Acute varicella-zoster virus necrotizing meningoencephalomyelitis with sudden visual loss and paraparesis in an HIV-infected patient

We describe a case of acute varicella-zoster virus (VZV) hemorrhagic meningoencephalomyelitis in an HIV-infected patient. On admission the patient's CSF was mild haemorrhagic and xanthochromic after centrifugation and he had thoracic skin blisters. VZV DNA was isolated from both the thoracic blisters and CSF. Treatment consisted of aggressive antiviral, steroid and immunoglobulin therapy, which was able to stop disease progression. The patient survived but was left blind and paretic. In conclusion, a diagnosis of CNS infection caused by VZV, based upon CSF analysis and examination of the skin for typical blisters, requires aggressive empiric antiviral therapy in order to maximise patient survival

Acute varicella-zoster virus necrotizing meningoencephalomyelitis with sudden visual loss and paraparesis in an HIV-infected patient

We describe a case of acute varicella-zoster virus (VZV) hemorrhagic meningoencephalomyelitis in an HIV-infected patient. On admission the patient's CSF was mild haemorrhagic and xanthochromic after centrifugation and he had thoracic skin blisters. VZV DNA was isolated from both the thoracic blisters and CSF. Treatment consisted of aggressive antiviral, steroid and immunoglobulin therapy, which was able to stop disease progression. The patient survived but was left blind and paretic. In conclusion, a diagnosis of CNS infection caused by VZV, based upon CSF analysis and examination of the skin for typical blisters, requires aggressive empiric antiviral therapy in order to maximise patient survival

Effects on the incidence of cardiovascular events of the addition of pioglitazone versus sulfonylureas in patients with type 2 diabetes inadequately controlled with metformin (TOSCA.IT): a randomised, multicentre trial

Background The best treatment option for patients with type 2 diabetes in whom treatment with metformin alone fails to achieve adequate glycaemic control is debated. We aimed to compare the long-term effects of pioglitazone versus sulfonylureas, given in addition to metformin, on cardiovascular events in patients with type 2 diabetes. Methods TOSCA.IT was a multicentre, randomised, pragmatic clinical trial, in which patients aged 50\ue2\u80\u9375 years with type 2 diabetes inadequately controlled with metformin monotherapy (2\ue2\u80\u933 g per day) were recruited from 57 diabetes clinics in Italy. Patients were randomly assigned (1:1), by permuted blocks randomisation (block size 10), stratified by site and previous cardiovascular events, to add-on pioglitazone (15\ue2\u80\u9345 mg) or a sulfonylurea (5\ue2\u80\u9315 mg glibenclamide, 2\ue2\u80\u936 mg glimepiride, or 30\ue2\u80\u93120 mg gliclazide, in accordance with local practice). The trial was unblinded, but event adjudicators were unaware of treatment assignment. The primary outcome, assessed with a Cox proportional-hazards model, was a composite of first occurrence of all-cause death, non-fatal myocardial infarction, non-fatal stroke, or urgent coronary revascularisation, assessed in the modified intention-to-treat population (all randomly assigned participants with baseline data available and without any protocol violations in relation to inclusion or exclusion criteria). This study is registered with ClinicalTrials.gov, number NCT00700856. Findings Between Sept 18, 2008, and Jan 15, 2014, 3028 patients were randomly assigned and included in the analyses. 1535 were assigned to pioglitazone and 1493 to sulfonylureas (glibenclamide 24 [2%], glimepiride 723 [48%], gliclazide 745 [50%]). At baseline, 335 (11%) participants had a previous cardiovascular event. The study was stopped early on the basis of a futility analysis after a median follow-up of 57\uc2\ub73 months. The primary outcome occurred in 105 patients (1\uc2\ub75 per 100 person-years) who were given pioglitazone and 108 (1\uc2\ub75 per 100 person-years) who were given sulfonylureas (hazard ratio 0\uc2\ub796, 95% CI 0\uc2\ub774\ue2\u80\u931\uc2\ub726, p=0\uc2\ub779). Fewer patients had hypoglycaemias in the pioglitazone group than in the sulfonylureas group (148 [10%] vs 508 [34%], p<0\uc2\ub70001). Moderate weight gain (less than 2 kg, on average) occurred in both groups. Rates of heart failure, bladder cancer, and fractures were not significantly different between treatment groups. Interpretation In this long-term, pragmatic trial, incidence of cardiovascular events was similar with sulfonylureas (mostly glimepiride and gliclazide) and pioglitazone as add-on treatments to metformin. Both of these widely available and affordable treatments are suitable options with respect to efficacy and adverse events, although pioglitazone was associated with fewer hypoglycaemia events. Funding Italian Medicines Agency, Diabete Ricerca, and Italian Diabetes Society