Different Prognostic Value of Functional Right Ventricular Parameters in Arrhythmogenic Right Ventricular Cardiomyopathy/Dysplasia

BACKGROUND -The value of standard two-dimensional transthoracic echocardiographic (TTE) parameters for risk stratification in patients with arrhythmogenic right ventricular cardiomyopathy/dysplasia (ARVC/D) is controversial. METHODS AND RESULTS -We investigated the impact of right ventricular fractional area change (FAC) and tricuspid annulus plane systolic excursion (TAPSE) for prediction of major adverse cardiovascular events (MACE) defined as the occurrence of cardiac death, heart transplantation, survived sudden cardiac death, ventricular fibrillation, sustained ventricular tachycardia or arrhythmogenic syncope. Among 70 patients who fulfilled the 2010 ARVC/D Task Force Criteria and underwent baseline TTE, 37 (53%) patients experienced a MACE during a median follow-up period of 5.3 (IQR 1.8-9.8) years. Average values for FAC, TAPSE, and TAPSE indexed to body surface area (BSA) decreased over time (p=0.03 for FAC, p=0.03 for TAPSE and p=0.01 for TAPSE/BSA, each vs. baseline). In contrast, median right ventricular end-diastolic area (RVEDA) increased (p=0.001 vs. baseline). Based on the results of Kaplan-Meier estimates, the time between baseline TTE and experiencing MACE was significantly shorter for patients with FAC <23% (p<0.001), TAPSE <17mm (p=0.02) or right atrial (RA) short axis/BSA ≥25mm/m(2) (p=0.04) at baseline. A reduced FAC constituted the strongest predictor of MACE (hazard ratio 1.08 per 1% decrease; 95% confidence interval 1.04-1.12; p<0.001) on bivariable analysis. CONCLUSIONS -This long-term observational study indicates that TAPSE and dilation of right-sided cardiac chambers are associated with an increased risk for MACE in ARVC/D patients with advanced disease and a high risk for adverse events. However, FAC is the strongest echocardiographic predictor of adverse outcome in these patients. Our data advocate a role for TTE in risk stratification in patients with ARVC/D, although our results may not be generalizable to lower risk ARVC/D cohorts.

Usefulness of inducible ventricular tachycardia to predict long-term adverse outcomes in arrhythmogenic right ventricular cardiomyopathy

The role of the electrophysiologic (EP) study for risk stratification in patients with arrhythmogenic right ventricular cardiomyopathy is controversial. We investigated the role of inducible sustained monomorphic ventricular tachycardia (SMVT) for the prediction of an adverse outcome (AO), defined as the occurrence of cardiac death, heart transplantation, sudden cardiac death, ventricular fibrillation, ventricular tachycardia with hemodynamic compromise or syncope. Of 62 patients who fulfilled the 2010 Arrhythmogenic Right Ventricular Cardiomyopathy Task Force criteria and underwent an EP study, 30 (48%) experienced an adverse outcome during a median follow-up of 9.8 years. SMVT was inducible in 34 patients (55%), 22 (65%) of whom had an adverse outcome. In contrast, in 28 patients without inducible SMVT, 8 (29%) had an adverse outcome. Kaplan-Meier analysis showed an event-free survival benefit for patients without inducible SMVT (log-rank p = 0.008) with a cumulative survival free of an adverse outcome of 72% (95% confidence interval [CI] 56% to 92%) in the group without inducible SMVT compared to 26% (95% CI 14% to 50%) in the other group after 10 years. The inducibility of SMVT during the EP study (hazard ratio [HR] 2.99, 95% CI 1.23 to 7.27), nonadherence (HR 2.74, 95% CI 1.3 to 5.77), and heart failure New York Heart Association functional class II and III (HR 2.25, 95% CI 1.04 to 4.87) were associated with an adverse outcome on univariate Cox regression analysis. The inducibility of SMVT (HR 2.52, 95% CI 1.03 to 6.16, p = 0.043) and nonadherence (HR 2.34, 95% CI 1.1 to 4.99, p = 0.028) remained as significant predictors on multivariate analysis. This long-term observational data suggest that SMVT inducibility during EP study might predict an adverse outcome in patients with arrhythmogenic right ventricular cardiomyopathy, advocating a role for EP study in risk stratification.

