Search

Background: The ABC classification has recently been proposed as a comprehensive classification system for posterior shoulder instability (PSI). The purpose of this study was to analyze the comprehensiveness as well as inter-rater and intrarater reliability of the ABC classification., Methods: All consecutive patients presenting with unidirectional PSI from June 2019 to June 2021 were included in a prospective study. No patients were excluded, leaving a consecutive series of 100 cases of PSI in 91 patients. All recorded clinical and imaging data were used to create anonymized clinical case vignettes, which were evaluated twice according to the ABC classification at the end of the recruitment period in random sequential order by 4 independent raters (2 experienced shoulder surgeons and 2 orthopedic residents) to analyze the comprehensiveness as well as inter-rater and intrarater reliability of the ABC classification for PSI and to describe differences in characteristics among subtypes. Group A was defined as a first-time singular PSI event <3 months in the past regardless of etiology and is further subdivided into type 1 and type 2 depending on the occurrence of a subluxation (A1) or dislocation (A2). Group B comprises recurrent dynamic PSI regardless of time since onset and is further subdivided by the cause of instability into functional (B1) and structural (B2) dynamic PSI. Group C includes chronic static PSI with posterior humeral decentering that can be either constitutional (C1) or acquired (C2)., Results: None of the cases was deemed unsuitable to be classified based on the proposed system by the observers. After consensus agreement between the 2 expert raters, 16 cases were attributed to group A (8 type A1 and 8 type A2); 64, to group B (33 type B1 and 31 type B2); and 20, to group C (11 type C1 and 9 type C2). The expert raters agreed on the classification subtypes in 99% and 96% of the cases during the first rating and second rating, respectively (intraclass correlation coefficients [ICCs], 0.998 and 0.99, respectively). The intraobserver reliability was excellent for both raters. The beginners reached the same conclusion as the consensus agreement in 94% of the cases (ICC, 0.99) and 89% of the cases (ICC, 0.97) during the first round and 94% each (ICC, 0.97) during the second round. The intraobserver reliability was excellent for both beginners. Overall, discrepancies between raters were found between groups B1 and B2 (n = 14), groups B2 and C2 (n = 4), groups B1 and C1 (n = 1), and groups A1 and B2 (n = 1). In general, each subtype showed distinctive clinical and imaging characteristics that facilitated the diagnosis., Conclusion: The presented ABC classification for PSI is a comprehensive classification with a high reliability and reproducibility. However, a gradual transition and potential progression between the subtypes of PSI must be considered. The reliable distinction between different subtypes of PSI based on etiology and pathomechanism provides a standardized basis for future investigations on treatment recommendations., (Copyright © 2024 Journal of Shoulder and Elbow Surgery Board of Trustees. Published by Elsevier Inc. All rights reserved.)

Multiple studies have hinted at a complex connection between maternal stress and preterm birth (PTB). This article describes the potential of computational methods to provide new insights into this relationship. For this, we outline existing approaches for stress assessments and various data modalities available for profiling stress responses, and review studies that sought either to establish a connection between stress and PTB or to predict PTB based on stress-related factors. Finally, we summarize the challenges of computational methods, highlighting potential future research directions within this field., Competing Interests: Disclosure The authors have nothing to disclose., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: Up to now, there is no gold standard concerning the optimal graft choice in the surgical therapy of chronic elbow instability. As donor site morbidity represents a rare (1%-4%) but severe complication of graft harvest, using an allograft seems favorable. Fascia lata mimics the anatomy through its fan-shaped configuration of the ligamentous complex of the elbow joint, making it questionable for use as a graft. The aims of the study are (1) to evaluate the biomechanical suitability of fascia lata allograft and (2) to compare clinical and radiological outcome between ligament reconstruction of the lateral collateral ligament complex using either FiberTape augmented triceps autograft or FibreTape augmented fascia lata allograft., Methods: Biomechanical testing of fascia lata was performed using a 10 kN uniaxial test system with a 1 kN load cell. The retrospective cohort study evaluated all patients who received a ligament reconstruction of the elbow due to chronic instability with allogenic fascia lata or autologous triceps tendon. Exclusion criteria were any type of coexisting fracture or nerval injury. Demographic parameters, patient-reported outcome parameters and radiological stability parameters (sonography and fluoroscopy) were evaluated., Results: Tensile testing of 39 fascia lata allografts revealed an ultimate load of 234.8 ± 23.1 N and ultimate strength of 33.4 ± 4.4 MPa. Twenty one patients were included in the clinical substudy (57.1% men, 42.9% women, age 41.0 ± 12.2 years, body mass index 24.9 ± 4.1 kg/m 2 ) with average follow-up of 21.6 ± 17.1 months. No significant differences were found concerning pain level, patient-reported outcome measures, or range of motion, between fascia lata and triceps group. There was also no difference concerning sonographic stability of lateral ulnar collateral ligament between the 2 groups ( P  = .14). One revision occurred in fascia lata allograft group and 2 in triceps autograft group due to graft elongation., Conclusion: Currently, there is no clinical evidence demonstrating the superiority of either autograft or allograft tissue. Due to its demonstration of sufficient biomechanical properties, fascia lata allograft seems an appropriate treatment option for ligamentous reconstruction of chronic elbow instability., (© 2024 The Authors.)

In the National database (NDB) of the German regional collaborative arthritis centres, annual data on the rheumatological care of patients with inflammatory rheumatic diseases have been collected since 1993. This first annual report presents current cross-sectional data on medication and patient-reported outcomes gathered in 2022., (© 2024. The Author(s).)

The aim of this study is to present the current care situation of patients with giant cell arteritis (GCA), Takayasu arteritis (TAK), ANCA-associated vasculitis (AAV) and Behçet's disease (BD). Trends over the last 15 years will reflect improvements and remaining deficits in the management of vasculitides. Consecutive cross-sectional data from patients with vasculitides from the German National Database (NDB) of the Collaborative Arthritis Centres between 2007 and 2021 were included. Medication, physician- and patient-reported outcomes on disease activity and disease burden, inpatient stays and occupational participation are compared for different vasculitis entities and over time. Employment rates were compared to German population rates. Between 502 and 854 vasculitis patients were annually documented. GCA and AAV were the most common vasculitides. Median disease duration ranged from 2 to 16 years. Over the years, glucocorticoids decreased in proportion and dose, most markedly in GCA and TAK, while biologic therapies increased up to 27%. Physicians rated disease activity as low for the vast majority of patients, while patients-reported moderate outcomes in many dimensions. PROs remained largely unchanged. The proportion of employed patients (< 65 years) increased from 47 to 57%. In recent years, biologics are increasingly used in patients with vasculitides, while glucocorticoids decreased significantly. PRO's have not improved. Work participation increased but remains lower than that in the German population., (© 2023. The Author(s).)

Innovations in viral vaccine manufacturing are crucial for pandemic preparedness and to meet ever-rising global demands. For influenza, however, production still mainly relies on technologies established decades ago. Although modern production shifts from egg-based towards cell culture technologies, the full potential has not yet been fully exploited. Here, we evaluate whether implementation of state-of-the-art technologies for cell culture-based recombinant protein production are capable to challenge outdated approaches in viral vaccine process development. For this, a fully automated single-cell cloning strategy was established to generate monoclonal suspension Madin-Darby canine kidney (MDCK) cells. Among selected cell clones, we could observe distinct metabolic and growth characteristics, with C59 reaching a maximum viable cell concentration of 17.3 × 10 6 cells/mL and low doubling times in batch mode. Screening for virus production using a panel of human vaccine-relevant influenza A and B viruses in an ambr15 system revealed high titers with yields competing or even outperforming available MDCK cell lines. With C113, we achieved cell-specific virus yields of up to 25,000 virions/cell, making this cell clone highly attractive for vaccine production. Finally, we confirmed process performance at a 50-fold higher working volume. In summary, we present a scalable and powerful approach for accelerated development of high-yield influenza virus production in chemically defined medium starting from a single cell., Competing Interests: Y.G. and U.R. have declared no conflict of interest. T.Z. was supported by a grant from Sartorius Stedim Biotech GmbH. N.B., D.A., and K.T. were employed at Sartorius Stedim Biotech GmbH., (© 2024 The Authors. Engineering in Life Sciences published by Wiley‐VCH GmbH.)

