Hepatitis C virus as possible etiologic factor in idiopathic nephrotic syndrome among Egyptian patients

Hepatitis C virus (HCY) infection is associated with a variety of extrahepatic disorders. including cryoglobulinaernia and glomerulonephritis. Hepatitis C virus (HCV) glornerulopathy may be present as a primary glomerular disease. Our study included 50 adult Egyptian patients who were diagnosed as idiopathic nephrotic syndrome (NS). We described the clinical, pathological and immunological features of these patients. There was a high prevalence (50%) of HCV infection among these patients. The studied risk factors included history of; blood transfusion (16%) operation (24%) or antibilharzial drugs (76%). Hepatomegaly was observed in 24% of cases.Mernbranoproliferative glomerulonephritis (MPGN) was the commonest pathological  type associated with HCV (48%). Other patterns included focal segmental glomerulosclerosis (FSGS) in 32%, membranous in 8% and minimal change glomerulonephritis in 12%. Cryoglobulins were detected in 5.6% of 18 patients with HCV and idiopathic NS.Patients having HCV infection and membranoproliferative glomerulonephritis had hypocomplementemia and antinuclear antibodies were detected in 41.6%.Realising that HCV infection may be linked to different glomerulopathies, thus routine screening for HCV should be considered in serologic work-up of patients with glomerulopathy. Nevertheless, seroepiderniological studies including larger number of patients with glornerulopathy are therefore necessary to specify its relation with HCV infection

Anaphylaxis triggers in a large tertiary care hospital in Qatar: a retrospective study

Anaphylaxis is a serious allergic disease that may lead to death if not immediately recognized and treated. Triggers of anaphylaxis including food, drugs, and insect stings can vary widely. The incidence of anaphylaxis seems to be affected by age, sex, atopy, and geographic location. This study aims to examine the common triggers of anaphylaxis in Qatar. A total of 1068 electronic medical records were audited using power chart system: 446 from the medical coding system of anaphylaxis and 622 from the epinephrine auto-injectors (EAIs) dispensed during January 2012-December 2017. Of 1068 patients, 574 (53.5%) had anaphylaxis; male to female ratio was 1.2, and 300 patients (77.9%) were less than 10 years old. The common triggers were food ( = 316, 55.0%), insect stings ( = 161, 28.0%), and drugs ( = 103, 17.9%). Common anaphylaxis food triggers were nuts ( = 173, 30.1%), eggs ( = 89, 15.5%), and seafood ( = 72, 12.5%), and common anaphylaxis medication triggers were antibiotics ( = 49, 8.5%) and nonsteroidal anti-inflammatory drugs ( = 30, 5.2%). Interestingly, 135 anaphylactic patients (23.5%) were due to black ant stings. The anaphylaxis triggers varied significantly between children and adults. Among children (less than 10 years), three quarters of the events were triggered by food (223, 74.3%) while among adults (20-55 years), insect stings ( = 59, 43.0%) and drugs ( = 44, 32.0%) were dominant. This is the first national study stratifying anaphylaxis triggers among different age groups in Qatar. This study will serve as a guide for clinical practice in allergy clinics in Qatar and will help to assess future trends of anaphylaxis in Qatar

The Burden of Revision Sinonasal Surgery in the UK – Data from the Chronic Rhinosinusitis Epidemiology Study (CRES); a cross sectional study

