Exploring promising minor natural phenolic compounds in neuroprotection-related preclinical models.

Neurodegenerative diseases, such as Alzheimer's disease and Parkinson's disease, are characterised by the progressive loss of specific neuronal cell populations due to multifactorial factors, including neurochemical and immunological disturbances. Consequently, patients can develop cognitive, motor and behavioural dysfunctions, which lead to impairments in their quality of life. Over the years, studies have reported on the neuroprotective properties inherent in phenolic compounds. Therefore, this review highlights the most recent scientific findings regarding phenolic compounds as promising neuroprotective molecules against neurodegenerative diseases.

Organ damage is a major determinant of work productivity impairment in Behçet's Syndrome: a post-hoc analysis of the BODI validation study.

OBJECTIVES: To evaluate the prevalence, magnitude, and potential determinants of work productivity impairment in patients with Behçet's Syndrome (BS), focusing on the role of irreversible organ damage. METHODS: A post-hoc analysis of the BS overall damage index (BODI) prospective validation study was performed. Demographics and clinical features were recorded in all patients. The Work Productivity and Activity Impairment: General Health (WPAI: GH) questionnaire was administered to assess the work limitation and the BODI to measure organ damage. The independent effect of BS features on WPAI: GH outcomes was evaluated by regression analysis. RESULTS: Out of 148 patients, 34.5% were unemployed, with age (OR 1.035) and BODI score (OR 1.313 for 1-unit increase) as the only factors significantly (p< 0.05) associated with the unemployment state. An overall work impairment was reported in about 64.2% of the employed patients. Indeed, 22.7% reported missing work h due to their health (absenteeism), with a mean time loss of 34.4%; whereas 60.2% declared a reduced performance at work because of their health (presenteeism), with a mean productivity impairment of 45.4%. Ocular damage was associated with absenteeism (ß 0.225); female sex (ß 0.260), physician global assessment of disease activity (ß 0.502) and an increased BODI score (ß 0.166 for 1-point increase) with presenteeism; fibromyalgia (ß 0.246), physician global assessment (ß 0.469), and musculoskeletal damage (ß 0.325) with overall work impairment. CONCLUSIONS: Disease activity and organ damage accrual remarkably affect work productivity in BS patients. Achieving remission and preventing damage accrual are crucial and complementary objectives.

Intranasal Liposomal Formulation of Spike Protein Adjuvanted with CpG Protects and Boosts Heterologous Immunity of hACE2 Transgenic Mice to SARS-CoV-2 Infection.

Mucosal vaccination appears to be suitable to protect against SARS-CoV-2 infection. In this study, we tested an intranasal mucosal vaccine candidate for COVID-19 that consisted of a cationic liposome containing a trimeric SARS-CoV-2 spike protein and CpG-ODNs, a Toll-like receptor 9 agonist, as an adjuvant. In vitro and in vivo experiments indicated the absence of toxicity following the intranasal administration of this vaccine formulation. First, we found that subcutaneous or intranasal vaccination protected hACE-2 transgenic mice from infection with the wild-type (Wuhan) SARS-CoV-2 strain, as shown by weight loss and mortality indicators. However, when compared with subcutaneous administration, the intranasal route was more effective in the pulmonary clearance of the virus and induced higher neutralizing antibodies and anti-S IgA titers. In addition, the intranasal vaccination afforded protection against gamma, delta, and omicron virus variants of concern. Furthermore, the intranasal vaccine formulation was superior to intramuscular vaccination with a recombinant, replication-deficient chimpanzee adenovirus vector encoding the SARS-CoV-2 spike glycoprotein (Oxford/AstraZeneca) in terms of virus lung clearance and production of neutralizing antibodies in serum and bronchial alveolar lavage (BAL). Finally, the intranasal liposomal formulation boosted heterologous immunity induced by previous intramuscular vaccination with the Oxford/AstraZeneca vaccine, which was more robust than homologous immunity.

Accrual of organ damage in Behçet's syndrome: trajectory, associated factors, and impact on patients' quality of life over a 2-year prospective follow-up study.