Study Question: How do plasma progesterone (P) and dydrogesterone (D) concentrations together with endometrial histology, transcriptomic signatures, and immune cell composition differ when oral dydrogesterone (O-DYD) or micronized vaginal progesterone (MVP) is used for luteal phase support (LPS)?, Summary Answer: Although after O-DYD intake, even at steady-state, plasma D and 20αdihydrodydrogesterone (DHD) concentrations spiked in comparison to P concentrations, a similar endometrial signature was observed by histological and transcriptomic analysis of the endometrium., What Is Known Already: O-DYD for LPS has been proven to be noninferior compared to MVP in two phase III randomized controlled trials. Additionally, a combined individual participant data and aggregate data meta-analysis indicated that a higher pregnancy rate and live birth rate may be obtained in women receiving O-DYD versus MVP for LPS in fresh IVF/ICSI cycles. Little data are available on the pharmacokinetic (PK) profiles of O-DYD versus MVP and their potential molecular differences at the level of the reproductive organs, particularly at the endometrial level., Study Design, Size, Duration: Thirty oocyte donors were planned to undergo two ovarian stimulation (OS) cycles with dual triggering (1.000 IU hCG + 0.2 mg triptorelin), each followed by 1 week of LPS: O-DYD or MVP, in a randomized, cross-over, double-blind, double-dummy fashion. On both the first and eighth days of LPS, serial blood samples upon first dosing were harvested for plasma D, DHD, and P concentration analyses. On Day 8 of LPS, an endometrial biopsy was collected for histologic examination, transcriptomics, and immune cell analysis., Participants/materials, Setting, Methods: All oocyte donors were <35 years old, had regular menstrual cycles, no intrauterine contraceptive device, anti-Müllerian hormone within normal range and a BMI ≤29 kg/m2. OS was performed on a GnRH antagonist protocol followed by dual triggering (1.000 IU hCG + 0.2 mg triptorelin) as soon as ≥3 follicles of 20 mm were present. Following oocyte retrieval, subjects initiated LPS consisting of MVP 200 mg or O-DYD 10 mg, both three times daily. D, DHD, and P plasma levels were measured using liquid chromatography-tandem mass spectrometry. Histological assessment was carried out using the Noyes criteria. Endometrial RNA-sequencing was performed for individual biopsies and differential gene expression was analyzed. Endometrial single-cell suspensions were created followed by flow cytometry for immune cell typing., Main Results and the Role of Chance: A total of 21 women completed the entire study protocol. Subjects and stimulation characteristics were found to be similar between groups. Following the first dose of O-DYD, the average observed maximal plasma concentrations (Cmax) for D and DHD were 2.9 and 77 ng/ml, respectively. The Cmax for D and DHD was reached after 1.5 and 1.6 h (=Tmax), respectively. On the eighth day of LPS, the first administration of that day gave rise to a Cmax of 3.6 and 88 ng/ml for D and DHD, respectively. For both, the observed Tmax was 1.5 h. Following the first dose of MVP, the Cmax for P was 16 ng/ml with a Tmax of 4.2 h. On the eighth day of LPS, the first administration of that day showed a Cmax for P of 21 ng/ml with a Tmax of 7.3 h. All 42 biopsies showed endometrium in the secretory phase. The mean cycle day was 23.9 (±1.2) in the O-DYD group versus 24.0 (±1.3) in the MVP group. RNA-sequencing did not reveal significantly differentially expressed genes between samples of both study groups. The average Euclidean distance between samples following O-DYD was significantly lower than following MVP (respectively 12.1 versus 18.8, Mann-Whitney P = 6.98e-14). Immune cell profiling showed a decrease of CD3 T-cell, γδ T-cell, and B-cell frequencies after MVP treatment compared to O-DYD, while the frequency of natural killer (NK) cells was significantly increased., Limitations, Reasons for Caution: The main reason for caution is the small sample size, given the basic research nature of the project. The plasma concentrations are best estimates as this was not a formal PK study. Whole tissue bulk RNA-sequencing has been performed not correcting for bias caused by different tissue compositions across biopsies., Wider Implications of the Findings: This is the first study comparing O-DYD/MVP, head-to-head, in a randomized design on a molecular level in IVF/ICSI. Plasma serum concentrations suggest that administration frequency is important, in addition to dose, specifically for O-DYD showing a rapid clearance. The molecular endometrial data are overall comparable and thus support the previously reported noninferior reproductive outcomes for O-DYD as compared to MVP. Further research is needed to explore the smaller intersample distance following O-DYD and the subtle changes detected in endometrial immune cells., Study Funding/competing Interest(s): Not related to this work, C.Bl. has received honoraria for lectures, presentations, manuscript writing, educational events, or scientific advice from Abbott, Ferring, Organon, Cooper Surgical, Gedeon-Richter, IBSA, and Merck. H.T. has received honoraria for lectures, presentations, manuscript writing, educational events, or scientific advice from Abbott, Ferring, Cooper Surgical, Gedeon-Richter, Cook, and Goodlife. S.M. has received honoraria for lectures, presentations, educational events, or scientific advice from Abbott, Cooper Surgical, Gedeon-Richter, IBSA, and Merck and Oxolife. G.G. has received honoraria for lectures, presentations, educational events, or scientific advice from Merck, MSD, Organon, Ferring, Theramex, Gedeon-Richter, Abbott, Biosilu, ReprodWissen, Obseva, PregLem, Guerbet, Cooper, Igyxos, and OxoLife. S.V.-S. is listed as inventor on two patents (WO2019115755A1 and WO2022073973A1), which are not related to this work., Trial Registration Number: EUDRACT 2018-000105-23., (© The Author(s) 2023. Published by Oxford University Press on behalf of European Society of Human Reproduction and Embryology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

So far, tendon regeneration has mainly been analyzed independent from its adjacent tissues. However, the subacromial bursa in particular appears to influence the local inflammatory milieu in the shoulder. The resolution of local inflammation in the shoulder tissues is essential for tendon regeneration, and specialized pro-resolving mediators (SPMs) play a key role in regulating the resolution of inflammation. Here, we aimed to understand the influence of the bursa on disease-associated processes in neighboring tendon healing. Bursa tissue and bursa-derived cells from patients with intact, moderate and severe rotator cuff disease were investigated for the presence of pro-resolving and inflammatory mediators, as well as their effect on tenocytes and sensitivity to mechanical loading by altering SPM signaling mediators in bursa cells. SPM signal mediators were present in the bursae and altered depending on the severity of rotator cuff disease. SPMs were particularly released from the bursal tissue of patients with rotator cuff disease, and the addition of bursa-released factors to IL-1β-challenged tenocytes improved tenocyte characteristics. In addition, mechanical loading modulated pro-resolving processes in bursa cells. In particular, pathological high loading (8% strain) increased the expression and secretion of SPM signaling mediators. Overall, this study confirms the importance of bursae in regulating inflammatory processes in adjacent rotator cuff tendons.

