Machine learning analysis of humoral and cellular responses to SARS-CoV-2 infection in young adults.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) induces B and T cell responses, contributing to virus neutralization. In a cohort of 2,911 young adults, we identified 65 individuals who had an asymptomatic or mildly symptomatic SARS-CoV-2 infection and characterized their humoral and T cell responses to the Spike (S), Nucleocapsid (N) and Membrane (M) proteins. We found that previous infection induced CD4 T cells that vigorously responded to pools of peptides derived from the S and N proteins.

Learning how to perform ultrasound-guided interventions with and without augmented reality visualization: a randomized study.

Objectives: Augmented reality (AR), which entails overlay of in situ images onto the anatomy, may be a promising technique for assisting image-guided interventions. The purpose of this study was to investigate and compare the learning experience and performance of untrained operators in puncture of soft tissue lesions, when using AR ultrasound (AR US) compared with standard US (sUS).

Methods: Forty-four medical students (28 women, 16 men) who had completed a basic US course, but had no experience with AR US, were asked to perform US-guided biopsies with both sUS and AR US, with a randomized selection of the initial modality.

Results of Arthroscopic Revision Rotator Cuff Repair for Failed Open or Arthroscopic Repair: A Prospective Multicenter Study on 100 Cases.

Background: Retears after rotator cuff repair (RCR) have been associated with poor clinical results. Meaningful data regarding the role of arthroscopic revision RCR are sparse thus far.

Purpose/hypothesis: To investigate results after arthroscopic revision RCR.

The Schulthess local Shoulder Arthroplasty Registry (SAR): cohort profile.

Purpose: Clinical registries are essential for evaluation of surgical outcomes. The Schulthess Shoulder Arthroplasty Registry (SAR) was established in 2006 to evaluate safety, function, quality-of-life and patient satisfaction in patients undergoing shoulder arthroplasty.

Participants: Adult patients undergoing anatomic or reverse shoulder joint replacement at the Schulthess Klinik, a high-volume, leading orthopaedic surgery centre in Zürich, Switzerland.

Plating and cortical bone grafting of clavicular nonunions: clinical outcome and its relation to clavicular length restoration.

Background: The goal of this study was to evaluate whether plating and cortical bone grafting of shortened clavicular nonunions would restore clavicular length and enable bone healing. The association between the clavicular length difference (CLD) between sides and long-term functional outcome was also explored.

Methods: For this retrospective 2-center study, patients who underwent plate fixation with cortical bone grafting of a clavicular nonunion were assessed after ≥2 years.

Re-intervention and revision rates following primary reverse total shoulder arthroplasty - review of a local shoulder arthroplasty registry.

Purpose: Our primary aim was to describe the re-intervention and revision rates after primary reverse shoulder arthroplasty (RSA) documented in a local shoulder arthroplasty registry. We also identify the main indication for revision and re-intervention, which may be relevant for patient outcome post-RSA.

Methods: Since July 2006, RSAs are consecutively documented in our clinic registry and prospectively controlled with follow-ups.

Latissimus dorsi muscle transfer reduces external rotation deficit at the cost of internal rotation in reverse shoulder arthroplasty patients: a cohort study.

Hypothesis: We hypothesized that treatment of rotator cuff arthropathy (RCA) with reverse shoulder arthroplasty (RSA) and an additional latissimus dorsi transfer (LDT) in patients with an active external rotation deficit (ERD) would restore external rotation (ER) with concomitant deterioration in internal rotation.

Methods: In our cohort study, 26 RCA patients with an active ERD (ie, positive lag sign and maximum active ER of 0°) underwent RSA between September 2007 and February 2015; LDT was completed in 13 of these patients. In addition, 88 control patients without ERD who underwent only RSA were identified.

Limited reliability of grading scapular notching according to Nerot-Sirveaux on anteroposterior radiographs.

Introduction: Incidences of scapular notching (SN) in reverse shoulder arthroplasty (RSA) range between 0% and 96%, and controversy remain as to its relevance for patient outcome. We assessed the reliability of scapular notching (SN) grading based on the Sirveaux classification system using anteroposterior radiographs.

Materials And Methods: 206 RSA procedures with 5-year postoperative anteroposterior shoulder radiographs were classified independently by seven assessors according to Sirveaux (session 1).

Evaluating the bromodomain protein BRD1 as a therapeutic target in rheumatoid arthritis.