Radiofrequency ablation of multiple accessory pathways

The aim of the study was to review the clinical and electrophysiological characteristics and results of radiofrequency catheter ablation in patients with multiple accessory pathways to compare them with those of patients with single accessory pathways. Electrophysiological study and radiofrequency catheter ablation were performed in 1010 consecutive cases with Wolff Parkinson White Syndrome. Presence of multiple accessory pathways was documented in 31 patients (3.1%); 30 had two, and 1 had three accessory pathways. Of the 63 accessory pathways, 42 were manifest and 21 concealed. Nine patients had Ebstein's anomaly associated with atrioventricular bypass tracts. The most common combination was right posteroseptal with right free wall bypass tracts (15 patients with 30 accessory pathways). Fifty-one of the sixty-three accessory pathways (81%) were ablated successfully without complications. The duration of the procedure was 100 +/- 58 min and the fluoroscopic time 40 +/- 17 min. A follow up of 5 +/- 3 years after ablation, demonstrated recurrences of six accessory pathways (9.5%). In conclusion, patients with multiple accessory pathways can be treated by radiofrequency ablation in only one session with a high success rate although slightly less than that in patients with a single accessory pathway (81% vs 93%, P<0.01).

The role of mundane mobility and contact in dialect death and dialect birth

Urry begins his 2007 book, Mobilities, by throwing some quite stunning statistics at his readers: in 2010, there were one billion legal international arrivals at ports and airports; in 1800 people in the US travelled on average 50 metres per day, today it is 50 kilometres per day; 8.7% of world employment is in tourism; and, at any one time, there are 360,000 passengers in flight above the United States (2007: 3-4). But very many of these mobilities for the individuals concerned are or have become rather unexceptional – a flight to a holiday in Majorca or Florida, a journey on a crowded commuter train into Madrid or Tokyo, a cross-Channel ferry to Calais in France to pick up some cheap wine and a camembert. Whilst much of the theoretically influential dialectological literature on mobility reports on long-distance, often permanent, often dangerous migrations, I turn our attention here to the dialectological consequences of this unexceptional everyday movement. I will argue here that, just as more dramatic and long-distance mobilities can trigger linguistic change, so too can the much more mundane movements we engage in in everyday life. I demonstrate that the linguistic consequences of that contact are similar if not the same – perhaps less dramatic, perhaps involving the convergence of an initially less divergent array of variants – but typologically of the same ilk. And I demonstrate that because these mobilities have been long-term, intensive and ongoing, their consequences on the dialect landscape have been highly significant. Important to remember, however, is that these mobilities are socially stratified and unevenly distributed. As Wolff put it: “the suggestion of free and equal mobility is … a deception, since we don’t all have the same access to the road” (1993: 253).

The Great Silk Alternative Multiple Co-Evolution of Web Loss and Sticky Hairs in Spiders

Spiders are the most important terrestrial predators among arthropods. Their ecological success is reflected by a high biodiversity and the conquest of nearly every terrestrial habitat. Spiders are closely associated with silk, a material, often seen to be responsible for their great ecological success and gaining high attention in life sciences. However, it is often overlooked that more than half of all Recent spider species have abandoned web building or never developed such an adaptation. These species must have found other, more economic solutions for prey capture and retention, compensating the higher energy costs of increased locomotion activity. Here we show that hairy adhesive pads (scopulae) are closely associated with the convergent evolution of a vagrant life style, resulting in highly diversified lineages of at least, equal importance as the derived web building taxa. Previous studies often highlighted the idea that scopulae have the primary function of assisting locomotion, neglecting the fact that only the distal most pads (claw tufts) are suitable for those purposes. The former observations, that scopulae are used in prey capture, are largely overlooked. Our results suggest the scopulae evolved as a substitute for silk in controlling prey and that the claw tufts are, in most cases, a secondary development. Evolutionary trends towards specialized claw tufts and their composition from a low number of enlarged setae to a dense array of slender ones, as well as the secondary loss of those pads are discussed further. Hypotheses about the origin of the adhesive setae and their diversification throughout evolution are provided.

