Academic accountability to local communities and society through Programme Science: a case study from the HPV self-sampling programme HOPE in Peru.

INTRODUCTION: Health challenges in the 21st century underscore the need for adaptable and innovative approaches in public health. Academic institutions can and should contribute much more effectively to generate and translate scientific knowledge that will result in better programmes to improve societal health. Academic accountability to local communities and society requires universities to actively engage with local communities, understanding the context, their needs, and leveraging their knowledge and local experience. The Programme Science initiative provides a framework to optimize the scale, quality and impact of public health programmes, by integrating diverse approaches during the iterative cycle of research and practice within the strategic planning, programme implementation and programme management and evaluation. We illustrate how the Programme Science framework could be a useful tool for academic institutions to accomplish accountability to local communities and society through the experience of Project HOPE in Peru. DISCUSSION: Project HOPE applied the Programme Science framework to introduce HPV self-sampling into a women's health programme in Peru. Collaboration with local authorities and community members was pivotal in all phases of the project, ensuring interventions aligned with community needs and addressing social determinants of health. The HOPE Ladies-community women trained and empowered to promote and provide the HPV kits-crafted the messages used through the study and developed strategies to reach individuals and provided support to women's journey through health centres. By engaging communities in co-creating knowledge and addressing health inequities, academic institutions can generate contextually relevant and socially just scientific knowledge. The active participation of community women in Project HOPE was instrumental in improving service utilization and addressing barriers to self-sampling. CONCLUSIONS: The Programme Science approach offers a pathway for academic institutions to enhance their accountability to communities and society at large. By embedding researchers within public health programmes and prioritizing community engagement, academic institutions can ensure that research findings directly inform policy improvements and programmatic decisions. However, achieving this requires a realignment of research agendas and recognition of the value of community engagement. Establishing Programme Science networks involving academia, government and funding entities can further reinforce academic accountability and enhance the impact of public health programmes.

Outcomes of Bladder Washout for the Treatment of Recurrent Urinary Tract Infections After Renal Transplantation.

Background Current literature suggests that anywhere from 2.9-27% of renal transplant recipients (RTR) will develop recurrent urinary tract infections (UTIs) (≥2 UTIs over six months or ≥3 UTIs over 12 months). Recurrent UTIs are of particular importance to RTR given its increased risk for allograft fibrosis and overall patient survival. Alternative solutions are needed for the management of recurrent UTIs, especially given the vulnerability of RTR to UTIs. We hypothesize that bladder washout (BW) reduces the incidence and recurrence of UTIs in RTR. Methods This is a retrospective study evaluating the utility of BW procedures on RTR diagnosed with recurrent UTIs between December 2013 and July 2021 at a single center. Results A total of 106 patients were included in the study with a total of 118 BW performed. 69% of patients were successfully treated with BW, meaning they no longer met the criteria for recurrent UTIs (<1 UTI) in the six-month post-BW period. The mean number of UTIs was 2.76 (range 2-7) before the BW and 1.16 (range 0-5) after the BW. On average, there were 1.60 fewer UTIs in the post-BW period compared to the pre-BW period (p<0.0001). There is no statistically significant difference in success rates stratified by bacterial class (p=1) or antimicrobial resistance class (p=0.6937). Conclusion BW decreased the incidence of UTIs in the six-month post-operative period as nearly 70% of patients did not have UTI recurrence. This data provides evidence that BW may have utility in transplant recipients with recurrent UTIs. We hope this will stimulate further prospective randomized studies in this area.

Fatores correlacionados a Síndrome de Burnout entre acadêmicos: estudo transversal / Factors correlated with Burnout Syndrome among academic students: cross-sectional study / Factores correlacionados con el Síndrome de Burnout en estudiantes académicos: estudio transversal

Apesar de predominante no ambiente de trabalho, a Síndrome de Burnout (SB) torna-se cada vez mais frequente no ambiente universitário. Com objetivo de verificar a prevalência da SB entre acadêmicos e correlacionar essa variável com aspectos sociodemográficos e de saúde, esse estudo transversal foi conduzido com uma amostra composta por 72 participantes. O protocolo de avaliação foi composto por um questionário sociodemográfico, avaliação da Síndrome de Burnout, de sintomas depressivos, saúde geral, aspectos sociais e sintomas osteomusculares. A correlação de Spearman foi utilizada para análise estatística. Houve predomínio da SB entre a amostra (65,2%). Observou-se correlações significativas entre aspectos sociais e descrença (p=0.016; r=-0.283), eficácia estudantil (p=<0.001; r=-0.399) e sintomas depressivos (p=<0.001; r=-0.547), bem como entre a saúde geral e sintomas depressivos (p=0.012; r=-0.295). Estabelecer esse tipo de medida permite planejar ações voltadas à assistência estudantil, priorizando intervenções e práticas preventivas que colaborem com a promoção da saúde no ambiente universitário.

