Tumor Microenvironment Modulates Invadopodia Activity of Non-Selected and Acid-Selected Pancreatic Cancer Cells and Its Sensitivity to Gemcitabine and C18-Gemcitabine.

BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) is a deadly disease with high mortality due to early metastatic dissemination and high chemoresistance. All these factors are favored by its extracellular matrix (ECM)-rich microenvironment, which is also highly hypoxic and acidic. Gemcitabine (GEM) is still the first-line therapy in PDAC. However, it is quickly deaminated to its inactive metabolite. Several GEM prodrugs have emerged to improve its cytotoxicity. Here, we analyzed how the acidic/hypoxic tumor microenvironment (TME) affects the response of PDAC cell death and invadopodia-mediated ECM proteolysis to both GEM and its C18 prodrug. METHODS: For this, two PDAC cell lines, PANC-1 and Mia PaCa-2 were adapted to pHe 6.6 or not for 1 month, grown as 3D organotypic cultures and exposed to either GEM or C18 in the presence and absence of acidosis and the hypoxia inducer, deferoxamine. RESULTS: We found that C18 has higher cytotoxic and anti-invadopodia activity than GEM in all culture conditions and especially in acid and hypoxic environments. CONCLUSIONS: We propose C18 as a more effective approach to conventional GEM in developing new therapeutic strategies overcoming PDAC chemoresistance.

Multimodality imaging to assess diagnosis and evaluate complications of large vessel arteritis.

Different types of vasculitis can be distinguished according to the blood vessel's size that is preferentially affected: large-vessel, medium-vessel, and small-vessel vasculitides. Giant cell arteritis (GCA) and Takayasu's arteritis (TAK) are the main forms of large-vessel vasculitis, and may lead to lumen narrowing. Clinical manifestations of arterial narrowing on the short- and long term include vision loss, stroke, limb ischaemia and heart failure. Imaging tools are well established diagnostic tests for large-vessel vasculitis and may aid therapy monitoring in selected cases, while providing important information regarding the occurrence of vascular damage, tissue and organ complications. This review aims to provide the current status of multimodality imaging for diagnosis and identification of vascular complications in the field of large vessel vasculitis.

A new characid species with remarkable sexual dimorphism (Characiformes: Characidae: Stevardiinae) from the upper Guayabero River, Orinoco basin, Colombia.

A new species of characid with remarkable sexual characteristics is described from the upper Guayabero River drainage from the Orinoco basin in Colombia. The new species is included in the genus Monotocheirodon by sharing most of the previously proposed diagnostic features of this genus. It differs from all Stevardiinae by the combination, in adult males, of an enlarged urogenital papilla in contact with the first anal-fin unbranched ray and a highly modified anal fin with enlarged and distally elongated first and second branched anal-fin rays, forming a gonopodium-like structure. In addition, it differs from congeners by the presence of an adipose fin, an incomplete lateral line, an ascending process of the premaxilla dorsally oriented, and a long snout. The new species was discovered from a poorly sampled region in Colombia and is an unexpected new record given its disjunct geographic distribution from other species of the genus. Monotocheirodon species were previously known from piedmont drainages in Bolivia and Peru. The conservation status of the new species is herein categorized following IUCN criteria.

Dissecting the complex genetic basis of pre- and post-harvest traits in Vitis vinifera L. using genome-wide association studies.

Addressing the pressing challenges in agriculture necessitates swift advancements in breeding programs, particularly for perennial crops like grapevines. Moving beyond the traditional biparental quantitative trait loci (QTL) mapping, we conducted a genome-wide association study (GWAS) encompassing 588 Vitis vinifera L. cultivars from a Chilean breeding program, spanning three seasons and testing 13 key yield-related traits. A strong candidate gene, Vitvi11g000454, located on chromosome 11 and related to plant response to biotic and abiotic stresses through jasmonic acid signaling, was associated with berry width and holds potential for enhancing berry size in grape breeding. We also mapped novel QTL associated with post-harvest traits across chromosomes 2, 4, 9, 11, 15, 18, and 19, broadening our grasp on the genetic intricacies dictating fruit post-harvest behavior, including decay, shriveling, and weight loss. Leveraging gene ontology annotations, we drew parallels between traits and scrutinized candidate genes, laying a robust groundwork for future trait-feature identification endeavors in plant breeding. We also highlighted the importance of carefully considering the choice of the response variable in GWAS analyses, as the use of best linear unbiased estimators (BLUEs) corrections in our study may have led to the suppression of some common QTL in grapevine traits. Our results underscore the imperative of pioneering non-destructive evaluation techniques for long-term conservation traits, offering grape breeders and cultivators insights to improve post-harvest table grape quality and minimize waste.

