Low-grade endometrial stromal sarcoma with inferior vena cava tumor thrombus and intracardiac extension: radical resection may improve recurrence free survival

BACKGROUND: Endometrial stromal sarcoma (ESS) represents 0.2% of all uterine malignancies. Based on the mitotic activity, a distinction is made between low and high-grade ESS. Although the overall five-year survival rate for low-grade ESS exceeds 80%, about 50% of the patients show tumor recurrence, mostly after a long latency period. Tumor invasion of the great vessels is extremely rare. We describe a patient with advanced low-grade ESS with tumor invasion of the infrarenal aorta and the inferior vena cava. The patient presented with a large tumor thrombus extending from the inferior vena cava into the right atrium. METHODS: Review of literature and identification of 19 patients, including our own case report, with advanced low-grade ESS with invasion of the great vessels and formation of an inferior vena cava tumor thrombus. RESULTS: All 19 patients presented with an abdominal tumor mass and a tumor thrombus protruding into the inferior vena cava. The tumor thrombus extended into the right heart cavities in nine patients reaching the right atrium in four, the right ventricle in three and the pulmonary artery in two patients. There were 5 patients with an advanced primary tumor and 14 patients with an advanced recurrent tumor. Seven patients presented with synchronous metastatic disease and six patients with a pelvic tumor infiltrating the bladder, the rectosigmoid colon or the infrarenal aorta. Mean age at surgery was 45.9+/-12.3 years (median 47, range 25-65 years). Tumor thrombectomy was accomplished by cavatomy or by right atriotomy after installation of a cardiopulmonary bypass. There was no peri-operative mortality and a very low morbidity. Radical tumor resections were achieved in 10 patients. The follow-up for these 10 patients was 2+/-1.3 years (median 2, range 0.3-4.5 years). Nine patients remained recurrence free whereas one patient suffered an asymptomatic local recurrence. CONCLUSIONS: Low-grade ESS is a rare angioinvasive tumor with a high recurrence rate. Resection of an inferior vena cava tumor thrombus, even with extension into the right heart cavities, can be performed safely. Extensive radical surgery is therefore justified in the treatment of advanced tumor manifestations of a low-grade ESS potentially improving recurrence free survival.

The Prevention of cerebrovascular and cardiovascular Events of ischemic origin with teRutroban in patients with a history oF ischemic strOke or tRansient ischeMic attack (PERFORM) study: baseline characteristics of the population

BACKGROUND: The Prevention of cerebrovascular and cardiovascular Events of ischemic origin with teRutroban in patients with a history oF ischemic strOke or tRansient ischeMic attack (PERFORM) study is an international double-blind, randomized controlled trial designed to investigate the superiority of the specific TP receptor antagonist terutroban (30 mg/day) over aspirin (100 mg/day), in reducing cerebrovascular and cardiovascular events in patients with a recent history of ischemic stroke or transient ischemic attack. Here we describe the baseline characteristics of the population. METHODS AND RESULTS: Parameters recorded at baseline included vital signs, risk factors, medical history, and concomitant treatments, as well as stroke subtype, stroke-associated disability on the modified Rankin scale, and scores on scales for cognitive function and dependency. Eight hundred and two centers in 46 countries recruited a total of 19,119 patients between February 2006 and April 2008. The population is evenly distributed and is not dominated by any one country or region. The mean +/- SD age was 67.2 +/- 7.9 years, 63% were male, and 83% Caucasian; 83% had hypertension, and about half the population smoked or had quit smoking. Ninety percent of the qualifying events were ischemic stroke, 67% of which were classified as atherothrombotic or likely atherothrombotic (pure or coexisting with another cause). Modified Rankin scale scores showed slight or no disability in 83% of the population, while the scores on the Mini-Mental State Examination, Isaacs' Set Test, Zazzo's Cancellation Test, and the instrumental activities of daily living scale showed a good level of cognitive function and autonomy. CONCLUSIONS: The PERFORM study population is homogeneous in terms of demographic and disease characteristics. With 19,119 patients, the PERFORM study is powered to test the superiority of terutroban over aspirin in the secondary prevention of cerebrovascular and cardiovascular events in patients with a recent history of ischemic stroke or transient ischemic attack.

