Scaffold based on castor oil as an osteoconductive matrix in bone repair: biocompatibility analysis

To analyze the biocompatibility of the scaffold produced from a natural polymer derived from castor oil through hemolytic activity and antimicrobial activity, to enable the clinical application. Three in vitro tests were performed: Hemolytic activity test - Polymer partially dissolved in contact with blood agar; Hemolytic activity test in sheep's blood - Polymer extract with red blood cells solution; Antimicrobial activity test - Solid polymer in direct contact with E. Coli and S. Aureus. For hemolytic tests, none of the samples showed hemolysis. Negative hemolytic activity is a good indicator, as the maintenance of the blood clot in the area of the lesion is essential for the formation of new tissue. For the antimicrobial activity test, no significant activity was observed against the bacteria used. The polymer is not toxic to red blood cells, being viable for clinical application as a matrix for tissue regeneration.info:eu-repo/semantics/publishedVersio

Influence of genetic polymorphisms and impact of dental caries rehabilitation on oral health-related quality of life

Esta tese apresentou dois objetivos específicos: i) avaliar a evidência científica sobre a reabilitação da cárie dentária na qualidade de vida relacionada à saúde bucal (QVRSB) de crianças, adolescentes e membros da família ii) avaliar o impacto da severidade da experiência de cárie dentária na QVRSB de crianças e também avaliar se polimorfismos genéticos nos genes MTR (rs1805087) e MTRR (rs1801394) são potenciais biomarcadores para QVRSB nos participantes com experiência de cárie. Para o primeiro objetivo, uma revisão sistemática e metanálise foi delineada. Uma busca eletrônica da literatura foi realizada utilizando cinco bases de dados (Pubmed, Web of Science, Scopus, Lilacs e Cochrane Library) assim como uma pesquisa manual e na literatura cinzenta. Os critérios de elegibilidade para população, intervenção, comparação e desfecho foram descritos da seguinte forma: P – crianças, adolescentes e família, I – reabilitação da cárie dentária sob anestesia local, C – QVRSB antes e depois da reabilitação da cárie dentária, O – QVRSB depois da reabilitação da cárie dentária. Dois autores independentes aplicaram os critérios de elegibilidade, extraíram dados qualitativos e avaliaram o risco de viés. Uma metanálise foi realizada utilizando-se o software RevMan 5.4. A certeza de evidência foi avaliada utilizando-se o sistema GRADE. Dos 520 artigos, 19 foram incluídos; 13 apresentaram baixo risco de viés. Oito tipos de instrumentos foram aplicados (Child-OIDP, OIDP, CPQ8-10, CPQ11-14, SOHO-5, ECOHIS, OHIP-14 e P-CPQ). A metanálise demonstrou uma melhora na QVRSB de famílias de crianças de 1-9 anos (p=0,003; CI 1,74[0,60,2,88]); adolescentes de 10-15 anos (p=0,03; CI 6,48[0,50,12,45]); crianças de 4-9 anos (p<0,00001; CI 1,23[0,99, 1,46]), 1-9 anos (p=0,001; CI 3,17[1,23,5,10]) e 8-10 anos (p=0,0002; CI 12,05[5,78,18,32]). A certeza de evidência foi muito baixa. Pôde-se concluir que a reabilitação da cárie dentária teve influência na redução do impacto na QVRSB de crianças/adolescentes de 1 a 15 anos e em famílias com crianças entre 1 e 9 anos de idade no entanto a certeza de evidência denota a necessidade de mais estudos. Para responder ao segundo objetivo, um estudo transversal foi delineado. Crianças entre 2 e 5 anos foram selecionadas, avaliadas clinicamente e classificadas como alta ou baixa severidade em relação à experiência de cárie. A versão brasileira em português do Early Chilhood Oral Health Impact Scale (ECOHIS) foi aplicada para avaliar a QVRSB. A análise da presença do polimorfismo genético nos genes MTR e MTRR foi realizada por meio de reações em cadeia da polimerase em tempo real utilizando ensaio Taqman (Aglient Technologies, Stratagene Mx3005P). Considerando os grupos de alta e baixa severidade em relação à experiência de cárie e QVRSB, a média geral do ECOHIS registrada foi 3,90 (DP, 3,79) e 4,55 (DP, 3,15), enquanto a mediana foi 3,00 (1-6) e 4,00 (2-7) (p<0,129), respectivamente. Crianças com alta