BACKGROUND: This study aimed to investigate the trajectory of damage accrual, associated factors, and impact on health-related quality of life (HR-QoL) in a multicenter cohort of patients with Behçet's syndrome (BS) over 2 years of follow-up. METHODS: Patients recruited in the BS Overall Damage Index (BODI) validation study were prospectively monitored for 2 years and assessed for damage accrual, defined as an increase ≥1 in the BODI score, and HR-QoL was evaluated by the SF-36 questionnaire. Logistic and multiple linear regression models were built to determine factors associated with damage accrual and impairment in the different SF-36 domains. RESULTS: During follow-up, 36 out of 189 (19.0%) patients had an increase ≥1 in the BODI score with a mean (SD) difference of 1.7 (0.8) (p <0.001). The incidence rate of damage accrual was stable over time, regardless of the disease duration. Out of 61 new BODI items, 25 (41.0%) were considered related to glucocorticoid (GC) use. In multivariate analysis, duration of GC therapy (OR per 1-year 1.15, 95% CI 1.07-1.23; p <0.001) and occurrence of ≥1 disease relapse (OR 3.15, 95% CI 1.09-9.12; p 0.038) were identified as predictors of damage accrual, whereas the use of immunosuppressants showed a protective effect (OR 0.20, 95% CI 0.08-0.54, p<0.001). Damage accrual was independently associated with the impairment of different physical domains and, to a greater extent, in emotional domains of the SF-36 questionnaire. Female sex, higher disease activity, and fibromyalgia were also significantly associated with impairment in HR-QoL. CONCLUSION: In BS, organ damage accrues over time, also in long-standing disease, resulting in an impairment of the perceived physical and mental health. Adequate immunosuppressive treatment, preventing disease flares and minimizing exposure to GCs have a crucial role in lowering the risk of damage accrual.

Predictive value of common genetic variants in idiopathic pulmonary fibrosis survival.

Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive, fibrosing interstitial pneumonia of unknown etiology. The role of genetic risk factors has been the focus of numerous studies probing for associations of genetic variants with IPF. We aimed to determine whether single-nucleotide polymorphisms (SNPs) of four candidate genes are associated with IPF susceptibility and survival in a Portuguese population. A retrospective case-control study was performed with 64 IPF patients and 74 healthy controls. Ten single-nucleotide variants residing in the MUC5B, TOLLIP, SERPINB1, and PLAU genes were analyzed. Single- and multi-locus analyses were performed to investigate the predictive potential of specific variants in IPF susceptibility and survival. Multifactor dimensionality reduction (MDR) was employed to uncover predictive multi-locus interactions underlying IPF susceptibility. The MUC5B rs35705950 SNP was significantly associated with IPF: T allele carriers were significantly more frequent among IPF patients (75.0% vs 20.3%, P < 1.0 × 10-6). Genotypic and allelic distributions of TOLLIP, PLAU, and SERPINB1 SNPs did not differ significantly between groups. However, the MUC5B-TOLLIP T-C-T-C haplotype, defined by the rs35705950-rs111521887-rs5743894-rs5743854 block, emerged as an independent protective factor in IPF survival (HR = 0.37, 95% CI 0.17-0.78, P = 0.009, after adjustment for FVC). No significant multi-locus interactions correlating with disease susceptibility were detected. MUC5B rs35705950 was linked to an increased risk for IPF, as reported for other populations, but not to disease survival. A haplotype incorporating SNPs of the MUC5B-TOLLIP locus at 11p15.5 seems to predict better survival and could prove useful for prognostic purposes and IPF patient stratification. KEY MESSAGES : The MUC5B rs35705950 minor allele is associated with IPF risk in the Portuguese. No predictive multi-locus interactions of IPF susceptibility were identified by MDR. A haplotype defined by MUC5B and TOLLIP SNPs is a protective factor in IPF survival. The haplotype may be used as a prognostic tool for IPF patient stratification.

Benefits of adding food education sessions to an exercise programme on cardiovascular risk factors in patients with type 2 diabetes.