Background: The treatment of lateral epicondylitis remains unsatisfactory in certain cases. The aim of this study is to investigate the efficiency of an ultrasound-guided infiltration combined with fenestration of the extensor tendon postulating a 50% reduction in pain on exertion within 6 months., Methods: In a prospective, nonrandomized, multicenter study design, 68 patients with chronic lateral epicondylitis and symptoms lasted for at least 6 weeks were included. Each hospital has been assigned for Traumeel (A), autologous whole blood (B), or dextrose (C) in advance. Preinterventional, 6 weeks, 12 weeks, 6 and 12 months after infiltration, patient-related outcome parameter, and dorsal wrist extension strength were documented. Preinterventional (obligate) and after 6 months (optional) radiological evaluation (magnetic resonance imaging) was performed., Results: The Visual Analog Scale showed a significant reduction after 6 months in all groups (A. 4.8-2.5, B. 6.2-2.3, C. 5.8-2.4). Similar results could be observed with Subjective elbow value, Disabilities of Arm, Shoulder, and Hand Score, Mayo Elbow Performance Score, and Patient Rated Tennis Elbow Evaluation. The loss of strength could be completely compensated after about 6 months. Magnetic resonance imaging did not fully reflect clinical convalescence. Re-infiltrations were sometimes necessary for final reduction of symptoms (A = 11, B = 8, C = 4). Switching to surgical intervention was most frequently observed in group C (A = 2, B = 1, C = 5). In 14.5% of the cases, no improvement of the symptoms could be achieved with this method., Conclusion: The primary hypothesis of a significant long-term pain reduction of at least 50% could be achieved regardless of the medication chosen., (© 2023 The Authors.)

Taxonomic data are a scientific common. Unlike nomenclature, which has strong governance institutions, there are currently no generally accepted governance institutions for the compilation of taxonomic data into an accepted global list. This gap results in challenges for conservation, ecological research, policymaking, international trade, and other areas of scientific and societal importance. Consensus on a global list and its management requires effective governance and standards, including agreed mechanisms for choosing among competing taxonomies and partial lists. However, governance frameworks are currently lacking, and a call for governance in 2017 generated critical responses. Any governance system to which compliance is voluntary requires a high level of legitimacy and credibility among those by and for whom it is created. Legitimacy and credibility, in turn, require adequate and credible consultation. Here, we report on the results of a global survey of taxonomists, scientists from other disciplines, and users of taxonomy designed to assess views and test ideas for a new system of taxonomic list governance. We found a surprisingly high degree of agreement on the need for a global list of accepted species and their names, and consistent views on what such a list should provide to users and how it should be governed. The survey suggests that consensus on a mechanism to create, manage, and govern a single widely accepted list of all the world's species is achievable. This finding was unexpected given past controversies about the merits of list governance.

Pregnancy is likely nature's most elaborate model of dynamic adaptations occurring over a distinct period of time at specific sites of the maternal body. Spatially-resolved transcriptomic analyses now enable the comprehensive decoding of these dynamic adaptations during the early onset stages of mammalian pregnancies and throughout fetal development., Competing Interests: Declaration of interests The authors declare no conflicts of interest., (Copyright © 2023. Published by Elsevier Ltd.)

Neonatal health is determined by the transfer of maternal antibodies from the mother to the fetus. Besides antibodies, maternal cells cross the placental barrier and seed into fetal organs. Contrary to maternal antibodies, maternal microchimeric cells (MMc) show a high longevity, as they can persist in the offspring until adulthood. Recent evidence highlights that MMc leukocytes promote neonatal immunity against early-life infections in mice and humans. As shown in mice, this promotion of immunity was attributable to an improved fetal immune development. Besides this indirect effect, MMc may be pathogen-specific and thus, directly clear pathogen threats in the offspring postnatally. By using ovalbumin recombinant Listeria monocytogenes (LmOVA), we here provide evidence that OVA-specific T cells are transferred from the mother to the fetus, which is associated with increased activation of T cells and a milder course of postnatal infection in the offspring. Our data highlight that maternally-derived passive immunity of the neonate is not limited to antibodies, as MMc have the potential to transfer immune memory between generations., (© 2023 The Authors. Published under the terms of the CC BY 4.0 license.)

A displaced anterior glenoid rim fracture, the so-called bony Bankart lesion, occurs after a traumatic shoulder dislocation resulting from a high energy trauma and is associated with recurrent shoulder instability. Different surgical techniques have been described in the literature to address this pathology, including open reduction and fixation, as well as arthroscopic transosseous, and single-row or double-row approaches with the use of suture anchors. However, there is currently no gold standard of treatment and the stability of fixation and the healing of the bony fragment are still a concern. The purpose of this report was to introduce an arthroscopic independent double-row (IDR) bony Bankart repair technique for fixation of large glenoid fractures., Competing Interests: Author PM receives royalties from Arthrex Inc. and consultant payments from Arthrex Inc., Medacta and Depuy/Synthes., (Thieme. All rights reserved.)

The national database (NDB) of the German regional collaborative rheumatology centers was switched to the RheMIT documentation software last year. Rheumatology centers that already use RheMIT for care contracts or other research projects can therefore use the software to also participate in the NDB. Experiences from a hospital, a medical care center and a specialist practice show how the changeover to RheMIT from an existing documentation system or a new participation in the NDB with RheMIT can be implemented. The NDB team at the German Rheumatism Research Center in Berlin (DRFZ) welcomes new participating rheumatology centers., (© 2023. The Author(s).)

The long-term outcome of connective tissue diseases is associated with the time from symptom onset to diagnosis. To understand gaps in care, we determine whether the length of time between symptom onset and first presentation to a rheumatologist has changed in Germany in recent decades. We analyzed data on patients diagnosed with connective tissue diseases (n = 19,662) collected from the German National Database of the Regional Cooperative Rheumatology Centers. We reviewed the onset of relevant symptoms listed at first presentations from 1993 to 2018 and performed a quantitative analysis of the intervals until first presentation to a rheumatologist. We compared time intervals and performed a linear mixed regression model with random effects to identify associated factors. Although the interval between the onset of symptoms and first presentation to a rheumatologist has diminished since 1980 for all connective tissue diseases, there has been no relevant improvement during the past 2 decades. The interval between symptoms and presentation increases with patients age for all connective tissue diseases (e.g., Systemic sclerosis; for each 10-year-increment of patients age: β 0.41, CI 0.38; 0.44). Among those diagnosed with systemic sclerosis, the mean interval was 1.5 years (95% CI 1.1; 1.8) for male patients and 2.6 years (95% CI 2.4; 2.8) for females. Patients presenting with different degrees of disease severity on their first visits and with different educational levels had similar mean intervals between symptoms and first presentation regardless of their final diagnoses. Over the past 2 decades, the time to first consultation with a rheumatologist has not continued to improve in Germany, but has stagnated at the same level. Selected patient subgroups, such as older patients with suspected connective tissue diseases and female patients with suspected systemic sclerosis, are at risk to present late and may in particular benefit from an earlier referral to a rheumatologist., (© 2023. The Author(s).)

The indication for surgical treatment of lateral snapping elbow syndrome is recurrent joint blockage in combination with pain of the affected elbow joint. Different parts of the lateral synovial capsule sleeve complex, including the annular ligament itself, a hypertrophic synovial fold, or meniscus-like soft tissue interposition can lead to painful entrapment. Surgical treatment options can include an arthroscopic or open procedure. The aim of this technical note is to provide a step-by-step illustration of the authors' preferred arthroscopic approach with a comprehensive review of literature on clinical outcome., Competing Interests: The authors declare that they have no conflict of interest., (Thieme. All rights reserved.)

