Additional chromosome 1q aberrations and der(16)t(1;16), correlation to the phenotypic expression and clinical behavior of the Ewing family of tumors

The cytogenetic hallmark of the Ewing family of tumors is t(11;22)(q24;q12) in its simple, complex or variant forms and/or its molecular equivalent EWS/FLI, EWS/ERG rearrangement. Additional secondary consistent chromosomal aberrations include the der(16)t(1;16) and, frequently, other chromosome 1q abnormalities leading to 1q overdosage. We studied whether these secondary cytogenetic changes are correlated to clinical features and phenotypic expression which may have a prognostic impact.Successful cytogenetic evaluation was performed in eight patients with a Ewing family tumor. In four of these, in addition to the primary aberration, chromosome 1q overdosage (including two with der(16)t(1;16)) was noted. Out of these four patients, two had metastatic disease at the time of evaluation, while in the other four, disease was localized. Morphologically, the tumors with the additional 1q aberration, revealed the pPNET subtype more frequently than the typical Ewing. They also expressed a higher degree of neural differentiation by neural marker immunocytochemistry, in comparison to tumors without the 1q aberration.Determination of the prognostic significance of this finding requires a longer follow-up with a larger group of patients.     

Accuracy of ECG electrode placement by emergency department clinicians

Objectives: Misplaced ECG electrodes can cause changes in ECG recordings, which could have an impact on clinical decisions. We aimed to determine the inter‐rater reliability of ECG electrode placement by senior clinical staff in the ED. Methods: A prospective observational study was conducted in adult patients undergoing an ECG as part of their routine ED care. Adhesive electrodes were left in place after an ECG had been performed by the treating nurse, and subsequently each patient was assessed by two of the three investigators. Each investigator independently recorded the location of the chest electrodes relative to the recommended standard positions. Displacement of the electrodes from the standard positions was measured in the vertical and horizontal planes. The age, sex, weight, height and chest circumference was also recorded. Comparisons were made between investigators to determine variability in assessment of the standard positions. Results: Measurement of horizontal and vertical displacement for each of the six chest leads in the 77 patients resulted in 924 paired measurements. There was substantial inter‐rater variation in the measurement of both vertical (mean 13.5 mm, range 0–105 mm) and horizontal (mean 16.5 mm, range 0–120 mm) displacement. This variation was greater in the lateral chest leads and was more marked in women than in men, especially in the vertical plane (lead V6: men 14.5 mm vs women 27.0 mm, P < 0.01). Conclusion: Among clinical ‘experts’, there is wide variation in the identification of the correct location for electrode placement, particularly in the lateral leads and in women. This has significant implications when comparing ECG in which electrodes have been placed by different clinicians.     

Xenogenic bone matrix extracts induce osteoblastic differentiation of human bone marrow-derived mesenchymal stem cells

Colloss and Colloss-E are sterile acellular lyophilizates extracted from bovine and equine bone matrix, respectively. Animal and clinical studies have shown that these xenogenic bone matrix extracts (BMEs) are effective as bone graft substitutes. In this report, we investigated the effect of Colloss and Colloss-E on human adult in vitro-expanded bone marrow-derived mesenchymal stem cells (BMMSCs). Specifically, we assessed whether these xenogenic BMEs induced osteoblastic differentiation of cultured BMMSC. We show that BMMSCs treated with either Colloss or Colloss-E exhibited characteristic osteoblastic morphological changes accompanied by the expression of osteoblast-specific markers, such as alkaline phosphatase activity, osteopontin secretion and calcium deposits, explicitly demonstrating that these bone matrix extracts induce osteoblastic differentiation of BMMSCs in vitro. Hence, xenogenic BMEs induce bone-specific differentiation of BMMSCs, presumably through providing stem cells with structural and soluble mediators that mimic the in vivo microenvironment. These results may explain the in vivo mode of action of these medical devices, and potentially provide a novel tissue engineering-based treatment of bone defect, using autologous BMMSCs pretreated with BMEs.     

Cigarette and nargileh smoking practices among school students in Beirut, Lebanon

OBJECTIVES: To determine the prevalence and predictors of smoking nargileh and/or cigarettes among school students in Greater Beirut, Lebanon. METHODS: A proportionate random sample of 2443 students from 13 public and private schools was selected and asked to complete self-administered anonymous questionnaires. RESULTS: The prevalence of smoking cigarettes only, nargileh only, and both was 2.5%, 25.6%, and 6.3%, respectively. Stepwise regression analyses revealed that the predictors of smoking for either type are different, whereby nargileh smoking is more culturally accepted than cigarette smoking. CONCLUSIONS: Design interventions to increase awareness towards the hazards of the misconceived harmless effects of nargileh smoking.     