To evaluate the impact of adding food education sessions to an exercise programme on cardiovascular risk factors in middle-aged and older patients with type 2 diabetes (T2D), a randomised parallel-group study was performed. Glycated haemoglobin, body mass index (BMI), waist circumference, fat mass (FM) and blood pressure were assessed at baseline and after 9 months. The recruitment was made in three primary healthcare centres from Vila Real, Portugal. Thirty-three patients (65⋅4 ± 5⋅9 years old) were engaged in a 9-month community-based lifestyle intervention programme: a supervised exercise programme (EX; n = 15; combined aerobic, resistance, agility/balance and flexibility exercise; three sessions per week; 75 min per session); or the same exercise programme plus concomitant food education sessions (EXFE; n = 18; 15-min lectures and dual-task strategies during exercise (answer nutrition questions while walking); 16 weeks). Significant differences between groups were identified in the evolution of BMI (P < 0.001, ) and FM (P < 0.001, ), with best improvements observed in the EXFE group. The addition of a simple food education dietary intervention to an exercise programme improved body weight and composition, but not glycaemic control and blood pressure in middle-aged and older patients with T2D.

Protein Mannosylation as a Diagnostic and Prognostic Biomarker of Lupus Nephritis: An Unusual Glycan Neoepitope in Systemic Lupus Erythematosus.

OBJECTIVE: Changes in protein glycosylation are a hallmark of immune-mediated diseases. Glycans are master regulators of the inflammatory response and are important molecules in self-nonself discrimination. This study was undertaken to investigate whether lupus nephritis (LN) exhibits altered cellular glycosylation to identify a unique glycosignature that characterizes LN pathogenesis. METHODS: A comprehensive tissue glycomics characterization was performed in kidney specimens from patients with systemic lupus erythematosus and biopsy-proven LN. A combination of advanced tissue mass spectrometry, in situ glyco-characterization, and ex vivo glycophenotyping was performed to structurally map the repertoire of N-glycans in LN tissue samples. RESULTS: LN exhibited a unique glycan signature characterized by increased abundance and spatial distribution of unusual mannose-enriched glycans that are typically found in lower microorganisms. This glycosignature was specific for LN, as it was not observed in other kidney diseases. Exposure of mannosylated glycans in LN was shown to occur at the cell surface of kidney cells, promoting increased recognition by specific glycan-recognizing receptors expressed by immune cells. This abnormal glycosignature of LN was shown to be due to a deficient complex N-glycosylation pathway and a proficient O-mannosylation pathway. Moreover, mannosylation levels detected in kidney biopsy samples from patients with LN at the time of diagnosis were demonstrated to predict the development of chronic kidney disease (CKD) with 93% specificity. CONCLUSION: Cellular mannosylation is a marker of LN, predicting the development of CKD, and thus representing a potential glycobiomarker to be included in the diagnostic and prognostic algorithm of LN.

The impact of a community-based food education programme on dietary pattern in patients with type 2 diabetes: Results of a pilot randomised controlled trial in Portugal.

The purpose of this study was to analyse the effects of a food education programme, with easy-to-implement strategies integrated in a community-based exercise programme, on dietary pattern of patients with type 2 diabetes (T2D). Thirty-three patients (65.4 ± 5.9 years old) were engaged in a 9-month randomised controlled trial: a supervised exercise programme (control group [CON]; n = 15; combined exercise; three sessions per week; 75 min per session) or the same exercise programme plus a concomitant 16-week food education programme (experimental group [EXP]; n = 18; 15-min. group classes and dual-task strategies during exercise). Dietary pattern was assessed using a 3-day food record at baseline and at 9 months. The intake of total fat, polyunsaturated fat, and the daily servings of vegetables significantly increased in EXP compared with the CON group. Retention and adherence to the programme were 54% and 49.5 ± 27.2%, respectively. This food education programme improved dietary pattern of patients with T2D. Special attention should be given to strategies that support participants' attendance.

Macrophagic myofasciitis: an atypical presentation for a rare disease with a challenging approach.

