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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

As taxas de complicacoes na remocao de terceiros molares impactados varia de 4,6% a 30,9%. Mesmo que as complicacoes estejam sujeitas a acontecer, para evitar a incidencia das mesmas, o diagnostico cuidadoso e planejamento pre-cirurgico e de fundamental importância. O deslocamento dental para espacos fasciais contiguos, e um acidente raro com poucos casos descritos na literatura, tal condicao ocorre por exames clinico-radiograficos inadequados, a falta de conhecimentos da anatomia local, a acessos cirurgicos inadequados e a movimentos cirurgicos excessivos ou descontrolados. Quando tal situacao, se apresenta e necessario avaliacao meticulosa riscos/beneficios da remocao do elemento dentario, como estruturas anatomicas possivelmente envolvidas, risco de infeccao, tipo de acesso e possiveis complicacoes transcirurgico na busca do elemento dentario. O presente artigo relata o caso de remocao de terceiro molar do espaco submandibular devido a iatrogenia ocorrida durante o processo de extracao do mesmo, em um paciente jovem do genero masculino.

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.

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.

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.

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

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.

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.

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

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.

Telomere deregulation is a hallmark of cancer. Telomere length measured in lymphocytes (LTL) has been shown to be a risk marker for several cancers. For pancreatic ductal adenocarcinoma (PDAC) consensus is lacking whether risk is associated with long or short telomeres. Mendelian randomization approaches have shown that a score built from SNPs associated with LTL could be used as a robust risk marker. We explored this approach in a large scale study within the PANcreatic Disease ReseArch (PANDoRA) consortium. We analyzed 10 SNPs (ZNF676-rs409627, TERT-rs2736100, CTC1-rs3027234, DHX35-rs6028466, PXK-rs6772228, NAF1-rs7675998, ZNF208-rs8105767, OBFC1-rs9420907, ACYP2-rs11125529 and TERC-rs10936599) alone and combined in a LTL genetic score ("teloscore", which explains 2.2% of the telomere variability) in relation to PDAC risk in 2,374 cases and 4,326 controls. We identified several associations with PDAC risk, among which the strongest were with the TERT-rs2736100 SNP (OR = 1.54; 95%CI 1.35-1.76; p = 1.54 × 10-10 ) and a novel one with the NAF1-rs7675998 SNP (OR = 0.80; 95%CI 0.73-0.88; p = 1.87 × 10-6 , ptrend = 3.27 × 10-7 ). The association of short LTL, measured by the teloscore, with PDAC risk reached genome-wide significance (p = 2.98 × 10-9 for highest vs. lowest quintile; p = 1.82 × 10-10 as a continuous variable). In conclusion, we present a novel genome-wide candidate SNP for PDAC risk (TERT-rs2736100), a completely new signal (NAF1-rs7675998) approaching genome-wide significance and we report a strong association between the teloscore and risk of pancreatic cancer, suggesting that telomeres are a potential risk factor for pancreatic cancer.

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.

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.

BACKGROUND: Noninvasive ventilation (NIV) reduces intubation and mortality in patients with COPD exacerbation who present with respiratory failure, and the type of mask may affect its success. Our objective was to compare the performance of 3 different NIV masks in a lung model. METHODS: We set the lung simulator mechanics and respiratory rate, and tested a small oronasal mask, a total face mask, and a large oronasal mask. We added CO2 at a constant rate into the system and monitored the end-tidal carbon dioxide. We used a mechanical ventilator to deliver NIV in 8 different combinations of inspiratory effort, pressure support, and expiratory positive airway pressure. We measured end-tidal carbon dioxide mask leakage, tidal volume, trigger time, time to achieve 90% of the inspiratory target during inspiration, and excess inspiratory time. RESULTS: We presented the mean ± SD of the 8 simulated conditions for each mask. The mean ± SD leakage was higher for the total face mask (51 ± 6 L/min) than for the small oronasal mask (37 ± 5 L/min) and for the large oronasal mask (21 ± 3 L/min), P CONCLUSIONS: In this model, we found that the type of mask had no impact on CO2 washout or on most synchrony variables.