Despite being predominant in the workplace, Burnout Syndrome (BS) is becoming more and more frequent in the university environment. With the objective of verifying the prevalence of BS among students and correlating this variable with sociodemographic and health aspects, this cross-sectional study was conducted with a sample of 72 participants. The evaluation protocol consisted of a sociodemographic questionnaire, evaluation of Burnout Syndrome, depressive symptoms, general health, social aspects, and musculoskeletal symptoms. Spearman's correlation was used for statistical analysis. There was a predominance of BS among the sample (65.2%). Significant correlations were observed between social aspects and disbelief (p=0.016; r=-0.283), student efficacy (p=<0.001; r=-0.399) and depressive symptoms (p=<0.001; r=-0.547), as well as between general health and depressive symptoms (p=0.012; r=-0.295). Establishing this type of measure allows planning actions aimed at student assistance, prioritizing interventions and preventive practices that collaborate with health promotion in the university environment.

A pesar de ser prevalente en el ámbito laboral, el Síndrome de Burnout (SB) es cada vez más frecuente en el ámbito universitario. Con el objetivo de verificar la prevalencia de SB entre los estudiantes y correlacionar esta variable con aspectos sociodemográficos y de salud, este estudio transversal se realizó con una muestra de 72 participantes. El protocolo de evaluación consistió en un cuestionario sociodemográfico, evaluación del Síndrome de Burnout, síntomas depresivos, salud general, aspectos sociales y síntomas musculoesqueléticos. Para el análisis estadístico se utilizó la correlación de Spearman. Hubo predominio de SB en la muestra (65,2%). Se observaron correlaciones significativas entre los aspectos sociales y la incredulidad (p=0.016; r=-0.283), la eficacia acadêmica (p=<0.001; r=-0.399) y síntomas depresivos (p=<0.001; r=-0.547), así como entre la salud general y los síntomas depresivos (p=0.012; r=-0.295). Establecer este tipo de medidas permite planificar acciones dirigidas a la asistencia estudiantil, priorizar intervenciones y prácticas que colaboren con la promoción de la salud en el ámbito universitario.

Syagrus coronata fixed oil prevents rotenone-induced movement disorders and oxidative stress in Drosophila melanogaster.

One prominent aspect of Parkinson's disease (PD) is the presence of elevated levels of free radicals, including reactive oxygen species (ROS). Syagrus coronata (S. coronata), a palm tree, exhibits antioxidant activity attributed to its phytochemical composition, containing fatty acids, polyphenols, and flavonoids. The aim of this investigation was to examine the potential neuroprotective effects of S. coronata fixed oil against rotenone-induced toxicity using Drosophila melanogaster. Young Drosophila specimens (3-4 d old) were exposed to a diet supplemented with rotenone (50 µM) for 7 d with and without the inclusion of S. coronata fixed oil (0.2 mg/g diet). Data demonstrated that rotenone exposure resulted in significant locomotor impairment and increased mortality rates in flies. Further, rotenone administration reduced total thiol levels but elevated lipid peroxidation, iron (Fe) levels, and nitric oxide (NO) levels while decreasing the reduced capacity of mitochondria. Concomitant administration of S. coronata exhibited a protective effect against rotenone, as evidenced by a return to control levels of Fe, NO, and total thiols, lowered lipid peroxidation levels, reversed locomotor impairment, and enhanced % cell viability. Molecular docking of the oil lipidic components with antioxidant enzymes showed strong binding affinity to superoxide dismutase (SOD) and glutathione peroxidase (GPX1) enzymes. Overall, treatment with S. coronata fixed oil was found to prevent rotenone-induced movement disorders and oxidative stress in Drosophila melanogaster.

[Faecal microbiota study reveals specific dysbiosis in spondyloarthritis according to subtype, disease activity and treatment]. / Estudio de microbiota fecal revela disbiosis específica en espondiloartritis, según subtipo, actividad de la enfermedad y tratamiento.

OBJECTIVE: To compare the diversity and composition of the gastrointestinal microbiome of patients with SpA. METHODS: MiSeq sequencing of the V3-V4 region of the 16S ribosomal RNA gene was performed on DNA isolated from stool. Patients with concurrent SpA and IBD were excluded. Differences were assessed for richness and diversity indices by QIIME 2™. Differences between means >0,2% with a p-value<0,05 were assumed significant. Institutional Ethics Committee endorsement. RESULTS: 69 individuals included, 49 with SpA (ankylosing spondylitis-AS 72,9%, psoriatic arthritis-PsA 18,8%, reactive arthritis-ReA 8,3%) 5 positive controls-dysbiosis and 15 controls-eubiosis. Conventional treatment in 42,9%, anti-IL-17 16,3% and anti-TNF 40,8%. By subtype, statistically significant differences in favour of AS were found for the diversity indices. AS vs PsA there was a difference in favour of AS for Clostridium clostridioforme (p=0,002), Gemmiger formicilis (p=0,009), Roseburia inulivorans (p=0,008) and Lachnospira pectinoschiza. AS vs ReA there was a difference in favour of AS for L. pectinoschiza (p=0,009), Ruminococcus callidus (p=0.006), Clostridium ruminantium (p=0.031); G. formicilis (p=0,034). Diversity and richness showed differences in patients with high activity for Simpson's and Pielou's indices. In high activity, lower enrichment of Bacteroides eggerthii (p= 0,0003), C. ruminantium (p= 0,026) and Alistipes putredinis (p=0,035) was found. The number of ASV was higher in the anti-IL-17 vs conventional group (p=0.025) and a trend between anti-IL-17 vs anti-TNF (p=0.09). In anti-TNF there was a lower proportion for C. clostridioforme (p=0.023), G. formicilis (p=0.030) and R. callidus (p= 0.003). In anti IL-17, Alistipes indistinctus (p= 0.012) was decreased. CONCLUSIONS: There are differences in microbial diversity for SpA subtypes. The level of disease activity is plausible to influence the composition of the faecal microbiota. Anti-TNFα treatment may influence the microbiome environment favouring restoration of the gut microbiota, while anti-IL-17 may maintain an inflammatory environment.

