[Sarcomas and mixed mesodermal tumors of the uterus]

Malignant mesodermal tumors of the uterus are an inhomogenous group of uterine malignancies with different pathogenesis, clinical presentation and prognosis. These rare tumors represent approximately 1 % of all uterine malignancies. The aggressive carcinosarcomas or mixed muellerian tumors are defined by mixed malignant epithelial and malignant mesodermal histopathology and are of the same precursor cell origin like endometrial cancer. Thus, carcinosarcomas were reclassified by the FIGO as an aggressive type of endometrial cancer and treated like type II endometrial cancer. Adenosarcomas are also mixed tumors with benign epithelial proliferation and malignant mesodermal cell growth, have a good prognosis and represent less than 5 % of all mesodermal uterine malignancies. Besides carcinosarcomas, the pure mesodermal leiomyosarcomas are the most common mesodermal malignancies. Patients with leiomyosarcamos are usually perimenopausal, and although more than half of the patients present with symptoms, diagnosis occurs incidentally in most cases in final histopathologic workup of an excised putative myoma or uterus. Adequate anamnesis, gynecologic examination and careful imaging by transvaginal ultrasound in the preoperative setting might hint to correct differential diagnosis in many cases. Overall the prognosis of uterine leiomyomas is poor. Malignancies of the endometrial stroma are very rare and divided in two subgroups, the mostly estrogen receptor positive endometrial stromal sarcoma, which occur preferably in premenopausal women and show a favorable prognosis, and the very aggressive undifferentiated endometrial sarcomas. The more rare undifferentiated endometrial sarcomas occur in postmenopausal women and most patients die in the first two years after diagnosis. Risk stratification of preoperative differential diagnosis requires improvements and the correct histopathologic workup of mesodermal uterine malignancies is still a challenge for pathologists.

Implantation of the biodegradable polymer biolimus-eluting stent in patients with high SYNTAX score is associated with decreased cardiac mortality compared to a permanent polymer sirolimus-eluting stent: two year follow-up results from the "all-comers" LEADERS trial

Background: The SYNTAX score (SXscore) has been shown to be an effective predictor of clinical outcomes in patients undergoing percutaneous coronary intervention (PCI). Methods and results: The SXscore was prospectively collected in 1,397 of the 1,707 patients enrolled in the “all-comers” LEADERS trial (patients post-surgical revascularisation were excluded). Post hoc analysis was performed by stratifying clinical outcomes at two-year follow-up, according to one of three SXscore tertiles: SXlow ≤8 (n=464), 816 (n=461). At two-year follow-up the rate of major adverse cardiovascular events was 18.4%, 12.0% and 9.4% in the SXhigh, SXmid, and SXlow tertile, respectively (HR 1.45; CI 1.21-1.74; p<0.01). There was a significantly higher rate of cardiac death in patients in the highest SXscore tertile (7% SXhigh versus 2.4% SXmid versus 1.8% SXlow; HR 2.22; CI 1.5-3.27; p<0.001). Within the SXhigh tertile the rate of cardiac death was significantly lower in patients treated with the biolimus-eluting stent compared with the sirolimus-eluting stent (4.7% versus 9.6%, HR 0.48; CI 0.23-0.99; p=0.046). Conclusions: The SXscore when applied to an “all-comers” patient population allows for prospective risk stratification of patients undergoing PCI up to two years follow-up. In addition, the SXscore appears to separate the performance of devices in high risk patient groups.

Rapid and highly specific screening for NPM1 mutations in acute myeloid leukemia

NPM1 mutations, the most frequent molecular alterations in acute myeloid leukemia (AML), have become important for risk stratification and treatment decisions for patients with normal karyotype AML. Rapid screening for NPM1 mutations should be available shortly after diagnosis. Several methods for detecting NPM1 mutations have been described, most of which are technically challenging and require additional laboratory equipment. We developed and validated an assay that allows specific, rapid, and simple screening for NPM1 mutations. FAST PCR spanning exons 8 to 12 of the NPM1 gene was performed on 284 diagnostic AML samples. PCR products were visualized on a 2 % agarose E-gel and verified by direct sequencing. The FAST PCR screening method showed a specificity and sensitivity of 100 %, i.e., all mutated cases were detected, and none of negative cases carried mutations. The limit of detection was at 5-10 % of mutant alleles. We conclude that the FAST PCR assay is a highly specific, rapid (less than 2 h), and sensitive screening method for the detection of NPM1 mutations. Moreover, this method is inexpensive and can easily be integrated in the routine molecular diagnostic work-up of established risk factors in AML using standard laboratory equipment.