Introducao: A avaliacao do craving e importante para o tratamento de pacientes com Transtornos por uso de substâncias psicoativas. O objetivo deste estudo foi realizar a validacao do Alcohol Craving Questionnaire-Short Form Revised- Versao Brasileira (ACQ-SFR – Versao Brasileira). Metodos: Foi um estudo observacional transversal, com uma amostra nao aleatoria de 121 participantes alcoolistas, do sexo masculino, internados para desintoxicacao em unidade especializada. Os instrumentos utilizados foram: entrevista clinica com dados sociodemograficos e de padrao de uso de substâncias, MMSE, ACQ-SFR – Versao Brasileira, EAV do craving, BDI, BAI, estimulo visual indutor de craving. Resultados: Na analise fatorial, foram encontrados dois fatores: o fator 1 representa o craving pelo reforco positivo e negativo do alcool, e o fator 2, o proposito de consumir o alcool associado ao prazer. O alfa de Cronbach total foi de 0,91 (12 itens), o do Fator 1 foi 0,92 (8 itens) e o do Fator 2 foi 0,70 (3 itens). O total de pontos da escala foi correlacionado com a Escala Analogico-Visual (r=0,658; p

ObjectivesFirst, to assess the psychometric properties of key questions included in a public sector evaluation of primary dental care in Brazil; and second, to evaluate the performance of dental teams in relation to these items.MethodsSecondary analysis of a national primary care dataset monitoring quality and access to dental care. Data were collected through face-to-face interviews with representatives of dental teams participating in the 'National Programme for Improving Access and Quality of Primary Care'. Twenty-three mandatory questions about the dentists' reported delivery of dental procedures were included in the analysis. Item Response Theory (IRT) modelling was applied to measure the psychometric properties of the instrument-level of difficulty and discrimination parameter of each item-and then to estimate dental team performance scores based on these parameters. Based on IRT, possible scores ranged from -4 to +4.ResultsThree of the 23 mandatory items were removed due to poor internal consistency, resulting in a scale of 20 items for assessing dental team performance. The results showed variation in procedures delivered by the dental teams; whilst more than a half of the procedures were executed by at least 80% of the dental teams, those relating to dentures (partial/total) and frenectomy (lingual/labial) were performed by less than 30%. Amongst the 20 items included in the model, those related to partial/total dentures and oral cancer follow-up presented higher levels of difficulty and were less frequently provided. The items relating to the treatment of deciduous teeth and access to the dental pulp of permanent teeth had the highest discrimination parameters and, consequently, greater weight in the performance's score estimation; therefore, dental teams that did not perform these items had the lowest performance scores. In the present study, dental team performance scores ranged from -3.66 to +1.87 with a mean/median of -0.06/+0.01.ConclusionThe findings suggest that whilst the items within the instrument demonstrated some potential to discriminate between poor and very poor teams, they were ineffective in discriminating between poor and good teams. Whilst Brazilian dental teams perform many mandatory procedures, variation in the nature of their delivery of care requires further investigation to enhance service provision to the population.

