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Background: Erdafitinib is the first targeted therapy approved for the treatment of patients with metastatic urothelial carcinoma (mUC). Approval was based on a phase II single-arm trial that demonstrated significant activity of erdafitinib in patients with tumors harboring FGFR2/3 alterations. In Brazil, an Expanded Access Program (EAP) provided patients with early access to erdafitinib prior to market authorization. The current report describes characteristics and outcomes of patients with mUC on erdafitinib therapy. Methods: Patients with mUC that failed first- and second-line systemic therapies were screened for FGFR2/3 alterations in primary or metastatic tumor tissues. Patients with FGFR2/3 alterations were selected to receive erdafitinib at the standard dosing schedule and were followed prospectively to evaluate the efficacy and safety outcomes. Results: From 19 April 2019, through 13 March 2020, 47 patients with mUC from 10 Brazilian centers were tested for FGFR2/3 alterations. Alterations in FGFR2/3 were found in 12 patients (25.5%) and all of them were eligible for the EAP. Four patients (33%) had partial response, while two patients (17%) had stable disease. Progressive disease, the best response, was observed in five patients (42%). At a median follow-up of 16.2 months, the median time to treatment failure (TTF) was 2.8 months. When considering only patients with objective response, the median TTF was 5.3 months. Adverse events (AEs) were reported for any grade and grade 3 or higher in 10 patients (83%) and 5 patients (42%), respectively. The most common AE was hyperphosphatemia. Conclusion: This first real-world evidence report of heavily treated patients with mUC confirms the efficacy and safety of erdafitinib in a disease setting with a lack of treatment options.

PurposeThe outcome of RCC has improved considerably in the last few years, and the treatment options have increased. LACOG-GU and LARCG held a consensus meeting to develop guidelines to support the clinical decisions of physicians and other health professionals involved in the care of RCC patients.MethodsEighty questions addressing relevant advanced RCC treatments were previously formulated by a panel of experts. The voting panel comprised 26 specialists from the LACOG-GU/LARCG. Consensus was determined as 75% agreement. For questions with less than 75% agreement, a new discussion was held, and consensus was determined by the majority of votes after the second voting session.ResultsThe recommendations were based on the highest level of scientific evidence or by the opinion of the RCC experts when no relevant research data were available.ConclusionThis manuscript provides guidance for advanced RCC treatment according to the LACOG-GU/LARCG expert recommendations.

Werner’s syndrome is caused by the inactivation of both WRN alleles and is characterized by premature aging and increased risk of neoplasms, especially those of mesenchymal origins, such as sarcomas. Given the characteristic genomic instability, patients with this syndrome are more susceptible to develop toxicities when exposed to cytotoxic agents, such as alkylators and anthracyclines. The impact of the monoallelic WRN mutation on treatment-associated toxicities is poorly understood. Here, we report a patient with locally advanced dedifferentiated liposarcoma of the retroperitoneum harboring a heterozygous germline inactivation mutation in the WRN gene, who was treated with a classic regimen of ifosfamide and doxorubicin and developed exacerbated and prolonged hematological and renal toxicities.

Background: Renal cell cancer (RCC) is one of the 10 most common cancers in the world, and its incidence is increasing, whereas mortality is declining only in developed countries. Therefore, two collaborative groups, The Latin American Oncology Cooperative Group-Genitourinary Section (LACOG-GU) and the Latin American Renal Cancer Group (LARCG), held a consensus meeting to develop this guideline. Methods: Issues (134) related to the treatment of RCC were previously formulated by a panel of experts. The voting panel comprised 26 specialists (urologists and medical oncologists) from the LACOG-GU/LARCG. A consensus was reached if 75% agreement was achieved. If there was less concordance, a new discussion was undertaken, and a consensus was determined by the most votes after a second voting session. Results: The expert meeting provided recommendations that were in line with the global literature; 75.0% of the recommendations made by the panel of experts were evidence-based level A, 22.5% of the recommendations were level B, and 2.5% of the recommendations were level D. Conclusions: This review suggests recommendations for the surgical treatment of RCC according to the LACOG-GU/LARCG experts.

