Virus and Autoimmunity: Can SARS-CoV-2 Trigger Large Vessel Vasculitis?

Introduction: Viral infections can induce autoimmune diseases in susceptible patients. SARS-CoV-2 has been associated with the development of rheumatic disease, especially small vessel vasculitis and arthritis. Typically, onset occurs days to weeks after the antigenic challenge and in patients with mild COVID-19. We report a case of large vessel vasculitis (LVV) temporally related to SARS-CoV-2 infection. Case description: An otherwise healthy 19-year-old woman presented with fatigue, malaise, and chest and low back pain. The symptoms had begun 5 weeks earlier and 1 month after mild SARS-CoV-2 infection. Serological work-up revealed a marked proinflammatory state and anaemia without signs of infectious or autoimmune disease. Computerized tomography revealed thickening and blurring of the perivascular fat of the descending thoracic and abdominal aorta, progressing along the proximal iliac and renal arteries. Fluorodeoxyglucose positron emission tomography confirmed inflammatory activity. Symptoms and laboratory values normalized after prednisolone treatment. Discussion: Recent SARS-CoV-2 infection may be a trigger for LVV, including Takayasu arteritis, as well as other rheumatic diseases. A prompt and thorough differential diagnosis is essential to exclude aortitis and LVV mimickers. Moreover, physicians should be aware of the potential spectrum of systemic and autoimmune diseases that could be precipitated by SARS-CoV-2 infection. This will allow timely diagnosis and treatment, with significant improvement in prognosis. LEARNING POINTS: SARS-CoV-2 infection can trigger large vessel vasculitis and other rheumatic diseases.Awareness of the association between COVID-19 and autoimmune phenomena allows for timely diagnosis and treatment with significant improvements in prognosis.Vasculitis and other autoimmune diseases should be kept in mind in patients who develop proinflammatory states days to weeks after an initial antigenic challenge.

Intrathoracic Acute Cholecystitis.

The authors present the case of a 51-year-old woman with no history of surgical or traumatic injury or accident, who presented with right hypochondrium and epigastric discomfort, malaise, nausea, loss of appetite and episodes of dark urine and greenish stools. Initial laboratory work-up revealed elevated inflammatory markers including leucocytosis with left shift and C-reactive protein, and a slight elevation of gamma-glutamyltransferase and alkaline phosphatase, with no other significant alterations. Computed tomography (CT) showed intrathoracic acute cholecystitis with a large diaphragmatic hernia. A literature search revealed only one other case of acute cholecystitis complicated by intrathoracic gallbladder due to a non-traumatic diaphragmatic hernia. Symptoms are uncharacteristic and the absence of pain or fever, explained by the altered location of the gallbladder, makes the diagnosis a challenge. LEARNING POINTS: Only one other case of acute cholecystitis complicated by intrathoracic gallbladder due to a non-traumatic diaphragmatic hernia has been reported.Uncharacteristic symptoms make the diagnosis of intrathoracic acute cholecystitis a challenge.

L-TRUST: Long-term risk of cancer in patients under statins therapy. A systematic review and meta-analysis.

INTRODUCTION: Statins are widely prescribed drugs with established efficacy in primary and secondary prevention of cardiovascular events. Although they are mostly well tolerated, several authors have been emphasizing that the statins' safety profile is not totally clarified especially when considering risk of cancer in patients with long-term exposure to statins. This meta-analysis was aimed at evaluating the risk of cancer in patients with prolonged exposure to statins. METHODS: Medline, Cochrane library, and clinicaltrials.gov were searched in order to identify studies with a minimum average follow-up of 10 years of exposure to statins and a cancer-related outcome reported. Relative risk (RR) of the primary outcomes and the combined effect was presented using a random-effects model. In the selected randomized control trials (RCT), statin exposure was compared with placebo, and in the selected observational studies, it was compared with no exposure to statins. RESULTS: We retrieved 1627 studies, of which 15 full-papers were included for final review, five RCT, two cohort studies (CSs), and eight case-control studies (CCs), representing a total of 358 544 patients. Five RCT, two cohort studies (CSs), and eight case-control studies (CCs). No significant differences were found regarding risk of cancer occurrence (RR = 1.08, 0.96-1.21) or cancer mortality (RR = 0.91, 0.80-1.04) due to long-term statin exposure. Regarding all-cause mortality, a protective effect was found (RR = 0.93, 0.90-0.97). CONCLUSIONS: According to available and published evidence, statins are not associated with an increased risk of cancer after prolonged exposure. These findings strengthen the role of statins in the primary and secondary prevention of cardiovascular events.