Macrophagic myofasciitis (MMF) is a rare immune-mediated myopathy that seems to be triggered by aluminium hydroxide adjuvant used in vaccines. Its presentation is relatively heterogeneous and treatment with steroids leads to improvement, although there is little evidence regarding the role of other immunosuppressants. The histological findings in MMF seem to be the result of an abnormal presence in the inoculation site of aluminium, which can induce an immune-mediated muscular disease in susceptible persons. The authors describe the case of a patient with an atypical presentation of macrophagic myofasciitis, with histological confirmation in a muscle biopsy distant from the inoculation site, and a good therapeutic response to tacrolimus and mycophenolate mofetil, as well as a discussion on the pathologic basis, controversies and emerging treatments for this condition.

Eugenol and its association with levodopa in 6-hydroxydopamine-induced hemiparkinsonian rats: Behavioural and neurochemical alterations.

Parkinson's disease is a neurodegenerative disorder that affects the central nervous system and is mainly characterized by the loss of dopaminergic neurons and pro-oxidant mechanisms. Eugenol has been widely studied due to its anti-inflammatory and antioxidant activities, making it a promising neuroprotective agent. This study aimed to investigate the effects of eugenol and its combined action with levodopa in the 6-hydroxydopamine-induced Parkinson's disease model. Wistar rats were subjected to intrastriatal injection of 6-hydroxydopamine (21 µg) and then treated with eugenol (0.1, 1, or 10 mg/kg), levodopa (25 mg/kg) or their combination (eugenol 10 mg/kg + levodopa 12.5 mg/kg) orally for 14 days. On the 14th day, the animals were subjected to behavioural tests, and after euthanization and dissection of the brain areas, neurochemical analyses were performed. The results showed that eugenol reduced the oxidative stress and behavioural disturbances induced by 6-hydroxydopamine. The eugenol and levodopa combination was more effective in some behavioural parameters and body-weight gain in addition to promoting an increase in reduced glutathione levels compared to levodopa alone. Thus, the neuroprotective activity of eugenol was observed against motor and neurochemical disorders. Additionally, the eugenol and levodopa combination was promising when compared to conventional treatment.

Nutrition-related knowledge and its determinants in middle-aged and older patients with type 2 diabetes.

AIMS: To analyse nutrition-related knowledge and its determinants in middle-aged and older patients with T2D. METHODS: In a cross sectional study, a total of 116 participants with T2D, aged 50-80 years, were recruited in primary health care. Data was collected by a self-reported questionnaire - the modified version of General Nutrition Knowledge Questionnaire (0-56 points). Sociodemographic data was also collected: gender, age, personal monthly income, living situation, education level, and marital status. One-way analysis of variance (ANOVA) was performed to assess differences in nutrition-related knowledge score among the different levels of sociodemographic characteristics. RESULTS: Questions on general dietary recommendations, dietary behaviors to reduce cardiovascular disease and cancer are the items with higher proportion of correct answers. On the other hand, health problems related with lower intake of fruit, vegetables and fiber and knowledge about antioxidants vitamins presented the lower proportion of correct answers. Higher scores were found among those with lower age, higher personal monthly income, and higher education. CONCLUSIONS: Middle-aged and older patients with T2D showed alarming deficits on nutrition-related knowledge. Age, personal monthly income, and education level were observed as major determinants of nutrition-related knowledge. TRIAL REGISTRATION: NCT02631902.

The Impact of a Community-Based Food Education Program on Nutrition-Related Knowledge in Middle-Aged and Older Patients with Type 2 Diabetes: Results of a Pilot Randomized Controlled Trial.

The purpose of this study was to evaluate the impact of a community-based food education program on nutrition-related knowledge in middle-aged and older patients with type 2 diabetes (T2D). Participants (n = 36; 65.9 ± 6.0 years old) were recruited in primary health care to a 9-month community-based lifestyle intervention program for patients with T2D and randomly assigned to an exercise program (control group; n = 16) or an exercise program plus a food education program (experimental group; n = 20). Nutrition-related knowledge was assessed through a modified version of the General Nutrition Knowledge Questionnaire. The increase in total nutrition-related knowledge score and sources of nutrients area score was significantly higher in the experimental group compared to the control group. No significant changes in nutrition-related knowledge were found between groups in dietary recommendations and diet-disease relationship areas, although improvements were observed. This community-based food education program, with the use of easy to implement strategies (short-duration lectures and dual-task problem solving activities during exercise), had a positive and encouraging impact on nutrition-related knowledge in middle-aged and older patients with T2D.

