Smaller hippocampal volume following sexual assault in women is associated with post-traumatic stress disorder.

OBJECTIVE: Exposure to sexual assault is a significant risk factor to develop post-traumatic stress disorder (PTSD) in females. The early neurobiological changes leading to the development of PTSD remain understudied and unclear in this population. METHODS: Participants were 27 adult females recruited within a month following exposure to sexual assault (T1) and 20 age-matched non-exposed controls. Among the victims, 10 participants met (PTSD+) and 15 did not meet (PTSD-) DSM-IV criteria for PTSD 6 months post-trauma (T2). At both visits, hippocampal and amygdala volumes were extracted from magnetic resonance imaging scans, and indices of total diurnal cortisol changes were derived from individual areas under the curve relative to the ground (AUCg). Measures at T1 were compared between groups at T1, measures at T2 between groups at T2, and measures at T1 between groups at T2. RESULTS: At T1, victims had significantly smaller bilateral hippocampal volumes, but not AUCg, than controls. At T2, neither hippocampal volume nor AUCg significantly differed among the groups. However, the PTSD+ group had significantly smaller hippocampal volumes at T1 than the control group, but not compared to the PTSD- group. CONCLUSIONS: This study indicates that having smaller hippocampal volumes is a risk factor to develop PTSD in females exposed to sexual assault.

Using PET with 18F-AV-45 (florbetapir) to quantify brain amyloid load in a clinical environment.

PURPOSE: Positron emission tomography (PET) imaging of brain amyloid load has been suggested as a core biomarker for Alzheimer's disease (AD). The aim of this study was to test the feasibility of using PET imaging with (18)F-AV-45 (florbetapir) in a routine clinical environment to differentiate between patients with mild to moderate AD and mild cognitive impairment (MCI) from normal healthy controls (HC). METHODS: In this study, 46 subjects (20 men and 26 women, mean age of 69.0 ± 7.6 years), including 13 with AD, 12 with MCI and 21 HC subjects, were enrolled from three academic memory clinics. PET images were acquired over a 10-min period 50 min after injection of florbetapir (mean ± SD of radioactivity injected, 259 ± 57 MBq). PET images were assessed visually by two individuals blinded to any clinical information and quantitatively via the standard uptake value ratio (SUVr) in the specific regions of interest, which were defined in relation to the cerebellum as the reference region. RESULTS: The mean values of SUVr were higher in AD patients (median 1.20, Q1-Q3 1.16-1.30) than in HC subjects (median 1.05, Q1-Q3 1.04-1.08; p = 0.0001) in the overall cortex and all cortical regions (precuneus, anterior and posterior cingulate, and frontal median, temporal, parietal and occipital cortex). The MCI subjects also showed a higher uptake of florbetapir in the posterior cingulate cortex (median 1.06, Q1-Q3 0.97-1.28) compared with HC subjects (median 0.95, Q1-Q3 0.82-1.02; p = 0.03). Qualitative visual assessment of the PET scans showed a sensitivity of 84.6% (95% CI 0.55-0.98) and a specificity of 38.1% (95% CI 0.18-0.62) for discriminating AD patients from HC subjects; however, the quantitative assessment of the global cortex SUVr showed a sensitivity of 92.3% and specificity of 90.5% with a cut-off value of 1.122 (area under the curve 0.894). CONCLUSION: These preliminary results suggest that PET with florbetapir is a safe and suitable biomarker for AD that can be used routinely in a clinical environment. However, the low specificity of the visual PET scan assessment could be improved by the use of specific training and automatic or semiautomatic quantification tools.

Topical sirolimus solution for lingual microcystic lymphatic malformations in children and adults (TOPGUN): study protocol for a multicenter, randomized, assessor-blinded, controlled, stepped-wedge clinical trial.

