Quality of life measurement in rosacea. Position statement of the European Academy of Dermatology and Venereology Task Forces on Quality of Life and Patient Oriented Outcomes and Acne, Rosacea and Hidradenitis Suppurativa.

The European Academy of Dermatology and Venereology (EADV) Task Forces (TFs) on Quality of Life (QoL) and Patient-Oriented Outcomes and Acne, Rosacea and Hidradenitis Suppurativa (ARHS) do not recommend the use of any generic instrument as a single method of Health Related (HR) QoL assessment in rosacea, except when comparing quimp (quality of life impairment) in rosacea patients with that in other non-dermatologic skin diseases and/or healthy controls. The EADV TFs on QoL and Patient-Oriented Outcomes and ARHS recommend the use of the dermatology-specific HRQoL instrument the Dermatology Life Quality Index (DLQI) and the rosacea-specific HRQoL instrument RosaQoL in rosacea patients. The DLQI minimal clinically important difference may be used as a marker of clinical efficacy of the treatment and DLQI score banding of 0 or 1 corresponding to no effect on patients' HRQoL could be an important treatment goal. This information may be added to consensuses and guidelines for rosacea.

Transcriptional Regulation of Jaw Osteoblasts: Development to Pathology.

Craniofacial and jaw bones have unique physiological specificities when compared to axial and appendicular bones. However, the molecular profile of the jaw osteoblast (OB) remains incomplete. The present study aimed to decipher the bone site-specific profiles of transcription factors (TFs) expressed in OBs in vivo. Using RNA sequencing analysis, we mapped the transcriptome of confirmed OBs from 2 different skeletal sites: mandible (Md) and tibia (Tb). The OB transcriptome contains 709 TF genes: 608 are similarly expressed in Md-OB and Tb-OB, referred to as "OB-core"; 54 TF genes are upregulated in Md-OB, referred to as "Md-set"; and 18 TF genes are upregulated in Tb-OB, referred to as "Tb-set." Notably, the expression of 29 additional TF genes depends on their RNA transcript variants. TF genes with no previously known role in OBs and bone were identified. Bioinformatics analysis combined with review of genetic disease databases and a comprehensive literature search showed a significant contribution of anatomical origin to the OB signatures. Md-set and Tb-set are enriched with site-specific TF genes associated with development and morphogenesis (neural crest vs. mesoderm), and this developmental imprint persists during growth and homeostasis. Jaw and tibia site-specific OB signatures are associated with craniofacial and appendicular skeletal disorders as well as neurocristopathies, dental disorders, and digit malformations. The present study demonstrates the feasibility of a new method to isolate pure OB populations and map their gene expression signature in the context of OB physiological environment, avoiding in vitro culture and its associated biases. Our results provide insights into the site-specific developmental pathways governing OBs and identify new major OB regulators of bone physiology. We also established the importance of the OB transcriptome as a prognostic tool for human rare bone diseases to explore the hidden pathophysiology of craniofacial malformations, among the most prevalent congenital defects in humans.

Evaluation of the mobility of the shoulder and quality of life after perforator flaps for recalcitrant axillary hidradenitis.

BACKGROUND: Hidradenitis suppurativa is a very debilitating disease, treated by antibiotics and excision. The reconstruction is usually done by secondary wound healing and/or split-thichness skin graft. The aim of this study was to evaluate the reconstruction of the axilla with local perforator flaps as a single stage surgical treatment. METHODS: This was a monocentric retrospective study conducted between November 2013 and June 2015. We included the patients with a severe axillary localization of the disease. Between 6 months and 1 year postoperatively, we noted length of complete healing, complications, patients satisfaction score about the surgery, DASH functional score, maximum abduction angle of the arm, and recurrence of the disease. RESULTS: Thirteen patients were included, for a total of seventeen affected axillae. We performed seven thoracodorsal artery perforator flaps, seven lateral intercostal artery perforator flaps and three serratus anterior artery perforator flaps. The mean duration of follow-up was 279.1±84.1 days (180-365). The average complete healing time was 20.5±13.5 days (10-60). Six axillae were compounded (35%). The average recurrence rate of HS was 0%. The average score in the DASH questionnaire was 68.6±35.3 points (39-152) and the average maximum abduction angle of the arm was 160.6±18.5 degrees. The average score on the satisfaction questionnaire was 36.5±5.6 points (25-43). CONCLUSION: This is a single stage, reliable and effective surgical procedure. The results are very encouraging, with a good quality of life, a low functional disability and a shorter healing time.

[Misdiagnosis of hidradenitis suppurativa continues to be a major issue. The R-ENS Verneuil study]. / Errance médicale des patients atteints d'hidradénite suppurée : un problème majeur et persistant. Étude « R-ENS Verneuil ¼.

