (6/37, 16.3%). The individuals in the groups with cancer (ESCC and CM/ESCC) had a higher frequency of HPV-16 (4/9, 44.5% and 2/8, 25.0%). The other types of high-risk HPVs detected were HPV-31, 45, 51, 53, 56, 66, and 73. We also observed in some samples HPV coinfection by more than one viral type. Despite the high incidence of HPV, it did not show any association with the patient's clinical-pathological and molecular (TP53 mutation status) characteristics. Conclusion: This is the first report of the presence of HPV DNA in CM associated with ESCC. HPV infection was more presence in megaesophagus lesions. Further studies are needed to confirm and better understand the role of persistent HPV infection in patients with CM. Molecular Oncology Research Center Barretos Cancer Hospital Center for Translational Research in Oncology Instituto Do Cancer Do Estado de Sao Paulo-ICESP, Cerqueira César Department of Digestive Surgery Barretos Cancer Hospital Department of Pathology Diagnosis of Biopsies and Surgical Specimens Barretos Cancer Hospital Department of Digestive Surgery and Pathology Medical School UFTM Federal University of Triangulo Mineiro Departament of Gastroenterology Surgery and Pathology Medical School UNESP São Paulo State University Department of Endoscopy Barretos Cancer Hospital Barretos Life and Health Sciences Research Institute (ICVS) School of Medicine University of Minho ICVS/3B's-PT Government Associate Laboratory, Guimarães Department of Radiology and Oncology Faculdade de Medicina Universidade de Sao Paulo Department of Radiology and Oncology Medical School University of São Paulo, Butanta Medical Laboratory of Medical Investigation (LIM) 14 Department of Pathology Medical School University of São Paulo, Butanta Departament of Gastroenterology Surgery and Pathology Medical School UNESP São Paulo State University

This paper responds to a resurgence of interest in constructing long-term time proxies of human activity, especially but not limited to models of population change over the Pleistocene and/or Holocene. While very much agreeing with the need for this increased attention, we emphasize three important issues that can all be thought of as modifiable reporting unit problems: the impact of (i) archaeological periodization, (ii) uneven event durations and (iii) geographical nucleation-dispersal phenomena. Drawing inspiration from real-world examples from prehistoric Britain, Greece and Japan, we explore their consequences and possible mitigation via a reproducible set of tactical simulations. This article is part of the theme issue ‘Cross-disciplinary approaches to prehistoric demography’.

Metabolic syndrome is a major health problem worldwide associated with obesity, thus drawing attention to its relation to osteoarthritis (OA). However, it is still uncertain whether metabolic syndrome or body fat distribution is associated with knee OA. The aim of this longitudinal study was to elucidate the association between metabolic obesity and adverse structural changes of knee OA assessed by magnetic resonance imaging (MRI).Participants were recruited from the Hallym Aging Study cohort in Korea. Knee MRI scans, along with dual-energy X-ray absorptiometry, were assessed in 226 participants at baseline and after 3 years. The structural progression in the tibiofemoral joint was evaluated using the semi-quantitative Whole-Organ MRI Score (WORMS) for cartilage morphology and bone marrow lesions (BML). Logistic regression with generalized estimating equation was performed for associations of metabolic risk factors with worsening of WORMS scores at the subregional level.In the medial compartment, fat mass in women was associated with cartilage loss, but the statistical significance disappeared after adjusting for body mass index. Metabolic syndrome and each of its components were not associated with cartilage loss or increase of BML. On the other hand, the interaction effects of metabolic syndrome on the association between obesity and knee OA progression were not significant.In this cohort, metabolic effects of obesity on knee cartilage damage and BML were not demonstrated. Further large-scale studies are required to prove the causal relationship between metabolic obesity and knee OA.

