Autoimmune cerebellar hypermetabolism: Report of three cases and literature overview.

We report three cases of vermian cerebellar hypermetabolism in patients with autoimmune encephalitis. One of our patients was positive for anti-Ma2 antibodies and one for anti-Zic4 antibodies while the remaining patient did not present any known antibodies. The seronegative patient deteriorated after immune checkpoint inhibitor treatment for a pulmonary adenocarcinoma and improved with immunosuppressive drugs, which is in favour of an underlying autoimmune mechanism. They all presented with subacute neurological symptoms. Brain magnetic resonance imaging was normal except in one patient, where hyperintensities were present on FLAIR sequence around the third ventricle and the cerebral aqueduct. 18F-FDG brain positron emission tomography with computed tomography (18F-FDG PET-CT) demonstrated an unusual vermian cerebellar hypermetabolism in the three cases. While cerebellar hypermetabolism on 18F-FDG PET-CT has been described in various neurological diseases, such vermian - and more broadly cerebellar - hypermetabolism was seldom described in previous studies on autoimmune encephalitis. When differential diagnoses have been ruled out, this pattern may be of interest for the positive diagnosis of autoimmune encephalitis in difficult diagnostic cases.

Frequency and predictors of confirmed hypoglycaemia in type 1 and insulin-treated type 2 diabetes mellitus patients in a real-life setting: results from the DIALOG study.

AIM: DIALOG assessed the prevalence and predictors of hypoglycaemia in patients with type 1 (T1DM) or insulin-treated type 2 diabetes mellitus (T2DM) in a real-life setting. METHODS: In this observational study, insulin-treated patients (n=3048) completed prospective daily questionnaires reporting the frequency and consequences of severe/confirmed non-severe hypoglycaemia over 30 days. Patients (n=3743) also retrospectively reported severe hypoglycaemia over the preceding year. RESULTS: In this prospective survey, 85.3% and 43.6% of patients with T1DM and T2DM, respectively, reported experiencing at least one confirmed hypoglycaemic event over 30 days, while 13.4% and 6.4%, respectively, reported at least one severe event. Hypoglycaemia frequency increased with longer duration of diabetes and insulin therapy. Strongly predictive factors for hypoglycaemia were previous hypoglycaemia, >2 injections/day, BMI<30kg/m(2) and duration of insulin therapy>10 years. HbA1c level was not predictive of hypoglycaemia in either T1DM or T2DM. The confirmed hypoglycaemia rate was increased in the lowest compared with the highest tertile of HbA1c in T1DM, but not T2DM. At the time of enrolment, physicians reported severe hypoglycaemia in 23.6% and 11.9% of T1DM and T2DM patients, respectively, during the preceding year; the retrospective survey yielded frequencies of 31.5% and 21.7%, respectively. Also, severe hypoglycaemia led to medical complications in 10.7% and 7.8% of events in T1DM and T2DM patients, respectively, over 30 days. CONCLUSION: Using a unique combined prospective and retrospective approach, the DIALOG study found a relatively high frequency of hypoglycaemia among insulin-treated patients. These findings emphasize the importance of a patient-centred approach for managing diabetes in which hypoglycaemia risk evaluation is critical. TRIAL REGISTRATION: ClinicalTrials.gov: NCT01628341.

(18)F-FDG PET/CT in tuberculosis: an early non-invasive marker of therapeutic response.

