Ultrasonography of the Superficial Temporal and Axillary Arteries in Giant Cell Arteritis diagnosis.

OBJECTIVES: Giant cell arteritis (GCA) is the main systemic vasculitis in individuals aged ≥ 50 years. Color Doppler ultrasound (CDS) has an established role in GCA diagnosis and management. This study aims to assess the clinical characteristics associated with a positive CDS evaluation and the impact of additional axillary artery examination on diagnostic sensitivity. MATERIAL AND METHODS: We conducted a retrospective analysis of patients undergoing CDS of the superficial temporal arteries, with or without axillary artery assessment, at our hospital, between 2009 and 2023. Patients meeting the new 2022 diagnostic criteria for GCA were included and their characteristics were analyzed according to the presence of the halo sign on CDS. RESULTS: Of the 135 included patients (54% female, mean age 75±8 years), the halo sign was observed in 57%, correlating with higher systemic symptom prevalence (61% vs 42%, p=0.035), lower hemoglobin (p<0.001), and higher erythrocyte sedimentation rate (p=0.028). The halo sign inversely related to prior corticosteroid therapy (p=0.033). Patients with axillary halo sign had fewer external carotid symptoms and a higher vertebral halo sign prevalence. Vertebral halo sign was associated with posterior circulation ischemic stroke (65%, p < 0.001). Axillary artery studies improved diagnostic sensitivity by 9%. CONCLUSION: In our study, the halo sign correlated with higher systemic symptoms and analytical abnormalities. Axillary artery examination enhanced CDS sensitivity, linked to severe outcomes like stroke. Prior corticosteroid therapy reduced CDS sensitivity. The correlation of clinical, laboratory, and ultrasound findings provides a more comprehensive understanding of GCA pathogenesis and evolution.

Biomarkers: Are They Useful in Severe Community-Acquired Pneumonia?

Community acquired pneumonia (CAP) is a prevalent infectious disease often requiring hospitalization, although its diagnosis remains challenging as there is no gold standard test. In severe CAP, clinical and radiologic criteria have poor sensitivity and specificity, and microbiologic documentation is usually delayed and obtained in less than half of sCAP patients. Biomarkers could be an alternative for diagnosis, treatment monitoring and establish resolution. Beyond the existing evidence about biomarkers as an adjunct diagnostic tool, most evidence comes from studies including CAP patients in primary care or emergency departments, and not only sCAP patients. Ideally, biomarkers used in combination with signs, symptoms, and radiological findings can improve clinical judgment to confirm or rule out CAP diagnosis, and may be valuable adjunctive tools for risk stratification, differentiate viral pneumonia and monitoring the course of CAP. While no single biomarker has emerged as an ideal one, CRP and PCT have gathered the most evidence. Overall, biomarkers offer valuable information and can enhance clinical decision-making in the management of CAP, but further research and validation are needed to establish their optimal use and clinical utility.

DIMINISHED HAND GRIP STRENGTH AND CIRRHOSIS: PREVALENCE AND ASSOCIATED FACTORS.

BACKGROUND: Sarcopenia is a syndrome characterized by progressive and generalized loss of muscle mass and strength, observed to varying degrees in patients with various chronic conditions. In cirrhotic patients, it reflects protein-energy malnutrition due to metabolic protein imbalance and is associated with worsened prognosis and reduced post-liver transplantation survival. OBJECTIVE: To evaluate the epidemiological distribution of diminished hand grip (HG) strength in cirrhotic patients at an outpatient clinic of Santa Casa de Misericórdia in Vitória-ES, Brazil, seeking its association with liver function and cirrhosis complications. METHODS: Cross-sectional, epidemiological, and single-center study. A questionnaire was administered to patients and HG strength was measured using a dynamometer, with three interval measures taken for 3 seconds each. RESULTS: The study's total population was 64 cirrhotic patients, with a mean age of 58 years and alcohol as the most prevalent etiology. Reduced HG strength was defined based on two reference values: using cutoff point 1, reduced HG strength was identified in 33 patients (51.6%); according to cutoff point 2, 23 (35.9%) had reduced HG strength. The study showed that, among the parameters observed, there was an association between the female gender and diminished HG strength in both cutoff points. Additionally, it was noted that patients with a score of 15 or more on the Model for End-Stage Liver Disease (MELD) had decreased HG strength at cutoff point 2. The study showed no association between decreased HG strength and the occurrence of cirrhosis complications in the population studied. CONCLUSION: In our study, we obtained a diminished HG strength variation of 35-52%, which was related to higher MELD scores, suggesting an association with worse clinical outcomes. Therefore, the presence of reduced muscle strength in cirrhotic patients may be linked to prognostic factors and should be valued as clinical data in the management of these patients.