Lipid biomarkers in Holocene and glacial sediments from ancient Lake Ohrid (Macedonia, Albania)

Abstract. Organic matter preserved in Lake Ohrid sediments originates from aquatic and terrestrial sources. Its variable composition reflects climate-controlled changes in the lake basin’s hydrology and related organic matter export, i.e. changes in primary productivity, terrestrial plant matter input and soil erosion. Here, we present first results from lipid biomarker investigations of Lake Ohrid sediments from two near-shore settings: site Lz1120 near the southern shore, with low-lying lands nearby and probably influenced by river discharge, and site Co1202 which is close to the steep eastern slopes. Variable proportions of terrestrial n-alkanoic acids and n-alkanols as well as compositional changes of !- hydroxy acids document differences in soil organic matter supply between the sites and during different climate stages (glacial, Holocene, 8.2 ka cooling event). Changes in the vegetation cover are suggested by changes in the dominant chain length of terrestrial n-alkanols. Effective microbial degradation of labile organic matter and in situ contribution of organic matter derived from the microbes themselves are both evident in the sediments. We found evidence for anoxic conditions within the photic zone by detecting epicholestanol and tetrahymanol from sulphur-oxidising phototrophic bacteria and bacterivorous ciliates and for the influence of a settled human community from the occurrence of coprostanol, a biomarker for human and animal faeces (pigs, sheep, goats), in an early Holocene sample. This study illustrates the potential of lipid biomarkers for future environmental reconstructions using one of Europe’s oldest continental climate archives, Lake Ohrid.

Gonadotrophin stimulation for in vitro fertilization significantly alters the hormone milieu in follicular fluid: a comparative study between natural cycle IVF and conventional IVF.

STUDY QUESTION Is the steroid hormone profile in follicular fluid (FF) at the time of oocyte retrieval different in naturally matured follicles, as in natural cycle IVF (NC-IVF), compared with follicles stimulated with conventional gonadotrophin stimulated IVF (cIVF)? SUMMARY ANSWER Anti-Mullerian hormone (AMH), testosterone (T) and estradiol (E2) concentrations are ∼3-fold higher, androstenedione (A2) is ∼1.5-fold higher and luteinizing hormone (LH) is ∼14-fold higher in NC-IVF than in cIVF follicles, suggesting an alteration of the follicular metabolism in conventional gonadotrophin stimulated IVF. WHAT IS KNOWN ALREADY In conventional IVF, the implantation rate of unselected embryos appears to be lower than in NC-IVF, which is possibly due to negative effects of the stimulation regimen on follicular metabolism. In NC-IVF, the intrafollicular concentration of AMH has been shown to be positively correlated with the oocyte fertilization and implantation rates. Furthermore, androgen treatment seems to improve the ovarian response in low responders. STUDY DESIGN, SIZE, DURATION This cross-sectional study involving 36 NC-IVF and 40 cIVF cycles was performed from 2011 to 2013. Within this population, 13 women each underwent 1 NC-IVF and 1 cIVF cycle. cIVF was performed by controlled ovarian stimulation with HMG and GnRH antagonists. PARTICIPANTS/MATERIALS, SETTING, METHODS Follicular fluid was collected from the leading follicles. AMH, T, A2, dehydroepiandrosterone (DHEA), E2, FSH, LH and progesterone (P) were determined by immunoassays in 76 women. Aromatase activity in follicular fluid cells was analysed by a tritiated water release assay in 33 different women. For statistical analysis, the non-parametric Mann-Whitney U or Wilcoxon tests were used. MAIN RESULTS AND ROLE OF CHANCE In follicular fluid from NC-IVF and from cIVF, median levels were 32.8 and 10.7 pmol/l for AMH (P < 0.0001), 47.2 and 18.8 µmol/l for T (P < 0.0001), 290 and 206 nmol/l for A2 (P = 0.0035), 6.7 and 5.6 pg/ml for DHEA (n.s.), 3292 and 1225 nmol/l for E2 (P < 0.0001), 4.9 and 7.2 mU/ml for FSH (P < 0.05), 14.4 and 0.9 mU/ml for LH (P < 0.0001) and 62 940 and 54 710 nmol/l for P (n.s.), respectively. Significant differences in follicular fluid concentrations for AMH, E2 and LH were also found in the 13 patients who underwent both NC-IVF and cIVF when they were analysed separately in pairs. Hormone analysis in serum excluded any relevant impact of AMH, T, A2, and E2 serum concentration on the follicular fluid hormone concentrations. Median serum concentrations were 29.4 and 0.9 mU/ml for LH (P < 0.0001) and 2.7 and 23.5 nmol/l for P (P < 0.0001) after NC-IVF and c-IVF, respectively. Positive correlations were seen for FF-AMH with FF-T (r = 0.35, P = 0.0002), FF-T with FF-LH (r = 0.48, P < 0.0001) and FF-E2 with FF-T (r = 0.75, P < 0.0001). The analysis of aromatase activity was not different in NC-IVF and cIVF follicular cells. LIMITATION, REASONS FOR CAUTION Any association between the hormone concentrations and the implantation potential of the oocytes could not be investigated as the oocytes in cIVF were not treated individually in the IVF laboratory. Since both c-IVF and NC-IVF follicles were stimulated by hCG before retrieval, the endocrine milieu in the natural cycle does not represent the pure physiological situation. WIDER IMPLICATIONS OF THE FINDINGS The endocrine follicular milieu and the concentration of putative markers of oocyte quality, such as AMH, are significantly different in gonadotrophin-stimulated conventional IVF compared with natural cycle IVF. This could be a cause for the suggested lower oocyte quality in cIVF compared with naturally matured oocytes. The reasons for the reduced AMH concentration might be low serum and follicular fluid LH concentrations due to LH suppression, leading initially to low follicular androgen concentrations and then to low follicular AMH production. STUDY FUNDING/COMPETING INTERESTS Funding for this study was obtained from public universities (for salaries) and private industry (for consumables). Additionally, the study was supported by an unrestricted grant from MSD Merck Sharp & Dohme GmbH and IBSA Institut Biochimique SA. The authors are clinically involved in low-dose monofollicular stimulation and IVF therapies, using gonadotrophins from all gonadotrophin distributors on the Swiss market, including Institut Biochimique SA and MSD Merck Sharp & Dohme GmbH. Otherwise, the authors have no competing interests. TRIAL REGISTRATION NUMBER Not applicable.