OBJECTIVE: To evaluate the potential of (18)F-fluoro-deoxyglucose positron emission tomography/computed tomography ((18)F-FDG PET/CT) for early therapeutic intervention in patients with probable or confirmed tuberculosis (TB). METHODS: Twenty-one consecutive human immunodeficiency virus negative patients were prospectively included. All patients underwent (18)F-FDG PET/CT before and after 1 month of anti-tuberculosis treatment. The maximum standardised uptake value (SUV(max)) of the most (18)F-FDG avid lesions was recorded. RESULTS: The median age of patients was 36 years (range 18-84); 33.3% were male, 80.9% were born in endemic countries, and 23.8% had a past history of TB. TB was confirmed on culture in 8, on histology in 9 and on the basis of clinical symptoms in 4 patients. (18)F-FDG PET/CT detected active pulmonary TB (n = 1), extra-pulmonary (n = 10) or both (n = 10). The second (18)F-FDG PET/CT showed reduced radiotracer uptake intensity in 19 of 21 patients, with a median percentage decrease of SUV(max) of 31% (range 2-84). Two patients showed no improvement. TB was ruled out in one patient during follow-up; the final diagnosis was a non-Hodgkin's lymphoma. The other patient was smear-positive for 3 months. CONCLUSION: (18)F-FDG PET/CT allows an easy evaluation of early therapeutic response in patients with TB, particularly extra-pulmonary TB.

[Flecainide acetate utilisation review among general practitioners and hospital or office-based cardiologists in France. Obepine: observational study of flecainide]. / Etude de l'usage de l'acétate de flécainide auprès des médecins généralistes et des cardiologues hospitaliers ou libéraux en France. OBEPINE: etude observationnelle des prescriptions de flécaïnide.

A pharmacoepidemiological cross-sectional observational study was performed among a representative sample of French general practitioners and cardiologists. The aim of this study was to describe the prescription modalities of flecainide acetate, an Ic class antiarrhythmic, and how these modalities match the marketing authorization and the current summary of product characteristics. A total of 941 physicians participated in the study, 496 GPs and 445 cardiologists, and 1116 patients treated with flecainide for more than one month were included. On average, the patients were 68.7-years-old and 54% of them were women. Most of the initial flecainide prescriptions came from cardiologists (96%) and the check-up included an electrocardiogram (98%), a Holter monitoring (56%) and/or an echocardiography (71%). The preferred indication was supraventricular rhythm disorders (95%) and mostly atrial fibrillation (63%). A small proportion of coronary patients (7%) and of patient suffering from cardiac insufficiency (4%) was found. Flecainide was prescribed with a median posology of 150 mg per day, mostly as LP form (64%). Overall, the indications specified in the summary of product characteristics were respected in 90% of the cases, the contraindications in 91% of the cases and the patient follow-up was appropriate in 99% of the cases. In conclusion, the study showed that the prescription's conditions of flecainide in France complied with the summary of product characteristics data for most of the prescribing physicians with a respect of the indications, contraindications and management recommendations in 84% of the cases.

Cross-sectional study of care, socio-economic status and complications in young French patients with type 1 diabetes mellitus.

OBJECTIVES: To describe the present status of type 1 diabetes care in France and study the relations between clinical and socio-economic variables on one hand and disease management and prevalence of complications on the other hand. METHODS: A random sample of 365 French specialists in diabetes care performed a cross-sectional study and included consecutively 562 children aged 10-16 and 1691 adults aged 16-45, with more than 2 years of type 1 diabetes. The main outcome measures were the prevalence of complications (retinal, renal, lower-limb, cardiovascular, ketoacidosis); disease management parameters (blood pressure, HbA1c, daily number of insulin injections, frequency of visits to a specialist in diabetes, membership of a patient association); socio-economic status as a score, and treatments received. RESULTS: Retinal complications were rare in children (0.7%) and common in adults (28.3%). 10.2% children and 15.2% adults had micro- or macro-albuminuria, 4.7% adults had plasma creatinine >or=150 micromol/L. Only 15% children and 26% adults had HbA1c<7%, 86.2% children and 62.7% adults had blood pressure<130/85 mmHg; 58% children and 80% adults had at least 3 daily insulin injections. In adults, the risk of experiencing at least one complication was linked significantly with diabetes duration, HbA1c, and socio-economic status. Age, sex, type of insulin therapy, tobacco consumption, and blood pressure control were not significant parameters. Ketoacidosis in the preceding year was only linked with HbA1C and socio-economic status. CONCLUSION: Although this sample of patients had overall a fair socio-economic status and were followed-up by specialists of diabetes care, metabolic and blood pressure control were not optimal. The care of French type 1 diabetics could probably be improved by a stricter control of glycaemia and blood pressure, and an earlier use of intensive insulin treatment, with a particular focus on adolescents and patients with the lowest socio-economic status.