Clear cell acanthoma (CCA) is a rare, benign epidermal lesion of clear glycogen-containing keratinocytes. The exact etiology is unknown. Although CCA usually appear as solitary lesions, cases of multiple CCAs have also been described. The rare eruptive CCA variant describes cases with more than 30 lesions.Current therapeutic evidence for the management of multiple CCAs is limited. CO2 laser remains the most widely used laser in clinical practice. However, literature describing its effectiveness on CCA is sparse, and previous reports have described its use for a maximum of three lesions. To our knowledge, this is the first report of successful CO2 laser treatment of the multiple eruptive CCA variant with an excellent cosmetic outcome.Our case adds to the evidence that CO2 laser is an effective treatment for this condition. Particularly in those patients with refractory or multiple eruptive CCAs, or for those who may not tolerate repeated courses of cryotherapy, or who are concerned about scarring and cosmetic outcome.

Objective: Despite its prevalence, there are few worldwide hand osteoarthritis (HOA) cohorts. The main objective of DIGItal COhort Design (DIGICOD) cohort is to investigate prognostic clinical, biological, genetic and imaging factors of clinical worsening after 6 years follow-up.Methods: DIGICOD is a hospital-based prospective cohort including patients > 35 years-old with symptomatic HOA fulfilling: (i) ACR criteria for HOA with > 2 symptomatic joints among proximal/distal interphalangeal joints or 1st interphalangeal joint with Kellgren-Lawrence (KL) > 2; or (ii) symptomatic thumb base OA with KL > 2. Main exclusion criteria were inflammatory arthritis and crystal arthropathies. Annual clinical evaluations were scheduled with imaging (X-rays of the hands and of other OA symptomatic joints) and biological sampling every 3 years. Hand radiographs are scored using KL and anatomical Verbruggen-Veys scores. Follow-up visits are ongoing. Cohort methodology and baseline characteristics are presented.Results: Between April 2013 and June 2017, from the 436 HOA included patients, 426 have been analysed of whom 357 (84%) are women. Mean age +/- standard deviation was 66.7 +/- 7.3 years and mean disease duration was 12.6 +/- 9.6 years. Metabolic syndrome affected 151 (36.5%) patients. Mean Visual Analog Scale (VAS) hand pain (0-100 mm) was 44.4 +/- 26.7 mm at activity. Mean FIHOA (0-100) was 19.9 + 18.6. Elevated serum CRP level (>= 5 mg/L) involved 10% patients. Mean KL score (0-128) was 46.7 +/- 18 and the mean number ofjoint with KL >= 2 was 15.1 +/- 6.3. Erosive HOA (defined as >= 1 Erosive or Remodeling phase joint according to Verbruggen-Veys score) involved 195/426 (45.8%) patients and the median number (interquartile range) of erosive joints in erosive patients was 3.0 (1.0-5.0).Conclusion: DIGICOD is a unique prospective HOA cohort with a long-term 6 years standardized assessment and has included severe radiologically HOA patients with a high prevalence of erosive disease. 2021 Societe francaise de rhumatologie. Published by Elsevier Masson SAS. All rights reserved.

A clear correlation exists between microbiota and the dysregulation of the immune response in Inflammatory Bowel Diseases (IBD), which comprise Crohn’s disease (CD) and ulcerative colitis (UC). These unbalanced reactions also involve humoral responses, with antibodies against Saccharomyces cerevisiae. Thus, here we aimed to quantify IgA and IgG specific to S. cerevisiae (ASCA) in quiescent CD and UC, to correlate the production of these antibodies with patient’s inflammatory response and disease clinical presentation. Twenty-nine subjects (16 CD and 13 UC) and 45 healthy controls were enrolled in this study and had plasma samples tested for ASCA and cytokines (IL-2, IL-4, IL-6, IL-10, IFN-γ, TNF-α), besides clinical evaluation. IBD patients had increase IgA and IgG ASCA, especially those with colonic (L2) and fistulizing (B3) CD. Similarly, patients who dropped out the treatment had augmented ASCA, while IgG was reduced in those receiving sulfasalazine treatment. Furthermore, the quiescent CD patients had elevated IL-6 on plasma, especially in the absence of treatment, together with increased counter regulatory response of IL-10. There was a positive correlation between IgA and IgG on CD but not UC, as well as between IgA and TNF in total IBD patients. In addition, the levels of IgG x TNF, IgA x IL-10 and IgG x IL-10 were also correlated in CD, indicating that ASCA production may be influenced by the inflammatory response. Finally, we concluded that ASCA could be pointed as relevant biomarker of CD presentation and residual inflammation, even in clinical remission patients.