Targeting epigenetic reader proteins by small molecule inhibitors represents a new therapeutic concept in autoimmune diseases such as rheumatoid arthritis (RA). Although inhibitors targeting bromodomain protein 1 (BRD1) are in development, the function of BRD1 has hardly been studied. We investigated the therapeutic potential of BRD1 inhibition in joint-resident cells in RA, synovial fibroblasts (SF) and macrophages.

Analysis of early changes in DNA methylation in synovial fibroblasts of RA patients before diagnosis.

DNA methylation is an important epigenetic modification that is known to be altered in rheumatoid arthritis synovial fibroblasts (RASF). Here, we compared the status of promoter DNA methylation of SF from patients with very early RA with SF from patients with resolving arthritis, fully established RA and from non-arthritic patients. DNA was hybridized to Infinium Human methylation 450k and 850k arrays and differential methylated genes and pathways were identified.

TLR3 Ligand Poly(I:C) Exerts Distinct Actions in Synovial Fibroblasts When Delivered by Extracellular Vesicles.

Extracellular vesicles (EV) can modulate the responses of cells to toll-like receptor (TLR) ligation; conversely, TLR ligands such as double-stranded RNA (dsRNA) can enhance the release of EV and influence of the composition and functions of EV cargos. Inflamed synovial joints in rheumatoid arthritis (RA) are rich in EV and extracellular RNA; besides, RNA released from necrotic synovial fluid cells can activate the TLR3 signaling in synovial fibroblasts (SFs) from patients with RA. Since EV occur prominently in synovial joints in RA and may contribute to the pathogenesis, we questioned whether EV can interact with dsRNA, a TLR3 ligand, and modify its actions in arthritis.

Return to sports after reverse shoulder arthroplasty-the Swiss perspective.

Purpose: This patient survey evaluated the return to previous sports activities in Swiss patients up to five years after reverse shoulder arthroplasty (RSA).

Methods: We screened our local shoulder arthroplasty registry for patients registered with a unilateral RSA due to rotator cuff deficiency between May 2010 and May 2015. Revision cases and patients already known as unwilling or unable to complete a German language questionnaire were excluded.

Glenosphere size in reverse shoulder arthroplasty: is larger better for external rotation and abduction strength?

Background: The role of glenosphere size in reverse shoulder arthroplasty (RSA) may be important in prosthetic stability, joint kinematics, rotator cuff tension and excursion, scapular impingement, humeral lateralization, deltoid wrap, and the occurrence of "notching." This study compared short- and midterm clinical and radiographic outcomes for 2 different glenosphere sizes of a single RSA type with respect to implant positioning, glenoid size, and morphology.

Methods: This retrospective analysis included 68 RSA procedures that were prospectively documented in a local register during a 5-year postoperative period.

The epigenetic architecture at gene promoters determines cell type-specific LPS tolerance.

Synovial fibroblasts (SF) drive inflammation and joint destruction in chronic arthritis. Here we show that SF possess a distinct type of LPS tolerance compared to macrophages and other types of fibroblasts. In SF and dermal fibroblasts, genes that were non-tolerizable after repeated LPS stimulation included pro-inflammatory cytokines, chemokines and matrix metalloproteinases, whereas anti-viral genes were tolerizable.

Epigenetically-driven anatomical diversity of synovial fibroblasts guides joint-specific fibroblast functions.

A number of human diseases, such as arthritis and atherosclerosis, include characteristic pathology in specific anatomical locations. Here we show transcriptomic differences in synovial fibroblasts from different joint locations and that HOX gene signatures reflect the joint-specific origins of mouse and human synovial fibroblasts and synovial tissues. Alongside DNA methylation and histone modifications, bromodomain and extra-terminal reader proteins regulate joint-specific HOX gene expression.

Expression and Regulation of PIWIL-Proteins and PIWI-Interacting RNAs in Rheumatoid Arthritis.

Objective: The PIWIL (P-element induced wimpy testis like protein) subfamily of argonaute proteins is essential for Piwi-interacting RNA (piRNA) biogenesis and their function to silence transposons during germ-line development. Here we explored their presence and regulation in rheumatoid arthritis (RA).

Methods: The expression of PIWIL genes in RA and osteoarthritis (OA) synovial tissues and synovial fibroblasts (SF) was analysed by Real-time PCR, immunofluorescence and Western blot.

Radiological and functional 24-month outcomes of resurfacing versus stemmed anatomic total shoulder arthroplasty.

Purpose: This study compared clinical and radiographic outcomes of patients undergoing resurfacing total shoulder arthroplasty (TSA) with those treated with a stemmed TSA.