Firework-related ocular trauma in Pernambuco, Brazil / Trauma ocular por fogos de artifício em Pernambuco, Brasil

ABSTRACT Purpose: This study aimed to describe the demographic and clinical characteristics of victims of fireworkrelated ocular trauma treated at the ophthalmologic emergency de partments of two reference centers in Pernambuco, Brazil, and to identify risk factors related to poor visual prognosis. Methods: We retrospectively evaluated the medical records of patients admitted in emergency departments with a report of firework-related trauma between January 2012 and December 2018. Data collected included patient's age, sex, place of origin, month and year of the accident, ocular structures affected, characteristics of the injuries, and type of treatment that patients received. For patients who were followed for >30 days, the final visual acuity and patient's origin were analyzed. Results: Three hundred and seventy eyes from 314 patients were included, of which 248 (79.0%) were male and 160 (51.0%) were from the metropolitan region of Recife. The mean patient age was 25.6 ± 18.8 years. In 56 (17.8%) patients, the ocular trauma was bilateral. A total of 152 (48.4%) cases occurred in June. The most affected sites were the eyelids in 91 (24.6%) eyes and ocular surface in 252 (68.1%). Surgical treatment was required in 87 (23.5%) eyes. After clinical and surgical management, 37 (10.0%) eyes presented final visual acuity of <20/400. Of these, 34 (91.9%) eyes were from patients from the countryside or from another state. Patients from the countryside presented higher risk of developing blindness after a firework trauma than those from the metropolitan area (odds ratio of 5.46). Conclusions: Victims of firework-related ocular trauma were mostly male, from the metropolitan region of Pernambuco state and mainly pediatric patients or economically active. Those coming from the countryside and other states had higher risk of developing blindness

RESUMO Objetivos: Descrever as características demográficas e clínicas das vítimas de trauma ocular por fogos de artifício atendidas nas emergências oftalmológicas de dois centros de referência em Pernambuco e identificar fatores relacionados a mau prognóstico visual. Métodos: Avaliação retrospectiva dos prontuários de pacientes admitidos na emergência oftalmológica com história de trauma por fogos de artifício entre janeiro de 2012 e dezembro de 2018. A coleta de dados incluiu idade, gênero, procedência, mês e ano do acidente, estruturas oculares acometidas e características das lesões, além do tipo de tratamento a que os pacientes foram submetidos. Naqueles pacientes acompanhados por mais de 30 dias, analisou-se a acuidade visual final e a associação com sua procedência. Resultados: Foram incluídos 370 olhos de 314 pacientes. Destes, 248 (79,0%) vítimas eram do sexo masculino e 160 (51,0%) da região metropolitana do Recife, com uma média de idade de 25.6 ± 18.8 anos. Em 56 (17,8%) dos casos o trauma foi bilateral. No mês de junho ocorreu um total de 152 (48,4%) casos. Os sítios mais acometidos foram pálpebras em 91 (24,6%) olhos e superfície ocular em 252 (68,1%). O tratamento cirúrgico foi necessário em 87 (23,5%) olhos. Após manejo clínico-cirúrgico, 37 (10.0%) olhos desenvolveram visão pior do que 20/400. Destes, 34 (91,9%) olhos eram de pacientes do interior do estado de Pernambuco ou de outro estado. Os pacientes provenientes do interior do estado apresentaram maior chance de desenvolver cegueira quando comparados aos que eram provenientes da região metropolitana (Odds Ratio de 5,46). Conclusões: As vítimas de trauma ocular por fogos de artificio foram em sua maioria do sexo masculino, procedentes da região metropolitana do estado e das faixas etárias pediátrica e economicamente ativa. Aqueles provenientes do interior ou de outros estados apresentaram maior chance de desenvolver cegueira.