Preconditioning during coronary angioplasty: no influence of collateral perfusion or the size of the area at risk.

AIMS: It is unclear whether the protection observed in human heart following repetition of brief episodes of ischaemia is due to opening of coronary collaterals or to ischaemic preconditioning. We investigated whether the improvement in ST segment change following repeated episodes of brief ischaemia during coronary angioplasty is due to preconditioning when the size of the area at risk and the collateral flow are taken into account. METHODS AND RESULTS: Thirty-six patients underwent percutaneous transluminal coronary angioplasty. Intracoronary ST segment changes were measured throughout the procedure and used as an endpoint. The size of the area at risk and the collateral perfusion within the ischaemic bed were measured using single photon emission computerized tomography (SPECT). Mean ST segment shift observed in all patients significantly decreased from 11.0+/-2.6 mm during the first balloon inflation to 8.5+/-2.3 mm during the second inflation. This protective effect occurred in the absence of any change in the size of the area at risk (mean: 46+/-5% of LV) and of the collateral perfusion to the ischaemic zone (mean: 23+/-4% of flow in the non-ischaemic zone). CONCLUSION: These results suggest that ischaemic preconditioning does occur during repeated brief coronary artery occlusion in the human heart.

Experimental assessment of new stent technologies: validation of a comparative paired rabbit iliac artery study model.

Preventing coronary in-stent restenosis is a major challenge for physicians and industry. To assess new stent technologies, a comparative paired iliac artery model in rabbits is proposed. One tubular stent was implanted in each external iliac artery in 12 rabbits (i.e., 24 stents). An artery overdilatation level of 20% was strictly observed. Restenosis was examined at 30 days by angiography, intravascular ultrasound (IVUS) examination, and histomorphometry. On quantitative angiography, the mean loss of angiographic diameter was 9.8 +/- 4.4% in the right as compared to 9.3 +/- 55% in the left artery (p = 0.75). On IVUS, the volume of intrastent neointimal proliferation was 26.6 +/- 4.9 mm(3) in the right and 25.8 +/- 3.5 mm(3) in the left artery (p = 0.58). In histomorphometry, the neointimal proliferation area was 0.78 +/- 17 mm(2) in the right and 0.76 +/- 0.17 mm(2) in the left artery (p = 0.87). Intrastent neointimal proliferation was comparable between the left and right arteries of all rabbits. The model has three main advantages: (1) arterial dilatation and thus arterial wall aggression are controlled, (2) pairing makes each animal its own control subject, and (3) the statistical power for comparative testing is maximized. The model enables the effect of a new drug-delivery device to be assessed.

Use of IgG Avidity test in case definitions of toxoplasmosis in pregnancy.

A survey network for congenital toxoplasmosis (TOXO-NET) was set up in December 1996 in Piedmont (Italy). Participants were asked to classify the infections in pregnant mothers and newborns by the criteria of the European Network on Congenital Toxoplasmosis published by Lebech in 1996. Because the IgG Avidity test is largely employed as a 2nd level test in toxoplasmosis diagnosis and it could be helpful to date infection, the co-ordinators of TOXO-NET suggested including it in the "case definition" of "probable" infection and "unlikely" infection. 117 cases of toxoplasmosis in pregnancy divided into the risk categories under Lebech's criteria were re-examined using the "new" case definitions. 77 out of 117 (65.8%) Toxoplasma gondii infections during pregnancy could be defined with only one serum sample using the IgG Avidity test. The IgG Avidity test proved a useful method to classify the Toxoplasma gondii infections in pregnancy, especially when we had only one serum sample.

Angiotensin-I-converting enzyme insertion/deletion polymorphism and high urinary albumin concentration in French Type 2 diabetes patients.

