Mouse embryonic stem cell-derived motor neurons are susceptible to ferroptosis.

Ferroptosis is a regulated form of cell death driven by the lethal accumulation of lipid peroxides in cell membranes. Several regulators of ferroptosis have been identified using cancer cell lines. However, the cellular pathways of ferroptosis in neurons remain poorly characterized. In this study, we used a mouse embryonic stem cell-derived motor neuron model to investigate how motor neurons respond to ferroptosis inducers. Pharmacological and genetic inhibition of glutathione peroxidase 4 (GPx4) induced ferroptosis in motor neurons, while system xc - inhibition by erastin had no effect. RNA-seq analysis showed that the expression levels of several genes were altered during RSL3-induced ferroptosis. Subsequent bioinformatic analysis revealed alterations in several biological pathways during ferroptosis, including synaptogenesis and calcium signaling. Finally, we found that edaravone, an FDA-approved drug for treating amyotrophic lateral sclerosis (ALS) disease, rescued motor neurons from RSL3-induced ferroptosis. Our data highlight the crucial role of GPx4 in ferroptosis regulation and demonstrate that stem cell-derived motor neuron culture is a valuable model to study ferroptosis at the single-cell level in a neuronal context.

[A perimyocarditis revealing eosinophilic granulomatosis with polyangiitis]. / Une périmyocardite révélatrice d'une granulomatose éosinophilique avec polyangéite : une nouvelle observation.

Churg-Strauss syndrome (CSS) or eosinophilic granulomatosis with polyangiitis is a systemic vasculitis characterized by necrotizing arteritis, eosinophilic infiltration and extravascular granuloma; that may involve several organs. Cardiac involvement is the first cause of death in this vasculitis. These include myocarditis, pericarditis, coronary heart disease, dysrhythmias, and rarely valvular involvement. We report the observation of CSS revealed by acute perimyocarditis.

[Cerebral amyloid angiopathy revealed or hypertension-related cerebral small vessel diseases: A clinical challenge]. / Angiopathie amyloïde cérébrale ou atteinte des microvaisseaux cérébraux en rapport avec l'HTA : un challenge clinique.

Cerebral amyloid angiopathy (CAA) is a entity characterized by degenerative Amyloïd deposits in the walls of the meningeal and cortical vessels. It is considered as the second cause of primitives cerebral hemorrhage in elderly. The differential diagnosis between AAC and hypertension-related cerebral small vessel diseases is difficult and represent a true challenge for the clinician. We report two cases of cerebral small vessel diseases revealed by malignant hypertension.

Pulmonary hypertension on systemic sclerosis-lupus erythematosus overlap syndrome.

