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BACKGROUND An increasing number of studies report the beneficial effects of regional hyperthermia in association with chemotherapy (CHT) and radiotherapy for the treatment of pancreatic cancer; in particular, the use of modulated electro-hyperthermia (mEHT) results in increased survival and tumor response. AIM To compare outcomes of CHT alone or in association with mEHT for the treatment of stage III and IV pancreatic cancer. METHODS This was an observational retrospective study; data were collected for patients with stage III-IV pancreatic cancer that were treated with CHT alone or in combination with mEHT from 2003 to 2019. A total of 158 patients were included in the study out 270 patients screened in four Italian hospitals; 58 (37%) of these received CHT + mEHT and 100 (63%) CHT. CHT was mainly gemcitabine-based regimens in both groups. RESULTS Overall (19.5 mo vs 11.02 mo, P < 0.001) and progression-free (12 mo vs 3 mo, P < 0.001) survival were better for the CHT + mEHT group compared to the CHT group. The association of mEHT resulted also in an improvement of tumor response with disease control rate 95% vs 58% (P < 0.001) at 3 mo. Toxicity was comparable in the two study groups, and mEHT related adverse events were limited in 8 patients presenting G1-2 skin burns. CONCLUSION The addition of mEHT to systemic CHT improved overall and progression-free survival and local tumor control with comparable toxicity.

Summary Background The triplet FOLFOXIRI (fluorouracil, leucovorin, oxaliplatin, and irinotecan) plus bevacizumab showed improved outcomes for patients with metastatic colorectal cancer, compared with FOLFIRI (fluorouracil, leucovorin, and irinotecan) plus bevacizumab. However, the actual benefit of the upfront exposure to the three cytotoxic drugs compared with a preplanned sequential strategy of doublets was not clear, and neither was the feasibility or efficacy of therapies after disease progression. We aimed to compare a preplanned strategy of upfront FOLFOXIRI followed by the reintroduction of the same regimen after disease progression versus a sequence of mFOLFOX6 (fluorouracil, leucovorin, and oxaliplatin) and FOLFIRI doublets, in combination with bevacizumab. Methods TRIBE2 was an open-label, phase 3, randomised study of patients aged 18–75 years with an Eastern Cooperative Oncology Group (ECOG) performance status of 2, with unresectable, previously untreated metastatic colorectal cancer, recruited from 58 Italian oncology units. Patients were stratified according to centre, ECOG performance status, primary tumour location, and previous adjuvant chemotherapy. A randomisation system incorporating a minimisation algorithm was used to randomly assign patients (1:1) via a masked web-based allocation procedure to two different treatment strategies. In the control group, patients received first-line mFOLFOX6 (85 mg/m2 of intravenous oxaliplatin concurrently with 200 mg/m2 of leucovorin over 120 min; 400 mg/m2 intravenous bolus of fluorouracil; 2400 mg/m2 continuous infusion of fluorouracil for 48 h) plus bevacizumab (5 mg/kg intravenously over 30 min) followed by FOLFIRI (180 mg/m2 of intravenous irinotecan over 120 min concurrently with 200 mg/m2 of leucovorin; 400 mg/m2 intravenous bolus of fluorouracil; 2400 mg/m2 continuous infusion of fluorouracil for 48 h) plus bevacizumab after disease progression. In the experimental group, patients received FOLFOXIRI (165 mg/m2 of intravenous irinotecan over 60 min; 85 mg/m2 intravenous oxaliplatin concurrently with 200 mg/m2 of leucovorin over 120 min; 3200 mg/m2 continuous infusion of fluorouracil for 48 h) plus bevacizumab followed by the reintroduction of the same regimen after disease progression. Combination treatments were repeated every 14 days for up to eight cycles followed by fluorouracil and leucovorin (at the same dose administered at the last induction cycle) plus bevacizumab maintenance until disease progression, unacceptable adverse events, or consent withdrawal. Patients and investigators were not masked. The primary endpoint was progression-free survival 2, defined as the time from randomisation to disease progression on any treatment given after first disease progression, or death, analysed by intention to treat. Safety was assessed in patients who received at least one dose of their assigned treatment. Study recruitment is complete and follow-up is ongoing. This trial is registered with Clinicaltrials.gov , NCT02339116 . Findings Between Feb 26, 2015, and May 15, 2017, 679 patients were randomly assigned and received treatment (340 in the control group and 339 in the experimental group). At data cut-off (July 30, 2019) median follow-up was 35·9 months (IQR 30·1–41·4). Median progression-free survival 2 was 19·2 months (95% CI 17·3–21·4) in the experimental group and 16·4 months (15·1–17·5) in the control group (hazard ratio [HR] 0·74, 95% CI 0·63–0·88; p=0·0005). During the first-line treatment, the most frequent of all-cause grade 3–4 events were diarrhoea (57 [17%] vs 18 [5%]), neutropenia (168 [50%] vs 71 [21%]), and arterial hypertension (25 [7%] vs 35 [10%]) in the experimental group compared with the control group. Serious adverse events occurred in 84 (25%) patients in the experimental group and in 56 (17%) patients in the control group. Eight treatment-related deaths were reported in the experimental group (two intestinal occlusions, two intestinal perforations, two sepsis, one myocardial infarction, and one bleeding) and four in the control group (two occlusions, one perforation, and one pulmonary embolism). After first disease progression, no substantial differences in the incidence of grade 3 or 4 adverse events were reported between the control and experimental groups, with the exception of neurotoxicity, which was only reported in the experimental group (six [5%] of 132 patients). Serious adverse events after disease progression occurred in 20 (15%) patients in the experimental group and 25 (12%) in the control group. Three treatment-related deaths after first disease progression were reported in the experimental group (two intestinal occlusions and one sepsis) and four in the control group (one intestinal occlusion, one intestinal perforation, one cerebrovascular event, and one sepsis). Interpretation Upfront FOLFOXIRI plus bevacizumab followed by the reintroduction of the same regimen after disease progression seems to be a preferable therapeutic strategy to sequential administration of chemotherapy doublets, in combination with bevacizumab, for patients with metastatic colorectal cancer selected according to the study criteria. Funding The GONO Cooperative Group, the ARCO Foundation, and F Hoffmann–La Roche.

Purpose: To explore the effects of hippotherapy for children with cerebral palsy (CP) with different ages, topographies and severities. Method: Before-after study with three longitudinal measurements: (T1) initial, (T2) 3-months, (T3) 6-months after T1. CP children (n=31) stratified by age (4-7; 8-12 years), severity (mild, moderate, severe), topography (hemiplegia, diplegia, quadriplegia), previous hippotherapy time (3-6m, 6 months) undertook their individual weekly 30-minute hippotherapy sessions. Postural control and balance (PCB) was the primary outcome; gross-motor function (GMF) and quality of life (QL) were the secondary outcomes. Results: Changes in PCB associated with changes in GMF. Older children, with mild severity and diplegia had higher PCB and GMF scores between T1 and T3. Age groups’ initial differences in QL disappeared after 6 months. The Rehabilitation Treatment Taxonomy (RTT) guided interpretation of effects. Conclusion: The positive changes in motor and psychosocial outcomes depended on children’s age, time in rehabilitation and type of CP.

Background: Previous studies on oxaliplatin and fluoropyrimidines as adjuvant therapy in older patients with stage III colon cancer (CC) produced conflicting results. Patients and methods: We assessed the impact of age on time to tumour recurrence (TTR), disease-free survival (DFS), cancer-specific survival (CSS), and overall survival (OS) in 2360 patients with stage III CC (1667 aged

Purpose To evaluate bridging stent geometry in patients who underwent branched endovascular aortic repair (B-EVAR) and to correlate the outcomes with intrinsic bridging stent characteristics aiming to identify the stent(s) that guarantees the best performance. Methods Pre-operative and post-operative computed tomography images of all patients undergoing B-EVAR between September 2016 and April 2019 were retrospectively analyzed. Following geometrical features were measured: target vessel take-off angle (TOA); longitudinal stent shortening; shape index (SI), intended as ratio between minimum and maximum diameter of the lumen cross sections, averaged on three segments: zone 1 (proximal stented zone), zone 2 (intermediate), and zone 3 (distal). Results Thirty-eight branches (8 right (RRA) and 8 left renal arteries (LRA), 11 superior mesenteric arteries (SMA), 11 celiac trunks (CTR)) were treated. Fluency (Bard Peripheral Vascular), COVERA (Bard Peripheral Vascular), and VBX (WLGore&Assoc) stent-grafts were implanted in 10, 12, and 16 branches, respectively. Pre-operative TOA was more acute in RRA and LRA when compared to CTR and SMA, and straightened in post-operative configuration (109.86 ± 28.65° to 150.27 ± 21.0°; P P = 0.08), whereas higher SI in VBX group was detected in zones 2 (P P P = 0.001). Conclusion Our early experience showed that the VBX stent offers greater stent circularity than the other devices even if a greater shortening has been observed drawing attention with regards to the decision of the nominal stent length.