ObjectivesThe association between obesity and atrial fibrillation (AF) is well-established. We aimed to evaluate the impact of index body mass index (BMI) on AF recurrence at 12 months following catheter ablation using propensity-weighted analysis. In addition, periprocedural complications and fluoroscopy details were examined to assess overall safety in relationship to increasing BMI ranges.MethodsBaseline, periprocedural and follow-up data were collected on consecutive patients scheduled for AF ablation. There were no specific exclusion criteria. Patients were categorised according to baseline BMI in order to assess the outcomes for each category.ResultsAmong 3333 patients, 728 (21.8%) were classified as normal (BMI 2), 1537 (46.1%) as overweight (BMI 25.5–29.0 kg/m2) and 1068 (32.0%) as obese (BMI ≥30.0 kg/m2). Procedural duration and radiation dose were higher for overweight and obese patients compared with those with a normal BMI (p=0.002 and p2led to a 1.2-fold increased likelihood of experiencing recurrent AF at 12-months follow-up as compared with overweight patients (HR 1.223; 95% CI 1.047 to 1.429; p=0.011), while no significant correlation was found between overweight and normal BMI groups (HR 0.954; 95% CI 0.798 to 1.140; p=0.605) and obese versus normal BMI (HR 1.16; 95% CI 0.965 to 1.412; p=0.112).ConclusionsPatients with a baseline BMI ≥30 kg/m2have a higher recurrence rate of AF following catheter ablation and therefore lifestyle modification to target obesity preprocedure should be considered in these patients.

Introduction Therapeutic plasma exchange (TPE) is considered a treatment option for steroid-refractory multiple sclerosis (MS) relapses. Our objective was to assess long-term clinical response to TPE in MS steroid-refractory exacerbations. Methods Retrospective study of relapsing remitting MS (RRMS) patients presenting intravenous methylprednisolone (IVMPS)-refractory relapses, who underwent TPE. Response to TPE was assessed at 1, 3, 6, 12 and 24-months post-treatment, and compared to a second group of RRMS patients with similar demographic and clinical characteristics presenting, IVMPS-refractory relapses but not treated with TPE. Multivariate regression analysis was used to assess potential predictors of significant clinical response. Results Between 2011 to 2020, a total of 23 RRMS patients were treated with TPE. Twenty-one patients not receiving the treatment served as controls. No differences in demographic or clinical characteristics, or predictors of clinical improvement after TPE were detected between groups. Seventy-eight percent of patients treated with TPE presented clinical improvement at 24 months. TPE-treated patients presented lower EDSS scores at 6 and at 24 months. Younger age, presence of gadolinium-enhancing lesions and TPE treatment were associated with better clinical outcomes. No life-threatening side effects were reported. Conclusions TPE is a safe and well tolerated procedure that decreases long-term disability in RRMS patients with IVMPS-refractory relapses.