The aim of the study is to describe the surgical technique and to report the outcomes of triceps reflecting anconeus pedicle (TRAP) approach for intercondylar fractures of the humerus. Twenty two patients with intercondylar fractures of the humerus were operated on by open reduction via the TRAP approach and internal fixation with dual precontoured locking plates. Data were collected on union time, postoperative complications, range of motion (ROM), triceps power, and objective clinical measurement. All fractures were united with a mean union time of 16.5 weeks (range 12-22). All patients had good-to-excellent Mayo Elbow Performance (MEP) score results with a mean ROM of 118.2 degrees (range 90-135). Triceps power was grade 5 in 16 patients and grade 4 in 6. There were 3 transient ulnar nerve palsy and 1 heterotopic ossification. TRAP approach is safe and effective in terms of utility for articular reduction, restoration of elbow motion, and triceps function for intercondylar fractures of the humerus.

Background: Isolated soft tissue injuries of the posterior capsulolabral complex can be addressed arthroscopically, with various anchor systems available for repair., Purpose: To evaluate clinical and patient-reported outcomes after arthroscopic capsulolabral repair in patients with posterior shoulder instability (PSI) and to compare differences in outcomes between patients treated with a suture-first technique (PushLock anchor) and an anchor-first technique (FiberTak all-suture anchor)., Study Design: Cohort study; Level of evidence, 3., Methods: Included were 32 patients with dynamic structural PSI (type B2 according to the ABC classification) treated with an arthroscopic posterior capsulolabral repair. After a mean follow-up time of 4.8 ± 3.4 years (range, 2-11) patients were evaluated clinically, and standardized outcome scores were obtained for the Subjective Shoulder Value (SSV), the Western Ontario Shoulder Instability Index (WOSI), Rowe, Kerlan-Jobe Orthopaedic Clinic (KJOC), patient satisfaction (0-5 [best]), and pain on a visual analog scale (VAS; 0-10 [worst])., Results: The overall satisfaction level with the outcome of the surgery was 4.6 ± 0.5 (range, 4-5). No patient suffered from instability events. The mean VAS level for pain was 0.4 ± 0.9 (range, 0-4) at rest and 1.9 ± 2.0 (range, 0-6) during motion. The mean SSV was 80 ± 17 (range, 30-100), the mean postoperative WOSI score 75% ± 19% (range, 18-98), the mean Rowe score 78 ± 20 (range, 10-100), and the mean KJOC score was 81 ± 18 (range, 40-100) for the entire cohort. There was no significant difference between the techniques with regard to range of motion, strength, or clinical outcome scores., Conclusion: Arthroscopic posterior capsulolabral repair was a satisfactory method to treat structural PSI type B2 with regard to stability, pain relief, and functional restoration. The majority of patients had good outcomes. No differences in outcomes were observed between the anchor-first and suture-first techniques., Competing Interests: The authors declared that there are no conflicts of interest in the authorship and publication of this contribution. AOSSM checks author disclosures against the Open Payments Database (OPD). AOSSM has not conducted an independent investigation on the OPD and disclaims any liability or responsibility relating thereto., (© The Author(s) 2023.)

The therapy of the lateral epicondylopathy (tennis elbow) includes drug injection into the extensor tendon insertion in chronic cases. The choice of medication and the type of injection is decisive for the success of therapy. Furthermore, accurate application is indispensable for therapy success (e.g. peppering injection technique, ultrasound-supported injection technique). Corticosteroid injection is often associated with short-term success, so that other options have found their way into everyday practice. Objectification of treatment success is usually defined by Patient-Reported Outcome Measurements (PROM). With the introduction of Minimal Clinically Important Differences (MCID), statistically significant results are put into perspective in terms of clinical significance. Therapy for lateral epicondylopathy was considered effective if the mean difference in score results between baseline and follow-up exceeded 1.5 points for the Visual Analogue Scale (VAS), 16 points for Disabilities of Arm, Shoulder and Hand Score (DASH), 11 points for Patient-Rated Tennis Elbow Evaluation (PRTEE), and 15 points for Mayo Elbow Performance Score (MEPS). However, the effectiveness must still be critically questioned according to meta-analytical evaluations, in which healing within 12 months was found in 90% of the cases of untreated chronic tennis elbow in the placebo groups. The use of substances, such as Traumeel (Biologische Heilmittel Heel GmbH, Baden-Baden, Germany), hyaluronic acid, botulinum toxin, platelet rich plasma (PRP), autologous blood or polidocanol, are based on various mechanisms. In particular, the use of PRP or autologous blood for the treatment of musculotendinous and degenerative articular pathologies has become popular, although the studies regarding effectiveness are inconsistent. PRP can be divided into leukocyte-rich (LR-PRP) and leukocyte-poor plasma (LP-PRP) according to its preparation. In contrast to LP-PRP, LR-PRP incorporates the middle and intermediate layers, but there is no standardized preparation described in the literature. Conclusive data regarding effective efficacy are still pending., (© 2023. The Author(s), under exclusive licence to Springer Medizin Verlag GmbH, ein Teil von Springer Nature.)

This study evaluated the reliability and comprehensiveness of the Unified classification system (UCPF), Wright & Cofield, Worland and Kirchhoff classifications and related treatment recommendations for periprosthetic shoulder fractures (PPSFx). Two shoulder arthroplasty specialists (experts) and two orthopaedic residents (non-experts) assessed 20 humeral-sided and five scapula-sided cases of PPSFx. We used the unweighted Cohen's Kappa (κ) for measuring the intra-observer reliability and Krippendorff's alpha (α) for measuring the inter-observer reliability. The inter-rater reliabilities for the Wright & Cofield and Worland classifications were substantial for all groups. The expert and non-expert groups for UCPF also showed substantial inter-rater agreement. The all-rater group for the UCPF and the expert and non-expert group for the Kirchhoff classification revealed moderate inter-rater reliability. For the Kirchhoff classification, only fair inter-rater reliability was found for the non-expert group. Almost perfect intra-rater reliability was measured for all groups of the Wright & Cofield classification and the all-rater and expert groups of the UCPF. All groups of the Kirchhoff and Worland classifications and the group of non-experts for the UCPF had substantial intra-rater reliabilities. Regarding treatment recommendations, substantial inter-rater and moderate intra-rater reliabilities were found. Simple classification systems for PPSFx (Wright & Cofield, Worland) show the highest inter- and intra-observer reliability but lack comprehensiveness as they fail to describe scapula-sided fractures. The complex Kirchhoff classification shows limited reliability. The UCPF seems to offer an acceptable combination of comprehensiveness and reliability.

