Laurence Seidel

Efficacy of coenzyme Q10 in migraine prophylaxis: A randomized controlled trial

Riboflavin, which improves energy metabolism similarly to coenzyme Q10 (CoQ10), is effective in migraine prophylaxis. We compared CoQ10 (3 × 100 mg/day) and placebo in 42 migraine patients in a double-blind, randomized, placebo-controlled trial. CoQ10 was superior to placebo for attack-frequency, headache-days and days-with-nausea in the third treatment month and well tolerated; 50%-responder-rate for attack frequency was 14.4% for placebo and 47.6% for CoQ10 (number-needed-to-treat: 3). CoQ10 is efficacious and well tolerated.

Difference in risk factors for postoperative nausea and vomiting.

Background It is commonly stated that risk factors for postoperative nausea are the same as for vomiting. The authors designed a prospective study to identify and differentiate the risk factors for postoperative nausea and vomiting in various surgical populations in a clinical audit setting. Methods The study included 671 consecutive surgical inpatients, aged 15 yr or more, undergoing various procedures. The study focused on postoperative nausea visual analog scale scores every 4 h and vomiting episodes within 72 h. Both vomiting and retching were considered as emetic events. Patient-, anesthesia-, and surgery-related variables that were considered to have a possible effect on the proportion of patients experiencing postoperative nausea and/or vomiting were examined. The bivariate Dale model for binary correlated outcomes was used to identify selectively the potential risk factors of postoperative nausea and vomiting. Results Among the 671 patients in the study, 126 (19%) reported one or more episodes of nausea, and 66 patients (10%) suffered one or more emetic episodes during the studied period. There was a highly significant association between the two outcomes. Some risk factors were predictive of both nausea and vomiting (female gender, nonsmoking status, and general anesthesia). History of migraine and type of surgery were mainly responsible for nausea but not for vomiting. The predictive effect of risk factors was controlled for postoperative pain and analgesic drugs. Conclusion This study shows that differences exist in risk factors of postoperative nausea and vomiting. These could be explained by differences in the physiopathology of the two symptoms.

Cotransplantation of Mesenchymal Stem Cells Might Prevent Death from Graft-versus-Host Disease (GVHD) without Abrogating Graft-versus-Tumor Effects after HLA-Mismatched Allogeneic Transplantation following Nonmyeloablative Conditioning

Recent studies have suggested that coinfusion of mesenchymal stem cells (MSCs) the day of hematopoietic cell transplantation (HCT) might promote engraftment and prevent graft-versus-host disease (GVHD) after myeloablative allogeneic HCT. This prompted us to investigate in a pilot study whether MSC infusion before HCT could allow nonmyeloablative (NMA) HCT (a transplant strategy based nearly exclusively on graft-versus-tumor effects for tumor eradication) from HLA-mismatched donors to be performed safely. Twenty patients with hematologic malignancies were given MSCs from third party unrelated donors 30-120 minutes before peripheral blood stem cells (PBSCs) from HLA-mismatched unrelated donors, after conditioning with 2 Gy total body irradiation (TBI) and fludarabine. The primary endpoint was safety, defined as a 100-day incidence of nonrelapse mortality (NRM) <35%. One patient had primary graft rejection, whereas the remaining 19 patients had sustained engraftment. The 100-day cumulative incidence of grade II-IV acute GVHD (aGVHD) was 35%, whereas 65% of the patients experienced moderate/severe chronic GVHD (cGVHD). One-year NRM (10%), relapse (30%), overall survival (OS) (80%) and progression-free survival (PFS) (60%), and 1-year incidence of death from GVHD or infection with GVHD (10%) were encouraging. These figures compare favorably with those observed in a historic group of 16 patients given HLA-mismatched PBSCs (but no MSCs) after NMA conditioning, which had a 1-year incidence of NRM of 37% (P = .02), a 1-year incidence of relapse of 25% (NS), a 1-year OS and PFS of 44% (P = .02), and 38% (P = .1), respectively, and a 1-year rate of death from GVHD or infection with GVHD of 31% (P = .04). In conclusion, our data suggest that HLA-mismatched NMA HCT with MSC coinfusion appeared to be safe.

Subclinical cerebellar impairment in the common types of migraine: A three-dimensional analysis of reaching movements

Mutations in the CACNA1A gene can cause familial hemiplegic migraine (FHM) and/or cerebellar ataxia. CACNA1A codes for the α1 subunit of P/Q‐Ca2+ channels and is highly expressed in the cerebellum. Using a pointing paradigm and infrared optoelectronic tracking system, we found subclinical hypermetria and other subtle cerebellar signs in the common forms of migraine. These were more pronounced in migraine with than without aura. Whether this reflects involvement of Ca2+ channel genes in the common types of migraine needs to be investigated by genetic analyses.

