Quantitative multiparameter assays to measure the effect of adjuvants on human antigen-specific CD8 T-cell responses

Large numbers and functionally competent T cells are required to protect from diseases for which antibody-based vaccines have consistently failed (1), which is the case for many chronic viral infections and solid tumors. Therefore, therapeutic vaccines aim at the induction of strong antigen-specific T-cell responses. Novel adjuvants have considerably improved the capacity of synthetic vaccines to activate T cells, but more research is necessary to identify optimal compositions of potent vaccine formulations. Consequently, there is a great need to develop accurate methods for the efficient identification of antigen-specific T cells and the assessment of their functional characteristics directly ex vivo. In this regard, hundreds of clinical vaccination trials have been implemented during the last 15 years, and monitoring techniques become more and more standardized.

Absence of prosthesis-patient mismatch with the new generation of Edwards stented aortic bioprosthesis

Prosthesis-patient mismatch (PPM) remains a controversial issue with the most recent stented biological valves. We analyzed the incidence of PPM after implantation of the Carpentier-Edwards Perimount Magna Ease aortic valve (PMEAV) bioprosthesis and assessed the early clinical outcome. Two hundred and seventy consecutive patients who received a PMEAV bioprosthesis between January 2007 and July 2008 were analyzed. Pre-, peri- and postoperative data were assessed and echocardiographic as well as clinical follow-up was performed. Mean age was 72+/-9 years, 168 (62.2%) were males. Fifty-seven patients (21.1%) were below 65 years of age. Absence of PPM, corresponding to an indexed effective orifice area >0.85 cm(2)/m(2), was 99.5%. Observed in-hospital mortality was 2.2% (six patients), with a predicted mortality according to the additive EuroSCORE of 7.6+/-3.1%. At echocardiographic assessment after a mean follow-up period of 150+/-91 days, mean transvalvular gradient was 11.8+/-4.8 mmHg (all valve sizes). No paravalvular leakage was seen. Nine patients died during follow-up. The Carpentier-Edwards PMEAV bioprosthesis shows excellent hemodynamic performance. This valve can be implanted in all sizes with an incidence of severe PPM below 0.5%.

Gender-related differences in patients undergoing mechanical aortic valve replacement with the CarboMedics valve

The aim of this paper was to evaluate gender-related differences in patients undergoing mechanical aortic valve replacement with the CarboMedics valve.

Two-year clinical follow-up from the randomized comparison of biolimus-eluting stents with biodegradable polymer and sirolimus-eluting stents with durable polymer in routine clinical practice

Objectives This study sought to investigate safety and efficacy of biolimus-eluting stents (BES) with biodegradable polymer as compared with sirolimus-eluting stents (SES) with durable polymer through 2 years of follow-up. Background BES with a biodegradable polymer provide similar efficacy and safety as SES with a durable polymer at 9 months. Clinical outcomes beyond the period of biodegradation of the polymer used for drug release and after discontinuation of dual antiplatelet therapy are of particular interest. Methods A total of 1,707 patients were randomized to unrestricted use of BES (n = 857) or SES (n = 850) in an all-comers patient population. Results At 2 years, BES remained noninferior compared with SES for the primary endpoint, which was a composite of cardiac death, myocardial infarction, or clinically indicated target vessel revascularization (BES 12.8% vs. SES 15.2%, hazard ratio [HR]: 0.84, 95% confidence interval [CI]: 0.65 to 1.08, pnoninferiority < 0.0001, psuperiority = 0.18). Rates of cardiac death (3.2% vs. 3.9%, HR: 0.81, 95% CI: 0.49 to 1.35, p = 0.42), myocardial infarction (6.3% vs. 5.6%, HR: 1.12, 95% CI: 0.76 to 1.65, p = 0.56), and clinically indicated target vessel revascularization (7.5% vs. 8.6%, HR: 0.86, 95% CI: 0.62 to 1.20, p = 0.38) were similar for BES and SES. The rate of definite stent thrombosis through 2 years was 2.2% for BES and 2.5% for SES (p = 0.73). For the period between 1 and 2 years, event rates for definite stent thrombosis were 0.2% for BES and 0.5% for SES (p = 0.42). After discontinuation of dual antiplatelet therapy, no very late definite stent thrombosis occurred in the BES group. Conclusions At 2 years of follow-up, the unrestricted use of BES with a biodegradable polymer maintained a similar safety and efficacy profile as SES with a durable polymer. (Limus Eluted From a Durable Versus Erodable Stent Coating [LEADERS]; NCT00389220)

Schmerzmanagement bei Kindern in der Schweiz

Hintergrund Schmerzen bei stationär aufgenommenen Kindern werden häufig unzureichend behandelt. Bisher gab es keine Informationen zum Schmerzmanagement von Kinderkrankenhäusern in der Schweiz. Ziel der vorliegenden Studie war, den aktuellen Stand der Schmerzerfassung, -interpretation und -behandlung zu bestimmen. Studiendesign Ein Fragebogen wurde an alle pädiatrischen Krankenhäuser in der Schweiz gesendet. Ergebnisse Insgesamt antworteten 27 von 45 Einheiten (Antwortrate: 60%). Die meisten Abteilungen verwenden Schmerzerfassungstools (96%) und führten diesbezügliche Leitlinien ein (78%). Die Behandlung von Schmerzen erfolgt ebenfalls meist nach hausinterner Leitlinie (78%). Prozedurale und postoperative Schmerzen werden stets (100%) analgetisch behandelt. Bei Frühgeborenen und Kindern auf Intensivpflegestationen werden bei invasiven Eingriffen häufig Analgetika (> 87%) verwendet. Auf Intensivstationen liegen in 44% diesbezügliche Leitlinien vor. Resümee Der Nutzen eines effektiven Schmerzmanagements bei Kindern ist eindeutig belegt. Viele Ansätze zur Verbesserung werden in der Schweiz gut umgesetzt. Vor allem im internationalen Vergleich verbesserte sich das Schmerzmanagement. Es gibt aber noch Optimierungsmöglichkeiten. Beispielsweise besitzen weniger als die Hälfte aller schweizerischen Intensivstationen eine Leitlinie für die Behandlung von Schmerzen bei invasiven Eingriffen.

