Electrode location and clinical outcome in hippocampal electrical stimulation for mesial temporal lobe epilepsy.

PURPOSE: To study the clinical outcome in hippocampal deep brain stimulation (DBS) for the treatment of patients with refractory mesial temporal lobe epilepsy (MTLE) according to the electrode location. METHODS: Eight MTLE patients implanted in the hippocampus and stimulated with high-frequency DBS were included in this study. Five underwent invasive recordings with depth electrodes to localize ictal onset zone prior to chronic DBS. Position of the active contacts of the electrode was calculated on postoperative imaging. The distances to the ictal onset zone were measured as well as atlas-based hippocampus structures impacted by stimulation were identified. Both were correlated with seizure frequency reduction. RESULTS: The distances between active electrode location and estimated ictal onset zone were 11±4.3 or 9.1±2.3mm for patients with a >50% or <50% reduction in seizure frequency. In patients (N=6) showing a >50% seizure frequency reduction, 100% had the active contacts located <3mm from the subiculum (p<0.05). The 2 non-responders patients were stimulated on contacts located >3mm to the subiculum. CONCLUSION: Decrease of epileptogenic activity induced by hippocampal DBS in refractory MTLE: (1) seems not directly associated with the vicinity of active electrode to the ictal focus determined by invasive recordings; (2) might be obtained through the neuromodulation of the subiculum.

Are initial radiographic and clinical scales associated with subsequent intracranial pressure and brain oxygen levels after severe traumatic brain injury?

BACKGROUND: Prediction of clinical course and outcome after severe traumatic brain injury (TBI) is important. OBJECTIVE: To examine whether clinical scales (Glasgow Coma Scale [GCS], Injury Severity Score [ISS], and Acute Physiology and Chronic Health Evaluation II [APACHE II]) or radiographic scales based on admission computed tomography (Marshall and Rotterdam) were associated with intensive care unit (ICU) physiology (intracranial pressure [ICP], brain tissue oxygen tension [PbtO2]), and clinical outcome after severe TBI. METHODS: One hundred one patients (median age, 41.0 years; interquartile range [26-55]) with severe TBI who had ICP and PbtO2 monitoring were identified. The relationship between admission GCS, ISS, APACHE II, Marshall and Rotterdam scores and ICP, PbtO2, and outcome was examined by using mixed-effects models and logistic regression. RESULTS: Median (25%-75% interquartile range) admission GCS and APACHE II without GCS scores were 3.0 (3-7) and 11.0 (8-13), respectively. Marshall and Rotterdam scores were 3.0 (3-5) and 4.0 (4-5). Mean ICP and PbtO2 during the patients' ICU course were 15.5 ± 10.7 mm Hg and 29.9 ± 10.8 mm Hg, respectively. Three-month mortality was 37.6%. Admission GCS was not associated with mortality. APACHE II (P = .003), APACHE-non-GCS (P = .004), Marshall (P < .001), and Rotterdam scores (P < .001) were associated with mortality. No relationship between GCS, ISS, Marshall, or Rotterdam scores and subsequent ICP or PbtO2 was observed. The APACHE II score was inversely associated with median PbtO2 (P = .03) and minimum PbtO2 (P = .008) and had a stronger correlation with amount of time of reduced PbtO2. CONCLUSION: Following severe TBI, factors associated with outcome may not always predict a patient's ICU course and, in particular, intracranial physiology.

Hypervitaminémie B12: implications cliniques et prise en charge [Therapeutic and clinical implications of elevated levels of vitamin B12].

In general practice, vitamin B12 levels are measured when searching an origin for an anemic status (usually megaloblastic anemia), for various neurological disorders (usually polyneuropathy) or for neurocognitive disorders. Although the pathologies associated with vitamin B12 deficiency are well known, hypervitaminemic B12 status is often fortuitous and frequent finding. The aim of this article is to present the disease entities associated with hypervitaminemia B12, the clinical implications of this dysvitaminosis and a practical approach when this laboratory abnormality is found.

Analysis and clinical relevance of microparticles from red blood cells.