Role of cAMP modulator supplementations during oocyte in vitro maturation in domestic animals.

Cyclic adenosine monophosphate (cAMP) is an important molecule in signal transduction within the cell, functioning as a second cell messenger of gonadotrophin stimulation. The concentration of cAMP in cumulus-oocyte complexes (COCs) is known to be controlled through modulation of its synthesis by adenylyl cyclase (AC) and by degradation through the cyclic nucleotide phosphodiesterase (PDE) enzymes. One of the main obstacles for in vitro embryo production is the optimization of reproduction processes that occur in oocyte maturation. The function of cAMP is important in maintaining meiotic arrest in mammalian oocytes. When the oocyte is physically removed from the antral follicle for in vitro maturation (IVM), intra-oocyte cAMP concentrations decrease and spontaneous meiotic resumption begins, due to the depletion of inhibitory factors from the follicle. In many studies, relatively greater cAMP concentrations before IVM has been reported to improve oocyte competence, leading to subsequent benefits in embryonic development in different species. There, therefore, has been an increase in oocyte cAMP concentrations with several treatments and different approaches, such as invasive AC, stimulators of AC activity, PDE inhibitors, and cAMP analogs. The aim of this review is to comprehensively evaluate and provide data related to (i) the use of cAMP modulators during IVM and the effects on completion of meiosis and cytoplasmic reorganization, which are required for development of oocytes with the capacity to contribute to fertilization and subsequent embryonic development; and (ii) the main cAMP modulators and the effects when used in oocyte IVM.

Case of newly diagnosed bilateral anorchia in a 42-year-old male patient.

A 42-year-old African man presented with hypogonadic phenotypical features, including gynoid body distribution, gynaecomastia, absent facial and truncal hair and micropenis. He denied ever experiencing development of male secondary sex characteristics. Endocrine testing revealed hypergonadotropic hypogonadism and undetectable AMH. Human chorionic gonadotropin (hCG) stimulation test failed to increase testosterone levels. Peripheral blood karyotype was 46, XY. Clinical examination and abdominal/pelvic/scrotal ultrasound and MRI failed to identify any testicular structures/remnants. Given the clinical course and the biochemical-radiological presentation, the diagnosis of bilateral anorchia was made (after more than four decades of its probable onset), and surgical exploration was decided against. The patient was subsequently started on monthly intramuscular testosterone experiencing progressive normal virilisation.

Non-adenomatous sellar lesions: single-centre 10-year experience.

OBJECTIVE: A minority of lesions found in the sellar region are non-adenomatous neoplastic, inflammatory, or cystic masses. Our study aims to describe the prevalence and characteristics of these lesions in a multidisciplinary pituitary outpatient clinic. DESIGN: We conducted an observational study which included 36 patients (15.9% of those followed up in this outpatient clinic between 2006 and 2016 who had pituitary surgery) submitted to pituitary surgery with histological results showing a non-adenomatous sellar lesion. We evaluated clinical, radiological, and biochemical (pituitary function) characteristics during the pre-operative and post-operative period. RESULTS: Thirty-six patients (50% female) with a mean age of 41.3 ± 21.9 years and a mean follow-up duration of 8.0 ± 9.0 years were included. Histologic diagnoses were divided into benign neoplasms (80.6%), malignant neoplasms (11.1%), inflammatory lesions (5.6%), and cystic masses (2.8%). The most common clinical presentation was headache (66.7%) and visual defects (61.1%). Forty-seven percent of patients had at least one pituitary axis insufficiency at the time of diagnosis. In the majority of cases (58.3%), a transsphenoidal approach was used for the initial pituitary surgery. Thirteen patients had more than one pituitary surgery and eight also had radiotherapy. At the time of data retrieval, five patients had no pituitary hormonal insufficiency and 13 patients had some visual defect improvement. CONCLUSIONS: Although rare, non-adenomatous sellar lesions may be associated with significant causes of morbidity, such as hypopituitarism and visual defects, per se or due to the various treatment modalities employed. Moreover, since the lesions are difficult to distinguish from adenomas, these patients require a careful multidisciplinary approach.