Development of labial gingival recessions in orthodontically treated patients

INTRODUCTION Our aim was to assess the prevalence of gingival recessions in patients before, immediately after, and 2 and 5 years after orthodontic treatment. METHODS Labial gingival recessions in all teeth were scored (yes or no) by 2 raters on initial, end-of-treatment, and posttreatment (2 and 5 years) plaster models of 302 orthodontic patients (38.7% male; 61.3% female) selected from a posttreatment archive. Their mean ages were 13.6 years (SD, 3.6; range, 9.5-32.7 years) at the initial assessment, 16.2 years (SD, 3.5; range, 11.7-35.1 years) at the end of treatment, 18.6 years (SD, 3.6; range, 13.7-37.2 years) at 2 years posttreatment, and 21.6 (SD, 3.5; range, 16.6-40.2 years) at 5 years posttreatment. A recession was noted (scored "yes") if the labial cementoenamel junction was exposed. All patients had a fixed retainer bonded to either the mandibular canines only (type I) or all 6 mandibular front teeth (type II). RESULTS There was a continuous increase in gingival recessions after treatment from 7% at end of treatment to 20% at 2 years posttreatment and to 38% at 5 years posttreatment. Patients less than 16 years of age at the end of treatment were less likely to develop recessions than patients more than 16 years at the end of treatment (P = 0.013). The prevalence of recessions was not associated with sex (P = 0.462) or extraction treatment (P = 0.32). The type of fixed retainer did not influence the development of recessions in the mandibular front region (P = 0.231). CONCLUSIONS The prevalence of gingival recessions steadily increases after orthodontic treatment. The recessions are more prevalent in older than in younger patients. No variable, except for age at the end of treatment, seems to be associated with the development of gingival recessions.

Dental phobia is no contraindication for oral implant therapy

OBJECTIVES Dental phobia is a psychological disease and a possible contraindication for implant therapy. The study aimed to show that implant therapy in dental-phobic patients (DP, test group) after adequate psychological and dental pretreatment (PDPT) is successfully possible and results in a similar implant prognosis as in nonfearful patients (NF, control group). METHOD AND MATERIALS 15 DP with PDPT and 15 NF were treated with dental implants and were re-evaluated 2 to 4 years after denture-mounting regarding: alteration of dental anxiety (Hierarchical Anxiety Questionnaire [HAQ], Visual Analog Scale [VAS]), patient satisfaction and compliance, implant success, and peri-implant health. Statistical tests of non-inferiority DP versus NF were performed with Hodges-Lehmann estimators and respective one-sided 97.5% confidence intervals of Moses, and pairwise testings with Mann-Whitney test. RESULTS The DP test group rated its anxiety significantly lower at follow- up than at baseline (PHAQ < .001). However, at follow-up, anxiety was still higher in DP than in NF (PHAQ = .046; PVAS < .001). Implant success at follow-up was 100%. Oral health was equally good in DP and NF patients. At follow-up, all patients were satisfied with implant therapy, but compliance was better for NF (100%) than for DP (73% dental checkup; 67% dental hygienist). CONCLUSION Implant therapy can be successfully performed in DP patients with PDPT as phobia is not negatively influenced by the invasive implant therapy. However, motivation for professional maintenance programs remains challenging.

Repeat chlamydia screening among adolescents: cohort study in a school-based programme in New Orleans

OBJECTIVES To describe uptake of chlamydia screening, determine rates of repeated yearly screening and investigate determinants of repeated participation in an organised school-based screening programme. METHODS The authors analysed data from 1995 to 2005 from female and male students in up to 13 schools in New Orleans, Louisiana, USA. The authors calculated proportions of students tested among all enrolled students and among those with parental consent and the percentage of positive chlamydia tests in each school year. The authors used random effects logistic regression to examine the effect of past screening history on subsequent participation. RESULTS 35 041 students were registered for at least one school year. Overall coverage was >30% in all school years. Among all students registered for 4 years, 10.6% (95% CI 9.3% to 12.0%) of women and 12.7% (95% CI 11.2% to 14.2%) of men had a test every year. Among students with parental consent for 4 years, 49.3% (95% CI 44.6% to 54.1%) of women and 59.3% (95% CI 54.5% to 64.0%) of men had a test every year. Among students registered for 2 or more years, those with a previous positive chlamydia test were less likely to have a subsequent test (female adjusted OR 0.77, 95% CI 0.67 to 0.88 and male adjusted OR 0.84, 95% CI 0.69 to 1.02). Chlamydia positivity increased over time. CONCLUSIONS High levels of uptake can be achieved in school-based chlamydia screening programmes, but repeated yearly screening is difficult to sustain over time.

