Brazilian Society of Angiology and Vascular Surgery 2023 guidelines on the diabetic foot.

The diabetic foot interacts with anatomical, vascular, and neurological factors that challenge clinical practice. This study aimed to compile the primary scientific evidence based on a review of the main guidelines, in addition to articles published on the Embase, Lilacs, and PubMed platforms. The European Society of Cardiology system was used to develop recommendation classes and levels of evidence. The themes were divided into six chapters (Chapter 1 - Prevention of foot ulcers in people with diabetes; Chapter 2 - Pressure relief from foot ulcers in people with diabetes; Chapter 3 -Classifications of diabetic foot ulcers; Chapter 4 - Foot and peripheral artery disease; Chapter 5 - Infection and the diabetic foot; Chapter 6 - Charcot's neuroarthropathy). This version of the Diabetic Foot Guidelines presents essential recommendations for the prevention, diagnosis, treatment, and follow-up of patients with diabetic foot, offering an objective guide for medical practice.

PCM4EU and PRIME-ROSE: Collaboration for implementation of precision cancer medicine in Europe.

BACKGROUND: In the two European Union (EU)-funded projects, PCM4EU (Personalized Cancer Medicine for all EU citizens) and PRIME-ROSE (Precision Cancer Medicine Repurposing System Using Pragmatic Clinical Trials), we aim to facilitate implementation of precision cancer medicine (PCM) in Europe by leveraging the experience from ongoing national initiatives that have already been particularly successful. PATIENTS AND METHODS: PCM4EU and PRIME-ROSE gather 17 and 24 partners, respectively, from 19 European countries. The projects are based on a network of Drug Rediscovery Protocol (DRUP)-like clinical trials that are currently ongoing or soon to start in 11 different countries, and with more trials expected to be established soon. The main aims of both the projects are to improve implementation pathways from molecular diagnostics to treatment, and reimbursement of diagnostics and tumour-tailored therapies to provide examples of best practices for PCM in Europe. RESULTS: PCM4EU and PRIME-ROSE were launched in January and July 2023, respectively. Educational materials, including a podcast series, are already available from the PCM4EU website (http://www.pcm4eu.eu). The first reports, including an overview of requirements for the reimbursement systems in participating countries and a guide on patient involvement, are expected to be published in 2024. CONCLUSION: PCM4EU and PRIME-ROSE were launched in January and July 2023, respectively. Educational materials, including a podcast series, are already available from the PCM4EU website (http://www.pcm4eu.eu). The first reports, including an overview of requirements for the reimbursement systems in participating countries and a guide on patient involvement, are expected to be published in 2024. CONCLUSION: European collaboration can facilitate the implementation of PCM and thereby provide affordable and equitable access to precision diagnostics and matched therapies for more patients.

Spatio-temporal analysis of American Tegumentary Leishmaniasis incidences in the Brazilian state of Amazonas: 2011 to 2022.

This study aimed to conduct a spatio-temporal analysis of tegumentary leishmaniasis occurrences in the Amazonas state, Brazil. An ecological study encompassing time series and spatial analysis was performed, exploring the geographic distribution and temporal trends of American Tegumentary Leishmaniasis (ATL) in Amazonas between 2011 and 2022. Secondary data extracted from the Department of Informatics of the Unified Health System (DATASUS) were utilized for this analysis. The study evaluated the relationship between disease cases and environmental/climatic variables (deforestation, temperature, precipitation, and relative humidity). Over the study period, 19,730 cases of tegumentary leishmaniasis were recorded, averaging an incidence of 41.4/100,000 inhabitants across the 62 municipalities of Amazonas state. Disease intensity varied with seasons. Generally, Amazonas state displayed a declining trend in ATL cases. However, certain municipalities, notably Rio Preto da Eva and Presidente Figueiredo, exhibited high incidence rates, while Canutama, Envira, Eirunepé, and Pauini municipalities demand closer attention due to their demonstrated increasing temporal trend of ATL cases. The analysis indicated a correlation between the number of ATL cases reported and relative humidity as well as precipitation. These findings underscore the significance of tegumentary leishmaniasis as a public health issue in the region and emphasize the necessity for public initiatives aimed at preventing this endemic illness.

