Outcomes of Primary Flexor Tendon Repairs in Zones 2 and 3: A Retrospective Cohort Study.

PURPOSE The aims of this retrospective cohort study were to present outcomes of zone 2 and 3 primary flexor tendon repairs and to evaluate how clinical outcomes change over time within and between zones of injury at weeks 6, 13, and 26. METHODS Data were retrieved from a multicenter flexor tendon cohort registry from 2014 to 2021. The inclusion criteria were: (1) adult patients after primary flexor tendon surgery in zone 2 or 3, (2) flexor digitorum profundus laceration of >50%, (3) 4-6 multistrand flexor digitorum profundus core suture, and (4) early active motion protocol. The primary outcome was the range of motion. Secondary outcomes were strength, patient satisfaction on an 11-point Likert scale, and self-reported physical function measured with the Disability of the Arm, Shoulder, and Hand questionnaire 6, 13, and 26 weeks after surgery. RESULTS We evaluated 33 patients after 39 tendon repairs in zone 3 and 174 repairs in zone 2 of 163 patients. Range of motion significantly improved over time in both zones (P < .001 to .01). Between-group range of motion differences were nonsignificant except for week 26 (P < .001) for the zone 3 group. Hand strength significantly improved in both zones over time (P < .001 to .01), while between-zone strength differences were statistically nonsignificant (P = .37 to .93). Patient satisfaction was generally good to high (mean 6.8 to 8.0 points) with significant within-group changes in both zones (P < .001). There were no relevant between-zone differences in Disability of the Arm, Shoulder, and Hand scores at any time point. CONCLUSIONS Patients had significantly improved clinical outcomes in both zones. The zone of injury significantly affected the total active motion scores at the final assessment after 26 weeks for the zone 3 injuries. For the secondary outcomes hand strength, patient satisfaction, and Disability of the Arm, Shoulder, and Hand scores, we discovered no significant between-group differences. TYPE OF STUDY/LEVEL OF EVIDENCE Therapeutic IV

Outcomes of Primary Flexor Tendon Repairs in Zones 2 and 3: A Retrospective Cohort Study

PURPOSE The aims of this retrospective cohort study were to present outcomes of zone 2 and 3 primary flexor tendon repairs and to evaluate how clinical outcomes change over time within and between zones of injury at weeks 6, 13, and 26. METHODS Data were retrieved from a multicenter flexor tendon cohort registry from 2014 to 2021. The inclusion criteria were: (1) adult patients after primary flexor tendon surgery in zone 2 or 3, (2) flexor digitorum profundus laceration of >50%, (3) 4-6 multistrand flexor digitorum profundus core suture, and (4) early active motion protocol. The primary outcome was the range of motion. Secondary outcomes were strength, patient satisfaction on an 11-point Likert scale, and self-reported physical function measured with the Disability of the Arm, Shoulder, and Hand questionnaire 6, 13, and 26 weeks after surgery. RESULTS We evaluated 33 patients after 39 tendon repairs in zone 3 and 174 repairs in zone 2 of 163 patients. Range of motion significantly improved over time in both zones (P < .001 to .01). Between-group range of motion differences were nonsignificant except for week 26 (P < .001) for the zone 3 group. Hand strength significantly improved in both zones over time (P < .001 to .01), while between-zone strength differences were statistically nonsignificant (P = .37 to .93). Patient satisfaction was generally good to high (mean 6.8 to 8.0 points) with significant within-group changes in both zones (P < .001). There were no relevant between-zone differences in Disability of the Arm, Shoulder, and Hand scores at any time point. CONCLUSIONS Patients had significantly improved clinical outcomes in both zones. The zone of injury significantly affected the total active motion scores at the final assessment after 26 weeks for the zone 3 injuries. For the secondary outcomes hand strength, patient satisfaction, and Disability of the Arm, Shoulder, and Hand scores, we discovered no significant between-group differences. TYPE OF STUDY/LEVEL OF EVIDENCE Therapeutic IV

Agile Methoden in Entwicklungsprojekten zur Innovation digitaler Hochschullehre

Hochschulen stehen vor der Herausforderung, ihre Lehre im Rahmen der digitalen Transformation laufend zu innovieren. Dabei zielen sie vielfach auf eine Anreicherung der Lehre mit neuen digitalen Technologien ab. Um derartige Technologien nachhaltig und bedarfsorientiert zu entwickeln, bietet sich der Einsatz agiler Entwicklungsmethoden an, deren Umsetzung jedoch häufig mit universitären Strukturen und Prozessen kollidiert. Entsprechende Projekte sehen sich mit der Schwierigkeit konfrontiert, die Werte agiler Projektmethoden dennoch umzusetzen und zu leben. Dieser Beitrag berichtet von einem Good-Practice-Beispiel, in dem mithilfe von angepassten agilen Methoden interdisziplinär nutzbare Plugins zur digitalen Unterstützung von Feedback- und Gruppenkooperationsszenarien für das an der Universität Augsburg genutzte LMS entwickelt wurden