Merkel cell carcinoma and the challenge in its approach: a review based on a clinical context of immunosuppression.

Merkel cell carcinoma (MCC) is a rare and aggressive neuroendocrine cancer with high rate to local relapse and metastasis. Its connection to immunosuppression is well known, with reported association to human immunodeficiency virus (HIV). The authors present an 87-year-old woman, infected by HIV type 2 at advanced stage of the disease, whom presented a painless papule on left cheek in 2011. After its total excision, the histopathology confirmed MCC "in situ," with no regional or distant metastases. Simultaneously, she revealed a viral load of 2220 copies/mL and 224 CD4/mm3. Five months later, the patient presented a local and distance relapse with an aggressive behavior and positive regional lymph node. Stage IV disease was confirmed due to presence of liver metastases. Concurrently to the relapse, it was detected low CD4 levels. In our multidisciplinary team decision meeting, it has been decided conservative treatment due to low Karnofsky status, comorbidities, and stage of disease.

[Vitamin B12 Deficiency in Type 2 Diabetes Mellitus]. / Défice de Vitamina B12 na Diabetes Mellitus Tipo 2.

INTRODUCTION: Type 2 diabetes mellitus is a common disease, affecting up to 13.1% of the Portuguese population. In addition to the known micro and macrovascular complications, drug side effects constitute a major concern, leading to changes in the treatment guidelines, which favor safety over efficacy. Metformin is the first-line pharmacological treatment for most patients with type 2 diabetes mellitus; however, it has been associated with vitamin B12 deficiency in up to 30% of treated patients. The authors describe the prevalence of vitamin B12 deficiency in a diabetic population and explore the possible underlying factors. MATERIAL AND METHODS: Retrospective, observational study. Clinical and laboratory data of type 2 diabetes mellitus patients whose vitamin B12 status was evaluated in the last decade (2005 - 2016) were analyzed. Patients with known malabsorptive syndromes or having undergone bariatric surgery were excluded from the study. Statistical analysis of the data was done and the results were considered statistically significant at p values < 0.05. RESULTS: The study included a total of 1007 patients (58% women) with a mean age of 66.4 ± 12.2 years and 11 ± 10.4 years of type 2 diabetes mellitus duration. These patients had a high prevalence of complications: diabetic renal disease 47.7%, neuropathy 9.2%, retinopathy 14.9%, coronary artery disease 8.4%, cerebrovascular disease 10.9%, and peripheral arterial disease 5.5%. Vitamin B12 deficiency (< 174 ng / dL) was present in 21.4% of the population and this subgroup was older (68.4 vs 65.8 years, p = 0.006), had a longer type 2 diabetes mellitus duration (13.35 vs 10.36 years; p = 0.001), higher prevalence of retinopathy (20.9% vs 13.3%; p = 0.005) and thyroid dysfunction (34% vs 23.7%; p = 0.002). Vitamin B12 deficiency was also more frequent in patients treated with metformin (24.7% vs 15.8%; p = 0.017), antiplatelet agents (25.4% vs 16.2%, p < 0.001), and calcium channel blockers (26.8% vs 18.2%; p = 0.001). After adjustment for possible confounders, the variables associated with B12 deficiency were: metformin, hypothyroidism, age and type 2 diabetes mellitus duration. DISCUSSION: Despite the retrospective design, the results report a high prevalence of vitamin B12 deficiency in the type 2 diabetic population. This study also demonstrates that the B12 deficiency risk is higher in older people, with longer diabetes mellitus duration, hypothyroidism and treated with metformin. CONCLUSION: Further studies are needed to identify the risk factors for the B12 deficit. The recognition of these variables will contribute to optimize the screening and prevention of the B12 deficiency in type 2 diabetes mellitus.