Objective: To determine the prevalence, distribution and characteristics associated with radiographic metacarpophalangeal (MCP) osteoarthritis (OA). Methods: This is a cross‐sectional study of baseline data from the DIGItal Cohort Osteoarthritis Design, a French monocentric cohort including patients with symptomatic hand OA (HOA). We evaluated the prevalence of radiographic MCP OA defined as ≥2 MCP joints with a Kellgren and Lawrence score ≥2. We compared the prevalence of MCP OA in the dominant and non‐dominant hands. Associations between radiographic MCP OA and patient characteristics were studied using univariable and multivariable logistic regression. Results: Radiographic MCP OA was present in 138 of the 425 patients (32.5%) but was not severe. Patients with MCP OA had a mean age of 69.2±6.9 years, a BMI of 25±4.2 kg/m2, and 86.2% were women. MCP OA was more frequent in the dominant hand and predominated at the 1st and 2nd MCP joints. In the multivariable analysis, MCP OA was associated with older age (OR 1.05, 95%CI [1.01,1.10] for each year), manual occupation (OR 3.74, 95%CI [1.21,11.54]), scaphotrapezial OA (OR 2.18, 95%CI [1.27,3.72]), and a high number of proximal interphalangeal joints with radiographic OA. MCP OA was not associated with metabolic syndrome or HOA symptoms. Conclusion: In this cross‐sectional study using a hospital‐based HOA cohort, radiographic MCP OA was frequent and associated with structural HOA features rather than with symptom severity. Our results suggest that the involvement of MCP joints in HOA is predominantly related to mechanical rather than systemic factors in this population.

To compare the diagnostic performance of two different sets of magnetic resonance imaging (MRI) for the detection of subchondral erosions in the sacroiliac joints regarding the application of fat-water separation techniques when acquiring T1-weighted (T1w) images, using multi-detector computed tomography (MDCT) as the reference standard.We retrospectively included 31 consecutive patients having or being suspected for axial spondyloarthritis (SpA) assessed using both MRI and MDCT. Three sets of images were independently assessed for the presence of erosions by two musculoskeletal radiologists (R1, R2): (1) MRI with standard T1w without fat suppression, (2) MRI with both T1w with and without fat suppression, and (3) MDCT. The diagnostic performance of both sets of MRIs was assessed using MDCT as the referent.The assessment of T1w images with fat suppression substantially increased sensitivity (76% vs. 63% R1; 70% vs. 60% R2), specificity (97% vs. 84% R1; 96% vs. 81% R2), positive predictive value (85% vs. 45% R1; 81% vs. 40% R2), and overall accuracy (94% vs. 80% R1; 92% vs. 77% R2) in the detection of erosions when compared to the assessment using T1w images without fat suppression.The assessment of T1w images with fat suppression substantially improves the diagnostic performance of MRI in the detection of erosions in the sacroiliac joints.• The presence of erosions in the sacroiliac joints may influence the decision on the diagnosis of axial spondyloarthritis. • T1w fat-suppressed MR imaging relatively increases the contrast between the joint space (high signal) and the adjacent subchondral bone (low signal), potentially improving the detection of erosions in the sacroiliac joints. • T1w fat-suppressed images improve the diagnostic performance of MRI in the detection of erosions in the sacroiliac joints compared to T1w without fat suppression, using MDCT as the reference.

To describe the occurrence of imaging-depicted sports-related injuries (bone, muscle, tendon, and ligament injuries) during the Rio 2016 Summer Paralympic Games.Descriptive data on all imaging examinations by using radiography, ultrasonography (US), and MRI were collected and retrospectively analyzed centrally by five musculoskeletal radiologists according to imaging modality, country of origin of the athletes, type of sport, type of disability, and type and location of injury.We report 109 injuries in 4378 athletes. A total of 382 radiologic examinations were performed in 261 athletes, including 118 (31%) radiographic, 22 (6%) US, and 242 (63%) MRI examinations. Para athletes from Africa had the highest utilization rate (20.1%, 67 out of 333). Athletes from Europe underwent the most examinations with 29 radiographic, 12 US, and 66 MRI examinations. The highest utilization rate of imaging modalities by sport was among Judo para athletes (16.7%, 22 out of 132). Most injuries were reported in athletics discipline (37.6%, 41 out of 109). Most injuries were also reported among para athletes with visual impairment (40 injuries, 36.7% of all injuries). Bone stress injuries were most common among para athletes with visual impairment (6 out of 7). Para athletes with visual impairment were also more prone to bone stress injuries than traumatic fractures, unlike para athletes with neurologic and musculoskeletal impairments.Imaging was used in 6.0% of para athletes. MRI comprised 63% of imaging utilization. Identification of patterns of injuries may help building future prevention programs in elite para athletes.• The highest imaging utilization rates were found among para athletes competing in Judo, sitting volleyball, powerlifting, and football. • Utilization of diagnostic imaging at the Rio 2016 Paralympic Games demonstrated similar trends to what was observed at the Rio 2016 Olympic Games. • Comparison of the rate of imaging-depicted injuries between Olympic and Paralympic athletes is limited due to inherent differences between the two athlete populations and the manner in which injury risk in the Paralympic athlete varies dependent on impairment type, which is not the case for the Olympic athlete.