Diminuição da força no teste de Hand Grip e cirrose hepática: prevalência e fatores associados / Diminished hand grip strength and cirrhosis: prevalence and associated factors

ABSTRACT Background: Sarcopenia is a syndrome characterized by progressive and generalized loss of muscle mass and strength, observed to varying degrees in patients with various chronic conditions. In cirrhotic patients, it reflects protein-energy malnutrition due to metabolic protein imbalance and is associated with worsened prognosis and reduced post-liver transplantation survival. Objective: To evaluate the epidemiological distribution of diminished hand grip (HG) strength in cirrhotic patients at an outpatient clinic of Santa Casa de Misericórdia in Vitória-ES, Brazil, seeking its association with liver function and cirrhosis complications. Methods: Cross-sectional, epidemiological, and single-center study. A questionnaire was administered to patients and HG strength was measured using a dynamometer, with three interval measures taken for 3 seconds each. Results: The study's total population was 64 cirrhotic patients, with a mean age of 58 years and alcohol as the most prevalent etiology. Reduced HG strength was defined based on two reference values: using cutoff point 1, reduced HG strength was identified in 33 patients (51.6%); according to cutoff point 2, 23 (35.9%) had reduced HG strength. The study showed that, among the parameters observed, there was an association between the female gender and diminished HG strength in both cutoff points. Additionally, it was noted that patients with a score of 15 or more on the Model for End-Stage Liver Disease (MELD) had decreased HG strength at cutoff point 2. The study showed no association between decreased HG strength and the occurrence of cirrhosis complications in the population studied. Conclusion: In our study, we obtained a diminished HG strength variation of 35-52%, which was related to higher MELD scores, suggesting an association with worse clinical outcomes. Therefore, the presence of reduced muscle strength in cirrhotic patients may be linked to prognostic factors and should be valued as clinical data in the management of these patients.

RESUMO Contexto: Sarcopenia é uma síndrome caracterizada por perda progressiva e generalizada de massa e força muscular, observada em diferentes graus em pacientes com afecções crônicas diversas. Nos cirróticos, reflete uma desnutrição proteico-energética por desequilíbrio metabólico de proteínas, e associa-se ao pior prognóstico e redução da sobrevida pós transplante hepático. Objetivo: Avaliar a distribuição epidemiológica da diminuição da força no teste de Hand Grip (HG) nos pacientes cirróticos do ambulatório da Santa Casa de Misericórdia de Vitória-ES, buscando sua associação com a função hepática e complicações. Métodos: Estudo transversal, epidemiológico e unicêntrico. Aplicou-se um questionário aos pacientes e mediu-se a força de preensão manual HG com o auxílio de um dinamômetro, sendo realizadas 3 medidas intervaladas durante 3 segundos cada. Resultados: A população total foi de 64 pacientes cirróticos, sendo a média de idade 58 anos e a etiologia mais prevalente o álcool. Definiu-se a presença de redução da força do HG a partir de dois valores de referência: com base no ponto de corte 1, a redução da força do HG foi identificada em 33 pacientes (51,6%); pelo ponto de corte 2, 23 (35,9%) tinham diminuição da força do HG. O estudo evidenciou que, dentre os parâmetros observados, houve associação entre o sexo feminino e a diminuição da força no teste de HG nos dois pontos de corte. Além disso, notou-se que pacientes com pontuação de 15 ou mais no Modelo para Doença Hepática Terminal (MELD) tiveram mais redução da força do HG de acordo com o ponto de corte 2. O estudo evidenciou que não houve associação entre a diminuição da força no teste de HG e o evento de complicações da cirrose na população estudada. Conclusão: Em nossa casuística, obtivemos uma variação da diminuição da força muscular entre 35-52% pelo teste de HG, o que teve relação com o MELD mais elevado, podendo demonstrar associação com piores desfechos clínicos. Dessa forma, concluiu-se que a presença de diminuição da força muscular no teste de HG nos cirróticos pode estar ligada a fatores prognósticos, e deve ser valorizada como dado clínico no manejo destes pacientes.