Transcatheter aortic valve implantation: prevention and management of complications

Assessment of elderly patients with severe aortic stenosis and decisions in terms of management strategy (conservative with or without balloon aortic valvuloplasty, transcatheter aortic valve implantation (TAVI) or surgical aortic valve replacement) are complex and warrant a multidisciplinary approach involving collaboration between experienced cardiac surgeons, interventional cardiologists, cardiac imaging specialists, anaesthesiologists, geriatricians and a specialised nursing staff. Patient history, comorbid conditions, perioperative risk stratification as well as anatomical and procedural considerations require careful review on an individual, case-by-case basis and have a major impact on treatment allocation. The aims of this article are to provide insights into the fundamental role of appropriate patient screening and selection, and to review the nature, management and prevention of the most important procedural complications associated with the TAVI procedure.

Updated standardized endpoint definitions for transcatheter aortic valve implantation: the Valve Academic Research Consortium-2 consensus document

The aim of the current Valve Academic Research Consortium (VARC)-2 initiative was to revisit the selection and definitions of transcatheter aortic valve implantation (TAVI) clinical endpoints to make them more suitable to the present and future needs of clinical trials. In addition, this document is intended to expand the understanding of patient risk stratification and case selection.

Updated standardized endpoint definitions for transcatheter aortic valve implantation: the Valve Academic Research Consortium-2 consensus document (VARC-2)

The aim of the current Valve Academic Research Consortium (VARC)-2 initiative was to revisit the selection and definitions of transcatheter aortic valve implantation (TAVI) clinical endpoints to make them more suitable to the present and future needs of clinical trials. In addition, this document is intended to expand the understanding of patient risk stratification and case selection.

Updated standardized endpoint definitions for transcatheter aortic valve implantation: the Valve Academic Research Consortium-2 consensus document

The aim of the current Valve Academic Research Consortium (VARC)-2 initiative was to revisit the selection and definitions of transcatheter aortic valve implantation (TAVI)clinical endpoints to make them more suitable to the present and future needs of clinical trials. In addition, this document is intended to expand the understanding of patient risk stratification and case selection.

Updated standardized endpoint definitions for transcatheter aortic valve implantation: the Valve Academic Research Consortium-2 consensus document

The aim of the current Valvular Academic Research Consortium (VARC)-2 initiative was to revisit the selection and definitions of transcatheter aortic valve implantation (TAVI)- clinical endpoints to make them more suitable to the present and future needs of clinical trials. In addition, this document is intended to expand understanding of patient risk stratification and case selection.

A 10-year longitudinal analysis of surgical management for acute ischemic colitis

Our objective was to review our 10-year experience of surgical resection for acute ischemic colitis (IC) and to assess the predictive value of previously reported risk-stratification methods.

Registry for the Evaluation of the Prognostik value of a novel integrated imaging approach combining Single Photon Emission Computed Tomography with coronary calcification imaging (REPROSPECT)

AIMS: Although an added diagnostic and prognostic value of the global coronary artery calcification (CAC) score as an adjunct to single-photon emission computed tomography (SPECT)-myocardial perfusion image (MPI) has been repeatedly documented, none of the previous studies took advantage of the anatomic information provided by the unenhanced cardiac CT. Therefore, no co-registration has so far been used to match a myocardial perfusion defect with calcifications in the subtending coronary artery. To evaluate the prognostic value of integrating SPECT-MPI with CAC images were obtained from non-enhanced cardiac computed tomography (CT) for attenuation correction to predict major adverse cardiac events (MACE). METHODS AND RESULTS: Follow-up was obtained in 462 patients undergoing a 1-day stress/rest (99m)Tc-teterofosmin SPECT and non-enhanced cardiac CT for attenuation correction. Survival free of MACE was determined using the Kaplan-Meier method. After integrating MPI and CT findings, patients were divided into three groups (i) MPI defect matched by calcification (CAC ≥ 1) in the subtending coronary artery (ii) unmatched MPI and CT finding (iii) normal finding by MPI and CT. At a mean follow-up of 34.5 ± 13 months, a MACE was observed in 80 patients (33 death, 6 non-fatal myocardial infarction, 9 hospitalizations due to unstable angina, and 32 revascularizations). Survival analysis revealed the most unfavourable outcome (P < 0.001 log-rank test) for patients with a matched finding. CONCLUSION: In the present study, a novel approach using a combined integration of cardiac SPECT-CAC imaging allows for refined risk stratification, as a matched defect emerged as an independent predictor of MACE.