RESUMO: Introdução: A inflamação exerce um importante papel no processo de envelhecimento. Objetivo: Este estudo transversal objetiva examinar a associação entre marcadores inflamatórios e a ocorrência de hospitalizações entre idosos, considerando fatores predisponentes e facilitadores do uso de serviços de saúde e condições de saúde como potenciais fatores de confusão. Métodos: Foram utilizados dados de 1.393 participantes (≥ 60 anos) da linha de base da coorte de Bambuí. Os marcadores considerados foram dez citocinas e quimiocinas (interleucina (IL)-1, IL-6, IL-10, IL-12, fator de necrose tumoral (TNF), CCL2, CCL5, CXCL8, CXCL9 e CXCL10). A variável de desfecho foi a ocorrência de uma ou mais hospitalizações nos 12 meses precedentes. Resultados: Níveis séricos elevados da IL-6 apresentaram associações significantes com a ocorrência de hospitalizações (razão de prevalência - RP = 1,38; intervalo de confiança - IC95% 1,01 - 1,87; e RP = 1,38; IC95% 1,01 - 1,88, para os tercis intermediário e superior, respectivamente). Níveis elevados da CXCL9 também apresentaram associações independentes com o desfecho (RP = 1,38; IC95% 1,02 - 1,89 e RP = 1,46; IC95% 1,07 - 2,00, respectivamente). Os demais marcadores não apresentaram associações estatisticamente significantes com a ocorrência de hospitalizações. Conclusão: Entre os 10 marcadores examinados, IL-6 e CXCL9 apresentaram associação com a ocorrência de hospitalizações. ABSTRACT: Introduction: Inflammation plays an important role in the aging process. Objective: This cross-sectional study aims to examine the association between inflammatory markers and hospitalizations among older adults, considering as potential confounding factors the predisposing and enabling factors for the use of health services and health conditions. Methods: We used data from 1,393 participants (≥ 60 years) in the baseline cohort from Bambuí. The markers assessed were ten cytokines and chemokines [interleukin (IL)-1, IL-6, IL-10, IL-12, tumor necrosis factor (TNF), CCL2, CCL5, CXCL8, CXCL9, and CXCL10]. The outcome variable was one or more hospitalizations in the preceding 12 months. Results: Elevated serum levels of IL-6 were significantly associated with hospitalizations [prevalence ratio (PR) = 1.38; confidence interval of 95% (95%CI) 1.02 - 1.87 and PR = 1.38; 95%CI 1.01 - 1.88 for the intermediate and highest tertiles, respectively]. High levels of CXCL9 were also independently associated with the outcome (PR = 1.38; 95%CI 1.01 - 1.89 and PR = 1.46; 95%CI 1.07 - 2.00, respectively). Other markers showed no statistically significant association with hospitalizations. Conclusion: Among the ten markers analyzed, only IL-6 and CXCL9 were associated with hospitalizations.

Background: The triplet FOLFOXIRI (fluorouracil, L-leucovorin, oxaliplatin, and irinotecan) plus bevacizumab showed improved outcomes of patients with metastatic colorectal cancer, when compared to FOLFIRI (fluorouracil, Lleucovorin, and irinotecan) plus bevacizumab. However, the actual benefit of the upfront exposure to the three cytotoxics when compared with a preplanned sequential strategy of doublets was not clear, as well as the feasibility and efficacy of therapies after progression. To this purpose, we aimed at comparing a pre-planned strategy of upfront FOLFOXIRI followed by the reintroduction of the same regimen after disease progression to a sequence of mFOLFOX6 (fluorouracil, L-leucovorin, and oxaliplatin) and FOLFIRI doublets, in combination with bevacizumab. Methods: TRIBE2 was an open-label, prospective, phase 3 randomised study of patients (aged 18-70 years with Eastern Cooperative Oncology Group [ECOG] performance status of 2 or less and aged 71-75 years with an ECOG performance status of 0), with unresectable, previously untreated metastatic colorectal cancer, who were recruited from 58 Italian Oncology Units. Patients were stratified according to center, ECOG performance status, primary tumour location and previous adjuvant chemotherapy, and randomly assigned (1:1) via a web-based procedure to two different strategies: first-line mFOLFOX6 plus bevacizumab followed by FOLFIRI plus bevacizumab after disease progression (control group) or FOLFOXIRI plus bevacizumab followed by the reintroduction of the same regimen after disease progression (experimental group). Combination treatments were administered up to 8 cycles followed by fluorouracil/L-leucovorin plus bevacizumab maintenance until disease progression, unacceptable adverse events, or consent withdrawal. Both patients and investigators were aware of treatment assignment. The primary endpoint was progression-free survival 2, defined as the time from randomization to disease progression on any treatment given after first disease progression or death, analysed by intention to treat. Safety was assessed in the population of patients who received at least one dose of their assigned treatment. The study recruitment was completed, and follow-up of participants is still ongoing. Findings: Between February 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). 81% of enrolled patients had a right-sided and/or RAS or BRAF mutated tumour. At data cut-off (July 30, 2019) the 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 (95% CI 15·1-17·5) in the control group (hazard ratio [HR] 0·74, 95% CI 0·63-0·88; p