OBJETIVO: Comparar la diversidad y composición del microbioma gastrointestinal de pacientes con EspA. MÉTODOS: La secuenciación MiSeq de la región V3-V4 del gen ARN ribosomal 16, se realizó en ADN aislado de heces. Se excluyeron pacientes con EspA y EII simultánea. Se evaluaron diferencias para los índices de riqueza y diversidad por medio de QIIME 2™. Las diferencias entre medias> 0,2%, con un valor de p< 0,05, se asumieron significativas. Aval del Comité de Ética Institucional. RESULTADOS: 69 individuos incluidos, 49 con EspA (espondilitis anquilosante-EA 72,9%, artritis psoriásica-APs 18,8%, artritis reactiva-ARe 8,3%), cinco controles positivos-disbiosis y 15 controles-eubiosis. El tratamiento convencional en 42,9%, anti-IL-17 16,3%, y anti-TNF 40,8%. Por subtipo-EasP, se encontraron diferencias estadísticamente significativas a favor de EA para los índices de diversidad. Entre EA vs APs, hubo diferencia a favor de EA para Clostridium clostridioforme (p=0,002), Gemmiger formicilis (p=0,009), Roseburia inulivorans (p=0,008) y Lachnospira pectinoschiza. Entre EA vs ARe hubo diferencia a favor de EA para L. pectinoschiza (p=0,009), Ruminococcus callidus (p = 0,006), Clostridium ruminantium (p=0,031); G. formicilis (p=0,034). La diversidad y riqueza mostraron diferencias en pacientes con alta actividad para los índices de Simpson y Pielou. En alta actividad, se encontró menor enriquecimiento de Bacteroides eggerthii (p=0,0003), C. ruminantium (p= 0,026) y Alistipes putredinis (p= 0,035). El número de ASV fue superior en el grupo de anti IL-17 vs convencional (p=0.025), y una tendencia entre anti IL-17 vs anti-TNF (p=0,09). En anti TNF hubo menor proporción para C. clostridioforme (p=0,023), G. formicilis (p=0,030) y R. callidus (p= 0,003). Y en anti IL-17, Alistipes indistinctus (p= 0,012), estuvo disminuida. CONCLUSIONES: Existen diferencias en la diversidad microbiana para los subtipos de EspA. El nivel de actividad de la enfermedad es plausible para influir en la composición de microbiota fecal. El tratamiento con anti-TNFα, puede influenciar el ambiente del microbioma favoreciendo la restauración de la microbiota intestinal, mientras los anti IL-17 podrían mantener un ambiente inflamatorio.

Enteropathogenic Escherichia coli modulates the virulence and pathogenicity of Entamoeba dispar.

Amoebiasis is a disease caused by Entamoeba histolytica, affecting the large intestine of humans and occasionally leading to extra-intestinal lesions. Entamoeba dispar is another amoeba species considered commensal, although it has been identified in patients presenting with dysenteric and nondysenteric colitis, as well as amoebic liver abscess. Amoebic virulence factors are essential for the invasion and development of lesions. There is evidence showing that the association of enterobacteria with trophozoites contributes to increased gene expression of amoebic virulence factors. Enteropathogenic Escherichia coli is an important bacterium causing diarrhea, with high incidence rates in the world population, allowing it to interact with Entamoeba sp. in the same host. In this context, this study aims to evaluate the influence of enteropathogenic Escherichia coli on ACFN and ADO Entamoeba dispar strains by quantifying the gene expression of virulence factors, including galactose/N-acetyl-D-galactosamine-binding lectin, cysteine proteinase 2, and amoebapores A and C. Additionally, the study assesses the progression and morphological aspect of amoebic liver abscess and the profile of inflammatory cells. Our results demonstrated that the interaction between EPEC and ACFN Entamoeba dispar strains was able to increase the gene expression of virulence factors, as well as the lesion area and the activity of the inflammatory infiltrate. However, the association with the ADO strain did not influence the gene expression of virulence factors. Together, our findings indicate that the interaction between EPEC, ACFN, and ADO Entamoeba dispar strains resulted in differences in vitro and in vivo gene expression of Gal/GalNAc-binding lectin and CP2, in enzymatic activities of MPO, NAG, and EPO, and consequently, in the ability to cause lesions.

Routine Use of Neck Drains Following Thyroid Operations to Prevent Complications Is No Longer Advisable.