AIMS: Family-based studies suggest a genetic basis for nephropathy in Type 2 diabetes. The angiotensin-I-converting enzyme (ACE) gene is a candidate gene for Type 1 diabetes nephropathy. We assessed the association between high urinary albumin concentration and ACE insertion/deletion (I/D) polymorphism, in French Type 2 diabetes patients. METHODS: We studied 3139 micro/macroalbuminuric French patients recruited in the DIABHYCAR Study, an ACE inhibition trial in Type 2 diabetes patients with renal and cardiovascular outcomes. The main inclusion criteria were age >/= 50 years, urinary albumin concentration >/= 20 mg/l assessed centrally during two consecutive screening visits, and plasma creatinine concentration

[Cost analysis of toxoplasma infection control in pregnancy]. / Analisi dei costi relativi al controllo dell'infezione toxoplasmica in corso di gravidanza.

In Italy, the management of Toxoplasma infection screening in pregnant women is often unproductive and inefficient and generates a wide variability of costs. This study evaluated performance parameters in the screening management of a population of pregnant women, estimated its costs and compared them with the costs of a full application of Ministerial Documents of 1995 and 1998. We controlled until delivery 830 pregnant women who had done the first blood test between September 1st and December 31st 1997. The costs of direct and indirect testing were analysed using the Excel database and statistical software package. Of the 573 pregnant women defined 'susceptible' at the first test, only 240 (42%) did further blood tests during the II and III trimesters, 30% did no more tests and the remaining women adopted a heterogeneous behaviour. The mean cost of each screening was found to be euro 54.47/pregnancy and euro 60.05/pregnancy with a full application of the Ministerial Document of 1995. A full application of Ministerial Document of 1998, instead, would have involved a cost of euro 94.28/pregnancy for 5 tests, euro 111.40/pregnancy for 6 tests and euro 128.51 for 7 tests. The study shows that the management of toxoplasmosis screening during pregnancy needs greater attention to the prescription of tests, so that useless testing can be reduced and the efficacy of the screening improved, two important goals the Ministerial Documents were designed to achieve.

[Type 2 diabetes and cardiovascular risk: lessons from therapeutic trials]. / Diabète de type 2 et risque cardiovasculaire: enseignements des essais thérapeutiques.

Cardiovascular risk reduction in diabetic patients is a multidimensional task. Long-term decrease of glycaemia by the use of insulin or sulfonylureas had disappointing effects on cardiovascular events, whereas metformin effects are ambiguous. On the contrary, controlling risk factors like hypertension or hypercholesterolaemia decrease the incidence of cardiovascular events in diabetic as in non-diabetic patients. Similarly, clinical trials have shown the efficacy of treatments that decrease cardiovascular risk whatever the cause, such as antiplatelet drugs in secondary prevention and high-dose ramipril in secondary prevention or in hypertensive patients. The absolute benefit conferred by efficient therapies is higher in diabetic patients because they are at an increased risk of events compared with their non-diabetic counterparts.

Oral Beraprost sodium, a prostaglandin I(2) analogue, for intermittent claudication: a double-blind, randomized, multicenter controlled trial. Beraprost et Claudication Intermittente (BERCI) Research Group.

