Determination of sensitivity and specificity of a novel gene dosage assay for prenatal screening of trisomy 21 syndrome

ObjectiveTo compare the gene dosage results achieved by a novel multiplex quantitative assay with cytogenetic and quantitative fluorescent polymerase chain reaction (QF-PCR) analysis for prenatal screening of trisomy 21 syndrome on corresponding fetal samples.Design and methodsFetal samples (n = 134) were collected from pregnant women considered high risk for having trisomy 21 affected fetus. Cytogenetic analysis and QF-PCR were performed. Then, the relative gene dosage of DSCAM and DYRK1A2 genes was determined on corresponding samples using comparative delta cycle of threshold (ΔC_T) method.ResultsThe mean gene dosage ratio was 1.55 ± 0.11 (95% CI:1.51–1.58) in trisomy 21 cases and 1.01 ± 0.12 (95% CI:0.98–1.03) in normal samples (p value < 0.001). The results were in agreement to the results of cytogenetic and QF-PCR analysis with the overall specificity of 0.96 (95% CI:0.91–0.98) and the sensitivity of 0.80 (95% CI:0.49–0.94).ConclusionsThis gene dosage assay is appropriate for the screening of high risk pregnant women and is readily amenable to automation.     

Adrenal insufficiency due to primary bilateral adrenal non-Hodgkin's lymphoma.

A case of primary adrenal insufficiency, secondary to primary bilateral adrenal lymphoma is reported. A 50-year-old woman presented with features of primary adrenal insufficiency (darkening of skin, asthenia, anorexia, constipation) for at least 8 months. Clinical examination was unremarkable except for low body mass index and generalized skin and buccal mucosal pigmentation. Routine investigations including complete hemogram, serum chemistry, urine analysis, chest radiograph and electrocardiogram were normal; serum lactate dehydrogenase was moderately elevated. Primary adrenal insufficiency was confirmed on cortisol dynamics (very low basal and peak cortisol) after insulin-induced hypoglycemia. Routinely detected adrenal masses on ultrasonography were confirmed by contrast enhanced CT abdomen. A diagnosis of primary adrenal non- Hodgkin's lymphoma (B-cell) was made after exploratory laprotomy and further staging. The patient was put on combination chemotherapy (CHOP) protocol, but was lost to follow-up after receiving two cycles of treatment. Primary adrenal lymphoma, although a rare entity, needs to be suspected in patients with features of primary adrenal insufficiency who have evidence of bilateral adrenal masses on imaging.     

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.     

Comparison of bronchopulmonary collaterals and collateral blood flow in patients with chronic thromboembolic and primary pulmonary hypertension.

OBJECTIVE: To compare the visualisation of bronchopulmonary collaterals and bronchopulmonary collateral blood flow in patients with chronic thromboembolic pulmonary hypertension 2nd primary pulmonary hypertension. SETTING: Referral centre for cardiology at an academic hospital. PATIENTS: Nine patients with chronic thromboembolic pulmonary hypertension and 17 with primary pulmonary hypertension. INTERVENTIONS: Bronchopulmonary collaterals were visualised by selective bronchial arteriography or thoracic aortography. Bronchopulmonary collateral blood flow was estimated by injecting indocyanine green into the ascending aorta and sampling below the mitral valve from the left ventricle. RESULTS: The degree of pulmonary hypertension was comparable in the two groups. Large bronchopulmonary collaterals were visualised in all the patients with thromboembolic pulmonary hypertension who had bronchial arteriography or aortography or both. None of the primary pulmonary hypertension group studied by aortography had bronchopulmonary collaterals (P < < 0.001). All the patients with chronic thromboembolic pulmonary hypertension had significant bronchopulmonary collateral blood flow, which was (mean (SD)) 29.8 (18.6)% of the systemic blood flow. There was no recordable collateral blood flow in 11 of 15 patients with primary pulmonary hypertension. In the remaining four patients the mean value was 1.1 (1.8)% of the systemic blood flow (P < < 0.001). CONCLUSIONS: Visualisation of bronchopulmonary collaterals by thoracic aortography or by bronchial arteriography, or the demonstration of an increased bronchopulmonary collateral flow, helps to distinguish patients with chronic thromboembolic pulmonary hypertension from those with primary pulmonary hypertension.     