In the article by De Amicis et al. entitled "Patients with Severe Obesity during the COVID- 19 Pandemic: How to Maintain an Adequate Multidisciplinary Nutritional Rehabilitation Program?" [Obes Facts. 2021, DOI: 10.1159/000513283], the author list is incorrect. The correct author list is: De Amicis R. Cancello R. Capodaglio P. Gobbi M. Brunani A. Gilardini L. Castelnuovo G. Molinari E. Barbieri V. Mambrini S.P. Battezzati A. Bertoli S. © 2021 S. Karger AG. All rights reserved.

Little is known about vitamin D status in older adults in South America, where exposures to ultra-violet radiation are high. We examined the distribution of serum 25-hydroxyvitamin D (25OHD) concentration and its determinants in a nationally representative sample of Brazilians aged 50 years and older. Explanatory variables included environment and individuals’ characteristics from the ELSI baseline survey (2015–16). Among the 2,264 participants (mean age = 62.6 years), the geometric mean of 25OHD concentration was 66.8 nmol/L. The prevalence of vitamin D deficiency (

Objective The aim of this study was to evaluate the mandibular and articular dynamics and the presence of complications associated with surgical or nonsurgical treatments of condylar fractures. Study Design Clinical trials that compared open reduction internal fixation and maxillomandibular fixation in patients with condylar fractures were included. We performed an electronic search of PubMed, Scopus, Cochrane Library, Web of Science, and LILACS (Latin American and Caribbean Health Sciences) databases starting from February 2017 and updated in January 2019 and found 467 articles. We evaluated methodologic quality by using the criteria from Cochrane's Collaboration Tool. Results After independent screening of abstracts, we assessed the full texts of 88 articles; 9 studies were included for qualitative synthesis; but only 8 were included for the meta-analysis. Four studies were considered to have high risk of bias, and 5 were considered to have low risk. The risk ratio (RR = 0.20; 95% confidence interval [CI] 0.13–0.32) was observed for complications. The quality of evidence, using GRADE software, was considered low for maximum mouth opening and protrusive movement and moderate for lateral excursion movement and complications. Conclusions This review suggested that open reduction internal fixation and maxillomandibular fixation are effective. However, surgical treatment presented higher objective parameters. Nonsurgical treatment presented a high index of complications, such as malocclusion, pain and deviation.

Introduction: Firearm injuries rank second in the deaths and deaths of people in the urban area. The severity of the injury varies according to the caliber of the weapon used and the distance between a weapon and a victim. The maxillofacial complex has been the target of this type of injury, due to the aggravating increase in the rates of violence, especially in large urban centers. This article presents a case of serious gunshot injury to the jaw. Presentation of Case: Male patient, victim of urban violence, shot by a firearm projectile in the face, presenting comminuted fracture in the mandible with the projectile housed in the posterior, upper medial region of the mandibular branch. Being the patient submitted to treatment of the mandibular fracture. Results: Patient submitted to erich bar installation, and maxillomandibular block and after regression of the face edema, under general anesthesia, the jaw fracture was fixed with a 2.4 reconstruction plate, with 60-day outpatient follow-up. satisfactorily. Discussion and Conclusion: The treatment of maxillofacial injuries by firearm projectiles is a great challenge for surgeons and still controversial in the literature, in relation to the type of approach, whether conservative or surgical, and in relation to the optimal time to perform a possible intervention, with With the advent of synthetic materials. The surgical approach has become the choice for the vast majority of cases of facial injuries caused by firearms.

A 42 year old patient was referred to the Department of Oral and Maxillofacial Surgery of the Federal University of Uberlândia, for treatment of mandibular fractures (condyles and symphysis), a victim of a run over. The symphysis was surgically approached, using as surgical access the pre-existing laceration in the submental region. Five days after discharge, the patient returned with dehiscence of the wound and physical examination showed infestation by larvae in the symphysis. Mechanical removal and debridement were performed under local anesthesia, where plate exposure was noted. The patient underwent oral ivermectin therapy, intravenous antibiotic therapy and a thorough debridement was performed under general anesthesia due to the invasion of deep spaces in the supra-hyoid region. After 2 weeks, it presented with purulent drainage at the site. The miniplates were replaced by a 2.4 mm reconstruction plate and antibiotic therapy was maintained. Due to the social risk, the patient remained hospitalized for 45 days, when he was discharged with outpatient return, but did not attend the returns.

Background Local ablation of pancreatic cancer has been suggested as an option to manage locally advanced pancreatic cancer (LAPC) although no robust evidence has been published to date to support its application. The aim of this study is to compare overall survival (OS) and progression-free survival (PFS) in patients receiving both radiofrequency ablation (RFA) and conventional chemoradiotherapy (CHRT) with patients receiving CHRT only. Methods This is a multicentre prospective randomized controlled trial (RCT). Patients with LAPC diagnosed by the Pancreas-Ablation-Team-Verona were randomly assigned to open RFA (Group A) or CHRT (Group B). Survival analyses were performed using the Kaplan-Meier method and compared using the log-rank test. Statistical significance was set at p Results One hundred LAPC patients were enrolled from January 2014 to August 2016. 33% of patients in Group A did not receive the designated procedure because of intraoperative findings of liver (18.7%) or peritoneal metastases (43.8%), or technical contraindications (37.5%). We did not observe any statistically significant survival benefit from RFA compared to CHRT, neither in terms of OS (medians of 14.2 months and 18.1 months, respectively, p = 0.639) nor PFS (medians of 8 months and 6 months respectively, p = 0.570). Mortality was nil and RFA-related morbidity was 15.6%. In 13% of subjects, conversion to surgery occurred (2 after RFA and 11 after CHRT). Conclusions This is the first RCT evaluating the impact of upfront RFA in the multimodal treatment of LAPC. Compared to CHRT, RFA alone did not provide any advantage in terms of OS or PFS. It could be considered as a therapeutic option for LAPC within a multimodal context and after neoadjuvant therapies.

This paper describes the steps taken to model a valency lexicon for Latin (Latin Vallex) according to the principles of the Linked Data paradigm, and to interlink its valency frames with the lexical senses recorded in a manually checked subset of the Latin WordNet. The valency lexicon and the WordNet share lexical entries and are part of the LiLa Knowledge Base, which interlinks multiple linguistic resources for Latin. After describing the overall architecture of LiLa, as well as the structure of the lexical entries of Latin Vallex and Latin WordNet, the paper focuses on how valency frames have been modeled in LiLa, in line with a submodule of the Predicate Model for Ontologies (PreMOn) specifically created for the representation of grammatical valency. A mapping of the valency frames and the WordNet synsets assigned to the lexical entries shared by the two resources is detailed, as well as a number of queries that can be run across the interoperable resources for Latin currently included in LiLa.

BackgroundMost cases of pancreatic ductal adenocarcinoma (PDAC) are asymptomatic in early stages, and the disease is typically diagnosed in advanced phases, resulting in very high mortality. Tools to identify individuals at high risk of developing PDAC would be useful to improve chances of early detection.ObjectiveWe generated a polygenic risk score (PRS) for PDAC risk prediction, combining the effect of known risk SNPs, and carried out an exploratory analysis of a multifactorial score.MethodsWe tested the associations of the individual known risk SNPs on up to 2851 PDAC cases and 4810 controls of European origin from the PANcreatic Disease ReseArch (PANDoRA) consortium. Thirty risk SNPs were included in a PRS, which was computed on the subset of subjects that had 100% call rate, consisting of 839 cases and 2040 controls in PANDoRA and 6420 cases and 4889 controls from the previously published Pancreatic Cancer Cohort Consortium I–III and Pancreatic Cancer Case-Control Consortium genome-wide association studies. Additional exploratory multifactorial scores were constructed by complementing the genetic score with smoking and diabetes.ResultsThe scores were associated with increased PDAC risk and reached high statistical significance (OR=2.70, 95% CI 1.99 to 3.68, p=2.54×10−10 highest vs lowest quintile of the weighted PRS, and OR=14.37, 95% CI 5.57 to 37.09, p=3.64×10−8, highest vs lowest quintile of the weighted multifactorial score).ConclusionWe found a highly significant association between a PRS and PDAC risk, which explains more than individual SNPs and is a step forward in the direction of the construction of a tool for risk stratification in the population.