BACKGROUND: The use of cervical drains to prevent cervical hematoma or seroma after thyroidectomy remains a controversial issue. OBJECTIVE: Identify clinical and surgical risk factors for hematoma or seroma and evaluate the usefulness of routine use of drains following thyroid surgery. MATERIAL AND METHODS: The authors conducted a retrospective multicentric study related to consecutive patients submitted to thyroid surgery in seven Portuguese hospitals between January 2018 and December 2020 (n=945). The data collected included the following parameters: age and gender of the patients, anticoagulation or anti-aggregating therapy, histological diagnoses, type of surgery, the presence or absence of postoperative drains, thyroid weight, length of hospital stay, postoperative complications, and reinterventions. In this study, surgical complications evaluated were limited to the presence of hematoma or seroma. A total of 945 patients who underwent thyroid surgery were included in the study. Twenty-seven patients (2.9%, n=27) experienced complications classified as hematomas or seromas. In the series, significant differences were observed between the two groups according to hypocoagulation or anti-aggregation status (OR=3.62; 95% CI 1.14-11.4) (p=0.001) and the nature of histological diagnosis (toxic vs. non-toxic benign disease) (OR=6.59; 95% CI 1.83-23.7). Hypocoagulation or anti-aggregation status were independently associated with a higher risk of complications. The presence of drains was associated with longer hospitalization periods (p<0.001) and not a decreased need for reintervention. CONCLUSION: Cervical hematoma or seroma are rare complications associated with both hypocoagulation and anti-aggregation therapy and with the presence of benign toxic pathology. The use of drains does not decrease the need for reintervention and is even associated with a longer length of hospital stay; therefore, their routine use should not be advised.

Hereditary breast cancer next-generation sequencing (NGS) panel evaluation in the south region of Brazil: a novel BRCA2 candidate pathogenic variant is reported.

In this article, we delineate a loosely selected cohort comprising patients with a history of early-onset breast cancer and/or a familial occurrence of cancer. The aim of this study was to gain insights into the presence of breast cancer-related gene variants in a population from a micro-region in southern Brazil, specifically the Metropolitan Region of Curitiba. This area exhibits a highly genetically mixed population, mirroring the general characteristics of the Brazilian people. Comprehensive next-generation sequencing (NGS) multigene panel testing was conducted, involving the evaluation of twelve patients. Two pathogenic variants and one candidate pathogenic variant were identified: BRCA2:c.8878C>T, p.Gln2960Ter; CHEK2:c.1100delAG>A, p.Thr367Metfs*15 and BRCA2:c.3482dupG>GA, p.Asp1161Glufs*3, a novel variant, previously unpublished, is reported.

Clinical factors associated with severity in patients with inflammatory bowel disease in Brazil based on 2-year national registry data from GEDIIB.

The Brazilian Organization for Crohn's Disease and Colitis (GEDIIB) established a national registry of inflammatory bowel disease (IBD). The aim of the study was to identify clinical factors associated with disease severity in IBD patients in Brazil. A population-based risk model aimed at stratifying the severity of IBD based on previous hospitalization, use of biologics, and need for surgery for ulcerative colitis (UC) and Crohn's Disease (CD) and on previous complications for CD. A total of 1179 patients (34.4 ± 14.7y; females 59%) were included: 46.6% with UC, 44.2% with CD, and 0.9% with unclassified IBD (IBD-U). The time from the beginning of the symptoms to diagnosis was 3.85y. In CD, 41.2% of patients presented with ileocolic disease, 32% inflammatory behavior, and 15.5% perianal disease. In UC, 46.3% presented with extensive colitis. Regarding treatment, 68.1%, 67%, and 47.6% received biological therapy, salicylates and immunosuppressors, respectively. Severe disease was associated with the presence of extensive colitis, EIM, male, comorbidities, and familial history of colorectal cancer in patients with UC. The presence of Montreal B2 and B3 behaviors, colonic location, and EIM were associated with CD severity. In conclusion, disease severity was associated with younger age, greater disease extent, and the presence of rheumatic EIM.

Analysis of durability and replacement of vocal prostheses in total laryngectomy patients at a head and neck surgery referral center.

PURPOSE: The use of tracheoesophageal prostheses has become the gold standard in vocal rehabilitation of patients undergoing total laryngectomy. However, this method also has limitations, such as the need for frequent replacement of prostheses due to leakage or other complications. We have designed a study to access the clinical profile of patients using tracheoesophageal prostheses as vocal rehabilitation after total laryngectomy and to determine the average rate of changes, as well as the main causes of prostheses replacement. METHODS: A retrospective cohort study was performed based on patients who underwent rehabilitation with voice prostheses after total laryngectomy between 2008 and 2017. RESULTS: The sample consisted of 93 patients and 432 vocal prostheses replacement events. The median change of prostheses per patient was 210.25 days, (range 57.33 to 651.50). The most frequent cause of prostheses replacement was leakage through the prostheses, 218 (50.46%). Lower level of education was associated to higher prostheses replacement rate. CONCLUSION: The results of this study show that the median of prostheses durability is higher than that presented in the literature, the main cause of replacement was protheses leakage and that low educational level is associated to higher replacement rate.