Hfe mutations and iron overload in patients with alcoholic liver disease.

CONTEXT: Alcoholic liver disease (ALD) is generally associated with iron overload, which may contribute to its pathogenesis, through increased oxidative stress and cellular damage. There are conflicting reports in literature about hemochromatosis (HFE) gene mutations and the severity of liver disease in alcoholic patients. OBJECTIVES: To compare the prevalence of mutations in the hemochromatosis (HFE) gene between patients with ALD and healthy controls; to assess the relation of HFE mutations with liver iron stores and liver disease severity. METHODS: Liver biopsy specimens were obtained from 63 ALD patients (during routine treatment) and 52 healthy controls (during elective cholecystectomy). All individuals underwent routine liver function tests and HFE genotyping (to detect wild-type sequences and C282Y, H63D, S65C, E168Q, E168X, V59M, H63H, P160delC, Q127H, Q283P, V53M and W164X mutations). Associations between HFE mutations and risk of excessive liver iron stores, abnormal serum ferritin, liver fibrosis, or necroinflammatory activity were assessed by multivariate logistic regression analysis. RESULTS: ALD patients had significantly higher serum ferritin and transferrin saturation than controls (both P<0.05), but the distribution of HFE mutations was similar between the two groups. For ALD patients, the odds ratio for having at least one HFE mutation and excessive liver iron stores was 17.23 (95% confidence interval (CI): 2.09-142.34, P = 0.008). However, the presence of at least one HFE mutation was not associated with an increased risk of liver fibrosis or necroinflammatory activity. Active alcohol ingestion showed the strongest association to increased serum ferritin (OR = 8.87, 95% CI: 2.11-34.78, P = 0.003). CONCLUSION: s ALD patients do not present with a differential profile of HFE mutations from healthy controls. In ALD patients, however, the presence of at least one HFE mutation increases the risk of having excessive liver iron stores but has no detectable effects on liver disease activity or severity.

Iron stores assessment in alcoholic liver disease.

BACKGROUND: The relation between alcoholic liver disease (ALD) and iron overload is well known. Liver biopsy is the gold standard for assessing iron stores. MRI is also validated for liver iron concentration (LIC) assessment. We aimed to assess the effect of active drinking in liver iron stores and the practicability of measuring LIC by MRI in ALD patients. MATERIALS AND METHODS: We measured LIC by MRI in 58 ALD patients. We divided patients into two groups - with and without active alcoholism - and we compared several variables between them. We evaluated MRI-LIC, liver iron stores grade, ferritin and necroinflammatory activity grade for significant correlations. RESULTS: Significant necroinflammation (40.0% vs. 4.3%), LIC (40.1 vs. 24.3 µmol/g), and ferritin (1259.7 vs. 568.7 pmol/L) were significantly higher in drinkers. LIC values had a strong association with iron stores grade (r s = 0.706). Ferritin correlated with LIC (r s = 0.615), iron stores grade (r s = 0.546), and necroinflammation (r s = 0.313). The odds ratio for elevated serum ferritin when actively drinking was 7.32. CONCLUSION: Active alcoholism is associated with increased ALD activity. It is also the key factor in iron overload. Scheuers' semiquantitative score with Perls' staining gives a fairly accurate picture of liver iron overload. Serum ferritin also shows a good correlation with LIC values and biopsy iron stores grade. As most patients present only with mild iron overload, serum ferritin measurement and semiquantitative evaluation of iron stores are adequate, considering MRI high cost. However, if MRI is required to evaluate liver structure, LIC assessment could be performed without added cost.

Hfe mutations add iron overload in patients with alcoholic liver disease

Context Alcoholic liver disease (ALD) is generally associated with iron overload, which may contribute to its pathogenesis, through increased oxidative stress and cellular damage. There are conflicting reports in literature about hemochromatosis (HFE) gene mutations and the severity of liver disease in alcoholic patients. Objectives To compare the prevalence of mutations in the hemochromatosis (HFE) gene between patients with ALD and healthy controls; to assess the relation of HFE mutations with liver iron stores and liver disease severity. Methods Liver biopsy specimens were obtained from 63 ALD patients (during routine treatment) and 52 healthy controls (during elective cholecystectomy). All individuals underwent routine liver function tests and HFE genotyping (to detect wild-type sequences and C282Y, H63D, S65C, E168Q, E168X, V59M, H63H, P160delC, Q127H, Q283P, V53M and W164X mutations). Associations between HFE mutations and risk of excessive liver iron stores, abnormal serum ferritin, liver fibrosis, or necroinflammatory activity were assessed by multivariate logistic regression analysis. Results ALD patients had significantly higher serum ferritin and transferrin saturation than controls (both P<0.05), but the distribution of HFE mutations was similar between the two groups. For ALD patients, the odds ratio for having at least one HFE mutation and excessive liver iron stores was 17.23 (95% confidence interval (CI): 2.09-142.34, P = 0.008). However, the presence of at least one HFE mutation was not associated with an increased risk of liver fibrosis or necroinflammatory activity. Active alcohol ingestion showed the strongest association to increased serum ferritin (OR = 8.87, 95% CI: 2.11-34.78, P = 0.003). Conclusions ALD patients do not present with a differential profile of HFE mutations from healthy controls. In ALD patients, however, ...