Background.Idiopathic Pulmonary Fibrosis is a progressive disease with short life expectancy and no disease-modifying pharmacological therapy. The continuous refinement of animal models and the integration of in-vivo imaging techniques is fundamental for the selection of new antifibrotic drugs.Indocyanine Green (ICG), a fluorescent dye, was administered by oropharyngeal aspiration (OA) to mice with Bleomycin (BLM) to map the lung exposure.Methods.Female mice C57bl/6 were treated via OA with BLM+ICG or ICG. Animals were imaged at 7, 14 and 21 days either with the fluorescent system or Micro-CT. At each time point subsets of mice were sampled for ex-vivo assessment. Histological assessment of fibrosis by Ashcroft score, airspace enlargements and mean linear intercept (MLI) were evaluated at 7, 14 and 21 days. Leukocytes and cytokines were measured in bronchoalveolar lavage fluid. Results.Fluorescence imaging revealed a persistent lung signal in both groups until 21 days. In BLM+ICG group, Micro-CT detected a marked increase in hypo- and non-aerated tissues throughout the study. At later time points hyper-inflated tissue was detected. Histology revealed high Ashcroft score throughout the time-course with a prominent increase in airspace size and MLI at day 21. ICG mice had healthy lungs.Conclusions.We showed that ICG can be used as a tracer to map the distribution of BLM in lungs. However, BLM+ICG produced unexpected severe lung changes different from pure BLM model, such as emphysema-like features which progressively worsened. The multimodalities approach warranted characterization of the distinctive features of this new pulmonary fibrosis model and provided fundamentals for in-vivo translation.

Chronic bacterial infections are associated with changes in the immunosenescence process and immunological biomarkers can assist in monitoring these changes. The identification of this immunological profile is important because Chlamydia pneumoniae (C. pneumoniae) and Helicobacter pylori (H. pylori) infections are important factors of morbidity and mortality among the older adults. This study aimed to identify changes in the immunological profile in the presence of C. pneumoniae and H. pylori infections among community-dwelling older adults. This is a cross-sectional study that used data from 1432 participants from the Bambui Cohort Study of Aging, Minas Gerais, Brazil. The presence of immunoglobulin G (IgG) for C. pneumoniae and H. pylori was considered a dependent variable and assessed in the participants' serum using the enzyme-linked immunosorbent assay (ELISA). In assessing the immunological profile, the following inflammatory markers were considered: CXCL8, CXCL9, CXCL10, CCL2, CCL5, IL-1β, IL-6, IL-10, IL-12, TNF, and CRP. Associations were assessed by logistic regression, estimating odds ratios and confidence intervals (95%) using the Stata® V.13.1 software. The seroprevalence of anti-C. pneumoniae and anti-H. pylori antibodies was 55.9% and 70.3%, respectively. While high levels of anti-C. pneumoniae antibodies were associated with higher concentrations of CXCL10 and IL-10, higher levels of IL-1β and IL-6 were inversely associated with the titration of anti-H. pylori antibodies. The results characterize immunological profiles associated with these chronic infections and reinforce the potential effects of biomarkers on infections by these bacteria and on the immunosenescence process.

Background: Many bimanual activities are challenging for children with unilateral spastic cerebral palsy (USCP).Aims: To investigate hand use by children with USCP in daily activities of their inte...

Rare truncating BRCA2 K3326X (rs11571833) and pathogenic CHEK2 I157T (rs17879961) variants have previously been implicated in familial pancreatic ductal adenocarcinoma (PDAC), but not in sporadic cases. The effect of both mutations in important DNA repair genes on sporadic PDAC risk may shed light on the genetic architecture of this disease. Both mutations were genotyped in germline DNA from 2,935 sporadic PDAC cases and 5,626 control subjects within the PANcreatic Disease ReseArch (PANDoRA) consortium. Risk estimates were evaluated using multivariate unconditional logistic regression with adjustment for possible confounders such as sex, age and country of origin. Statistical analyses were two-sided with p values

O presente estudo procura verificar a relação entre os indicadores de desempenho ao final do primeiro ano do ensino superior e aqueles que resumem a performance final, quando da conclusão do Curso para os mesmos sujeitos. O que se quer, portanto, é verificar a validade preditiva que aquela variável tem para esta segunda. A intenção do estudo que se coaduna com tal objetivo surge da preocupação com a descoberta de indicadores que permitam um diagnóstico antecipado das tendências de desempenho acadêmico, permitindo, assim, atuação da Administração Universitária no sentido de intervir com ações de gestão acadêmica mais ativa para tratar dos casos tempestivamente. Para a realização da análise foi feito estudo de caso incidente sobre os dados dos ingressantes nos Cursos de Administração, Direito e Pedagogia de uma Universidade Federal no ano de 2009. Após coleta das informações de performance acadêmica dos sujeitos, operações para verificação de correlação foram feitas entre o desempenho na conclusão do primeiro ano e na conclusão do Curso para verificar se aquele fator antecipa este. O estudo de caso quali-quantitativo, com ênfase na segunda componente do título metodológico, identificou que em todos os recortes existe forte correlação (resultados de r variando entre 0.7 e 0.9) entre as variáveis, apontando que – ao menos para os casos em análise – o desempenho no primeiro ano seria forte preditor da tendência de desempenho global dos estudantes.

Background Brazil and England are 2 countries at different stages in their demographic, epidemiological, and nutritional transitions and with distinct socioeconomic and politic contexts, but with similar universal health systems. We aimed to examine disability and its association with objective anthropometric indicators of nutritional status, including BMI, waist circumference, and waist-to-height ratio, comparing older Brazilian and English adults. Methods We used cross-sectional data from 2 nationally representative aging studies. For Brazil, we included 9412 participants who participated in the baseline (2015-2016) of the Brazilian Longitudinal Study of Aging (ELSI-Brazil). The English data were from 8024 participants of the wave 6 (2012-2013) of the English Longitudinal Study of Aging (ELSA). Disability was defined as difficulty to perform at least 1 activity of daily living. We used logistic regression models to examine the association between anthropometric indicators and disability, adjusted for sociodemographic and health-related characteristics, considering the interaction term between each anthropometric indicator and country. Results All health-related characteristics were worse in Brazil than England, although the prevalence of disability was similar among Brazilian (17.85%) and English (16.27%) older adults. Fully adjusted models showed statistically significant interaction terms between country and anthropometric indicators. The strength of the associations in Brazil was weaker compared with England. All anthropometric indicators were positively associated with disability: elevated BMI, in Brazil (OR: 1.27; 95% CI: 1.06, 1.51) and in England (OR: 1.80; 95% CI: 1.51, 2.14); elevated waist circumference, in Brazil (OR: 1.21; 95% CI: 1.02, 1.44) and in England (OR: 1.90; 95% CI: 1.51, 2.37); and elevated waist-to-height ratio, in Brazil (OR: 1.20; 95% CI: 0.96, 1.52) and in England (OR: 1.83; 95% CI: 1.37, 2.44). Conclusions Elevated BMI and waist circumference increased the odds of disability in both populations. However, these associations were stronger in England than in Brazil.