Coronary evaginations are associated with positive vessel remodelling and are nearly absent following implantation of newer-generation drug-eluting stents: an optical coherence tomography and intravascular ultrasound study

OBJECTIVES The purpose of this study was to assess the occurrence, predictors, and mechanisms of optical coherence tomography (OCT)-detected coronary evaginations following drug-eluting stent (DES) implantation. BACKGROUND Angiographic ectasias and aneurysms in stented segments have been associated with a risk of late stent thrombosis. Using OCT, some stented segments show coronary evaginations reminiscent of ectasias. METHODS Evaginations were defined as outward bulges in the luminal contour between struts. They were considered major evaginations (MEs) when extending ≥3 mm along the vessel length, with a depth ≥10% of the stent diameter. A total of 228 patients who had sirolimus (SES)-, paclitaxel-, biolimus-, everolimus (EES)-, or zotarolimus (ZES)-eluting stents implanted in 254 lesions, were analysed after 1, 2, or 5 years; and serial assessment using OCT and intravascular ultrasound (IVUS) was performed post-intervention and after 1 year in 42 patients. RESULTS Major evaginations occurred frequently at all time points in SES (∼26%) and were rarely seen in EES (3%) and ZES (2%, P = 0.003). Sirolimus-eluting stent implantation was the strongest independent predictor of ME [adjusted OR (95% CI) 9.1 (1.1-77.4), P = 0.008]. Malapposed and uncovered struts were more common in lesions with vs. without ME (77 vs. 25%, P < 0.001 and 95 vs. 20%, P < 0.001, respectively) as was thrombus [49 vs. 14%, OR 7.3 (95% CI: 1.7-31.2), P = 0.007]. Post-intervention intra-stent dissection and protrusion of the vessel wall into the lumen were associated with an increased risk of evagination at follow-up [OR (95% CI): 2.9 (1.8-4.9), P < 0.001 and 3.3 (1.6-6.9), P = 0.001, respectively]. In paired IVUS analyses, lesions with ME showed a larger increase in the external elastic membrane area (20% area change) compared with lesions without ME (5% area change, P < 0.001). CONCLUSION Optical coherence tomography-detected MEs are a specific morphological footprint of early-generation SES and are nearly absent in newer-generation ZES and EES. Evaginations appear to be related to vessel injury at baseline; are associated with positive vessel remodelling; and correlate with uncoverage, malapposition, and thrombus at follow-up.

High-resolution mineral dust and sea ice proxy records from the Talos Dome ice core

In this study we report on new non-sea salt calcium (nssCa2+, mineral dust proxy) and sea salt sodium (ssNa+, sea ice proxy) records along the East Antarctic Talos Dome deep ice core in centennial resolution reaching back 150 thousand years (ka) before present. During glacial conditions nssCa2+ fluxes in Talos Dome are strongly related to temperature as has been observed before in other deep Antarctic ice core records, and has been associated with synchronous changes in the main source region (southern South America) during climate variations in the last glacial. However, during warmer climate conditions Talos Dome mineral dust input is clearly elevated compared to other records mainly due to the contribution of additional local dust sources in the Ross Sea area. Based on a simple transport model, we compare nssCa2+ fluxes of different East Antarctic ice cores. From this multi-site comparison we conclude that changes in transport efficiency or atmospheric lifetime of dust particles do have a minor effect compared to source strength changes on the large-scale concentration changes observed in Antarctic ice cores during climate variations of the past 150 ka. Our transport model applied on ice core data is further validated by climate model data. The availability of multiple East Antarctic nssCa2+ records also allows for a revision of a former estimate on the atmospheric CO2 sensitivity to reduced dust induced iron fertilisation in the Southern Ocean during the transition from the Last Glacial Maximum to the Holocene (T1). While a former estimate based on the EPICA Dome C (EDC) record only suggested 20 ppm, we find that reduced dust induced iron fertilisation in the Southern Ocean may be responsible for up to 40 ppm of the total atmospheric CO2 increase during T1. During the last interglacial, ssNa+ levels of EDC and EPICA Dronning Maud Land (EDML) are only half of the Holocene levels, in line with higher temperatures during that period, indicating much reduced sea ice extent in the Atlantic as well as the Indian Ocean sector of the Southern Ocean. In contrast, Holocene ssNa+ flux in Talos Dome is about the same as during the last interglacial, indicating that there was similar ice cover present in the Ross Sea area during MIS 5.5 as during the Holocene.