PURPOSE OF REVIEW: The mechanisms involved in the formation of red blood cell (RBC) microparticles in vivo as well as during erythrocyte storage are reviewed, and the potential role of microparticles in transfusion medicine is described. RECENT FINDINGS: Microparticles release is an integral part of the erythrocyte ageing process, preventing early removal of RBCs. Proteomics analyses have outlined the key role of band 3-ankyrin anchoring complex and the occurrence of selective RBC membrane remodelling mechanisms in microparticles formation. The presence of several RBC antigens, expressed on microparticles, has been demonstrated. The potential deleterious effects of RBC microparticles in transfused recipients, including hypercoagulability, microcirculation impairment and immunosuppression, are discussed. SUMMARY: Formation and role of RBC microparticles are far from being completely understood. Combining various approaches to elucidate these mechanisms could improve blood product quality and transfusion safety. Implementation of RBC microparticles as biomarkers in the laboratory routine needs to overcome technical barriers involved in their analysis.

Population pharmacokinetics and clinical response for artemether-lumefantrine in pregnant and nonpregnant women with uncomplicated Plasmodium falciparum malaria in Tanzania.

Artemether-lumefantrine (AL) is the first-line treatment for uncomplicated malaria in the second and third trimesters of pregnancy. Its efficacy during pregnancy has recently been challenged due to altered pharmacokinetic (PK) properties in this vulnerable group. The aim of this study was to determine the PK profile of AL in pregnant and nonpregnant women and assess their therapeutic outcome. Thirty-three pregnant women and 22 nonpregnant women with malaria were treated with AL (80/480 mg) twice daily for 3 days. All patients provided five venous plasma samples for drug quantification at random times over 7 days. Inter- and intraindividual variability was assessed, and the effects of covariates were quantified using a nonlinear mixed-effects modeling approach (NONMEM). A one-compartment model with first-order absorption and elimination with linear metabolism from drug to metabolite fitted the data best for both arthemether (AM) and lumefantrine (LF) and their metabolites. Pregnancy status and diarrhea showed a significant influence on LF PK. The relative bioavailability of lumefantrine and its metabolism rate into desmethyl-lumefantrine were, respectively, 34% lower and 78% higher in pregnant women than in nonpregnant patients. The overall PCR-uncorrected treatment failure rates were 18% in pregnant women and 5% in nonpregnant women (odds ratio [OR] = 4.04; P value of 0.22). A high median day 7 lumefantrine concentration was significantly associated with adequate clinical and parasitological response (P = 0.03). The observed reduction in the relative bioavailability of lumefantrine in pregnant women may explain the higher treatment failure in this group, mostly due to lower posttreatment prophylaxis. Hence, a modified treatment regimen of malaria in pregnancy should be considered.

Initial assessment of safety and clinical feasibility of irreversible electroporation in the focal treatment of prostate cancer.

BACKGROUND: To evaluate the safety and clinical feasibility of focal irreversible electroporation (IRE) of the prostate. METHODS: We assessed the toxicity profile and functional outcomes of consecutive patients undergoing focal IRE for localised prostate cancer in two centres. Eligibility was assessed by multi-parametric magnetic resonance imaging (mpMRI) and targeted and/or template biopsy. IRE was delivered under transrectal ultrasound guidance with two to six electrodes positioned transperineally within the cancer lesion. Complications were recorded and scored accordingly to the NCI Common Terminology Criteria for Adverse Events; the functional outcome was physician reported in all patients with at least 6 months follow-up. A contrast-enhanced MRI 1 week after the procedure was carried out to assess treatment effect with a further mpMRI at 6 months to rule out evidence of residual visible cancer. RESULTS: Overall, 34 patients with a mean age of 65 years (s.d.=±6) and a median PSA of 6.1 ng ml(-1) (interquartile range (IQR)= 4.3-7.7) were included. Nine (26%), 24 (71%) and 1 (3%) men had low, intermediate and high risk disease, respectively (D'Amico criteria). After a median follow-up of 6 months (range 1-24), 12 grade 1 and 10 grade 2 complications occurred. No patient had grade >/= 3 complication. From a functional point of view, 100% (24/24) patients were continent and potency was preserved in 95% (19/20) men potent before treatment. The volume of ablation was a median 12 ml (IQR=5.6-14.5 ml) with the median PSA after 6 months of 3.4 ng ml(-1) (IQR=1.9-4.8 ng ml(-1)). MpMRI showed suspicious residual disease in six patients, of whom four (17%) underwent another form of local treatment. CONCLUSIONS: Focal IRE has a low toxicity profile with encouraging genito-urinary functional outcomes. Further prospective development studies are needed to confirm the functional outcomes and to explore the oncological potential.

