CytoSorb Rescue for COVID-19 Patients With Vasoplegic Shock and Multiple Organ Failure: A Prospective, Open-Label, Randomized Controlled Pilot Study.

OBJECTIVES: To investigate the effect of extracorporeal cytokine reduction by CytoSorb (CytoSorbents, Monmouth Junction, NJ) on COVID-19-associated vasoplegic shock. DESIGN: Prospective, randomized controlled pilot study. SETTING: Eight ICUs at three sites of the tertiary-care university hospital Charité-Universitätsmedizin Berlin. PATIENTS: COVID-19 patients with vasoplegic shock requiring norepinephrine greater than 0.2 µg/kg/min, C-reactive protein greater than 100 mg/L, and indication for hemodialysis. INTERVENTIONS: Randomization of 1:1 to receive CytoSorb for 3-7 days or standard therapy. To account for inadvertent removal of antibiotics, patients in the treatment group received an additional dose at each adsorber change. MEASUREMENTS AND MAIN RESULTS: The primary endpoint was time until resolution of vasoplegic shock, estimated by Cox-regression. Secondary endpoints included mortality, interleukin-6 concentrations, and catecholamine requirements. The study was registered in the German Registry of Clinical Trials (DRKS00021447). From November 2020 to March 2021, 50 patients were enrolled. Twenty-three patients were randomized to receive CytoSorb and 26 patients to receive standard of care. One patient randomized to cytokine adsorption was excluded due to withdrawal of informed consent. Resolution of vasoplegic shock was observed in 13 of 23 patients (56.5%) in the CytoSorb and 12 of 26 patients (46.2%) in the control group after a median of 5 days (interquartile range [IQR], 4-5 d) and 4 days (IQR, 3-5 d). The hazard ratio (HR) for the primary endpoint, adjusted for the predefined variables age, gender, extracorporeal membrane oxygenation-therapy, or time from shock onset to study inclusion was HR, 1.23 (95% CI, 0.54-2.79); p = 0.63. The mortality rate was 78% in the CytoSorb and 73% in the control group (unadjusted HR, 1.17 [95% CI, 0.61-2.23]; p = 0.64). The effects on inflammatory markers, catecholamine requirements, and the type and rates of adverse events were similar between the groups. CONCLUSIONS: In severely ill COVID-19 patients, CytoSorb did not improve resolution of vasoplegic shock or predefined secondary endpoints.

Interactions between nocturnal melatonin secretion, metabolism, and sleeping behavior in adolescents with obesity.

BACKGROUND/OBJECTIVES: Sleeping behavior and individual prospensity in sleep timing during a 24 h period, known as chronotypes, are underestimated factors, which may favor the development of obesity and metabolic diseases. Furthermore, melatonin is known to play an important role in circadian rhythm, but was also suggested to directly influence metabolism and bodyweight regulation. Since disturbed and shifted sleep rhythms have been observed in adolescents with obesity, this study aimed to investigate potential interactions between melatonin secretion, chronobiology, and metabolism. In addition, the influence of artificial light especially emitted by electronic devices on these parameters was of further interest. SUBJECTS/METHODS: We performed a cross-sectional study including 149 adolescents (mean age 14.7 ± 2.1 years) with obesity. Metabolic blood parameters (e.g., cholesterol, triglycerides, uric acid, and insulin) were obtained from patients and correlated with nocturnal melatonin secretion. Melatonin secretion was determined by measuring 6-sulfatoxymelatonin (MT6s), the major metabolite of melatonin in the first-morning urine, and normalized to urinary creatinine levels to account for the urinary concentration. Chronobiologic parameters were further assessed using the Munich ChronoType Questionnaire. RESULTS: Subjects with insulin resistance (n = 101) showed significantly lower nocturnal melatonin levels compared to those with unimpaired insulin secretion (p = 0.006). Furthermore, triglyceride (p = 0.012) and elevated uric acid levels (p = 0.029) showed significant associations with melatonin secretion. Patients with late chronotype showed a higher incidence of insulin resistance (p = 0.018). Moreover, late chronotype and social jetlag were associated with the time and duration of media consumption. CONCLUSION: We identified an association of impaired energy metabolism and lower nocturnal melatonin secretion in addition to late chronotype and increased social jetlag (misalignment of biological and social clocks) in adolescents with obesity. This might point towards a crucial role of chronotype and melatonin secretion as risk factors for the development of pediatric and adolescent obesity.