Background: The COVID-19 pandemic is spreading all over the world, particularly in developed countries where obesity is also widespread. There is a high frequency of increased BMI in patients admitted to intensive care for SARS-CoV-2 infection with a major severity in patients with an excess of visceral adiposity. Patients at risk of severe SARS-CoV-2 acute respiratory syndrome are characterised by the high prevalence of pre-existing diseases (high blood pressure and cardiovascular disease, diabetes, chronic respiratory disease, or cancer), most of them typically present in severely obese patients. Indeed, the biological role of adipose tissue in sustaining SARS-CoV-2 infection is not completely elucidated. Summary: The forced isolation due to pandemic containment measures abruptly interrupted the rehabilitation programs to which many patients with severe obesity were enrolled. People affected by obesity, and especially those with severe obesity, should continue clinical rehabilitation programs, taking extra measures to avoid COVID-19 infection and reinforcing the adoption of preventive procedures. In this review, the available data on obesity and COVID-19 are discussed along with evidence-based strategies for maintaining the necessary continuous rehabilitation programs. Key Messages: Greater attention is needed for obese and severely obese patients in the face of the current COVID-19 pandemic, which represents a huge challenge for both patients and healthcare professionals. The adoption of new strategies to guarantee adequate and continuous multidisciplinary nutritional rehabilitation programs will be crucial to control the severity of SARS-CoV-2 infection in high-risk populations as well as the worsening of obesity-linked complications. Health authorities should be urged to equip hospitals with tools for the diffusion of telemedicine to maintain physician-patient communication, which is fundamental in chronic and complicated obese patients.

ObjectiveThe primary aim of this review is to verify whether the warning against the use of electromedical instruments in the cosmetic professional or medical cancer patient settings is consistent with evident oncological risks supported by experimentalin vitro/in vivostudies or anecdotal clinical reports, or any other reasonable statement.MethodsMEDLINE, PubMed, Embase, AMED, Ovid, Cochrane Controlled Trials Register, and Google Scholar databases were electronically searched. Data relating to research design, sample population, type of electro-cosmetic devices used, were extracted.ResultsThe search strategy identified 50 studies, 30 of which were potentially relevant.ConclusionsOur research is in favor of moderate periodical use of cosmetic medical devices in patients bearing tumors, in any stage, like in healthy people. Special consideration is dedicated to massage, manipulation, and pressure delivery upon the cytoskeleton of cancer cells that has proven to be sensitive to mechanical stress at least in some specific locally relapsing cancers such as osteosarcoma.

To evaluate the association between dentists’ profile and health work management with the performance of primary care dental teams in the Brazilian National Health System, both nationally and regionally. Secondary data analysis from a Brazilian National Programme that evaluated 18,114 Brazilian dental teams, working in the public sector, between 2013 and 2014. Twenty-four independent variables taken from dentists’ profile and dental team management characteristics were analysed to assess their influence on reported “dental team performance.” An estimated score was generated from their performance on 20 dental procedures by an item response theory model. Multiple linear regression models were performed for each Brazilian geographical region, separately and for the whole of Brazil. p values ≤ 0.05 were considered significant. Two variables related to dentists’ profile, “having graduate studies” ( β = 0.151 ) and “undertaking continuing professional development training” ( β = 0.101 ), were associated with enhanced dental team performance in all five Brazilian geographical regions and nationally. The dental team management variables of “having a flexible dental appointment list” ( β = 0.218 ) and “monitoring oral health indicators” ( β = 0.132 ) also contributed to improve team performance in each of the regions and nationally. Dentists’ profile influenced the performance of dental teams from south region more than the other regions. The findings suggest that continuing professional development, including postgraduate education, and strategic management characteristics are important for primary dental care performance and should be reflected in health policy initiatives in support of quality care. Regional factors could be considered for health care management.

This article aims to evaluate the joint and separate association between abdominal and general adiposity indicators and mortality. Data was collected from 1,366 older adults in the Bambuí Cohort Study of Aging with complete information for all variables of interest. The outcome variable was all-cause time until death; exposure variables were a body shape index (ABSI), waist circumference (WC), waist-to-height ratio (WHtR) and body mass index (BMI), assessed at the beginning of the study, and at the 3rd, 5th and 11th year of follow-up. Association between the quartiles of anthropometric indicators and mortality was calculated using an extended Cox proportional hazards model and adjusted for socioeconomic and behavioral confounding factors. Older adults in the 4th ABSI quartile had a higher risk of mortality regardless of BMI (1.27; 95%CI: 1.01-1.58), but this association was not observed in sensitivity analyses. Older adults in the 2nd, 3rd and 4th BMI quartiles had a lower risk of mortality, even when adjusted for WC or ABSI. WC and WHtR showed no association consistent with all-cause mortality after adjustment for confounding factors. Considering the loss of significance in the sensitivity analyses, ABSI’s predictive capacity for mortality is still weak. Thus, adopting ABSI in clinical practice or in epidemiological surveys, in conjunction or replacing BMI and WC, requires more in-depth studies. O estudo teve como objetivo avaliar a associação isolada e independente entre indicadores de adiposidade abdominal e índice de massa corporal (IMC) e mortalidade. O estudo usou dados de 1.366 idosos que tinham informações completos para todas as variáveis independentes no Estudo de Coorte de Idosos de Bambuí, Brasil. A variável dependente foi o tempo até o óbito por todas as causas, e as variáveis de exposição foram o índice de forma corporal (a body shape index - ABSI), circunferência de cintura (CC), razão cintura/estatura (RCE) e IMC, medidos na linha de base e aos 3º, 5º e 11º anos de seguimento. A associação entre os quartis de indicadores antropométricos e a mortalidade foi investigada usando um modelo estendido de riscos proporcionais de Cox ajustado por fatores de confusão socioeconômicos e comportamentais. Os idosos do 4º quartil do ABSI mostraram maior risco de mortalidade, independentemente de IMC (1,27; IC95%: 1,01-1,58), mas a associação não foi mantida nas análises de sensibilidade. Os idosos do 2º, 3º e 4º quartis de IMC mostraram risco menor de mortalidade, associação esta que foi mantida após ajustar para CC ou ABSI. Por outro lado, a CC e a RCE não mostraram associações consistentes com a mortalidade geral depois de ajustar para fatores de confusão. As análises mostraram que a capacidade preditiva do ABSI para mortalidade ainda é fraca, considerando a perda de significância nas análises de sensibilidade. Portanto, a possibilidade de adoção do ABSI na prática clínica ou em inquéritos epidemiológicos para complementar ou substituir o IMC e CC ainda precisa ser explorada com maior profundidade em estudos futuros. El objetivo de este artículo es evaluar la asociación conjunta y separada entre los indicadores de adiposidad abdominal y general, y la mortalidad. Los datos se recogieron de 1.366 adultos mayores en el estudio de Cohorte Ancianos de Bambuí, Brasil, con información completa para todas las variables de interés. El resultado de la variable fue por cualquier causa hasta la muerte; las variables de exposición fueron índice de forma corporal (a body shape index - ABSI por sus siglas en inglés), circunferencia de cintura (WC), proporción cintura-altura (WHtR) e índice de masa corporal (BMI), evaluados al principio del estudio, y en el 3º, 5º y 11º año de seguimiento. Se calculó la asociación entre los cuartiles de indicadores antropométricos y mortalidad, usando un modelo extendido de Cox de riesgos proporcionales, y ajustado por factores de confusión socioeconómicos y comportamentales. Los adultos más viejos en el 4º cuartil ABSI tuvieron un riesgo mayor de mortalidad, independientemente del BMI (1,27; 95%CI: 1,01-1,58), pero esta asociación no fue observada en los análisis de sensibilidad. Los adultos más viejos en los 2º, 3º y 4º cuartiles de BMI tuvieron un riesgo más bajo de mortalidad, incluso cuando fue ajustado por WC o ABSI. WC y WHtR no mostraron asociación consistente con todas las causas de mortalidad tras el ajuste para factores de confusión. Considerando la pérdida de significación en los análisis de sensibilidad, la capacidad predictiva de ABSI para la mortalidad es todavía débil. De este modo, adoptar ABSI en la práctica clínica o en encuestas epidemiológicas, en conjunción o reemplazando BMI y WC, requiere más estudios en profundidad.

Intraoral injuries affect the stomatognathic system, creating difficulties in mastication and speech articulation, especially when they affect the tongue. In this context, the quality of the suture and local care are important to proper recovery and the patient’s brief return to their normal functions. Oral lacerations resulting from trauma require specific approaches. Treatments of this type of trauma may primarily be performed by professionals who conduct emergency care; however, they may require the attention of specialists. This article contains recommendations for the primary approach, treatment, and postoperative care of complex lacerations in the tongue.