MicroRNA in diagnosis and therapy monitoring of early-stage triple-negative breast cancer

Breast cancer is a heterogeneous disease with distinct molecular subtypes including the aggressive subtype triple-negative breast cancer (TNBC). We compared blood-borne miRNA signatures of early-stage basal-like (cytokeratin-CK5-positive) TNBC patients to age-matched controls. The miRNAs of TNBC patients were assessed prior to and following platinum-based neoadjuvant chemotherapy (NCT). After an exploratory genome-wide study on 21 cases and 21 controls using microarrays, the identified signatures were verified independently in two laboratories on the same and a new cohort by RT-qPCR. We differentiated the blood of TNBC patients before NCT from controls with 84% sensitivity. The most significant miRNA for this diagnostic classification was miR-126-5p (two tailed t-test p-value of 1.4 × 10−5). Validation confirmed the microarray results for all tested miRNAs. Comparing cancer patients prior to and post NCT highlighted 321 significant miRNAs (among them miR-34a, p-value of 1.2 × 10−23). Our results also suggest that changes in miRNA expression during NCT may have predictive potential to predict pathological complete response (pCR). In conclusion we report that miRNA expression measured from blood facilitates early and minimally-invasive diagnosis of basal-like TNBC. We also demonstrate that NCT has a significant influence on miRNA expression. Finally, we show that blood-borne miRNA profiles monitored over time have potential to predict pCR

Linking functional and structural brain organisation with behaviour in autism: a multimodal EU-AIMS Longitudinal European Autism Project (LEAP) study

Neuroimaging analyses of brain structure and function in autism have typically been conducted in isolation, missing the sensitivity gains of linking data across modalities. Here we focus on the integration of structural and functional organisational properties of brain regions. We aim to identify novel brain-organisation phenotypes of autism. We utilised multimodal MRI (T1-, diffusion-weighted and resting state functional), behavioural and clinical data from the EU AIMS Longitudinal European Autism Project (LEAP) from autistic (n = 206) and non-autistic (n = 196) participants. Of these, 97 had data from 2 timepoints resulting in a total scan number of 466. Grey matter density maps, probabilistic tractography connectivity matrices and connectopic maps were extracted from respective MRI modalities and were then integrated with Linked Independent Component Analysis. Linear mixed-effects models were used to evaluate the relationship between components and group while accounting for covariates and non-independence of participants with longitudinal data. Additional models were run to investigate associations with dimensional measures of behaviour. We identified one component that differed significantly between groups (coefficient = 0.33, p$_{adj}$ = 0.02). This was driven (99%) by variance of the right fusiform gyrus connectopic map 2. While there were multiple nominal (uncorrected p < 0.05) associations with behavioural measures, none were significant following multiple comparison correction. Our analysis considered the relative contributions of both structural and functional brain phenotypes simultaneously, finding that functional phenotypes drive associations with autism. These findings expanded on previous unimodal studies by revealing the topographic organisation of functional connectivity patterns specific to autism and warrant further investigation

Low Energy Electron Irradiation Is a Potent Alternative to Gamma Irradiation for the Inactivation of (CAR-)NK-92 Cells in ATMP Manufacturing

Background: With increasing clinical use of NK-92 cells and their CAR-modified derivatives in cancer immunotherapy, there is a growing demand for efficient production processes of these “off-the-shelf” therapeutics. In order to ensure safety and prevent the occurrence of secondary tumors, (CAR-)NK-92 cell proliferation has to be inactivated before transfusion. This is commonly achieved by gamma irradiation. Recently, we showed proof of concept that low energy electron irradiation (LEEI) is a new method for NK-92 inactivation. LEEI has several advantages over gamma irradiation, including a faster reaction time, a more reproducible dose rate and much less requirements on radiation shielding. Here, LEEI was further evaluated as a promising alternative to gamma irradiation yielding cells with highly maintained cytotoxic effector function. Methods: Effectiveness and efficiency of LEEI and gamma irradiation were analyzed using NK-92 and CD123-directed CAR-NK-92 cells. LEE-irradiated cells were extensively characterized and compared to gamma-irradiated cells via flow cytometry, cytotoxicity assays, and comet assays, amongst others. Results: Our results show that both irradiation methods caused a progressive decrease in cell viability and are, therefore, suitable for inhibition of cell proliferation. Notably, the NKmediated specific lysis of tumor cells was maintained at stable levels for three days postirradiation, with a trend towards higher activities after LEEI treatment as compared to gamma irradiation. Both gamma irradiation as well as LEEI led to substantial DNA damage and an accumulation of irradiated cells in the G2/M cell cycle phases. In addition, transcriptomic analysis of irradiated cells revealed approximately 12-fold more differentially expressed genes two hours after gamma irradiation, compared to LEEI. Analysis of surface molecules revealed an irradiation-induced decrease in surface expression of CD56, but no changes in the levels of the activating receptors NKp46, NKG2D, or NKp30. Conclusions: The presented data show that LEEI inactivates (CAR-)NK-92 cells as efficiently as gamma irradiation, but with less impact on the overall gene expression. Due to logistic advantages, LEEI might provide a superior alternative for the manufacture of (CAR-)NK-92 cells for clinical application