Hypothermic Oxygenated Machine Perfusion Reduces Early Allograft Injury and Improves Post-transplant Outcomes in Extended Criteria Donation Liver Transplantation From Donation After Brain Death: Results From a Multicenter Randomized Controlled Trial (HOPE ECD-DBD).

OBJECTIVE: The aim of this study was to evaluate peak serum alanine aminotransferase (ALT) and postoperative clinical outcomes after hypothermic oxygenated machine perfusion (HOPE) versus static cold storage (SCS) in extended criteria donation (ECD) liver transplantation (LT) from donation after brain death (DBD). BACKGROUND: HOPE might improve outcomes in LT, particularly in high-risk settings such as ECD organs after DBD, but this hypothesis has not yet been tested in a randomized controlled clinical trial (RCT). METHODS: Between September 2017 and September 2020, 46 patients undergoing ECD-DBD LT from four centers were randomly assigned to HOPE (n = 23) or SCS (n = 23). Peak-ALT levels within 7 days following LT constituted the primary endpoint. Secondary endpoints included incidence of postoperative complications [Clavien-Dindo classification (CD), Comprehensive Complication Index (CCI)], length of intensive care- (ICU) and hospital-stay, and incidence of early allograft dysfunction (EAD). RESULTS: Demographics were equally distributed between both groups [donor age: 72 (IQR: 59-78) years, recipient age: 62 (IQR: 55-65) years, labMELD: 15 (IQR: 9-25), 38 male and 8 female recipients]. HOPE resulted in a 47% decrease in serum peak ALT [418 (IQR: 221-828) vs 796 (IQR: 477-1195) IU/L, P = 0.030], a significant reduction in 90-day complications [44% vs 74% CD grade ≥3, P = 0.036; 32 (IQR: 12-56) vs 52 (IQR: 35-98) CCI, P = 0.021], and shorter ICU- and hospital-stays [5 (IQR: 4-8) vs 8 (IQR: 5-18) days, P = 0.045; 20 (IQR: 16-27) vs 36 (IQR: 23-62) days, P = 0.002] compared to SCS. A trend toward reduced EAD was observed for HOPE (17% vs 35%; P = 0.314). CONCLUSION: This multicenter RCT demonstrates that HOPE, in comparison to SCS, significantly reduces early allograft injury and improves post-transplant outcomes in ECD-DBD liver transplantation.

Safe procedures despite ultra low radiation doses during catheter ablations of atrial and ventricular arrhythmias-A multicenter experience.

INTRODUCTION: Despite the development of non-fluoroscopic catheter visualization options, fluoroscopy is still used in most ablation procedures. The aim of this multicenter study was to evaluate the safety and efficacy of a new ultra-low dose radiation protocol for EP procedures in a large number of patients. METHODS AND RESULTS: A total of 3462 consecutive patients (male 1926 (55.6%), age 64.4 ± 14.0 years, BMI 26.65 ± 4.70) undergoing radiofrequency ablation (left atrial (n = 2316 [66.9%], right atrial (n = 675 [19.5%], or ventricular (n = 471 [13.6%]) in three German centers were included in the analysis. Procedures were performed using a new ultra-low dose protocol operating at 8nGy for fluoroscopy and 36nGy for cine-loops. Additionally a very low framerate (2-3FPS) was used. Using the new protocol very low Air kerma-area product (KAP) values were achieved for left atrial ablations (104.25 ± 84.22 µGym2 ), right atrial ablations (70.98 ± 94.79 µGym2 ) and ablations for ventricular tachycardias or PVCs (78.62 ± 66.59 µGym2 ). Acute procedural success was achieved in 3289/3388 (97.1%) while the rate of major complications was very low compared to previously published studies not using low dose settings (n = 20, 0.6%). CONCLUSION: The ultra-low dose, low framerate protocol leads to very low radiation doses for all EP procedures while neither procedural time, fluoroscopy time nor success or complication rates were compromised. When compared to current real-world Air KAP data the new ultra-low dose fluoroscopy protocol reduces radiation exposure by more than 90%.

Prolonged multimodal fasting modulates periodontal inflammation in female patients with metabolic syndrome: A prospective cohort study.