severidade em relação à experiência de cárie apresentaram impacto negativo na QVRSB no domínio função (p=0,017). O gene MTR (rs1805087) apresentou associação limítrofe (0,058) na subscala infantil da QVRSB no modelo dominante (GG + AG), assim como o gene MTRR (rs1801394) mostrou associação limítrofe (p=0,087) no domínio função da QVRSB no modelo recessivo (GG). Este estudo concluiu que a severidade em relação à experiência de cárie impactou o domínio função da QVRSB em crianças. Os polimorfismos de nucleotídeo único, nos genes MTR e MTRR, podem influenciar no impacto na QVRSB em crianças com experiência de cárie severa.This thesis presented the objective to evaluate the impact of dental caries and its rehabilitation on oral health-related quality of life with two specific objective: i) to answer the following questions: does dental caries rehabilitation influences Oral Health-Related Quality of Life (OHRQoL) of children, adolescents, and family members? ii) to evaluate the impact of the severity of dental caries experience on OHRQoL in children and also to evaluate whether genetic polymorphisms in MTR and MTRR genes are potential biomarkers for OHRQoL in children with caries experience. For the first objective a systematic review and meta-analysis was designed. An electronic literature search was performed utilizing five databases (i.e., PubMed, Web of Science, Scopus, Lilacs, and Cochrane Library) as well as a manual search and in the grey literature. Eligibility criteria for the population, intervention, comparison, and outcome (PICO) were outlined as follows: P – children, adolescents and family, I – dental caries rehabilitation under local anesthesia, C – OHRQoL before dental caries rehabilitation, O – OHRQoL after dental caries rehabilitation. Two authors independently applied the eligibility criteria, extracted qualitative data, and assessed risk of bias. A meta-analysis was performed using the RevMan 5.4 program. The certainty of evidence was evaluated using the GRADE system. Out of 520 articles, 19 were included; 13 presented low-risk of bias. Eight types of instruments were employed (i.e., Child- OIDP, OIDP, CPQ8-10, CPQ11-14, SOHO-5, ECOHIS, OHIP-14 and P-CPQ). The meta-analysis demonstrated improvement on OHRQoL of: family from 1-9 year- old children (P=0.003;CI 1.74[0.60,2.88]); adolescents from 10-15 year-old (P=0.03;CI 6.48[0.50,12.45]); children from 4-9 year-old (P<0.00001;CI 1.23[0.99,1.46]), 1-9 year-old (P=0.001;CI 3.17[1.23,5.10]) and 8-10 year-old (P=0.0002;CI 12.05[5.78,18.32]). The certainty of evidence was very low. It was concluded that the rehabilitation of dental caries had an influence on the reduction of the impact on the OHRQoL of children/adolescents from 1 to 15 years old and in families with children between 1 and 9 years old. To answer the second objective, a cross-sectional study was designed. Children aged 2–5 years were selected, clinically evaluated and classified as high or low severity caries experience. The Brazilian Portuguese version of Early Childhood Oral Health Impact Scale (ECOHIS) was applied to assess the OHRQoL. The analysis of the presence of gene polymorphism in MTR and MTRR was performed using real-time polymerase chain reactions using the Taqman assay (Agilent Technologies, Stratagene Mx3005P). Considering the high and low severity groups and OHRQoL, the overall mean ECOHIS score recorded was 3.90 (SD, 3.79) and 4.55 (SD, 3.15), while the median scores were 3.00 (1-6) and 4.00 (2-7) (p < 0.129), respectively. Children with high severity caries experience presented negative impact on OHRQoL in function domain (p=0.017). The MTR gene (rs1805087) showed a borderline association (0.058) in the children's OHRQoL subscale in the dominant model (GG + AG), as well as the MTRR gene (rs1801394) showed a borderline association (p=0.087) in the OHRQoL function domain in the recessive model (GG). This study concluded that severity caries experience impacted the function domain of OHRQoL in children. Single nucleotide polymorphisms in MTR and MTRR genes may confer an increased risk for poor OHRQoL in children with caries experience.73 f