The treatment of type A acute aortic dissection is a challenge for the surgeon, and serious late complications may occur even after surgical repair. We report treatment after a type A postdissection thoracoabdominal aneurysm in a patient who previously underwent ascending aortic reconstruction using a biological aortic valve and Dacron prosthetic graft implantation in emergency conditions. The multistaged approach involved removing the right kidney and performing a heterotopic autotransplantation in the left iliac fossa before positioning a fenestrated endograft (celiac trunk, superior mesenteric artery, and left renal artery). The final step should have been the implantation of an aorto-bifurcated endograft, which, however, was postponed because the patient was injured during rehabilitation therapy. After 12 months, the computed tomography angiography scan showed complete thrombosis of the false lumen associated with large iliac entry tear closure and aortic diameter stability. These findings prompted us to desist from completing the aorto-bi-iliac implantation. This case demonstrates that in selected patients in whom treatment of a postdissection thoracoabdominal aneurysm with fenestrated endoprosthesis requires a challenging revascularization of the renal artery, a heterotopic kidney transplant using a mini-invasive technique may represent a viable and sufficiently safe alternative that guarantees renal blood perfusion.

Background: There are interesting studies on glioma therapy with modulated electrohyperthermia (mEHT), which combines heat therapy with an electric field. Clinical researchers not only found the mEHT method feasible for palliation but also reported evidence of therapeutic response. Purpose: To study the efficacy and safety of mEHT for the treatment of relapsed malignant glioma and astrocytoma versus best supportive care (BSC). Methods: We collected data retrospectively on 149 patients affected by malignant glioma and astrocytoma. Inclusion criteria were informed consent signed; >18 years old; histological diagnosis of malignant glioma or astrocytoma; relapsed after surgery, adjuvant temozolomide-based chemotherapy, and radiotherapy; and indication for treatment with mEHT in palliative setting. mEHT was performed with capacitive coupling technique keeping the skin surface at 26°C and the tumor temperature at 40°C to 42.5°C for > 90% of treatment duration (20-60 minutes). The applied power was 40 to 150 W using a step-up heating protocol. Results from patients treated with mEHT were compared with those treated with BSC. Results: A total of 149 consecutive patients were enrolled in the study, 111 (74%) had glioblastoma multiforme (GBM), and 38 (26%) had astrocytoma (AST). mEHT was performed for 28 (25%) of GBM and 24 (63%) of AST patients. Tumor response at the 3-month follow-up was observed in 29% and 48% of GBM and AST patients after mEHT, and in 4% and 10% of GBM and AST patients after BSC, respectively. The survival rate at first and second year in the mEHT group was 77.3% and 40.9% for AST, and 61% and 29% for GBM, respectively. The 5-year overall survival of AST was 83% after mEHT versus 25% after BSC and 3.5% after mEHT versus 1.2% after BSC for GBM. The median overall survival of mEHT was 14 months (range 2-108 months) for GBM and 16.5 months (range 3-156 months) for the AST group. We observed 4 long-term survivors in the AST and 2 in the GBM group. Two of the long survivors in AST and 1 in GBM group were treated by mEHT. Conclusions: mEHT in integrative therapy may have a promising role in the treatment and palliation of relapsed GBM and AST.

