European seroepidemiology network 2: Standardisation of assays for seroepidemiology of varicella zoster virus.

BACKGROUND: The aim of the European Sero-Epidemiology Network (ESEN2) is to harmonise the serological surveillance of vaccine-preventable diseases in Europe. OBJECTIVE: To allow comparison of antibody prevalence in different countries by standardising results into common units. STUDY DESIGN: For varicella zoster virus (VZV), a reference laboratory established a panel of 148 samples, characterised by indirect enzyme-immunoassay (ELISA), indirect immunofluorescence, and complement fixation test. Fifty-seven samples were also studied by the fluorescence antibody to membrane antigen test. The geometric mean of the antibody activity (GMAA) obtained from four ELISA determinations was used to characterise each sample of the panel as positive (GMAA: >100 mIU/ml), equivocal (GMAA: 50-100 mIU/ml) or negative (GMAA: <50 mIU/ml) for antibody to VZV (anti-VZV). Thirteen laboratories, using five different ELISA tests, tested the panel. RESULTS: Agreement with the reference laboratory was above 85% in all cases, and the R(2) values obtained from regression analysis of the quantitative results were always higher than 0.87. Finally, the regression equations could be used to convert national values into a common unitage. CONCLUSION: This study confirmed that results for anti-VZV obtained by different ELISA methods can be converted into common units, enabling the comparison of the seroprevalence profiles obtained in the participant countries.     

Prognostic Implications of Declining Hemoglobin Content in Patients Hospitalized With Acute Coronary Syndromes

BackgroundContemporary definitions of bleeding endpoints are restricted mostly to clinically overt events. Whether hemoglobin drop per se, with or without overt bleeding, adversely affects the prognosis of patients with acute coronary syndrome (ACS) remains unclear.ObjectivesThe aim of this study was to examine in the MATRIX (Minimizing Adverse Haemorrhagic Events by Transradial Access Site and Systemic Implementation of Angiox) trial the incidence, predictors, and prognostic implications of in-hospital hemoglobin drop in patients with ACS managed invasively stratified by the presence of in-hospital bleeding.MethodsPatients were categorized by the presence and amount of in-hospital hemoglobin drop on the basis of baseline and nadir hemoglobin values and further stratified by the occurrence of adjudicated in-hospital bleeding. Hemoglobin drop was defined as minimal (<3 g/dl), minor (≥3 and <5 g/dl), or major (≥5 g/dl). Using multivariate Cox regression, we modeled the association between hemoglobin drop and mortality in patients with and without overt bleeding.ResultsAmong 7,781 patients alive 24 h after randomization with available hemoglobin data, 6,504 patients (83.6%) had hemoglobin drop, of whom 5,756 (88.5%) did not have overt bleeding and 748 (11.5%) had overt bleeding. Among patients without overt bleeding, minor (hazard ratio [HR]: 2.37; 95% confidence interval [CI]: 1.32 to 4.24; p = 0.004) and major (HR: 2.58; 95% CI: 0.98 to 6.78; p = 0.054) hemoglobin drop were independently associated with higher 1-year mortality. Among patients with overt bleeding, the association of minor and major hemoglobin drop with 1-year mortality was directionally similar but had wider CIs (minor: HR: 3.53 [95% CI: 1.06 to 11.79]; major: HR: 13.32 [95% CI: 3.01 to 58.98]).ConclusionsAmong patients with ACS managed invasively, in-hospital hemoglobin drop ≥3 g/dl, even in the absence of overt bleeding, is common and is independently associated with increased risk for 1-year mortality. (Minimizing Adverse Haemorrhagic Events by Transradial Access Site and Systemic Implementation of Angiox; NCT01433627)     

Mechanisms of resistance to imatinib mesylate in gastrointestinal stromal tumors and activity of the PKC412 inhibitor against imatinib-resistant mutants