Novel Insights on the Role of Epigenetics in Androgen Receptor's Expression in Prostate Cancer.

The androgens/androgen receptor (AR) axis is the main therapeutic target in prostate cancer (PCa). However, while initially responsive, a subset of tumors loses AR expression through mechanisms putatively associated with epigenetic modifications. In this study, we assessed the link between the presence of CpG methylation in the 5'UTR and promoter regions of AR and loss of AR expression. Hence, we characterized and compared the methylation signature at CpG resolution of these regulatory regions in vitro, both at basal levels and following treatment with 5-aza-2-deoxycytidine (DAC) alone, or in combination with Trichostatin A (TSA). Our results showed heterogeneity in the methylation signature of AR negative cell lines and pinpointed the proximal promoter region as the most consistently methylated site in DU-145. Furthermore, this region was extremely resistant to the demethylating effects of DAC and was only significantly demethylated upon concomitant treatment with TSA. Nevertheless, no AR re-expression was detected at the mRNA or protein level. Importantly, after treatment, there was a significant increase in repressive histone marks at AR region 1 in DU-145 cells. Altogether, our data indicate that AR region 1 genomic availability is crucial for AR expression and that the inhibition of histone methyltransferases might hold promise for AR re-expression.

Eco-sustainable coatings based on chitosan, pectin, and lemon essential oil nanoemulsion and their effect on strawberry preservation.

Films and coatings manufactured with bio-based renewable materials, such as biopolymers and essential oils, could be a sustainable and eco-friendly alternative for protecting and preserving agricultural products. In this work, we developed films and coatings from pectin and chitosan to protect strawberries (Fragaria x ananassa Duch.) from spoilage and microbial contamination. We developed three coatings containing equal amounts of glycerol and Sicilian lemon essential oil (LEO) nanoemulsion. We identified seventeen chemicals from LEO by GC-MS chromatogram, including d-limonene, α-Pinene, ß-Pinene, and γ-Terpinene. The pectin and chitosan coatings were further characterized using different physicochemical, mechanical, and biological methods. The films demonstrated satisfactory results in strength and elongation at the perforation as fruit packaging. In addition, the coatings did not influence the weight and firmness of the strawberry pulps. We observed that 100 % essential oil was released in 1440 min resulting from the erosion process. Also, the oil preserved the chemical stability of the films. Antioxidant activity (AA), measured by Electron Paramagnetic Resonance (EPR), showed that the coatings loaded with 2 % LEO nanoemulsion (PC + oil) showed that almost 50 % of AA from LEO nanoemulsion was preserved. The chitosan and the pectin-chitosan coatings (PC + oil) inhibited filamentous fungi and yeast contaminations in strawberries for at least 14 days, showing a relationship between the AA and antimicrobial results.

Eicosapentaenoic acid-rich oil supplementation activates PPAR-γ and delays skin wound healing in type 1 diabetic mice.

Delayed wound healing is a devastating complication of diabetes and supplementation with fish oil, a source of anti-inflammatory omega-3 (ω-3) fatty acids including eicosapentaenoic acid (EPA), seems an appealing treatment strategy. However, some studies have shown that ω-3 fatty acids may have a deleterious effect on skin repair and the effects of oral administration of EPA on wound healing in diabetes are unclear. We used streptozotocin-induced diabetes as a mouse model to investigate the effects of oral administration of an EPA-rich oil on wound closure and quality of new tissue formed. Gas chromatography analysis of serum and skin showed that EPA-rich oil increased the incorporation of ω-3 and decreased ω-6 fatty acids, resulting in reduction of the ω-6/ω-3 ratio. On the tenth day after wounding, EPA increased production of IL-10 by neutrophils in the wound, reduced collagen deposition, and ultimately delayed wound closure and impaired quality of the healed tissue. This effect was PPAR-γ-dependent. EPA and IL-10 reduced collagen production by fibroblasts in vitro. In vivo, topical PPAR-γ-blockade reversed the deleterious effects of EPA on wound closure and on collagen organization in diabetic mice. We also observed a reduction in IL-10 production by neutrophils in diabetic mice treated topically with the PPAR-γ blocker. These results show that oral supplementation with EPA-rich oil impairs skin wound healing in diabetes, acting on inflammatory and non-inflammatory cells.

Gitelman Syndrome: A Case Report.