O objetivo do trabalho foi identificar os pontos de corte dos marcadores inflamatórios que melhor discriminassem a ocorrência da síndrome metabólica entre idosos residentes na comunidade. Foram utilizados os dados da linha de base da coorte de idosos conduzida na cidade de Bambuí, Minas Gerais, Brasil. A exposição de interesse foi a presença da síndrome metabólica, definida pelo critério Adult Treatment Panel III, e os desfechos incluíram os seguintes marcadores inflamatórios: citocinas (IL-1β, IL-6, IL-10, IL-12 e TNF), quimiocinas (CXCL8, CXCL9, CCL2, CXCL10 e CCL5) e proteína C-reativa (PCR). A definição dos pontos de corte dos marcadores inflamatórios foi baseada no método Classification and Regression Tree (CART). As associações entre esses marcadores e a síndrome metabólica foram estimadas por modelos de regressão logística, obtendo-se odds ratio e intervalos de 95% de confiança (IC95%), considerando o ajustamento por fatores de confusão. A prevalência da síndrome metabólica foi de 49,1%, e os níveis de IL-1β, IL-12 e TNF não se mostraram associados a essa exposição. Após ajustamento, a presença da síndrome metabólica foi associada a maiores valores de IL-6 e PCR e a menores valores de CXCL8 e CCL5. Associações significativas ainda foram observadas com níveis séricos intermediários de CXCL9 e CXCL10. Além disso, a combinação dos marcadores apresentou associação significativa e consistente com a síndrome metabólica. Além de demonstrar associação entre síndrome metabólica e uma ampla gama de biomarcadores, alguns ainda não descritos na literatura, os resultados ressaltam que essa associação ocorre em níveis muito inferiores aos já demonstrados, sugerindo que a síndrome metabólica desempenha importante papel no perfil inflamatório dos idosos. El objetivo del trabajo fue identificar los puntos de corte de los marcadores inflamatorios que mejor discriminaran la ocurrencia del síndrome metabólico entre ancianos residentes en comunidades. Se utilizaron datos de referencia de una cohorte de ancianos, realizada en la ciudad de Bambuí, Minas Gerais, Brasil. La exposición de interés fue la presencia del síndrome metabólico, definida por el criterio Adult Treatment Panel III, y los desenlaces incluyeron los siguientes marcadores inflamatorios: citocinas (IL-1β, IL-6, IL-10, IL-12 e TNF), quimiocinas (CXCL8, CXCL9, CCL2, CXCL10 y CCL5) y proteína C-reactiva (PCR). La definición de los puntos de corte de los marcadores inflamatorios se basó en el método Classification and Regression Tree (CART). Las asociaciones entre esos marcadores y el síndrome metabólico se estimaron mediante modelos de regresión logística, obteniéndose odds ratio e intervalos con 95% de confianza, considerando el ajuste por factores de confusión. La prevalencia del síndrome metabólico fue de 49,1%, y los niveles de IL-1β, IL12 y TNF no se mostraron asociados a esa exposición. Tras el ajuste, la presencia del síndrome metabólico se asoció a mayores valores de IL-6 y PCR y a menores valores de CXCL8 y CCL5. Las asociaciones significativas se observaron incluso con niveles séricos intermedios de CXCL9 y CXCL10. Asimismo, la combinación de los marcadores presentó una asociación significativa y consistente con el síndrome metabólico. Además de demostrar asociación entre el síndrome metabólico y una amplia gama de biomarcadores, algunos todavía no descritos en la literatura, los resultados resaltan que esa asociación ocurre en niveles muy inferiores a los ya demostrados, sugiriendo que el síndrome metabólico desempeña un importante papel en el perfil inflamatorio de los ancianos. The study aimed to identify the cutoff points for inflammatory markers that best discriminate the occurrence of metabolic syndrome in community-dwelling older adults. Baseline data were used from the elderly cohort in the city of Bambuí, Minas Gerais State, Brazil. The target exposure was presence of metabolic syndrome, defined according to the Adult Treatment Panel III criterion, and the outcomes included the following inflammatory markers: cytokines (IL-1β, IL-6, IL-10, IL-12 e TNF), chemokines (CXCL8, CXCL9, CCL2, CXCL10, and CCL5), and C-reactive protein (CRP). Definition of the cutoff points for the inflammatory markers was based on the Classification and Regression Tree (CART) method. The associations between these markers and metabolic syndrome were estimated by logistic regression models, obtaining odds ratios and 95% confidence intervals, considering adjustment for confounding factors. Prevalence of metabolic syndrome was 49.1%, and IL-1β, IL-12, and TNF levels were not associated statistically with this exposure. After adjustment, presence of metabolic syndrome was associated with higher IL-6 and CRP levels and lower CXCL8 and CCL5. Significant associations were also observed with intermediate serum CXCL9 and CXCL10 levels. The combination of markers also showed a significant and consistent association with metabolic syndrome. In addition to demonstrating an association between metabolic syndrome and a wide range of biomarkers (some not previously described in the literature), the results highlight that this association occurs at much lower levels than previously demonstrated, suggesting that metabolic syndrome plays an important role in the inflammatory profile of the older adults.

Vascular surgeons play an important role in surgical oncology. Outcomes of surgical oncology could be improved by increasing the radicality and safety of surgical procedures and, in selected cases, by broadening the range of surgical indications. A detailed collegial discussion of the individual case during oncological disease management team (DMT) meetings is equally important in order to accurately plan the surgery. Cooperation among the various specialists is the only way to broaden indications and improve outcomes. Despite the appealing possibility of dealing with injuries of almost any kind, oncological and surgical common sense is the main criterion when establishing indications to surgery.