Objectives/Hypothesis The aim of this study was to investigate the surgical revision rate in patients with Chronic Rhinosinusitis (CRS) in the UK CRS Epidemiology Study (CRES). Previous evidence from national Sinonasal Audit showed that 1459 CRS patients demonstrated a surgical revision rate 19.1% at 5 years, with highest rates seen in those with polyps (20.6%). Setting Thirty secondary care centres around the UK. Participants A total of 221 controls and 1249 patients with CRS were recruited to the study including those with polyps (CRSwNPs), without polyps (CRSsNPs) and with allergic fungal rhinosinusitis (AFRS). Interventions Self-administered questionnaire. Primary outcome measure The need for previous sinonasal surgery. Results A total of 651 patients with CRSwNPs, 553 with CRSsNPs and 45 with AFRS were included. A total of 396 (57%) of patients with CRSwNPs/AFRS reported having undergone previous endoscopic nasal polypectomy (ENP), of which 182 of the 396 (46%) reported having received more than one operation. The mean number of previous surgeries per patient in the revision group was 3.3 (range 2 to 30) and a mean duration of time of 10 years since the last procedure. The average length of time since their first operation up to inclusion in the study was 15.5 years (range 0-74). Only 27.9% of all patients reporting a prior ENP had received concurrent endoscopic sinus surgery (ESS) (n=102). For comparison, surgical rates in patients with CRSsNPs were significantly lower; 13% of cases specifically reported ESS and of those only 30% reported multiple procedures (chi-squared p < 0.001). Conclusions This study demonstrated there is a high burden of both primary and revision surgery in patients with CRS, worst in those with AFRS and least in those with CRSsNPs. The burden of revision surgery appears unchanged in the decade since the Sinonasal Audit

Safety and Efficacy of miltefosine alone and in combination with sodium stibogluconate and liposomal amphotericin B for the treatment of primary visceral leishmaniasis in East Africa: study protocol for a randomized controlled trial

<p>Abstract</p> <p>Background</p> <p>Treatment options for Visceral Leishmaniasis (VL) in East Africa are far from satisfactory due to cost, toxicity, prolonged treatment duration or emergence of parasite resistance. Hence there is a need to explore alternative treatment protocols such as miltefosine alone or in combinations including miltefosine, sodium stibogluconate (SSG) or liposomal amphotericin B. The aim of this trial is to identify regimen(s) which are sufficiently promising for future trials in East Africa.</p> <p>Methods/Design</p> <p>A phase II randomized, parallel arm, open-labelled trial is being conducted to assess the efficacy of each of the three regimens: liposomal amphotericin B with SSG, Liposomal amphotericin B with miltefosine and miltefosine alone. The primary endpoint is cure at day 28 with secondary endpoint at day 210 (6 months). Initial cure is a single composite measure based on parasitologic evaluation (bone marrow, spleen or lymph node aspirate) and clinical assessment. Repeated interim analyses have been planned after recruitment of 15 patients in each arm with a maximum sample size of 63 for each. These will follow group-sequential methods (the triangular test) to identify when a regimen is inadequate (<75% efficacy) or adequate (>90% efficacy). We describe a method to ensure consistency of the sequential analysis of day 28 cure with the non-sequential analysis of day 210 cure.</p> <p>Discussion</p> <p>A regimen with adequate efficacy would be a candidate for treatment of VL with reasonable costs. The design allows repeated testing throughout the trial recruitment period while maintaining good statistical properties (Type I & II error rates) and reducing the expected sample sizes.</p> <p>Trial Registration</p> <p>ClinicalTrials.gov: <a href="http://www.clinicaltrials.gov/ct2/show/NCT01067443">NCT01067443</a></p

The regulation of RhoA at focal adhesions by StarD13 is important for astrocytoma cell motility

Malignant astrocytomas are highly invasive into adjacent and distant regions of the normal brain. Rho GTPases are small monomeric G proteins that play important roles in cytoskeleton rearrangement, cell motility, and tumor invasion. In the present study, we show that the knock down of StarD13, a GTPase activating protein (GAP) for RhoA and Cdc42, inhibits astrocytoma cell migration through modulating focal adhesion dynamics and cell adhesion. This effect is mediated by the resulting constitutive activation of RhoA and the subsequent indirect inhibition of Rac. Using Total Internal Reflection Fluorescence (TIRF)-based Förster Resonance Energy Transfer (FRET), we show that RhoA activity localizes with focal adhesions at the basal surface of astrocytoma cells. Moreover, the knock down of StarD13 inhibits the cycling of RhoA activation at the rear edge of cells, which makes them defective in retracting their tail. This study highlights the importance of the regulation of RhoA activity in focal adhesions of astrocytoma cells and establishes StarD13 as a GAP playing a major role in this process