Cardiac Shock Wave Therapy for Chronic Refractory Angina Pectoris. A Prospective Placebo-Controlled Randomized Trial

Background: Cardiac shock wave therapy (CSWT) delivered to the myocardium increases capillary density and regional myocardial blood flow in animal experiments. In addition, nonenzymatic nitric oxide production and the upregulation of vascular growth factor's mRNA by CSWT have been described. The aim of the study was therefore to test its potential to relieve symptoms in patients with chronic stable angina pectoris. Methods: Twenty-one patients (mean age 68.2 ± 8.3 years, 19 males) with chronic refractory angina pectoris and evidence of inducible myocardial ischemia during MIBI-SPECT imaging, were randomized into a treatment (n = 11) and a placebo arm (n = 10). The region of exercise-induced ischemia was treated with echocardiographic guidance during nine sessions over a period of 3 months. One session of CSWT consisted of 200 shots/spot (9--12 spots/session) with an energy intensity of 0.09 mJ/mm2. In the control group acoustic simulation was performed without energy application. Medication was kept unchanged during the whole treatment period. Results: In the treatment group, symptoms improved in 9/11 patients, and the ischemic threshold, determined by cardiopulmonary exercise stress testing, increased from 80 ± 28 to 95 ± 28 W (P= 0.036). In the placebo arm, only 2/10 patients reported an improvement and the ischemic threshold remained unchanged (98 ± 23 to 107 ± 23 W; P= 0.141). The items “physical functioning” (P= 0.043), “general health perception” (P= 0.046), and “vitality” (P= 0.035) of the SF-36 questionnaire significantly improved in the treatment arm, whereas in the placebo arm, no significant change was noted. Neither arrhythmias, troponin rise nor complications were observed during treatment. Conclusions: This placebo controlled trial shows a significant improvement in symptoms, quality of life parameters and ischemic threshold during exercise in patients with chronic refractory angina pectoris treated with CSWT. Thus, CSWT represents a new option for the treatment of patients with refractory AP.

Mid- to late Holocene Indian Ocean Monsoon variability recorded in four speleothems from Socotra Island, Yemen

Four stalagmites covering the last 7.0 ka were sampled on Socotra, an island in the northern Indian Ocean to investigate the evolution of the northeast Indian Ocean Monsoon (IOM) since the mid Holocene. On Socotra, rain is delivered at the start of the southwest IOM in May–June and at the start of the northeast IOM from September to December. The Haggeher Mountains act as a barrier forcing precipitation brought by the northeast winds to fall preferentially on the eastern side of the island, where the studied caves are located. δ18O and δ13C and Mg/Ca and Sr/Ca signals in the stalagmites reflect precipitation amounts brought by the northeast winds. For stalagmite STM6, this amount effect is amplified by kinetic effects during calcite deposition. Combined interpretation of the stalagmites' signals suggest a weakening of the northeast precipitation between 6.0 and 3.8 ka. After 3.8 ka precipitation intensities remain constant with two superimposed drier periods, between 0 and 0.6 ka and from 2.2 to 3.8 ka. No link can be established with Greenland ice cores and with the summer IOM variability. In contrast to the stable northeast rainy season suggested by the records in this study, speleothem records from western Socotra indicate a wettening of the southwest rainy season on Socotra after 4.4 ka. The local wettening of western Socotra could relate to a more southerly path (more over the Indian Ocean) taken by the southwest winds. Stalagmite STM5, sampled at the fringe between both rain areas displays intermediate δ18O values. After 6.2 ka, similar precipitation changes are seen between eastern Socotra and northern Oman indicating that both regions are affected similarly by the monsoon. Different palaeoclimatologic records from the Arabian Peninsula currently located outside the ITCZ migration pathway display an abrupt drying around 6 ka due to their disconnection from the southwest rain influence. Records that are nowadays still receiving rain by the southwest winds, suggest a more gradual drying reflecting the weakening of the southwest monsoon.