Percentage of Pancreatic Cysts on MRI With a Pancreatic Carcinoma: Systematic Review and Meta-Analysis.

BACKGROUND: Pancreatic cystic lesions (PCLs) are frequent on MRI and are thought to be associated with pancreatic adenocarcinoma (PDAC) necessitating long-term surveillance based on older studies suffering from selection bias. PURPOSE: To establish the percentage of patients with PCLs on MRI with a present or future PDAC. STUDY TYPE: Systematic review, meta-analysis. POPULATION: Adults with PCLs on MRI and a present or future diagnosis of PDAC were eligible. MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials, and Scopus were searched to April 2022 (PROSPERO:CRD42022320502). Studies limited to PCLs not requiring surveillance, <100 patients, or those with a history/genetic risk of PDAC were excluded. FIELD STRENGTH/SEQUENCE: ≥1.5 T with ≥1 T2-weighted sequence. ASSESSMENT: Two investigators extracted data, with discrepancies resolved by a third. QUADAS-2 assessed bias. PDAC was diagnosed using a composite reference standard. STATISTICAL TESTS: A meta-analysis of proportions was performed at the patient-level with 95% confidence intervals (95% CI). RESULTS: Eight studies with 1289 patients contributed to the percentage of patients with a present diagnosis of PDAC, and 10 studies with 3422 patients to the percentage with a future diagnosis. Of patients with PCLs on MRI, 14.8% (95% CI 2.4-34.9) had a PDAC at initial MRI, which decreased to 6.0% (2.2-11.3) for studies at low risk of bias. For patients without PDAC on initial MRI, 2.0% (1.1-3.2) developed PDAC during surveillance, similar for low risk of bias studies at 1.9% (0.7-3.6), with no clear trend of increased PDAC for longer surveillance durations. For patients without worrisome features or high-risk stigmata, 0.9% (0.1-2.2) developed PDAC during surveillance. Of 10, eight studies had a median surveillance ≥3 years (range 3-157 months). Sources of bias included retrospectively limiting PCLs to those with histopathology and inconsistent surveillance protocols. DATA CONCLUSION: A low percentage of patients with PCLs on MRI develop PDAC while on surveillance. The first MRI revealing a PCL should be scrutinized for PDAC. LEVEL OF EVIDENCE: 3 TECHNICAL EFFICACY: Stage 2.

Health and economic effects of introducing single-dose or two-dose human papillomavirus vaccination in India.

BACKGROUND: Cervical cancer is a major public health problem in India, where access to prevention programmes is low. The WHO-Strategic Advisory Group of Experts recently updated their recommendation for human papillomavirus (HPV) vaccination to include a single-dose option in addition to the two-dose option, which could make HPV vaccination programmes easier to implement and more affordable. METHODS: We combined projections from a type-specific HPV transmission model and a cancer progression model to assess the health and economic effects of HPV vaccination at national and state level in India. The models used national and state-specific Indian demographic, epidemiological and cost data, and single-dose vaccine efficacy and immunogenicity data from the International Agency for Research on Cancer India vaccine trial with 10-year follow-up. We compared single-dose and two-dose HPV vaccination for a range of plausible scenarios regarding single-dose vaccine protection, coverage and catch-up. We used a healthcare sector payer perspective with a time horizon of 100 years. RESULTS: Under the base-case scenario of lifelong protection of single-dose vaccination in 10-year-old girls with 90% coverage, the discounted incremental cost-effectiveness ratio (ICER) of nationwide vaccination relative to no vaccination was US$406 (₹INR30 000) per DALY (disability-adjusted life-years) averted. This lay below an opportunity-cost-based threshold of 30% Indian gross domestic product per capita in each Indian state (state-specific ICER range: US$67-US$593 per DALY averted). The ICER of two-dose vaccination versus no vaccination vaccination was US$1404 (₹INR104 000). The ICER of two-dose vaccination versus single-dose vaccination, assuming lower initial efficacy and waning of single-dose vaccination, was at least US$2282 (₹INR169 000) per DALY averted. CONCLUSIONS: Nationwide introduction of single-dose HPV vaccination at age 10 in India is highly likely to be cost-effective whereas extending the number of doses from one to two would have a less favourable profile.

