Status Epilepticus in an Internal Medicine Ward: Different Patients Therefore Distinct Approaches.

Background Status epilepticus (SE) is a medical condition that bestows substantial morbidity and mortality. Literature is scarce regarding SE in elderly patients, particularly in the context of internal medicine wards. Aim To characterize SE patients admitted to an internal medicine ward, identify potential outcome predictors and differences between young and elderly, as well as convulsive (CSE) and non-convulsive SE (NCSE) patients. Methods We enrolled 135 consecutive patients in an observational, retrospective cohort study. We established elderly patients as more than 64 years old and defined worse prognosis as a modified Rankin Scale (mRS)>4. Results The SE population was 73% elderly, and 75% presented with NCSE, mainly metabolic, idiopathic, or vascular SE. The intra-hospital mortality was 51%, and 62% had an mRS>4 at discharge. NCSE and electroencephalogram (EEG) with paroxysmal activity at discharge were predictive of a worse prognosis. Elderly patients had increased disability at admission, most had NCSE (81%), and the SE etiology differed with more idiopathic and vascular causes. In the elderly, mortality was increased, as was the number of patients with mRS>4 at discharge. NCSE patients had the more neurodegenerative disease (30%) and presented predominantly with vascular and anoxic causes. Morbidity and mortality were also increased in the NCSE group. There was no difference in the antiepileptic drugs used or in the percentage of patients achieving an EEG with no paroxysmal activity between the subpopulations. Conclusion SE in elderly patients should be addressed distinctly. Current approaches based on the strategies used for standard CSE have shown little or no efficacy overall.

Wilson's Disease: First Report of Two Combined Mutational Variants in a Portuguese Patient.

Wilson's disease is a rare autosomal recessive condition. A defect on the copper carrier protein ATP7B prevents the excretion of copper, which then accumulates in several organs. The prognosis of Wilson's disease is favourable if the diagnosis is made early. The Leipzig criteria standardized phenotypic classification and diagnostic criteria, thus simplifying the diagnostic approach. A search for ATP7B mutations is not necessary for diagnostic purposes and studies of genotype-phenotype correlation have not produced any conclusive evidence so far. More information is needed to reliably assess the prognosis for each patient. Here we describe a young patient with a combination of two mutational variants: c.3402del and c.3061-12T>A. To our knowledge, this is the first report of this compound heterozygote genotype. LEARNING POINTS: Wilson's disease should be suspected in a young patient with subacute liver failure.The diagnostic approach to Wilson's disease can be difficult as there are a great variety of clinical scenarios.Further studies on matching genotypic variations with clinical phenotypes could improve the diagnosis and treatment of these patients.

Copper-induced Haemolytic Anaemia.

Acute copper toxicity is uncommon in Western countries and is often the result of accidental consumption or a suicide attempt. We report the case of a 65-year-old man presenting to the accident and emergency department after a suicide attempt with ingestion of Bordeaux mixture, ibuprofen, acetaminophen and bleach. Primary evaluation showed caustic oesophagitis, toxic hepatitis and acute renal injury, which were treated with supportive care. During admission, he developed a non-immune haemolytic anaemia associated with high levels of copper in urine and blood. Chelation treatment with penicillamine was started and evolution was favourable after 1 month of treatment. Copper poisoning can be lethal. Prompt diagnosis and treatment are key for a favourable prognosis. LEARNING POINTS: Acute copper intoxication is rare and early clinical suspicion and diagnosis are essential to reduce mortality.The diagnosis of copper poisoning should be based on clinical presentation and measurement of urine and blood copper levels in addition to serum ceruloplasmin levels.Treatment includes reduction of absorption, supportive measures, management of complications and chelation therapy.

Antibodies against HDL Components in Ischaemic Stroke and Coronary Artery Disease.