Prospective genetic screening decreases the incidence of abacavir hypersensitivity reactions in the Western Australian HIV cohort study

Abacavir therapy is associated with significant drug hypersensitivity in approximately 8% of recipients, with retrospective studies indicating a strong genetic association with the HLA-B*5701 allele. In this prospective study, involving 260 abacavir-naive individuals (7.7% of whom were positive for HLA-B*5701), we confirm the usefulness of genetic risk stratification, with no cases of abacavir hypersensitivity among 148 HLA-B*5701-negative recipients.

A simple presurgical necrotizing enterocolitis-mortality scoring system

OBJECTIVE: To assess the relationship between early laboratory parameters, disease severity, type of management (surgical or conservative) and outcome in necrotizing enterocolitis (NEC). STUDY DESIGN: Retrospective collection and analysis of data from infants treated in a single tertiary care center (1980 to 2002). Data were collected on disease severity (Bell stage), birth weight (BW), gestational age (GA) and pre-intervention laboratory parameters (leukocyte and platelet counts, hemoglobin, lactate, C-reactive protein). RESULTS: Data from 128 infants were sufficient for analysis. Factors significantly associated with survival were Bell stage (P<0.05), lactate (P<0.05), BW and GA (P<0.01, P<0.001, respectively). From receiver operating characteristics curves, the highest predictive value resulted from a score with 0 to 8 points combining BW, Bell stage, lactate and platelet count (P<0.001). At a cutoff level of 4.5 sensitivity and specificity for predicting survival were 0.71 and 0.72, respectively. CONCLUSION: Some single parameters were associated with poor outcome in NEC. Optimal risk stratification was achieved by combining several parameters in a score.

[Acute lower gastrointestinal bleeding--an evidence-based algorithm for diagnosis and treatment]

Novel means to locate and treat lower gastrointestinal bleeding (lGB) allow to reduce the rate of required surgical interventions and help to limit the extend of resection. The risk stratification of patients with lGB is the primary step of our recommended treatment algorithm. Accordingly, risk stratifying instruments, which are only partly validated up to now, are gaining significance in lGB. Whereas, gastro-duodenoscopy and colonoscopy prior to angiography or scintigraphy are established diagnostic tools, capsule enteroscopy offers a novel approach to hemodynamic stable patients with lGB that are difficult to localize. With its every increasing sensitivity, Angio-Computer Tomography is likely to replace scintigraphy and diagnostic angiography in the very near future. In addition, recent advances in superselective microembolisation have been shown to have the potential rendering surgical interventions in a majority of patients with acute lGB unnecessary. The extend of required surgical resection is largely dependent on the success to localize the bleeding source of prior diagnostics. Only if the source is identified, a limited segmental resection should be performed. Should surgery be required, we suggest to maintain the effort to localize the bleeding, either by prior laparoscopy and/or by intraoperative entero-colonoscopy. Eventually, if the source of bleeding remains unclear total colectomy with ileorectal anastomosis represents the procedure of choice in patients with acute lGB.