Pancreatic cancer is the fourth leading cause of cancer death in the developed world. Both inherited high-penetrance mutations in BRCA2 (ref. 2), ATM, PALB2 (ref. 4), BRCA1 (ref. 5), STK11 (ref. 6), CDKN2A and mismatch-repair genes and low-penetrance loci are associated with increased risk. To identify new risk loci, we performed a genome-wide association study on 9,925 pancreatic cancer cases and 11,569 controls, including 4,164 newly genotyped cases and 3,792 controls in 9 studies from North America, Central Europe and Australia. We identified three newly associated regions: 17q25.1 (LINC00673, rs11655237, odds ratio (OR) = 1.26, 95% confidence interval (CI) = 1.19-1.34, P = 1.42 × 10(-14)), 7p13 (SUGCT, rs17688601, OR = 0.88, 95% CI = 0.84-0.92, P = 1.41 × 10(-8)) and 3q29 (TP63, rs9854771, OR = 0.89, 95% CI = 0.85-0.93, P = 2.35 × 10(-8)). We detected significant association at 2p13.3 (ETAA1, rs1486134, OR = 1.14, 95% CI = 1.09-1.19, P = 3.36 × 10(-9)), a region with previous suggestive evidence in Han Chinese. We replicated previously reported associations at 9q34.2 (ABO), 13q22.1 (KLF5), 5p15.33 (TERT and CLPTM1), 13q12.2 (PDX1), 1q32.1 (NR5A2), 7q32.3 (LINC-PINT), 16q23.1 (BCAR1) and 22q12.1 (ZNRF3). Our study identifies new loci associated with pancreatic cancer risk.

Objective: To investigate the moderating effect of an increasing number of clustered metabolic syndrome (MetS) components on the association between MetS and depressive symptoms in a population-based cohort of older adults in Brazil. Methods: This analysis used data from the Bambuí Cohort Aging Study. Participants in this cross-sectional study comprised 1,469 community-dwelling older people aged ≥ 60 years. Analyses were performed to assess both the association between depressive symptoms and each individual MetS component and the association between depressive symptoms and clustering of an increasing number of MetS components. Results: High triglyceride level was the individual component that showed the strongest association with depressive symptoms (odds ratio [OR]: 1.47; 95% confidence intervals [95%CI] 1.19-1.81; p < 0.0001). Only the presence of three MetS components was associated with depressive symptoms (OR = 1.53; 95%CI 1.05-2.23; p = 0.025). No graded association was detected between increasing number of clustered MetS components and depressive symptoms. Conclusions: Increasing the number of MetS components did not impact the association with depressive symptoms. The association between high triglyceride level and depressive symptoms highlights the relevance of lipid metabolism abnormalities for the emergence of depressive symptoms in older adults.

Purpose Adjuvant chemotherapy improves survival of patients with gastric cancer. Intergroup Trial of Adjuvant Chemotherapy in Adenocarcinoma of the Stomach (ITACA-S) was a phase III study comparing sequential FOLFIRI followed by docetaxel/cisplatin versus 5-fluorouracil monotherapy. The intensive regimen was not superior in terms of disease-free survival (DFS) and overall survival (OS). Methods The treatment was to be started within 8 weeks from surgery. This analysis evaluates the impact of time from surgery to chemotherapy start (TSC) on outcomes. Results Out of 1,106 randomized, 1,072 patients without major violations of eligibility criteria and receiving at least one treatment cycle were analyzed. Median TSC was 50 days. Chemotherapy was interrupted in 201 (18.8%) cases, whereas it was completed without or with modifications in 277 (25.8%) and 594 (55.4%), respectively. At a median follow-up of 56.9 months, 513 progressions and 472 deaths occurred. A longer TSC was significantly associated with longer DFS (hazard ratio [HR] 0.95; 95% confidence interval [CI] 0.89-1.00; p = 0.05) and OS (HR 0.91; 95% CI 0.86-0.97; p = 0.004), after adjustment for treatment arm, age, sex, primary tumor site, number of resected nodes, and tumor stage. Better treatment compliance was associated with improved survival. Conclusions Our findings suggest that longer TSC had at least no detrimental effect on DFS and OS, whereas treatment completion had a protective effect. Our findings need to be confirmed prospectively.