Introdução: A diabetes mellitus tipo 2 é uma entidade comum, afetando até 13,1% da população portuguesa. Para além das conhecidas complicações micro e macrovasculares, as iatrogenias medicamentosas tornaram-se uma crescente preocupação contribuindo para as observadas alterações das recomendações terapêuticas, que cada vez mais privilegiam a segurança em detrimento da eficácia. A metformina é o agente farmacológico de primeira linha na maioria dos doentes com diabetes mellitus tipo 2, contudo, está descrita a associação com défice de vitamina B12 em até 30% dos doentes. Os autores descrevem a prevalência de défice de vitamina B12 numa população diabética e os possíveis fatores associados à mesma. Material e Métodos: Foi efectuado um estudo retrospectivo, observacional no qual foram registados os dados clínico-laboratoriais de doentes com diabetes mellitus tipo 2 com doseamentos de B12 na última década (2005 - 2016). Foram excluídos doentes submetidos a cirurgia bariátrica e com síndromes malabsorptivos conhecidos. Foi efectuada análise estatística dos dados e os resultados foram considerados estatisticamente significativos para p < 0,05. Resultados: Foram estudados 1007 doentes com uma idade média de 66,4 ± 12,2 anos e 11 ± 10,4 anos de evolução da diabetes mellitus tipo 2, das quais 58% eram mulheres. Apresentavam uma elevada prevalência de complicações: doença renal diabética 47,7%, neuropatia 9,2%, retinopatia 14,9%, doença coronária 8,4%, doença vascular cerebral 10,9% e doença arterial periférica 5,5%. O défice de B12 (< 174 ng/dL) foi documentado em 21,4% da população e neste subgrupo constatou-se uma idade mais avançada (68,4 vs 65,8 anos; p = 0,006), maior duração da diabetes (13,35 vs 10,36 anos; p = 0,001), maior prevalência de retinopatia (20,9% vs 13,3%; p = 0,005) e disfunção tiroideia (34% vs 23,7%; p = 0,002). O défice de B12 foi mais frequente nos doentes expostos à metformina (24,7% vs 15,8%; p = 0,017), antiagregantes (25,4% vs 16,2%; p < 0,001) e bloqueadores dos canais de cálcio (26,8% vs 18,2%; p = 0,001). Após ajuste para factores de confundimento, a metformina, hipotiroidismo, idade e anos de evolução da diabetes mellitus tipo 2 mantiveram uma associação estatisticamente significativa, o que não se verificou com a retinopatia e os bloqueadoresdos canais de cálcio. Discussão: Apesar do desenho retrospectivo, os resultados alertam para a elevada prevalência do défice de vitamina B12 na população com diabetes mellitus tipo 2. O presente estudo demonstra que o risco parece ser maior em populações com idades mais avançadas, com maior tempo de evolução da diabetes mellitus, com hipotiroidismo e sob metformina. Conclusão: São necessários mais estudos para que se possam identificar os factores de risco para o défice de B12. O reconhecimento dessas variáveis contribuirá para optimizar o rastreio e prevenção do défice de B12 na diabetes mellitus tipo 2.

Diabetes mellitus and hyperkalemic renal tubular acidosis: case reports and literature review / Diabetes mellitus e acidose tubular renal hipercalêmica: relatos de caso e revisão da literatura

ABSTRACT Hyporeninemic hypoaldosteronism, despite being common, remains an underdiagnosed entity that is more prevalent in patients with diabetes mellitus. It presents with asymptomatic hyperkalemia along with hyperchloraemic metabolic acidosis without significant renal function impairment. The underlying pathophysiological mechanism is not fully understood, but it is postulated that either aldosterone deficiency (hyporeninemic hypoaldosteronism) and/or target organ aldosterone resistance (pseudohypoaldosteronism) may be responsible. Diagnosis is based on laboratory parameters. Treatment strategy varies according to the underlying pathophysiological mechanism and etiology and aims to normalize serum potassium. Two clínical cases are reported and the relevant literature is revisited.