Background To investigate the frequency of pain among subjects with advanced radiographic knee osteoarthritis (OA) defined as Kellgren–Lawrence (KL) grade 4 and clinical features associated with pain. Methods Subjects from the Hallym Aging Study (HAS), the Korean National Health and Nutrition Examination Survey (KNHANES), and the Osteoarthritis Initiative (OAI) were included. Participants were asked knee-specific questions regarding the presence of knee pain. Clinical characteristics associated with the presence of pain were evaluated with multivariable logistic regression analysis. Results The study population consisted of 504, 10,152 and 4796 subjects from HAS, KNHANES, and OAI, respectively. KL grade 4 OA was identified in 9.3, 7.6, and 11.5% of subjects, while pain was absent in 23.5, 31.2, and 5.9% of subjects in KL grade 4 knee OA, respectively. After multivariable analysis, female gender showed a significant association with pain in the KNHANES group, while in the OAI group, younger age did. Advanced knee OA patients without pain did not differ from non-OA subjects in most items of SF-12 in both Korean and OAI subjects. Total WOMAC score was not significantly different between non-OA and advanced knee OA subjects without pain in the OAI. Conclusions Our study showed that a considerable number of subjects with KL grade 4 OA did not report pain. In patients whose pain arises from causes other than structural damage of the joint, therapeutic decision based on knee X-ray would lead to suboptimal result. In addition, treatment options focusing solely on cartilage engineering, should be viewed with caution.

At the beginning of the SARS-COV-2 outbreak in Brazil, there was a striking difference between the contamination rate in the Amazonian States and the South and the Southeast States. The regions near the Amazon rainforest presented much higher and faster contaminations. This paper attempts to explain this phenomenon through a global analysis of the COVID-19 epidemic in Brazil. It also investigates the relationship between climate conditions and airborne transmission with the evolution of contagion in the Amazonian states. The method of investigation of the spread of SARS-COV-2 in these different macro-environments was based on the analysis of three extensive daily official databases on the number of deaths, the percentage of adherence of the populations to the restriction policies, and the local climatic conditions. Besides, the social conditions in those States were also taken into account. Then, it was compared the epidemiologic results for States with very different climatic characteristics and that had adopted, almost simultaneously, similar social isolation measures. However, all these analyses were not able to explain the remarkable difference in the evolution of the pandemic among Brazilian regions. So, it was necessary to invoke airborne transmission, facilitated by the very high air humidity, as a decisive factor to explain the faster evolution of contagion in the rainforest region. Air humidity seems to be the most important climatic factor in viral spreading, while usual ambient temperatures do not have a strong influence. Another very important result of this analysis was the observation that the onset of collective immunity may have been achieved with a contamination rate of about 15% of the Amazonian population., Graphical abstract Unlabelled Image, Highlights • The transmission of SARS-COV-2 is much faster in the Amazon rainforest region. • An onset of collective immunity may have been achieved with a low contamination rate. • The airborne transmission played a key role in the pandemic in the Amazonian region. • Air humidity is the most important climatic factor in viral spreading. • Usual ambient temperatures do not have a strong influence on viral spreading.

