bluuebunny/crossref_metadata_2025_split huggingface dataset:
Reasons to switch: a noninterventional study evaluating immunotherapy switches in a large German multicentre cohort of patients with relapsing-remitting multiple sclerosis
Authors: Mäurer Mathias , Tiel-Wilck Klaus , Oehm Eckard , Richter Nils , Springer Michael , Oschmann Patrick , Manzel Arndt , Hieke-Schulz Stefanie , Zingler Vera , Kandenwein Julia A. , Ziemssen Tjalf , Linker Ralf A. 
Published: December 2019

Background: With a large array of disease modifying therapies (DMTs) for relapsing-remitting MS (RRMS), identifying the optimal treatment option for the individual patient is challenging and switching of immunotherapies is often required. The objective of this study was to systematically investigate reasons for DMT switching in patients on immunotherapies for mild/moderate MS, and provide real-life insights into currently applied therapeutic strategies. Methods: This noninterventional, cross-sectional study (ML29913) at 50 sites in Germany included RRMS patients on therapies for mild/moderate MS who switched immunotherapy in the years 2014–2017. The key outcome variable was the reason to switch, as documented in the medical charts, based on failure of current therapy, cognitive decline, adverse events (AEs), patient wish, or a woman’s wish to become pregnant. Expectations of the new DMT and patients’ assessment of the decision maker were also recorded. Results: The core analysis population included 595 patients, with a mean age of 41.6 years, of which 69.7% were female. More than 60% of patients had at least one relapse within 12 months prior to the switch. The main reasons to switch DMT were failure of current therapy (53.9%), patient wish (22.4%), and AEs (19.0%). Most patients (54.3%) were switched within DMTs for mild/moderate MS; only 43.5% received a subsequent DMT for active/highly active MS. While clinical and outcome-oriented aspects were the most frequently mentioned expectations of the new DMT for physicians, aspects relating to quality of life played a major role for patients. Conclusions: Our data indicate suboptimal usage of DMTs, including monoclonal antibodies, for active/highly active MS in German patients. This illustrates the medical need for DMTs combining high efficacy, low safety risk, and low therapy burden.
Predictors of pre-rehabilitation exercise capacity in elderly European cardiac patients – The EU-CaRE study
Authors: Marcin Thimo , Eser Prisca , Prescott Eva , Mikkelsen Nicolai , Prins Leonie F , Kolkman Evelien K , Lado-Baleato Óscar , Cardaso-Suaréz Carmen , Bruins Wendy , van der Velde Astrid E , Peña Gil Carlos , Iliou Marie Christine , Ardissino Diego , Zeymer Uwe , Meindersma Esther P , Van’t Hof Arnoud WJ , de Kluiver Ed P , Wilhelm Matthias 
Published: December 2019

Aims Functional capacity is an important endpoint for therapies oriented to older adults with cardiovascular diseases. The literature on predictors of exercise capacity is sparse in the elderly population. In a longitudinal European study on effectiveness of cardiac rehabilitation of seven European countries in elderly (>65 years) coronary artery disease or valvular heart disease patients, predictors for baseline exercise capacity were determined, and reference ranges for elderly cardiac patients provided. Methods Mixed models were performed in 1282 patients (mean age 72.9 ± 5.4 years, 79% male) for peak oxygen consumption relative to weight (peak VO2; ml/kg per min) with centre as random factor and patient anthropometric, demographic, social, psychological and nutritional parameters, as well as disease aetiology, procedure, comorbidities and cardiovascular risk factors as fixed factors. Results The most important predictors for low peak VO2 were coronary artery bypass grafting or valve surgery, low resting forced expiratory volume, reduced left ventricular ejection fraction, nephropathy and peripheral arterial disease. Each cumulative comorbidity or cardiovascular risk factors reduced exercise capacity by 1.7 ml/kg per min and 1.1 ml/kg per min, respectively. Males had a higher peak VO2 per body mass but not per lean mass. Haemoglobin was significantly linked to peak VO2 in both surgery and non-surgery patients. Conclusions Surgical procedures, cumulative comorbidities and cardiovascular risk factors were the factors with the strongest relation to reduced exercise capacity in the elderly. Expression of peak VO2 per lean mass rather than body mass allows a more appropriate comparison between sexes. Haemoglobin is strongly related to peak VO2 and should be considered in studies assessing exercise capacity, especially in studies on patients after cardiac surgery.
Aortic root remodelling in competitive athletes
Authors: Abulí Marc , Grazioli Gonzalo , Sanz de la Garza Maria , Montserrat Silvia , Vidal Bàrbara , Doltra Adelina , Sarquella-Brugada Georgia , Bellver Montserrat , Pi Ramon , Brotons Daniel , Oxborough David , Sitges Marta 
Published: December 2019

