Door to disposition times for obstetric triage visits: Is there a July phenomenon?

The July phenomenon refers to a change in patient outcomes within teaching hospitals with the arrival of new and inexperienced house staff at the start of the academic year (July to June). In our obstetric triage unit we retrospectively evaluated the door to disposition time (DTDT) for 1817 patients who presented across July, December and May of academic years 2009-2010 and 2010-2011. DTDT was examined for three visit levels: non-urgent, urgent and emergent. No significant differences in disposition time were found for emergent visits. For urgent visits the median DTDT significantly decreased from 171 min in July to 155 min in December and 135 min in May (p < 0.001). Similarly for non-urgent visits, the median DTDT was greater during July than May (179 min vs. 133 min; p < 0.05). Electronic medical records (EMRs) were implemented in November 2010. Following the introduction of EMR shorter DTDT was seen in December 2010 versus December 2009 (median, 171 min vs. 150 min; p < 0.05), respectively. Our findings suggest a 'July Phenomenon' of greater disposition intervals for urgent and non-urgent obstetric triage visits across the academic year. Additionally the use of EMRs may facilitate patient flow through the OB triage unit.

Extracellular vesicle-transported Semaphorin3A promotes vascular permeability in glioblastoma.

Glioblastoma are malignant highly vascularized brain tumours, which feature large oedema resulting from tumour-promoted vascular leakage. The pro-permeability factor Semaphorin3A (Sema3A) produced within glioblastoma has been linked to the loss of endothelial barrier integrity. Here, we report that extracellular vesicles (EVs) released by patient-derived glioblastoma cells disrupt the endothelial barrier. EVs expressed Sema3A at their surface, which accounted for in vitro elevation of brain endothelial permeability and in vivo vascular permeability, in both skin and brain vasculature. Blocking Sema3A or its receptor Neuropilin1 (NRP1) hampered EV-mediated permeability. In vivo models using ectopically and orthotopically xenografted mice revealed that Sema3A-containing EVs were efficiently detected in the blood stream. In keeping with this idea, sera from glioblastoma multiforme (GBM) patients also contain high levels of Sema3A carried in the EV fraction that enhanced vascular permeability, in a Sema3A/NRP1-dependent manner. Our results suggest that EV-delivered Sema3A orchestrates loss of barrier integrity in glioblastoma and may be of interest for prognostic purposes.

YGLF motif in the Kaposi sarcoma herpes virus G-protein-coupled receptor adjusts NF-κB activation and paracrine actions.

Kaposi sarcoma (KS) and primary effusion lymphoma (PEL) are two pathologies associated with KS herpes virus (KSHV/HHV-8) infection. KSHV genome contains several oncogenes, among which, the viral G-protein-coupled receptor (vGPCR open reading frame 74) has emerged as a major factor in KS pathogenicity. Indeed, vGPCR is a constitutively active receptor, whose expression is sufficient to drive cell transformation in vitro and tumour development in mice. However, neither the role of vGPCR in KSHV-infected B-lymphocytes nor the molecular basis for its constitutive activation is well understood. Here, we show that vGPCR expression contributes to nuclear factor-κB (NF-κB)-dependent cellular survival in both PEL cells and primary B cells from HIV-negative KS patients. We further identified within vGPCR an AP2 consensus binding motif, Y326GLF, that directs its localization between the plasma membrane and clathrin-coated vesicles. The introduction of a mutation in this site (Y326A) increased NF-κB activity and proinflammatory cytokines production. This correlated with exacerbated morphological rearrangement, migration and proliferation of non-infected monocytes. Collectively, our work raises the possibility that KSHV-infected B-lymphocytes use vGPCR to impact ultimately the immune response and communication within the tumour microenvironment in KSHV-associated pathologies.

Remodeling of VE-cadherin junctions by the human herpes virus 8 G-protein coupled receptor.

Kaposi Sarcoma (KS) are opportunistic tumors, associated with human herpes virus 8 (HHV8) infection. KS development is highly favored by immune-depression and remains the second most frequent tumor in acquired immune deficiency syndrome patients. Although it has been shown that experimental expression of the HHV8 G-protein-coupled receptor (vGPCR) in the endothelial compartment is alone sufficient to recapitulate the formation and progression of KS-like lesions, its functional effects on endothelial homeostasis are not fully understood. Here we show that vGPCR expression in endothelial cells induces an increase in paracellular permeability both in vivo and in vitro. By using pharmacological inhibitors and small interference RNA-based knockdown, we demonstrate an essential role for the PI(3)Kinase-γ/Rac nexus in vGPCR-mediated permeability. This was further accompanied by dramatic remodeling of VE-cadherin-dependent cell-cell junctions. Importantly, this in vitro vGPCR-initiated signaling signature was observed in a large panel of human KS. Altogether, our results support the hypothesis that endothelial vGPCR signaling is co-opted in KS, and unveil new key cellular targets for therapeutic intervention.