PURPOSE: There are authentic observations of combination of systemic lupus erythematosus (SLE) with systemic sclerosis (SS) and with polymyositis defined as overlap syndromes. The prevalence of pulmonary hypertension is unknown in SS-SLE overlap syndrome because of its rarity. The aim of our study was to precise clinical, paraclinical and evolutive features of pulmonary hypertension in patients with systemic sclerosis-systemic lupus erythematosus (SS-SLE) overlap syndrome. METHODS: Sixteen cases of SS-SLE overlap syndrome were retrospectively studied in a period of 16 years (2000-2015). SS-SLE overlap syndrome was diagnosed in the presence of at least 4 criteria of the American College of Rheumatology (ACR) for the diagnosis of SLE and a major criterion or 2 minor criteria of ACR of SS classification. Pulmonary arterial pressure (PAP) was estimated with doppler echocardiography. Pulmonary hypertension (PAH) was defined by a PAP superior than 30mmHg. We distributed groups according to the existence (Group 1) or not (Group 2) of a PAH. Epidemiological, clinical and evolutive features were compared between the two groups with bilateral fisher test (P significant if inferior at 0.05) RESULTS: Sixteen cases of female patients with SS-SLE overlap syndrome with a middle-age of 39 years, extreme (29-58 years) were studied. PAH complicated the evolution of SS-SLE overlap syndrome in six cases with a middle-age of 41 years. Ten patients of the group 2 had an average age of 40 years. The average age of the beginning of the disease was 28 years in the group 1 and 31 years in the group 2. SS preceded SLE in 6 among 16 cases (Group 1: 2/6, Group 2: 4/10). SS was revealed most frequently by Raynauw's Syndrome in both groups (Group 1: 4/6, Group 2: 7/10). Cutaneous and articular involvements were the most frequent observed manifestations of SLE (Group 1: 5/6, Group 2: 6/10). In the group 1, the PAH was discovered approximatively11 years after the beginning of the SS-SLE overlap syndrome. The average PAP was 52mmHg, extreme (32-80mmHg). A right cardiac insufficiency complicated the evolution of the PAH in 3 cases. The PAH was primitive in 3 cases. There was no significant difference concerning the SS-SLE overlap syndrome onset disease symptoms, the frequency of lung involvement and esophageal, neurological, articular and trophic manifestations. PAH was not associated with lupic proliferative renal disease, neither with cutaneous proximal sclerosis nor with anti-Scl70 positivity. Patients were treated with vasodilator treatment in eleven cases: prostacyclin derivates in five cases and endothelin receptor antagonist in six cases. Two patients received corticosteroids and boli of cyclophosphamide for renal involvement and neurologic involvement in each case. Stabilization of PAP was observed in these two cases. Mean follow-up disease was 67 months, extreme (4-124 months) Cutaneous sclerosis evolution was not significantly different between both groups. Global cardiac insufficiency secondary to PAH caused death in one case. CONCLUSION: According to the results of our study, SS-SLE overlap syndrome complicated with PAH seems to be associated more frequently with limited and distal cutaneous manifestations. Patients that have developed lupus nephropathy and/or had positive anti-Scl70 seem to be protected from appearance of PAH during the SS-SLE overlap syndrome.

Travel medicine consultation: An opportunity to improve coverage for routine vaccinations.

BACKGROUND: Travelers may be responsible for the spread of vaccine-preventable diseases upon return. Travel physicians and family physicians may play a role in checking and updating vaccinations before traveling. Our aim was to evaluate the vaccine coverage for mandatory and recommended vaccination in travelers attending a travel medicine clinic (TMC). METHODS: Vaccine coverage was measured using the current French immunization schedule as reference for correct immunization, in travelers providing a vaccination certificate during the TMC visit (university hospital of Saint-Étienne), between August 1, 2013 and July 31, 2014. RESULTS: In total, 2336 travelers came to the TMC during the study period. Among the 2019 study participants, only 1216 (60.3%) provided a vaccination certificate. Travelers who provided a vaccination certificate were significantly younger than travelers who did not (mean age: 34.8±17.8 vs. 46±18.4 years, P<0.005) and were less likely to be Hajj pilgrims. Vaccine coverage against Tetanus, Diphtheria, and Poliomyelitis (Td/IPV vaccine) was 91.8%, 78.6% against Measles, Mumps, and Rubella (MMR), and 59.4% against Viral Hepatitis B (HBV). BCG vaccine coverage was 71.9%. Older travelers were less likely to be correctly vaccinated, except against HBV as vaccinated travelers were significantly older than unvaccinated travelers. CONCLUSION: Obtaining information about immunization in travelers is difficult. Coverage for routine vaccines should be improved in this population. Travel medicine consultations could be the opportunity to vaccinate against MMR, HBV, and Td/IPV.

[Epidemiological, clinical and evolutionary peculiarities of interstitial lung disease in systemic sclerosis]. / Particularités épidémiologiques, cliniques et évolutives des pneumopathies interstitielles au cours de la sclérodermie systémique.

