A phase two randomised trial of neratinib monotherapy versus lapatinib plus capecitabine combination therapy in patients with HER2+ advanced breast cancer

Martin, M.,Bonneterre, J.,Geyer, C.E.,Ito, Y.,Ro, J.,Lang, I.,Kim, S.B.,Germa, C.,Vermette, J.,Wang, K.,Wang, K.,Awada, A. Pergamon Press 2013 European journal of cancer Vol.49 No.18

Background: The safety and efficacy of neratinib monotherapy were compared with that of lapatinib plus capecitabine in patients with human epidermal growth factor receptor-2-positive (HER2+), locally advanced/metastatic breast cancer and prior trastuzumab treatment. Methods: Patients received neratinib 240mg/d continuously (n=117) or lapatinib 1250mg/d continuously plus capecitabine 2000mg/m<SUP>2</SUP> per day on days 1-14 of each 21-d cycle (n=116). The primary aim was to demonstrate non-inferiority of neratinib for progression-free survival (PFS). Findings: The non-inferiority of neratinib was not demonstrated when compared with lapatinib plus capecitabine (hazard ratio, 1.19; 95% confidence interval, 0.89-1.60; non-inferiority margin, 1.15). Median PFS for neratinib was 4.5months versus 6.8months for lapatinib plus capecitabine and median overall survival was 19.7months versus 23.6months. Objective response rate (neratinib, 29% versus lapatinib plus capecitabine, 41%; P=0.067) and clinical benefit rate (44% versus 64%; P=0.003) were lower for the neratinib arm but consistent with previously reported results. In both treatment arms, diarrhoea was the most frequently reported treatment-related adverse event of any grade (neratinib, 85% versus lapatinib plus capecitabine, 68%; P=0.002) and of grade ¾ (28% versus 10%; P<0.001), but was typically managed with concomitant anti-diarrhoeal medication and/or study treatment modification. Importantly, neratinib had no significant skin toxicity. Interpretation: The results are considered as inconclusive since neither inferiority nor non-inferiority of treatment with neratinib versus lapatinib plus capecitabine could be demonstrated. The study confirmed relevant single-agent clinical activity and acceptable overall tolerability of neratinib in patients with recurrent HER2+ advanced breast cancer.

Efficacy and Safety Results of a Drug-Free Cosmetic Fluid for Perioral Dermatitis: The Toleriane Fluide Efficacy in Perioral Dermatitis (TOLPOD) Study

( Laura Ehmann ),( Markus Reinholz ),( Tanja Maier ),( Martin Lang ),( Andreas Wollenberg ) 대한피부과학회 2014 Annals of Dermatology Vol.26 No.4

Background: Perioral dermatitis (POD) is a common inflammatory skin disease without standard therapy. Objective: We sought to evaluate the clinical value of a soothing fluid for the treatment of POD. Methods: We included 51 patients with POD in this 8-week clinical trial. The Toleriane Fluide Efficacy in Perioral Dermatitis (TOLPOD) study had an open-label design and involved twice-daily application of Toleriane Fluide, a soothing cosmetic fluid. Clinical assessment of POD was performed with a predefined questionnaire including the POD severity index (PODSI). Control visits were made after 4 and 8 weeks of treatment. Results: The results were compared with those of a historical control group treated with a vehicle cream. Patients treated with the soothing fluid showed a continuous and significant improvement of the PODSI over time. The improvement of PODSI observed with the soothing fluid was better, but not significantly better, than that observed in the historical controls. In addition, the subjective complaints of patients such as disease burden, itching, distension of the skin, and appearance improved during treatment. Conclusion: A soothing fluid could be a clinically useful treatment option for POD. (Ann Dermatol 26(4) 462~468, 2014)

Youth Olympic Games (YOG) 2012—Mission Accomplished? A Retrospective Analysis of Intangible Legacies and the Fulfillment of the YOG’s Goals

Maximilian Seidl,Roman Nagiller,Anna Lang,Sabrina Scheiber,Martin Schnitzer 글로벌지식마케팅경영학회 2021 Journal of Global Sport Management Vol.6 No.3

Even though intangible legacies play an important role in the context of major sports events, research lacks both in depth and breadth. This paper, therefore, investigates intangible legacies of the Innsbruck 2012 Youth Olympic Games by surveying young residents (n = 1,338) 3 years after the event was staged. Special attention was paid to the youth’s level of involvement in the event. Additionally, the fulfillment of the YOG’s goals was analyzed. The results revealed that the YOG’s goals were mostly perceived as fulfilled. Although the local youth had overwhelmingly positive associations with and a positive opinion about the YOG, the event affected their lives only to a minor extent. Overall, our findings confirmed the extant literature and extended it by providing fundamental insights into the event’s image, which can be useful for future YOGs.