OBJECTIVE: To provide physicians with an understanding of the factors behind significant delays in the diagnosis of hidradenitis suppurativa (HS) in France. PATIENTS AND METHODS: This prospective multicentre national study conducted from October 2015 to March 2016 included all patients consulting for HS. Patient data were collected by means of a standardized questionnaire. Univariate and multivariate analyses were conducted to collect factors associated with a significant time to diagnosis of at least 5.5years, defined as the period between the onset of initial clinical signs and the time of formal diagnosis. RESULTS: The 16 participating centres enrolled 312 patients (62% women), of average age 35years. The average age at onset of HS was 22years. Before formal diagnosis by a dermatologist (64% of cases), 170 (54%), 114 (37%) and 45 (15%) patients had previously consulted at least 3, 5 and 10 general physicians, respectively. The average time between the initial clinical signs of HS, the first dermatology visit and the definitive diagnosis was 6.2 and 8.4 years, respectively. Active smoking (OR adjusted 1.85; P=0.027) and disease onset at a younger age (adjusted OR 0.92; P<0.001) were both associated with significant delays in diagnosis. CONCLUSION: These results emphasized misdiagnosis among HS patients but did not evidence any association between either sociodemographic or economic characteristics and the existence of significant times to diagnosis.

Feasibility of gadoxetate disodium-enhanced MR cholangiography in chronic cholestatic biliary disease.

AIM: To investigate the feasibility of gadoxetate disodium-enhanced magnetic resonance (MR) cholangiography in chronic obstructive cholestatic biliary disease in the clinical setting. MATERIALS AND METHODS: Twenty-three patients with dilated bile duct trees and ten volunteers underwent gadoxetate disodium-enhanced liver MR cholangiography and were enrolled in the present retrospective study. Gadoxetate disodium was given in a standardized manner as a bolus injection at a dose of 0.25 mmol/kg of body weight (0.1 ml/kg). Region of interest-based measurement of mean enhancement of the dilated bile ducts was performed in series before gadoxetate disodium administration and during hepatobiliary phases. RESULTS: Direct comparison of mean bile duct enhancement during hepatobiliary phases in the clinical imaging window between healthy volunteers [4.7 ± 2.2 arbitrary units (au)] and patients with dilated bile ducts (0.1 ± 0.3 au) revealed significantly lower or absent enhancement in dilated bile ducts (p = 0.001). CONCLUSION: Standard clinical gadoxetate disodium-enhanced MR cholangiography is not a reliable technique for the evaluation of the biliary trees, because of altered biliary gadoxetate disodium elimination in patients with chronic obstructive biliary diseases.

Compartment-specific gene regulation of the CAR inducer efavirenz in vivo.

Nuclear receptors such as the constitutive androstane receptor (CAR) are central factors that link drug exposure to the activities of drug metabolism and elimination. In order to determine the in vivo effects of efavirenz, a CAR activator, the expression of target genes was determined in duodenal biopsies obtained from 12 healthy volunteers before treatment and after 10 days of treatment with efavirenz; concomitant administration of the cholesterol inhibitor ezetimibe produced no significant difference. However, in in vitro studies, efavirenz significantly increased CYP2B6 expression in several cell types, suggesting that the drug transactivates CAR. This hypothesis is supported by our findings that there is significant induction of CAR target genes in in vivo peripheral blood mononuclear cells (PBMCs) isolated from healthy volunteers treated with multiple doses of efavirenz. The impact of efavirenz on hepatic metabolism in vivo was confirmed by significant changes in plasma 4ß-hydroxycholesterol and bilirubin levels and the area under the curve (AUC) of efavirenz. Induction of CYP2B6 mRNA expression correlated with the decrease in the AUC of efavirenz (r = 0.61; P = 0.036). Taken together, our results provide evidence that efavirenz exerts compartment-specific inductive capacity in vivo.

Impact of efavirenz on intestinal metabolism and transport: insights from an interaction study with ezetimibe in healthy volunteers.

Hypercholesterolemia frequently occurs in patients treated with efavirenz who cannot be treated adequately with statins because of drug interactions. These patients may benefit from cholesterol-lowering therapy with ezetimibe. This study determined the influence of single-dose and multiple-dose efavirenz (400 mg/day for 9 days) on the pharmacokinetics and sterol-lowering of ezetimibe (10 mg) in 12 healthy subjects. In addition, the influence of efavirenz on genome-wide intestinal expression and in vitro function of ABCB1, ABCC2, UGT1A1, and OATP1B1 was studied. Efavirenz (multiple dose) had no influence on the pharmacokinetics and lipid-lowering functions of ezetimibe. Intestinal expression of enzymes and transporters (e.g., ABCB1, ABCC2, and UGT1A1) was not affected by chronic efavirenz. Efavirenz (single dose) slightly increased ezetimibe absorption and markedly decreased exposure to ezetimibe-glucuronide (single dose and multiple dose), which may be explained by inhibition of UGT1A1 and ABCB1 (in vitro data). Ezetimibe had no effect on the disposition of efavirenz. Consequently, ezetimibe may be a safe and efficient therapeutic option in patients with HIV infection.