Assessment of postoperative nausea using a visual analogue scale.

Background: Assessment of postoperative nausea intensity is difficult because nausea is a subjective and unpleasant sensation. We propose using the Visual Analogue Scale (VAS) device to increase the efficiency and precision in the assessment of nausea. We carried out a pilot study on postoperative patients suffering from nausea to measure the degree of agreement between the VAS scores and those given on a 4‐point verbal descriptive scale (VDS).

Exhaled nitric oxide thresholds associated with a sputum eosinophil count ≥3% in a cohort of unselected patients with asthma

Background It has been claimed that exhaled nitric oxide (FeNO) could be regarded as a surrogate marker for sputum eosinophil count in patients with asthma. However, the FeNO threshold value that identifies a sputum eosinophil count ≥3% in an unselected population of patients with asthma has been poorly studied. Methods This retrospective study was conducted in 295 patients with asthma aged 15–84 years recruited from the asthma clinic of University Hospital of Liege. Receiver-operating characteristic (ROC) curve and logistic regression analysis were used to assess the relationship between sputum eosinophil count and FeNO, taking into account covariates such as inhaled corticosteroids (ICS), smoking, atopy, age and sex. Results Derived from the ROC curve, FeNO ≥41 ppb gave 65% sensitivity and 79% specificity (AUC=0.777, p=0.0001) for identifying a sputum eosinophil count ≥3%. Using logistic regression analysis, a threshold of 42 ppb was found to discriminate between eosinophilic and non-eosinophilic asthma (p<0.0001). Patients receiving high doses of ICS (≥1000 μg beclometasone) had a significantly lower FeNO threshold (27 ppb) than the rest of the group (48 ppb, p<0.05). Atopy also significantly altered the threshold (49 ppb for atopic vs 30 ppb for non-atopic patients, p<0.05) and there was a trend for a lower threshold in smokers (27 ppb) compared with non-smokers (46 ppb, p=0.066). Age and sex did not affect the relationship between FeNO and sputum eosinophilia. When combining all variables into the logistic model, FeNO (p<0.0001), high-dose ICS (p<0.05) and smoking (p<0.05) were independent predictors of sputum eosinophilia, while there was a trend for atopy (p=0.086). Conclusion FeNO is able to identify a sputum eosinophil count ≥3% with reasonable accuracy and thresholds which vary according to dose of ICS, smoking and atopy.

Distribution of sputum cellular phenotype in a large asthma cohort: predicting factors for eosinophilic vs neutrophilic inflammation.

BackgroundPhenotyping asthma according to airway inflammation allows identification of responders to targeted therapy. Induced sputum is technically demanding. We aimed to identify predictors of sputum inflammatory phenotypes according to easily available clinical characteristics.MethodsThis retrospective study was conducted in 508 asthmatics with successful sputum induction recruited from the University Asthma Clinic of Liege. Receiver-operating characteristic (ROC) curve and multiple logistic regression analysis were used to assess the relationship between sputum eosinophil or neutrophil count and a set of covariates. Equations predicting sputum eosinophils and neutrophils were then validated in an independent group of asthmatics.ResultsEosinophilic (≥3%) and neutrophilic (≥76%) airway inflammation were observed in 46% and 18% of patients respectively. Predictors of sputum eosinophilia ≥3% were high blood eosinophils, FENO and IgE level and low FEV1/FVC. The derived equation was validated with a Cohen’s kappa coefficient of 0.59 (p < 0.0001). ROC curves showed a cut-off value of 220/mm3 (AUC = 0.79, p < 0.0001) or 3% (AUC = 0.81, p < 0.0001) for blood eosinophils to identify sputum eosinophilia ≥3%. Independent predictors of sputum neutrophilia were advanced age and high FRC but not blood neutrophil count.ConclusionEosinophilic and paucigranulocytic asthma are the dominant inflammatory phenotypes. Blood eosinophils provide a practical alternative to predict sputum eosinophilia but sputum neutrophil count is poorly related to blood neutrophils.

Induction of long‐lasting changes of visual cortex excitability by five daily sessions of repetitive transcranial magnetic stimulation (rTMS) in healthy volunteers and migraine patients

We have shown that in healthy volunteers (HV) one session of 1 Hz repetitive transcranial magnetic stimulation (rTMS) over the visual cortex induces dishabituation of visual evoked potentials (VEPs) on average for 30 min, while in migraineurs one session of 10 Hz rTMS replaces the abnormal VEP potentiation by a normal habituation for 9 min. In the present study, we investigated whether repeated rTMS sessions (1 Hz in eight HV; 10 Hz in eight migraineurs) on 5 consecutive days can modify VEPs for longer periods. In all eight HV, the 1 Hz rTMS-induced dishabituation increased in duration over consecutive sessions and persisted between several hours (n = 4) and several weeks (n = 4) after the fifth session. In six out eight migraineurs, the normalization of VEP habituation by 10 Hz rTMS lasted longer after each daily stimulation but did not exceed several hours after the last session, except in two patients, where it persisted for 2 days and 1 week. Daily rTMS can thus induce long-lasting changes in cortical excitability and VEP habituation pattern. Whether this effect may be useful in preventative migraine therapy remains to be determined.