Contexto A doença hepática alcoólica (DHA) está geralmente associada à sobrecarga de ferro, que pode contribuir para a sua patogênese, através do aumento do estresse oxidativo e dano celular. As descrições existentes na literatura sobre a associação entre mutações HFE e a gravidade da DHA nem sempre são concordantes. Objetivos Comparar a prevalência de mutações HFE entre um grupo de pacientes com DHA e uma população de controle. Avaliar a relação entre mutações HFE e os depósitos de ferro hepático. Avaliar se a presença dessas mutações está associada com a gravidade da DHA. Métodos Compararam-se 63 pacientes com DHA que efetuaram biopsia hepática com 52 controles saudáveis. A genotipagem HFE (wild type, C282Y, H63D, S65C, E168Q, E168X, V59M, H63H, P160delC, Q127H, Q283P, V53M, W164X) e uma avaliação laboratorial de rotina (incluindo cinética do ferro) foram feitos em todos os indivíduos. Realizou-se regressão logística multivariada nos casos para avaliar se a presença de mutações HFE estava relacionada com risco aumentado de depósitos de ferro hepático aumentados, ferritina sérica anormal, fibrose hepática significativa ou atividade necroinflamatória. Resultados Os pacientes apresentaram ferritina sérica e saturação da transferrina mais elevadas que os controles, mas não existiram diferenças significativas na distribuição de mutações HFE entre pacientes e controles. Considerando apenas os pacientes, o risco relativo de estes apresentarem pelo menos uma mutação HFE e depósitos de ferro hepático significativos foi de 17.23 (CI 95% 2.09-142.34, P = 0.008). Contudo, a presença ...

Liver hepcidin mRNA expression is inappropriately low in alcoholic patients compared with healthy controls.

BACKGROUND AND AIMS: Hepcidin plays a crucial role in iron metabolism, preventing its absorption at the basolateral enterocyte membrane. Hepcidin regulation is complex and regulated at the transcriptional level. The relation between iron overload and alcoholic liver disease is well known, but its mechanism is not clear. We present an observational, case-control study, aimed at evaluating the effects of alcohol on the expression of hepcidin in human participants. We intended to assess whether iron overload related to alcohol ingestion was caused by hepcidin-impaired expression by determining hepcidin mRNA expression and relating it to iron stores, both in alcoholic patients and in normal controls. METHODS: We compared liver hepcidin mRNA expression between 25 active drinkers with alcoholic liver disease, without cirrhosis, and 20 healthy controls. All individuals were evaluated for HFE mutations, complete blood count, coagulation, glucose, kidney function, liver function, viral hepatitis, C-reactive protein, interleukin 6, tumor necrosis factor α, and serum iron, ferritin, and transferrin saturation. Total RNA was isolated from liver samples, cDNA was obtained by reverse transcription, and hepatic expression levels of hepcidin were determined by real-time PCR using the comparative Ct method (2(-ΔΔCt)). RESULTS: Serum ferritin and transferrin saturation were significantly higher in patients. Hepcidin was downregulated in patients compared with the controls by a mean factor of -0.44 (log10 2(-ΔΔCt)) (P=0.009). Hepcidin expression was not significantly different between the several grades of fibrosis, necroinflammatory activity, and liver iron stores. Heavy alcohol consumption caused the highest hepcidin mRNA suppression. The hepcidin mRNA expression/serum ferritin ratio was significantly lower in alcoholic patients (P<0.0001). CONCLUSION: Hepcidin liver expression is inappropriately low in alcoholic patients with active alcoholism and preserved hepatic function, and we conclude that this is the mechanism for alcohol consumption-associated iron overload in humans.

[Dural sinus thrombosis]. / Trombose de seios durais.

Dural sinus thrombosis is a rare condition and is often underdiagnosed. Because of its potentially lethal complications, it should always be considered in acute headache differential diagnosis. The authors present a report of two cases, both diagnosed on our department. They make an approach to clinical presentation, diagnosis and treatment of this disease.