Prevalence and clinical significance of small joint synovitis detected by ultrasonography in axial SpA

Objectives:¦The aim of this study was to estimate the prevalence of subclinical small joint synovitis detected by ultrasonography in patients with axial SpA, and to evaluate their relevance in terms of function or and disease activity.¦Methods:¦Forty axial SpA patients, 40 RA and 20 healthy subjects were evaluated by ultrasonography, using a reproducible semi-quantitative score by B-mode and Doppler, for synovitis, while disease activity and function were assessed using validated instruments (DAS28, BASDAI, BASFI, m-SACRAH and HAQ).¦Results:¦Median B-mode score were respectively 8.2 for axial SpA, 11.5 for RA and 6.0 for healthy subjects, corresponding to a prevalence of clinical significant synovitis of respectively 37.5%, 60% and 11% for a level of significance at > 8 chosen to¦classify as active > 75% of RA patient with DAS28 >2.6 and < 10% of controls. Addtionally, Doppler was positive in 8% of SpA, 30 % of RA and none of the healthy subjects. Echographic synovitis correlated with disease activity (DAS28) and function¦(HAQ, mSACRAH) in RA patients, but no correlation were found for SpA patients with disease activity (BASDAI) or function (BASFI, HAQ, mSACRAH). Cases of synovitis using classification by Doppler positivity were insufficient to allow any¦statistical analysis.¦Conclusions:¦B-mode ultrasonographic evaluation can demonstrate subclinical synovitis in almost 40% of SpA patients, but they do not appear to correlate with disease activity or function on the contrary to what is observed in RA patients, representing potentially different processes

The gap between scientific evidence and clinical practice : 5-aminosalicylates are frequently used for the treatment of Crohn's disease

BACKGROUND: There is uncertain evidence of effectiveness of 5-aminosalicylates (5-ASA) to induce and maintain response and remission of active Crohn's disease (CD), and weak evidence to support their use in post-operative CD. AIM: To assess the frequency and determinants of 5-ASA use in CD patients and to evaluate the physicians' perception of clinical response and side effects to 5-ASA. METHODS: Data from the Swiss Inflammatory Bowel Disease Cohort, which collects data since 2006 on a large sample of IBD patients, were analysed. Information from questionnaires regarding utilisation of treatments and perception of response to 5-ASA were evaluated. Logistic regression modelling was performed to identify factors associated with 5-ASA use. RESULTS: Of 1420 CD patients, 835 (59%) were ever treated with 5-ASA from diagnosis to latest follow-up. Disease duration >10 years and colonic location were both significantly associated with 5-ASA use. 5-ASA treatment was judged to be successful in 46% (378/825) of treatment episodes (physician global assessment). Side effects prompting stop of therapy were found in 12% (98/825) episodes in which 5-ASA had been stopped. CONCLUSIONS: 5-Aminosalicylates were frequently prescribed in patients with Crohn's disease in the Swiss IBD cohort. This observation stands in contrast to the scientific evidence demonstrating a very limited role of 5-ASA compounds in the treatment of Crohn's disease.

The Growing Importance of CNVs: New Insights for Detection and Clinical Interpretation.

Differences between genomes can be due to single nucleotide variants, translocations, inversions, and copy number variants (CNVs, gain or loss of DNA). The latter can range from sub-microscopic events to complete chromosomal aneuploidies. Small CNVs are often benign but those larger than 500 kb are strongly associated with morbid consequences such as developmental disorders and cancer. Detecting CNVs within and between populations is essential to better understand the plasticity of our genome and to elucidate its possible contribution to disease. Hence there is a need for better-tailored and more robust tools for the detection and genome-wide analyses of CNVs. While a link between a given CNV and a disease may have often been established, the relative CNV contribution to disease progression and impact on drug response is not necessarily understood. In this review we discuss the progress, challenges, and limitations that occur at different stages of CNV analysis from the detection (using DNA microarrays and next-generation sequencing) and identification of recurrent CNVs to the association with phenotypes. We emphasize the importance of germline CNVs and propose strategies to aid clinicians to better interpret structural variations and assess their clinical implications.