Identification of potential biomarkers for systemic lupus erythematosus diagnosis using two-dimensional differential gel electrophoresis (2D-DIGE) and mass spectrometry

<p>Systemic lupus erythematosus (SLE) is an autoimmune disease of the connective tissue with a large spectrum of clinical manifestations. Immune deregulation leads to autoantibody and immune complexes overproduction, complement activation, and persistent tissue inflammation. Considering that the current diagnosis depends on the interpretation of the complex criteria established by the American College of Rheumatology and that the disease course is characterized by unpredictable activations and remissions, each patient develops different manifestations, and therefore, the discovery of specific biomarkers is urgently required. Therefore, this study aimed to identify putative biomarkers for active and inactive SLE potentially capable in distinguishing laboratorial SLE from other autoimmune diseases. The 2D-DIGE proteomics technique was used to evaluate the differential abundance of proteins between patients with active SLE, inactive SLE, patients with other autoimmune disease, and healthy individuals. Six proteins showed increased abundance in active SLE (A) and inactive SLE (I) compared to the C and O groups, but not between groups A and I. There were two transthyretin (TTR) fragments or proteins with a structure similar to TTR (accession numbers: PDB: 1GKO_A and 2PAB_A), retinol-binding protein 4 (RBP4) isoform X1 (no information in databases such as UNIPROT), and antibody fragments. Two proteins, APO-AIV and SP-40,40, were upregulated in group A than in O and C and in group I versus C, but not in group I versus O. Therefore, we suggest these proteins to be considered as candidates for the diagnosis of SLE.</p

Delayed colorectal cancer care during covid-19 pandemic (decor-19). Global perspective from an international survey

Background The widespread nature of coronavirus disease 2019 (COVID-19) has been unprecedented. We sought to analyze its global impact with a survey on colorectal cancer (CRC) care during the pandemic. Methods The impact of COVID-19 on preoperative assessment, elective surgery, and postoperative management of CRC patients was explored by a 35-item survey, which was distributed worldwide to members of surgical societies with an interest in CRC care. Respondents were divided into two comparator groups: 1) ‘delay’ group: CRC care affected by the pandemic; 2) ‘no delay’ group: unaltered CRC practice. Results A total of 1,051 respondents from 84 countries completed the survey. No substantial differences in demographics were found between the ‘delay’ (745, 70.9%) and ‘no delay’ (306, 29.1%) groups. Suspension of multidisciplinary team meetings, staff members quarantined or relocated to COVID-19 units, units fully dedicated to COVID-19 care, personal protective equipment not readily available were factors significantly associated to delays in endoscopy, radiology, surgery, histopathology and prolonged chemoradiation therapy-to-surgery intervals. In the ‘delay’ group, 48.9% of respondents reported a change in the initial surgical plan and 26.3% reported a shift from elective to urgent operations. Recovery of CRC care was associated with the status of the outbreak. Practicing in COVID-free units, no change in operative slots and staff members not relocated to COVID-19 units were statistically associated with unaltered CRC care in the ‘no delay’ group, while the geographical distribution was not. Conclusions Global changes in diagnostic and therapeutic CRC practices were evident. Changes were associated with differences in health-care delivery systems, hospital’s preparedness, resources availability, and local COVID-19 prevalence rather than geographical factors. Strategic planning is required to optimize CRC care

Global variation in postoperative mortality and complications after cancer surgery: a multicentre, prospective cohort study in 82 countries