Full-fat corn germ improves the performance and milk fat yield of Girolando cows fed sugarcane bagasse and cactus cladodes as forage sources.

We investigated the effects of replacing ground corn with full-fat corn germ (FFCG) on milk production, milk composition, and nutrient use in cows fed sugarcane bagasse and cactus cladodes. Ten multiparous Girolando cows (average body weight 500 ± 66 kg, 90 ± 15 days in milk) were distributed in a replicated 5 × 5 Latin Square and assigned to five dietary treatments containing 0%, 25%, 50%, 75%, or 100% of full-fat corn germ in substitution to ground corn. Full-fat corn germ increased fat-corrected milk yield by 2.2 kg/day and the synthesis of fat, lactose, and total solids in milk by 94.4, 60.0, and 201.10 g/day, respectively (p < 0.05). Cows fed corn germ quadratically increased (p < 0.05) dry matter intake by 1.01 kg/day, with the intake of crude protein and total digestible nutrients following the same pattern. Conversely, the substitution of corn for full-fat corn germ linearly reduced (p < 0.05) the total non-fiber carbohydrate intake from 5.79 to 4.40 kg/d. Except for ether extract and non-fiber carbohydrates, full-fat corn germ did not alter (p > 0.05) nutrient digestibility. Cows fed corn germ excreted less (p < 0.05) urea-N in milk and urine N. These results demonstrate that full-fat corn germ can partially replace ground corn to enhance the milk production efficiency of crossbred cows fed cactus cladodes and sugarcane bagasse. Furthermore, including sugarcane bagasse in FFCG-supplemented diets prevents milk fat depression in cows fed cactus cladodes.

EORTC-SPECTA Arcagen study, comprehensive genomic profiling and treatment adaptation of rare thoracic cancers.

Arcagen (NCT02834884) is a European prospective study aiming at defining the molecular landscape of rare cancers for treatment guidance. We present data from the cohort of rare thoracic tumors. Patients with advanced pleural mesothelioma (PM) or thymic epithelial tumors (TET) underwent genomic profiling with large targeted assay [>300 genes, tumor mutational burden (TMB), microsatellite instability (MSI) status] on formalin-fixed paraffin-embedded (FFPE) or plasma samples. EORTC molecular tumor board (MTB) advised for biomarker-guided treatments. 102 patients recruited from 8 countries between July 2019 and May 2022 were evaluable: 56 with PM, 46 with TET (23 thymomas, 23 thymic carcinomas). Molecular profiling was performed on 70 FFPE samples (42 PM, 28 TET), and 32 cases on ctDNA (14 PM, 18 TET), within a median turnaround time of 8 days from sample reception. We detected relevant molecular alterations in 66 out of 102 patients (65%; 79% PM, 48% TET), 51 of 70 FFPE samples (73%; 90% PM, 46% TET), and 15 of 32 plasma samples (47%; 43% PM, 50% TET). The most frequently altered genes were CDKN2A/B, BAP1, MTAP in PM and TP53, CDKN2A/B, SETD2 in TET. The TMB was low (mean 3.2 Muts/MB), 2 PM had MSI-high status. MTB advised molecular-guided treatment options in 32 situations, for 17 PM and 15 TET patients (75% clinical trial option, 22% off-label drug or compassionate use, 3% early access program). Molecular testing and MTB discussion were feasible for patients with rare thoracic cancers and allowed the broadening of treatment options for 30% of the cases.

Brazilian guidelines on diagnosis and management of traumatic vascular injuries.