Gitelman syndrome is a rare hereditary tubulopathy characterized by hypokalemic metabolic alkalosis, hypomagnesemia, and hypocalciuria. In this case report, we describe a 21-year-old male who presented with myalgias, asthenia, general muscle weakness, and hypokalemia after receiving oral potassium supplementation for six months. Additional biochemical studies showed hypomagnesemia, metabolic alkalosis, and increased urinary potassium and magnesium excretion. Calcium urinary excretion was within the normal range, but 25-hydroxycholecalciferol levels were low. Systolic arterial hypertension was found, probably reflecting chronic hyperreninemic hyperaldosteronism. Genetic testing for SCL12A3 mutations identified a pathogenic variant in homozygosity, which confirmed the Gitelman syndrome diagnosis. Treatment with chronic potassium and magnesium oral supplementation was started, as well as eplerenone and amiloride, with sustained correction of hypokalemia and hypomagnesemia.

ST3GalIV drives SLeX biosynthesis in gastrointestinal cancer cells and associates with cancer cell motility.

Expression of sialyl Lewis X (SLeX) is a well-documented event during malignant transformation of cancer cells, and largely associates with their invasive and metastatic properties. Glycoproteins and glycolipids are the main carriers of SLeX, whose biosynthesis is known to be performed by different glycosyltransferases, namely by the family of ß-galactoside-α2,3-sialyltransferases (ST3Gals). In this study, we sought to elucidate the role of ST3GalIV in the biosynthesis of SLeX and in malignant properties of gastrointestinal (GI) cancer cells. By immunofluorescent screening, we selected SLeX-positive GI cancer cell lines and silenced ST3GalIV expression via CRISPR/Cas9. Flow cytometry, immunofluorescence and western blot analysis showed that ST3GalIV KO efficiently impaired SLeX expression in most cancer cell lines, with the exception of the colon cancer cell line LS174T. The impact of ST3GalIV KO in the biosynthesis of SLeX isomer SLeA and non sialylated Lewis X and A were also evaluated and overall, ST3GalIV KO led to a decreased expression of SLeA and an increased expression in both LeX and LeA. In addition, the abrogation of SLeX on GI cancer cells led to a reduction in cell motility. Furthermore, ST3GalVI KO was performed in LS174T ST3GalIV KO cells, resulting in the complete abolishment of SLeX expression and consequent reduced motility capacity of those cells. Overall, these findings portray ST3GalIV as the main, but not the only, enzyme driving the biosynthesis of SLeX in GI cancer cells, with a functional impact on cancer cell motility.

Antinuclear Antibody (ANA) and Anti-Mi-2-Alpha Positive Dermatomyositis Hinting a Cancer Diagnosis.

Dermatomyositis (DM) is a relatively uncommon inflammatory myopathy that has been linked to cancer. We report the case of an 81-year-old woman with cecum adenocarcinoma presenting with antinuclear antibody (ANA) and anti-Mi-2-alpha antibody-positive DM. The patient complained of anorexia, symmetric proximal muscle weakness and skin rash and presented with elevated muscle enzymes. A skin and muscle biopsy supported the diagnosis of DM as did the limbs magnetic resonance imaging (MRI) and electromyography. A diagnosis of localized adenocarcinoma of the cecum was made through colonoscopy and the patient was successfully surgically managed, with decreasing muscle enzymes at discharge and gradual recovery of muscle strength. The presence of both ANA and anti-Mi-2 autoantibodies has classically been described as comprising a better prognosis with a lower risk of underlying malignancy. This case highlights the importance of pursuing a cancer diagnosis in elderly patients presenting with DM even in presence of less predisposing immunological profiles.

Current aspects of renal dysfunction after liver transplantation.

The development of chronic kidney disease (CKD) after liver transplantation (LT) exerts a severe effect on the survival of patients. The widespread adoption of the model for end-stage liver disease score strongly impacted CKD incidence after the procedure, as several patients are transplanted with previously deteriorated renal function. Due to its multifactorial nature, encompassing pre-transplantation conditions, perioperative events, and nephrotoxic immunosuppressor therapies, the accurate identification of patients under risk of renal disease, and the implementation of preventive approaches, are extremely important. Methods for the evaluation of renal function in this setting range from formulas that estimate the glomerular filtration rate, to non-invasive markers, although no option has yet proved efficient in early detection of kidney injury. Considering the nephrotoxicity of calcineurin inhibitors (CNI) as a factor of utmost importance after LT, early nephroprotective strategies are highly recommended. They are based mainly on delaying the application of CNI during the immediate postoperative-period, reducing their dosage, and associating them with other less nephrotoxic drugs, such as mycophenolate mofetil and everolimus. This review provides a critical assessment of the causes of renal dysfunction after LT, the methods of its evaluation, and the interventions aimed at preserving renal function early and belatedly after LT.