Objectives Emerging evidence suggests a potential link between OA and gout; however, the association between serum uric acid (UA) itself and knee OA remains uncertain due to a lack of longitudinal studies. Here, we investigated the association between serum UA and knee OA according to cartilage status in elderly community residents without gout. Methods In this longitudinal study, participants without a history of gout were recruited from among the Korean cohort of the Hallym Aging Study (n = 296 for radiography study and n = 223 for MRI study). Weight-bearing knee radiographs and 1.5-T MRI scans, along with blood collection for analysis of serum UA, were performed at baseline and after 3 years. The severity and structural progression of knee OA were evaluated using the Kellgren–Lawrence grading system and the Whole-Organ MRI Score (WORMS) cartilage scoring method. Multivariable logistic regression analysis was conducted using generalized estimating equation (GEE) models. Results Serum UA levels were not associated with radiographic progression after adjusting for age, sex and BMI. There was no significant association between serum UA and tibiofemoral cartilage loss on MRI. However, baseline serum UA levels were negatively associated with patellofemoral cartilage loss over 3 years (adjusted odd ratio 0.70 per 1 mg/dl increase, 95% CI: 0.49, 0.98). Conclusion In this population-based cohort, serum UA was not a risk factor for knee OA progression. Further large-scale longitudinal studies in other populations are needed to validate the effects of UA on cartilage damage.

Intestinal ischemia/reperfusion (I/R) injury has severe consequences on myenteric neurons, which can be irreversibly compromised resulting in slowing of transit and hindered food digestion. Myenteric neurons synthesize hyaluronan (HA) to form a well-structured perineuronal net, which undergoes derangement when myenteric ganglia homeostasis is perturbed, i.e. during inflammation. In this study we evaluated HA involvement in rat small intestine myenteric plexus after in vivo I/R injury induced by clamping a branch of the superior mesenteric artery for 60 min, followed by 24 h of reperfusion. In some experiments, 4-methylumbelliferone (4-MU, 25 mg/kg), a HA synthesis inhibitor, was intraperitoneally administered to normal (CTR), sham-operated (SH) and I/R animals for 24 h. In longitudinal muscle myenteric plexus (LMMP) whole-mount preparations, HA binding protein staining as well as HA levels were significantly higher in the I/R group, and were reduced after 4-MU treatment. HA synthase 1 and 2 (HAS1 and HAS2) labelled myenteric neurons and mRNA levels in LMMPs increased in the I/R group with respect to CTR, and were reduced by 4-MU. The efficiency of the gastrointestinal transit was significantly reduced in I/R and 4-MU-treated I/R groups with respect to CTR and SH groups. In the 4-MU-treated I/R group gastric emptying was reduced with respect to the CTR, SH and I/R groups. Carbachol (CCh) and electrical field (EFS, 0.1–40 Hz) stimulated contractions and EFS-induced (10 Hz) NANC relaxations were reduced in the I/R group with respect to both CTR and SH groups. After I/R, 4-MU treatment increased EFS contractions towards control values, but did not affect CCh-induced contractions. NANC on-relaxations after I/R were not influenced by 4-MU treatment. Main alterations in the neurochemical coding of both excitatory (tachykinergic) and inhibitory pathways (iNOS, VIPergic) were also observed after I/R, and were influenced by 4-MU administration. Overall, our data suggest that, after an intestinal I/R damage, changes of HA homeostasis in specific myenteric neuron populations may influence the efficiency of the gastrointestinal transit. We cannot exclude that modulation of HA synthesis in these conditions may ameliorate derangement of the enteric motor function preventing, at least in part, the development of dysmotility.

Aim: To determine whether transcutaneous electrical nerve stimulation (TENS) is more efficient than placebo TENS and control groups for pain relief. Design: Randomized, single-blinded, placebo-controlled trial. Setting & participants: A total of 78 adults with postoperative pain, after cholecystectomy, at the University Hospital. They were randomized into active TENS, placebo TENS and control. Intervention: A total of 30-min interventions applied in the first 24 h after the surgery. Outcome: Pain intensity. Results: Pain significantly decreased for both TENS; however, the active TENS was better. A decrease of 2 points or more on the visual analog scale for 53.8% active TENS and 11.5% placebo. Conclusion: There was a greater reduction in pain of important clinical relevance in the active TENS group. Clinical Trial registration: Brazilian Clinical Trial (REBEC): RBR-6cgx2k.

