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. The experimental setup aimed to simulate biopsies of superficial soft tissue lesions, such as for example breast masses in clinical practice, by use of a turkey breast containing olives. Time to puncture(s) and success (yes/no) of the biopsies was documented. All participants completed questionnaires about their coordinative skills and their experience during the training. RESULTS: Despite having no experience with the AR technique, time to puncture did not differ significantly between AR US and sUS (median [range]: 17.0 s [6-60] and 14.5 s [5-41], p = 0.16), nor were there any gender-related differences (p = 0.22 and p = 0.50). AR US was considered by 79.5% of the operators to be the more enjoyable means of learning and performing US-guided biopsies. Further, a more favorable learning curve was achieved using AR US. CONCLUSIONS: Students considered AR US to be the preferable and more enjoyable modality for learning how to obtain soft tissue biopsies; however, they did not perform the biopsies faster than when using sUS. KEY POINTS: • Performance of standard and augmented reality US-guided biopsies was comparable • A more favorable learning curve was achieved using augmented reality US. • Augmented reality US was the preferred technique and was considered more enjoyable.

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. Any intervention after primary RSA requiring a return to the operating room for any shoulder-related indication was termed a re-intervention. Revisions were defined as surgeries involving any exchange, removal, or addition of at least one component. The study endpoints were survival rates at two, five and ten years follow-up for both definitions. RESULTS: Until July 2017, 63 from a total of 1480 primary RSAs required at least one re-intervention and 33 patients had a revision. Open reduction and internal fixation for fractures around the implant (n = 14) were the predominating indications for re-intervention. The re-intervention rate for instability was 0.5%. For re-interventions, survival rates were 97.7, 95.4 and 90.8% at two, five and ten years, respectively, and the respective rates for revisions were 98.7, 97.5 and 95.3%. CONCLUSION: The revision rate after primary RSA for our patient registry is low. A relevant number of additional interventions were noted that did not require any component revision but may impair the final outcome post-RSA. By only reporting revision rates, the number of post-RSA re-interventions is clearly underestimated. We recommend the documentation of all events leading to any re-intervention in arthroplasty registries.

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. Clinical outcomes of strength, range of motion, Constant-Murley score, and Shoulder Pain and Disability Index score, as well as complications, were documented 6, 12, 24, and 60 months postoperatively. We made comparative analyses using statistical mixed models. RESULTS: The LDT procedure extended the surgical time by 26 minutes (P = .003). LDT patients had up to 22° better postoperative active ER than control patients (P < .001), although this was accompanied by an internal rotation deficit (77% vs 46% of control patients could not reach the lumbosacral region, P = .010). We calculated a 23% risk of local procedure-related complications for RSA patients with an active ERD and LDT. CONCLUSION: Patients with RCA and an active ERD seem to benefit from an LDT, although this is accompanied by the potential loss of internal rotation. This additional procedure is associated with an extended surgical time as well as a possible increase in the risk of a complication occurring.

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). After a review meeting, three assessors re-classified the radiographs along with quality criteria (session 2). SN grading by the majority of assessors was taken as the reference. Classification interobserver reliability was analyzed using Kappa statistics. RESULTS: The incidence of SN was estimated at 53% and 37% at the first and second sessions, respectively. Interobserver reliability Kappa coefficients resulting from the first and second sessions were 0.27 and 0.43, respectively. Case selection based on radiographic quality criteria did not improve SN grading reliability in the second session. CONCLUSION: Agreement between individual surgeons was low when grading SN in RSA according to Sirveaux using anteroposterior radiographs. Consensus among several assessors may increase reliability in research settings.

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. Two glenosphere diameter sizes of 36 mm (n = 33) and 44 mm (n = 35) were used. Standard radiographs were made preoperatively (ie, baseline) and at 6, 12, 24, and 60 months after surgery. Range of motion, strength, the Constant-Murley score, and the Shoulder Pain and Disability Index were also assessed at all follow-up visits. The effect of glenosphere size on measured outcomes was adjusted for baseline values, patient gender, and humeral head diameter. RESULTS: No significant differences were found in the functional scores between treatment groups at all follow-up assessments. At the 12-month follow-up, patients with a 44-mm glenosphere had greater external rotation in adduction (mean difference, 12°; P = .001) and abduction strength (mean difference, 1.4 kg; P = .026) compared with those with the smaller implant. These differences remained at 60 months. Scapular notching was observed in 38% of all patients, without any relevant difference between the groups. CONCLUSION: An increase in glenosphere diameter leads to a clinically moderate but significant increase in external rotation in adduction and abduction strength at midterm follow-up.