Assessment of Potential Orthodontic Mini-implant Insertion Sites Based on Anatomical Hard Tissue Parameters: A Systematic Review

To estimate the applicability of potential sites for insertion of orthodontic mini-implants (OMIs) by a systematic review of studies that used computed tomography (CT) or cone beam CT to evaluate anatomical bone quality and quantity parameters, such as bone thickness, available space, and bone density.

National institutes of health stroke scale score and vessel occlusion in 2152 patients with acute ischemic stroke

Background and Purpose—There is some controversy on the association of the National Institutes of Health Stroke Scale (NIHSS) score to predict arterial occlusion on MR arteriography and CT arteriography in acute stroke. Methods—We analyzed NIHSS scores and arteriographic findings in 2152 patients (35.4% women, mean age 66±14 years) with acute anterior or posterior circulation strokes. Results—The study included 1603 patients examined with MR arteriography and 549 with CT arteriography. Of those, 1043 patients (48.5%; median NIHSS score 5, median time to clinical assessment 179 minutes) showed an occlusion, 887 in the anterior (median NIHSS score 7/0–31), and 156 in the posterior circulation (median NIHSS score 3/0–32). Eight hundred sixty visualized occlusions (82.5%) were located centrally (ie, in the basilar, intracranial vertebral, internal carotid artery, or M1/M2 segment of the middle cerebral artery). NIHSS scores turned out to be predictive for any vessel occlusions in the anterior circulation. Best cut-off values within 3 hours after symptom onset were NIHSS scores ≥9 (positive predictive value 86.4%) and NIHSS scores ≥7 within >3 to 6 hours (positive predictive value 84.4%). Patients with central occlusions presenting within 3 hours had NIHSS scores <4 in only 5%. In the posterior circulation and in patients presenting after 6 hours, the predictive value of the NIHSS score for vessel occlusion was poor. Conclusions—There is a significant association of NIHSS scores and vessel occlusions in patients with anterior circulation strokes. This association is best within the first hours after symptom onset. Thereafter and in the posterior circulation the association is poor.

Puberty and microvascular function in healthy children and adolescents

To determine the role of pubertal status on microvascular function in healthy children and adolescents.

The Swiss Childhood Cancer Registry: rationale, organisation and results for the years 2001-2005

QUESTIONS UNDER STUDY: Childhood cancer is a rare but severe disease. Therefore central registration of all cases is essential for surveillance and management. This paper describes the methodology and basic results of the Swiss Childhood Cancer Registry (SCCR). METHODS: The SCCR was established in 1976, originally as a national hospital-based registry of childhood malignancies. All 9 paediatric oncology-haematology clinics in Switzerland provide baseline and follow-up information on all children diagnosed with cancer. These data are registered centrally and diagnoses are coded according to the International Classification of Childhood Cancer. RESULTS: From 2001-2005, 887 cases of childhood cancer in Swiss residents under the age of 15 years were registered in the SCCR. Of these, 281 (31.7%) were leukaemias, 223 (24.0%) were CNS tumours, and 116 (13.1%) were lymphomas. The age-standardised annual incidence per 1 Million person-years (age below 15 years; world standardisation) was 154.0 (95% CI 143.7-164.3; N = 887). The incidence was higher for boys (170.2, 155.0-185.4; N = 501) than for girls (136.9, 123.0-150.8; N = 386). CONCLUSION: The close collaboration between all paediatric oncologists-haematologists in Switzerland and a university department allowed the creation of a national population-based cancer registry with detailed clinical information. The SCCR produces cancer type specific incidence and survival estimates and allows the development of nested research projects on childhood cancer aetiology, management and outcome, both on a national and on an international level.

Molecular characterisation of BSR4, a novel bradyzoite-specific gene from Neospora caninum

Here we present the identification and cloning of the NcBSR4 gene, the putative Neospora caninum orthologue to the Toxoplasma gondii TgBSR4 gene. To isolate NcBSR4, genome walking PCR was performed on N. caninum genomic DNA using the expressed sequence tag NcEST3c28h02.y1 sequence, which shares a 44% identity with the TgBSR4 gene, as a framework. Nucleotide sequencing of amplified DNA fragments revealed a single uninterrupted 1227 bp open reading frame that encodes a protein of 408 amino acids with 66% similarity to the TgBSR4 antigen. A putative 39-residue signal peptide was found at the NH2-terminus, followed by a hydrophilic region. At the COOH-terminus, a potential site for a glycosylphosphatidylinositol anchor was identified at amino acid 379. A polyclonal serum against recombinant NcBSR4 protein was raised in rabbits, and immunolabelling demonstrated stage-specific expression of the NcBSR4 antigen in N. caninum bradyzoites produced in vitro and in vivo. Furthermore, RT-PCR analysis showed a slight increase of NcBSR4 transcripts in bradyzoites generated during in vitro tachyzoite-to-bradyzoite stage-conversion, suggesting that this gene is specifically expressed at the bradyzoite stage and that its transcription relies on the switch to this stage.