BACKGROUND: Beraprost sodium (BPS) is a new stable, orally active prostaglandin I(2) analogue with antiplatelet and vasodilating properties. We report the results of a phase III clinical trial of BPS in patients with intermittent claudication. METHODS AND RESULTS: Patients (n=549) with a pain-free walking distance of between 50 and 300 m were entered into a 4-week single-blind placebo run-in phase. Patients whose pain-free walking distance had changed by <25% were then randomized to receive either BPS (40 microg TID, n=209) or placebo (n=213) in a double-blind manner for 6 months. Pain-free and maximum walking distances were measured on the occasion of treadmill exercise tests performed at baseline and 1.5, 3, 4.5, and 6 months after randomization. Success was defined as an improvement of >50% in pain-free walking distance at month 6 and in > or =1 earlier treadmill exercise test in the absence of critical cardiovascular events. Success was observed more frequently in the BPS group (43.5%) than in the placebo group (33.3%, P=0.036). Pain-free walking distances increased by 81.5% and 52.5%, respectively, in the BPS and placebo groups (P=0.001) and maximum walking distances by 60.1% and 35.0%, respectively (P=0.004). The incidence of critical cardiovascular events was 4.8% in the BPS group and 8.9% in the placebo group. CONCLUSIONS: These results show that BPS is an effective symptomatic treatment of patients with intermittent claudication. The beneficial effects of BPS on critical cardiovascular events should be confirmed in appropriate clinical trials.

The non-insulin-dependent diabetes, hypertension, microalbuminuria or proteinuria, cardiovascular events, and ramipril (DIABHYCAR) study: design, organization, and patient recruitment. DIABHYCAR Study Group.

The non-insulin-dependent DIABetes, HYpertension, microalbuminuria or proteinuria, CARdiovascular events, and Ramipril (DIABHYCAR) study is a randomized, prospective, double-blind, placebo-controlled, multicenter international trial of the ACE inhibitor ramipril (1.25 mg/day) in patients with type II diabetes and micro- or macroalbuminuria. The main outcome of the study is the time to first occurrence of either death from a cardiovascular origin, including sudden death, nonfatal myocardial infarction, stroke, or congestive heart failure, or requirement of hemodialysis or renal transplantation. The study was launched in France in early 1995 with the participation of general practitioners only, but had to be extended to 15 other countries in 1997 due to difficulties in recruitment. Since 2.5 years after the beginning of the trial the observed event rate was much less than anticipated, it was decided to increase recruitment and follow-up duration and to include congestive heart failure in the definition of the main outcome to keep the study power at a satisfactory level. Recruitment ended on April 1, 1998 with 4937 randomized patients. Following the early discontinuation for efficacy of another study of ramipril in high cardiovascular risk patients, the Heart Outcomes Prevention Evaluation study (HOPE), the second interim analysis of DIABHYCAR was performed early (when 406 instead of 500 patients presented a main outcome) and the Data Safety and Monitoring Board recommended that the study continue. Follow-up is planned to end on March 31, 2001.

Determinants of elevated urinary albumin in the 4,937 type 2 diabetic subjects recruited for the DIABHYCAR Study in Western Europe and North Africa.

OBJECTIVE: Whether ACE inhibition is useful for type 2 diabetic patients with micro- and macroalbuminuria remains unknown. The Non-Insulin-Dependent Diabetes, Hypertension, Microalbuminuria, Cardiovascular Events and Ramipril (DIABHYCAR) Study was set up to address this issue through a multicenter double-blind parallel placebo-controlled > or = 3-year trial in Europe and North Africa. In this article, we report the characteristics of the randomized patients. RESEARCH DESIGN AND METHODS: The main selection criteria were as follows: men or women aged > or = 50 years with type 2 diabetes treated with oral antidiabetic drugs, with or without hypertension, with a plasma creatinine level < 150 mumol/l, and with persistent micro- or macroalbuminuria, as assessed centrally by two successive urine samples containing a urinary albumin concentration > or = 20 mg/l. Patient characteristics were studied by comparing patients who were randomized to those who were not, taking their geographical origin into account. RESULTS: There were 25,455 patients screened for urinary albumin (20,296 from France, 918 from Germany, 1,019 from Northwest Europe, 969 from Central Europe, 959 from Mediterranean Europe, and 1,294 from North Africa). Of these patients, 4,937 were randomized. Compared with the nonrandomized patients, the randomized patients were older, more often men, more obese, had higher systolic/diastolic blood pressure and plasma glucose, smoked more tobacco, drank more alcohol, and had complications more frequently. Using a logistic regression analysis, all the above-mentioned items appeared as independent determinants for randomization into the study, with the exception of alcohol intake. The contribution of each item varied slightly from one geographical origin to another. CONCLUSIONS: The physical, biological, and behavioral characteristics create a poor renal and cardiovascular prognosis for the type 2 diabetic patients randomized to the DIABHYCAR Study because of micro- and macroalbuminuria. Testing the usefulness of ACE inhibition for the type 2 diabetic patients with microalbuminuria seems feasible through the DIABHYCAR Study.