Ameloblastoma is a benign odontogenic tumor that is locally invasive and that grows slowly. Its etiology is not completely understood, and the types of treatment are widely discussed. Because it is an aggressive tumor, it has a high percentage of recurrence. Patients with multicystic ameloblastoma have been treated in many ways from enucleation and curettage to more aggressive resections, with or without loss of bone continuity. This study aims to report a case of multicyst ameloblastoma located in the mandible of a 16-year-old female patient with notable facial asymmetry and treated by marsupialization followed by surgical enucleation as a conservative approach. At the last clinic visit 2 years after the surgery, a radiographic examination was performed, and the lesion recurrence was not verified. The importance of clinical follow-up in cases of ameloblastoma is evident given the high recurrence rates of this lesion.

Background We report endovascular treatment of a patient with an isolated Internal Iliac Artery (IIA) aneurysm who was treated by positioning a novel covered stent that could adapt to different proximal and distal diameters. Case report A 68-year-old man who had already had several previous aortic surgeries underwent endovascular treatment for a 41 mm isolated right IIA aneurysm. Two Viabahn VBX (W. L. Gore & Associates, Flagstaff, AZ) covered stents (7 × 79 mm and 8Lx59 mm) were placed from a 6 mm gluteal artery to an 11 mm Dacron hypogastric artery via contralateral femoral surgical access. No complications occurred. One-month follow-up computed tomography angiography (CTA) scan showed the complete exclusion of the aneurysmal sac with spontaneous endoleak resolution and patency of the covered stents. Geometric analysis of the postoperative CTA highlighted VBX conformability to the native vessel. Maximum stented vessel diameter ranged between 9 and 13 mm, and circularity was maintained along the whole stent length, even in zones of higher centerline curvature. Conclusions The Viabahn VBX covered stent could be used to treat aneurysms of the IIA.

Telomere deregulation is a hallmark of cancer. Telomere length measured in lymphocytes (LTL) has been shown to be a risk marker for several cancers. For pancreatic ductal adenocarcinoma (PDAC) consensus is lacking whether risk is associated with long or short telomeres. Mendelian randomization approaches have shown that a score built from SNPs associated with LTL could be used as a robust risk marker. We explored this approach in a large scale study within the PANcreatic Disease ReseArch (PANDoRA) consortium. We analyzed 10 SNPs (ZNF676-rs409627, TERT-rs2736100, CTC1-rs3027234, DHX35-rs6028466, PXK-rs6772228, NAF1-rs7675998, ZNF208-rs8105767, OBFC1-rs9420907, ACYP2-rs11125529 and TERC-rs10936599) alone and combined in a LTL genetic score ("teloscore", which explains 2.2% of the telomere variability) in relation to PDAC risk in 2,374 cases and 4,326 controls. We identified several associations with PDAC risk, among which the strongest were with the TERT-rs2736100 SNP (OR = 1.54; 95%CI 1.35-1.76; p = 1.54x10-10 ) and a novel one with the NAF1-rs7675998 SNP (OR = 0.80; 95%CI 0.73-0.88; p = 1.87x10-6 , ptrend = 3.27x10-7 ). The association of short LTL, measured by the teloscore, with PDAC risk reached genome-wide significance (p = 2.98x10-9 for highest vs. lowest quintile; p = 1.82x10-10 as a continuous variable). In conclusion, we present a novel genome-wide candidate SNP for PDAC risk (TERT-rs2736100), a completely new signal (NAF1-rs7675998) approaching genome-wide significance and we report a strong association between the teloscore and risk of pancreatic cancer, suggesting that telomeres are a potential risk factor for pancreatic cancer. This article is protected by copyright. All rights reserved.