AIM: To determine the potential anti-inflammatory effect of a multimodal periodic fasting programme on surrogate parameters of periodontal inflammation in hospitalized patients diagnosed for metabolic syndrome (MetS). MATERIAL AND METHODS: A total of 47 patients were recruited and hospitalized in an integrative ward for an intensified two-week multimodal fasting, diet and lifestyle programme. Patients were periodontally examined at baseline (t1), after the 2-week fasting protocol (t2) and, subsequently, 4 months after fasting (t3). The following parameters were determined: periodontal screening index (PSI), bleeding on probing (BOP), gingival crevicular fluid volume (GCF), plaque index (PI), C-reactive protein (CRP), blood pressure (BP), waist circumference (WC), fasting glucose (FGLU), triglycerides (TRG), high-density lipoprotein (HDL) and HbA1c. RESULTS: A total of 28 female and 8 male patients fulfilled the defined criteria for MetS and were analysed separately by gender. At t2, BOP and GCF were reduced when compared to t1 (median: t2 = 39; t1 = 33.1%; p < .001 and t2 = 73.9; t1 = 59.3 Periotron units p = .02, respectively). BOP reduction correlated to FGLU (R = .37, p = .049) and weight reduction (R = .4, p = .04). CONCLUSION: This study showed for the first time that clinically supervised periodic fasting in female patients with MetS may facilitate the reduction of periodontal inflammation.

Cardiac arrhythmias in patients with COVID-19: Lessons from 2300 telemetric monitoring days on the intensive care unit.

BACKGROUND: Patients with COVID-19 seem to be prone to the development of arrhythmias. The objective of this trial was to determine the characteristics, clinical significance and therapeutic consequences of these arrhythmias in COVID-19 patients requiring intensive care unit (ICU) treatment. METHODS AND RESULTS: A total of 113 consecutive patients (mean age 64.1 ± 14.3 years, 30 (26.5%) female) with positive PCR testing for SARS-CoV2 as well as radiographically confirmed pulmonary involvement admitted to the ICU from March to May 2020 were included and observed for a cumulative time of 2321 days. Fifty episodes of sustained atrial tachycardias, five episodes of sustained ventricular arrhythmias and thirty bradycardic events were documented. Sustained new onset atrial arrhythmias were associated with hemodynamic deterioration in 13 cases (35.1%). Patients with new onset atrial arrhythmias were older, showed higher levels of Hs-Troponin and NT-proBNP, and a more severe course of disease. The 5 ventricular arrhythmias (two ventricular tachycardias, two episodes of ventricular fibrillation, and one torsade de pointes tachycardia) were observed in 4 patients. All episodes could be terminated by immediate defibrillation/cardioversion. Five bradycardic events were associated with hemodynamic deterioration. Precipitating factors could be identified in 19 of 30 episodes (63.3%), no patient required cardiac pacing. Baseline characteristics were not significantly different between patients with or without bradycardic events. CONCLUSION: Relevant arrhythmias are common in severely ill ICU patients with COVID-19. They are associated with worse courses of disease and require specific treatment. This makes daily close monitoring of telemetric data mandatory in this patient group.

Orally applied bacterial lysate in infants at risk for atopy does not prevent atopic dermatitis, allergic rhinitis, asthma or allergic sensitization at school age: Follow-up of a randomized trial.

BACKGROUND: The allergy preventive effects of gut immune modulation by bacterial compounds are still not fully understood. OBJECTIVE: We sought to evaluate the effect of bacterial lysate applied orally from the second until seventh months of life on the prevalence of allergic diseases at school age. METHODS: In a randomized, placebo-controlled trial, 606 newborns with at least one allergic parent received orally a bacterial lysate consisting of heat-killed Gram-negative Escherichia coli Symbio and Gram-positive Enterococcus faecalis Symbio or placebo from week 5 until the end of month 7. A total of 402 children were followed until school age (6-11 years) for the assessment of current atopic dermatitis (AD), allergic rhinitis (AR), asthma and sensitization against aeroallergens. RESULTS: AD was diagnosed in 11.0% (22/200) of children in the active and in 10.4% (21/202) of children in the placebo group. AR was diagnosed in 35% (70/200) of children in the active and in 38.1% (77/202) children in the placebo group. Asthma was diagnosed in 9% (18/199) of children in the active and in 6.6% (13/197) of children in the placebo group. Sensitization occurred in 46.5% (66/142) of participants in the active and 51.7% (76/147) in the placebo group. CONCLUSION: An oral bacterial lysate of heat-killed Gram-negative Escherichia coli and Gram-positive Enterococcus faecalis applied during the first 7 months of life did not influence the development of AD, asthma and AR at school age.

Prevalence of chronic urticaria in children and adults across the globe: Systematic review with meta-analysis.

