Glioblastoma and malignant melanoma: Serendipitous or anticipated association?

We describe a patient who had primary glioblastoma (GB) and malignant melanoma (MM). A 78‐year‐old man presented with several weeks to months of history of gait disturbance, confusion, memory disturbance, and worsening speech. Imaging studies performed on admission revealed a large frontotemporal lobe mass associated with the surrounding zone of vasogenic edema. Given the patient's medical history of incomplete biopsy of a midback tumor performed three weeks before, the presumptive clinical diagnosis was metastatic MM. Pathological examination of frozen sections of fragmented specimens obtained at stereotactic biopsy performed on admission revealed a high‐grade malignant neoplasm characterized by discohesive cells in a blue myxoid background and abundant foci of tumor necrosis. Given these features, in conjunction with the abovementioned pathological report, the frozen section diagnosis by the neuropathologist was “neoplasm identified, favor melanoma.” Due to the paucity of lesional tissue, a limited immunohistochemistry performed on the permanent sections revealed positive staining of lesional cells for Sox10 alone using a multiplex MART1/Sox10 immunostain and S‐100 protein, an immunohistochemical profile supporting the presumptive frozen section diagnosis. A tumor debulk procedure, performed two weeks later, revealed histopathologic features most compatible with GB, IDH wild‐type. Thus, additional immunohistochemistry on the permanent sections revealed positive staining of glial fibrillary acidic protein (GFAP), Sox10, and S‐100 protein as well as negative staining of gp100, a complex carbohydrate matrix protein in embryonic melanosomes, using a specific antibody HMB45. The concomitant occurrence of MM and GB in our patient underscores the association between these two entities. Our literature review suggests that the sporadic co‐occurrence of these two conditions is likely not serendipitous.     

Hepatitis C virus infection and primary hepatic large B-cell lymphoma: a non-fortuitous association. Case report and review of literature

We report a case of hepatitis C virus infection in association with primary hepatic large B-cell non-Hodgkin's lymphoma. Primary hepatic non-Hodgkin's lymphoma is a rare disease. Association of hepatitis C virus infection with primary hepatic B-cell non-hodgkin's lymphoma is probably not fortuitous. Indeed, in case of primary hepatic non-hodgkin's lymphoma' patients are often hepatitis C virus positive. Moreover, several studies have reported a high prevalence of chronic hepatitis C virus infection among patients with B-cell non-Hodgkin's lymphoma whatever the localization of the lymphoma. A recent study found a high rate of remission of a splenic form of lymphoma after treatment of hepatitis C virus infection. Our case report confirms the hypothesis of a key role of hepatitis C virus in the pathogenesis of various forms of B-cell lymphoproliferative disorders and in particular in primary hepatic lymphoma.     

Hockey Games and the Incidence of ST-Elevation Myocardial Infarction

Background

The association between diagnosed acute ST-elevation myocardial infarction (STEMI) and hockey games in the Canadian population is unknown.

Are the results of electrophysiological study different in patients with a pre-excitation syndrome, with and without syncope?

AIMS: Syncope in Wolff-Parkinson-White (WPW) syndrome may reveal an arrhythmic event or is not WPW syndrome related. The aim of the study is to evaluate the results of electrophysiological study in WPW syndrome according to the presence or not of syncope and the possible causes of syncope. METHODS AND RESULTS: Among 518 consecutive patients with diagnosis of WPW syndrome, 71 patients, mean age 34.5 +/- 17, presented syncope. Transoesophageal electrophysiological study in control state and after isoproterenol infusion was performed in the out-patient clinic. Atrioventricular re-entrant tachycardia (AVRT) was more frequently induced than in asymptomatic patients (n = 38, 53.5%, P < 0.01), less frequently than in those with tachycardia; atrial fibrillation (AF) and/or antidromic tachycardia (ATD) was induced in 28 patients (39%) more frequently (P < 0.05) than in asymptomatic patients or those with tachycardia. The incidence of high-risk form [rapid conduction over accessory pathway (AP) and AF or ATD induction] was higher in syncope group (n = 18, 25%, P < 0.001) than in asymptomatic subjects (8%) or those with tachycardias (7.5%). Maximal rate conducted over AP was similar in patients with and without syncope, and higher in patients with spontaneous AF, but without syncope. Results were not age-related. CONCLUSION: Tachycardia inducibility was higher in patients with syncope than in the asymptomatic group. The incidence of malignant WPW syndrome was higher in patients with syncope than in asymptomatic or symptomatic population, but the maximal rate conducted over AP was not higher and another mechanism could be also implicated in the mechanism of syncope.     