Efficacy of diuretics and beta-blockers in diabetic hypertensive patients. Results from a meta-analysis. The INDANA Steering Committee.

OBJECTIVE: To review the effectiveness of diuretic or beta-blocker-based treatment of hypertension in diabetic patients. RESEARCH DESIGN AND METHODS: A meta-analysis on individual patient data was performed on four trials of the treatment of hypertension in which diabetic patients were included and treated with first-line diuretics or beta-blockers. The main outcomes were the relative risk of death, fatal or nonfatal stroke, fatal or nonfatal coronary events, and major cardiovascular events. RESULTS: There were 92 diabetic patients who received first-line beta-blockers and 1,008 who received diuretics. In the control groups, diabetic patients had nearly twice the risk of any outcome when compared with nondiabetic patients. The same blood pressure reduction was achieved under treatment in the diabetic and nondiabetic patients, except for systolic pressure, which decreased more in the nondiabetic patients at 1 year. In the 15,843 nondiabetic patients, the risk of all four outcomes was reduced significantly in the treated group. In the 2,254 diabetic patients, the risk reduction was significant only for fatal and nonfatal stroke (36%, P = 0.011) and major cardiovascular events (20%, P = 0.032), but not for death (5%, P = 0.65) and fatal or nonfatal coronary events (15%, P = 0.23). However, no heterogeneity was detected between diabetic patients and nondiabetic patients for any outcome. The numbers of outcomes avoided for 1,000 patients treated for 5 years were higher in diabetic patients (e.g., 38 major cardiovascular events) than with nondiabetic patients (e.g., 28 major cardiovascular events). CONCLUSIONS: These results show that hypertensive diabetic patients benefit from first-line treatment with diuretics. No conclusion can be drawn for beta-blockers, owing to the small sample size.

[Clinical benefits of cholesterol lowering treatments. Meta-analysis of randomized therapeutic trials]. / Bénéfices cliniques des traitements hypocholestérolémiants. Méta-analyse des essais thérapeutiques randomisés.

PRIMARY PREVENTION: A meta-analysis of the 7 available randomized cholesterol lowering trials (2 on statins, 2 on fibrates, 2 on resins and 1 on diet) demonstrates a significant 24% relative reduction in the frequency of fatal and non-fatal coronary events, leading to a significant 14% relative reduction in coronary disease related mortality. For total mortality, the statin trials were not comparable with other treatments where there was a trend to overmortality. With the 2 statin trials, there was a nonsignificant 13% reduction in total mortality. SECONDARY PREVENTION: A meta-analysis of the 13 available randomized trials (3 with clofribrate, 1 with gemfibrozil, 2 with nicotinic acid, and 4 with diet) showed a significant 21% reduction in the frequency of fatal and non-fatal coronary events, coronary mortality and total mortality. For total mortality, only the result of the 2 statin trials was significant (-20%). BENEFICIAL EFFECT OF STATINS, ABSOLUTE VALUES: Measured as the number of patients to treat for 5 years in order to avoid 1 event (NNT), there is a clinically pertinent benefit of secondary prevention (NNT = 15 for events, NNT = 30 for coronary mortality). The absolute value is weaker when patients with minimally elevated cholesterol levels are included. For primary prevention, the absolute value is low with NNT = 44 for events and NNT = 300 for coronary mortality. In addition, as these results were obtained in trials including populations with a much higher risk than the general French population, the absolute beneficial effect may not be pertinent in France except in high-risk patients who present, in addition to a high cholesterol level, other cardiovascular risk factors.