Single-dose liposomal amphotericin B (AmBisome®) for the treatment of Visceral Leishmaniasis in East Africa: study protocol for a randomized controlled trial

BACKGROUND: AmBisome® is an efficacious, safe anti-leishmanial treatment. There is growing interest in its use, either as a single dose or in combination treatments. In East Africa, the minimum optimal single-dosage has not been identified. METHODS/DESIGN: An open-label, 2-arm, non-inferiority, multi-centre randomised controlled trial is being conducted to determine the optimal single-dose treatment with AmBisome®.Patients in the single-dose arm will receive one infusion on day 1, at a dose depending on body weight. For the first group of patients entered to the trial, the dose will be 7.5 mg/kg, but if this dose is found to be ineffective then in subsequent patient series the dose will be escalated progressively to 10, 12.5 and 15 mg/kg. Patients in the reference arm will receive a multi-dose regimen of AmBisome® (3 mg/kg/day on days 1-5, 14 and 21: total dose 21 mg/kg). Patients will be hospitalised for approximately one month after the start of treatment and then followed up at three and six months. The primary endpoint is the status of patients six months after treatment. A secondary endpoint is assessment at day 30. Treatment success is determined as the absence of parasites on microscopy samples taken from bone marrow, lymph node or splenic aspirates. Interim analyses to assess the comparative efficacy of the single dose are planned after recruitment of 20 and 40 patients per arm. The final non-inferiority analysis will include 120 patients per arm, to determine if the single-dose efficacy 6 months after treatment is not more than 10% inferior to the multi-dose. DISCUSSION: An effective, safe single-dose treatment would reduce hospitalization and treatment costs. Results will inform the design of combination treatment studies. TRIAL REGISTRATION: ClinicalTrials.gov NCT00832208

Efficacy and Safety of AmBisome in Combination with Sodium Stibogluconate or Miltefosine and Miltefosine Monotherapy for African Visceral Leishmaniasis: Phase II Randomized Trial.

BACKGROUND: SSG&PM over 17 days is recommended as first line treatment for visceral leishmaniasis in eastern Africa, but is painful and requires hospitalization. Combination regimens including AmBisome and miltefosine are safe and effective in India, but there are no published data from trials of combination therapies including these drugs from Africa. METHODS: A phase II open-label, non-comparative randomized trial was conducted in Sudan and Kenya to evaluate the efficacy and safety of three treatment regimens: 10 mg/kg single dose AmBisome plus 10 days of SSG (20 mg/kg/day), 10 mg/kg single dose AmBisome plus 10 days of miltefosine (2.5mg/kg/day) and miltefosine alone (2.5 mg/kg/day for 28 days). The primary endpoint was initial parasitological cure at Day 28, and secondary endpoints included definitive cure at Day 210, and pharmacokinetic (miltefosine) and pharmacodynamic assessments. RESULTS: In sequential analyses with 49-51 patients per arm, initial cure was 85% (95% CI: 73-92) in all arms. At D210, definitive cure was 87% (95% CI: 77-97) for AmBisome + SSG, 77% (95% CI 64-90) for AmBisome + miltefosine and 72% (95% CI 60-85) for miltefosine alone, with lower efficacy in younger patients, who weigh less. Miltefosine pharmacokinetic data indicated under-exposure in children compared to adults. CONCLUSION: No major safety concerns were identified, but point estimates of definitive cure were less than 90% for each regimen so none will be evaluated in Phase III trials in their current form. Allometric dosing of miltefosine in children needs to be evaluated. TRIAL REGISTRATION: The study was registered with ClinicalTrials.gov, number NCT01067443