© 2021 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY-NC-ND 4.0 licenseBackground: 80% of individuals with cancer will require a surgical procedure, yet little comparative data exist on early outcomes in low-income and middle-income countries (LMICs). We compared postoperative outcomes in breast, colorectal, and gastric cancer surgery in hospitals worldwide, focusing on the effect of disease stage and complications on postoperative mortality. Methods: This was a multicentre, international prospective cohort study of consecutive adult patients undergoing surgery for primary breast, colorectal, or gastric cancer requiring a skin incision done under general or neuraxial anaesthesia. The primary outcome was death or major complication within 30 days of surgery. Multilevel logistic regression determined relationships within three-level nested models of patients within hospitals and countries. Hospital-level infrastructure effects were explored with three-way mediation analyses. This study was registered with ClinicalTrials.gov, NCT03471494. Findings: Between April 1, 2018, and Jan 31, 2019, we enrolled 15 958 patients from 428 hospitals in 82 countries (high income 9106 patients, 31 countries; upper-middle income 2721 patients, 23 countries; or lower-middle income 4131 patients, 28 countries). Patients in LMICs presented with more advanced disease compared with patients in high-income countries. 30-day mortality was higher for gastric cancer in low-income or lower-middle-income countries (adjusted odds ratio 3·72, 95% CI 1·70–8·16) and for colorectal cancer in low-income or lower-middle-income countries (4·59, 2·39–8·80) and upper-middle-income countries (2·06, 1·11–3·83). No difference in 30-day mortality was seen in breast cancer. The proportion of patients who died after a major complication was greatest in low-income or lower-middle-income countries (6·15, 3·26–11·59) and upper-middle-income countries (3·89, 2·08–7·29). Postoperative death after complications was partly explained by patient factors (60%) and partly by hospital or country (40%). The absence of consistently available postoperative care facilities was associated with seven to 10 more deaths per 100 major complications in LMICs. Cancer stage alone explained little of the early variation in mortality or postoperative complications. Interpretation: Higher levels of mortality after cancer surgery in LMICs was not fully explained by later presentation of disease. The capacity to rescue patients from surgical complications is a tangible opportunity for meaningful intervention. Early death after cancer surgery might be reduced by policies focusing on strengthening perioperative care systems to detect and intervene in common complications. Funding: National Institute for Health Research Global Health Research Unit

Effects of hospital facilities on patient outcomes after cancer surgery: an international, prospective, observational study

© 2022 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 licenseBackground: Early death after cancer surgery is higher in low-income and middle-income countries (LMICs) compared with in high-income countries, yet the impact of facility characteristics on early postoperative outcomes is unknown. The aim of this study was to examine the association between hospital infrastructure, resource availability, and processes on early outcomes after cancer surgery worldwide. Methods: A multimethods analysis was performed as part of the GlobalSurg 3 study—a multicentre, international, prospective cohort study of patients who had surgery for breast, colorectal, or gastric cancer. The primary outcomes were 30-day mortality and 30-day major complication rates. Potentially beneficial hospital facilities were identified by variable selection to select those associated with 30-day mortality. Adjusted outcomes were determined using generalised estimating equations to account for patient characteristics and country-income group, with population stratification by hospital. Findings: Between April 1, 2018, and April 23, 2019, facility-level data were collected for 9685 patients across 238 hospitals in 66 countries (91 hospitals in 20 high-income countries; 57 hospitals in 19 upper-middle-income countries; and 90 hospitals in 27 low-income to lower-middle-income countries). The availability of five hospital facilities was inversely associated with mortality: ultrasound, CT scanner, critical care unit, opioid analgesia, and oncologist. After adjustment for case-mix and country income group, hospitals with three or fewer of these facilities (62 hospitals, 1294 patients) had higher mortality compared with those with four or five (adjusted odds ratio [OR] 3·85 [95% CI 2·58–5·75]; p<0·0001), with excess mortality predominantly explained by a limited capacity to rescue following the development of major complications (63·0% vs 82·7%; OR 0·35 [0·23–0·53]; p<0·0001). Across LMICs, improvements in hospital facilities would prevent one to three deaths for every 100 patients undergoing surgery for cancer. Interpretation: Hospitals with higher levels of infrastructure and resources have better outcomes after cancer surgery, independent of country income. Without urgent strengthening of hospital infrastructure and resources, the reductions in cancer-associated mortality associated with improved access will not be realised. Funding: National Institute for Health and Care Research