Epigenetic Editing in Prostate Cancer: Challenges and Opportunities.

Epigenome editing consists of fusing a predesigned DNA recognition unit to the catalytic domain of a chromatin modifying enzyme leading to the introduction or removal of an epigenetic mark at a specific locus. These platforms enabled the study of the mechanisms and roles of epigenetic changes in several research domains such as those addressing pathogenesis and progression of cancer. Despite the continued efforts required to overcome some limitations, which include specificity, off-target effects, efficacy, and longevity, these tools have been rapidly progressing and improving.Since prostate cancer is characterized by multiple genetic and epigenetic alterations that affect different signalling pathways, epigenetic editing constitutes a promising strategy to hamper cancer progression. Therefore, by modulating chromatin structure through epigenome editing, its conformation might be better understood and events that drive prostate carcinogenesis might be further unveiled.This review describes the different epigenome engineering tools, their mechanisms concerning gene's expression and regulation, highlighting the challenges and opportunities concerning prostate cancer research.

Identidade médica: o impacto do primeiro contato com pacientes na empatia do estudante de Medicina / Medical identity: the impact of first contact with patient in medicine student's empathy

Resumo: Introdução: Empatia é definida como a capacidade de ouvir e compreender o outro, e, portanto, é um componente essencial na relação médico-paciente. Estudos apontam que proporcionar aos alunos a oportunidade de contato com o paciente logo no início do curso desperta a consciência da importância da empatia nas relações. Dessa forma, tal contato, nos primeiros semestres da Faculdade de Medicina, permite que os estudantes potencializem suas habilidades empáticas, oportunizando a construção de uma identidade profissional mais ampla e completa. Objetivo: O estudo tem como objetivo avaliar a influência do contato com o paciente na disciplina de Semiologia I, durante o segundo ano da graduação, sobre a empatia de estudantes de Medicina. Método: Trata-se de um estudo observacional e prospectivo, realizado com estudantes de Medicina de uma faculdade privada em Vitória, no Espírito Santo, matriculados na disciplina teórico-prática Semiologia I em 2019/2 e 2020/1, por meio de aplicação de questionários antes da primeira atividade prática em enfermaria e após a última. Analisaram-se as variáveis sociodemográficas e o escore de empatia. Diferenças entre os semestres foram avaliadas pelos testes qui-quadrado, exato de Fisher e de Mann-Whitney. Com os testes de Mann-Whitney e Kruskal-Wallis, investigou-se a relação entre as variáveis sociodemográficas e a empatia. A influência do contato com o paciente na empatia foi averiguada pelo teste de Wilcoxon, todos com 95% de significância. Resultado: Participaram do estudo 38 alunos em 2019/2 e 60 em 2020/1. Foram significativas somente as associações entre o contato com o paciente nas enfermarias e o escore de empatia (p = 0,008), e entre o sexo e o escore de empatia (p = 0,000), sendo esta maior para mulheres e ao final da experiência da disciplina. Conclusão: A disciplina Semiologia I se mostrou capaz de afetar positivamente a empatia, que se apresentou maior no sexo feminino, corroborando a literatura. Os resultados obtidos refletem somente um semestre específico do curso, não o perfil global de empatia dos estudantes, os níveis de empatia em momentos distintos da graduação ou o comportamento dos discentes.