Prevalence of advanced liver fibrosis and steatosis in type-2 diabetics with normal transaminases: A prospective cohort study

BACKGROUND Nonalcoholic fatty liver disease(NAFLD)and type-2 diabetes mellitus(T2DM)have an intricate bidirectional relationship.Individuals with T2DM,not only have a higher prevalence of non-alcoholic steatosis,but also carry a higher risk of progression to nonalcoholic steatohepatitis.Experts still differ in their recommendations of screening for NAFLD among patients with T2DM.AIM To study the prevalence of NAFLD and advanced fibrosis among our patient population with T2DM.METHODS During the study period(November 2018 to January 2020),59 adult patients with T2DM and 26 non-diabetic control group individuals were recruited prospectively.Patients with known significant liver disease and alcohol use were excluded.Demographic data and lab parameters were recorded.Liver elastography was performed in all patients.RESULTS In the study group comprised of patients with T2DM and normal alanine aminotransferase levels(mean 17.8±7 U/L),81%had hepatic steatosis as diagnosed by elastography.Advanced hepatic fibrosis(stage F3 or F4)was present in 12%of patients with T2DM as compared to none in the control group.Patients with T2DM also had higher number of individuals with grade 3 steatosis[45.8%vs 11.5%,(P<0.00001)and metabolic syndrome(84.7%vs 11.5%,P<0.00001)].CONCLUSION A significant number of patients with T2DM,despite having normal transaminase levels,have NAFLD,grade 3 steatosis and advanced hepatic fibrosis as measured by liver elastography.     

Herpes Simplex Virus 1 and 2 Infections during Differentiation of Human Cortical Neurons

Herpes simplex virus 1 (HSV-1) and 2 (HSV-2) can infect the central nervous system (CNS) with dire consequences; in children and adults, HSV-1 may cause focal encephalitis, while HSV-2 causes meningitis. In neonates, both viruses can cause severe, disseminated CNS infections with high mortality rates. Here, we differentiated human induced pluripotent stem cells (iPSCs) towards cortical neurons for infection with clinical CNS strains of HSV-1 or HSV-2. Progenies from both viruses were produced at equal quantities in iPSCs, neuroprogenitors and cortical neurons. HSV-1 and HSV-2 decreased viability of neuroprogenitors by 36.0% and 57.6% (p < 0.0001), respectively, 48 h post-infection, while cortical neurons were resilient to infection by both viruses. However, in these functional neurons, both HSV-1 and HSV-2 decreased gene expression of two markers of synaptic activity, CAMK2B and ARC, and affected synaptic activity negatively in multielectrode array experiments. However, unaltered secretion levels of the neurodegeneration markers tau and NfL suggested intact axonal integrity. Viral replication of both viruses was found after six days, coinciding with 6-fold and 22-fold increase in gene expression of cellular RNA polymerase II by HSV-1 and HSV-2, respectively. Our results suggest a resilience of human cortical neurons relative to the replication of HSV-1 and HSV-2.     

Accessibility to biologics and its impact on disease activity and quality of life in patients with rheumatoid arthritis in Kuwait

Clinical Rheumatology - Biologics are indicated in rheumatoid arthritis (RA) in case of persistent high disease activity despite conventional disease-modifying anti-rheumatic drugs (cDMARDs) or...     

Impact of a high-density grid catheter on long-term outcomes for structural heart disease ventricular tachycardia ablation

Journal of Interventional Cardiac Electrophysiology - Substrate mapping has highlighted the importance of targeting diastolic conduction channels and late potentials during ventricular tachycardia...