BACKGROUND AND OBJECTIVES: Urticaria is a frequent skin condition, but reliable prevalence estimates from population studies particularly of the chronic form are scarce. The objective of this study was to systematically evaluate and summarize the prevalence of chronic urticaria by evaluating population-based studies worldwide. METHODS: We performed a systematic search in PUBMED and EMBASE for population-based studies of cross-sectional or cohort design and studies based on health insurance/system databases. Risk of bias was assessed using a specific tool for prevalence studies. For meta-analysis, we used a random effects model. RESULTS: Eighteen studies were included in the systematic evaluation and 11 in the meta-analysis including data from over 86 000 000 participants. Risk of bias was mainly moderate, whereas the statistical heterogeneity (I2 ) between the studies was high. Asian studies combined showed a higher point prevalence of chronic urticaria (1.4%, 95%-CI 0.5-2.9) than those from Europe (0.5%, 0.2-1.0) and Northern American (0.1%, 0.1-0.1). Women were slightly more affected than men, whereas in children < 15 years we did not find a sex-specific difference in the prevalence. The four studies that examined time trends indicated an increasing prevalence of chronic urticaria over time. CONCLUSIONS: On a global level, the prevalence of chronic urticaria showed considerable regional differences. There is a need to obtain more sex-specific population-based and standardized international data particularly for children and adolescents, different chronic urticaria subtypes and potential risk and protective factors.

Antagonistic Autoantibodies to Insulin-Like Growth Factor-1 Receptor Associate with Poor Physical Strength.

Natural autoantibodies to the IGF1 receptor (IGF1R-aAb) have been described in relation to Graves' ophthalmopathy. Other physiological roles of natural IGF1R-aAb are not known. We hypothesized that IGF1R-aAb may be related to muscle development. Serum samples (n = 408) from young overweight subjects (n = 143) were collected during a lifestyle intervention study. Anthropometric parameters, along with leptin, IGF1 and IGF1R-aAb concentrations, were analyzed, and the subjects were categorized into positive or negative for IGF1R-aAb. Eleven out of 143 subjects (7.7%) were positive for IGF1R-aAb. Identified IGF1R-aAb were molecularly characterized and showed antagonistic activity in vitro impairing IGF1-mediated IGF1R activation. Mean body weight, height or age were similar between IGF1R-aAb-positive and -negative subjects, but IGF1 concentrations differed. Jumping ability, as well as right and left handgrip strengths, were lower in the IGF1R-aAb-positive as compared to the IGF1R-aAb-negative subjects. We conclude that natural IGF1R-aAb are detectable in apparently healthy subjects and are capable of antagonizing IGF1-dependent IGF1R activation. Moreover, the presence of IGF1R-aAb is associated with poor physical strength. Although the causality of this association is unclear, the data imply a potential influence of IGF1R autoimmunity on muscle development.

Serum vitamin D levels in Berliners of Turkish descent -a cross-sectional study.

BACKGROUND: Vitamin D levels may differ between migrant and non-migrant populations, especially among non-western immigrants living in a country with limited sun exposure such as Germany. This study examined serum vitamin D concentration and associated factors among Berliners with and without Turkish background. METHODS: Two samples (with and without Turkish roots) were recruited in the inner city of Berlin for a cross-sectional study assessing serum vitamin D concentration. Linear regression analyses were used to examine sociodemographic, lifestyle and medical factors associated with serum vitamin D levels. RESULTS: In the analyses, we included 537 subjects (39% men and 61% women, age 43.2 ± 12.5 (mean ± standard deviation) years) with and 112 without Turkish background (46% men and 54% women, age 46.7 ± 14.6 years). The Turkish sample had lower mean (95%-Confidence Interval) vitamin D levels than the non-Turkish sample: 22.7 nmol/L (21.5;23.9) vs 34.7 nmol/L (31.9;37.5), p < 0.001. In the Turkish female subgroup, veiled women had considerably lower levels than unveiled women: 14.4 nmol/L (11.5;17.3) vs 24.9 nmol/L (23.1;26.7), p < 0.001. Multivariable regression analysis revealed that among the Berliners of Turkish descent, being active less than 150 min per day, and being overweight/obese were independently associated with a lower vitamin D concentration. In the non-migrant sample besides being overweight and obese, female sex was associated with lower vitamin D concentrations. CONCLUSIONS: Serum vitamin D levels were considerably low in Berliners of Turkish descent, and especially in veiled women. Potentially modifiable factors of low vitamin D levels were high BMI and low physical activity. These findings should be considered in the development of future public health strategies for subpopulations with Turkish migration background.

The Montreal Cognitive Assessment (MoCA) in a population-based sample of Turkish migrants living in Germany.