An open-label pilot study of the effectiveness of adalimumab in patients with rheumatoid arthritis and previous infliximab treatment: relationship to reasons for failure and anti-infliximab antibody status

This prospective open-label pilot study evaluated the effectiveness and safety of adalimumab and the relationship to antibodies against infliximab (IFX) in adult patients with active rheumatoid arthritis (RA) who had been treated previously with IFX and experienced treatment failure owing to lack or loss of response or intolerance. Patients self-administered adalimumab 40 mg subcutaneously every other week for 16 weeks, followed by maintenance therapy for up to Week 56. Measures of effectiveness included American College of Rheumatology (ACR) and European League Against Rheumatism (EULAR) response criteria, 28-joint Disease Activity Score, and the Health Assessment Questionnaire Disability Index. Serum IFX concentrations, human antichimeric antibody against IFX (HACA), adalimumab serum concentrations, antiadalimumab antibody, and safety also were assessed. Of the 41 enrolled patients, 37 completed 16 weeks and 30 completed 56 weeks of treatment. Patients experienced clinically meaningful improvements in all measures of RA activity, with greater response rates observed for patients who had experienced loss of initial response to or intolerance of IFX. At Week 16, 46% of patients achieved an ACR20 and 28% achieved an ACR50; 61% achieved an at least moderate and 17% achieved a good EULAR response. Clinical benefit was maintained through Week 56 in all effectiveness parameters. Baseline HACA status did not significantly impact effectiveness. No new safety signals were observed; neither former IFX intolerance status nor baseline HACA status had a clinically relevant impact on adverse event frequency or severity. Adalimumab was effective and well-tolerated in patients with RA who previously failed IFX therapy, irrespective of reason for discontinuation and of HACA status

Genome-wide meta-analysis of common variant differences between men and women

The male-to-female sex ratio at birth is constant across world populations with an average of 1.06 (106 male to 100 female live births) for populations of European descent. The sex ratio is considered to be affected by numerous biological and environmental factors and to have a heritable component. The aim of this study was to investigate the presence of common allele modest effects at autosomal and chromosome X variants that could explain the observed sex ratio at birth. We conducted a large-scale genome-wide association scan (GWAS) meta-analysis across 51 studies, comprising overall 114 863 individuals (61 094 women and 53 769 men) of European ancestry and 2 623 828 common (minor allele frequency >0.05) single-nucleotide polymorphisms (SNPs). Allele frequencies were compared between men and women for directly-typed and imputed variants within each study. Forward-time simulations for unlinked, neutral, autosomal, common loci were performed under the demographic model for European populations with a fixed sex ratio and a random mating scheme to assess the probability of detecting significant allele frequency differences. We do not detect any genome-wide significant (P < 5 × 10−8) common SNP differences between men and women in this well-powered meta-analysis. The simulated data provided results entirely consistent with these findings. This large-scale investigation across ∼115 000 individuals shows no detectable contribution from common genetic variants to the observed skew in the sex ratio. The absence of sex-specific differences is useful in guiding genetic association study design, for example when using mixed controls for sex-biased trait

From pattern classification to stratification: towards conceptualizing the heterogeneity of Autism Spectrum Disorder

Pattern classification and stratification approaches have increasingly been used in research on Autism Spectrum Disorder (ASD) over the last ten years with the goal of translation towards clinical applicability. Here, we present an extensive scoping literature review on those two approaches. We screened a total of 635 studies, of which 57 pattern classification and 19 stratification studies were included. We observed large variance across pattern classification studies in terms of predictive performance from about 60% to 98% accuracy, which is among other factors likely linked to sampling bias, different validation procedures across studies, the heterogeneity of ASD and differences in data quality. Stratification studies were less prevalent with only two studies reporting replications and just a few showing external validation. While some identified strata based on cognition and intelligence reappear across studies, biology as a stratification marker is clearly underexplored. In summary, mapping biological differences at the level of the individual with ASD is a major challenge for the field now. Conceptualizing those mappings and individual trajectories that lead to the diagnosis of ASD, will become a major challenge in the near future