Patient self-management of oral anticoagulation with vitamin k antagonists in everyday practice: efficacy and safety in a nationwide long-term prospective cohort study.

Patient self-management (PSM) of oral anticoagulation is under discussion, because evidence from real-life settings is missing. Using data from a nationwide, prospective cohort study in Switzerland, we assessed overall long-term efficacy and safety of PSM and examined subgroups. Data of 1140 patients (5818.9 patient-years) were analysed and no patient were lost to follow-up. Median follow-up was 4.3 years (range 0.2-12.8 years). Median age at the time of training was 54.2 years (range 18.2-85.2) and 34.6% were women. All-cause mortality was 1.4 per 100 patient-years (95% CI 1.1-1.7) with a higher rate in patients with atrial fibrillation (2.5; 1.6-3.7; p<0.001), patients>50 years of age (2.0; 1.6-2.6; p<0.001), and men (1.6; 1.2-2.1; p = 0.036). The rate of thromboembolic events was 0.4 (0.2-0.6) and independent from indications, sex and age. Major bleeding were observed in 1.1 (0.9-1.5) per 100 patient-years. Efficacy was comparable to standard care and new oral anticoagulants in a network meta-analysis. PSM of properly trained patients is effective and safe in a long-term real-life setting and robust across clinical subgroups. Adoption in various clinical settings, including those with limited access to medical care or rural areas is warranted.

The Most Extensive Holocene Advance in the Stauning Alper, East Greenland, Occurred in the Little Ice Age

We present glacial geologic and chronologic data concerning the Holocene ice extent in the Stauning Alper of East Greenland. The retreat of ice from the late-glacial position back into the mountains was accomplished by at least 11 000 cal years B.P. The only recorded advance after this time occurred during the past few centuries (the Little Ice Age). Therefore, we postulate that the Little Ice Age event represents the maximum Holocene ice extent in this part of East Greenland.

New Data on Welshite, e.g. Ca2Mg3.8Mn0.62+Fe0.12+Sb1.55+O2 [Si2.8Be1.7Fe0.653+Al0.7As0.17O18], an Aenigmatite-Group Mineral

Electron and ion microprobe data on two samples of welshite from the type locality of Langban, Sweden, gave analytical totals of 99.38-99.57 wt.% and BeO contents of 4.82-5.11 wt.%, corresponding to 1.692-1.773 Be/20 O. Mossbauer and optical spectra of one of these samples gave Fe-[iv](3+)/Sigma Fe = 0.91, Fe-[iv](2+)/Sigma Fe = 0.09, and no evidence of Mn3+. The resulting formula for this sample is Ca2Mg3.8Mn0.62+Fe0.12+Sb1.55+O2[Si2.8Be1.7Fe0.653+Al0.7As0.17O18], and that for the second sample, Ca2Mg3.8Mn0.12+Fe0.12+F0.83+Sb1.25+O2[Si2.8Be1.8F0.653+Al0.25As0.25O18], is related by the substitution involving tetrahedral and octahedral sites: 0.59([vi,iv])(Fe,Al)(3+) approximate to 0.42([vi])(Mg,Mn,Fe)(2+) + 0.21(Sb-[vi],As-[iv])(5+), i.e. 3([vi,iv]) M3+ = 2([vi])M(2+) + M-[vi,iv](5+). WelShite is distinctive among aenigmatite-group minerals in the high proportion of Fe 3+ in tetrahedral coordination and is unique in its Be content, substantially exceeding 1Be per formula unit. Given the cation distributions in other minerals related to aenigmatite, we think it is reasonable to assume that at least one tetrahedral site is >50% occupied by Be and that one octahedral site is >50% occupied by Sb, so that welshite should be retained as a distinct species with its own name in the aenigmatite group.

