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.

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.

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.

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.

Seismic preparedness of families with children: Measures and dynamics.

Earthquakes are unpredictable events, thus seismic preparedness of households should be fostered, considering the specific needs of each family. Children, for example, are particularly vulnerable to disasters and to the effects of their consequences, but can also act as promoters of preparedness within families. Being part of a wider research, this qualitative study intends to better understand seismic preparedness within families with children in S. Miguel, the largest and most populated island of the volcanic archipelago of the Azores. Two semi-structured interviews were conducted. The first interview was conducted with 125 family representatives, addressing their current preparedness measures. From these representatives, 105 families that had non-existent or insufficient preparedness were selected for a second interview. In the time between the two interviews, the families were instructed to develop seismic preparedness measures. The process of development of these measures was also assessed. Data were analysed using content analysis and frequency analysis. Results point to low levels of preparedness, both at the time of the initial interview and developed subsequently, and families adopted few preparedness measures specifically targeting their children's needs. The results highlight, therefore, that household seismic preparedness should be promoted, with clear indications regarding preparedness specifically for families with children.

Multimodality Screening of Hepatic Nodules in Patients With Congenital Heart Disease After Fontan Procedure: Role of Ultrasound, ARFI Elastography, CT, and MRI.

OBJECTIVE: Currently, there is no consensus in the literature regarding the screening of hepatic nodules in patients who have undergone the Fontan procedure. The objectives of this study are to evaluate in this population the frequency of hepatic nodules at ultrasound (US), CT, and MRI; to measure liver stiffness using acoustic radiation force impulse (ARFI) elastography; and to investigate predictive factors for hepatic nodules. SUBJECTS AND METHODS: In this cross-sectional study, 49 patients who underwent the Fontan procedure were prospectively recruited from August 2014 through June 2016. These patients underwent clinical evaluation for hepatic disorders, ARFI elastography, US, CT, and MRI. RESULTS: Most of the patients had no symptoms, and hepatic nodules were detected in three of 49 (6.1%) patients at US, 14 of 44 (31.8%) patients at CT, and 19 of 48 (39.6%) patients at MRI. Liver stiffness at ARFI elastography was significantly higher in patients with hepatic nodules than in patients without such nodules (2.64 ± 0.81 m/s vs 1.94 ± 0.49 m/s; p = 0.002) and was a significant predictor of hepatic nodule (AUC, 0.767; p = 0.002). No clinical or laboratory data had any significant correlation with the existence of hepatic nodules, including time since Fontan procedure. CONCLUSION: In our study, more than one-third of patients had hepatic nodules at CT or MRI, but US did not detect most hepatic nodules. Liver stiffness at ARFI elastography was significantly higher in patients with hepatic nodules, and it may help guiding which patient should be further imaged with CT or MRI.

Ovarioleukodystrophy Due to EIF2B Genes: Systematic Review and Case Report.

Leukodystrophies comprise a spectrum of genetic disorders affecting white matter (WM) formation in the central nervous system (CNS), of which vanishing white matter disease (VWMD) is one. VWMD presents with progressive neurological deterioration and a variety of manifestations. Ovarioleukodystrophy, a subtype of VWMD, exhibits a distinctive clinical profile encompassing both CNS WM alterations and ovarian dysfunction. Variants in genes of the eukaryotic translation initiation factor 2B (EIF2B) complex affect the full form and are implicated in VWMD, including ovarioleukodystrophy. This work aimed to systematically review all published cases of ovarioleukodystrophy associated with variants in the EIF2B1-5 gene complex based on the first case identified in a Mexican population. We performed a systematic review according to the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) guidelines of published cases of ovarioleukodystrophy associated with the EIF2B gene complex, including a newly identified case from Mexico. We identified 207 publications using PUBMED, SCOPUS, and PMC databases. One hundred fifty-one publications were eliminated due to duplicates, titles, abstracts, or other reasons, while 56 publications were revised, of which 29 were eliminated because they dealt with other genes or non-human research, and 27 reports were assessed for eligibility. Finally, 14 reports describing ovarian involvement, neuroimaging, and molecular variants were included. Our review identified 20 cases worldwide, with a median age of onset of 19 years. Clinical features included WM involvement, ovarian abnormalities, gait disturbances, epilepsy, cognitive and language impairment, and other neurological manifestations. Neuroimaging showed characteristic WM changes, highlighting the importance of MRI in diagnosis. Missense variants predominated among the identified genetic mutations, especially in the EIF2B4 and EIF2B5 genes. Ovarioleukodystrophy is an ultra-rare disorder with a wide range of clinical manifestations and ovarian changes. Gynecological evaluation is crucial in suspected cases of ovarioleukodystrophy, as ovarian manifestations may precede neurological symptoms. The role of MRI is crucial in the diagnostic approach to this entity. Continued collaborative efforts are essential to elucidate genotype-phenotype correlations, improve clinical management, and promote therapeutic advances for this rare disorder.

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.

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.

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.

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.

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.

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.

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.

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.

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.

Report of Two Cases of Acquired Idiopathic Haemophilia.

Acquired haemophilia is a rare haemorrhagic dyscrasia caused by autoantibodies against coagulation factors, most commonly factor VIII (FVIII). Even though about half of the cases are classified as idiopathic, acquired haemophilia is more common in the elderly and/or in individuals diagnosed with other immunogenic conditions such as malignancies, autoimmune diseases, or during puerperium. It can be life-threatening, presenting more frequently with major bleeding. We report two cases of acquired haemophilia classified as idiopathic in middle-aged patients with no predisposing factors identified during the diagnostic approach: their disease's progression and complications, choice of treatment, and why and when to change it.

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 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.