Quantitative and qualitative defects of high-density lipoprotein (HDL) are important in atherogenesis. In this study, we investigated whether antibodies against HDL components had additional value to conventional cardiovascular risk factors for the diagnosis of ischaemic stroke (IS) and coronary artery disease (CAD). Cross-sectional study was conducted on 53 patients with IS, 51 with CAD and 55 healthy controls, and in vitro studies to validate findings of the clinical study. We determined serum immunoglobulin G (IgG) antibodies against HDL (aHDL), apolipoproteins (aApoA-I, aApoA-II and aApoC-I) and paraoxonase-1 (aPON1) as well as PON1 activity (PON1a), total antioxidant capacity and biomarkers of endothelial activation (serum nitric oxide metabolites, 3-nitrotyrosine, VCAM-1 and ICAM-1); in vitro assays tested the capacity of IgG aHDL purified from high titer patients to inhibit PON1a and to reverse protective effect of HDL on endothelial cells. IgG aHDL, aApoA-I and aPON1 were higher in IS and CAD than controls (p < 0.001), predicted negatively PON1a and positively VCAM-1 and ICAM-1. By adding IgG aHDL and aApoA-I to a traditional cardiovascular risk factors model for IS and by adding IgG aHDL in a similar model for CAD, we obtained better discrimination of IS and CAD from healthy controls. IgG aHDL purified from IS and CAD inhibited PON1a by 38% (p < 0.01) and abrogated the protective effect of HDL on VCAM-1 expression by 126% compared with non-specific human IgG (p < 0.001). IgG against HDL components interfere with the antioxidant and anti-inflammatory properties of HDL and may represent novel biomarkers for vascular disease that need to be investigated in prospective studies.

A Rare Case of Bilateral Proptosis.

A 65-year-old man presented with a 2-year history of severe bilateral proptosis, palpable lymphadenopathy and moderate hepatosplenomegaly. A blood test was positive for hepatitis C infection. CT showed palpebral infiltrative lesions with regional progression through the temporal and masticatory spaces to the pharynx and hypopharynx causing almost complete airway obstruction. A palpebral biopsy was consistent with low-grade Bcl-2+ extra-nodal MALT non-Hodgkin B-cell lymphoma. The patient received six cycles of rituximab-based chemotherapy with clinical remission at 9-month follow-up. Bilateral proptosis is a rare presentation of several diseases. When brain CT excludes cavernous sinus pathology, thyroid ophthalmopathy or haematological malignancy should be considered. LEARNING POINTS: Bilateral proptosis is a rare presentation with a broad differential diagnosis, and is most frequently is caused by cavernous sinus disease, thyroid ophthalmopathy or haematological malignancy.Hepatitis C may be associated with MALT lymphoma and presents mainly at non-gastric locations even with few hepatic manifestations of the infection.Long-term low-grade lymphoma may present with severe disseminated disease at diagnosis, but treatment response is generally good.

Extended-release niacin increases anti-apolipoprotein A-I antibodies that block the antioxidant effect of high-density lipoprotein-cholesterol: the EXPLORE clinical trial.

AIMS: Extended-release niacin (ERN) is the most effective agent for increasing high-density lipoprotein-cholesterol (HDL-C). Having previously identified anti-HDL antibodies, we investigated whether ERN affected the antioxidant capacity of HDL and whether ERN was associated with the production of antibodies against HDL (aHDL) and apolipoprotein A-I (aApoA-I). METHODS: Twenty-one patients older than 18 years, with HDL-C ≤40 mg dl-1 (men) or ≤50 mg dl-1 (women) were randomly assigned to receive daily ERN (n = 10) or placebo (n = 11) for two sequential 12-week periods, with 4 weeks of wash-out before cross-over. Primary outcome was change of paraoxonase-1 (PON1) activity and secondary outcomes were changes in aHDL and aApoA-I antibodies. Clinical Trial Unique Identifier: EudraCT 2006-006889-42. RESULTS: The effect of ERN on PON1 activity was nonsignificant (coefficient estimate 20.83 U l-1 , 95% confidence interval [CI] -9.88 to 51.53; P = 0.184). ERN was associated with an increase in HDL-C levels (coefficient estimate 5.21 mg dl-1 , 95% CI 1.16 to 9.25; P = 0.012) and its subclasses HDL2 (coefficient estimate 2.46 mg dl-1 , 95% CI 0.57 to 4.34; P = 0.011) and HDL3 (coefficient estimate 2.73 mg dl-1 , 95% CI 0.47 to 4.98; P = 0.018). ERN was significantly associated with the production of aApoA-I antibodies (coefficient estimate 0.25 µg ml-1 , 95% CI 0.09-0.40; P = 0.001). aApoA-I titres at baseline were correlated with decreased PON activity. CONCLUSIONS: The rise in HDL-C achieved with ERN was not matched by improved antioxidant capacity, eventually hampered by the emergence of aApoA-I antibodies. These results may explain why Niacin and other lipid lowering agents fail to reduce cardiovascular risk.