A specific expression profile of heat-shock proteins and glucose-regulated proteins is associated with response to neoadjuvant chemotherapy in oesophageal adenocarcinomas

BACKGROUND Oesophageal adenocarcinomas often show resistances to chemotherapy (CTX), therefore, it would be of high interest to better understand the mechanisms of resistance. We examined the expression of heat-shock proteins (HSPs) and glucose-regulated proteins (GRPs) in pretherapeutic biopsies of oesophageal adenocarcinomas to assess their potential role in CTX response. METHODS Ninety biopsies of locally advanced adenocarcinomas before platin/5-fluorouracil (FU)-based CTX were investigated by reverse phase protein arrays (RPPAs), immunohistochemistry (IHC) and quantitative RT-PCR. RESULTS CTX response strongly correlated with survival (P=0.001). Two groups of tumours with specific protein expression patterns were identified by RPPA: Group A was characterised by low expression of HSP90, HSP27 and p-HSP27((Ser15, Ser78, Ser82)) and high expression of GRP78, GRP94, HSP70 and HSP60; Group B exhibited the inverse pattern. Tumours of Group A were more likely to respond to CTX, resulting in histopathological tumour regression (P=0.041) and post-therapeutic down-categorisation from cT3 to ypT0-T2 (P=0.040). High HSP60 protein (IHC) and mRNA expression were also associated with tumour down-categorisation (P=0.016 and P=0.004). CONCLUSION Our findings may enhance the understanding of CTX response mechanisms, might be helpful to predict CTX response and might have translational relevance as they highlight the role of potentially targetable cellular stress proteins in the context of CTX response.

Schnitte, Knoten und Netze – 100 Jahre Schweizerische Gesellschaft für Chirurgie

Vom Nobelpreis für die Schilddrüsenoperation zur Osteosynthese als weltweit praktizierter Technik: Die Chirurgie in der Schweiz der letzten einhundert Jahre kann als Erfolgsgeschichte gelesen werden. Der Sammelband zum 100-Jahr-Jubiläum der Schweizerischen Gesellschaft für Chirurgie geht tiefer und analysiert in vier medizinhistorischen Detailstudien die Hintergründe von medizinischen Erfolgen und organisatorischen Herausforderungen. Einige Reflexionen beleuchten zudem die heutige Chirurgie von der Ökonomisierung bis zur neueren Sakralisierung des von Chirurgen behandelten Körpers. Beiträge aus der chirurgischen Praxis skizzieren technisch-therapeutische Trends dieses Faches von der Organtransplantation bis zur «Schlüsselloch-Chirurgie».