OBJECTIVES: Data on cognitive testing in migrants in Germany are scarce. We aimed to evaluate the Montreal Cognitive Assessment (MoCA) in Turkish migrants in Berlin and its association with demographics and health-related variables. METHOD: For this cross-sectional study, a random sample of persons with Turkish names was drawn from the registration-office. Cognitive function was assessed using the MoCA; 0 = worst, 30 = best total score. Multivariable linear regression models were calculated to determine associated factors with the total MoCA-score. RESULTS: In our analyses we included 282 participants (50% female), mean age 42.3 ± 11.9 years (mean ± standard deviation (SD)). The mean ± SD MoCA score was 23.3 ± 4.3. In the multivariable analysis, higher education (ß = 2.68; p < 0.001), and chosing the German version of the MoCA (ß = -1.13; p = 0.026), were associated with higher MoCA-scores, whereas higher age (ß = -0.08; p = 0.002) was associated with lower MoCA scores. CONCLUSION: In our study, a higher educational level, lower age, and German as the preferred test language (as compared to Turkish) were positively associated with the cognitive performance of Berliners with Turkish roots. To examine neurocognitive health of migrants, longitudinal population-based and clinical cohort studies that specifically compare migrants and their descendants with the original population of their home countries are required.

Sex-Related Allergic Rhinitis Prevalence Switch from Childhood to Adulthood: A Systematic Review and Meta-Analysis.

BACKGROUND: A sex-related switch in the prevalence of asthma from childhood (male predominance) to adulthood (female predominance) has been described, but for allergic rhinitis this remains unclear. We aimed to examine sex- and age-group-specific differences in allergic rhinitis prevalence by systematically evaluating studies from across the globe. METHODS: A systematic search of MEDLINE and Embase for population-based cross-sectional studies was performed regardless of the language of publication. The search was restricted to the present millennium (2000 to June 2014). Study quality was defined by the sampling method, response rate, sample size, and data collection method. To assess sex differences in the prevalence of self- or parent-reported symptoms of rhinitis, calculated pooled estimates of the male-female ratio (MFR) were obtained using random-effects model meta-analyses due to heterogeneity. A meta-regression analysis was also performed. RESULTS: Out of 6,539 publications identified, 67 cross-sectional population-based studies (291,726 males and 301,781 females) were included in our meta-analysis. In children (<11 years of age) significantly more boys than girls had rhinitis symptoms (MFR 1.21, 95% CI 1.17-1.25), whereas in adolescents (11 to <18 years of age) males were significantly less often affected than females (MFR 0.90, 95% CI 0.85-0.95). No sex-specific prevalence difference was observed in adults (MFR 0.96, 95% CI 0.83-1.17). These findings were consistent in all continents except in Asia, where the male predominance remained beyond childhood. CONCLUSIONS: The male predominance of rhinitis prevalence in childhood changed towards a female predominance in adolescence across the globe, except in Asia. Longitudinal studies are needed to confirm these cross-sectional data and examine possible determinants and underlying mechanisms.

[Evaluation of the Babylotse-Plus screening form : Evaluation of a simple instrument to systematically identify parents of newborns with severe psychosocial stress at Charité Berlin]. / Evaluation des Babylotse-Plus-Screeningbogens : Untersuchung eines einfachen Instruments zur Identifizierung psychosozial belasteter Eltern von Neugeborenen der Berliner Charité.

BACKGROUND: The well-being and healthy development of children are at risk in families with severe psychosocial stress. In Germany, simple and valid screening instruments are lacking to identify families in need of early support. OBJECTIVES: We aimed to examine the diagnostic accuracy of a simple perinatal screening form to identify families at high psychosocial risk. METHODS: For every mother giving birth at Charité Berlin between January and August 2013 the short Babylotse-Plus screening form with 27 items was filled out by medical staff. Completing the form took about 5 min. After calculating a sum score, values of ≥3 were defined as "likely at risk". A one-hour comprehensive standardized interview with the parents after birth served as the reference standard for assessing family resources and stress factors. RESULTS: Among the 279 participants included in the analyses, 215 were "likely at risk" and 64 had a low or no risk, the latter were randomly selected among all families with scores <3. The screening form had an excellent sensitivity (98.9 %; 95 % confidence interval 93.4-99.9 %) to detect families likely at risk, whereas its specificity was only low (33.0 %; 95 % confidence interval 30.5-33.5 %). This resulted in a rather poor positive likelihood ratio of 1.5 but a very good negative likelihood ratio of 0.03. CONCLUSIONS: The screening form identified families with psychosocial risks well, but many families with low or no risk were falsely defined as being at risk. Before recommending the screening instrument for clinical practice, further studies are needed in different settings to improve the specificity without reducing its high sensitivity.