Pulmonary involvement during systemic sclerosis (SS) is dominated by interstitial lung disease and arterial pulmonary hypertension. It is about a retrospective study analyzing 65 cases of SS over a period of 13 years. We compared cases with and without interstitial lung disease. The diagnosis of SS was retained according to American College of Rheumatology (ACR)/EULAR 2013 criteria. The diagnosis of interstitial lung disease was retained in TDM and EFR. Pulmonary hypertension is defined by a pulmonary arterial pression higher than 25 mmHg. The mean delay of diagnosis of interstitial lung disease and the diagnosis was of 48 months (extremes 0-78 months). The comparison between both groups according to average age of the patients, prevalence of pulmonary hypertension, frequency of Raynaud phenomenon and trophic disorders did not find any significant difference. Lung involvement was associated with an esophageal involvement in 71% of the cases (P=0.059). Antibodies anti-Scl 70 were noted more frequently in patient's with interstitial lung disease (79% of the cases, P=0.001). Patients were treated with colchicine and vitamin E. A corticotherapy had been indicated at a single patient. The evolution of SS was marked by the stabilisation of the restrictive syndrome in 71.8% of the cases and a worsening in 25% of the cases. Early and appropriate diagnosis of SS and screening of lung involvement are essential for a early care.

[Systemic sarcoidosis and membranous glomerulonephritis]. / Sarcoïdose systémique et glomérulonéphrite extra-membraneuse.

Renal involvement in sarcoidosis is rare and more often related to calcium metabolism disorders or granulomatous interstitial nephritis. Glomerulonephritis is exceptional. There may be a long latency period between the development of active sarcoidosis and glomerular involvement and inversely. We report a case membranous glomerulonephritis revealing systemic sarcoidosis.

Management of acute perianal sepsis in neutropenic patients with hematological malignancy.

In neutropenic patients with acute perianal sepsis in the setting of hematological malignancy, the classical clinical features of abscess formation are lacking. Additionally, the role of surgical intervention is not well established. In this review, we discuss the challenges and controversy regarding diagnosis and optimal management when clear surgical guidelines are absent. In the literature, there is great diversity in the surgical approach to these patients, which leads to a high percentage of diagnostic errors, risks of complications, and unnecessary interventions. We review the literature and assess whether surgical intervention produces better outcomes than a non-surgical approach. Studies published on perianal sepsis in neutropenic cancer patients were identified by searching PubMed using the following key words: "perianal sepsis/abscesses, anorectal sepsis/abscess, neutropenia, hematological malignancy, cancer". No randomized or prospective studies on the management of acute perianal sepsis in hematological malignancies were found. The largest retrospective study and most comprehensive clinical data demonstrated that 42% of patients were treated successfully without surgical intervention and without morbidity or mortality related to treatment chosen. Small retrospective studies advocated surgical intervention, while the majority of successes were in a non-operative treatment. It is difficult to formulate a conclusion given the small retrospective series on management of neutropenic patients with hematological malignancies. While there is no evidence mandating a routine surgical approach in this category of patients, non-surgical management including careful follow-up to determine whether the patient's condition is deteriorating or treatment has failed is an acceptable approach in selected patients without pathognomonic features of abscess. Comprehensive and well-designed prospective studies are needed to firmly establish the guidelines of treatment protocols.

3-year real-world outcomes with the Swedish adjustable gastric band™ in France.

The study objective was to ascertain outcomes with the Swedish adjustable gastric band (SAGB) on an intention-to-treat basis in multiple centers across the French social health insurance system. SAGB results at 3-year follow-up are reported. The noncomparative, observational, prospective, consecutive cohort study design sought a 500-patient minimum recruitment geographically representative of continental France. Safety (adverse events [AEs], device-related morbidity, and mortality) and effectiveness (change in body mass index [BMI, kilograms per square meter], percentage excess weight loss, comorbidities, quality of life [QoL]) were assessed. Adjustable gastric band survival was calculated. Thirty-one surgeons in 28 multidisciplinary teams/sites enrolled patients between September 2, 2007 and April 30, 2008. SAGB was successfully implanted in 517 patients: 88.0 % female; mean age, 37.5 years; obesity duration, 15.3 years (baseline: mean BMI, 41.0; comorbidities, 773 in 74.3 % of patients; Bariatric Analysis and Reporting Outcome System (BAROS), 1.4; EuroQoL 5-Dimensions (EQ-5D), 0.61; EuroQoL-visual analog scale (EQ-VAS), 52.3). At 3 years: BMI, 32.2 (mean change, -9.0; p < 0.0001); excess weight loss, 47.4 %; comorbidities, 161 in 27.2 %; BAROS, 3.6 (+2.2, p < 0.0001); EQ-5D, 0.84 (+0.22, p < 0.0001); EQ-VAS, 73.4 (+21.4, p < 0.0001). SAGB-induced weight loss was associated with substantially improved QoL. One death occurred and was unrelated to the treatment. No AE was reported in 68.3 % of patients, and no confirmed device-related AE in 77.0 %. Overall AE rate was 0.19 per patient year. Device retention was 87.0 %. Analysis of patients lost to follow-up showed a nonsignificant effect on overall study results. In a prospective, consecutive cohort, "real-world", nationwide study, the Swedish Adjustable Gastric Band was found safe and effective at 3-year follow-up.