Purpose: Besides the multi-layered capsule-ligamentous complex of the elbow joint the high bony congruence in the ulnohumeral joint contributes to elbow stability. Therefore, we assume that specific anatomical configurations of the trochlear notch predispose to dislocation. In case of ligamentous elbow dislocation both conservative and surgical treatment is possible without a clear treatment algorithm. Findings of constitutional bony configurations could help deciding for the best treatment option., Methods: In this retrospective matched-pair analysis we compared MRI imaging from patients sustaining a primary traumatic elbow dislocation (instability group) with patients suffering from chronic lateral epicondylitis (control group), treated between 2009 and 2019. Two independent observers measured different anatomical landmarks of the trochlear notch in a multiplanar reconstructed standardized sagittal trochlear plane (SSTP). Primarily, opening angle and relative depth of the trochlear notch were determined. After adjustment to the proximal ulnar rim in the SSTP, coronoid and olecranon angle, the articular angle as well as the ratio of the tip heights of the trochlear notch were measured., Results: We compared 34 patients in the instability group (age 48 ± 14 years, f/m 19/15) with 34 patients in the control group (age 47 ± 16 years, f/m 19/15). Instability group showed a significantly larger opening angle (94.1° ± 6.9° vs. 88.5° ± 6.9°, p = 0.0002), olecranon angle (60.9° ± 5.3° vs. 56.1° ± 5.1°, p < 0.0001) and articular angle (24.7° ± 6.4° vs. 22.3° ± 5.8°, p = 0.02) compared to the control group. Measuring the height from the coronoid (ch) and olecranon (oh) tip also revealed a significantly larger tip ratio (tr = ch/oh) in the instability group (2.7 ± 0.8 vs. 2.2 ± 0.5, p < 0.0001). The relative depth (61.0% ± 8.3% vs. 62.7% ± 6.0%, p = 0.21) of the trochlear notch as well as the coronoid angle (32.8° ± 4.5° vs. 31.7° ± 5.2°, p = 0.30) showed no significant difference in the instability group compared to the control group. The interrater reliability of all measurements was between 0.83 and 0.94., Conclusion: MRI of patients with elbow dislocation show that there seems to be a bony anatomical predisposition. According to the results, it seems reasonable to include predisposing bony factors in the decision-making process when surgical stabilization and conservative treatment is possible. Further biomechanical studies should prove these assumptions to generate critical bony values helping surgeons with decision making., Level of Evidence: III., (© 2021. The Author(s).)

Background: Different joint-preserving techniques for treatment of preosteoarthritic, constitutional static (type C1) posterior shoulder instability (PSI) have been proposed, including posterior glenoid open wedge osteotomy and bone graft augmentation. However, the techniques are demanding, the reported complication and reoperation rates are high, and posterior decentering cannot reliably be reversed., Purpose: To assess the clinical and radiological longitudinal outcomes of patients with type C1 PSI after arthroscopic posterior articular coverage and shift (PACS) surgery., Study Design: Case series; Level of evidence, 4., Methods: We performed a retrospective analysis of a prospective database with longitudinal follow-up including 14 shoulders in 13 patients who underwent an arthroscopic PACS procedure for symptomatic preosteoarthritic constitutional static posterior instability (type C1) with previous failed nonoperative treatment. Patients were clinically evaluated before surgery and at 3, 6, 12, and 24 months postoperatively in terms of satisfaction and pain levels as well as standardized physical examination, Subjective Shoulder Value (SSV), Western Ontario Shoulder Instability Index (WOSI) score, Constant score, and Rowe score. Preoperative, postoperative, and follow-up magnetic resonance imaging scans were obtained in all patients. A paired 2-sample t test was used to compare changes in continuous variable parameters over time. Correlation analyses were performed using the Pearson correlation coefficient., Results: All outcome scores and the pain level improved significantly from preoperatively to postoperatively, and the improvement was sustained over the follow-up period of 2 years (pain level, 6.4 preoperatively vs 3.3 at 2 years, P < .001; SSV, 40 vs 70, P = .001; WOSI, 33 vs 56, P = .001; Constant, 70 vs 79, P = .049; Rowe, 52 vs 76, P < .001). The mean glenohumeral and scapulohumeral subluxation indices were significantly lower in the early postoperative period compared with preoperative measurements (glenohumeral, 52% ± 6% vs 58% ± 10%, P = .02; scapulohumeral, 70% ± 8%; vs 77% ± 9%, P = .002, respectively); however, they returned to baseline values at follow-up (57% ± 7% vs 58% ± 10%, P = .7; 75% ± 6% vs 77% ± 9%, P = .4, respectively). A high scapulohumeral subluxation index, excessive glenoid retroversion, and increased posterior positioning of the humeral head in relation to scapular blade axis and older age were correlated with worse clinical outcomes., Conclusion: Over the follow-up period of 2 years, the PACS procedure significantly improved outcome scores in patients who had preosteoarthritic constitutional static posterior shoulder instability, especially in younger patients with less severe glenoid retroversion and posterior decentering of the humeral head. However, similar to other techniques, the PACS procedure needs to be considered a symptomatic therapy that does not reverse the underlying cause or stop the progressive pathology.

The conception of how the immune system is organized has been significantly challenged over the last years. It became evident that not all lymphocytes are mobile and recirculate through secondary lymphoid organs. Instead, subsets of immune cells continuously reside in tissues until being reactivated, e.g., by a recurring pathogen or other stimuli. Consequently, the concept of tissue-resident immunity has emerged, and substantial evidence is now available to support its pivotal function in maintaining tissue homeostasis, sensing challenges and providing antimicrobial protection. Surprisingly, insights on tissue-resident immunity in the barrier tissues of the female reproductive tract are sparse and only slowly emerging. The need for protection from vaginal and amniotic infections, the uniqueness of periodic tissue shedding and renewal of the endometrial barrier tissue, and the demand for a tailored decidual immune adaptation during pregnancy highlight that tissue-resident immunity may play a crucial role in distinct compartments of the female reproductive tract. This review accentuates the characteristics of tissue-resident immune cells in the vagina, endometrium, and the decidua during pregnancy and discusses their functional role in modulating the risk for infertility, pregnancy complications, infections, or cancer. We here also review data published to date on tissue-resident immunity in the male reproductive organs, which is still a largely uncharted territory., (© 2022. The Author(s).)

The pathogenesis of long-Covid symptoms remains incompletely understood. Therefore, we aimed to determine cardiopulmonary limitations 6 months after surviving COVID-19 using pulmonary function tests, echocardiographic studies to the point of analysis of global-longitudinal-strain (GLS), which describes the cycling myocardium deformation and provides better data on left ventricular (LV) dysfunction than LV ejection fraction (LVEF), and validated questionnaires. Overall, 60 consecutive hospitalized patients were included (61 ± 2 years, 40% treated in the ICU). At follow-up (194 ± 3 days after discharge), fatigue was the most prevalent symptom (28%). Patients with fatigue were more symptomatic overall and characterized by worse quality of life (QoL) scores compared to patients without fatigue (all p < 0.05), mainly due to limited mobility and high symptom burden. While PFT variables and LVEF were normal in the vast majority of patients (LVEF = 52% (45-52%)), GLS was significantly reduced (- 15% (- 18 to - 14%)). However, GLS values were not different between patients with and without fatigue. In conclusion, fatigue was the most prevalent long-Covid symptom in our cohort, which was associated with worse QoL mainly due to limited mobility and the high burden of concomitant symptoms. Patients showed a subtle myocardial dysfunction 6 months after surviving COVID-19, but this did not relate to the presence of fatigue., (© 2022. The Author(s).)