Lipoprotein(a) and Lung Function Are Associated in Older Adults: Longitudinal and Cross-Sectional Analyses.

While numerous studies have confirmed a causal association between lipoprotein(a) [Lp(a)] and cardiovascular diseases, only a few studies have assessed the relationship between Lp(a) and pulmonary health, with inconsistent findings regarding this topic. This study's aim was to examine whether levels of serum Lp(a) are associated with lung function in a dataset of relatively healthy older adults. We used longitudinal data collected at two time points 7.4 ± 1.5 years apart from 679 participants (52% women, 68 [65-71] years old) from the Berlin Aging Study II (BASE-II). Multiple linear regression models adjusting for covariates were applied to examine the association between Lp(a) and lung function. The forced expiratory volume in one second (FEV1) and the forced vital capacity (FVC) were higher in both men and women with higher Lp(a) levels. However, since this association between lung function parameters and Lp(a) was not supported by Mendelian randomization analyses using recent genome-wide association study data, these relationships should be investigated in future work, as the observed differences are, in part, considerable and potentially clinically relevant.

Improved outcomes after hypothermic oxygenated machine perfusion in liver transplantation-Long-term follow-up of a multicenter randomized controlled trial.

BACKGROUND: While 4 randomized controlled clinical trials confirmed the early benefits of hypothermic oxygenated machine perfusion (HOPE), high-level evidence regarding long-term clinical outcomes is lacking. The aim of this follow-up study from the HOPE-ECD-DBD trial was to compare long-term outcomes in patients who underwent liver transplantation using extended criteria donor allografts from donation after brain death (ECD-DBD), randomized to either HOPE or static cold storage (SCS). METHODS: Between September 2017 and September 2020, recipients of liver transplantation from 4 European centers receiving extended criteria donor-donation after brain death allografts were randomly assigned to HOPE or SCS (1:1). Follow-up data were available for all patients. Analyzed endpoints included the incidence of late-onset complications (occurring later than 6 months and graded according to the Clavien-Dindo Classification and the Comprehensive Complication Index) and long-term graft survival and patient survival. RESULTS: A total of 46 patients were randomized, 23 in both arms. The median follow-up was 48 months (95% CI: 41-55). After excluding early perioperative morbidity, a significant reduction in late-onset morbidity was observed in the HOPE group (median reduction of 23 Comprehensive Complication Index-points [p=0.003] and lower incidence of major complications [Clavien-Dindo ≥3, 43% vs. 85%, p=0.009]). Primary graft loss occurred in 13 patients (HOPE n=3 vs. SCS n=10), resulting in a significantly lower overall graft survival (p=0.029) and adverse 1-, 3-, and 5-year survival probabilities in the SCS group, which did not reach the level of significance (HOPE 0.913, 0.869, 0.869 vs. SCS 0.783, 0.606, 0.519, respectively). CONCLUSIONS: Our exploratory findings indicate that HOPE reduces late-onset morbidity and improves long-term graft survival providing clinical evidence to further support the broad implementation of HOPE in human liver transplantation.

Cenicriviroc for the treatment of COVID-19: first interim results of a randomised, placebo-controlled, investigator-initiated, double-blind phase II trial.

OBJECTIVES: C-C-chemokine receptors (CCRs) are expressed on a variety of immune cells and play an important role in many immune processes, particularly leukocyte migration. Comprehensive preclinical research demonstrated CCR2/CCR5-dependent pathways as pivotal for the pathophysiology of severe COVID-19. Here we report human data on use of a chemokine receptor inhibitor in patients with COVID-19. METHODS: Interim results of a 2:1 randomised, placebo-controlled, investigator-initiated trial on the CCR2/CCR5-inhibitor Cenicriviroc (CVC) 150 mg BID orally for 28 d in hospitalised patients with moderate to severe COVID-19 are reported. The primary endpoint is the subject's responder status defined by achieving grade 1 or 2 on the 7-point ordinal scale of clinical improvement on day 15. RESULTS: Of the 30 patients randomised, 18 were assigned to receive CVC and 12 to placebo. Efficient CCR2- and CCR5 inhibition was demonstrated through CCL2 and CCL4 elevation in CVC-treated patients (485% and 80% increase on day 3 compared to the baseline, respectively). In the modified intention-to-treat population, 82.4% of patients (14/17) in the CVC group met the primary endpoint, as did 91.7% (11/12) in the placebo group (OR = 0.5, 95% CI = 0.04-3.41). One patient treated with CVC died of progressive acute respiratory distress syndrome, and the remaining had a favourable outcome. Overall, treatment with CVC was well tolerated, with most adverse events being grade I or II and resolving spontaneously. CONCLUSIONS: Our interim analysis provides proof-of-concept data on CVC for COVID-19 patients as an intervention to inhibit CCR2/CCR5. Further studies are warranted to assess its clinical efficacy.