Persistently normal alanine aminotransferase levels in HIV/HCV-coinfected patients: the role of steatosis.

OBJECTIVE: The frequency and significance of, and liver biopsy findings associated with, a persistently normal alanine aminotransferase (ALT) level in HIV/hepatitis C virus (HCV)-coinfected patients are poorly characterized. We analysed factors associated with persistently normal ALT levels, defined as at least three consecutive normal ALT values over a 6-month period, in a group of 381 HIV/HCV-coinfected patients. METHODS: Patients were categorized into two groups according to ALT values: group 1, patients with persistently normal ALT levels; and group 2, patients with elevated ALT values. Possible interactions with host factors, HIV and HCV viral factors, antiretroviral treatment and histological features were examined. RESULTS: Thirty-six patients (9.4%) had persistently normal ALT levels. None of the 36 patients had cirrhosis. Seven patients (19.4%) had a METAVIR fibrosis score of F3. In multivariate analysis, a lower mean METAVIR inflammation score [odds ratio (OR) 0.50, 95% confidence interval (CI) 0.28-0.89; P=0.017], the absence of steatosis (OR 0.43, 95% CI 0.20-0.90; P=0.026) and HCV genotype 4 infection (OR 2.81, 95% CI 1.15-6.68; P=0.023) were associated with persistently normal ALT levels. CONCLUSION: The slower progression of chronic hepatitis in patients with persistently normal ALT levels could be related, in part, to a lower frequency of steatosis.

[Medicoeconomic evaluation of the treatment of morbid obesity by Swedish adjustable gastric banding (SAGB)]. / Evaluation médicoéconomique du traitement de l'obésité morbide par anneau gastrique ajustable suédois (SAGB).

INTRODUCTION: Aim of the present study was to analyze the medicoeconomic impact of each treatment for obesity in France, taking into account morbid obesity-associated comorbidities from a health insurance perspective and to calculate the cost-effectiveness ratio of SAGB compared to the non-surgical treatment for various kinds of patients, as well as the budget impact on a given cohort of patients. METHODS: The model studied surgery-eligible patients and compared the effectiveness of the SAGB treatment to the conventional treatment. The follow-up extended from 1 to 5 years. Costs analyzed were treatment-related direct medical costs, as well as potential comorbidities costs. The effectiveness is determined according to the BMI loss and its maintenance over time, together with the level of improved quality of life. RESULTS: An evaluation on a series of 1,000 patients shows that the treatment with SAGB is dominant (less expensive, more effective in terms of loss of BMI and its duration) compared to the conventional treatment for patients suffering from type II diabetes or obstructive sleep apnea. The same evaluation in terms of QALYs shows that the treatment with SAGB is dominant compared to the conventional treatment for patients with a BMI >or= 35 kg/m(2) and a type II diabetes, as well as for patients whose BMI >or= 40 kg/m(2) (with or without type II diabetes mellitus).

[Treatment interruption in HIV infected patients: clinical and biological evolution]. / Interruption thérapeutique chez des patients infectés par le virus de l'immunodéficience humaine: évolution clinique et biologique.