In SARS-CoV-2 diagnostics, cycle threshold (Ct) values from qRT-PCRs semi-quantitatively estimate a patient's viral load. However, relevant analytical differences between qRT-PCR assays are often neglected. This study was designed (i) to identify such differences between five commonly used assays and (ii) to demonstrate a straightforward strategy to harmonize them. QRT-PCRs for SARS-CoV-2 were carried out in 85 oropharyngeal swab samples using three fully automated (Alinity m, cobas ® 6800 and GeneXpert) and two semi-automated (genesig ® and RIDA ® GENE) assays. Qualitative results (positive/negative) showed excellent comparability between the fully automated assays, but not between the Alinity m and semi-automated methods. Ct values significantly varied between all the methods, with the median values ranging from 22.76 (Alinity m) to 30.89 (RIDA ® GENE) and 31.50 (genesig ® ), indicating the lowest sensitivity for semi-automated methods. Passing-Bablok analysis further revealed systemic biases. Assay-specific viral load concentration calculations-based on generated individual standard curves-resulted in much better comparability between the assays. Applying these calculations, significant differences were no longer detectable. This study highlights relevant analytical differences between SARS-CoV-2 qRT-PCR assays, leading to divergent decisions about the mandatory isolation of infected individuals. Secondly, we propose a strategy to harmonize qRT-PCR assays to achieve better comparability. Our findings are of particular interest for laboratories utilizing different assays.

Life-long brain function and mental health are critically determined by developmental processes occurring before birth. During mammalian pregnancy, maternal cells are transferred to the fetus. They are referred to as maternal microchimeric cells (MMc). Among other organs, MMc seed into the fetal brain, where their function is unknown. Here, we show that, in the offspring's developing brain in mice, MMc express a unique signature of sensome markers, control microglia homeostasis and prevent excessive presynaptic elimination. Further, MMc facilitate the oscillatory entrainment of developing prefrontal-hippocampal circuits and support the maturation of behavioral abilities. Our findings highlight that MMc are not a mere placental leak out, but rather a functional mechanism that shapes optimal conditions for healthy brain function later in life., (© 2022. The Author(s).)

Aims: In this prospective, placebo-controlled, double-blind, exploratory study, we examined early and more delayed effects of empagliflozin treatment on haemodynamic parameters (primary endpoint: cardiac output) and kidney function including parameters of acute kidney injury (AKI) in patients with acute decompensated heart failure (HF)., Methods and Results: Patients with acute decompensated HF with or without diabetes were randomized to empagliflozin 10 mg or placebo for 30 days. Haemodynamic, laboratory, and urinary parameters were assessed after 6 h, 1 day, 3 days, 7 days, and 30 days of treatment. Median time between hospital admission and randomization was 72 h. Baseline characteristics were not different in the empagliflozin (n = 10) and placebo (n = 9) groups. Empagliflozin led to a significant increase in urinary glucose excretion throughout the study (baseline: 37 ± 15 mg/24 h; Day 1: 14 565 ± 8663 mg/24 h; P = 0.001). Empagliflozin did not affect the primary endpoint of cardiac index or on systemic vascular resistance index at any time point. However, empagliflozin significantly reduced parameters of AKI (urinary TIMP-2 and IGFBP7 by NephroCheck® as indicators of tubular kidney damage), which became significant after 3 days of treatment [placebo: 1.1 ± 1.1 (ng/mL) 2 /1000; empagliflozin: 0.3 ± 0.2 (ng/mL) 2 /1000; P = 0.02] and remained significant at the 7 day time point [placebo: 2.5 ± 3.8 (ng/mL) 2 /1000; empagliflozin: 0.3 ± 0.2 (ng/mL) 2 /1000; P = 0.003]., Conclusions: In this study, empagliflozin treatment did not affect haemodynamic parameters but significantly reduced markers of tubular injury in patients with acute decompensated HF., (© 2022 The Authors. ESC Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.)

Distal radius fractures are common and account for approximately 14% to 18% of all adult extremity injuries. On rare occasions, ipsilateral elbow dislocation can be observed additionally. However, this can be missed without careful examination, especially in patients experiencing altered mental status. The aim of this study was to analyze the mechanism, level of injury, demographics, and associated injuries in distal radius fracture with ipsilateral elbow dislocation. Between 2012 and 2019, we searched our trauma database for distal radius fracture with ipsilateral elbow dislocation. All patients older than 18 years old were included. Data on demographics, mechanism of injury, level of energy, and subsequent treatment were collected. A total of seven patients were identified. The mean age in this cohort was 68.7 ± 13.3 years old, and the left side was involved in 71.4% of the patients. Females were affected in 85.7% ( n = 6/7) of cases, all of whom suffered from low-energy monotrauma at a mean age of 71.5 ± 12.3 years old. One male patient suffered from high-energy trauma (52 years old). Mainly, posterior elbow dislocations were observed (66.7%; n = 4/6). Distal radius fracture patterns, in accordance with the AO classification, included two C2-, two C3-, one C1-, and one B1-type fractures. In the patient suffering from high-energy trauma, the closed distal radius fracture was classified as type C3. Associated injures included open elbow dislocation, ulnar artery rupture, and damage to the flexor digitorum superficialis. Although distal radius fracture with ipsilateral elbow dislocation is thought to be from high-energy trauma, this study shows that most patients were elderly females suffering from low-energy mechanisms. It is important for clinicians to maintain a high level of suspicion for any concomitant injury in this population.

ObjectiveTo analyse the performance of the rheumatoid arthritis impact of disease (RAID) score in patients with ankylosing spondylitis, polymyalgia rheumatica, systemic lupus erythematosus, primary Sjögren's syndrome, idiopathic inflammatory myositis and systemic sclerosis, as compared with rheumatoid arthritis (RA). Methods A total of 12 398 patients from the German National Database were included. For each diagnosis, we calculated age-adjusted/sex-adjusted partial correlation coefficients between RAID and patient global (PtGl) health, PtGl disease activity, physician global (PhGl) disease activity, Well-Being Index (WHO-5) and EuroQoL-5 Dimensions (EQ-5D). As a measure of agreement, the mean differences between the RAID and other outcomes were compared with the respective differences for RA. The effect of each diagnosis on the difference between RAID and the other scores was assessed with linear regression, with RA as the reference. Results Across all diagnoses, RAID correlated strongly with PtGl health (0.71-0.83), moderately to strongly with PtGl disease activity (0.59-0.79), WHO-5 (0.65-0.81) and EQ-5D (0.68-0.73) and weakly with PhGl disease activity (0.23-0.38). Mean differences were calculated for RAID and PtGl disease activity (0 to -0.6), PtGl health (-0.4 to -0.9), WHO-5 (-0.7 to -1.3), EQ-5D (1.1 to 1.7) and PhGl disease activity (1.4 to 2.2). Discrepancies between other scores and RAID were comparable to RA. Linear regression revealed no clinically relevant effect of any of the diagnoses on the difference between RAID and the other outcomes. Conclusion The RAID score performs comparably across all diagnoses investigated. This supports the use of RAID for measuring the impact also of other rheumatic diseases., Competing Interests: Competing interests: KT, KA, AZ, MA, KK and UvH: None declared, SS: Speakers bureau: BMS, Gilead, GSK, Janssen, Lilly, Novartis, Pfizer, Sanofi, UCB, Consultant of: Abbvie, Gilead, GSK, UCB, Novartis. JC: Paid instructor for Rheumatologische Fortbildungsakademie GmbH, Grant/research support from Abbvie, AstraZeneca, BMS, GALAPAGOS, GSK, Lilly, Medac, MSD, Pfizer, Sanofi, UCB., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Deficiency in vitamin D3 and its metabolites has been linked to dismal outcomes in patients with chronic diseases, including cardiovascular disease and heart failure (HF). It remains unclear if a vitamin D3 status is a prognostic feature in patients with acute decompensated HF. Methods: We assessed serum levels of 25-OH-vitamin D3 and 1,25-(OH)2-vitamin D3 in 139 patients with acute HF who had been admitted to the intermediate care unit of a maximum care hospital. The follow-up period was one year. After exclusion of patients with sampling errors and those who were lost to follow-up, 118 patients remained in the final study cohort. Outcome estimates by 25-OH-vitamin D3 and 1,25-(OH)2-vitamin D3 levels were compared to the Seattle Heart Failure (SHF) Model. Results: More than two-thirds (79.7%) of the patients showed inadequate 25-OH-vitamin D3 levels (i.e., <30 ng/mL) upon admission. Low levels of 1,25-(OH)2-vitamin D3 (i.e., <19.9 pg/mL) were observed in 16.1% of patients. Of the 118 HF patients, 22 (19%) died during the following 12 months. There were no differences in vitamin D3 levels between patients who died and those who survived, neither in 25-OH-vitamin D3 (23.37 ± 19.14 ng/mL vs. 19.11 ± 12.25 ng/mL; p = 0.19) nor in 1,25-(OH)2-vitamin D3 levels (31.10 ± 19.75 ng/mL vs. 38.25 ± 15.73 ng/mL; p = 0.02); therefore, vitamin D3 levels alone did not predict one-year survival (AUC [25-OH-vitamin D3] 0.50; 95% CI 0.34−0.65; AUC [1,25-(OH)2-vitamin D3] 0.62; 95% CI 0.48−0.76). Moreover, whilst the SHF model exhibited acceptable discriminatory ability for predicting one-year mortality (AUC 0.79; 95% CI 0.66−0.91), adding vitamin D levels on admission to the SHF score did not improve its discriminatory value. Conclusion: Our data do not support the use of vitamin D3 screening in patients admitted with acute decompensated HF to aid prognostication.