Background Controversy remains about the cut-off limits for detecting aortic dilatation in athletes, particularly in large-sized individuals. The allometric scaling model has been used to obtain size-independent measurements in cardiovascular structures in the general population. Aim The purpose of this study was to validate the use of allometric scaling in the measurement of the aortic root for competitive athletes and to offer reference values. Methods This was a cross-sectional study that analyses the dimensions of aortic root found in the echocardiogram performed as part of pre-participation sports screening in competitive athletes between 2012–2015. Beta exponents were calculated for height and body surface area in the whole cohort. In order to establish whether a common exponent could be used in both genders the following model was assessed y = a xb*exp(c*sex). If a common exponent could not be applied then sex-specific beta exponents were calculated. Results Two thousand and eighty-three athletes (64% men) were included, from a broad spectrum of 44 different sports disciplines, including basketball, volleyball and handball. The mean age was 18.2 ± 5.1 years (range 12–35 years) and all athletes were Caucasian, with a training load of 12.5 ± 5.4 h per week. Indexed aortic root dimension showed a correlation with ratiometric scaling by body surface area (r: −0.419) and generated size independence values with a very light correlation with height (r: −0.084); and with the allometric scaling by body surface area (r: −0.063) and height (r: −0.070). The absolute value of aortic root was higher in men than in women ( p < 0.001). These differences were maintained with allometric scaling. Conclusion Size-independent aortic root dimension values are provided using allometric scaling by body surface area and height in a large cohort of competitive athletes. Aortic root values were larger in men than in women, both in absolute values and after allometric scaling. The use of these indexed aortic reference ranges can be useful for the early detection of aortic pathologies.
Feasibility of Single-Staged Bilateral Anterior Scoliosis Correction in Growing Patients
Authors: Baroncini Alice , Rodriguez Luis , Verma Kushagra , Trobisch Per D. 
Published: December 2019

Study Design: Retrospective analysis. Objectives: The objective of this study was to analyze the feasibility of correcting double-curve scoliosis using dynamic scoliosis correction (DSC, also known as vertebral body tethering), which requires a bilateral anterior approach with deflation of both lungs. Typically, this approach falls under the exclusionary criteria for the eligibility for anterior scoliosis surgery. No data exists on the feasibility of single-staged bilateral DSC. Methods: A retrospective analysis was performed utilizing the data from 25 patients who underwent a bilateral anterior thoracic approach and instrumentation. Thirty-day postoperative complication rates were analyzed. A learning curve subanalysis was also performed to compare the first 12 patients to the remainder of the 13 patients, with a T-test ( P ≤ .05). Results: Of the 25 patients treated, there was 1 intraoperative event: After performing lumbar DSC, the contralateral DSC was abandoned due to unexpected pleural scarring and staged selective thoracic fusion was performed. We observed 4 postoperative complications: 2 patients had recurrent pleural effusions, 1 patient was diagnosed with pneumonia, and 1 patient had a minor pulmonary embolism without cardiopulmonary consequences (after an international 24 hour flight). All patients recovered well. We observed a significant influence of learning curve on surgical time (328 vs 280 min, P = .03) and blood loss (480 vs 197 mL, P = .03). Conclusion: Data suggests that bilateral, single-stage surgery for DSC is feasible albeit with an elevated complication rate that may partially attributable to the learning curve. Future research should focus on the cause of pulmonary complications and include a matched comparative analysis with traditional posterior fusion.
Association Between Isokinetic Knee Strength and Perceived Function and Patient Satisfaction With Sports and Recreational Ability After Matrix-Induced Autologous Chondrocyte Implantation
Authors: Ebert Jay R. , Smith Anne , Janes Gregory C. , Wood David J. 
Published: December 2019