Increased mortality after coronary artery bypass graft surgery is associated with increased levels of postoperative creatine kinase-myocardial band isoenzyme release: results from the GUARDIAN trial.

OBJECTIVES: We sought to determine if elevated cardiac serum biomarkers after coronary artery bypass graft surgery (CABG) are associated with increased medium-term mortality and to identify patients that may benefit from better postoperative myocardial protection. BACKGROUND: The relationship between the magnitude of cardiac serum protein elevation and subsequent mortality after CABG is not well defined, partly because of the lack of large, prospectively studied patient cohorts in whom postoperative elevations of cardiac serum markers have been correlated to medium- and long-term mortality. METHODS: The GUARD during Ischemia Against Necrosis (GUARDIAN) study enrolled 2,918 patients assigned to the entry category of CABG and considered as high risk for myocardial necrosis. Creatine kinase-myocardial band (CK-MB) isoenzyme measurements were obtained at baseline and at 8, 12, 16 and 24 h after CABG. RESULTS: The unadjusted six-month mortality rates were 3.4%, 5.8%, 7.8% and 20.2% for patients with a postoperative peak CK-MB ratio (peak CK-MB value/upper limits of normal [ULN] for laboratory test) of < 5, > or = 5 to <10, > or =10 to < 20 and > or =20 ULN, respectively (p < 0.0001). The relationship remained statistically significant after adjustment for ejection fraction, congestive heart failure, cerebrovascular disease, peripheral vascular disease, cardiac arrhythmias and the method of cardioplegia delivery. Receiver operating characteristic curve analysis revealed an area under the curve of 0.648 (p < 0.001); the optimal cut-point to predict six-month mortality ranged from 5 to 10 ULN. CONCLUSIONS: Progressive elevation of the CK-MB ratio in clinically high-risk patients is associated with significant elevations of medium-term mortality after CABG. Strategies to afford myocardial protection both during CABG and in the postoperative phase may serve to improve the clinical outcome.

[Endoscopic aspect of ulcerated tumor-like gastritis associated with Helicobacter heilmannii]. / Aspect de gastrite ulcérée pseudo-tumorale due à Helicobacter heilmannii.

We report on 5 cases with an endoscopic aspect exceptionally described of ulcerated tumor-like gastritis associated with Helicobacter heilmannii. This rare but ubiquitary bacteria, belonging to the same family as Helicobacter pylori, is epidemiologically and structuraly different. When these endoscopic lesions are detected, Helicobacter heilmannii has to be looked for carefully. The treatment, which is the same than for Helicobacter pylori, must lead to complete repair of endoscopic and histologic lesions.

Screening for depression in pregnancy: characteristics of the Beck Depression Inventory.

OBJECTIVE: To determine the test characteristics of a self-report questionnaire, the Beck Depression Inventory, when used as a screening test for depression in a population of ambulatory pregnant women. METHODS: One hundred five pregnant women completed the Beck Depression Inventory and underwent a structured interview using the National Institute of Mental Health Diagnostic Interview Schedule-version III. Current depression was diagnosed according to the criteria of the Diagnostic and Statistical Manual of Mental Disorders-III-R. A receiver operating characteristic curve was constructed for the Beck Depression Inventory score as a predictor of current depression. A table of sensitivities, specificities, predictive values, and likelihood ratios was created for various cutoff values. RESULTS: For the 105 women enrolled, the median Beck Depression Inventory score was 8.0. Twelve women (11%) were diagnosed with current depression and had a median Beck Depression Inventory score of 25.5, compared with those without current depression, who had a median score of 8.0 (P = .001). The area under the receiver operating characteristic curve was 0.9940. Using a cutoff range of greater than 16, the sensitivity of the Beck Depression Inventory to detect current depression was 0.83, the specificity was 0.89, the positive predictive value was 0.50, and the negative predictive value was 0.98. CONCLUSIONS: The Beck Depression Inventory can serve as a rapid screening test for depression during pregnancy. A higher cutoff value is required for pregnant women than is customarily used outside of pregnancy.

Prevalence of depression in adults with diabetes. An epidemiological evaluation.