Análise da clareza metodológica como dimensão de qualidade do Cadastro Nacional de Estabelecimentos de Saúde / Analysis of methodological clarity as a quality dimension of the National Register of Health Establishments

RESUMO Este artigo analisa a dimensão de qualidade clareza metodológica do Cadastro Nacional de Estabelecimentos de Saúde (CNES), considerando a abordagem das formas de contratação inseridas no sistema. Trata-se de uma pesquisa documental com abordagem qualitativa, que analisou o CNES e seus documentos. Foram selecionados os documentos que contemplaram os descritores: tabela de vínculos de profissionais e/ou formas de contratação. A partir do conceito adotado para a dimensão de qualidade clareza metodológica, foram delineadas as categorias acessibilidade, conteúdo, variáveis, linguagem e usabilidade. No período de 2005 a 2020, foram publicados 17 documentos. Desses, três documentos se sobressaíram: o Leia-me da versão, a Tabela de Domínios e o Manual de preenchimento do CNES. O site do CNES passava por uma reestruturação, e nem todas as funcionalidades estavam devidamente implementadas. O site atual apresentou uma interface mais moderna e de fácil compreensão. A mudança da variável esfera administrativa para natureza jurídica, em 2015, pode dificultar a análise em série histórica. Evidencia-se que o CNES carece de melhor atenção quanto à clareza metodológica, considerando a abordagem das formas de contratação dos profissionais de saúde, inseridas no sistema.

ABSTRACT This article analyzes the quality dimension of methodological clarity of the National Registry of Health Establishments (CNES), considering the approach to forms of contracting in the system. This is a documentary research with a qualitative approach, which analyzed the CNES and its documents. Documents that included the following were selected: table of professional relationships and/or forms of hiring. Based on the concept adopted for the dimension of methodological clarity quality, the categories accessibility, content, variables, language, and usability were outlined. In the period from 2005 to 2020, 17 documents were published. Of those, three documents stood out: The version's Readme, the Domain Table, and the CNES Filling Manual. The CNES website underwent restructuring and not all features were completed. The current website has a more modern and easy-to-understand interface. The change from the administrative sphere variable to the legal nature, in 2015, may make historical series analysis difficult. It is evident that the CNES pays more attention to methodological clarity, considering the approach to the ways of hiring health professionals, included in the system.

ENAM gene polymorphisms associated with dental anomalies in individuals with cleft lip and palate

Aim: This study aimed to investigate the occurrence of enamelin gene (ENAM) single nucleotide polymorphisms (SNP) and ENAM polymorphism association with dental anomalies (DA) in individuals with unilateral or bilateral cleft lip and palate (CLP). Methods: Saliva samples were collected from 147 individuals aged between 6 and 15 years-old, both genders, and divided into 4 groups: Group 1 (G1) - CLP and DA; Group 2 (G2) - CLP without DA; Group 3 (G3) - without CLP with DA; Group 4 (G4) - without CLP and DA. The genomic DNA was extracted from saliva samples and the following ENAM SNPs markers were genotyped: rs3796703, rs3796704, rs3796705, rs7671281, rs2609428, and rs35951442. Fisher exact and Pearson's Chi-square tests statistically analyzed the results (α=5%). Results: Individuals without CLP with DA (Group 3 - 19.2%) showed statistically higher prevalence of SNP rs2609428 heterozygotes (p=0.006) than individuals with CLP and DA (Group 1 - 0%). Individuals without CLP (10%) exhibited statistically higher prevalence of mutated heterozygotes/homozygous (p=0.028) than in individuals with CLP (1.3%). Conclusion: SNP rs2609428 marker of ENAM gene may be associated with dental anomalies in individuals without cleft lip and palate

Long-term outcomes after endovascular aortic treatment in patients with thoracic aortic diseases.

Background: Endovascular treatments for thoracic aortic diseases have been adopted rapidly, and long-term studies are relevant for durability evaluation. Objective: To evaluate the long-term results of a prospective observational study of endovascular treatment in patients with thoracic aortic diseases who underwent percutaneous implantation of self-expandable endoprostheses. Methods: Procedural success was defined as the absence of endoleak into the aneurysm or dissection-induced false lumen, no migration, and no conversion to open surgery. Intraoperative, postoperative, and late postoperative outcomes were evaluated in terms of complications, mortality, and evolution of the endoprosthesis over a follow-up of up to 179 months (median: 46 months). Results: A total of 150 endoprostheses were implanted in 112 patients. Primary success was observed in 100 (82.14%) patients. Immediate mortality occurred in 7 patients (6.25%). Late mortality occurred in 31 patients (27.68%), 10 (8.93%) of whom died from cardiovascular causes, 12 (10.71%) from non-cardiovascular causes, and 2 (1.78%) from natural causes, while 7 (6.25%) had no diagnosis for cause of death. Types I, II, and IV endoleaks occurred during hospitalization in 4 (3.57%), 5 (4.46%), and 3 (2.68%) patients, respectively. Late types I and IV endoleaks occurred in 5 (4.46%) and 3 (2.68%) patients respectively. Twenty-two patients (19.64%) had clinical complications in the immediate postoperative period. Actuarial survival free from death from cardiovascular causes was 79.3% (95% confidence interval, 67.0-91.7%) at 132 months. Conclusions: The low levels of intraoperative and postoperative complications demonstrate that endovascular treatment is safe and effective. The high rate of late survival for these critically ill patients indicates that the endovascular technique is beneficial for treatment of thoracic aortic diseases in terms of long-term outcomes.