Multicentre evaluation of a new point-of-care test for the determination of NT-proBNP in whole blood

BACKGROUND: The Roche CARDIAC proBNP point-of-care (POC) test is the first test intended for the quantitative determination of N-terminal pro-brain natriuretic peptide (NT-proBNP) in whole blood as an aid in the diagnosis of suspected congestive heart failure, in the monitoring of patients with compensated left-ventricular dysfunction and in the risk stratification of patients with acute coronary syndromes. METHODS: A multicentre evaluation was carried out to assess the analytical performance of the POC NT-proBNP test at seven different sites. RESULTS: The majority of all coefficients of variation (CVs) obtained for within-series imprecision using native blood samples was below 10% for both 52 samples measured ten times and for 674 samples measured in duplicate. Using quality control material, the majority of CV values for day-to-day imprecision were below 14% for the low control level and below 13% for the high control level. In method comparisons for four lots of the POC NT-proBNP test with the laboratory reference method (Elecsys proBNP), the slope ranged from 0.93 to 1.10 and the intercept ranged from 1.8 to 6.9. The bias found between venous and arterial blood with the POC NT-proBNP method was < or =5%. All four lots of the POC NT-proBNP test investigated showed excellent agreement, with mean differences of between -5% and +4%. No significant interference was observed with lipaemic blood (triglyceride concentrations up to 6.3 mmol/L), icteric blood (bilirubin concentrations up to 582 micromol/L), haemolytic blood (haemoglobin concentrations up to 62 mg/L), biotin (up to 10 mg/L), rheumatoid factor (up to 42 IU/mL), or with 50 out of 52 standard or cardiological drugs in therapeutic concentrations. With bisoprolol and BNP, somewhat higher bias in the low NT-proBNP concentration range (<175 ng/L) was found. Haematocrit values between 28% and 58% had no influence on the test result. Interference may be caused by human anti-mouse antibodies (HAMA) types 1 and 2. No significant influence on the results with POC NT-proBNP was found using volumes of 140-165 muL. High NT-proBNP concentrations above the measuring range of the POC NT-proBNP test did not lead to false low results due to a potential high-dose hook effect. CONCLUSIONS: The POC NT-proBNP test showed good analytical performance and excellent agreement with the laboratory method. The POC NT-proBNP assay is therefore suitable in the POC setting.

Anemia is associated with abdominal aortic aneurysm (AAA) size and decreased long-term survival after endovascular AAA repair

OBJECTIVE: Anemia is a common comorbid condition in various inflammatory states and an established predictor of mortality in patients with chronic heart failure, ischemic heart disease, and end-stage renal disease. The present study of patients with abdominal aortic aneurysm (AAA) undergoing endovascular repair (EVAR) assessed the relationships between baseline hemoglobin concentration and AAA size, as well as anemia and long-term survival. METHODS: Between March 1994 and November 2006, 711 patients (65 women, mean age 75.8 +/- 7.8 years) underwent elective EVAR. Anemia was defined as a hemoglobin level <13 g/dL in men and <12 g/dL in women. Post-EVAR mean follow-up was 48.3 +/- 32.0 months. Association of hemoglobin level with AAA size was assessed with multiple linear regression. Mortality was determined with use of the internet-based Social Security Death Index and the electronic hospital record. Kaplan-Meier survival curves of anemic and nonanemic patient groups were compared by the log-rank method. Multivariable logistic regression models were used to determine the influence of anemia on vital status after EVAR. RESULTS: A total of 218/711 (30.7%) of AAA patients undergoing EVAR had anemia at baseline. After adjustment for various risk factors, hemoglobin level was inversely related to maximum AAA diameter (beta: - .144, 95%-CI: -1.482 - .322, P = .002). Post-EVAR survival was 65.5% at 5 years and 44.4% at 10 years. In long-term follow-up, survival was significantly lower in patients with anemia as compared to patients without anemia (P < .0001 by log-rank). Baseline hemoglobin levels were independently related to long-term mortality in multivariable Cox regression analysis adjusted for various risk factors (adjusted HR: 0.866, 95% CI: .783 to .958, P = .005). Within this model, statin use (adjusted HR: .517, 95% CI: .308 to .868, P = .013) was independently related to long-term survival, whereas baseline AAA diameter (adjusted HR: 1.022, 95% CI: 1.009 to 1.036, P = .001) was an independently associated with increased mortality. CONCLUSIONS: Baseline hemoglobin concentration is independently associated with AAA size and reduced long-term survival following EVAR. Thus, the presence or absence of anemia offers a potential refinement of existing risk stratification instruments.