Firework-related ocular trauma in Pernambuco, Brazil.

PURPOSE: This study aimed to describe the demographic and clinical characteristics of victims of fireworkrelated ocular trauma treated at the ophthalmologic emergency de partments of two reference centers in Pernambuco, Brazil, and to identify risk factors related to poor visual prognosis. METHODS: We retrospectively evaluated the medical records of patients admitted in emergency departments with a report of firework-related trauma between January 2012 and December 2018. Data collected included patient's age, sex, place of origin, month and year of the accident, ocular structures affected, characteristics of the injuries, and type of treatment that patients received. For patients who were followed for >30 days, the final visual acuity and patient's origin were analyzed. RESULTS: Three hundred and seventy eyes from 314 patients were included, of which 248 (79.0%) were male and 160 (51.0%) were from the metropolitan region of Recife. The mean patient age was 25.6 ± 18.8 years. In 56 (17.8%) patients, the ocular trauma was bilateral. A total of 152 (48.4%) cases occurred in June. The most affected sites were the eyelids in 91 (24.6%) eyes and ocular surface in 252 (68.1%). Surgical treatment was required in 87 (23.5%) eyes. After clinical and surgical management, 37 (10.0%) eyes presented final visual acuity of <20/400. Of these, 34 (91.9%) eyes were from patients from the countryside or from another state. Patients from the countryside presented higher risk of developing blindness after a firework trauma than those from the metropolitan area (odds ratio of 5.46). CONCLUSIONS: Victims of firework-related ocular trauma were mostly male, from the metropolitan region of Pernambuco state and mainly pediatric patients or economically active. Those coming from the countryside and other states had higher risk of developing blindness.

Extracellular Matrix Collagen I Differentially Regulates the Metabolic Plasticity of Pancreatic Ductal Adenocarcinoma Parenchymal Cell and Cancer Stem Cell.

Pancreatic ductal adenocarcinoma (PDAC) has a 5-year survival rate of less than 10 percent largely due to the intense fibrotic desmoplastic reaction, characterized by high levels of extracellular matrix (ECM) collagen I that constitutes a niche for a subset of cancer cells, the cancer stem cells (CSCs). Cancer cells undergo a complex metabolic adaptation characterized by changes in metabolic pathways and biosynthetic processes. The use of the 3D organotypic model in this study allowed us to manipulate the ECM constituents and mimic the progression of PDAC from an early tumor to an ever more advanced tumor stage. To understand the role of desmoplasia on the metabolism of PDAC parenchymal (CPC) and CSC populations, we studied their basic metabolic parameters in organotypic cultures of increasing collagen content to mimic in vivo conditions. We further measured the ability of the bioenergetic modulators (BMs), 2-deoxyglucose, dichloroacetate and phenformin, to modify their metabolic dependence and the therapeutic activity of paclitaxel albumin nanoparticles (NAB-PTX). While all the BMs decreased cell viability and increased cell death in all ECM types, a distinct, collagen I-dependent profile was observed in CSCs. As ECM collagen I content increased (e.g., more aggressive conditions), the CSCs switched from glucose to mostly glutamine metabolism. All three BMs synergistically potentiated the cytotoxicity of NAB-PTX in both cell lines, which, in CSCs, was collagen I-dependent and the strongest when treated with phenformin + NAB-PTX. Metabolic disruption in PDAC can be useful both as monotherapy or combined with conventional drugs to more efficiently block tumor growth.

ECM Composition Differentially Regulates Intracellular and Extracellular pH in Normal and Cancer Pancreatic Duct Epithelial Cells.