Contexto: Os tratamentos endovasculares para doenças da aorta torácica têm sido adotados rapidamente e estudos de longo prazo são relevantes para avaliação de durabilidade. Objetivo: Avaliar através de estudo observacional e prospectivo, os resultados a longo prazo do tratamento endovascular em pacientes com doenças da aorta torácica submetidos a implante percutâneo de endoprótese autoexpansível. Métodos: O sucesso do procedimento foi definido como ausência de vazamento interno para o aneurisma ou falso lúmen induzido por dissecção, ausência de migração e sem necessidade de conversão para cirurgia aberta. Os resultados intraoperatórios, pós-operatórios e tardios foram avaliados quanto a complicações, mortalidade e evolução da endoprótese em um seguimento de até 179 meses (mediana de 46 meses). Resultados: Um total de 150 endopróteses foram implantadas em 112 pacientes. Sucesso primário foi observado em 100 (82,14%) pacientes. Mortalidade imediata ocorreu em sete pacientes (6,25%). A mortalidade tardia ocorreu em 31 pacientes (27,68%), dos quais 10 (8,93%) morreram por causas cardiovasculares; 12 (10,71%), por causas não cardiovasculares; dois (1,78%), por causas naturais e sete (6,25%) não tiveram a causa da morte diagnosticada. Vazamentos tipo I, II e IV ocorreram durante a internação em quatro (3,57%), cinco (4,46%) e três (2,68%) pacientes, respectivamente. Vazamentos tardios tipo I e IV ocorreram em cinco (4,46%) e três (2,68%) pacientes, respectivamente. Complicações clínicas no pós-operatório imediato foram observadas em 19,64% dos pacientes. A sobrevida atuarial por causas cardiovasculares foi de 79,3% em 132 meses. Conclusões: Os baixos índices de complicações intra e pós-operatórias demonstram que o tratamento endovascular é seguro e eficaz. A alta taxa de sobrevida em 132 meses em pacientes críticos indica que a técnica é benéfica para o tratamento de doenças da aorta torácica em resultados a longo prazo.

COLD SNARE POLYPECTOMY: A SAFE PROCEDURE FOR REMOVING SMALL NON-PEDUNCULATED COLORECTAL LESIONS.

BACKGROUND: Polypectomy is an important treatment option for preventing colorectal cancer. Incomplete polyp resection (IPR) is re-cognized as a risk factor for interval cancer. OBJECTIVE: The primary objective was to evaluate the complete polyp resection (CPR) rate for cold snare polypectomy (CSP) in small non-pedunculated polyps and, secondarily, specimen retrieval and complication rates. METHODS: We prospectively evaluated 479 polyps <10 mm removed by CSP in 276 patients by an inexperienced endoscopist. RESULTS: A total of 476 polyps (99.4%) were resected en bloc. A negative margin (classified as CPR) was observed in 435 polyps (90.8%). An unclear or positive margin (classified as IPR) was observed in 43 cases (9.0%) and 1 case (0.2%), respectively, for an overall IPR rate of 9.2% (44/479). The IPR rate was 12.2% in the first half of cases and 5.9% in the second half (P=0.02). Dividing into tertiles, the IPR rate was 15.0% in the first tertile, 6.9% in the second tertile, and 5.7% in the third tertile (P=0.01). Dividing into quartiles, the IPR rate was 15.8% in the first quartile and 5.9% in the fourth quartile (P=0.03). The IPR rate was 6.3% for type 0-IIa lesions and 14.1% for type 0-Is lesions (P=0.01). For serrated and adenomatous lesions, the IPR rate was 9.2%. Specimen retrieval failed in 3.6% of cases. Immediate bleeding (>30 s) occurred in 1 case (0.2%), treated with argon plasma coagulation. No delayed bleeding or perforation occurred. CONCLUSION: CSP is a safe technique that provides good results for the resection of small non-pedunculated polyps, with a short learning curve.

The implication of next-generation sequencing in the diagnosis and clinical management of non-Hodgkin lymphomas.

Next generation sequencing (NGS) is a technology that broadens the horizon of knowledge of several somatic pathologies, especially in oncological and oncohematological pathology. In the case of NHL, the understanding of the mechanisms of tumorigenesis, tumor proliferation and the identification of genetic markers specific to different lymphoma subtypes led to more accurate classification and diagnosis. Similarly, the data obtained through NGS allowed the identification of recurrent somatic mutations that can serve as therapeutic targets that can be inhibited and thus reducing the rate of resistant cases. The article's purpose is to offer a comprehensive overview of the best ways of integrating of next-generation sequencing technologies for diagnosis, prognosis, classification, and selection of optimal therapy from the perspective of tailor-made medicine.