Trauma is a leading cause of death, permanent disability, and health care cost worldwide. The young and economically active are the most affected population. Exsanguination due to noncompressible torso hemorrhage is one of the most frequent causes of early death, posing a significant challenge to trauma and vascular surgeons. The possibility of limb loss due to vascular injuries must also be considered. In recent decades, the approach to vascular injuries has been significantly modified. Angiotomography has become the standard method for diagnosis, endovascular techniques are currently incorporated in treatment, and damage control, such as temporary shunts, is now the preferred approach for the patients sustaining physiological derangement. Despite the importance of this topic, few papers in the Brazilian literature have offered guidelines on vascular trauma. The Brazilian Society of Angiology and Vascular Surgery has developed Projetos Diretrizes (Guideline Projects), which includes this publication on vascular trauma. Since treating trauma patients is a multidisciplinary effort, the Brazilian Trauma Society (SBAIT) was invited to participate in this project. Members of both societies reviewed the literature on vascular trauma management and together wrote these guidelines on vascular injuries of neck, thorax, abdomen, and extremities.

Guidelines on vascular access for hemodialysis from the Brazilian Society of Angiology and Vascular Surgery.

Chronic kidney disease is a worldwide public health problem, and end-stage renal disease requires dialysis. Most patients requiring renal replacement therapy have to undergo hemodialysis. Therefore, vascular access is extremely important for the dialysis population, directly affecting the quality of life and the morbidity and mortality of this patient population. Since making, managing and salvaging of vascular accesses falls within the purview of the vascular surgeon, developing guideline to help specialists better manage vascular accesses for hemodialysis if of great importance. Thus, the objective of this guideline is to present a set of recommendations to guide decisions involved in the referral, evaluation, choice, surveillance and management of complications of vascular accesses for hemodialysis.

A doença renal crônica é um problema de saúde pública global e em seu estágio terminal está associada à necessidade de terapia dialítica. A grande maioria dos pacientes que necessitam realizar a terapia renal substitutiva, a fazem através da hemodiálise. Portanto, o acesso vascular é de extrema importância para a população dialítica, implicando diretamente na qualidade de vida e na morbimortalidade deste grupo de pacientes. Sendo a confecção, gerenciamento e resgate dos acessos vasculares uma das áreas de atuação do cirurgião vascular, é de grande importância a elaboração de uma diretriz que oriente o especialista no manejo mais adequado do acesso vascular para hemodiálise. Assim, o objetivo desta diretriz é apresentar um conjunto de recomendações para guiar as decisões na referenciação, avaliação, escolha, vigilância e gestão das complicações do acesso vascular para hemodiálise.

Brazilian guidelines on chronic venous disease of the Brazilian Society of Angiology and Vascular Surgery.

The Brazilian Society of Angiology and Vascular Surgery has set up a committee to provide new evidence-based recommendations for patient care associated with chronic venous insufficiency. Topics were divided in five groups: 1. Classification, 2. Diagnosis, 3. Conservative or non-invasive treatment, 4. Invasive treatment and 5. Treatment of small vessels. This last series is closely related to the activities of Brazilian angiologists and vascular surgeons, who are heavily involved in the treatment of small superficial veins. These guidelines are intended to assist in clinical decision-making for attending physicians and health managers. The decision to follow a guideline recommendation should be made by the responsible physician on a case-by-case basis taking into account the patient's specific condition, as well as local resources, regulations, laws, and clinical practice recommendations.

A Sociedade Brasileira de Angiologia e de Cirurgia Vascular organizou uma comissão para fornecer novas recomendações baseadas em evidências sobre questões críticas de atendimento ao paciente com insuficiência venosa crônica. São abordados aqui os temas de classificação, diagnóstico, tratamento conservador, tratamento invasivo e tratamento de pequenos vasos. Esta última série está muito relacionada à atividade de angiologistas e cirurgiões vasculares, que possuem forte atuação no tratamento de pequenas veias superficiais. Estas diretrizes destinam-se a auxiliar na tomada de decisões clínicas de médicos assistentes e gestores de saúde. A decisão de seguir uma recomendação de diretriz deve ser feita pelo médico responsável caso a caso, levando em consideração a condição específica do paciente, bem como recursos locais, regulamentos, leis e recomendações de prática clínica.