Methods: Patients with primary osteoarthritis who underwent humeral resurfacing (RES) or stemmed (STA) TSA were identified in our shoulder arthroplasty register for retrospective analysis. Standard radiographs and clinical/patient-rated assessments were made up to 24 months post-surgery.

AAA-ATPase p97 suppresses apoptotic and autophagy-associated cell death in rheumatoid arthritis synovial fibroblasts.

Valosin containing protein (p97) is a chaperone implicated in a large number of biological processes including endoplasmic reticulum (ER)-associated protein degradation and autophagy. Silencing of p97 in rheumatoid arthritis (RA) synovial fibroblasts (RASFs) increased the amount of polyubiquitinated proteins, whereas silencing of its interaction partner histone deacetylase 6 (HDAC6) had no effect. Furthermore, silencing of p97 in RASFs increased not only rates of apoptotic cell death induced by TRAIL but also induced an autophagy-associated cell death during ER stress that was accompanied by the formation of polyubiquitinated protein aggregates and large vacuoles.

Conversion to hemiarthroplasty as a salvage procedure for failed reverse shoulder arthroplasty.

Background: Optimal treatment of a failed reverse shoulder arthroplasty (RSA) is unclear. In the case of poor glenoid bone stock, retaining a RSA may be infeasible. We report our experience with conversions to hemiarthroplasty.

Risk of insufficient internal rotation after bilateral reverse shoulder arthroplasty: clinical and patient-reported outcome in 57 patients.

Background: Bilateral reverse shoulder arthroplasty (RSA) is controversial because of potential rotational deficits impairing daily living activities. We assessed achievement of insufficient internal rotation (IR) and associated factors in bilateral RSA patients.

Methods: Fifty-seven staged bilateral RSA patients with a minimum of 1 year of follow-up after the second intervention were identified from our local monocentric register.

Protein tyrosine phosphatase nonreceptor type 2: an important regulator of lnterleukin-6 production in rheumatoid arthritis synovial fibroblasts.

Objective: To investigate the role of protein tyrosine phosphatase nonreceptor type 2 (PTPN2) in the pathogenesis of rheumatoid arthritis (RA).

Methods: Synovial tissue samples from patients with RA and patients with osteoarthritis (OA) were stained for PTPN2. Synovial fibroblasts were stimulated with tumor necrosis factor (TNF) and interleukin-1β (IL-1β), lipopolysaccharide (LPS), TRAIL, or thapsigargin.

The bromodomain protein inhibitor I-BET151 suppresses expression of inflammatory genes and matrix degrading enzymes in rheumatoid arthritis synovial fibroblasts.

Objective: To investigate the effects of BET bromodomain protein inhibition on inflammatory activation and functional properties of rheumatoid arthritis synovial fibroblasts (RASF).

Methods: The expression of the BET bromodomain proteins BRD2, BRD3 and BRD4 was analysed in synovial tissue by immunohistochemistry. RASF were stimulated with tumour necrosis factor (TNF)-α, interleukin (IL)-1β and toll-like receptor (TLR) ligands (Pam3, pIC and lipopolysaccharide (LPS)) in the presence or absence of the BET inhibitor I-BET151, or siRNA targeting BRD2, BRD3 and BRD4.

Survival of Norway spruce remains higher in mixed stands under a dryer and warmer climate.

Shifts in tree species distributions caused by climatic change are expected to cause severe losses in the economic value of European forestland. However, this projection disregards potential adaptation options such as tree species conversion, shorter production periods, or establishment of mixed species forests. The effect of tree species mixture has, as yet, not been quantitatively investigated for its potential to mitigate future increases in production risks.

Patterns of proximal humeral bone resorption after total shoulder arthroplasty with an uncemented rectangular stem.

Background: The aim of this study was to assess the timing and location of cortical bone resorption after total shoulder arthroplasty with an uncemented rectangular stem and investigate its effect on shoulder function up to 5 years after implantation.

Methods: Between June 2003 and September 2006, 183 consecutive total shoulder arthroplasties were performed, 133 of which received a cementless rectangular stem as indicated by primary or post-traumatic osteoarthritis (OA). The 5-year postoperative follow-up rate was 80%.

Smoking induces transcription of the heat shock protein system in the joints.

Objectives: Smoking increases the risk of developing rheumatoid arthritis (RA) and worsens the course of the disease. In the current study we analysed whether smoking can affect gene expression directly in the joints.

Methods: Synovial fibroblasts were incubated with 5% cigarette smoke extract and changes in gene expression were detected using whole genome microarrays and verified with real-time PCR.