Combined Multichannel Intraluminal Impedance-pH (MII-pH): Multicenter Report of Normal Values from 117 Children

Pancreatic cancer is the fourth leading cause of cancer deaths in the USA. Although some patients will present with premalignant pancreatic lesions (i.e., intraductal papillary mucinous neoplasms) or localized tumors amenable to curative resection, the majority of patients will unfortunately present with technically unresectable or metastatic disease. This review of the recent medical literature will discuss the optimal work-up and management of premalignant pancreatic lesions and the surgical management of localized, borderline resectable, and locally advanced (i.e., unresectable) pancreatic tumors. It will focus on new criteria used to define surgical “resectability,” the significance and clinical impact of surgical margins, the role of multimodality therapy in the management of patients with borderline resectable or locally advanced tumors, the role of surgery for local or distant recurrence, and minimally invasive surgical approaches.     

Central macular thickness in patients with sickle cell disease and no signs of retinopathy: a cross-sectional study of Jordanian patients

ObjectivesTo measure central macular thickness in Jordanian patients with sickle cell disease who did not have retinopathy and compare the findings with age- and sex-matched controls using spectral domain optical coherence tomography (SDOCT).MethodsIn this cross-sectional study, participants underwent visual acuity testing, slit-lamp bio-microscopy, dilated ophthalmoscopy, and SDOCT imaging to measure central macular thickness. Macular quadrant measurements and thickness difference indexes (TDIs) were compared between groups.ResultsTwenty eyes with sickle cell disease and 20 control eyes were enrolled. The median visual acuity in both groups was 20/20. The mean macular thickness was significantly lower in eyes with sickle cell disease than in matched controls (mean difference, 22.15 ± 6.44 µm). Peripheral quadrants were all significantly thinner in eyes with sickle cell disease, especially in superior and temporal quadrants. TDIs were lower in eyes with sickle cell disease than in control eyes.ConclusionsEyes with sickle cell disease that had no clinical evidence of retinopathy exhibited significantly lower central macular thickness in all quadrants, compared with eyes in age- and sex-matched controls. SDOCT is a non-invasive imaging modality that can detect preclinical changes in eyes with sickle cell disease and can be used to screen and monitor the disease process.     

Rapid Point-of-Contact Tool for Mapping and Integrated Surveillance of Wuchereria bancrofti and Onchocerca volvulus Infection

Elimination programs for Wuchereria bancrofti and Onchocerca volvulus are in critical need of sensitive, specific, and point-of-contact (POC) tools that can be used for surveillance years beyond cessation of mass drug administration when infection intensities are low. Previously, Wb123 and Ov16 were identified individually as potential filarial antigens for an antibody-based POC test. The present study compares single-antigen Wb123- and Ov16-based POC tests with an integrated configuration to detect antibodies to Wb123 and Ov16 simultaneously. Wb123 and Ov16 isolates were striped onto lateral flow strips containing anti-IgG4. Sera from W. bancrofti-, O. volvulus-, and other helminth-infected or -uninfected individuals were added to the strips with buffer. Strips were read for the appearance of a positive or negative test line for both antigens at 20 min and following drying. Sensitivity, specificity, and predictive values were calculated for the single-antigen and biplex strips. Single and biplex lateral flow strips showed nearly identical results, with >90% sensitivity for Ov16 and >92% sensitivity for Wb123. Overall specificities for the single and biplex tests were 98% and 96% for Ov16 and Wb123, respectively. Biplex tests performed as well as the single-antigen tests regardless of the intensity of patient IgG4 response. The high sensitivity and specificity make these new biplex tests extremely useful for POC long-term surveillance following mass drug administration in Africa that should reduce time and cost in areas where bancroftian filariasis and onchocerciasis are coendemic.     

Rapid Wuchereria bancrofti-Specific Antigen Wb123-Based IgG4 Immunoassays as Tools for Surveillance following Mass Drug Administration Programs on Lymphatic Filariasis

The Global Programme to Eliminate Lymphatic Filariasis has an urgent need for rapid assays to detect ongoing transmission of lymphatic filariasis (LF) following multiple rounds of mass drug administration (MDA). Current WHO guidelines support using the antigen card immunochromatographic test (ICT), which detects active filarial infection but does not detect early exposure to LF. Recent studies found that antibody-based assays better serve this function. In the present study, two tests, a rapid IgG4 enzyme-linked immunosorbent assay (ELISA) and a lateral-flow strip immunoassay, were developed based on the highly sensitive and specific Wuchereria bancrofti antigen Wb123. A comparison of W. bancrofti-infected and -uninfected patients (with or without other helminth infections) demonstrated that both tests had high sensitivities and specificities (93 and 97% [ELISA] and 92 and 96% [strips], respectively). When the W. bancrofti-uninfected group was separated into those with other filarial/helminth infections (i.e., onchocerciasis, loiasis, and strongyloidiasis) and those who were parasite uninfected, the specificities of the assays varied between 91 and 100%. In addition, the geometric mean response by ELISA of W. bancrofti-infected patients was significantly higher than the response of those without W. bancrofti infection (P < 0.0001). Furthermore, the Wb123 ELISA and the lateral-flow strips had high positive and negative predictive values, giving valuable information on the size of survey population needed to be reasonably certain whether or not transmission is ongoing. These highly sensitive and specific IgG4 tests to the W. bancrofti Wb123 protein give every indication that they will serve as useful tools for post-MDA monitoring.     