Maternal sildenafil for severe fetal growth restriction (STRIDER): a multicentre, randomised, placebo-controlled, double-blind trial

Background Severe early-onset fetal growth restriction can lead to a range of adverse outcomes including fetal or neonatal death, neurodisability, and lifelong risks to the health of the affected child. Sildenafil, a phosphodiesterase type 5 inhibitor, potentiates the actions of nitric oxide, which leads to vasodilatation of the uterine vessels and might improve fetal growth in utero. Methods We did this superiority, placebo-controlled randomised trial in 19 fetal medicine units in the UK. We used random computer allocation (1:1) to assign women with singleton pregnancies between 22 weeks and 0 days' gestation and 29 weeks and 6 days' gestation and severe early-onset fetal growth restriction to receive either sildenafil 25 mg three times daily or placebo until 32 weeks and 0 days' gestation or delivery. We stratified women by site and by their gestational age at randomisation (before week 26 and 0 days or at week 26 and 0 days or later). We defined fetal growth restriction as a combination of estimated fetal weight or abdominal circumference below tenth percentile and absent or reversed end-diastolic blood flow in the umbilical artery on Doppler velocimetry. The primary outcome was the time from randomisation to delivery, measured in days. This study is registered with BioMed Central, number ISRCTN 39133303. Findings Between Nov 21, 2014, and July 6, 2016, we recruited 135 women and randomly assigned 70 women to sildenafil and 65 women to placebo. We found no difference in the median randomisation to delivery interval between women assigned to sildenafil (17 days [IQR 7–24]) and women assigned to placebo (18 days [8–28]; p=0·23). Livebirths (relative risk [RR] 1·06, 95% CI 0·84 to 1·33; p=0·62), fetal deaths (0·89, 0·54 to 1·45; p=0·64), neonatal deaths (1·33, 0·54 to 3·28; p=0·53), and birthweight (−14 g,–100 to 126; p=0·81) did not differ between groups. No differences were found for any other secondary outcomes. Eight serious adverse events were reported during the course of the study (six in the placebo group and two in the sildenafil group); none of these were attributed to sildenafil. Interpretation Sildenafil did not prolong pregnancy or improve pregnancy outcomes in severe early-onset fetal growth restriction and therefore it should not be prescribed for this indication outside of research studies with explicit participants' consent. Funding National Institute for Health Research and Medical Research Council

Effects of antiplatelet therapy on stroke risk by brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases: subgroup analyses of the RESTART randomised, open-label trial

Background Findings from the RESTART trial suggest that starting antiplatelet therapy might reduce the risk of recurrent symptomatic intracerebral haemorrhage compared with avoiding antiplatelet therapy. Brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases (such as cerebral microbleeds) are associated with greater risks of recurrent intracerebral haemorrhage. We did subgroup analyses of the RESTART trial to explore whether these brain imaging features modify the effects of antiplatelet therapy

Sodium Stibogluconate (SSG) & Paromomycin Combination Compared to SSG for Visceral Leishmaniasis in East Africa: A Randomised Controlled Trial

Visceral leishmaniasis (VL) is a parasitic disease with about 500,000 new cases each year and is fatal if untreated. The current standard therapy involves long courses, has toxicity and there is evidence of increasing resistance. New and better treatment options are urgently needed. Recently, the antibiotic paromomycin (PM) was tested and registered in India to treat this disease, but the same dose of PM monotherapy evaluated and registered in India was not efficacious in Sudan. This article reports the results of a clinical trial to test the effectiveness of injectable PM either alone (in a higher dose) or in combination with sodium stibogluconate (SSG) against the standard SSG monotherapy treatment in four East African countries—Sudan, Kenya, Ethiopia and Uganda. The study showed that the combination of SSG &PM was as efficacious and safe as the standard SSG treatment, with the advantages of being cheaper and requiring only 17 days rather than 30 days of treatment. In March 2010, a WHO Expert Committee recommended the use of the SSG & PM combination as a first line treatment for VL in East Africa