Summary Purpose Aim was to stratify the knee MRIs of the Foundation for National Institutes of Health Osteoarthritis Biomarkers Consortium (FNIH) cohort into distinct structural phenotypes based on semiquantitative assessment and to determine risk for pain and structural progression over 48 months. Methods The study sample from the FNIH project was selected as a nested case–control study with knees showing either 1) radiographic and pain progression (i.e., "composite" cases), 2) radiographic progression only ("JSL"), 3) pain progression only, and 4) neither radiographic nor pain progression. MRI was performed on 3T systems. MRIs were read according to the MOAKS scoring system. Knees were stratified into subchondral bone, cartilage/meniscus and inflammatory phenotypes using the baseline visits. The relation of each phenotype to risk of being in the combined JSL plus composite outcome or composite case only group compared to those not having that phenotype was determined using logistic regression. Only KL2 and 3 and those without root tears were included. Results 485 knees were included. 362 (75%) did not have any phenotype, while 95 (20%) had the bone phenotype, 22 (5%) the cartilage/meniscus phenotype and 19 (4%) the inflammatory phenotype. The bone phenotype was associated with a higher odds of the combined JSL plus composite outcome and composite outcome only (OR 1.81; [95%CI 1.14,2.85] and 1.65; 95%CI [1.04,2.61]) while the inflammatory (OR 0.96 [95%CI 0.38,2.42] and 1.25; 95%CI [0.48,3.25]) and the cartilage/meniscus phenotypes were not significantly associated with outcome (OR 1.30 95%CI [0.55,3.07] and 0.99; 95%CI [0.40,2,49]). Conclusions The bone phenotype was associated with increased risk of having both radiographic and pain progression. Phenotypic stratification may be useful to consider when selecting patients for inclusion in clinical trials.

Objective To describe the frequency and the distribution of degenerative disc disease (DDD) detected in athletes who underwent spine MRI in the 2016 Summer Olympic Games in Rio de Janeiro. Methods Data on spine MRI examinations from the 2016 Summer Olympics were retrospectively analyzed. We assessed the frequency of DDD of the cervical (Cs), thoracic (Ts), and lumbar (Ls) spine using Pfirrmann’s classification. Grade II and III were considered as mild, grade IV as moderate, and grade V as severe disc degeneration. Data were analyzed according to the location of the degenerative disc, type of sport, age-groups, and gender of the athletes. Results One hundred out of 11,274 athletes underwent 108 spine MRI’s (21 C, 6 T, and 81 L) (53% Females (F), 47% Males (M)). The frequency of DDD was 40% (42% F, 58% M) over the entire spine (28% mild, 9% moderate and 3% severe). There were 58% (12%F, 88%M) of the cervical spine discs that showed some degree of degeneration (44% mild, 13.5% moderate and 1% severe). Athletics, Boxing, and Swimming were the sports most affected by DDD in the Cs. There were 12.5% of the thoracic discs that showed some degree of degeneration, all were mild DDD and were exclusively seen in female athletes. There were 39% (53% F, 47% M) of the lumbar discs with DDD (26% mild, 9% moderate, and 4% severe). Conclusion Athletes who underwent spine MRI during the 2016 Summer Olympic Games show a high frequency of DDD of cervical and lumbar spines. Recognition of these conditions is important to develop training techniques that may minimize the development of degenerative pathology of the spine.

The purpose of this article is to describe knee abnormalities and the occurrence of MRI-detected sports-related knee abnormalities by evaluating MRI examinations performed during the Rio de Janeiro Olympic Games held in August 2016.There were 11,274 athletes at the Rio 2016 Olympic Games, and 113 of them underwent at least one knee MRI in the Olympic Village. Cartilage abnormalities, followed by meniscal tears and ligament sprains, were the most frequent abnormalities.