Abstract: Introduction: Empathy is defined as the ability to listen and understand the other, thus becoming an essential component in the doctor-patient relationship. Studies indicate that the opportunity to make contact with the patient early in the course raises awareness of the importance of empathy in the relationships. Thus, such contact, in the first semesters of medical school, enables students to enhance their empathic skills, permitting the construction of a broader and more complete professional identity. Objective: The study aims to evaluate the influence on the empathy of medical students through the interaction with patients in the discipline of Semiology I, during the second year of undergraduate school. Method: Observational and prospective study with medical students from a private medical school in Vitória (ES), enrolled in the theoretical-practical discipline of Semiology I in 2019/2 and 2020/1, through the application of questionnaires, before the first practical activity in the ward and after the last one. Sociodemographic variables and empathy score were analyzed. The differences between the semesters were evaluated by Chi-square, Fisher's exact or Mann-Whitney tests. The relationship between sociodemographic variables and empathy was assessed by the Mann-Whitney and Kruskal-Wallis tests. The influence of contact with patients on students' empathy was analyzed by the Wilcoxon test, all with 95% significance. Results: The sample consisted of 38 students in 2019/2 and 60 in 2020/1. Only the associations between contact with the patients in the wards and the empathy score (p=0.008) and gender and the empathy score (p=0.000) were significant; empathy was greater among women and at the end of the discipline experience. Conclusion: The interaction between medical students and patients during the discipline of Semiology I was able to positively affect empathy, corroborating the literature. The higher levels of empathy among women also corroborate the literature. The obtained results reflect only a specific semester of the course, not the students' overall empathy profile, levels of empathy at different moments of undergraduate school, or their behavior.

Simultaneous Systemic Lupus Erythematosus Flare and Disseminated Tuberculosis: Balancing Anti-Mycobacterial and Autoimmune Treatments.

Here, we report the case of a 53-year-old man with suspected autoimmune arthritis on low-dose corticosteroid therapy. He was recently hospitalized due to presumed bacterial pneumonia and a seizure episode attributed to high fever. His condition deteriorated after discharge, and he presented to our institution with a persistent cough, weight loss, skin rash, arthralgias, fever, and altered mental status. The investigation led to the simultaneous diagnosis of a systemic lupus erythematosus (SLE) flare and disseminated tuberculosis (TB), both pulmonary and intracranial. Proteinuria and peripheral edema were identified, suggesting renal involvement of SLE. Anti-mycobacterial drugs and high-dose corticosteroid therapy were initiated. Given the risk of starting other immunosuppressive drugs in the presence of intracranial TB, in a patient with stable renal function and a significant decrease in proteinuria with corticosteroids and supportive therapy alone, renal biopsy was postponed. Prednisolone was progressively tapered down during the next six months, always maintaining anti-mycobacterial therapy, which resulted in a second SLE flare and the need to increase corticosteroids again. At this time, a renal biopsy was performed, showing class II lupus nephritis and confirming the diagnosis of SLE. After one year of anti-mycobacterial therapy with complete resolution of cerebral and pulmonary TB lesions, we chose to initiate mycophenolate mofetil as an immunosuppressive steroid-sparing agent with increased SLE control, allowing for corticosteroid reduction.

Hydralazine and Panobinostat Attenuate Malignant Properties of Prostate Cancer Cell Lines.

Among the well-established alterations contributing to prostate cancer (PCa) pathogenesis, epigenetics is an important player in its development and aggressive disease state. Moreover, since no curative therapies are available for advanced stage disease, there is an urgent need for novel therapeutic strategies targeting this subset of patients. Thus, we aimed to evaluate the combined antineoplastic effects of DNA methylation inhibitor hydralazine and histone deacetylase inhibitors panobinostat and valproic acid in several prostate cell lines. The effect of these drugs was assessed in four PCa (LNCaP, 22Rv1, DU145 and PC-3) cell lines, as well as in non-malignant epithelial (RWPE-1) and stromal (WPMY-1) cell lines, using several assays to evaluate cell viability, apoptosis, proliferation, DNA damage and clonogenic potential. We found that exposure to each epidrug separately reduced viability of all PCa cells in a dose-dependent manner and that combined treatments led to synergic growth inhibitory effects, impacting also on colony formation, invasion, apoptotic and proliferation rates. Interestingly, antitumoral effects of combined treatment were particularly expressive in DU145 cells. We concluded that hydralazine and panobinostat attenuate malignant properties of PCa cells, constituting a potential therapeutic tool to counteract PCa progression.

Hydralazine and Enzalutamide: Synergistic Partners against Prostate Cancer.