Examining the Predictability of the Stratospheric Sudden Warming of January 2013 Using Multiple NWP Systems

Tripathi, Om P.,Baldwin, Mark,Charlton-Perez, Andrew,Charron, Martin,Cheung, Jacob C. H.,Eckermann, Stephen D.,Gerber, Edwin,Jackson, David R.,Kuroda, Yuhji,Lang, Andrea AMERICAN METEOROLOGICAL SOCIETY 2016 Monthly weather review Vol.144 No.5

<P>The first multimodel study to estimate the predictability of a boreal sudden stratospheric warming (SSW) is performed using five NWP systems. During the 2012/13 boreal winter, anomalous upward propagating planetary wave activity was observed toward the end of December, which was followed by a rapid deceleration of the westerly circulation around 2 January 2013, and on 7 January 2013 the zonal-mean zonal wind at 608N and 10 hPa reversed to easterly. This stratospheric dynamical activity was followed by an equatorward shift of the tropospheric jet stream and by a high pressure anomaly over the North Atlantic, which resulted in severe cold conditions in the United Kingdom and northern Europe. In most of the five models, the SSW event was predicted 10 days in advance. However, only some ensemble members in most of the models predicted weakening of westerly wind when the models were initialized 15 days in advance of the SSW. Further dynamical analysis of the SSW shows that this event was characterized by the anomalous planetary wavenumber-1 amplification followed by the anomalous wavenumber-2 amplification in the stratosphere, which resulted in a split vortex occurring between 6 and 8 January 2013. The models have some success in reproducing wavenumber-1 activity when initialized 15 days in advance, but they generally failed to produce the wavenumber-2 activity during the final days of the event. Detailed analysis shows that models have reasonably good skill in forecasting tropospheric blocking features that stimulate wavenumber-2 amplification in the troposphere, but they have limited skill in reproducing wavenumber-2 amplification in the stratosphere.</P>

The predictability of the extratropical stratosphere on monthly time‐scales and its impact on the skill of tropospheric forecasts

Tripathi, Om P.,Baldwin, Mark,Charlton‐,Perez, Andrew,Charron, Martin,Eckermann, Stephen D.,Gerber, Edwin,Harrison, R. Giles,Jackson, David R.,Kim, Baek‐,Min,Kuroda, Yuhji,Lang, Andrea,Mah John WileySons, Ltd 2015 Quarterly journal of the Royal Meteorological Soci Vol.141 No.689

<P>Extreme variability of the winter‐ and spring‐time stratospheric polar vortex has been shown to affect extratropical tropospheric weather. Therefore, reducing stratospheric forecast error may be one way to improve the skill of tropospheric weather forecasts. In this review, the basis for this idea is examined. A range of studies of different stratospheric extreme vortex events shows that they can be skilfully forecasted beyond 5 days and into the sub‐seasonal range (0–30 days) in some cases. Separate studies show that typical errors in forecasting a stratospheric extreme vortex event can alter tropospheric forecast skill by 5–7% in the extratropics on sub‐seasonal time‐scales. Thus understanding what limits stratospheric predictability is of significant interest to operational forecasting centres. Both limitations in forecasting tropospheric planetary waves and stratospheric model biases have been shown to be important in this context.</P>

Galectin-3 Reflects the Echocardiographic Grades of Left Ventricular Diastolic Dysfunction

Uzair Ansari,Michael Behnes,Julia Hoffmann,Michele Natale,Christian Fastner,Ibrahim El-Battrawy,Jonas Rusnak,김승현,Siegfried Lang,Ursula Hoffmann,Thomas Bertsch,Martin Borggrefe,Ibrahim Akin 대한진단검사의학회 2018 Annals of Laboratory Medicine Vol.38 No.4

Background: The level of Galectin-3 (Gal-3) protein purportedly reflects an ongoing cardiac fibrotic process and has been associated with ventricular remodeling, which is instrumental in the development of heart failure with preserved ejection fraction (HFpEF) syndrome. The aim of this study was to investigate the potential use of Gal-3 in improved characterization of the grades of diastolic dysfunction as defined by echocardiography. Methods: Seventy HFpEF patients undergoing routine echocardiography were prospectively enrolled in the present monocentric study. Blood samples for measurements of Gal-3 and amino-terminal pro-brain natriuretic peptide (NT-proBNP) were collected within 24 hours pre- or post-echocardiographic examination. The classification of patients into subgroups based on diastolic dysfunction grade permitted detailed statistical analyses of the derived data. Results: The Gal-3 serum levels of all patients corresponded to echocardiographic indices, suggesting HFpEF (E/A, P =0.03 and E/E’, P =0.02). Gal-3 was also associated with progressive diastolic dysfunction, and increased levels corresponded to the course of disease (P =0.012). Detailed analyses of ROC curves suggested that Gal-3 levels could discriminate patients with grade III diastolic dysfunction (area under the curve [AUC]=0.770, P =0.005). Conclusions: Gal-3 demonstrates remarkable effectiveness in the diagnosis of patients suffering from severe grade diastolic dysfunction. Increasing levels of Gal-3 possibly reflect the progressive course of HFpEF, as classified by the echocardiographic grades of diastolic dysfunction.