Hannoversche Kinderheilanstalt

Einleitung Ernährungsverhalten und gesundheitsbezogene Lebensqualität sind entscheidende Einflussfaktoren auf juvenile Adipositas. COVID-19 assoziierte Restriktionsmaßnahmen hatten einen erheblichen Einfluss auf Alltagsgestaltung, Lebensqualität und Ernährungsverhalten auch von Jugendlichen. Dies führte zu einer gestiegenen Adipositasprävalenz. Diese Arbeit untersucht Ernährungsverhalten und Lebensqualität von Jugendlichen mit Adipositas während der COVID-Pandemie im Vergleich zu den Vorpandemiejahren und die Auswirkungen einer strukturierten videobasierten Adipositasschulung darauf.

BackgroundGolimumab (GOL) is approved for treatment of polyarticular juvenile idiopathic arthritis (pJIA) in patients 2 years and older. Data on long-term safety of GOL in this indication are limited.ObjectivesTo assess long-term safety and effectiveness of GOL in pJIA patients.MethodsIn this ongoing non-interventional observational study, clinical characteristics, disease activity and safety parameters were analysed using the German Biologics in Paediatric Rheumatology (BiKeR) registry. A total of 141 pJIA-patients treated with GOL were frequency matched by body weight with 282 patients receiving alternative tumor necrosis factor inhibitors (aTNFi) and 135 biologic–naïve patients receiving methotrexate (MTX).ResultsBaseline disease activity (measured by number of active joints and JADAS10) of the GOL and other anti-TNF cohort was similar. The GOL cohort tended to have a longer disease duration and more patients were previously exposed to other biologic agents than the other anti-TNF cohort. Compared to MTX cohort, the GOL cohort had a lower baseline disease activity and less concomitant systemic steroids use (Table 1).The clinical effectiveness of GOL in pJIA is highlighted by a decrease of the mean JADAS 10 from 10.7 (±6.5) (baseline) to 4.4 (±5.0) at 24 months. By 24 months, a JADAS 10 minimal disease activity (JADAS 10 ≤3.8) was reached by 50.0% of patients, whereas 34.2 % of patients were in remission (JADAS 10 ≤1) and the PedACR 30/50/70/90 response rates were 73.7/65.8/60.5/47.4% respectively.In the GOL cohort, 12 SAEs were reported, while in the aTNFi cohort 25 SAEs and in the MTX cohort 5 SAEs were observed (Table 1). One serious infectious event (SI) in the GOL cohort, 6 SIs in the aTNFi and one SI in the MTX cohort were observed.A few incident autoimmune events were reported: 4 in the GOL cohort (1 uveitis, 2 psoriasis, 1 inflammatory bowel disease (IBD)), 10 in the aTNFi cohort (6 uveitis, 2 psoriasis, 2 IBD) and 7 in the MTX cohort (6 uveitis, 1 celiac disease) (Table 1).Among the patients with preexisting uveitis at baseline, 10 out of 39 in the GOL cohort and 5 out of 32 in the aTNFi cohort had uveitis flares, whereas there were no patients with preexisting uveitis in the MTX-cohort.No malignancies were reported in any cohort.ConclusionOur interim results show an acceptable safety profile of GOL therapy, comparable to treatment with aTNFi or MTX. AE and serious infection rates between the three cohorts were comparable. No new safety signals were identified. Available data supports the effectiveness of GOL in the treatment of pJIA.Table 1.Patient demographic and clinical parameters and adverse eventsGOL N=141aTNFi N=282MTX N=135Gender female °116 (82.3)215 (76.2)104 (77.0)Age (yrs)#12.6±3.512.1±4.011.3±4.3Disease duration (yrs)#7.1±4.44.2±3.81.0±2.3RF neg. Polyarthritis °76 (53.9)142 (50.4)85 (63.0)RF pos. Polyarthritis °8 (5.7)40 (14.2)22 (16.3)Extended Oligoarthritis °53 (37.6)88 (31.2)23 (17.0)Psoriatic arthritis °4 (2.8)12 (4.3)5 (3.7)Pretreatment bDMARD °113 (80.1)61 (21.6)0Concomitant systemic steroids°22 (15.6)69 (24.5)60 (44.4)Active joint count #4.1±4.95.1±6.49.7±7.1CHAQ DI #0.4±0.50.5±0.60.6±0.6JADAS10 #10.7±6.512.2±6.216.8±6.1JADAS 10 at month 24 ##4.4 ±5.0--AE *17295.8 (82.5-111.2)50385.1 (78.0-92.9)20093.7 (81.6-107.7)SAE *126.7 (3.8-11.8)254.2 (2.9-6.3)52.3 (1.0-5.6)Serious infections *10.6 (0.1-4.0)61.0 (0.5-2.3)10.5 (0.1-3.3)Autoimmune process *42.2 (0.8-5.9)101.7 (0.9-3.1)73.3 (1.6-6.9)Patients with uveitis flare events with preexisting uveitis at baseline+10 (of 39)5 (of 32)0 (of 0)Rheumatoid factor (RF), biologic disease modifying antirheumatic drug (bDMARD), childhood health assessment questionnaire disability index (CHAQ Di), juvenile arthritis disease activity index (JADAS), adverse event (AE), patient year (PY), ° n (%) at baseline, # mean±SD at baseline, ## mean±SD, * n, AE rate/100PY (95% CI), + n (of n patients).AcknowledgementsThe authors thank Zhiping Huang, also Rainer Berendes, Michael Borte, Ivan Földvari, Tilman Geikowski, Hermann Girschick, Johannes-Peter Haas, Maria Haller, Boris Hügle, Bernd-Ulrich Keck, Hans Kössel, Rolf-Michael Küster, Kirsten Minden, Prasad Oommen, Jürgen Quietzsch, Bettina Rogalski, Michael Rühlmann, Angelika Thon, Ralf Trauzeddel, Andreas Urban, Frank Weller-Heinemann, Daniel Windschall for contributing to the BIKER-Registry and all patients and their families.Disclosure of InterestsAngela Zimmer: None declared, Ariane Klein: None declared, Frank Dressler Speakers bureau: Abbvie, Novartis and Pfizer, Consultant of: Novartis and Mylan, Jasmin Kuemmerle-Deschner: None declared, Markus Hufnagel: None declared, Toni Hospach Consultant of: Consulting fees: Novartis, SOBI, Dirk Foell Speakers bureau: Speakers bureau: Novartis, Sobi, Biontech, Werfen, Consultant of: Consultant of: Novartis, Sobi, Boehringer, Grant/research support from: Grant/research support from: Novartis, Sobi, Boehringer, Normi Brueck: None declared, Nils Onken: None declared, Maria Fasshauer: None declared, Gerd Horneff Speakers bureau: Pfizer, Novartis, Sobi, Consultant of: MSD, Lilly, Grant/research support from: Novartis, MSD, Roche.