Drug interactions between the immunosuppressant tacrolimus and the cholesterol absorption inhibitor ezetimibe in healthy volunteers.

Immunosuppressive therapy is frequently associated with hypercholesterolemia, calling for lipid-lowering treatment without adverse drug interactions. One option is treatment with the cholesterol absorption inhibitor ezetimibe. We have shown in vitro that ezetimibe and tacrolimus may interact in competition for intestinal UGT1A1 and ABCB1 at concentrations reached in gut lumen after oral administration. However, this clinical study in healthy volunteers showed that the expected pharmacokinetic interaction between ezetimibe and tacrolimus is not of clinical relevance.

Pharmacokinetic and pharmacodynamic interactions between the immunosuppressant sirolimus and the lipid-lowering drug ezetimibe in healthy volunteers.

Organ transplant recipients who have dyslipidemia related to immunosuppression may benefit from cholesterol-lowering therapy with ezetimibe, a substrate of ABCB1, ABCC2, and OATP1B1. Adverse pharmacokinetic interactions are hypothesized with sirolimus, which is a substrate of OATP1B1 and OATP1B3 and an inhibitor of ABCB1, OATP1B1, and OATP1B3 but not of ABCC2. However, competition between sirolimus and ezetimibe for ABCB1 and OATP1B1 is not of major clinical relevance, as confirmed in our randomized, controlled, single-dose study in healthy subjects.

Wound healing in colonic anastomosis in hypothyroidism.

Colonic anastomosis healing in hypothyroidism was evaluated. Twenty Wistar rats were separated into two groups: the study group (n = 10), which underwent total thyroidectomy to induce hypothyroidism, and the control group (n = 10). After 10 weeks, hypothyroid status was confirmed by blood tests (p < 0.0001). Three days later, a colonic anastomosis was performed, and the animals were sacrificed 1 week later. The colon containing the anastomosis was resected for bursting strength tests and histological studies. The slides were stained with hematoxylin-eosin and with Sirius red to quantify and classify the collagen. Reduced values were found for the bursting strength test (p = 0.0006) and for collagen density in the experimental group. There was a prevalence of immature type III collagen (p < 0.0001) and a decrease in mature type I collagen (p < 0.0001) in the hypothyroid group.

Predictive value of hippocampal MR imaging-based high-dimensional mapping in mesial temporal epilepsy: preliminary findings.

BACKGROUND AND PURPOSE: We objectively assessed surface structural changes of the hippocampus in mesial temporal sclerosis (MTS) and assessed the ability of large-deformation high-dimensional mapping (HDM-LD) to demonstrate hippocampal surface symmetry and predict group classification of MTS in right and left MTS groups compared with control subjects. METHODS: Using eigenvector field analysis of HDM-LD segmentations of the hippocampus, we compared the symmetry of changes in the right and left MTS groups with a group of 15 matched controls. To assess the ability of HDM-LD to predict group classification, eigenvectors were selected by a logistic regression procedure when comparing the MTS group with control subjects. RESULTS: Multivariate analysis of variance on the coefficients from the first 9 eigenvectors accounted for 75% of the total variance between groups. The first 3 eigenvectors showed the largest differences between the control group and each of the MTS groups, but with eigenvector 2 showing the greatest difference in the MTS groups. Reconstruction of the hippocampal deformation vector fields due solely to eigenvector 2 shows symmetrical patterns in the right and left MTS groups. A "leave-one-out" (jackknife) procedure correctly predicted group classification in 14 of 15 (93.3%) left MTS subjects and all 15 right MTS subjects. CONCLUSION: Analysis of principal dimensions of hippocampal shape change suggests that MTS, after accounting for normal right-left asymmetries, affects the right and left hippocampal surface structure very symmetrically. Preliminary analysis using HDM-LD shows it can predict group classification of MTS and control hippocampi in this well-defined population of patients with MTS and mesial temporal lobe epilepsy (MTLE).

[Contact allergy to antiseptics: 75 cases analyzed by the dermato-allergovigilance network (Revidal)]. / Allergie de contact aux antiseptiques: 75 cas analysés par le réseau Revidal de dermato-allergovigilance.