Intracellular pH (pHi) regulation is a challenge for the exocrine pancreas, where the luminal secretion of bicarbonate-rich fluid is accompanied by interstitial flows of acid. This acid-base transport requires a plethora of ion transporters, including bicarbonate transporters and the Na+/H+ exchanger isoform 1 (NHE1), which are dysregulated in Pancreatic Ductal Adenocarcinoma (PDAC). PDAC progression is favored by a Collagen-I rich extracellular matrix (ECM) which exacerbates the physiological interstitial acidosis. In organotypic cultures of normal human pancreatic cells (HPDE), parenchymal cancer cells (CPCs) and cancer stem cells (CSCs) growing on matrices reproducing ECM changes during progression, we studied resting pHi, the pHi response to fluxes of NaHCO3 and acidosis and the role of NHE1 in pHi regulation. Our findings show that: (i) on the physiological ECM, HPDE cells have the most alkaline pHi, followed by CSCs and CPCs, while a Collagen I-rich ECM reverses the acid-base balance in cancer cells compared to normal cells; (ii) both resting pHi and pHi recovery from an acid load are reduced by extracellular NaHCO3, especially in HPDE cells on a normal ECM; (iii) cancer cell NHE1 activity is less affected by NaHCO3. We conclude that ECM composition and the fluctuations of pHe cooperate to predispose pHi homeostasis towards the presence of NaHCO3 gradients similar to that expected in the tumor.

A new species of rheophilic armored catfish of Rineloricaria (Siluriformes: Loricariidae) from the Vaupés River, Amazonas basin, Colombia.

A new rheophilic species of the genus Rineloricaria is described for the Amazon basin in Colombia. Rineloricaria cachivera n. sp. differs from its congeners by having anterior to the first predorsal plate, an inconspicuous saddle-like mark; the presence of dark, diffuse blotches, present as unified dark colouration along most of the dorsal portion of the head, without bands or spots on the head; a long snout that occupies more than half the head length (HL), between 58.0% and 66.3% HL; a naked portion on the cleithral area from the border of lower lip reaching the origin of pectoral fin; and by having five series of lateral plates in longitudinal rows below the dorsal fin. The new species is morphologically similar to Rineloricaria daraha; however, it can be distinguished by the presence of six branched pectoral fin rays (vs. seven) and the lower lip surface with short thick papillae (vs. long finger papillae). An identification key to the Rineloricaria species of the Amazon River basin in Colombia is provided. The new species is herein categorized as Least Concern, following the IUCN criteria.

Acidic Growth Conditions Promote Epithelial-to-Mesenchymal Transition to Select More Aggressive PDAC Cell Phenotypes In Vitro.

Pancreatic Ductal Adenocarcinoma (PDAC) is characterized by an acidic microenvironment, which contributes to therapeutic failure. So far there is a lack of knowledge with respect to the role of the acidic microenvironment in the invasive process. This work aimed to study the phenotypic and genetic response of PDAC cells to acidic stress along the different stages of selection. To this end, we subjected the cells to short- and long-term acidic pressure and recovery to pHe 7.4. This treatment aimed at mimicking PDAC edges and consequent cancer cell escape from the tumor. The impact of acidosis was assessed for cell morphology, proliferation, adhesion, migration, invasion, and epithelial-mesenchymal transition (EMT) via functional in vitro assays and RNA sequencing. Our results indicate that short acidic treatment limits growth, adhesion, invasion, and viability of PDAC cells. As the acid treatment progresses, it selects cancer cells with enhanced migration and invasion abilities induced by EMT, potentiating their metastatic potential when re-exposed to pHe 7.4. The RNA-seq analysis of PANC-1 cells exposed to short-term acidosis and pHe-selected recovered to pHe 7.4 revealed distinct transcriptome rewiring. We describe an enrichment of genes relevant to proliferation, migration, EMT, and invasion in acid-selected cells. Our work clearly demonstrates that upon acidosis stress, PDAC cells acquire more invasive cell phenotypes by promoting EMT and thus paving the way for more aggressive cell phenotypes.

Injectable Nanocomposite Hydrogels of Gelatin-Hyaluronic Acid Reinforced with Hybrid Lysozyme Nanofibrils-Gold Nanoparticles for the Regeneration of Damaged Myocardium.