Polipectomia a frio: um procedimento seguro para remover pequenas lesões colorretais não pediculadas / Cold snare polypectomy: a safe procedure for removing small non-pedunculated colorectal lesions

ABSTRACT Background: Polypectomy is an important treatment option for preventing colorectal cancer. Incomplete polyp resection (IPR) is re­cognized as a risk factor for interval cancer. Objective: The primary objective was to evaluate the complete polyp resection (CPR) rate for cold snare polypectomy (CSP) in small non-pedunculated polyps and, secondarily, specimen retrieval and complication rates. Methods: We prospectively evaluated 479 polyps <10 mm removed by CSP in 276 patients by an inexperienced endoscopist. Results: A total of 476 polyps (99.4%) were resected en bloc. A negative margin (classified as CPR) was observed in 435 polyps (90.8%). An unclear or positive margin (classified as IPR) was observed in 43 cases (9.0%) and 1 case (0.2%), respectively, for an overall IPR rate of 9.2% (44/479). The IPR rate was 12.2% in the first half of cases and 5.9% in the second half (P=0.02). Dividing into tertiles, the IPR rate was 15.0% in the first tertile, 6.9% in the second tertile, and 5.7% in the third tertile (P=0.01). Dividing into quartiles, the IPR rate was 15.8% in the first quartile and 5.9% in the fourth quartile (P=0.03). The IPR rate was 6.3% for type 0-IIa lesions and 14.1% for type 0-Is lesions (P=0.01). For serrated and adenomatous lesions, the IPR rate was 9.2%. Specimen retrieval failed in 3.6% of cases. Immediate bleeding (>30 s) occurred in 1 case (0.2%), treated with argon plasma coagulation. No delayed bleeding or perforation occurred. Conclusion: CSP is a safe technique that provides good results for the resection of small non-pedunculated polyps, with a short learning curve.

RESUMO Contexto: A polipectomia é uma importante opção terapêutica na prevenção do câncer colorretal (CCR). A ressecção incompleta do pólipo (RIP) é reconhecida como fator de risco para o câncer de intervalo. Objetivo: O principal objetivo foi avaliar o índice de ressecção completa da polipectomia a frio (PF) em pequenos pólipos não pediculados e, secundariamente, a recuperação do espécime e índice de complicações. Métodos: Avaliamos prospectivamente 479 pólipos <10 mm removidos por PF em 276 pacientes, por um endoscopista sem experiência com este método. Resultados: Foram ressecados em bloco 476 pólipos (99,4%). Tivemos margem negativa, considerada ressecção completa do pólipo (RCP), em 435 (90,8%) casos. Margem indefinida ou positiva (classificada como RIP) foi observada em 43 (9,0%) casos e em 1 (0,2%) caso, respectivamente, com um índice global de RIP de 9,2% (44/479). O índice de RIP foi de 12,5% na primeira metade dos casos e 5,9% na última metade (P=0,02). Dividindo em tercis, o índice de RIP foi de 15,0% no primeiro terço, 6,9% no segundo terço e 5,7% no terceiro quarto, P=0,01. Dividindo em quartis, o índice de RIP foi de 15,8% no primeiro quarto, enquanto o último quarto foi de 5,9%, P=0,03. O índice de RIP foi de 6,3% para lesões tipo 0-IIa e de 14,1% para lesões tipo 0-Is, P=0,01. O índice de RIP foi de 9,2% para lesões serrilhadas e adenomatosas. Houve falha na recuperação dos espécimes em 3,6% dos casos. Sangramento imediato (>30 s) ocorreu em um caso (0,2%), controlado com plasma de argônio. Sem sangramento tardio e perfuração. Conclusão: PF é uma técnica segura que apresenta bons resultados para a ressecção de pequenas lesões não pediculadas, com uma curta curva aprendizado.

Antral plexiform fibromyxoma: case report of a rare mesenchymal neoplasm

Plexiform fibromyxoma (PF) is a rare mesenchymal neoplasm of the stomach usually arising in the gastric antrum, and its main differential diagnosis is gastrointestinal stromal tumor. Most common symptoms are hematemesis, anemia. Immunohistochemically, positivity for smooth muscle actin (SMA) and vimentin suggests the diagnosis of PF. We report the case of a 56-year-old female patient with a 30- day history of nausea at presentation 4 years ago. Gastroscopy at that time revealed a subepithelial lesion (SEL) in the gastric antrum, measuring approximately 20 mm in diameter, with leakage of serous fluid after biopsy. Histopathology showed only an inflammatory process. Follow-up gastroscopies were performed 24, 36, and 48 months later, with surveillance biopsy at each follow-up. The last gastroscopies showed changes in lesion appearance, reduction in size, and absence of fluid leakage. Histopathology showed bland spindle cell proliferation, with a vaguely plexiform/multinodular pattern, in a fibromyxoid stroma with an arborizing capillary network without mitoses. The tumor cells were positive for SMA and negative for DOG1, CD117, CD34, S100, desmin, EMA, CD10, calponin, and beta-catenin. The choice of treatment and follow-up depends on the SEL features, but because no cases of malignancy or metastatic disease have previously been reported, the patient chose a conservative approach.