Inherited IL-17RC deficiency in patients with chronic mucocutaneous candidiasis

Chronic mucocutaneous candidiasis (CMC) is characterized by recurrent or persistent infections of the skin, nail, oral, and genital mucosae with Candida species, mainly C. albicans. Autosomal-recessive (AR) IL-17RA and ACT1 deficiencies and autosomal-dominant IL-17F deficiency, each reported in a single kindred, underlie CMC in otherwise healthy patients. We report three patients from unrelated kindreds, aged 8, 12, and 37 yr with isolated CMC, who display AR IL-17RC deficiency. The patients are homozygous for different nonsense alleles that prevent the expression of IL-17RC on the cell surface. The defect is complete, abolishing cellular responses to IL-17A and IL-17F homo- and heterodimers. However, in contrast to what is observed for the IL-17RA– and ACT1-deficient patients tested, the response to IL-17E (IL-25) is maintained in these IL-17RC–deficient patients. These experiments of nature indicate that human IL-17RC is essential for mucocutaneous immunity to C. albicans but is otherwise largely redundant.In humans, chronic mucocutaneous candidiasis (CMC) is characterized by infections of the skin, nail, digestive, and genital mucosae with Candida species, mainly C. albicans, a commensal of the gastrointestinal tract in healthy individuals (Puel et al., 2012). CMC is frequent in acquired or inherited disorders involving profound T cell defects (Puel et al., 2010b; Vinh, 2011; Lionakis, 2012). Human IL-17 immunity has recently been shown to be essential for mucocutaneous protection against C. albicans (Puel et al., 2010b, 2012; Cypowyj et al., 2012; Engelhardt and Grimbacher, 2012; Huppler et al., 2012; Ling and Puel, 2014). Indeed, patients with primary immunodeficiencies and syndromic CMC have been shown to display impaired IL-17 immunity (Puel et al., 2010b). Most patients with autosomal-dominant (AD) hyper-IgE syndrome (AD-HIES) and STAT3 deficiency (de Beaucoudrey et al., 2008; Ma et al., 2008; Milner et al., 2008; Renner et al., 2008; Chandesris et al., 2012) and some patients with invasive fungal infection and autosomal-recessive (AR) CARD9 deficiency (Glocker et al., 2009; Lanternier et al., 2013) or Mendelian susceptibility to mycobacterial diseases (MSMD) and AR IL-12p40 or IL-12Rβ1 deficiency (de Beaucoudrey et al., 2008, 2010; Prando et al., 2013; Ouederni et al., 2014) have low proportions of IL-17A–producing T cells and CMC (Cypowyj et al., 2012; Puel et al., 2012). Patients with AR autoimmune polyendocrine syndrome type 1 (APS-1) and AIRE deficiency display CMC and high levels of neutralizing autoantibodies against IL-17A, IL-17F, and/or IL-22 (Browne and Holland, 2010; Husebye and Anderson, 2010; Kisand et al., 2010, 2011; Puel et al., 2010a).These findings paved the way for the discovery of the first genetic etiologies of CMC disease (CMCD), an inherited condition affecting individuals with none of the aforementioned primary immunodeficiencies (Puel et al., 2011; Casanova and Abel, 2013; Casanova et al., 2013, 2014). AR IL-17RA deficiency, AR ACT1 deficiency, and AD IL-17F deficiency were described, each in a single kindred (Puel et al., 2011; Boisson et al., 2013). A fourth genetic etiology of CMCD, which currently appears to be the most frequent, has also been reported: heterozygous gain-of-function (GOF) mutations of STAT1 impairing the development of IL-17–producing T cells (Liu et al., 2011; Smeekens et al., 2011; van de Veerdonk et al., 2011; Hori et al., 2012; Takezaki et al., 2012; Tóth et al., 2012; Al Rushood et al., 2013; Aldave et al., 2013; Romberg et al., 2013; Sampaio et al., 2013; Soltész et al., 2013; Uzel et al., 2013; Wildbaum et al., 2013; Frans et al., 2014; Kilic et al., 2014; Lee et al., 2014; Mekki et al., 2014; Mizoguchi et al., 2014; Sharfe et al., 2014; Yamazaki et al., 2014). We studied three unrelated patients with CMCD without mutations of IL17F, IL17RA, ACT1, or STAT1. We used a genome-wide approach based on whole-exome sequencing (WES). We found AR complete IL-17RC deficiency in all three patients.     

Influence of Vancomycin Infusion Methods on Endothelial Cell Toxicity

Peripheral intravenous therapy is frequently used in routine hospital practice and, due to various factors, its most common side effect is phlebitis. The infusion of vancomycin is particularly associated with phlebitis despite its widespread use. French guidelines recommend central intravenous infusion for high concentrations of vancomycin, but peripheral intravenous therapy is often preferred in intensive care units. Methods of vancomycin infusion are either intermittent infusion or continuous infusion. A comparison of these methods under in vitro conditions simulating clinical use could result in better infusion efficacy. Human umbilical vein endothelial cells (HUVECs) were therefore challenged with clinical doses of vancomycin over a 24- to 72-h period using these infusion methods. Cell death was measured with the alamarBlue test. Concentration-dependent and time-dependent vancomycin toxicity on HUVECs was noted with a 50% lethal dose at 5 mg/ml after 24 h, reaching 2.5 mg/ml after 72 h of infusion, simulating long-term infusion. This toxicity does not seem to be induced by acidic pH. In comparing infusion methods, we observed that continuous infusion induced greater cell toxicity than intermittent infusion at doses higher than 1 g/day. The increasing use of vancomycin means that new guidelines are required to avoid phlebitis. If peripheral intravenous therapy is used to reduce infusion time, along with intermittent infusion, vein irritation and localized phlebitis may be reduced. Further studies have to be carried out to explore the causes of vancomycin endothelial toxicity.