The number needed to treat to prevent mortality and cirrhosis-related complications among patients with cirrhosis and HCV genotype 1 infection

Cirrhotic patients with chronic hepatitis C virus (HCV) infection remain at risk for complications following sustained virological response (SVR). Therefore, we aimed to evaluate treatment efficacy with the number needed to treat (NNT) to prevent clinical endpoints. Mortality and cirrhosis-related morbidity were assessed in an international multicentre cohort of consecutively treated patients with HCV genotype 1 infection and cirrhosis. The NNT to prevent death or clinical disease progression (any cirrhosis-related event or death) in one patient was determined with the adjusted (event-free) survival among patients without SVR and adjusted hazard ratio of SVR. Overall, 248 patients were followed for a median of 8.3 (IQR 6.2-11.1) years. Fifty-nine (24%) patients attained SVR. Among patients without SVR, the adjusted 5-year survival and event-free survival were 94.4% and 80.0%, respectively. SVR was associated with reduced all-cause mortality (HR 0.15, 95% CI 0.05-0.48, P = 0.002) and clinical disease progression (HR 0.16, 95% CI 0.07-0.36, P < 0.001). The NNT to prevent one death in 5 years declined from 1052 (95% CI 937-1755) at 2% SVR (interferon monotherapy) to 61 (95% CI 54-101) at 35% SVR (peginterferon and ribavirin). At 50% SVR, which might be expected with triple therapy, the estimated NNT was 43 (95% CI 38-71). The NNT to prevent clinical disease progression in one patient in 5 years was 302 (95% CI 271-407), 18 (95% CI 16-24) and 13 (95% CI 11-17) at 2%, 35% and 50% SVR, respectively. In conclusion, the NNT to prevent clinical endpoints among cirrhotic patients with HCV genotype 1 has declined enormously with the improvement of antiviral therapy.

Recurrent stroke predictors differ in medically treated patients with pathogenic vs other PFOs

OBJECTIVE: To examine predictors of stroke recurrence in patients with a high vs a low likelihood of having an incidental patent foramen ovale (PFO) as defined by the Risk of Paradoxical Embolism (RoPE) score.METHODS: Patients in the RoPE database with cryptogenic stroke (CS) and PFO were classified as having a probable PFO-related stroke (RoPE score of >6, n = 647) and others (RoPE score of points, n = 677). We tested 15 clinical, 5 radiologic, and 3 echocardiographic variables for associations with stroke recurrence using Cox survival models with component database as a stratification factor. An interaction with RoPE score was checked for the variables that were significant.RESULTS: Follow-up was available for 92%, 79%, and 57% at 1, 2, and 3 years. Overall, a higher recurrence risk was associated with an index TIA. For all other predictors, effects were significantly different in the 2 RoPE score categories. For the low RoPE score group, but not the high RoPE score group, older age and antiplatelet (vs warfarin) treatment predicted recurrence. Conversely, echocardiographic features (septal hypermobility and a small shunt) and a prior (clinical) stroke/TIA were significant predictors in the high but not low RoPE score group.CONCLUSION: Predictors of recurrence differ when PFO relatedness is classified by the RoPE score, suggesting that patients with CS and PFO form a heterogeneous group with different stroke mechanisms. Echocardiographic features were only associated with recurrence in the high RoPE score group.

Tracer applications of noble gas radionuclides in the geosciences

Noble gas radionuclides, including 81Kr (t1/2 = 229,000 years), 85Kr (t1/2 = 10.8 years), and 39Ar (t1/2 = 269 years), possess nearly ideal chemical and physical properties for studies of earth and environmental processes. Recent advances in Atom Trap Trace Analysis (ATTA), a laser-based atom counting method, have enabled routine measurements of the radiokrypton isotopes, as well as the demonstration of the ability to measure 39Ar in environmental samples. Here we provide an overview of the ATTA technique, and a survey of recent progress made in several laboratories worldwide.We review the application of noble gas radionuclides in the geosciences and discuss how ATTA can help advance these fields, specifically: determination of groundwater residence times using 81Kr, 85Kr, and 39Ar; dating old glacial ice using 81Kr; and an 39Ar survey of the main water masses of the oceans, to study circulation pathways and estimate mean residence times. Other scientific questions involving a deeper circulation of fluids in the Earth's crust and mantle are also within the scope of future applications. We conclude that the geoscience community would greatly benefit from an ATTA facility dedicated to this field, with instrumentation for routine measurements, as well as for research on further development of ATTA methods.