App-Based Relaxation Exercises for Patients With Chronic Neck Pain: Pragmatic Randomized Trial.

BACKGROUND: Chronic neck pain is a highly prevalent condition. Learning a relaxation technique is recommended by numerous guidelines for chronic neck pain. Smartphone apps can provide relaxation exercises; however, their effectiveness, especially in a self-care setting, is unclear. OBJECTIVE: The aim of this pragmatic randomized trial is to evaluate whether app-based relaxation exercises, including audio-based autogenic training, mindfulness meditation, or guided imagery, are more effective in reducing chronic neck pain than usual care alone. METHODS: Smartphone owners aged 18 to 65 years with chronic (>12 weeks) neck pain and the previous week's average neck pain intensity ≥4 on the Numeric Rating Scale (0=no pain to 10=worst possible pain) were randomized into either an intervention group to practice app-based relaxation exercises or a control group (usual care and app for data entry only). For both groups, the follow-up data were collected using app-based diaries and questionnaires. The primary outcome was the mean neck pain intensity during the first 3 months based on daily measurements. Secondary outcomes included neck pain based on weekly measurements, pain acceptance, neck pain-related stress, sick-leave days, pain medication intake, and adherence, which were all measured until the 6-month follow-up. For the primary analysis, analysis of covariance adjusted for baseline neck pain intensity was used. RESULTS: We screened 748 participants and enrolled 220 participants (mean age 38.9, SD 11.3 years; mean baseline neck pain 5.7, SD 1.3 points). The mean neck pain intensity in both groups decreased over 3 months; however, no statistically significant difference between the groups was found (intervention: 4.1 points, 95% CI 3.8-4.4; control: 3.8 points, 95% CI 3.5-4.1; group difference: 0.3 points, 95% CI -0.2 to 0.7; P=.23). In addition, no statistically significant between-group differences regarding neck pain intensity after 6 months, responder rate, pain acceptance, pain medication intake, or sick-leave days were observed. There were no serious adverse events that were considered related to the trial intervention. In week 12, only 40% (44/110) of the participants in the intervention group continued to practice the exercises with the app. CONCLUSIONS: The study app did not effectively reduce chronic neck pain or keep the participants engaged in exercising in a self-care setting. Future studies on app-based relaxation interventions should take into account the most recent scientific findings for behavior change techniques. TRIAL REGISTRATION: ClinicalTrials.gov NCT02019134; https://clinicaltrials.gov/ct2/show/NCT02019134. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): RR2-10.1186/1745-6215-15-490.

Dietary Patterns in Adolescent Obesity as Predictors of Long-Term Success Following an Intensive Inpatient Lifestyle Programme.

(1) Background: Lifestyle interventions for adolescents with obesity show minor long-term effects on anthropometric parameters. The persistence of dietary changes after obesity inpatient rehabilitation has not been sufficiently investigated. (2) Objectives: To analyse dietary patterns in German adolescents with obesity as predictors of long-term success following an intensive inpatient lifestyle programme regarding food choices as well as body weight and comorbidities. (3) Methods: Food consumption data of 137 German adolescents with obesity aged 10-17 years were collected by a nutrition interview. Cluster analysis was used to group the participants according to their food consumption. Dietary patterns, changes in body weight and insulin resistance were compared over a 2-year-period. (4) Results: Three dietary patterns were identified. Big Eaters (n = 32) consume high amounts of total sugar and meat, Moderate Eaters (n = 66) have a diet comparable to the national average, and Snackers (n = 39) have a particularly high consumption of total sugar. Big Eaters and Snackers significantly reduced the consumption of total sugar. Among Moderate Eaters, no persistent changes were observed. (5) Conclusion: Weight reduction interventions can induce long-lasting changes in the diet of adolescents with obesity. Therefore, the success of a weight reduction intervention should not be determined by weight reduction only.

The effect of osteopathic medicine on pain in musicians with nonspecific chronic neck pain: a randomized controlled trial.