RESUMO Apesar de comum, o hipoaldosteronismo hiporeninêmico continua a ser uma entidade sub-diagnosticada, com maior prevalência em pacientes com diabetes mellitus. A doença cursa com hipercalemia assintomática acompanhada de acidose metabólica hiperclorêmica sem disfunção renal significativa. O mecanismo fisiopatológico subjacente não é entendido em sua totalidade, mas postula-se que a deficiência de aldosterona (hipoaldosteronismo hiporeninêmico) e/ou a resistência à aldosterona no órgão-alvo (pseudo-hipoaldosteronismo) possam ser responsáveis. O diagnóstico é fundamentado em parâmetros laboratoriais. A estratégia terapêutica varia de acordo com o mecanismo fisiopatológico subjacente e a etiologia, mas seu objetivo é normalizar o potássio sérico. O presente artigo relata dois casos e analisa a literatura relevante sobre o assunto.

Diabetes insipidus and hypopituitarism in HIV: an unexpected cause.

Central diabetes insipidus (DI) is a rare clinical entity characterized by low circulating levels of antidiuretic hormone (ADH) presenting with polyuria and volume depletion. Pituitary surgery is the most common cause of central DI in adults. Pituitary and hypothalamic disease, particularly invasive neoplasms, rarely cause DI, being idiopathic cases responsible for the majority of non-surgical cases. HIV patients, especially those with poor virulogical control, are prone to the development of CNS neoplasms, particularly lymphomas. These neoplasms usually become manifest with mass effects and seizures. Central DI and hypopituitarism are uncommon initial manifestations of primary CNS lymphomas. The authors describe the case of 29-year-old female, HIV-positive patient whose CNS lymphoma presented with DI. LEARNING POINTS: Central diabetes insipidus has multiple causes and central nervous system lymphomas are not often considered in the differential diagnosis due to their low prevalence.Accurate biochemical diagnosis should always be followed by etiological investigation.The HIV population is at risk for many neoplasms, especially CNS lymphomas.New-onset polyuria in an HIV-positive patient in the absence of focal neurological signs should raise the suspicion for a central nervous system process of neoplastic nature.This clinical entity usually constitutes a therapeutical challenge, often requiring a multidisciplinary approach for optimal outcome.

Thyrotoxicosis leading to adrenal crises reveals primary bilateral adrenal lymphoma.

Primary adrenal lymphoma is a rare malignancy. It frequently presents bilaterally and with symptoms of adrenal insufficiency. Amiodarone may induce secondary organ dysfunction, and thyrotoxicosis develops in 15% of cases. The symptomatology of both conditions is nonspecific, especially in the elderly, and a high suspicion index is necessary for appropriate diagnosis. A 78-year-old female presented to the emergency department with confusion, nausea and vomiting. She had recently been to the emergency department with urinary tract infection, vomiting and acute hypochloremic hyponatremia. Upon re-evaluation, the leukocyturia persisted and because of TSH 0.01 µU/mL and free-T4 68 (10-18) pmol/L, she was admitted to the Endocrinology ward. Further evaluation supported amiodarone-induced thyroiditis type 2. Sepsis ensued, in the setting of nosocomial pneumonia. Hemodynamic instability, hyponatremia, hypoglycemia and vomiting raised the suspicion of adrenocortical insufficiency. Fluid resuscitation and hydrocortisone led to clinical improvement, and adrenal insufficiency was admitted. The thoracoabdominal tomography suggested an endobronchic primary lesion with hepatic and adrenal secondary deposits (6.6 and 7 cm), but this was confirmed neither on pleural effusion nor on bronchofibroscopic fluid analyses. The adrenals were not accessible for biopsy. Despite high-dose hydrocortisone maintenance, the patient died before definite diagnosis. The autopsy confirmed primary non-Hodgkin lymphoma. LEARNING POINTS: Primary adrenal lymphoma is a rare cause of adrenal insufficiency, but progression can be fast and fatal.Hyperpigmentation is frequently absent.The presenting symptoms are nonspecific and might mimic infection. Disproportion of the general state with signs of specific organ symptomatology is a diagnostic clue.Infection may precipitate adrenal crisis and worsen thyroid function with further adrenal insufficiency exacerbation.In the context of thyrotoxicosis, there may be little clinical response to a therapeutic trial with standard dose glucocorticoids.High-dose glucocorticoid substitution may be required to achieve clinical stability in thyrotoxic patients.