BACKGROUND: Lingual microcystic lymphatic malformations (LMLMs) are rare congenital vascular malformations presenting as clusters of cysts filled with lymph fluid or blood. Even small well-limited lesions can be responsible for a heavy burden, inducing pain, aesthetic prejudice, or oozing, bleeding, infections. The natural history of LMLMs is progressive worsening punctuated by acute flares. Therapeutic options include surgery, laser excision, and radiofrequency ablation but all are potentially detrimental and expose to local relapse. Therefore, the management frequently relies on a "watchful waiting" approach. In complicated LMLMs, treatment with oral sirolimus, a mammalian target of rapamycin (mTOR) inhibitor, is often used. Topical applications of sirolimus on the buccal mucosae have been reported in other oral diseases with good tolerance and none to slight detectable blood sirolimus concentrations. We aim to evaluate the efficacy and safety of a 1 mg/mL sirolimus solution applied once daily on LMLM of any stage in children and adults after 4, 8, 12, 16, 20, and 24 weeks of treatment compared to usual care (no treatment). METHODS: This is a randomized, multicentric study using an individually randomized stepped-wedge design over 24 weeks to evaluate topical application of a 1 mg/mL sirolimus solution once daily, on LMLM, versus usual care (no treatment), the control condition. Participants begin with an observational period and later switch to the intervention at a randomized time (week 0, 4, 8, or 12). Visits occur every 4 weeks, either in the study center or by teleconsulting. The primary outcome will be the evaluation of global severity of the LMLM on monthly standardized photographs by 3 independent blinded experts using the physical global assessment (PGA) 0 to 5 scale. Secondary outcomes will include lesion size measurement and quality of life assessment, investigator, and patient-assessed global disease and specific symptoms (oozing, bleeding, sialorrhea, eating impairment, taste modification, aesthetic impairment, pain, and global discomfort) assessment. A biological monitoring will be performed including residual blood sirolimus concentration and usual laboratory parameters. DISCUSSION: Given the disappointing state of current treatment options in LMLMs, topical sirolimus could become firstline therapy in treating LMLMs if its efficacy and safety were to be demonstrated. TRIAL REGISTRATION: ClinicalTrials.gov NCT04128722 . Registered on 24 September 2019. EudraCT: EUCTR2019-001530-33-FR Sponsor (University Hospital Center of Tours - CHRU Tours): DR190041-TOPGUN French regulatory authorities: ID RCB: 2019-001530-33.

[Gas embolism during protective ventilation for acute respiratory distress syndrome]. / Embolie gazeuse malgré une ventilation protectrice au cours du syndrome de détresse respiratoire aiguë

A 34-year-old woman with toxic coma developed inhalation pneumonia complicated by the acute respiratory distress syndrome. Marked parenchymal destruction and recurrent pneumothorax occurred despite protective ventilation. Altered consciousness persisted after sedative withdrawal, and the patient subsequently died. Computed tomography revealed multiple cerebral, renal and splenic infarcts. The only identified cause of systemic embolism was multiple gas embolisms. We discuss the physiopathological mechanisms, and the diagnostic and therapeutic management of such patients.

[Dysmetabolic hepatosiderosis, characteristics in 51 patients]. / Hépatosidéroses dysmétaboliques, caractéristiques chez 51 patients.

OBJECTIVE: Dysmetabolic hepatosiderosis is a recently described entity, which reunites iron overloads associated with polymetabolic syndromes, steatosis and steato-hepatitis. The aim of this study was to specify the relationship between iron overload, polymetabolic syndrome, HFE mutations of primary hemochromatosis and steatosis. METHOD: This was a 5-year retrospective study of 51 patients hospitalised and/or seen in consultation, non-alcoholic, presenting with hyperferritinemia associated with a polymetabolic syndrome and/or hepatic steatosis. RESULTS: Patients mean age was of 53 +/- 12 years with a sex ratio M/F of 5.4. Metabolic disorders were found in 97% of the non-steatosis patients (overweight: 40%, perturbed sugar metabolism: 47%, dyslipidemia: 79.5%). Hyperferritinemia was constant but moderate (513.4 +/- 280.3 ng/ml). Transferrin saturation was predominantly normal (0.44 +/- 0.17). The hepatic enzymes were normal or only slightly perturbed. Steatosis was revealed by sonography in 62% of cases. The hepatic iron overload, documented in 6 patients by hepatic needle biopsy, was discreet (concentration/age ratio of 1.64 +/- 0.19). Among the 59% patients screened for the HFE gene, 40% were positive for C282Y and/or H63D. There was no correlation between ferritin levels and iron parameters, polymetabolic syndrome parameters and hepatic enzymes. The HFE mutations had no influence on the iron parameters. CONCLUSION: Dysmetabolic hepatosiderosis must be know by hospital practitioners because of their prevalence in cases of hyperferritinemia and their therapeutic incidence.

[Horton's disease and hypereosinophilic syndrome: a non-fortuitous association]. / Maladie de Horton et syndrome hyperéosinophilique: une rencontre non fortuite.

Giant cell arteritis is a T-cell dependent auto-immune vasculitis that involves a T-helper l (Th1) cell response. We report the unusual case of a woman who developed successively a biopsy-proven temporal arteritis without tissue eosinophilia at age 65, an isolated blood eosinophilia at age 69 and an hypereosinophilic syndrome at age 71, while still taking corticosteroids at the dose of 3mg/day. Considering this temporal relationship, some characteristics of her hypereosinophilic syndrome pointing to a Th2-dependent disease (absence of definite signs of myeloproliferative syndrome, elevated IgE levels and quick normalisation of eosinophil counts under corticosteroid therapy) and the existence of an unexplained blood inflammatory response at the time of HES onset, we postulate that an unbalanced T helper response led in this exceptional case to both diseases.