El fibromixoma plexiforme (FP) es una rara neoplasia mesenquimatosa del estómago que generalmente surge en el antro gástrico. Su principal diagnóstico diferencial es el tumor del estroma gastrointestinal. Los síntomas más comunes de los FP son hematemesis y anemia. Inmunohistoquímicamente, la positividad para actina del músculo liso (SMA) y vimentina sugieren el diagnóstico de FP. Presentamos el caso de una paciente de 56 años de edad que inicia su enfermedad hace 4 años con náuseas de 30 días de evolución. La primera gastroscopia reveló una lesión subepitelial (SEL) en el antro gástrico, de aproximadamente 20 mm de diámetro, con fuga de líquido seroso después de la biopsia. La histopatología mostró sólo un proceso inflamatorio. Se realizaron gastroscopias de seguimiento a los 24, 36 y 48 meses con biopsia de vigilancia en cada seguimiento. Las gastroscopias siguientes mostraron cambios en la apariencia de la lesión, reducción de tamaño y ausencia de fuga de líquido. La última histopatología mostró una proliferación blanda de células fusiformes, con un patrón vagamente plexiforme/multinodular, en un estroma fibromixoide con una red de capilares arborizantes sin mitosis. Las células tumorales fueron positivas para SMA y negativas para DOG1, CD117, CD34, S100, desmina, EMA, CD10, calponina y beta-catenina. La elección del tratamiento y el seguimiento depende de las características del SEL, sin embargo, por ser una enfermedad que no presentaba rasgos de enfermedad maligna o metastásica, el paciente eligió un mantener un enfoque conservador.

Physicochemical and microbiological parameters of rumen fluid of lactating goats fed diets containing crude glycerin from waste frying oil used in biodiesel production.

Crude glycerin from the biodiesel industry is a alternative energy source used to replace part of the energy components of the diet, since the nutritional value of glycerol makes it suitable for use in ruminant diets. The objective was to analyze the effects including crude glycerin (CG) derived from the production of biodiesel from residual frying oil, in diets of lactating goats on the physicochemical and microbiological parameters of rumen fluid. Eight 2-year-old goats weighting approximately 42.06 ± 3.5 kg of body weight (BW) were kept in individual stalls, receiving diets containing 0, 7, 14 and 21% of CG (% DM). The experiment was carried out according to a double 4 × 4 Latin square and lasted for 80 days. Orthogonal contrasts were tested to determine linear and quadratic effects, as well as the effects of 0% CG in the diet in comparison to the other treatments. There was a linear decreasing effect on DM intake (P = 0.001) and neutral detergent fiber (P = 0.0001), as well as a quadratic effect (P = 0.0002) on ether extract (EE) intake with increasing level of CG in the diet. Including CG affected motility and density of the protozoa (P = 0.0001). Treatments had no effect on pH, N-NH3 concentration and percentage of protozoa in the rumen liquid. There was increasing linear effect on sedimentation and flotation time (P = 0.001). Therefore, including 14 and 21% CG in the diet as a source of glycerol decreased nutrient intake and altered the ruminal microbiota, but pH and N-NH3 were not affected. Thus, to avoid impairment to the physicochemical and microbiological parameters of the rumen liquid of goats, the inclusion of CG should not exceed 7% DM.

Pharmacological NF-κB inhibition decreases cisplatin chemoresistance in muscle-invasive bladder cancer and reduces cisplatin-induced toxicities.

Most patients with muscle-invasive bladder cancer (MIBC) are not cured with platinum chemotherapy. Up-regulation of nuclear factor kappa light-chain enhancer of activated B cells (NF-κB) is a major mechanism underlying chemoresistance, suggesting that its pharmacological inhibition may increase platinum efficacy. NF-κB signaling was investigated in two patient cohorts. The Cancer Genome Atlas (TCGA) was used to correlate NF-κB signaling and patient survival. The efficacy of cisplatin plus the NF-κB inhibitor dimethylaminoparthenolide (DMAPT) versus cisplatin or DMAPT alone was tested in vitro. Xenografted and immunocompetent MIBC mouse models were studied in vivo. Platinum-naive claudin-low MIBC showed constitutive NF-κB signaling and this was associated with reduced disease-specific survival in TCGA patients. Chemotherapy up-regulated NF-κB signaling and chemoresistance-associated genes, including SPHK1, PLAUR, and SERPINE1. In mice, DMAPT significantly improved the efficacy of cisplatin in both models. The combination preserved body weight, renal function, and morphology, reduced muscle fatigue and IL-6 serum levels, and did not aggravate immuno-hematological toxicity compared with cisplatin alone. These data provide a rationale for combining NF-κB inhibition with platinum-based chemotherapy and conducting a clinical trial in MIBC patients.

Chemical remodeling of a cellular chaperone to target the active state of mutant KRAS.

The discovery of small-molecule inhibitors requires suitable binding pockets on protein surfaces. Proteins that lack this feature are considered undruggable and require innovative strategies for therapeutic targeting. KRAS is the most frequently activated oncogene in cancer, and the active state of mutant KRAS is such a recalcitrant target. We designed a natural product-inspired small molecule that remodels the surface of cyclophilin A (CYPA) to create a neomorphic interface with high affinity and selectivity for the active state of KRASG12C (in which glycine-12 is mutated to cysteine). The resulting CYPA:drug:KRASG12C tricomplex inactivated oncogenic signaling and led to tumor regressions in multiple human cancer models. This inhibitory strategy can be used to target additional KRAS mutants and other undruggable cancer drivers. Tricomplex inhibitors that selectively target active KRASG12C or multiple RAS mutants are in clinical trials now (NCT05462717 and NCT05379985).