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.     

New inflammatory markers in pre-eclampsia: echocardiographic epicardial fat thickness and neutrophil to lymphocyte ratio

Background: Increased epicardial fat thickness (EFT) has been proposed as a new cardiometabolic risk factor. The neutrophil/lymphocyte ratio (NLR) has predictive and prognostic value in several cardiovascular diseases. The aim of this study was to explore the association between EFT and NLR in patients with pre-eclampsia.

Methods: Hundred and eight pregnant patients with a mean age of 30.6?±?6.3 years were included in the study. Patients were divided into two groups based on the presence of pre-eclampsia. All participants underwent transthoracic echocardiography imaging, and complete blood counts were measured by an automated hematology analyzer. Statistical analysis was performed using the Chi-square, Mann–Whitney U, correlation and logistic regression tests, and receiver operating characteristic (ROC) analysis.

Result: The mean EFT value of the pre-eclampsia group was significantly higher than the control group (6.9?±?0.6 versus 5.6?±?0.6; p?p?Conclusion: Unlike many other inflammatory markers and bioassays, NLR and echocardiographic EFT are inexpensive and readily available biomarkers that may be useful for risk stratification in patients with pre-eclampsia.     

Low Prevalence of Hepatitis C Virus Infection Among HIV-Positive Patients: Data From a Large-Scale Cohort Study in Istanbul,Turkey

Background:

Rate of coinfection with human immunodeficiency virus (HIV) and hepatitis C virus (HCV) varies in different countries. This may be attributable to common transmission routes as well as social, economic, and cultural factors.

Objectives:

The purpose of this study was to investigate the prevalence and risk factors of HCV infection among HIV-positive patients in Istanbul, Turkey.

Patients and Methods:

Since January 2006 to November 2013, 949 HIV-positive patients that were enrolled in this study by ACTHIV-IST (Action Against HIV in Istanbul) Study Group, which consists of five centers to follow up HIV-positive patients in Istanbul. Epidemiologic and clinical data were collected retrospectively from medical records and were transferred to an HIV database system.

Results:

Among 949 patients, 84% were men and the mean age was 37.92 ± 11.54 years (range, 17-79). The most frequent route of transmission was heterosexual intercourse (48.8%), followed by men having sex with men (30.5%). Only nine patients (0.9%) had history of injection drug use (IDU). The prevalence of HIV/HCV coinfection was 0.9% (9:949). The IDU rate was 44.4% (4:9) in patients with HIV/HCV coinfection (three of them were not Turkish citizens), whereas this rate was only 0.6% (5:881) in patients with only HIV infection (P < 0.01). Genotypes 1b, 2a/2c, and 3 were determined in five, one, and two patients, respectively. Genotype could not be determined in one patient. History of residence in a foreign country (P < 0.01) and imprisonment (P < 0.01) were also considered as risk factors in terms of HIV/HCV coinfection.

Conclusions:

Prevalence of HIV/HCV coinfection is considerably low in Turkey. The extremely rare prevalence of IDU might have a role in this low prevalence.     

Gemcitabine alone versus combination of gemcitabine and cisplatin for the treatment of patients with locally advanced and/or metastatic pancreatic carcinoma: a retrospective analysis of multicenter study

The majority of patients with pancreatic cancer is of advanced disease. Several randomized Phase II and III trials suggest that the combination of gemcitabine and cisplatin (GemCis) response rates were higher than Gemcitabine (Gem) alone, however the trials were not enough powered to indicate a statistically significant prolongation of survival in patients with advanced pancreatic adenocarcinoma. The aim of this retrospective multicenter study is to evaluated the efficiency of Gem alone versus GemCis in patients with locally advanced and/or metastatic pancreatic adenocarcinoma .A total of 406 patients, from fourteen centers were evaluated retrospectively. All patients received Gem or GemCis as first-line treatment between September 2005 to March 2011. Primary end of this study were to evaluate the toxicity, clinical response rate, progression-free survival (PFS) and overall survival (OS) between the arms. There were 156 patients (M: 98, F: 58) in Gem arm and 250 patients (M: 175, F: 75) in the combination arm. Gemcitabin arm patients older than the combination arm ( median 63 vs 57.5, p=0.001). In patients with the combination arm had a higher dose reduction (25.2% vs 11.3%, p=0.001) and dose delay (34% vs 16.8%, p=0.001). Among patients with the combination and Gemcitabin arm gender, diabetes mellitus, performance status, cholestasis, grade, stage did not have a statistically difference (p>0.05). Clinical response rate to the combination arm was higher than the Gem arm (69.0% vs 49.7%, p=0.001). PFS was more favorable in the GemCis arm than Gem alone, but the difference did not attain statistical significance (8.9 vs 6.0, p=0.08). OS was not significantly superior in the GemCis arm (12.0 vs 10.2, p>0.05). Grade III-IV hematologic and nonhematologic toxicity were higher in the combination arm. PFS was more favorable in the GemCis arm than Gem alone, but the difference did not attain statistical significance. OS was not significantly superior in the GemCis arm.     