Purpose Renal cell carcinoma is an aggressive disease with a high mortality rate. Management has drastically changed with the new era of immunotherapy, and novel strategies are being developed; however, identifying systemic treatments is still challenging. This paper presents an update of the expert panel consensus from the Latin American Cooperative Oncology Group and the Latin American Renal Cancer Group on advanced renal cell carcinoma management in Brazil. Methods A panel of 34 oncologists and experts in renal cell carcinoma discussed and voted on the best options for managing advanced disease in Brazil, including systemic treatment of early and metastatic renal cell carcinoma as well as nonclear cell tumours. The results were compared with the literature and graded according to the level of evidence. Results Adjuvant treatments benefit patients with a high risk of recurrence after surgery, and the agents used are pembrolizumab and sunitinib, with a preference for pembrolizumab. Neoadjuvant treatment is exceptional, even in initially unresectable cases. First-line treatment is mainly based on tyrosine kinase inhibitors (TKIs) and immune checkpoint inhibitors (ICIs); the choice of treatment is based on the International Metastatic Database Consortium (IMCD) risk score. Patients at favourable risk receive ICIs in combination with TKIs. Patients classified as intermediate or poor risk receive ICIs, without preference for ICI + ICIs or ICI + TKIs. Data on nonclear cell renal cancer treatment are limited. Active surveillance has a place in treating favourable-risk patients. Either denosumab or zoledronic acid can be used for treating metastatic bone disease. Conclusion Immunotherapy and targeted therapy are the standards of care for advanced disease. The utilization and sequencing of these therapeutic agents hinge upon individual risk scores and responses to previous treatments. This consensus reflects a commitment to informed decision-making, drawn from professional expertise and evidence in the medical literature.

This study aimed to compare the conventional soybean ( Glycine max L.) cultivation method with integrated systems in an Latossolo Vermelho Acriférrico típico and how these systems affect soil cover biomass production, initial nutrient concentration in plant residues, soil respiration and microclimate, as well as soybean growth, physiology and productivity. A comparative analysis of microclimate and soil respiration, plant physiology, and growth was conducted between a conventional soybean monoculture (soybean grown without plant residues on the soil from the previous crop) and soybean grown in soil containing maize residues. Additionally, experiments were conducted to evaluate the effect of monocultures and previous integration between maize, three cultivars of Panicum maximum (Zuri, Tamani, and Quênia guinea grass) and Pigeon pea ( Cajanus cajan cv. BRS Mandarim) on soil health, physiological aspects, and soybean production. Our results indicated that all cultivars of Panicum maximum can be used in integrated systems. The triple consortium resulted in greater production of ground cover biomass and a higher concentration of nitrogen, phosphorus, potassium and sulphur, which contributed to lower soil temperature and greater humidity, without a concomitant increase in soil respiration. Consequently, soybeans grown in the resulting integrated systems cover biomass showed a higher net photosynthesis rate and increased leaf chlorophyll index, resulting in taller plants, with higher above-ground biomass production and 21.0% and a 36.8% increase in grain yield when compared to soybean cultivated on maize biomass and on soil without cover residue, respectively. The data presented in this study demonstrated that integrated systems, with the presence of grasses and legumes, improve soil climatic conditions and nutrient availability, enhancing soybean physiology and productivity characteristics, thus contributing to the sustainability of agricultural production, even in the short term. Further long-term research is strongly recommended.

Inter-cropping between annual crops with tropical forages through integration crop-livestock systems (ICL) is considered a sustainable option to increase crop diversity and soybean productivity. In this study, we evaluated (1) the biomass production, desiccation efficiency, nutrient accumulation, and biomass decomposition of soil crop residues produced by Panicum maximum plants intercropped with maize in two different sowing methods during the second harvest and (2) investigated how soil crop residues impact the productivity of soybean. The experiment was conducted in a complete block design with three replicates. We compared conventional soybean cultivation with soybean cultivated over soil crop residues produced by a previous integration between maize and two Panicum maximum cultivars: Tamani and Zuri guinea grass, within and between rows of maize plants. Our results showed that Tamani guinea grass showed the highest desiccation efficiency. Zuri and Tamani guinea grass cultivated within and between maize plants resulted in higher biomass production and nutrient cycling potential, resulting in an increase of 28.4% in soybean productivity, compared to soybean grown without soil crop residues. We concluded that ICL system is an efficient method to increase the sustainability of soybean cultivation.