BACKGROUND: Nonspecific chronic neck pain (cNP) is common in adult violinists and violists and is often treated with osteopathic medicine (OM), although the effectiveness of this treatment has not been determined to date. This study aimed to evaluate the effectiveness and safety of OM in adult violinists and violists with cNP. METHODS: In a two-armed randomized controlled single-center open trial, adult violinists and violists, including music students, with cNP (⩾12 weeks) were randomized to either five individualized OM sessions (OM group) or to no intervention (control group, CG) in the outpatient clinic for integrative medicine, Charité - Universitätsmedizin Berlin, Germany. All patients received a musicians' medicine consultation and paracetamol on demand. The primary outcome parameter was the neck pain intensity on a visual analog scale (VAS, 0-100 mm, 0 = no pain, 100 = worst imaginable pain) after 12 weeks. Secondary outcomes included neck pain disability (Neck Disability Index, NDI, 0-100%) after 12 weeks. The last follow-up visit was after 52 weeks. Statistical analysis included analysis of covariance adjusted for respective baseline value. RESULTS: Altogether, 62 outpatients were included [OM group (n = 28), CG (n = 34); 81% female; mean age, 41.6 ± 11.1 years; mean baseline neck pain, 55.9 ± 11.6 mm]. After 12 weeks, OM was associated with an improvement in the OM group versus the CG in neck pain on the VAS [14.6 mm (95% confidence interval 8.0; 21.2) versus 40.8 mm (34.7; 46.9), p < 0.001, Cohen's d = 1.4], and neck pain disability as determined by the NDI [8.8% (6.7; 10.8) versus 17.2% (15.3; 19.1), p < 0.001]. Some improvements were maintained until 52 weeks of follow-up. No serious adverse events were observed. CONCLUSIONS: The results of this study suggest that OM might be effective in reducing pain intensity in adult violinists and violists with nonspecific cNP. Further studies should investigate the efficacy of OM in comparison with a sham procedure and with other effective therapy methods in high-quality multicenter trials. TRIAL REGISTRATION: WHO Trial Registration https://apps.who.int/trialsearch/NoAccess.aspx?aspxerrorpath=/trialsearch/Trial2.aspx by German Clinical Trials Register DRKS00009258, Universal Trial Number (UTN): U1111-1173-5943.

Group hypnosis for stress reduction and improved stress coping: a multicenter randomized controlled trial.

BACKGROUND: The aim of the trial was to investigate the effect of a hypnotherapeutic group program in healthy persons with increased levels of perceived stress. METHODS: In a randomized controlled multicenter trial participants with a self-assessed subjective stress level ≥ 40 mm on a visual analogue scale (0-100 mm; VAS) for the previous week and a stable state of health were randomized to either 5 weekly sessions of 120-min duration of a hypnotherapeutic group program for stress reduction and improved stress coping plus 5 hypnosis audiorecords for individual practice at home plus an educational booklet for stress coping (hypnosis group) versus an educational booklet only (control group). The primary outcome parameter was the VAS stress level for the previous week after 5 weeks. Secondary outcome parameters included the VAS stress level after 12 weeks, perceived stress (CPSS), depression (ADS-K), self efficacy (SWE) and quality of life (SF 36) after 5 weeks and 12 weeks. Analysis of covariance with a significance level of 5% using the full analysis set was used for analysis; the model included treatment (fixed effect), VAS baseline value (fixed covariate), and center (random effect). RESULTS: A total of 95 participants were randomized; 47 (40 female, 45 ± 13.4 years of age) were allocated to the hypnosis group, and 48 (41 female, 46.9 ± 14.3 years) were allocated to the control group. Regarding VAS stress level after 5 weeks, the adjusted VAS mean in the hypnosis group was 41.8 mm [95% confidence interval (CI): 35.2; 48.4] compared to 62.9 mm [56.2; 69.7] in the control group, and the group difference was - 21.2 mm [- 30.1; - 12.2] (P < 0.001). After 12 weeks, the stress intensity on the VAS showed a between-group difference of - 14.7 mm [- 25.1; - 4.4] (P = 0.006), and the adjusted means were 41.1 mm [33.4; 48.8] in the hypnosis group and 55.9 mm [48.4; 63.5] in the control group. Improvements were also reported for CPSS, SF-36, SWE and ADS-K after 5 and 12 weeks. CONCLUSION: Compared to the control group, the hypnosis group showed reduced perceived stress after 5 and 12 weeks. TRIAL REGISTRATION: ClinicalTrials.gov NCT03525093 ; date of registration: May 15, 2018.