Background Acute kidney injury (AKI) is associated with a significant increase in morbidity, mortality, and health care costs. In intensive care units (ICU), AKI is commonly multifactorial and frequently involves diverse factors, such as hypovolemia, sepsis, and the use of nephrotoxic drugs. We aimed to investigate drug therapy and other factors associated with the development of AKI in a Brazilian public hospital. Methods This is a cross-sectional study involving critically ill patients at an ICU of a tertiary hospital. All data on sequential serum creatinine (SCr) level, glomerular filtration rate (GFR), and urine output were collected during ICU stay. The primary outcome was the occurrence of AKI assessed by the Acute Kidney Injury Network (AKIN) criterion. Sociodemographics, clinical data and drug therapy were considered as covariates. Factors associated with AKI were assessed using logistic regression. Results Overall, 122 participants were included in the study. Median age was 46.0 (interquartile range, IQ = 29.0–69.0) years, with a predominance of men (58.2%). Mean number of prescribed drugs throughout ICU stay was 22.0 ± 9.4. The number of potentially nephrotoxic drugs ranged from two to 24 per patient. A total of 29 (23.8%) ICU patients developed AKI. In the AKI-group, patients were older and showed higher Acute Physiology and Chronic Health Evaluation II (APACHE II) scores at admission, higher rates of sedation, mechanical ventilation, and infection. More drugs in general and specifically more vasoactive drugs were prescribed for AKI group. Patients who developed AKI tended to have extended stays in the ICU and a lower probability of being discharged alive than patients with no AKI development. Model adjustments of logistic regression showed that the number of medications (OR 1.15; 95% CI [1.05–1.27]) was the only factor associated with AKI in this study. This association was independent of drug nephrotoxicity. Discussion Intensive care is characterized by its complexity that combines unstable patients, severe diseases, high density of medical interventions, and drug use. We found that typical risk factors for AKI showed statistical association on bivariate analysis. The contribution of drug therapy in the occurrence of AKI in medical ICUs reinforces the need for prevention strategies focused on early recognition of renal dysfunction and interventions in drug therapy. These actions would help improve the quality of patient care and ensure progress towards medication safety.

Background Thoracic endovascular repair (TEVAR) is currently considered the therapy of choice for complicated type B acute aortic dissection (TBAAD). Although several papers have reported good outcomes at short- and medium-term follow-up, some questions still remain regarding the long-term durability and re-intervention rate during follow-up. Methods We describe a case of a patient originally treated with TEVAR for TBAAD complicated by impending aortic rupture. Results Endovascular repair successfully excluded the flow through the primary entry tear but during the 12-year follow-up period the patient experienced several complications and re-interventions. Various full-size three-dimensional (3D) models of the patient-specific vasculature were printed to better explain the different interventional interventions over the 12 years of follow-up and as a hands-on tool for medical education. Conclusions The present case report, involving long-term follow-up, provides an example of the effectiveness and the safety of TEVAR for the treatment of complicated TBAAD shown at short and medium-term follow-up. However, the long-term complications that were observed in this patient during follow-up support the importance of lifelong CTA surveillance. Furthermore, this study confirms the capability of 3D printing technology as a powerful tool to support communication with patients and residents’ education through the physical analysis of the real cases.

BACKGROUND Endovascular treatment of thoracic aortic disease currently allows to treat high-risk patients with better results than open repair. It represents the first option for treatment according to the most recent guidelines. The aim of the study is to evaluate the early results of the low-profile Zenith Alpha Thoracic Endoprosthesis (ZATE). METHODS Between October 2012 and July 2015, 14 asymptomatic patients were treated with ZATE. 10 patients were male, mean age was 71, 7 years (range 58-85 years). 8 patients presented with atherosclerotic aortic aneurysm (7 thoracic aneurysm and 1 type I thoracoabdominal aneurysm), 2 chronic type B aortic dissection, 1 type IV endoleak 5 years after TEVAR, 3 aortic arch penetrating ulcers complicated by pseudoaneurysm. Hybrid staged procedures in 11 patients included 7 total aortic arch debranching (1 single [innominate] chimney stent-graft + carotid-carotid-subclavian), 2 carotid-carotid-subclavian artery bypass, 2 carotid-subclavian artery bypass. RESULTS No 30-day mortality or major complications were observed. The mean length of stay was 7.3 days (range 4-14 days). Mean procedure time, X ray time and Contrast load were 115 minutes (range 90-150 minutes), 20 minutes (range 10-30) and 79 mL (range 40-120 mL) respectively. 25 stent-grafts were implanted. The mean follow-up was 21 months (range 14-32 months). No mortality and no major complications were observed during the follow-up. In case of arch debranching with landing 0 and 1 zone the mean distance between the beginning of the endoprosthesis and the debranching inflow vessel was 5.5±2.4 mm. CONCLUSIONS The use of ZATE could be a viable alternative for treating patients with aortic arch proximal landing zone to facilitate the precise deployment. Larger case studies and longer follow-up are needed.