Biopolymeric injectable hydrogels are promising biomaterials for myocardial regeneration applications. Besides being biocompatible, they adjust themselves, perfectly fitting the surrounding tissue. However, due to their nature, biopolymeric hydrogels usually lack desirable functionalities, such as antioxidant activity and electrical conductivity, and in some cases, mechanical performance. Protein nanofibrils (NFs), such as lysozyme nanofibrils (LNFs), are proteic nanostructures with excellent mechanical performance and antioxidant activity, which can work as nanotemplates to produce metallic nanoparticles. Here, gold nanoparticles (AuNPs) were synthesized in situ in the presence of LNFs, and the obtained hybrid AuNPs@LNFs were incorporated into gelatin-hyaluronic acid (HA) hydrogels for myocardial regeneration applications. The resulting nanocomposite hydrogels showed improved rheological properties, mechanical resilience, antioxidant activity, and electrical conductivity, especially for the hydrogels containing AuNPs@LNFs. The swelling and bioresorbability ratios of these hydrogels are favorably adjusted at lower pH levels, which correspond to the ones in inflamed tissues. These improvements were observed while maintaining important properties, namely, injectability, biocompatibility, and the ability to release a model drug. Additionally, the presence of AuNPs allowed the hydrogels to be monitorable through computer tomography. This work demonstrates that LNFs and AuNPs@LNFs are excellent functional nanostructures to formulate injectable biopolymeric nanocomposite hydrogels for myocardial regeneration applications.

Increased demand for FAD synthesis in differentiated and stem pancreatic cancer cells is accomplished by modulating FLAD1 gene expression: the inhibitory effect of Chicago Sky Blue.

FLAD1, along with its FAD synthase (FADS, EC 2.7.7.2) product, is crucial for flavin homeostasis and, due to its role in the mitochondrial respiratory chain and nuclear epigenetics, is closely related to cellular metabolism. Therefore, it is not surprising that it could be correlated with cancer. To our knowledge, no previous study has investigated FLAD1 prognostic significance in pancreatic ductal adenocarcinoma (PDAC). Thus, in the present work, the FAD synthesis process was evaluated in two PDAC cell lines: (a) PANC-1- and PANC-1-derived cancer stem cells (CSCs), presenting the R273H mutation in the oncosuppressor p53, and (b) MiaPaca2 and MiaPaca2-derived CSCs, presenting the R248W mutation in p53. As a control, HPDE cells expressing wt-p53 were used. FADS expression/activity increase was found with malignancy and even more with stemness. An increased FAD synthesis rate in cancer cell lines is presumably demanded by the increase in the FAD-dependent lysine demethylase 1 protein amount as well as by the increased expression levels of the flavoprotein subunit of complex II of the mitochondrial respiratory chain, namely succinate dehydrogenase. With the aim of proposing FADS as a novel target for cancer therapy, the inhibitory effect of Chicago Sky Blue on FADS enzymatic activity was tested on the recombinant 6His-hFADS2 (IC50 = 1.2 µm) and PANC-1-derived CSCs' lysate (IC50 = 2-10 µm). This molecule was found effective in inhibiting the growth of PANC-1 and even more of its derived CSC line, thus assessing its role as a potential chemotherapeutic drug.

Hand-Foot-Mouth Disease in an Adult.

Hand-foot-mouth syndrome is a common childhood illness. Although occurrence in adults is rare, its incidence has been increasing. In such cases, it usually presents with atypical symptoms. The authors present the case of a 33-year-old male patient who presented with constitutional symptoms, feverish sensation, and macular palmoplantar rash associated with oral and oropharynx ulcers. The epidemiological history revealed exposure to two cohabitants (children) with a recent diagnosis of hand-foot-mouth disease (HFMD).

Levosimendan in outpatients with advanced heart failure: Single-center experience of 200 intermittent perfusions.