Background: Returning to a sound level of activity after matrix-induced autologous chondrocyte implantation (MACI) is important to patients. Evaluating the patient’s level of satisfaction with his or her sports and recreational ability is critical. Purpose: To investigate (1) satisfaction with sports and recreational ability after MACI and (2) the role that knee strength plays in self-reported knee function and satisfaction. Study Design: Case-control study; Level of evidence, 3. Methods: Isokinetic knee strength was assessed in 97 patients at 1, 2, and 5 years after MACI to calculate hamstrings-quadriceps ratios and peak knee extensor and flexor torque limb symmetry indices (LSIs). The Sports and Recreation subscale of the Knee injury and Osteoarthritis Outcome Score (KOOS Sports/Rec) was completed. A satisfaction scale was used to evaluate how satisfied the patients were with their ability to return to recreational activities and their ability to participate in sport. Associations between knee strength LSI, KOOS Sports/Rec, and satisfaction with recreational and sporting activities were assessed through use of multivariable linear and logistic regression, with adjustment for confounders. Mediation analysis was conducted to assess the extent to which self-reported knee function mediated associations between strength LSI and satisfaction. Results: Satisfaction with the ability to return to recreational activities was achieved in 82.4%, 85.6%, and 85.9% of patients at 1, 2, and 5 years, respectively, and satisfaction with sports participation was achieved in 55.7%, 73.2%, and 68.5% of patients at 1, 2, and 5 years, respectively. Knee extension torque LSIs were associated with KOOS Sports/Rec after adjustment for confounders over 1, 2, and 5 years (5-year regression coefficient, 6.0 points; 95% CI, 1.4-10.7; P = .012). KOOS Sports/Rec was associated with the likelihood of being satisfied at all time points (recreation: 5-year adjusted odds ratio [OR], 2.26; 95% CI, 1.48-3.46; P < .001; and sports: 5-year adjusted OR, 1.98; 95% CI, 1.47-2.68; P < .001). In a multivariable mediation model, the knee extension torque LSI was associated with satisfaction directly (standardized coefficient, 0.16; 95% CI, 0.03-0.28; P = .017) and indirectly via KOOS Sports/Rec (standardized coefficient, 0.19; 95% CI, 0.01-0.38; P = .027), the latter representing 55% of the total association of knee extension torque LSI with satisfaction. Conclusion: Knee extensor symmetry was associated with satisfaction in recreational and sporting ability, both directly and indirectly, via self-reported sports and recreation–related knee function. Restoring strength deficits after MACI is important for achieving optimal outcomes.
Outcomes of Arthroscopic Capsular Release in the Beach-Chair Versus Lateral Decubitus Position: A Systematic Review
Authors: Houck Darby A. , Belk John W. , Vidal Armando F. , McCarty Eric C. , Bravman Jonathan T. , Seidl Adam J. , Frank Rachel M. 
Published: December 2019