OBJECTIVE: The authors had for aim to evaluate the clinical and biological evolution in HIV-infected patients with viraemia lower than 30,000 copies/mL having decided to interrupt their treatment. PATIENTS AND METHODS: Patients with highly active antiretroviral therapy (HAART) for more than 3 months followed by treatment interruption longer than 1 month were included in a retrospective analysis. RESULTS: Forty-six patients having stopped treatment between November 1999 and July 2003 were included. The median duration of treatment interruption was 9.5 months. During the study, no clinical event occurred for 21 patients, and at least 1 clinical event occurred for the 25 others. The median CD4(+) cell counts (CD4) before and at the end of treatment interruption were 597/mm(3) and 437/mm(3), respectively (P<0.001). The median values of viral load before and at the end of treatment interruption were <50 and 23749 copies/mL, respectively (P<0.001). Among the 26 patients having started a new HAART, pre-treatment interruption and post-new HAART median CD4 (with a median delay after HAART of 9.7 months) were 548 and 432.5/mm(3) (P=0.02). Pre-treatment interruption and post-new HAART median viral load were 131.5 and 94.5 copies/mL (NS). CONCLUSIONS: Treatment interruption must be used with caution in spite of the absence of virological impact, because CD4 cell count after new HAART is lower than CD4 preceding treatment interruption. Treatment interruption is contraindicated for patients with AIDS. Physicians must carefully follow other patients who decide on a treatment interruption.

Colovesical fistula due to a lost gallstone following laparoscopic cholecystectomy: report of a case.

We report the case of a 74-year-old man with a colovesical fistula caused by a gallstone that was lost during a laparoscopic cholecystectomy 7 months earlier. The patient was cured after undergoing colonoscopic removal of the stone. To our knowledge this is the first case report of such a complication in the English literature. The report reviews the outcome and complications of retained intraperitoneal gallstones.

Management of gallbladder stones during pregnancy: conservative treatment or laparoscopic cholecystectomy?

BACKGROUND/AIMS: Safety of laparoscopic cholecystectomy (LC) during pregnancy is still controversial, we report our experience in the management of 42 pregnant patients suffering from symptomatic gallbladder stones. METHODOLOGY: Between June 1993 and July 1998, we performed 1700 LC's. During this period we dealt with 42 pregnant patients who had symptoms of gallbladder stones. Following an initial period of conservative management, only 16 patients underwent LC during pregnancy and 26 patients responded to medical management and were operated upon later on after delivery. RESULTS: Sixteen patients were operated upon successfully during pregnancy, 2 in the 1st trimester, 10 in the 2nd trimester and 4 in the 3rd trimester. No complications occurred and all patients carried on their pregnancies to term and delivered healthy babies. CONCLUSIONS: From our experience and from the review of the literature on this subject, LC during pregnancy is safe, however the indications should be restricted to patients with complications or to those suffering from repeated and persistent symptoms not responding to medical management.

Recurrent bilateral anterior uveitis with hypopyon and rifabutin therapy.

Rifabutin is used in patients with human immunodeficiency virus infection to prevent and treat Mycobacterium avium complex infection. We report a case of recurrent bilateral anterior uveitis with hypopyon in a patient who was taking 600 mg of rifabutin daily. The rate of recurrence with the continuation of rifabutin seems to be high, especially in the opposite eye (alternate uveitis with hypopyon); rifabutin should be discontinued if uveitis recurs.

Drug abuse in Jordan: an exploratory study.

The method used for obtaining data on the prevalence of licit and illicit drug abuse in Jordan during the period under study (1970 - 1977), included indirect measurements or indicators and direct estimates of abuse in different localities of Jordan. The study has shown changing patterns and trends of abuse of illicit drugs (hashish and other opiates) and licit psychoactive drugs (mainly tranquilizers and barbiturates) obtained on prescription. The incidence of licit drug abuse has been rising steadily in recent years. Drug abusers belong to a wide range of socio-economic backgrounds, occupations, and age groups. The findings were viewed in a broader socio-cultural context. The implications for prevention and intervention are discussed as well as the need for developing an adequate information system.

First-drawn pictures: a cross-cultural investigation.

Fifty Jordanian male and female students at the University of Jordan, Jordan were asked to draw a person. A significantly larger number of women than men drew a picture of the opposite-sex first. This appears in line with Craddick's finding for American college students. The frequency of drawing opposite-sex pictures first as a phenomenon characteristic of Jordanian and American female college students was discussed in terms of sociocultural factors and considered in the sex-role frame of reference. Suggestions for future research were presented.