Previous neuroimaging studies have shown that patients with chronic pain display altered functional connectivity across distributed brain areas involved in the processing of nociceptive stimuli. The aim of the present study was to investigate how pain chronification modulates whole-brain functional connectivity during evoked clinical and tonic pain. Patients with osteoarthritis of the hip (n = 87) were classified into 3 stages of pain chronification (Grades I-III, Mainz Pain Staging System). Electroencephalograms were recorded during 3 conditions: baseline, evoked clinical hip pain, and tonic cold pain (cold pressor test). The effects of both factors (recording condition and pain chronification stage) on the phase-lag index, as a measure of neuronal connectivity, were examined for different frequency bands. In women, we found increasing functional connectivity in the low-frequency range (delta, 0.5-4 Hz) across pain chronification stages during evoked clinical hip pain and tonic cold pain stimulation. In men, elevated functional connectivity in the delta frequency range was observed in only the tonic cold pain condition. Across pain chronification stages, we found that widespread cortical networks increase their synchronization of delta oscillations in response to clinical and experimental nociceptive stimuli. In view of previous studies relating delta oscillations to salience detection and other basic motivational processes, our results hint at these mechanisms playing an important role in pain chronification, mainly in women.

Abstract In diesem Beitrag wird der Problemstellung nachgegangen, welche übergeordneten Erfolgsfaktoren etablierte Automobilhersteller erfüllen müssen, um digitale Geschäftsmodelle umsetzen zu können. Nach der Herleitung der Faktoren wird ein Modell erbracht, das eine Evaluierung eben solcher Geschäftsmodelle erlaubt. Durch den Fokus auf diese Erfolgsfaktoren kann die zuvor gestellte Problemstellung gelöst werden.

Aims: To investigate the short-term effects of the first wave of COVID-19 on clinical parameters in children with type 1 diabetes (T1D) from 82 worldwide centers participating in the Better Control in Pediatric and Adolescent DiabeteS: Working to CrEate CEnTers of Reference (SWEET) registry. Materials and Methods: Aggregated data per person with T1D ≤21 years of age were compared between May/June 2020 (first wave), August/September 2020 (after wave), and the same periods in 2019. Hierarchic linear and logistic regression models were applied. Models were adjusted for gender, age-, and diabetes duration-groups. To distinguish the added burden of the COVID-19 pandemic, the centers were divided into quartiles of first wave COVID-19-associated mortality in their country. Results: In May/June 2019 and 2020, respectively, there were 16,735 versus 12,157 persons, 52% versus 52% male, median age 13.4 (Q1; Q3: 10.1; 16.2) versus13.5 (10.2; 16.2) years, T1D duration 4.5 (2.1; 7.8) versus 4.5 (2.0; 7.8) years, and hemoglobin A1c (HbA1c) 60.7 (53.0; 73.8) versus 59.6 (50.8; 70.5) mmol/mol [7.8 (7.0; 8.9) versus 7.6 (6.8; 8.6) %]. Across all country quartiles of COVID-19 mortality, HbA1c and rate of severe hypoglycemia remained comparable to the year before the first wave, while diabetic ketoacidosis rates increased significantly in the centers from countries with the highest mortality rate, but returned to baseline after the wave. Continuous glucose monitoring use decreased slightly during the first wave (53% vs. 51%) and increased significantly thereafter (55% vs. 63%, P < 0.001). Conclusions: Although glycemic control was maintained, a significant rise in DKA at follow-up was seen during first wave in the quartile of countries with the highest COVID mortality. Trial Registration: NCT04427189.

This prospective study was designed to investigate whether anti-Müllerian hormone (AMH) levels are associated with the presence of multiple pronuclei in zygotes as well as with the ovarian response, fertilization rate and pregnancy outcome in ICSI cycles. A total of 413 patients undergoing ICSI cycles were included in the study. The assessment included 3084 MII oocytes. Serum AMH measurements were performed at the first initial presence of the patient. The outcome measures were the presence of multiple pronuclei (PN), a number of retrieved oocytes, number of mature/immature oocytes, fertilization rate and clinical pregnancy. Obtained results showed a statistically significant correlation between AMH levels and maternal age, the number of follicles, the number of cumulus-oocyte complexes, mature and immature oocyte, fertilization rate and pregnancy rate. Linear regression analysis showed that AMH significantly correlates with the presence of multiple pronuclei in the zygote. The further analysis confirmed that the number of zygotes with the presence of multiple pronuclei increased when AMH levels were higher. This is the first examination of the prognostic value of the serum AMH on the presence of multiple pronuclei in the zygote and our data in the preliminary study suggest that AMH levels could be used as a predictive marker.