INTRODUCTION: Patients with advanced heart failure (HF) have high morbidity and mortality, with only a small proportion being eligible for advanced therapies. Intermittent outpatient levosimendan infusion has been shown to provide symptomatic relief and reduce the rate of HF events. Our aim was to assess the safety and efficacy of outpatient levosimendan administration in an advanced HF population. METHODS: This is a report of a single-center experience of consecutive advanced HF patients referred for intermittent intravenous outpatient administration of levosimendan, between January 2018 and March 2021. Baseline and follow-up evaluation included clinical assessment, laboratory tests, transthoracic echocardiography and cardiopulmonary exercise testing. Baseline and clinical follow-up data were compared using the Wilcoxon signed-rank test. RESULTS: A total of 24 patients (60.8 years, 83% male, mean left ventricular ejection fraction [LVEF] 24%), with a median of 1.5 HF hospitalizations in the previous six months, were referred for outpatient levosimendan pulses, the majority as a bridge to transplantation or due to clinical deterioration. At six-month follow-up there was a significant reduction in HF hospitalizations to 0.4±0.7 (p<0.001). NYHA class IV (52.2% to 12.5%, p=0.025) and NT-proBNP (8812.5 to 3807.4 pg/ml, p=0.038) were also significantly reduced. Exercise capacity was significantly improved, including peak oxygen uptake (p=0.043) and VE/VCO2 slope (p=0.040). LVEF improved from 24.0% to 29.7% (p=0.008). No serious adverse events were reported. CONCLUSION: Repeated levosimendan administration in advanced HF patients is a safe procedure and was associated with a reduction in HF hospitalizations, functional and LVEF improvement, and reduction in NT-proBNP levels during follow-up.

Dent's disease: An unusual cause of kidney failure.

Dent's disease is an X-linked recessive disease characterized by proximal tubulopathy with low-molecular weight proteinuria, hypercalciuria, nephrolithiasis, nephrocalcinosis, and kidney failure. It is mainly caused by mutations in the CLCN5 or OCRL1 genes, and only ~ 250 families have been identified with these mutations. We present a 31-year-old male referred to a nephrology consultation due to elevated serum creatinine and a history of nephrolithiasis. Complementary evaluation revealed protein/creatinine ratio of 1.9 g/g and albumin/creatinine ratio of 0.5 g/g, hypercalciuria and medullary nephrocalcinosis. These findings raised the suspicion of Dent's disease, which was confirmed by genetic testing. A missense mutation in the CLCN5 gene (c.810C>G, p.(Ser270Arg)), not previously reported in populational databases, was identified. During the evaluation of the patient, it came to our attention that a first-degree male cousin was being followed in our kidney transplantation unit. Given the unknown etiology of his chronic kidney disease, genetic testing was performed, identifying the same mutation. This case highlights the importance of considering the diagnosis of Dent's disease in the setting of a male patient with chronic kidney disease of unknown etiology, low-molecular-weight proteinuria, hypercalciuria, and nephrocalcinosis. Despite progression to end-stage kidney failure in a significant portion of male patients, there are no reports of recurrence after kidney transplantation.

Endovascular treatment of intracranial aneurysms using the Derivo Embolization Device: a multicenter experience.

BACKGROUND: Flow diversion is the first-line treatment for several types of intracranial aneurysms. We report on a large series of patients treated with the Derivo Embolization Device who underwent a 1-year angiographic control follow-up. METHODS: We performed a multicenter retrospective analysis of prospectively collected data, designed to evaluate the clinical and angiographic results of treatment of intracranial aneurysms with the Derivo Flow Diverter. The primary endpoint was complete occlusion of the aneurysm within 12 months, which was evaluated using DSA. The secondary endpoint was the absence of any serious adverse events. Univariate and multivariate logistic regression analyses were performed to analyze the data. RESULTS: The study was conducted from December 2016 to September 2019 and enrolled 127 patients with 177 intracranial aneurysms, treated at three different centers. Efficacy at 6 months was 70.1% (122/174) for total occlusion and 87.3% (152/174) for favorable occlusion and, at 12 months, it was 83.3% (145/174) for total occlusion and 97.7% (170/174) for favorable occlusion. Regarding safety concerns, 97.6% (124/127) of patients did not experience severe adverse effects during the follow-up period of 12 months, and there was no procedure-related mortality. CONCLUSIONS: The Derivo Embolization Device, achieving a total occlusion rate of 83.3% and a favorable occlusion rate of 97.7% in a 1-year angiographic control study of 174 aneurysms with minor morbidity and no intervention-related mortality, is a safe and effective treatment for intracranial aneurysms.