Advanced prostate cancers frequently develop resistance to androgen-deprivation therapy with serious implications for patient survival. Considering their importance in this type of neoplasia, epigenetic modifications have drawn attention as alternative treatment strategies. The aim of this study was to assess the antitumoral effects of the combination of hydralazine, a DNA methylation inhibitor, with enzalutamide, an antagonist of the androgen receptor, in prostate cancer cell lines. Several biological parameters, such as cell viability, proliferation, DNA damage, and apoptosis, as well as clonogenic and invasive potential, were evaluated. The individual treatments with hydralazine and enzalutamide exerted growth-inhibitory effects in prostate cancer cells and their combined treatment displayed synergistic effects. The combination of these two drugs was very effective in decreasing malignant features of prostate cancer and may become an alternative therapeutic option for prostate cancer patient management.

Double-Positive Anti-GBM and ANCA-MPO Vasculitis Presenting With Crescentic Glomerulonephritis.

We report the case of a 61-year-old man with rapidly progressing glomerulonephritis (RPGN) due to double-positive anti-neutrophil cytoplasmic antibodies (ANCA) and anti-glomerular basement membrane antibodies (GBM) vasculitis. The past medical history included stable untreated psoriatic arthritis and arterial hypertension. He presented with asthenia, anorexia, and rapidly deteriorating renal function with metabolic acidosis and hyperkalemia evolving with the need for hemodialysis. No nephrotoxic drugs were identified. Urinalysis showed proteinuria, erythrocyturia, and mild leukocyturia with no pathological casts and renal ultrasound excluded obstruction as the cause of the acute kidney injury. The subsequent study established the diagnosis of double-positive ANCA and anti-GBM vasculitis with renal biopsy confirming the presence of crescentic glomerulonephritis. The patient was started on corticosteroids, cyclophosphamide, and plasmapheresis with the improvement of symptoms and decrease of antibody titers. The renal function recovery was not obtained and referral for transplantation is ongoing.

Gastric perforation by fish bone with hepatic abscess formation presenting as prolonged fever.

A 70-year-old woman presented to the emergency department with a 3-week history of prolonged fever, asthenia and anorexia, denying other symptoms. Physical examination was unremarkable and the patient admitted for further investigation. Initial laboratory testing showed leucocytosis, elevated C-reactive protein and cholestasis, without hyperbilirubinemia or cytolysis. Abdominal ultrasonography found no abnormalities. Viral serologies, autoimmune tests and blood cultures were collected for further investigation of causes of prolonged fever with hepatic involvement. After two days, Citrobacter koseri was isolated in blood cultures and intravenous (IV) piperacillin-tazobactam initiated. Computed tomography (CT) scan of the abdomen showed a left lobe hepatic abscess with gas and a linear hyperdense image, possibly a foreign body, piercing through the gastric antrum into the abscess. Surgical exploration was done for source control. The abscess was drained and the foreign body, a 3.5 cm long fishbone, was removed. The patient's condition rapidly improved. Gastrointestinal perforation due to the ingestion of sharp and elongated foreign bodies usually occur in ileal loops, where the intestinal wall is thinner, causing extravasation of fluids and air into the peritoneum and typically presents with an acute abdomen. The uncommon location of perforation masked these symptoms leading to the unusual presentation with prolonged fever.

Pheochromocytoma: a retrospective study from a single center.

Objectives. Pheochromocytoma (PCC) is a neuroendocrine tumor derived from chromaffin tissue more frequently found in the adrenal medulla. Many discoveries over the last decade have significantly improved our understanding of PCC.Methods. We retrospectively reviewed all patients with a histological diagnosis of PCC at the Centro Hospitalar Universitario de Sao Joao, a tertiary and university hospital in Oporto, Portugal, between January 2009 and December 2017.Results. The study group included 33 patients. In most cases the diagnosis was suspected with more than half of patients presenting with hypertension and the third diagnosed during the work-up of an adrenal incidentaloma. About half of the patients was referred for genetic testing and 6 patients had a positive inherited susceptibility genetic pathogenic variant associated with classic cancer predisposition syndromes and also associated with newly described genes. In the incidentaloma group, genetic testing was performed in 3 (9%) patients with only 1 positive result. In the suspected group, 15 (45%) genetic tests were performed.Conclusions. In contrast to other studies, where only a minority of patients with PCC were referred for genetic counselling, in our study 54% of patients was referred for genetic testing. This study suggests that clinicians were correctly recognizing the need to refer young patients and patients with positive family history. However, opportunities for genetic testing are frequently missed due to low referral rates in patients with apparently sporadic PCC, particularly older than 30 years old. It is imperative that all the providers involved in the multidisciplinary care of patients with pheochromocytomas are aware of the genetic disorders associated with these unique tumors.