AIM: To determine the clinical features of contact dermatitis caused by antiseptics and to ascertain whether the substance responsible is the antiseptic itself or the excipients. PATIENTS AND METHODS: A multicenter, retrospective study based on analysis of all cases reported over a 2-year period to the Dermato-Allergology Vigilance network known as Revidal. Each dossier contained details of the clinical characteristics of lesions, the incriminated antiseptic, the mode of exposure and the results of patch tests done with the antiseptic in question. RESULTS: 75 patients (mean age: 44 years) were sensitized to chlorhexidine (14 cases), hexamidine (20 cases), povidone iodine (14 cases), mercuric antiseptics (3 cases), triclocarban (Septivon, 17 cases), hexamidine-chlorhexidine-chlorocresol (Cytéal, 4 cases), or chlorhexidine surfactant (Hibiscrub), cetrimide or chlorhexidine digluconate (Diaseptyl) (1 case each). Exposure was therapy-related (68 cases), work-related (6 cases; 5 in health workers and 1 in a cattle farmer due to povidone-iodine) or related to cosmetics (1 case, hexamidine). The clinical features consisted mainly of localized contact dermatitis, although generalized eczema occurred in 9 cases due to hexamidine contact. Sensitization was due to the antiseptic itself (53 cases) or to the excipients alone (22 cases), particularly in the 17 cases caused by Septivon. In 27/75 cases (35%), patients exhibited polysensitization to antiseptics belonging to different chemical classes or to other topical drugs. CONCLUSION: Sensitization to antiseptics is probably not rare, with various sources of exposure being present in everyday life. Patch tests are essential for diagnosis in order to distinguish between antiseptic-related and excipient-related sensitization and to screen for polysensitization to topical drugs.

MRI-based high-dimensional hippocampal mapping in mesial temporal lobe epilepsy.

MRI-based evaluation of the hippocampus is important in the assessment and treatment of patients with mesial temporal lobe epilepsy (MTLE). Using MRI-based large-deformation high-dimensional mapping (HDM-LD), which allows structural evaluation of regions of the hippocampus, we document the HDM-LD-defined pattern of hippocampal deformation in MTLE patients compared with matched controls. In 30 subjects with MTLE and confirmed medial temporal lobe sclerosis (MTS), we performed measurements of intracranial area, brain parenchymal volume and deformation-based hippocampal segmentations, and then grouped patients into right and left MTS groups (resulting in 15 subjects in each group). Using HDM-LD techniques, we compared the right and left MTS groups with a group of 15 matched controls. Analysis included both the MTS and contralateral hippocampi, and covariance for changes in brain parenchymal volume. Final results were interpreted using a segmentation showing normal hippocampal surface subfield anatomy. Comparing the MTS groups with controls, after covarying with brain parenchymal volume, the MTS hippocampi showed significant volume loss (P < 0.0001), contralateral hippocampi showed no significant volume loss. HDM-LD techniques showed significant shape changes, with marked inward deviation in the Sommer sector of the MTS hippocampi. In the contralateral hippocampi, the inferior surface of the hippocampal body showed inward deformation in the medial aspect of the subiculum, with minimal involvement of the Sommer sector. HDM-LD shows involvement of subregions of the hippocampus which are consistent with MTS histopathology. Contralateral hippocampi show different HDM-LD changes, suggesting that the underlying disease process in the contralateral hippocampi is different from MTS.

[Pulmonary embolization from migration of sclerotherapy material]. / Embolie pulmonaire par migration de matériel de sclérothérapie.

We present a case of pulmonary embolism which resulted from the migration of an oesophageal variceal sclerosing agent. Despite its frequency, this complication is rarely described in the literature.

Gemcitabine-associated posterior reversible encephalopathy syndrome: MR imaging and MR spectroscopy findings.

A 55 year old female receiving gemcitabine for stage IV non-small cell carcinoma of the lung developed the clinical-radiologic syndrome of posterior reversible encephalopathy syndrome (PRES). She had clinical manifestations of headaches, increasing somnolence and tonic-clonic seizures. The fluid-attentuated inversion recovery (FLAIR) MR imaging sequence conspicuously showed bihemispheric, symmetrical cortical and subcortical white matter hyperintensities that preponderantly involved the parietal and occipital lobes. Diffusion-weighted imaging (DWI) sequence reflected the preponderant existence of vasogenic edema in the involved areas. MR spectroscopy showed no significant N-acetyl aspartate (NAA) depletion or lactate elevation prospectively, indicating the absence of significant neuronal loss and reversibility of the brain parenchymal changes. The clinical and radiologic manifestations essentially resolved completely with discontinuation of the drug.