Atualização do enfermeiro paliativista na assistência ao paciente oncológico em fase terminal / Updating the palliativist nurse in the care of terminally ill cancer patients / Actualización de la enfermera paliativista en el cuidado de pacientes oncológicos terminales

O tratamento paliativo de pacientes com câncer tem um impacto importante não apenas sobre os pacientes, mas também sobre suas famílias e até mesmo sobre os profissionais de saúde envolvidos em seus cuidados. Neste contexto questionou-se Quais as evidências científicas acerca da perspectiva da equipe de enfermagem sobre os cuidados paliativos do paciente oncológico? O objetivo geral do estudo foi conhecer a perspectiva da equipe de enfermagem sobre os cuidados paliativos do paciente oncológico. A metodologia ultilizada foi uma revisão integrativa da literatura com pesquisa de dados em fontes secundárias de material de pesquisa previamente publicado sobre o assunto. Os resultados mostraram que desde o diagnóstico do câncer até o início dos cuidados paliativos, estabelece-se uma relação entre o enfermeiro e o paciente para proporcionar-lhes melhores cuidados, o enfermeira minimiza o sofrimento causado pela doença e também utiliza recursos de apoio, dá esperança para o tratamento e ajuda-os a lidar melhor com a doença. O estudo também mostra que o papel do enfermeiro clínico nos cuidados paliativos é muito importante para a implementação e aceitação do diagnóstico por parte dos pacientes. Assim conclui-se que a atitude humana, o abrigo, o conforto, a solidariedade e o apoio proporcionados pelo enfermeiro e pela família ao paciente com câncer durante a aplicação dos cuidados paliativos são indispensáveis e fundamentais nesta fase, oferecendo aos pacientes um tratamento menos doloroso e mais confortável.

The palliative care of cancer patients has an important impact not only on the patients, but also on their families and even on the health professionals involved in their care. In this context, the question was What is the scientific evidence about the perspective of the nursing team on palliative care of cancer patients? The general objective of the study was to know the perspective of the nursing team about the palliative care of cancer patients. The ultilized methodology was an integrative literature review with data search in secondary sources of previously published research material on the subject. The results showed that from the diagnosis of cancer until the beginning of palliative care, a relationship is established between the nurse and the patient to provide them with better care, the nurse minimizes the suffering caused by the disease and also uses supportive resources, gives hope for the treatment and helps them to cope better with the disease. The study also shows that the role of the nurse practitioner in palliative care is very important for the implementation and acceptance of the diagnosis by patients. Thus it is concluded that the humane attitude, shelter, comfort, solidarity and support provided by the nurse and family to the cancer patient during the application of palliative care are indispensable and fundamental in this phase, offering patients a less painful and more comfortable treatment.

Los cuidados paliativos de los pacientes con cáncer tienen un importante impacto no sólo en los pacientes, sino también en sus familias e incluso en los profesionales sanitarios implicados en su atención. En este contexto, la pregunta fue ¿Cuál es la evidencia científica sobre la perspectiva del equipo de enfermería en los cuidados paliativos de los pacientes con cáncer? El objetivo general del estudio fue conocer la perspectiva del equipo de enfermería sobre los cuidados paliativos de los pacientes con cáncer. La metodología ultilizada fue una revisión bibliográfica integradora con búsqueda de datos en fuentes secundarias de material de investigación previamente publicado sobre el tema. Los resultados mostraron que desde el diagnóstico del cáncer hasta el inicio de los cuidados paliativos, se establece una relación entre la enfermera y el paciente para proporcionarles una mejor atención, la enfermera minimiza el sufrimiento causado por la enfermedad y también utiliza recursos de apoyo, da esperanza para el tratamiento y les ayuda a sobrellevar mejor la enfermedad. El estudio también muestra que el papel de la enfermera profesional en los cuidados paliativos es muy importante para la aplicación y aceptación del diagnóstico por parte de los pacientes. Así, se concluye que la actitud humana, el cobijo, el consuelo, la solidaridad y el apoyo proporcionados por la enfermera y la familia al paciente con cáncer durante la aplicación de los cuidados paliativos son indispensables y fundamentales en esta fase, ofreciendo a los pacientes un tratamiento menos doloroso y más confortable.