Importance of concomitant local and systemic eosinophilia in uncontrolled asthma

Systemic and airway eosinophilia are recognised features of asthma. There are, however, patients who exhibit discordance between local and systemic eosinophilia. In this study, we sought to determine the prevalence and characteristics of patients with concordant and discordant systemic and bronchial eosinophilia. We conducted a retrospective study on 508 asthmatics with successful sputum induction. We assessed the relationship between blood and sputum eosinophils by breaking down the population into four groups according to blood (≥400 cells per mm3) and sputum (≥3%) eosinophils. Then, we prospectively reassessed the link between eosinophils and asthma control (Asthma Control Questionnaire (ACQ)) and exacerbation rate in a new cohort of 250 matched asthmatics. In our retrospective cohort, asthmatics without eosinophilic inflammation were the largest group (49%). The group with isolated sputum eosinophilia (25%) was, compared with noneosinophilic asthma, associated with lower forced expiratory volume in 1 s (FEV1) and FEV1/forced vital capacity ratio and higher bronchial hyperresponsiveness and exhaled nitric oxide fraction (FeNO). Asthmatics exhibiting isolated systemic eosinophilia (7%) had similar characteristics as noneosinophilic asthmatics. The group with concordant systemic and airway eosinophilia (19%) showed remarkable male predominance, and had the lowest airway calibre, asthma control and quality of life, and the highest bronchial hyperresponsiveness, FeNO and exacerbation rate. The prospective cohort confirmed the different subgroup proportions and the higher ACQ and exacerbation rates in cases of diffuse eosinophilia compared with noneosinophilic asthmatics. Concomitant systemic and bronchial eosinophilic inflammation contribute to poor asthma control. Concomitant systemic and bronchial eosinophilic inflammation contributes to poor asthma control http://ow.ly/sLtYr

Tumour necrosis factor (TNF) gene polymorphism in Crohn's disease (CD): influence on disease behaviour?

Crohns disease (CD) is a multifactorial disease with genetic heterogeneity. TNF‐α plays a key role in the development of the mucosal lesions. The aim of our work was to study a single base pair polymorphism located in the promoter region of TNF gene, in a large population of CD patients with well defined phenotypes. One hundred and ninety‐three patients with CD and 98 ethnically matched controls were studied. The −308 single base pair polymorphism of TNF gene was studied using an allele‐specific polymerase chain reaction. Genotype and allelic frequencies were compared between patients and controls and between subgroups of patients defined by sex, age at diagnosis, familial history, location of disease, type of disease, extra‐intestinal manifestations, and response to steroid treatment. In 29 patients a measure of TNF‐α production by colonic biopsies was performed. The frequency of the allele TNF2 as well as the proportion of carriers of the allele TNF2 were slightly but not significantly lower in CD than in controls (11.9% versus 14.8% and 21.5% versus 27.6%, respectively). A more prominent difference in frequencies of allele TNF2 and in proportions of TNF2 carriers was found when comparing subgroups of patients. The frequency of allele TNF2 was significantly higher in steroid‐dependent than in non‐steroid‐dependent disease (28.1% versus 10.3%; Δ = 17.8%, 95% confidence interval (CI) = 6.3–29.5%, P = 0.0027) and tended to be higher in colonic than in small bowel disease and in fistulizing than in stricturing disease. Furthermore, TNF2 carriers tended to be more frequent in patients with steroid‐dependent than non‐steroid‐dependent disease (43.8% versus 19.3%; Δ = 24.5%, 95% CI = 3.6–45.4%, P = 0.022), in patients with fistulizing than stricturing disease (26.5% versus 9.6%; Δ = 16.9%, 95% CI = 1.1–32.6%, P = 0.036), and in patients with colonic than small bowel disease (26.5% versus 11.1%; Δ = 15.4%, 95% CI = −0.8–31.6%, P = 0.063). Finally, patients carrying at least one copy of allele 2 were found to produce slightly more TNF‐α at the colonic level. The −308 TNF gene polymorphism may have a slight influence on the behaviour of CD. The carriage of allele 2 may favour steroid‐dependent disease and to a lesser extent fistulizing and colonic disease, possibly secondary to a more intense TNF‐α‐driven inflammatory reaction at the mucosal level.