Brazilian Society for Angiology and Vascular Surgery guidelines on abdominal aortic aneurysm.

The Brazilian Society of Angiology and Vascular Surgery, through the Guidelines Project, presents new Abdominal Aortic Aneurysm Guidelines, on the subject of care for abdominal aortic aneurysm patients. Its development prioritized descriptive guidelines, using the EMBASE, LILACS, and PubMed databases. References include randomized controlled trials, systematic reviews, meta-analyses, and cohort studies. Quality of evidence was evaluated by a pair of coordinators, aided by the RoB 2 Cochrane tool and the Newcastle Ottawa Scale forms. The subjects include juxtarenal aneurysms, infected aneurysms, and new therapeutic techniques, especially endovascular procedures. The current version of the guidelines include important recommendations for the primary topics involving diagnosis, treatment, and follow-up for abdominal aortic aneurysm patients, providing an objective guide for medical practice, based on scientific evidence and widely available throughout Brazil.

A Sociedade Brasileira de Angiologia e Cirurgia Vascular, por meio do projeto Diretrizes, apresenta as novas Diretrizes de Aorta Abdominal, referentes aos cuidados de pacientes com aneurisma de aorta abdominal. Para sua elaboração, foram priorizadas diretrizes descritivas, utilizando as bases EMBASE, LILACS e PubMed. As referências incluem ensaios clínicos randomizados, revisões sistemáticas, metanálises e estudos de coorte. A qualidade das evidências foi examinada por uma dupla de coordenadores, com auxílio da ferramenta RoB 2 da Colaboração Cochrane e dos formulários da Newcastle Ottawa Scale. Aneurismas justarrenais, infectados e novas técnicas terapêuticas, principalmente no âmbito endovascular, estão entre os temas estudados. A versão atual das Diretrizes apresenta importantes recomendações para os principais itens que envolvem o diagnóstico, tratamento e acompanhamento de pacientes com aneurisma de aorta abdominal, oferecendo um guia objetivo para prática médica, construído a partir de evidências científicas e amplamente acessível em todo o território nacional.

Cognitive abilities and medical students' practice of physical exams: A quasi-experimental study.

BACKGROUND: To highlight the importance of clinical simulations and simulated laboratories for student training, especially in physical examination teaching. OBJECTIVE: To evaluate the gains obtained by medical students in their cognitive and practical performance of physical examinations (abdominal, cardiological, and pulmonary), as well as satisfaction and self-confidence in what they have learned, after concentrated practice developed in a skills and simulation laboratory. DESIGN AND SETTING: A quantitative and quasi-experimental study in which 48 students were evaluated at the Faculdade de Odontologia de Bauru, São Paulo, Brazil. METHODS: A quantitative and descriptive study was conducted with regularly enrolled 2nd year medical students over 18 years of age who had content prior to data collection regarding anamnesis and physical examination remotely taught in a Moodle virtual learning environment. For data collection, the participants were subjected to a concentrated period of skill training (abdominal, cardiological, and pulmonary). Every day after the skill training session, they were subjected to a practical evaluation and completed a theoretical test before and after the practical activities. At the end of all activities, they answered the instrument to assess the simulated practices (self-confidence and satisfaction). RESULTS: Among the 49 students evaluated, positive and significant theoretical and practical gains were identified in all three components (abdominal, cardiological, and pulmonary) (P = 0.000), as well as in the general evaluation (Theoretical 1 and Theoretical 2) (P = 0.000), satisfaction, and self-confidence (P = 0.000). CONCLUSION: Concentrated laboratory practice resulted in positive improvements in students' physical examination skills.

Application of Mixed Reality to Ultrasound-guided Femoral Arterial Cannulation During Real-time Practice in Cardiac Interventions.