The risk of venous thromboembolism associated with the factor V Leiden mutation and low B-vitamin status.

Venous thromboembolism (VTE) is a multi-factorial disease involving numerous genetic and environmental risk factors. In this study we investigated the occurrence and the risk associated with factor V Leiden, hyperhomocysteinemia and low folate and vitamin B12 levels in young patients with thrombosis. We studied 78 patients (33 females/45 males, mean age 33 years) with a history of thrombosis in a lower limb. Additionally, 98 healthy subjects (45 females/54 males, mean age 44 years) were included. Serum levels of homocysteine (Hcy), folate and vitamin B12 were assayed. Factor V Leiden and methylenetetrahydrofolate reductase (MTHFR) C677T mutations were investigated in all subjects. Factor V Leiden was highly prevalent in the patients (39% heterozygous, 10% homozygous vs. 6.3% heterozygous in controls). An increase in the risk of idiopathic VTE was associated with Hcy levels > 15.2 micromol/l (odds ratio, OR = 2.83), folate < 15.1 nmol/l (OR = 7.49) and vitamin B12 < 182 pmol/l (OR = 11.97). Low levels of folate or vitamin B12 were independently and strongly associated with the risk of VTE in a multivariate model (OR for idiopathic thrombosis = 16.44 and 10.76, respectively). Twenty patients (53%), carriers of factor V Leiden, had low levels of vitamin B12, compared to 28% of patients who were non-carriers of the mutation (p = 0.03). In contrast, none of the control carriers of the mutation had a low level of vitamin B12. The risk of VTE associated with lower levels of vitamin B12 and folate was stronger than that introduced by elevated Hcy levels. The increased risk of VTE, accompanied by factor V Leiden, may be related to confounding environmental factors.     

Recurrent triploid digynic conceptions and mature ovarian teratomas: Are they different manifestations of the same genetic defect?

Miscarriages affect 15% of clinically recognized pregnancies. Recurrent miscarriage (RM) is defined by the occurrence of at least two consecutive pregnancy losses and affects 1%‐5% of couples trying to conceive. In an attempt to categorize patients with RM and identify the mechanisms leading to their miscarriages, we first used flow cytometry to assess the ploidy of 93 products of conception (POCs) from 53 patients with RM (≥3 miscarriages). We identified a single patient with four triploid POCs. We then used fluorescent in situ hybridization to confirm the triploidies and fluorescent microsatellite genotyping with distal and pericentromeric markers to determine their parental origin and the mechanisms leading to their formation. We found that all four triploidies were digynic and due to a failure in meiosis II (MII), suggesting a genetic predisposition. Upon further investigation into the family, we found a remarkable history of ovarian cysts and dysfunctions on the maternal side. Notably, one maternal cousin had a mature ovarian teratoma that we analyzed and found an identical mechanism at its origin, a failure in MII. The identification of two patients in the same family with two different manifestations—digynic triploid conceptions and mature ovarian teratomas, both resulting from the failure of MII—suggests an inherited genetic susceptibility toward an error in MII segregating in the family that may manifest in the form of a triploid digynic miscarriage or a mature ovarian teratoma. Our findings may facilitate the future identification of causative mutations for MII defects.     

Improving Emergency Department Door to Doctor Time and Process Reliability: A Successful Implementation of Lean Methodology

The aim of this study is to determine the effectiveness of using lean management methods on improving emergency department door to doctor times at a tertiary care hospital.We performed a before and after study at an academic urban emergency department with 49,000 annual visits after implementing a series of lean driven interventions over a 20 month period. The primary outcome was mean door to doctor time and the secondary outcome was length of stay of both admitted and discharged patients. A convenience sample from the preintervention phase (February 2012) was compared to another from the postintervention phase (mid-October to mid-November 2013). Individual control charts were used to assess process stability.Postintervention there was a statistically significant decrease in the mean door to doctor time measure (40.0 minutes ± 53.44 vs 25.3 minutes ± 15.93 P < 0.001). The postintervention process was more statistically in control with a drop in the upper control limits from 148.8 to 72.9 minutes. Length of stay of both admitted and discharged patients dropped from 2.6 to 2.0 hours and 9.0 to 5.5 hours, respectively. All other variables including emergency department visit daily volumes, hospital occupancy, and left without being seen rates were comparable.Using lean change management techniques can be effective in reducing door to doctor time in the Emergency Department and improving process reliability.     

The genetics of recurrent hydatidiform moles in Mexico: further evidence of a strong founder effect for one mutation in NLRP7 and its widespread

Journal of Assisted Reproduction and Genetics - To investigate the frequency of a founder mutation in NLRP7, L750V, in independent cohorts of Mexican patients with recurrent hydatidiform moles...