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. Eligible patients received a paper questionnaire asking about their past and current sports activities, return time point and level of activity. RESULTS: Of 305 patients, 89% responded at a mean post-operative follow-up of 2.9 years (SD 1.1). The respondents had a mean age of 77.1 years (SD 7.8) and included 62% females. The overall rate of patients returning to a previous sports activity was 77%. Sixty-one percent (166/271) participated in regular sports activities before the onset of their shoulder disorders. After RSA, 47% (127/271) participated in at least one sport type with the most frequent activities including hiking (66), swimming (53), cycling (45) and callisthenics (43). Most patients carried out their main sports activity after surgery with a moderate level of intensity (83%) and between one to three times per week (69%). Forty-two percent of the respondents indicated that returning to sports was among their key demands after RSA. CONCLUSIONS: Returning to previous sports activities is an important expectation of RSA patients, and the majority do. Patient expectations of post-operative sports activity need to be addressed when planning RSA.

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. In macrophages, all measured genes were tolerizable, whereas in gingival and foreskin fibroblasts these genes were non-tolerizable. Repeated stimulation of SF with LPS resulted in loss of activating histone marks only in promoters of tolerizable genes. The epigenetic landscape at promoters of tolerizable genes was similar in unstimulated SF and monocytes, whereas the basal configuration of histone marks profoundly differed in genes that were non-tolerizable in SF only. Our data suggest that the epigenetic configuration at gene promoters regulates cell-specific LPS-induced responses and primes SF to sustain their inflammatory response in chronic arthritis.

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. Implant revisions were assessed. Patients were frequency-matched in a 1:1 (RES:STA) ratio based on gender and age, and compared with regard to operation time and shoulder function (Constant, SPADI and Quick DASH scores). Mixed models with statistical adjustments were applied. RESULTS: From 2006 to 2014, 44 RES and 137 STA operations were performed in 157 patients; one and two revisions were recorded in the RES and STA group, respectively. The final matched cohort included a total of 69 patients and 37 operations per treatment group. Resurfacing TSA was 17 min shorter (95%CI: 5-28) compared to the stemmed procedure (p = 0.005). RES and STA patients showed significant functional improvement six months post-implantation, yet all measured scores did not differ between the groups at 2 years (p ≥ 0.131). The status of static centering of the humeral head, acromiohumeral distance, and a lack of signs of implant loosening were also similar between treatments. CONCLUSION: Similar 24-month post-operative radiological and functional outcome is achieved by RES and STA patients, even with a shorter RES surgery time. Larger cohorts and longer follow-up are required to better assess implant survival.

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)-1ß 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. RASF expression of inflammatory mediators, including MMP1, MMP3, IL-6 and IL-8, was measured by q-PCR, q-PCR array and ELISA. Cellular viability, apoptosis, proliferation and chemoattractive properties of RASF were investigated using MTT, cell apoptosis ELISA, BrdU-based proliferation and transwell migration assays. RESULTS: BRD2, BRD3 and BRD4 proteins were detected in rheumatoid arthritis (RA) synovial tissue, expressed in both RASF and macrophages. I-BET151 suppressed cytokine and TLR ligand-induced secretion of MMP1, MMP3, IL-6 and IL-8, and mRNA expression of more than 70% of genes induced by TNF-α and IL-1ß. Combined silencing of BRD2, BRD3 and BRD4 significantly reduced cytokine and TLR ligand-induced expression of a subset of gene products targeted by I-BET151, including MMP1, CXCL10 and CXCL11. I-BET151 treatment of RASF reduced RASF proliferation, and the chemotactic potential for peripheral blood leucocytes of RASF conditioned medium. CONCLUSIONS: Inhibition of BET family proteins suppresses the inflammatory, matrix-degrading, proliferative and chemoattractive properties of RASF and suggests a therapeutic potential in the targeting of epigenetic reader proteins in RA.