Resumo O objetivo foi estimar a prevalência e os fatores associados à queda grave em idosos brasileiros. Estudo transversal, incluindo 10.537 idosos participantes da Pesquisa Nacional de Saúde (2013). A variável dependente foi relato de queda grave último. As variáveis independentes incluíram, hierarquicamente, fatores sociodemográficos, comportamentais, condição de saúde e capacidade funcional. Foi utilizada regressão logística para obter os odds ratio (OR) e os respectivos intervalos de confiança (95%), utilizando-se o programa Stata 13.1. A prevalência de queda grave foi de 7,5% (IC95%: 6,7-8,3) e as maiores chances foram entre mulheres (OR: 1,35; IC95%: 1,03-1,77), 70 a 79 anos (OR: 1,47; IC95%: 1,12-1,95) e 80 anos e mais (OR: 2,00; IC95%: 1,46-2,74), vivendo sem cônjuge (OR: 1,37; IC95%: 1,08-1,74), sedentários no lazer (OR: 1,55; IC95%: 1,06-2,26), com multimorbidades (OR: 1,54; IC95%: 1,19-2,00), dificuldades no sono (OR: 2,18; IC95%: 1,65-2,88), limitações em atividades básicas de vida diária (OR: 2,25; IC95%: 1,63-3,10) e uso de dispositivo para marcha (OR: 1,89; IC95%: 1,30-2,73). A prevalência de queda grave foi elevada e multifatorial, permitindo a identificação de perfis de maior vulnerabilidade, o que deve ser considerado no direcionamento de políticas públicas para intervenções específicas. Abstract The scope of this study was to estimate the prevalence and factors associated with severe falls among elderly Brazilians. It included a transversal study of 10,537 elderly individuals who participated in the National Health Survey (2013). The dependent variable was a report of severe falls in the past year. The independent variables comprised, hierarchically, socio-demographic factors, behavior, health status and functional capacity. Logistic regression was used to obtain the odds ratio (OR) and the confidence interval (95%CI), using the 13.1 Stata program. The prevalence of severe falls was 7.5% (95%CI: 6.7-8.3) and the highest odds were among women (OR: 1.35; 95%CI: 1.03-1.77), 70 to 79 years of age (OR: 1.47; 95%CI: 1.12-1.95) and 80 years and above (OR: 2.00; 95%CI: 1.46-2.74), living without a spouse/partner (OR: 1.37; 95%CI: 1.08-1.74), sedentary in leisure time (OR: 1.55; 95%CI: 1.06-2.26), having multimorbities (OR: 1.54; 95%CI: 1.19-2.00), sleeping difficulties (OR: 2.18; 95%CI: 1.65-2.88), limitations in daily activities (OR: 2.25; 95%CI 1.63 -3.10) and use of a walking aid (OR: 1.89; 95%CI: 1.30-2.73). The prevalence of severe falls was high and multifactorial, enabling the identification of profiles of greater vulnerability, which should be considered in public policies for specific interventions.

Background Pancreaticoduodenal cancer (PDC) is a group of malignant tumors arising in the ampullary region, which lack approved targeted therapies for their treatment. Methods This retrospective, observational study is based on Secondary Data Use (SDU) previously collected during a multicenter collaboration, which were subsequently entered into a predefined database and analyzed. FoundationOne CDx or Liquid, a next-generation DNA sequencing (NGS) service, was used to identify genomic alterations of patients who failed standard treatments. Detected alterations were described according to ESMO Scale of Clinical Actionability for molecular Targets (ESCAT). Results NGS analysis was performed in 68 patients affected by PDC. At least one alteration ranking tier I, II, III, or IV according to ESCAT classification was detected in 8, 1, 9, and 12 patients respectively (44.1%). Ten of them (33.3%) received a matched therapy. Patients with ESCAT tier I to IV were generally younger than the overall population (median = 54, range = 26–71 years), had an EGOG performance status score = 0 (83.3%), and an uncommon histological or clinical presentation. The most common mutations with clinical evidence of actionability (ESCAT tier I-III) involved genes of the RAF (10.3%), BRCA (5.9%) or FGFR pathways (5.9%). We present the activity of the RAF kinases inhibitor sorafenib in patients with RAF-mutated advanced PDC. Conclusions In advanced PDC, NGS is a feasible and valuable method for enabling precision oncology. This genomic profiling method might be considered after standard treatments failure, especially in young patients maintaining a good performance status, in order to detect potentially actionable mutations and offer molecularly targeted therapeutic approaches.

TheLiLaproject aims to build a Knowledge Base of linguistic resources for Latin based on the Linked Data framework, with the goal of creating interoperability between them. To this end, LiLa integrates all types of annotation applied to a particular word/text into a common representation where all linguistic information conveyed by a specific linguistic resource becomes accessible. The recent inclusion in the Knowledge Base of information on word formation raised a number of theoretical and practical issues concerning its treatment and representation. This paper discusses such issues, detailing how they are addressed in the project, and introduces the web application to query the collection of lemmas of the Knowledge Base. A number of use-case scenarios that employ the information on word formation made available in the LiLa Knowledge Base are also presented, particularly focusing on the use of the Knowledge Base to compare the perspectives on word formation in different linguistic resources.

Chronic infections, such as cytomegalovirus (CMV) and herpes simplex virus type 1 (HSV-1), contribute to the inflammation process among older adults and are associated with the immunosenescence process. The aim was to identify the immunological profile associated with CMV and HSV-1 infections among older adults. This is a cross-sectional study, carried out with 1492 participants from the Bambui Cohort Study of Aging – Minas Gerais, Brazil. For analysis purposes, we considered the presence of immunoglobulin G (IgG) for CMV and HSV-1 in the participants' serum, assessed by the enzyme-linked immunosorbent assay (ELISA); outcomes were defined by titration above the median (>160 UR/mL for HSV-1 and >399.5 U/mL for CMV). In order to assess the immunological profile, the following biomarkers were considered: IL-1beta, IL-10, IL-12, TNF, CXCL8, CXCL9, CXCL10, CCL2, CCL5, IL-6 and CRP; the first four being categorized as detectable levels or not, and the others using the Classification and Regression Tree (CART) method. The analysis was adjusted for sociodemographic variables, health behaviors and health conditions. The seroprevalence of anti CMV and anti HSV-1 antibodies was 99.4% and 97.0%, respectively. Higher concentrations of CXCL8 and CCL5 chemokines were associated with lower antibody titers for CMV, and higher concentrations of CXCL9, IL-6 and CRP were associated with higher levels of antibodies to CMV. Moreover, intermediate levels of CXCL10 were also associated with higher levels of antibodies to CMV. In HSV-1 infection, intermediate levels of CXCL9, CCL5 and IL-6 were less likely to have higher antibody titers for this infection. On the other hand, higher levels of CXCL10 and CRP were positively associated with higher antibody titers for HSV-1. The results describe important immunological changes and reinforce the potential effect of CMV and HSV-1 on the immunosenescence process.

Background: Cancer patients are more susceptible to infections and potentially at higher risk to develop COVID-19 Tumor type and antitumor treatment may also affect both the susceptibility to and the severity of SARS COV-2 Methods: To analyze the distribution of patients who developed COVID-19 during active antineoplastic therapy and the related clinical course by tumor type, stage and class of oncologic treatment (chemo, immune, biologic, other) a multicenter, retro-prospective, observational study was proposed to the Hospital Medical Oncologic Units of the National Health Service in Italy (168 centers of the Collegio Italiano dei Primari Oncologi Medici Ospedalieri -CIPOMO) Data were collected on demographics, tumor characteristics, treatment setting, type of ongoing anti-cancer therapy and COVID-19 clinical course (phenotype, hospitalization, therapy, duration and outcome) Eligibility required a positive COVID-19 molecular test before May 4th, 2020 and at least 1 course of antitumor therapy delivered after January 15th Results: At the present analysis data are available for 116 of 168 centers (7 declined, 28 pending, 17 data awaited) 64 of 116 centers (55%) had COVID-19 positive cases (cases /center: median 3, range 1-40) At these 64 centers, 283 positive cases (males 158, 55 9% - females 125, 44 1%;median age 67 years, range 28-89) were observed among a total population of 40894 patients receiving active treatment between January 15 and May 4 2020 65 of 283 (23%) had cardiovascular comorbidities and 7 (2%) pre-existent pulmonary disease 239/283 patients (84 4%) were receiving treatment for metastatic disease and 44 (15 6%) in the adjuvant setting Breast, lung, colon and prostate cancer were the main tumor types accounting for 61 % of cases Conclusions: The occurrence of COVID-19 among cancer patients receiving active antitumor treatment appears to reflect tumor epidemiology Full analysis of the distribution of COVID-19 occurrence and clinical course by tumor type, stage and oncologic treatment will be presented Legal entity responsible for the study: The authors Funding: Has not received any funding Disclosure: All authors have declared no conflicts of interest