Background: Arthroscopic capsular release (ACR) for the treatment of adhesive capsulitis of the shoulder can be performed in either the beach-chair (BC) or lateral decubitus (LD) position. Purpose: To determine the clinical outcomes and recurrence rates after ACR in the BC versus LD position. Study Design: Systematic review; Level of evidence, 4. Methods: A systematic review using PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines was performed by searching PubMed, Embase, and the Cochrane Library databases for studies reporting clinical outcomes of patients undergoing ACR in either the BC or LD position. All English-language literature from 1990 through 2017 reporting on clinical outcomes after ACR with a minimum 3-month follow-up were reviewed by 2 independent reviewers. Recurrence rates, range of motion (ROM) results, and patient-reported outcome (PRO) scores were collected. Study methodological quality was evaluated using the modified Coleman Methodology Score (MCMS). Results: A total of 30 studies (3 level 1 evidence, 2 level 2 evidence, 4 level 3 evidence, 21 level 4 evidence) including 665 shoulders undergoing ACR in the BC position (38.1% male; mean age, 52.0 ± 3.9 years; mean follow-up, 35.4 ± 18.4 months) and 603 shoulders in the LD position (41.8% male; mean age, 53.0 ± 2.3 years; mean follow-up, 37.2 ± 16.8 months) were included. There were no significant differences in overall mean recurrence rates between groups (BC, 2.5%; LD, 2.4%; P = .81) or in any PRO scores between groups ( P > .05). There were no significant differences in improvement in ROM between groups, including external rotation at the side (BC, 36.4°; LD, 42.8°; P = .91), forward flexion (BC, 64.4°; LD, 79.3°; P = .73), abduction (BC, 77.8°; LD, 81.5°; P = .82), or internal rotation in 90° of abduction (BC, 40.8°; LD, 45.5°; P = .70). Significantly more patients in the BC group (91.6%) underwent concomitant manipulation than in the LD group (63%) ( P < .0001). There were significantly more patients with diabetes in the LD group (22.4%) versus the BC group (9.6%) ( P < .0001). Conclusion: Low rates of recurrent shoulder stiffness and excellent improvements in ROM can be achieved after ACR in either the LD or BC position. Concomitant manipulation under anesthesia is performed more frequently in the BC position compared with the LD position.
A Systematic Scoping Review of Ethical Issues in Mentoring in Surgery
Authors: Lee Fion Qian Hui , Chua Wen Jie , Cheong Clarissa Wei Shuen , Tay Kuang Teck , Hian Eugene Koh Yong , Chin Annelissa Mien Chew , Toh Ying Pin , Mason Stephen , Krishna Lalit Kumar Radha 
Published: December 2019

Background: Mentoring is crucial to the growth and development of mentors, mentees, and host organisations. Yet, the process of mentoring in surgery is poorly understood and increasingly mired in ethical concerns that compromise the quality of mentorship and prevent mentors, mentees, and host organisations from maximising its full potential. A systematic scoping review was undertaken to map the ethical issues in surgical mentoring to enhance understanding, assessment, and guidance on ethical conduct. Methods: Arksey and O’Malley’s methodological framework was used to guide a systematic scoping review involving articles published between January 1, 2000 and December 31, 2018 in PubMed, Embase, Scopus, ERIC, ScienceDirect, Mednar, and OpenGrey databases. Braun and Clarke’s thematic analysis approach was adopted to compare ethical issues in surgical mentoring across different settings, mentee and mentor populations, and host organisations. Results: A total of 3849 abstracts were identified, 464 full-text articles were retrieved, and 50 articles were included. The 3 themes concerned ethical lapses at the levels of mentor or mentee, mentoring relationships, and host organisation. Conclusions: Mentoring abuse in surgery involves lapses in conduct, understanding of roles and responsibilities, poor alignment of expectations, and a lack of clear standards of practice. It is only with better structuring of mentoring processes and effective support of host organisation tasked with providing timely, longitudinal, and holistic assessment and oversight will surgical mentoring overcome prevailing ethical concerns surrounding it.
Pluripotent stem cell–derived NK cells with high-affinity noncleavable CD16a mediate improved antitumor activity
Authors: Zhu Huang , Blum Robert H. , Bjordahl Ryan , Gaidarova Svetlana , Rogers Paul , Lee Tom Tong , Abujarour Ramzey , Bonello Gregory B. , Wu Jianming , Tsai Pei-Fang , Miller Jeffrey S. , Walcheck Bruce , Valamehr Bahram , Kaufman Dan S. 
Published: December 2019