OBJECTIVE: To determine the prevalence of depression in adult diabetic populations through a comprehensive literature review and to critically evaluate the methods and findings of such studies from an epidemiological perspective. RESEARCH DESIGN AND METHODS: A systematic review of the scientific literature revealed a total of 20 studies, 14 of which had been conducted since 1988. Nine of the studies were controlled investigations, whereas the remaining 11 studies did not contain comparison groups. The studies included both treatment and community samples. RESULTS: The range of the prevalence of current depression obtained from structured diagnostic interviews in diabetic samples was 8.5-27.3% (mean = 14.0%) in controlled studies and 11.0-19.9% (mean = 15.4%) in uncontrolled studies. These rates are at least three times the prevalence of major depressive disorder found in the general adult population of the U.S. Investigations using depression symptom scales corroborated these findings, as the range of clinically significant depression symptomatology in diabetic samples was 21.8-60.0% (mean = 32.4%) in controlled studies and 10.0-28.0% (mean = 19.6%) in uncontrolled studies. CONCLUSIONS: An increased prevalence of depression in diabetes relative to the general population is highly suggested by the literature, but biases and methodological problems commonly encountered in prevalence studies may interfere with the strength of this conclusion. An increased prevalence of depression in diabetes relative to other somatic illnesses remains unproven. The pervasive impact of depression on quality of life and its potential negative effect on diabetes management warrant recognition and treatment of the affective disorder in diabetic individuals.

Depression in adults with diabetes.

Depression in diabetes is a prevalent and chronic condition. The etiology is unknown but is probably complex; and biological, genetic, and psychological factors remain as potential contributors. Several neuroendocrine and neurotransmitter abnormalities common to both depression and diabetes have been identified, adding to etiological speculations. Pharmacotherapy of depression may improve both mood and glucose regulation in diabetes, although controlled studies of the efficacy of psychotherapy and pharmacotherapy for depression in diabetes are not yet available. Depression has potential interactions with diabetes on multiple levels and remains an important clinical focus independent of the medical disease.

Sex differences in secondary attack rate of IDDM to siblings of probands through older ages. Pittsburgh Etiology of IDDM Study.

OBJECTIVE: To determine the descriptive epidemiological patterns of the secondary attack rate of insulin-dependent diabetes mellitus (IDDM) among siblings of probands through older ages. RESEARCH DESIGN AND METHODS: A family history analysis was performed on 1774 IDDM probands who were diagnosed or seen within 1 yr of diagnosis at Children's Hospital of Pittsburgh from 1 January 1950 through 31 December 1981. The probands were discharged on insulin and were diagnosed at less than 17 yr of age. The time frame permitted the risk of IDDM for siblings of probands to be calculated over a broad spectrum of age. RESULTS: Risk estimates for the 3966 full natural siblings through 10, 20, and 30 yr of age were 1.6, 4.1, and 6.3%, respectively. Secondary attack rates were equivalent for male and female siblings through 15 yr of age (3%); however, the risk to males increased an additional 4% between 16 and 30 yr of age compared with 2.5% for females (P = 0.01). There was no evidence of an excess sex concordance among affected sibling pairs. CONCLUSIONS: Males have a greater secondary attack rate of IDDM at older ages than females. This may be due to an increased exposure to environmental agents among males or protective influences operating among females.

Clustering of premature mortality in 1,761 insulin-dependent diabetics and their family members.

The clustering of premature mortality was investigated in 1,761 insulin-dependent diabetics and their family members from the Children's Hospital of Pittsburgh Insulin-Dependent Diabetes Mellitus Registry from 1950-1981. At follow-up, 5% of the mothers and 13% of the fathers were deceased. Life table analyses revealed that fathers of deceased diabetics were significantly more likely to die prematurely than fathers of living diabetics (18% vs. 8% at age 55 years; p = 0.02). A father-diabetic son concordance of mortality appeared to be responsible for this effect. A similar overall trend was observed for maternal mortality, although the difference was not statistically significant. Cause-specific analyses revealed that the increased paternal mortality was primarily the result of cardiovascular disease. Overall mortality rates of parents of deceased diabetics were higher than those of the general population, reaching statistical significance in the age group 35-44 years (p less than 0.05). Mortality among diabetic siblings was also examined. Diabetic siblings of deceased diabetics had a markedly increased risk of dying compared with diabetic siblings of living diabetics (p = 0.001). These findings indicate that premature mortality among both diabetic and nondiabetic relatives of diabetics clusters in families in which there is a deceased insulin-dependent diabetic, and suggest that the marked increase in mortality among persons with insulin-dependent diabetes may be partly under familial control.