Stress-related mucosal disease: incidence of bleeding and the role of omeprazole in its prophylaxis.

BACKGROUND: Upper gastrointestinal bleeding is the severe complication of stress-related mucosal disease in hospitalized patients. In intensive care units (ICU), risk factors are well defined and only mechanical ventilation and coagulopathy proved to be relevant for significant bleeding. On the contrary, in non-ICU settings there is no consensus about this issue. Nevertheless, omeprazole is still widely used in prophylaxis of bleeding. The objective of our study was to evaluate the relevance of stress-related mucosal disease bleeding in patients admitted to an internal medicine ward, and the role of omeprazole in its prophylaxis. METHODS: We conducted a retrospective study in which we analysed consecutive patients who were admitted to our ward over a year. We recorded demographic characteristics of the patients, potential risk factors for stress-related mucosal disease (clinical data, laboratory, and medication), administration of prophylactic omeprazole, and total cost of this prophylaxis. Patients with active gastrointestinal bleeding on the admission were excluded. We recorded every upper gastrointestinal bleeding event with clinical relevance. RESULTS: Five hundred and thirty-five patients, mean age 70 years, mean length of stay 9.6+/-7.7 days; 140 (26.2%) patients were treated with 40 mg of omeprazole intravenously, 193 (36.1%) with 20mg of omeprazole orally, and 202 (37.8%) patients had no prophylaxis. There was only one episode (0.2%) of clinically relevant bleeding. CONCLUSION: In patients admitted to an internal medicine ward, incidence of upper gastrointestinal bleeding as a complication of stress-related mucosal disease is low. We found that there is no advantage in prophylaxis with omeprazole.

Persistency of low levels of anticardiolipin and anti-beta2 glycoprotein1 in thrombosis.

BACKGROUND: Antiphospholipid antibodies, the hallmark of the antiphospholipid syndrome, are associated with both venous and arterial thrombosis. Despite some reports stating that this association may be present in patients with low titres of anticardiolipin antibodies, a clear association has only been established in the presence of a moderate to high concentrations (above 40 GPL or MPL). METHODS: In order to study whether low antibody titres could be associated with thrombosis, we reviewed the files of 196 patients, 94 with and 102 without thrombotic events, for a period of 4.4 and 5.1 years respectively. Files from patients with persistent low titres of antiphospholipid antibodies recorded in the unit database were selected, independently of the associated clinical history or diagnosis. Epidemiology, clinical and treatment information were collected and the serum variability of the antibody titres was analysed in relation to the presence of thrombotic events. RESULTS: Thrombotic events were classified as venous 81.9% and arterial 18.1%. 23/94 (24.5%) patients with thrombosis had miscarriages. There were no significant differences between serum concentrations of antiphospholipid antibodies in the thrombotic and non-thrombotic groups. However, there was a higher consistency of the antibody concentrations in patients with thrombosis, as seen by the significantly lower variability of IgG aCL and abeta2GP1 titres in patients with thrombosis when compared to non-thrombotic controls (p=0.0025 and p<0.0001, respectively). CONCLUSION: Consistency of low titres of antiphospholipid antibody levels may be associated with a higher risk of thrombotic events overall.

B-cell-depletion therapy in SLE--what are the current prospects for its acceptance?

Analogous to the successful introduction of biologic agents to treat rheumatoid arthritis, it was widely envisaged that similar successful studies would follow in systemic lupus erythematosus (SLE), as much was known about the etiopathogenesis of the disease and appropriate agents to block the key cells and molecules were available. The reality, however, has been different. The failure of rituximab, a monoclonal antibody that induces B-cell depletion, to meet its primary and secondary end points in trials of nonrenal SLE (EXPLORER) and renal (LUNAR) lupus nephritis has been disappointing given the success reported in many open-label studies. Concluding that B-cell-depletion therapy is not effective in SLE seems rather extreme. Further analysis of the as-yet unpublished results and their comparison with data from published studies might provide insight into whether B-cell depletion will eventually be accepted as a useful approach for the treatment of SLE.