Splenic Artery Transposition Graft Usage for the Supply of the Right Hepatic Artery: A Case Report

Hepatic artery aneurysms are responsible for 12% to 20% of all visceral arterial aneurysms. Because most patients are asymptomatic, this disease is generally diagnosed incidentally during radiologic examination. Aneurysm rupture develops in 14% to 80% of cases, depending on the aneurysmatic segment''s diameter and location, as well as other etiologic factors. Mortality rates associated with rupture range between 20% and 70%. Thus, early diagnosis and timely initiation of medical interventions are critical to improve survival rates. Here, we present a male patient, age 69 years, with a hepatic artery aneurysm that was detected incidentally. The 3-cm aneurysm was detected on contrast-enhanced computed tomography and extended from the common hepatic artery to the hepatic trifurcation. A laparotomy was performed using a right subcostal incision. After dissection of the hepatoduodenal ligament, the common, right, and left hepatic arteries, as well as the gastroduodenal artery, were suspended separately. Then, the aneurysmatic hepatic artery segment was resected, and the gastroduodenal artery stump was ligated. An end-to-end anastomosis was formed between the left and common hepatic arteries, followed by an end-to-end anastomosis formed between the right hepatic artery and splenic artery using a splenic artery transposition graft. Postoperative follow-up examinations showed that both hepatic arterial circulations were good, and no splenic infraction had developed.     

An electrophysiologic evaluation of whether open and laparoscopic techniques used in pediatric inguinal hernia repairs affect the genitofemoral nerve

Background

A prospective study was performed to evaluate the effect of inguinal hernia repairs on the genitofemoral nerve (GFN), and to compare postoperative electrophysiologic changes in the GFN of patients who had undergone either open or laparoscopic surgery.

Methods

Seventy patients with a mean age of 6.48 ± 3.49 were enrolled in the study. Either open or laparoscopic techniques were used to operate on the patients' inguinal hernias. In all cases, bilateral GFN motor responses were investigated electrophysiologically using surface electrodes on three occasions: preoperatively, in the first month, and third month postoperatively. t-Tests were used to compare changes in the GFN.

Results

Preoperative mean latency of the GFN in all groups was found to be significantly prolonged on the hernia side, compared with the non-hernia side (P = 0.01). Although no difference was observed in the latency levels of the GFN on the operated side at the preoperative and early postoperative stages, GFN latency levels decreased significantly in the late postoperative period in the laparoscopic group (P < 0.05). In the late postoperative period, amplitudes of GFN motor responses were significantly higher in the laparoscopic group than the open repair group (0.91 ± 0.11 mV and 0.57 ± 0.053 mV, respectively; P < 0.05).

Conclusion

Preoperative prolonged latency of GFN on the hernia side is likely to occur due to the pressure on the nerve caused by the hernia mass. By surgically removing the hernia mass, this buildup of pressure is prevented, decreasing the latency of the GFN. The significantly higher motor response amplitudes and decreased latency in the late postoperative stage for the laparoscopic group may be due to the fact that this technique is less invasive.     

Dilatation of the ascending aorta and serum alpha 1-antitrypsin level in patients with bicuspid aortic valve

Predictors of aortic dilatation are not well described in patients with bicuspid aortic valves (BAV). This study sought to examine the relationship between proximal aortic dilatation and matrix metalloproteinase-9 (MMP-9) and alpha 1-antitrypsin (α1AT) levels in patients with BAV. All patients underwent echocardiography using a standard protocol, and aortic measurements were taken in end-diastole. We studied 82 patients with BAV and categorized them into two groups according to aortic dimensions corrected for body surface area and age. The plasma level of α1AT was routinely determined using a BN ProSpec analyzer (Siemens Healthcare Diagnostics, Marburg, Germany), and that of MMP-9 were determined by ELISA (RayBiotech Inc. Norcross, GA, USA). Statistical analysis was performed using the Statistical Package for Social Sciences (SPSS; SPSS Inc., Chicago, IL, USA) software for Windows version 12. This study included patients with BAV with no or mild valvular impairment. There were no significant differences between groups in terms of gender, body surface area, associated hypertension, diabetes mellitus, hyperlipidemia, or smoking. The mean ascending aortic diameter was 4.38?±?0.5?mm in group 1 and 3.34?±?0.35?mm in group 2 (p?相似文献