Modelo de estudo: Relato de Caso. Importância do problema: As fraturas panfaciais recebem essa denominação quando os terços faciais apresentam fraturas concomitantes. Com frequência, essas lesões estão relacionadas a danos importantes aos tecidos moles, cominuição e perda de segmentos ósseos e/ou dentários, que podem gerar má oclusão e graves deformidades faciais, visto que etiologia de tal condição se deve à acidentes de alta dissipação de energia. O tratamento das fraturas panfaciais com o uso de fixação interna rígida permite restaurar as funções mastigatórias, bem como os contornos faciais. Comentários: O objetivo desse trabalho é relatar a reconstrução de uma fratura panfacial, envolvendo a mandíbula e com elevado grau de cominuição do complexo zigomático orbitário e do arco zigomático, em uma paciente do sexo feminino, em que acesso hemicoronal e retromandibular foram escolhidos para reconstrução e reestruturação do complexo facial. Conclusão: O correto manejo das fraturas panfaciais, é um dos grandes desafios do cirurgião buco maxilo facial, visto o nível de dificuldade para reestabelecer de maneira satisfatória as condições estéticas e funcionais existentes previamente ao trauma. Diferentes sequências de tratamento vêm sendo propostas, podendo ser utilizadas com sucesso após análise adequada do caso clínico e correta indicação.

RESUMO: Objetivo: Investigar a associação de variáveis contextuais e individuais com a hipertensão arterial sistêmica (HAS) em idosos brasileiros. Métodos: Estudo transversal com dados da Pesquisa Nacional de Saúde (2013) e do Atlas de Desenvolvimento Humano no Brasil. A HAS foi definida pela medida direta da pressão arterial e/ou pelo uso de medicamentos para essa condição. As variáveis independentes contextuais foram o Índice de Desenvolvimento Humano Municipal (IDHM) e o índice de Gini, por Unidade da Federação (UF). As variáveis independentes individuais incluíram fatores sociodemográficos, comportamentos em saúde, condições de saúde e uso de serviço de saúde. Utilizaram-se modelos logísticos multiníveis para o estudo dos fatores associados. Resultados: Entre os 10.211 participantes com 60 anos ou mais, a prevalência de HAS foi de 66,7% (IC95% 65,1 - 68,3). Após ajuste para todas as variáveis, a chance de HAS foi maior nas UF com maior IDHM, em mulheres, com 70 anos ou mais, não brancas, com uma ou mais doenças crônicas, com excesso de peso e circunferência da cintura aumentada e entre aqueles que realizaram quatro ou mais consultas médicas no ano anterior. Por outro lado, foi observada associação negativa entre HAS e escolaridade. Conclusão: O perfil individual associado à HAS foi semelhante ao já reportado na literatura, mas chama atenção que os idosos residentes nas UF de maior IDHM apresentaram maior chance de ter essa condição, sugerindo maior sobrevida dos hipertensos dessas regiões. ABSTRACT: Objective: To investigate the association of contextual and individual variables with systemic arterial hypertension (SAH) among elderly Brazilians. Methods: Cross-sectional study with data from the National Health Survey (2013) and the Atlas of Human Development in Brazil. SAH was defined by direct measurement of blood pressure and/or the use of medications for this condition. The contextual independent variables were the Municipal Human Development Index (MHDI) and the Gini Index, by Federation Unit. The individual independent variables included sociodemographic factors, health behaviors, health conditions, and the use of health service. Multilevel logistic models were used to study the associated factors. Results: Among the 10,211 participants aged 60 years and older, the prevalence of hypertension was 66.7% (95%CI 65.1 - 68.3). After adjusting for all variables, the chance of hypertension was higher in the Federation Units with the highest MHDI, in women, aged 70 years or older, in non-whites, with one or more chronic diseases, overweight and obesity, high waist circumference, and among those who had four or more medical appointments in the previous year. On the other hand, a negative association was observed between hypertension and education. Conclusion: The individual profile associated with hypertension was similar to what had already been reported in the scientific literature, but it is noteworthy that the elderly residing in the higher MHDI Federation Units were more likely to have this condition, suggesting a higher survival of hypertensive patients in these regions.

Background Children with congenital Zika syndrome (CZS) maintain severe motor impairments at the end of the first year of life. Presence of certain symptoms and comorbidities increase these children's vulnerability. Aims To evaluate gross motor function of a group of Brazilian children with CZS at 24 months of age and to investigate the association between the presence of CZS symptoms and comorbidities with gross motor development. Methods and procedures Fifty children with CZS participated in the study. Information was collected from medical charts, and gross motor development was evaluated by the Gross Motor Function Measure (GMFM)-88. GMFM-88 scores were compared among comorbid groups. Three subgroups of children were identified by cluster analysis, based on information from head circumference at birth, symptoms, comorbidities and gross motor function. Outcomes and results Significant associations (p < 0.001) were observed between number of comorbidities/symptoms and dimensions A (r = -0.57) and B (r = -0.58) of the GMFM-88. Children were grouped into 3 clusters, with different gross motor skills. Children with epilepsy and dysphagia composed the cluster with smaller median scores for dimensions A and B of the GMFM-88. Conclusions and implications The presence of CZS symptoms and comorbidities compromise the gross motor repertoire of children with CZS at 24 months., Neuroscience; Virology; Disability; Musculoskeletal system; Nervous system; Pediatrics; Health promotion; Zika virus; Microcephaly; Dysphagia; Epilepsy; Motor skills

Background Chagas disease is endemic in Latin America and still represents an important public health problem in the region. Chronic cardiomyopathy is the most significant chronic form due to its association with morbidity and mortality. The last decade has seen increasing evidence that inflammatory cytokines and chemokines are responsible for the generation of inflammatory infiltrate and tissue damage, with chronic chagasic cardiomyopathy patients presenting a pro-inflammatory immune response. Although studies have evaluated the role of chemokines in experimental T. cruzi infection, few have addressed their systemic profile, especially for human infection and in aging populations. The present work aimed to use the data from a large population based study of older adults, conducted in an endemic area for Chagas disease, to examine the association between serum levels of cytokines and chemokines, T. cruzi infection and electrocardiogram (ECG) abnormality. Methods The present work evaluated serum levels of CCL2, CXCL9, CXCL10, CCL5, CXCL8, IL-1β, IL-6, TNF, IL-12 and IL-10 by Flow Cytometric Bead Array assay (CBA) and the results expressed in pg/ml. The baseline survey started in January 1st 1997, with 1284 participants of an aged population-based cohort. Participants signed an informed consent at baseline and at each subsequent visit and authorized death certificate and medical records verification. Results Our results demonstrated that Chagas disease patients had higher serum levels of CXCL9, CXCL10 and IL-1β and lower serum levels of CCL5 than non-infected subjects. Moreover, our data demonstrated that CXCL9 and CXCL10 increased in an age-dependent profile in Chagas disease patients. Conclusion Together, this study provided evidences that serum biomarkers increase along the age continuum and may have potential implications for establishing clinical management protocols and therapeutic intervention in Chagas disease patients.