Mixed reality opens interesting possibilities as it allows physicians to interact with both, the real physical and the virtual computer-generated environment and objects, in a powerful way. A mixed reality system, based in the HoloLens 2 glasses, has been developed to assist cardiologists in a quite complex interventional procedure: the ultrasound-guided femoral arterial cannulations, during real-time practice in interventional cardiology. The system is divided into two modules, the transmitter module, responsible for sending medical images to HoloLens 2 glasses, and the receiver module, hosted in the HoloLens 2, which renders those medical images, allowing the practitioner to watch and manage them in a 3D environment. The system has been successfully used, between November 2021 and August 2022, in up to 9 interventions by 2 different practitioners, in a large public hospital in central Spain. The practitioners using the system confirmed it as easy to use, reliable, real-time, reachable, and cost-effective, allowing a reduction of operating times, a better control of typical errors associated to the interventional procedure, and opening the possibility to use the medical imagery produced in ubiquitous e-learning. These strengths and opportunities were only nuanced by the risk of potential medical complications emerging from system malfunction or operator errors when using the system (e.g., unexpected momentary lag). In summary, the proposed system can be taken as a realistic proof of concept of how mixed reality technologies can support practitioners when performing interventional and surgical procedures during real-time daily practice.

Treatment patterns and healthcare resource utilization for triple negative breast cancer in the Brazilian private healthcare system: a database study.

In Brazil, data on the management of triple negative breast cancer (TNBC) as well as the burden of the disease in terms of health care resources utilization (HCRU) are scarce. To characterize the treatment patterns and HCRU associated with the management of Brazilian TNBC patients from the perspective of the private healthcare setting. Patients with at least one claim related to ICD-10 C50 from January 2012 until December 2017, and at least one claim for breast cancer treatment were assessed from a private claims database and classified as early and locally advanced, or metastatic. All patients with hormone and/or targeted therapy were excluded. Three thousand and four patients were identified, of which 82.8% were diagnosed in early and locally advanced stages. For early and locally advanced TNBC patients, 75.3% were treated in an adjuvant setting, mainly with anthracycline regimes. For mTNBC patients, bevacizumab regimens were the main treatment prescribed. More than 48% of mTNBC patients were switched to a second line of treatment. HCRU was higher for mTNBC patients when compared to early and locally advanced patients, with higher costs for metastatic disease management. The treatment setting has little influence on the HCRU pattern or the cost of disease management. The highest burden of disease was observed for metastatic management.

Neoadjuvant Durvalumab Alone or Combined with Novel Immuno-Oncology Agents in Resectable Lung Cancer: The Phase II NeoCOAST Platform Trial.

Neoadjuvant chemoimmunotherapy improves pathologic complete response rate and event-free survival in patients with resectable non-small cell lung cancer (NSCLC) versus chemotherapy alone. NeoCOAST was the first randomized, multidrug platform trial to examine novel neoadjuvant immuno-oncology combinations for patients with resectable NSCLC, using major pathologic response (MPR) rate as the primary endpoint. Eighty-three patients received a single cycle of treatment: 26 received durvalumab (anti-PD-L1) monotherapy, 21 received durvalumab plus oleclumab (anti-CD73), 20 received durvalumab plus monalizumab (anti-NKG2A), and 16 received durvalumab plus danvatirsen (anti-STAT3 antisense oligonucleotide). MPR rates were higher for patients in the combination arms versus durvalumab alone. Safety profiles for the combinations were similar to those of durvalumab alone. Multiplatform immune profiling suggested that improved MPR rates in the durvalumab plus oleclumab and durvalumab plus monalizumab arms were associated with enhanced effector immune infiltration of tumors, interferon responses and markers of tertiary lymphoid structure formation, and systemic functional immune cell activation. SIGNIFICANCE: A neoadjuvant platform trial can rapidly generate clinical and translational data using candidate surrogate endpoints like MPR. In NeoCOAST, patients with resectable NSCLC had improved MPR rates after durvalumab plus oleclumab or monalizumab versus durvalumab alone and tumoral transcriptomic signatures indicative of augmented immune cell activation and function. See related commentary by Cooper and Yu, p. 2306. This article is featured in Selected Articles from This Issue, p. 2293.