Hypo- and hyperglycemia predict outcome in patients with left ventricular dysfunction after acute myocardial infarction: data from EPHESUS

BackgroundHyperglycemia predicts death in cardiovascular disease, but intensive glucose-lowering strategies increase mortality rates in diabetes. The present analysis investigated the prognostic value of postadmission blood glucose (BG) concentration on clinical outcomes in high-risk patients with heart failure after acute myocardial infarction.Methods and ResultsA total of 6,496 patients from the Eplerenone Post–Acute Myocardial Infarction Heart Failure Efficacy and Survival Study (EPHESUS) were categorized into 4 groups by plasma glucose concentration: ≤4.5 mmol/L (hypoglycemia), 4.5–5.5 mmol/L (normoglycemia), 5.5–8.3 mmol/L (elevated glucose level), and >8.3 mmol/L (severe hyperglycemia). We evaluated the time to all-cause death (primary end point) and time to cardiovascular death or hospitalization (secondary end point). Hypo- and severe hyperglycemia were prevalent in 509 (8%) and 1,588 (24%) patients, respectively. There was a U-shaped relationship between BG level and incidence of all-cause death (11.8% in patients with normoglycemia vs 15.1% and 19.9% in those with hypo- and severe hyperglycemia; P < .001). The incidence of the secondary end point was increased only in hyperglycemic patients (36% vs 23% in normoglycemic patients; P < .001). In multivariate Cox regression analysis, hypoglycemia (hazard ratio [HR] 1.38, 95% confidence interval [CI] 1.06–1.81; P = .002) and severe hyperglycemia (HR 1.52, CI 1.27–1.83; P < .0001) proved to be strong predictors of all-cause death. There was no significant interaction between eplerenone treatment and blood glucose levels regarding clinical outcomes.ConclusionsIn heart failure after acute myocardial infarction, both hypo- and hyperglycemia at the postacute phase identify patients with increased risk of death during long-term follow-up.     

Genetic basis of neurodevelopmental disorders in 103 Jordanian families

We recruited 103 families from Jordan with neurodevelopmental disorders (NDD) and patterns of inheritance mostly suggestive of autosomal recessive inheritance. In each family, we investigated at least one affected individual using exome sequencing and an in-house diagnostic variant interpretation pipeline including a search for copy number variation. This approach led us to identify the likely molecular defect in established disease genes in 37 families. We could identify 25 pathogenic nonsense and 11 missense variants as well as 3 pathogenic copy number variants and 1 repeat expansion. Notably, 11 of the disease-causal variants occurred de novo. In addition, we prioritized a homozygous frameshift variant in PUS3 in two sisters with intellectual disability. To our knowledge, PUS3 has been postulated only recently as a candidate disease gene for intellectual disability in a single family with three affected siblings. Our findings provide additional evidence to establish loss of PUS3 function as a cause of intellectual disability.     

Beitrag zur Differentialdiagnose des Hirsutismus

Archives of Gynecology and Obstetrics - In 23 patients suffering from hirsutism, oestrogens, pregnandiol, FSR, 17-Ketosteroids and their fractions, the Thorn-test, cholesterol, sodium and potassium...     

Comparison of relative binding affinities of endocrine active compounds to fathead minnow and rainbow trout estrogen receptors

Twelve chemicals were tested for binding affinity to rainbow trout liver estrogen receptor (rbtER) and fathead minnow liver ER (fhmER). The chemicals included estradiol (E2), diethylstilbestrol (DES), ethinylestradiol (EE2), estrone (El), estriol, tamoxifen (TAM), genistein (GEN), p-nonylphenol (PNP), p-tert-octylphenol (PTOP), methoxychlor (MXC), testosterone, and methyltestosterone (MT). Relative binding affinity (RBA) was calculated for each chemical as a function of E2 binding to the receptor. The estrogens DES, EE2, and E1 bound with high affinity to both receptors, with respective RBAs of 583, 166, and 28% (fathead minnow) and 179, 89, and 5% (rainbow trout). Relative binding affinity of E3, TAM, and GEN for both fhmER and rbtER were moderate, with values between 0.3 and 5%. The alkylphenols had weak affinity for the ERs with RBAs for the fhmER of 0.1 and 0.01 for PNP and PTOP, respectively. Corresponding values for the rbtER are 0.027 and 0.009. Estradiol ([3H]E2) only partially was displaced from both the fhmER and the rbtER by MXC, T, and MT. Comparison of RBAs of the chemicals tested for fhmER and rbtER indicates that the rank order of RBAs essentially are the same for both species.