This study evaluated the factors associated with the performance of Brazilian Oral Health Teams (OHTs). This is multilevel research that used data from 12,386 Brazilian OHTs in 2012. The OHTs performance was estimated in previous research by using Item Response Theory model, which employed 20 questions about dental procedures in Primary Care. The first level covariates were based on OHTs procedures such as: the record of pregnant woman dental appointment, provision of dentistry home care, dental appointments scheduled choices, and OHTs in charge for more than 5000 individuals. Moreover, the use of guidelines was accessed concerning delivering prostheses in primary care, referring to secondary care, referring to suspected oral cancer, and providing care towards patients with special needs. Variables included in level 2 were GINI and Human Development Index. Multilevel linear regression models were constructed, estimating linear regression coefficients, 95% confidence intervals, and P values. OHTs performance was different among the 3,613 municipalities analyzed (P

Importance The addition of oxaliplatin to the standard 6-month fluorouracil-based adjuvant chemotherapy in stage II colorectal cancer has been reported to reduce the risk of relapse although it does not increase survival. The Three or Six Colon Adjuvant (TOSCA) trial compared 3 months with 6 months of adjuvant fluoropyrimidine and oxaliplatin-based chemotherapy in patients with stage III colon cancer. The utility remains unknown. Objective To assess the noninferiority and toxic effects of 3 vs 6 months of FOLFOX (fluorouracil, leucovorin, and oxaliplatin) or CAPOX (capecitabine plus oxaliplatin) adjunct chemotherapy among patients with high-risk stage II resected colorectal cancer enrolled in the TOSCA trial. Design, Setting, and Participants The TOSCA study was a noninferiority phase 3 randomized clinical trial conducted from June 2007 to March 2013 in 130 Italian centers. Included patients had resected colorectal cancer located 12 cm from the anal verge by endoscopy or above the peritoneal reflection at surgery. In this preplanned study assessing the per-protocol population, 5-year relapse-free survival was evaluated in 1254 patients with high-risk stage II resected colorectal cancer who had received adjuvant FOLFOX (fluorouracil, leucovorin, and oxaliplatin) or CAPOX (capecitabine plus oxaliplatin). Interventions Patients were originally randomized (1:1) in the TOSCA trial to receive 3 months (experimental group) or 6 months (control) of standard doses of FOLFOX or CAPOX at the discretion of the treating physician. Main Outcome and Measures A hazard ratio of at least 1.2 between the 3-month and 6-month chemotherapy groups was set to reject the null hypothesis of noninferiority. Results Overall, 1254 patients (mean [SD] age, 62.4 [9.8] years; 565 women [45.1%]) with clinical high-risk stage II resected colorectal cancer were analyzed at a median follow-up of 62 months (interquartile range, 53-71) months. Of them, 301 patients (24.0%) had pT4N0M0 tumors, and the remaining 953 patients (76.0%) had high-risk pT3N0M0 tumors; 776 patients (61.9%) received FOLFOX and 478 (38.1%) received CAPOX. The 5-year relapse-free survival was 82.2% for the 3-month arm and 88.2% for the 6-month arm, with an estimated hazard ratio of 1.41 (95% CI, 1.05-1.89;P = .86 for noninferiority). For CAPOX, the 5-year relapse-free survival was similar in the 2 arms (difference, 0.76% favoring the 6-month arm; 95% CI, −6.28% to 7.80%), whereas for FOLFOX, the difference was pronounced: 8.56% in favor of the longer-duration arm (95% CI, 3.45%-13.67%). Nevertheless, the test for an interaction between duration and regimen was not statistically significant. Neurotoxicity was approximately 5 times lower in the shorter duration arm than in the longer duration arm. Conclusions and Relevance In the 3-month arm, the treatment was significantly less toxic than in the 6-month arm. Noninferiority was not shown for 5-year relapse-free survival. However, a possible regimen effect was observed, suggesting that either 3 months of CAPOX or 6 months of FOLFOX therapy can be used whenever an oxaliplatin doublet is indicated for treatment of patients with stage II colorectal cancer. Trial Registration ClinicalTrials.gov Identifier:NCT0064660

The present study evaluates aneurysmal sac remodeling and the loss of the intercostal arteries after the first step of staged treatment of thoracoabdominal aortic aneurysms (TAAAs). The purpose of this approach is to keep the aneurysmal sac temporarily perfused to induce progressive thrombosis of the aneurysm while simultaneously allowing the spinal cord to establish adequate perfusion thereby promoting the development of collateral circulation.All patients with type II or type III TAAAs, having undergone 2-step endovascular treatment with at least a 2-branch endoprosthesis at our institution between April 2017 and May 2019, were retrospectively evaluated. Thirty-day mortality and spinal cord ischemia was assessed. The mean number of the intercostal and lumbar arteries, coverage length between the left subclavian artery and the stent graft proximal landing zone, total volume of the aneurysmal sac, lumen volume, and thrombosis volume were measured by preoperative and first-step postoperative computed tomography angiography. Patients were also grouped based on the chosen endoprosthesis (group A: double-branch aneurysmal sac reperfusion; group B: single-branch aneurysmal sac reperfusion).Eleven patients (mean age: 76.5 years; range: 61-86) were considered. No 30-day mortality was observed after the first-step procedure, and 1 patient died after second-step treatment. No permanent paraplegia was observed after either the first or second endovascular steps. The lumen volume significantly decreased (27%; P 0.001) after first-step endovascular treatment although there was a significant increase in aneurysm thrombosis (34% to 54%). The mean number of the intercostal arteries decreased from 19.7 to 9.3 (P 0.001) after first-step endovascular treatment. Volume variations and percentage of intercostal loss did not significantly differ between the 2 groups.Although aneurysm volume continued to increase after first-step treatment, two-step endovascular treatment is a feasible alternative to reduce the risk of severe ischemia in patients with extended TAAAs.

Resumo: O objetivo do estudo foi examinar a prevalência e fatores associados a ter saído para trabalhar durante a epidemia da COVID-19, entre adultos com 50 anos ou mais que exerciam trabalho remunerado antes do seu início. Foram utilizados dados da segunda onda do Estudo Longitudinal da Saúde dos Idosos Brasileiros (ELSI-Brasil), conduzida por meio de entrevista face a face, entre agosto de 2019 e março de 2020 (antes do início da epidemia), em amostra nacional representativa de adultos com 50 anos ou mais, e dados obtidos por meio de entrevistas telefônicas realizadas entre esses participantes (iniciativa ELSI-COVID-19), conduzidas entre 26 de maio e 8 de junho de 2020 (durante a epidemia). As análises foram baseadas nas odds ratios (OR) estimadas pela regressão logística. A média de idade dos participantes foi 59,9 anos (DP = 6,5). A prevalência de ter saído para trabalhar nos sete dias anteriores foi de 38,4% (IC95%: 31,3-46,1), 50,2% entre os homens e 25,1% entre as mulheres (trabalho formal, por conta própria e informal). Os resultados mostraram que, entre os homens, a chance de ter saído para trabalhar foi menor entre aqueles de 60 a 69 anos em comparação com aqueles de 50 a 59 anos (OR = 0,27; IC95%: 0,15-0,48). Entre as mulheres, a probabilidade de ter saído para trabalhar foi menor entre aquelas que trabalhavam por conta própria (OR = 0,28; IC95%: 0,12-0,64) ou tinham vínculo informal de trabalho antes da epidemia (OR = 0,25; IC95%: 0,09-0,69), em comparação àquelas com vínculo formal de trabalho. Uma das hipóteses para explicar essa associação é que as mulheres com vínculo informal tenham sido dispensadas e aquelas que trabalhavam por conta própria tenham deixado de trabalhar durante a epidemia.

The objectives of this 2-phase study were to elucidate pharmacokinetics (PK), in vivo 24-hour recovery, and red blood cell (RBC) survival properties of RBC-encapsulated dexamethasone sodium phosphate (DSP) prepared using the EryDex System (EDS). The 24-hour RBC recovery and T50 survival phase studied subjects were randomized to receive autologous RBCs loaded with either 15-20 mg DSP (Group 1A) or sham saline (Group 2A). Loaded RBCs were radiolabeled with 51-Cr, and the labeled RBCs were followed over time in vivo. The PK phase evaluated dose levels of 2.5-5 mg (Group 1B) and 15-20 mg (Group 2B) DSP encapsulated in RBCs infused into healthy randomized subjects. The mean ± SD 24-hour RBC recovery was 77.9% ± 3.3% and 72.7% ± 10.5% for Groups 1A and 2A, respectively. The mean ± SD RBC life span was 84.3 ± 8.3 days in Group 1A and 88.9 ± 6.2 days in Group 2A. The PK phase actual DSP loading doses (mean ± SEM) were 4.2 ± 0.27 mg and 16.9 ± 0.90 mg in Groups 1B and 2B, respectively. Release of dexamethasone from RBCs in vivo peaked at 1 hour, and a sustained release of dexamethasone could be detected until 35 days after the single intravenous infusion in Group 2B. The mean RBC in vivo recovery for DSP-loaded processed cells compares similarly to the 24-hour recovery of regulated RBC products intended for transfusion. There was a minimal but acceptable adverse impact on the survival of EDS-processed RBCs. DSP-loaded autologous RBCs, prepared using the EDS, delivered a sustained dose of dexamethasone in vivo.