Superficial Femoral Artery in-Stent Restenosis Treated with Paclitaxel-Coated Balloon Angioplasty - Results of Three-Year Follow-Up.

BACKGROUND: In-stent restenosis remains a common and important complication after endovascular treatment of superficial femoral artery peripheral artery disease. It occurs in 14 to 35% of cases in 1 year and there is still no efficient treatment for this condition. Paclitaxel-coated balloons have shown promising results. OBJECTIVE: Investigate the 3 year results of superficial femoral artery in-stent restenosis treated with paclitaxel-coated balloon angioplasty, using the Lutonix™ 035 device. METHODS: We conducted a retrospective observational study with patients with symptomatic (Rutherford 2 to 5) superficial femoral artery in-stent restenosis, that were treated with paclitaxel-coated balloon angioplasty using the Lutonix™ 035 device, in a single center from January 2016 to December 2020. Duplex scan was used to follow the patients. Primary patency was obtained through Kaplan-Meier analysis. Mortality, and amputation rates were also evaluated. RESULTS: 105 patients were included. Two patients had technical failure and required an additional stent, and were thus excluded. 103 patients were analyzed. Primary patency was 91.26, 80.47, and 67.71%, respectively, in the first, second, and third year after the procedure. There were no deaths 30 days after the procedure. There were no major amputations during the 3 year follow-up. CONCLUSION: Paclitaxel-coated balloon angioplasty with the Lutonix™ 035 device was a safe and effective treatment to superficial femoral artery in-stent restenoses. The results were maintained along the 3 year follow-up.

Nutritional Quality of Milk Fat from Cows Fed Full-Fat Corn Germ in Diets Containing Cactus Opuntia and Sugarcane Bagasse as Forage Sources.

We evaluated the performance, milk composition, and milk fatty acid profile of cows fed diets composed of cactus cladodes (Opuntia stricta [Haw.] Haw), sugarcane bagasse and increasing levels of full-fat corn germ (FFCG). We hypothesized that ground corn can be effectively replaced by FFCG when cactus cladodes and sugarcane bagasse are used as forage sources. The cows were randomly distributed into two 5 × 5 Latin Squares and fed five diets in which ground corn was progressively replaced with full-fat corn germ (FFCG; 0%, 25%, 50%, 75%, or 100% of substitution). Adding FFCG to the diet increased milk production and milk fat content and reduced milk protein content. Overall, FFCG reduced the proportion of saturated FAs and increased mono- and polyunsaturated FAs in milk, including CLA isomers. In addition, activity indices of stearoyl-CoA desaturase were reduced by increasing levels of FFCG. We conclude that the substitution of corn for FFCG in diets based on cactus cladodes and sugarcane bagasse positively modifies the FA profile of milk and could add commercial value to milk products (e.g., CLA-enriched milk). In addition, the milk fat response indicates that the basal diet was favorable to the rumen environment, preventing the trans-10 shift commonly associated with milk fat depression.

New Approaches in Early-Stage NSCL Management: Potential Use of PARP Inhibitors and Immunotherapy Combination.

Lung cancer is the second most common cancer in the world, being the first cause of cancer-related mortality. Surgery remains the only potentially curative treatment for Non-Small Cell Lung Cancer (NSCLC), but the recurrence risk remains high (30-55%) and Overall Survival (OS) is still lower than desirable (63% at 5 years), even with adjuvant treatment. Neoadjuvant treatment can be helpful and new therapies and pharmacologic associations are being studied. Immune Checkpoint Inhibitors (ICI) and PARP inhibitors (PARPi) are two pharmacological classes already in use to treat several cancers. Some pre-clinical studies have shown that its association can be synergic and this is being studied in different settings. Here, we review the PARPi and ICI strategies in cancer management and the information will be used to develop a clinical trial to evaluate the potential of PARPi association with ICI in early-stage neoadjuvant setting NSCLC.