The subacromial bursa has long been demolded as friction-reducing tissue, which is often linked to shoulder pain and, therefore, partially removed during shoulder surgery. Currently, the discovery of the stem cell potential of resident bursa-derived cells shed a new light on the subacromial bursa. In the meanwhile, this neglected tissue is gaining more attention as to how it can augment the regenerative properties of adjacent tissues such as rotator cuff tendons. Specifically, the tight fibrovascular network, a high growth factor content, and the large progenitor potential of bursa-derived cells could complement the deficits that a nearby rotator cuff injury might experience due to the fact of its low endogenous regeneration potential. This review deals with the question of whether bursal inflammation is only a pain generator or could also be an initiator of healing. Furthermore, several experimental models highlight potential therapeutic targets to overcome bursal inflammation and, thus, pain. More evidence is needed to fully elucidate a direct interplay between subacromial bursa and rotator cuff tendons. Increasing attention to tendon repair will help to guide future research and answer open questions such that novel treatment strategies could harvest the subacromial bursa's potential to support healing of nearby rotator cuff injuries.

Background and Aim: Sodium-glucose cotransporter-2 (SGLT2) inhibitors, glucose-lowering drugs that increase urinary glucose excretion have been shown to reduce CV events in patients with type 2 diabetes (T2D). Furthermore, several studies have demonstrated that treatment with SGLT2 inhibitors affect calcium and phosphate homeostasis, but the effect of empagliflozin on these biomarkers is hitherto not investigated in detail. Therefore, this analysis of the EMPA hemodynamics study examined effects of empagliflozin on calcium and phosphate homeostasis., Methods: In this placebo-controlled, randomized, double-blind study patients with T2D were randomized to empagliflozin 10 mg (n = 20) or placebo (n = 22). Biomarkers of calcium and phosphate homeostasis were assessed before, and after 3 days and 3 months of treatment., Results: After 3 days of treatment empagliflozin significantly increased serum levels of phosphate (baseline: 1.10 ± 0.21 mmol/L; day 3: 1.25 ± 0.23 mmol/L; p = 0.036), parathyroid hormone (PTH) (baseline: 57.40 ± 30.49 pg/mL; day 3: 70.23 ± 39.25 pg/mL; p = 0.025), fibroblast growth factor 23 (FGF23) (baseline: 77.92 ± 24.31 pg/mL; day 3: 109.18 ± 58.20 pg/mL; p = 0.001) and decreased 1,25-dihydroxyvitamin D (baseline: 35.01 ± 14.01 ng/L; day 3: 22.09 ± 10.02 mg/L; p < 0.001), while no difference of these parameters was recorded after 3 months of treatment. Empagliflozin had no significant effects on serum calcium and markers of bone resorption (collagen type 1 β-carboxy-telopeptide = β-CTX) or formation (osteocalcin) after 3 days and 3 months of treatment., Conclusions: Empagliflozin treatment of patients with T2D transiently increases serum phosphate, PTH and FGF23, and decreases 1,25-dihydroxyvitamin D. This might reflect a temporal increase of sodium driven phosphate reabsorption in the proximal tubule of the kidney caused by increased sodium availability in response to SGLT2 inhibition., Competing Interests: MR, KT, NUKH, JM, SW and MH report no potential conflict of interest. NM has received support for clinical trial leadership from Boehringer Ingelheim, Novo Nordisk, served as a consultant to Boehringer Ingelheim, Merck, Novo Nordisk, AstraZeneca, BMS, received grant support from Boehringer Ingelheim, Merck, Novo Nordisk, and served as a speaker for Boehringer Ingelheim, Merck, Novo Nordisk, Lilly, BMS, and Astra Zeneca. ML received grants and personal fees from Boehringer Ingelheim, MSD and Novo Nordisk, personal fees from Amgen, Sanofi, Astra Zeneca, Bayer and Lilly., (© 2022 The Authors.)

Background: The aim of this study was to evaluate the clinical outcome and complication spectrum after delayed repair surgery of distal biceps tendon ruptures, postulating that satisfactory results are possible contrary to previous literature., Methods: Forty-three of 92 patients with a full workup (= OPT in) undergoing primary distal biceps tendon repair were included in this study. The mean age of participants was 49.5 years (range = 22-66 years). This cohort was divided into two groups: patients undergoing acute repair (<21 days = AR group) and a group with delayed intervention (>21 days = SR group). Beside clinical evaluation, functional scores and detection of heterotopic ossification were documented. Strength of flexion and supination were measured using a BIODEX multipoint system. In addition, thirty-one patients were included only in the evaluation of complications in the absence of consent for clinical examination (= OPT out)., Results: Concerning the OPT-in group, twenty-eight patients (ø age = 48.9 years; 22-63 years) received acute repair after an average of 9.2 ± 3.7 days. On the contrary, 15 patients (ø age = 50.5 years; 32-66 years) were treated with a delay after an average of 31.4 ± 10.4 days. Regarding patient-reported outcome measures, conflicting results emerge (AR/SR: Subjective Elbow Value = 87/80%, P  > .05; Mayo score = 96/93 pts, P  > .05; the Disabilities of the Arm, Shoulder and Hand score = 6/13 pts, P  < .05; and Oxford Elbow Score = 44/39 pts, P  < .05). The main complication is the paresthesia of the lateral antebrachial cutaneous nerve, which occurs more in the group of delayed repair (AR: 21.0%, SR 31.8%). Forty-one percentage of patients in the SR group described pain in the elbow with exertion in contrast to 17.3% in the AR group. In terms of elbow strength, no significant difference in the AR or SR group compared with the contralateral side could be observed., Conclusion: The data suggest that delayed repair of distal biceps ruptures beyond 3 weeks may result in satisfactory clinical outcomes. However, exertional pain and paresthesia of the lateral antebrachial cutaneous nerve may diminish results., (© 2022 The Authors.)