ObjectivesVaccine hesitancy may represent a barrier to effective COVID-19 immunisation campaigns. This study assesses individual, disease-specific and contextual factors associated with COVID-19 vaccine acceptance among a nationally representative sample of older Brazilian adults.DesignCross-sectional analysis of data from household interviews and a supplementary telephone survey.SettingBrazil and its five geographic regions.ParticipantsData are derived from 6584 individuals aged 50 years and over who participated in the second wave of the Brazilian Longitudinal Study of Aging.Primary and secondary outcome measuresSurvey-weighted multinomial logistic regression assesses factors associated with intending, not intending or being uncertain about one’s intention to vaccinate against COVID-19.FindingsSeventy-one per cent of study participants intend to receive a COVID-19 vaccine once available, while 17% (representative of nearly 9 million people) have no intention to vaccinate, and 12% are still undecided. Besides age, demographic and health-related factors related to COVID-19 severity and complications were not associated with intention to vaccinate. Those who most trusted social media or friends and family for COVID-19 information and those who did not trust any information source were 68% and 78% more likely to refuse vaccination, respectively, as compared with those who trusted official information sources. People who inconsistently used face masks when outside were 3.4 times more likely than consistent face mask users to intend to refuse vaccination. Higher municipal COVID-19 fatality rates were negatively associated with vaccine refusal.ConclusionsMost national COVID-19 immunisation strategies identify older individuals as among those prioritised for early vaccination, given their increased risk of more severe symptoms and complications of the disease. Because individual, disease-specific, and contextual factors were associated with vaccine acceptance, there is a clear need for multilevel and multichannel information and outreach campaigns to increase COVID-19 vaccine acceptance among vulnerable older populations.

Inflammation, particularly elevated IL-6 serum levels, has been associated with increased mortality risk, mostly in Caucasians. The influence of genetic ethno-racial background on this association is unknown. We examined associations between baseline serum levels of Interleukin-6 (IL-6) and other cytokines (IL1-2, TNF, IL-10, and IL1β) and chemokines (CCL2, CCL5, CXCL8, CXCL9 and CXCL10) with 15-year mortality in 1,191 admixed Brazilians aged 60years and over. Elevated IL6 level (but not other biomarkers) was associated with increased risk of deaths with fully adjusted hazard ratios of 1.51 (95% CI=1.15, 1.97), 1.54 (95% CI=1.20, 1.96) and 1.79 (95% CI=1.40, 2.29) for the 2nd, 3rd and the highest quartiles, respectively. Genomic African and Native American proportions did not modify the association (p>0.05). The discriminatory ability to predict death of a model based on IL-6 alone was similar as that of a comprehensive morbidity score (C statistics=0.59 and 0.60, respectively). The abilities of IL-6 and the morbidity score models to predict death remained stable for very long term after the baseline measurement. Our results indicate that genome-based African and Native American ancestries have no impact on the prognostic value of IL-6 for mortality.

Pancreatic ductal adenocarcinoma (PDAC) is a very aggressive tumor with a five-year survival of less than 6%. Chronic pancreatitis (CP), an inflammatory process in of the pancreas, is a strong risk factor for PDAC. Several genetic polymorphisms have been discovered as susceptibility loci for both CP and PDAC. Since CP and PDAC share a consistent number of epidemiologic risk factors, the aim of this study was to investigate whether specific CP risk loci also contribute to PDAC susceptibility. We selected five common SNPs (rs11988997, rs379742, rs10273639, rs2995271 and rs12688220) that were identified as susceptibility markers for CP and analyzed them in 2,914 PDAC cases, 356 CP cases and 5,596 controls retrospectively collected in the context of the international PANDoRA consortium. We found a weak association between the minor allele of the PRSS1-PRSS2-rs10273639 and an increased risk of developing PDAC (ORhomozygous = 1.19, 95% CI 1.02-1.38, p = 0.023). Additionally all the SNPs confirmed statistically significant associations with risk of developing CP, the strongest being PRSS1-PRSS2-rs10273639 (ORheterozygous = 0.51, 95% CI 0.39-0.67, p = 1.10 × 10-6 ) and MORC4-rs 12837024 (ORhomozygous = 2.07 (1.55-2.77, ptrend = 0.7 × 10-11 ). Taken together, the results from our study do not support variants rs11988997, rs379742, rs10273639, rs2995271 and rs12688220 as strong predictors of PDAC risk, but further support the role of these SNPs in CP susceptibility. Our study suggests that CP and PDAC probably do not share genetic susceptibility, at least in terms of high frequency variants.

Aim: The aim is to report clinical outcomes of hepatic intra-arterial (IACHT) and systemic chemotherapy (SCHT), followed by gemcitabine-based maintenance therapy (maintenance), for the treatment of relapsed or unresectable cholangiocarcinoma. Patients & methods: In this retrospective observational study, 145 cholangiocarcinoma patients were treated with Epirubicin-Cisplatin as IACHT associated with Capecitabine or 5-fluorouracil as SCHT. Maintenance was performed with gemcitabine-based schedule. Toxicity was assessed with NCI-CTCAE and tumor response with RECIST 1.1. Results: Tumor response was complete in 1%, partial in 20%, stable disease in 48% and progression in 31% of patients (3 months after therapy). The most frequent adverse events were: anemia (24%), nausea and vomiting (33%), alopecia (60%). Conclusion: Cholangiocarcinoma patients may benefit from IAHCT-SCHT. Maintenance may prolong clinical benefits. ClinicalTrials.gov registry Identifier: NCT01920503.

Objectives Item response theory (IRT) is a method used to design, analyze, and score tests, questionnaires, and similar instruments measuring abilities, attitudes, or other variables. The aim of this study was to assess the psychometric properties of dental care questions in the “Programa Nacional de Melhoria do Acesso e Qualidade da Atencao Basica—PMAQ-AB,” Brazil, using IRT. Methods Dentists in primary health care units in Brazil (n = 12,403) were interviewed face-to-face using a structured questionnaire. The questions were primarily dichotomous, with a no answer/do not know option. The items about dental care from a Brazilian national evaluation survey were analyzed using the IRT model (20 items). Oral health teams (OHTs) received scores that varied from the lowest performance level to the highest performance level. Scores for the Brazilian states and the Federal District were calculated to evaluate the regional distribution of OHT performance. Results The questions about dental care exhibited higher discrimination power for OHTs with below average performance. In general, the teams, including those with low performance, performed the actions, and procedures included in the questionnaire. Actions such as making prostheses and tracking and monitoring oral cancer cases characterized the high-performing teams. The performance of the teams distributed throughout the Brazilian states indicated that OHTs in the south and southeast performed better than OHTs in the rest of the country. Conclusions Although the analyzed items are insufficient to determine the performance of OHTs, the items related to prosthesis and oral cancer tend to discriminate high-performing OHTs from other OHTs.

Objective Health literacy has been related to health-related conditions and health outcomes. Studies examining the association of health literacy and anticoagulation have had variable results. We sought to investigate the relations of health literacy and percentage of time in therapeutic range (TTR) in a vulnerable Brazilian cohort at two hospital-based anticoagulation clinics. Methods We measured health literacy with the Short Assessment of Health Literacy for Portuguese-speaking Adults (SAHLPA-18) in 2015–2016. We identified the demographic and clinical characteristics associated with health literacy and related health literacy to TTR. Results We enrolled 422 adults prescribed chronic warfarin therapy in our observational study (median age 62.1 years; 58.8% women; monthly income $200.00). The prevalence of inadequate health literacy (score 0–14 points) was 72.3% with a median score of 12 (quartiles, Q1=10; Q3=15) on the SAHLPA-18. The median TTR was 66.1%. In the multivariable logistic analysis, cognitive impairment and assistance with taking warfarin were associated with inadequate health literacy. Prosthetic heart valves and more school years were associated with adequate health literacy. Our analyses showed no significant relation between health literacy and TTR, analysing health literacy as a categorical (adjusted OR 1.05; 95% CI 0.65 to 1.70) or continuous variable (Spearman’s coefficient 0.02; p=0.70). Conclusions Inadequate health literacy was highly prevalent in this impoverished Brazilian cohort receiving anticoagulation with warfarin. However, we did not identify an association between health literacy and TTR. Future investigations may consider the systemic factors that contribute towards successful anticoagulation outcomes for vulnerable patient cohorts with inadequate health literacy.