Sepsis is one of the most common comorbidities observed in diabetic patients, associated with a deficient innate immune response. Recently, we have shown that glucagon possesses anti-inflammatory properties. In this study, we investigated if hyperglucagonemia triggered by diabetes might reduce the migration of neutrophils, increasing sepsis susceptibility. 21 days after diabetes induction by intravenous injection of alloxan, we induced moderate sepsis in Swiss-Webster mice through cecum ligation and puncture (CLP). The glucagon receptor (GcgR) antagonist des-his1-[Glu9]-glucagon amide was injected intraperitoneally 24h and 1h before CLP. We also tested the effect of glucagon on CXCL1/KC-induced neutrophil migration to the peritoneal cavity in mice. Neutrophil chemotaxis in vitro was tested using transwell plates, and the expression of total PKA and phospho-PKA was evaluated by western blot. GcgR antagonist restored neutrophil migration, reduced CFU numbers in the peritoneal cavity and improved survival rate of diabetic mice after CLP procedure, however, the treatment did no alter hyperglycemia, CXCL1/KC plasma levels and blood neutrophilia. In addition, glucagon inhibited CXCL1/KC-induced neutrophil migration to the peritoneal cavity of non-diabetic mice. Glucagon also decreased the chemotaxis of neutrophils triggered by CXCL1/KC, PAF, or fMLP in vitro . The inhibitory action of glucagon occurred in parallel with the reduction of CXCL1/KC-induced actin polymerization in neutrophils in vitro , but not CD11a and CD11b translocation to cell surface. The suppressor effect of glucagon on CXCL1/KC-induced neutrophil chemotaxis in vitro was reversed by pre-treatment with GcgR antagonist and adenylyl cyclase or PKA inhibitors. Glucagon also increased PKA phosphorylation directly in neutrophils in vitro . Furthermore, glucagon impaired zymosan-A-induced ROS production by neutrophils in vitro . Human neutrophil chemotaxis and adherence to endothelial cells in vitro were inhibited by glucagon treatment. According to our results, this inhibition was independent of CD11a and CD11b translocation to neutrophil surface or neutrophil release of CXCL8/IL-8. Altogether, our results suggest that glucagon may be involved in the reduction of neutrophil migration and increased susceptibility to sepsis in diabetic mice. This work collaborates with better understanding of the increased susceptibility and worsening of sepsis in diabetics, which can contribute to the development of new effective therapeutic strategies for diabetic septic patients.

The advance of digital agriculture combined with computational tools and Unmanned Aerial Vehicles (UAVs) has enabled the collection of data for reliably extracting vegetation indices and biophysical parameters derived from the Structure from Motion (SfM) algorithm. This work aimed to evaluate the accuracy of the photogrammetry technique using an SfM point cloud for the estimation of the height (h) and crown diameter (d) of coffee trees from aerial images obtained by UAV with an RGB (Red, Green, Blue) camera and compared the results with data measured in situ for 12 months. The experiment was carried out in a coffee plantation, Lavras, Minas Gerais, Brazil. A rotary-wing UAV was used in autonomous flight mode and coupled to a conventional camera, flying at a height of 30 m with an image overlap of 80% and a speed of 3 m/s. The images were processed using PhotoScan software, and the analyses were performed in Qgis. A correlation of 87% was obtained between the h values in the field and h values obtained by the UAV, and there was a 95% correlation between the d values obtained in the field and the values obtained by the UAV. It was possible to obtain significant estimates of the attributes, such as the h and d of coffee trees, using UAV–SfM images acquired with an RGB digital camera.

PurposeIodine deficiency disorder (IDD) is an ongoing worldwide recognized problem with over two billion individuals having insufficient iodine intake. School-aged children and pregnant women are often target groups for epidemiological studies, but there is a lack of knowledge on the general adult population. The aim of this study was to assess the iodine status among a Portuguese public university staff as a proxy for the adult working population.MethodsThe population study covered 103 adults within the iMC Salt randomized clinical trial, aged 24–69 years. Urinary iodine concentration was measured spectrophotometrically using the Sandell–Kolthoff reaction. Iodine food intake was assessed using a 24-h dietary recall. The contribution of discretionary salt to the iodine daily intake was assessed through 24-h urinary sodium excretion (UIE) and potentiometric iodine determination of household salt.ResultsThe mean urine volume in 24 h was 1.5 L. The median daily iodine intake estimated from 24-h UIE was 113 µg/day, being lower among women (p < 0.05). Only 22% of participants showed iodine intake above the WHO-recommended cutoff (150 µg/day). The median daily iodine intake estimated from the 24-h dietary recall was 58 µg/day (51 and 68 µg/day in women and men, respectively). Dairy, including yoghurt and milk products, were the primary dietary iodine source (55%). Iodine intake estimated from 24-h UIE and 24-h dietary recall was moderately correlated (Spearman rank correlation coefficient r = 0.34, p < 0.05). The average iodine concentration in household salt was 14 mg I/kg, with 45% of the samples below the minimum threshold preconized by WHO (15 mg I/kg). The contribution of discretionary salt to the daily iodine intake was around 38%.ConclusionThis study contributes new knowledge about iodine status in Portuguese working adults. The results revealed moderate iodine deficiency, particularly in women. Public health strategies and monitoring programs are needed to ensure iodine adequacy in all population groups.