BACKGROUND AND AIMS: Resistance is a major challenge in the treatment of patients with gastrointestinal stromal tumors (GISTs). We investigated the mechanisms of resistance in patients with progressive GISTs with primary KIT mutations and the efficacy of the kinase inhibitor PKC412 for the inhibition of imatinib-resistant mutants. METHODS: We performed a cytogenetic analysis and screened for mutations of the KIT and PDGFRA kinase domains in 26 resistant GISTs. KIT autophosphorylation status was assessed by Western immunoblotting. Imatinib-resistant GIST cells and Ba/F3 cells expressing these mutant proteins were tested for sensitivity to imatinib and PKC412. RESULTS: Six distinct secondary mutations in KIT were detected in 12 progressive tumors, with V654A and T670I found to be recurrent. One progressive tumor showed acquired PDGFRA -D842V mutation. Amplification of KIT or KIT / PDGFRA was found in 2 patients. Eight of 10 progressive tumors available for analysis showed phosphorylated KIT. Two remaining progressive tumors lost KIT protein expression. GIST cells carrying KIT -del557-558/T670I or KIT -InsAY502-503/V654A mutations were resistant to imatinib, while PKC412 significantly inhibited autophosporylation of these mutants. Resistance to imatinib and sensitivity to PKC412 of KIT -T670I and PDGFRA -D842V mutants was confirmed using Ba/F3 cells. CONCLUSIONS: This study shows the high frequency of KIT/PDGFRA kinase domain mutations in patients with secondary resistance and defines genomic amplification of KIT / PDGFRA as an alternative cause of resistance to the drug. In a subset of patients, cancer cells lost their dependence on the targeted tyrosine kinase. Our findings show the sensitivity of the imatinib-resistant KIT -T670I and KIT -V654A and of PDGFRA -D842V mutants to PKC412.     

PROPHYLACTIC VS. SYMPTOMATIC THIRD MOLAR REMOVAL: EFFECTS ON PATIENT POSTOPERATIVE MORBIDITY

PurposeThe present study aimed to assess differences in postoperative morbidity between prophylactic and symptomatic third molar removals, and to assess the effect of age on the recovery of the patient.MethodsPatients admitted for third molar removal were prospectively followed up four times during treatment in context of the M3BE study. Data were collected through pre-, peri and postoperative surveys (days 3 and 10). Uni- and multivariable logistic regression was used to assess the probability of postoperative symptoms of discomfort on day 3 and day 10 according to several patient- and surgery-related predictive factors (age, gender, indication for removal, method of extraction, anesthesia and number of extracted maxillary and/or mandibular third molars).ResultsIn total, 6010 patients with a mean age of 25.2 (± 11.2) underwent 6347 surgeries to have 15,357 third molars removed. Frequently observed symptoms of postoperative discomfort were pain, trismus and swelling, all of which were transient in nature with steep decreases from postoperative days 3 to 10. Increasing age was associated with an enhanced risk of persistent pain, trismus and swelling and a significantly higher risk of iatrogenic injury to the inferior alveolar nerve. Symptomatic indications for removal were more common in patients over age 25 years, but these pre-existing pathologies did not compromise the postoperative recovery process. Other factors related to postoperative morbidity were female gender, intraoperative osteotomy and the number of extractions.ConclusionThe results of this study suggest that there are convincing patient- and surgery-related factors that favor timely third molar removal, preferably before the age of 25, especially in order to avoid persistent morbidity and nerve complications.     

Impact of Sex on Comparative Outcomes of Radial Versus Femoral Access in Patients With Acute Coronary Syndromes Undergoing Invasive Management: Data From the Randomized MATRIX-Access Trial

Objectives

This study sought to assess whether transradial access (TRA) compared with transfemoral access (TFA) is associated with consistent outcomes in male and female patients with acute coronary syndrome undergoing invasive management.

Echocardiography remains the standard for the diagnostic evaluation of left ventricular tumors: a case report with anatomical correlation.

Primary cardiac tumors are rare. Although the majority are benign, they may cause significant morbidity and mortality. Two-dimensional transthoracic echocardiography (2D-TTE) is the primary imaging modality for the diagnosis of cardiac tumors. New and more complex non-invasive imaging modalities, such as cardiac magnetic resonance (CMR), do not always provide an added value. This is illustrated in the presented case report of a papillary fibroelastoma (PFE).     

Hydrosurgery as a new non-excisional treatment method for giant congenital melanocytic nevi

Giant congenital melanocytic nevi (GCMN) are a source of esthetic embarrassment and psychosocial distress but may also be complicated by involvement of the central nervous system and malignant deformation. GCMN treatment remains a point of discussion. We suggest hydrosurgery as a new non-excisional treatment method for GCMN. Hydrosurgery has a lot of advantages in comparison to other non-excisional techniques. We were able to remove the epidermis and upper layer of the dermis of these GCMN in a more precise and controlled manner. The operation time was shorter, there was less blood loss, and shorter anesthesia times. Hydrosurgery is an easier and more controllable alternative to dermabrasion and curettage in the treatment of GCMN. Level of Evidence: Level V, therapeutic study.