Background: The aim of this study was to categorize reasons for failure and to analyze the survivorship of multiple total knee arthroplasty (TKA) revisions., Methods: The study retrospectively evaluated all multiple TKA revisions performed between 2005 and 2015 at the authors' institutions. Sixty-three patients (35 female, 28 male, age 64 ± 10 years, follow-up 55 ± 36 months) underwent a total of 157 re-revision TKA surgeries (range 2-5). The revision indications were divided up into main diagnoses. Survivorship was evaluated by mixed model analysis., Results: The main overall reason for re-revision was periprosthetic joint infection (PJI) (48%), followed by instability (12%), polyethylene wear (11%), malpositioning (8%), and aseptic loosening (8%). Survivorship shortened with an increasing number of revision surgeries ( p = 0.003). While PJI was in 38% of all cases, the reason for the first revision, incidence increased constantly with the number of revisions (48% at second revision, 55% at third revision, 86% at fourth revision, and 100% at fifth revision, p = 0.022). If periprosthetic infection caused the first revision, patients showed an average of two more septic revisions at follow-up than patients with an aseptic first revision indication ( p < 0.001). In 36% of cases, the reason for follow-up surgery in case of periprosthetic infection was again PJI., Conclusion: The probability of survival of the implanted knee arthroplasty is significantly reduced with each subsequent revision. Periprosthetic infection is the main cause of multiple revisions.

Sodium-glucose cotransporter-2 (SGLT2) inhibitors have been shown to significantly reduce hospitalization for heart failure (HHF) and cardiovascular (CV) mortality in various CV outcome trials in patients with and without type 2 diabetes mellitus (T2D). SGLT2 inhibition further increased haemoglobin and haematocrit levels by an as yet unknown mechanism, and this increase has been shown to be an independent predictor of the CV benefit of these agents, for example, in the EMPA-REG OUTCOME trial. The present analysis of the EMPA haemodynamic study examined the early and delayed effects of empagliflozin treatment on haemoglobin and haematocrit levels, in addition to measures of erythropoiesis and iron metabolism, to better understand the underlying mechanisms. In this prospective, placebo-controlled, double-blind, randomized, two-arm parallel, interventional and exploratory study, 44 patients with T2D were randomized into two groups and received empagliflozin 10 mg or placebo for a period of 3 months in addition to their concomitant medication. Blood and urine was collected at baseline, on Day 1, on Day 3 and after 3 months of treatment to investigate effects on haematological variables, erythropoietin concentrations and indices of iron stores. Baseline characteristics were comparable in the empagliflozin (n = 20) and placebo (n = 22) group. Empagliflozin led to a significant increase in urinary glucose excretion (baseline: 7.3 ± 22.7 g/24 h; Day 1: 48.4 ± 34.7 g/24 h; P < 0.001) as well as urinary volume (baseline: 1740 ± 601 mL/24 h; Day 1: 2112 ± 837 mL/24 h; P = 0.011) already after 1 day and throughout the 3-month study period, while haematocrit and haemoglobin were only increased after 3 months of treatment (haematocrit: baseline: 40.6% ± 4.6%; Month 3: 42.2% ±  4.8%, P < 0.001; haemoglobin: baseline: 136 ± 19 g/L; Month 3: 142 ± 25 g/L; P = 0.008). In addition, after 3 months, empagliflozin further increased red blood cell count (P < 0.001) and transferrin concentrations (P = 0.063) and there was a trend toward increased erythropoietin levels (P = 0.117), while ferritin (P = 0.017), total iron (P = 0.053) and transferrin saturation levels (P = 0.030) decreased. Interestingly, the increase in urinary glucose excretion significantly correlated with the induction of erythropoietin in empagliflozin-treated patients at the 3-month timepoint (Spearman rho 0.64; P = 0.008). Empagliflozin increased haemoglobin concentrations and haematocrit with a delayed time kinetic, which was most likely attributable to increased erythropoiesis with augmented iron utilization and not haemoconcentration. This might be attributable to reduced tubular glucose reabsorption in response to SGLT2 inhibition, possibly resulting in diminished cellular stress as a mechanism for increased renal erythropoietin secretion., (© 2021 The Authors. Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd.)

A wealth of innate and adaptive immune cells and hormones are involved in mounting tolerance towards the fetus, a key aspect of successful reproduction. We could recently show that the specific cross talk between the pregnancy hormone progesterone and dendritic cells (DCs) is significantly engaged in the generation of CD4 + FoxP3 + regulatory T (Treg) cells while a disruption led to placental alterations and intra-uterine growth restriction. Apart from progesterone, also glucocorticoids affect immune cell functions. However, their functional relevance in the context of pregnancy still needs clarification. We developed a mouse line with a selective knockout of the glucocorticoid receptor (GR) on DCs, utilizing the cre/flox system. Reproductive outcome and maternal immune and endocrine adaptation of Balb/c-mated C57Bl/6 GR flox/flox CD11c cre/wt (mutant) females was assessed on gestation days (gd) 13.5 and 18.5. Balb/c-mated C57Bl/6 GR wt/wt CD11c cre/wt (wt) females served as controls. The number of implantation and fetal loss rate did not differ between groups. However, we identified a significant increase in fetal weight in fetuses from mutant dams. While the frequencies of CD11c + cells remained largely similar, a decreased expression of co-stimulatory molecules was observed on DCs of mutant females on gd 13.5, along with higher frequencies of CD4 + and CD8 + Treg cells. Histomorphological and gene expression analysis revealed an increased placental volume and an improved functional placental capacity in mice lacking the GR on CD11c + DCs. In summary, we here demonstrate that the disrupted communication between GCs and DCs favors a tolerant immune microenvironment and improves placental function and fetal development., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Diao, Hierweger, Wieczorek, Arck and Thiele.)

Background: The role of the subacromial bursa in the development or healing of shoulder pathologies is unclear. Due to this limited knowledge, we aimed to understand specific reactions of the subacromial bursa according to rotator cuff (RC) pathologies compared to non-tendon defects of the shoulder. We hypothesized that the tissue composition and inflammatory status of the bursa are likely to vary between shoulder pathologies depending on the presence and the extent of RC lesion., Method: Bursa samples from patients with either 1) shoulder instability with intact RC (healthy bursa, control), 2) osteochondral pathology with intact RC, 3) partial supraspinatus (SSP) tendon tear, or 4) full-thickness SSP tear were investigated histologically and on gene expression level., Result: Bursae from SSP tears differed from non-tendon pathologies by exhibiting increased chondral metaplasia and TGFβ1 expression. MMP1 was not expressed in healthy bursa controls, but strongly increased with full-thickness SSP tears. Additionally, the expression of the inflammatory mediators IL1β, IL6, and COX2 increased with the extent of SSP tear as shown by correlation analysis. In contrast, increased angiogenesis and nerve fibers as well as significantly upregulated IL6 and COX2 expression were features of bursae from patients with osteochondral pathology. Using immunohistochemistry, CD45+ leukocytes were observed in all examined groups, which were identified in particular as CD68+ monocytes/macrophages., Conclusion: In summary, besides the strong increase in MMP1 expression with SSP tear, molecular changes were minor between the investigated groups. However, expression of pro-inflammatory cytokines correlated with the severity of the SSP tear. Most pronounced tissue alterations occurred for the osteochondral pathology and full-thickness SSP tear group, which demonstrates that the bursal reaction is not exclusively dependent on the occurrence of an SSP tear rather than longstanding degenerative changes. The present bursa characterization contributes to the understanding of specific tissue alterations related to RC tears or non-tendon shoulder pathologies. This pilot study provides the basis for future studies elucidating the role of the subacromial bursa in the development or healing of shoulder pathologies., (© 2021. The Author(s).)