Abstract
Antibody-dependent cellular cytotoxicity (ADCC) is a key effector mechanism of natural killer (NK) cells that is mediated by therapeutic monoclonal antibodies (mAbs). This process is facilitated by the Fc receptor CD16a on human NK cells. CD16a appears to be the only activating receptor on NK cells that is cleaved by the metalloprotease a disintegrin and metalloproteinase-17 upon stimulation. We previously demonstrated that a point mutation of CD16a prevents this activation-induced surface cleavage. This noncleavable CD16a variant is now further modified to include the high-affinity noncleavable variant of CD16a (hnCD16) and was engineered into human induced pluripotent stem cells (iPSCs) to create a renewable source for human induced pluripotent stem cell–derived NK (hnCD16-iNK) cells. Compared with unmodified iNK cells and peripheral blood–derived NK (PB-NK) cells, hnCD16-iNK cells proved to be highly resistant to activation-induced cleavage of CD16a. We found that hnCD16-iNK cells were functionally mature and exhibited enhanced ADCC against multiple tumor targets. In vivo xenograft studies using a human B-cell lymphoma demonstrated that treatment with hnCD16-iNK cells and anti-CD20 mAb led to significantly improved regression of B-cell lymphoma compared with treatment utilizing anti-CD20 mAb with PB-NK cells or unmodified iNK cells. hnCD16-iNK cells, combined with anti-HER2 mAb, also mediated improved survival in an ovarian cancer xenograft model. Together, these findings show that hnCD16-iNK cells combined with mAbs are highly effective against hematologic malignancies and solid tumors that are typically resistant to NK cell–mediated killing, demonstrating the feasibility of producing a standardized off-the-shelf engineered NK cell therapy with improved ADCC properties to treat malignancies that are otherwise refractory.
Vitamin C stabilizes CD8+ iTregs and enhances their therapeutic potential in controlling murine GVHD and leukemia relapse
Authors: Iamsawat Supinya , Tian Linlu , Daenthanasanmak Anusara , Wu Yongxia , Nguyen Hung D. , Bastian David , Yu Xue-Zhong 
Published: December 2019

Key Points
Vit C promotes the generation and stability of CD8+ iTregs. Vit C–stabilized CD8+ iTregs have an increased potential to suppress GVHD while preserving the GVL effect.
An invasive alien bivalve apparently provides a novel food source for moulting and wintering benthic feeding sea ducks
Authors: Kottsieper Johanna , Schwemmer Philipp , Markones Nele , Fox Anthony D. , Garthe Stefan 
Published: December 2019

AbstractSince its introduction from North America in the 1970s, the American razor clam Ensis leei (M. Huber, 2015) has successfully spread throughout North Sea coasts from Spain to Norway and the United Kingdom to the western Baltic. We investigated the distribution and abundance of this non-indigenous bivalve species as a potential novel food resource for common scoter Melanitta nigra (Linnaeus, 1758) along the eastern German North Sea coast. Highest densities of flightless moulting and wintering common scoters coincided with areas of high E. leei abundance. Other European studies showed common scoters extensively feed on E. leei. Even with these findings, it remains difficult to demonstrate convincingly that E. leei constitutes a major food source for common scoter in the German North Sea during their non-breeding season. However, our study suggests that E. leei has become an important prey item for internationally important concentrations of common scoters at large spatial scales.
Influence of environmental factors on the genetic variation of the aquatic macrophyte Ranunculus subrigidus on the Qinghai-Tibetan Plateau
Authors: Wu Zhigang , Xu Xinwei , Zhang Juan , Wiegleb Gerhard , Hou Hongwei 
Published: December 2019

AbstractBackgroundDue to the environmental heterogeneity along elevation gradients, alpine ecosystems are ideal study objects for investigating how ecological variables shape the genetic patterns of natural species. The highest region in the world, the Qinghai-Tibetan Plateau, is a hotspot for the studies of evolutionary processes in plants. Many large rivers spring from the plateau, providing abundant habitats for aquatic and amphibious organisms. In the present study, we examined the genetic diversity of 13Ranunculus subrigiduspopulations distributed throughout the plateau in order to elucidate the relative contribution of geographic distance and environmental dissimilarity to the spatial genetic pattern.ResultsA relatively low level of genetic diversity within populations was found. No spatial genetic structure was suggested by the analyses of molecular variance, Bayesian clustering analysis and Mantel tests. Partial Mantel tests and multiple matrix regression analysis showed a significant influence of the environment on the genetic divergence of the species. Both climatic and water quality variables contribute to the habitat heterogeneity ofR. subrigiduspopulations.ConclusionsOur results suggest that historical processes involving long-distance dispersal and local adaptation may account for the genetic patterns ofR. subrigidusand current environmental factors play an important role in the genetic differentiation and local adaptation of aquatic plants in alpine landscapes.