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. METHODS: Within 7 years, 16 patients underwent conversion to hemiarthroplasty after failed RSA. All patients had insufficient bone stock for reimplantation of another RSA. Standard radiographs and Constant, Shoulder Pain and Disability Index, and the 11-item version of the Disabilities of the Arm, Shoulder and Hand scores were assessed preoperatively and up to a minimum of 24 months after surgery. Postoperative superior migration and complications were also documented. RESULTS: Glenoid loosening was the primary reason for RSA failure in 11 patients. Three required revision surgery because of infection. Postoperative functional outcome was generally poor at the latest follow-up, with mean Constant, Shoulder Pain and Disability Index, and 11-item version of the Disabilities of the Arm, Shoulder and Hand scores of 25, 37, and 63 points, respectively. Baseline pain also did not improve. Medialization progressed beyond the coracoid in 6 patients, and complete anterosuperior escape was reported in 3 patients. Three postoperative complications were recorded by the final follow-up, including 2 periprosthetic humeral fractures treated conservatively and 1 patient with painful humeral component medialization leading to resection arthroplasty. CONCLUSION: With excessive bone stock loss, hemiarthroplasty remains an option, despite the associated risks of uncertain pain relief and poor functional outcome. This technique offers a lower likelihood of undertaking further surgical interventions within the short-term to midterm postoperative period. Nevertheless, resection arthroplasty may still be considered another valuable solution.

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. Shoulder range of motion (including IR using the Apley scratch test), strength, and Constant and Shoulder Pain and Disability Index scores were assessed preoperatively and 6, 12, and 24 months postoperatively. RESULTS: Before surgery, both shoulders were similar regarding imaging parameters, but first operated shoulders tended to have poorer function. One year after the first RSA, 21% of patients had insufficient IR (not reaching the lumbosacral junction) compared with 33% after the second intervention (P = .180). At 2 years, 5% of patients had insufficient IR on both sides. Patients with insufficient IR on the second side at baseline (relative risk [RR], 1.8 [1.0-3.2]) and patients with insufficient IR 1 year after the first RSA (RR, 3.0 [1.6-5.6]) were more likely to have insufficient IR 1 year after the second RSA. Constant and Shoulder Pain and Disability Index scores and abduction of the second side were significantly worse 1 year after the second RSA (P ≤ .047); at 2 years, there were no differences in functional outcome between shoulders. CONCLUSION: A minority of bilateral RSA patients did not achieve sufficient IR on at least 1 side. Staged surgery is justified, particularly when the outcome of the initial operation is satisfactory.

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. Synovial tissues were obtained from smoking and non-smoking patients with RA undergoing joint replacement surgery and from mice exposed to cigarette smoke or ambient air in a whole body exposure chamber for 3 weeks. RESULTS: Microarray and real-time PCR analysis showed a significant upregulation of the heat shock proteins DnaJA4, DnaJB4, DnaJC6, HspB8 and Hsp70 after stimulation of synovial fibroblasts with 5% cigarette smoke extract. Similarly, in synovial tissues of smokers with RA the expression of DnaJB4, DnaJC6, HspB8 and Hsp70 was significantly higher compared with non-smokers with RA. Upregulation of DnaJB4 and DnaJC6 in joints by smoking was also confirmed in mice exposed to cigarette smoke. CONCLUSIONS: Our data clearly show that smoking can change gene expression in the joints, which can lead to the activation of signalling pathways that promote development of autoimmunity and chronic joint inflammation.

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%. Standardized radiographic controls and clinical assessments were performed at 6 weeks, 6 months, and 1, 2, and 5 years. RESULTS: Twenty-two patients (17%) showed full-thickness cortical bone resorption, 21 of whom were diagnosed with Sperling zone 2 resorption. The maximum craniocaudal distance of full resorption averaged 19.1 mm (range, 5.6-46.7 mm). The median distance progressed significantly from 9.6 mm to 13.8 mm between 6 and 12 months (P = .005). The risk of bone resorption was 3.1 times higher for post-traumatic OA patients than for those with primary OA. The occurrence of bone resorption increased significantly with increasing stem diameters relative to the humeral diameter. There was no significant effect of bone resorption on functional outcome. CONCLUSION: Full-thickness cortical bone resorption in the proximal posterolateral humerus after receipt of a cementless rectangular stem has a prevalence of 17%, mostly occurring within the first year after surgery. Risk factors include age, post-traumatic conditions, and larger stem sizes relative to the humerus. This is a radiographic phenomenon without significant impairment of function or need for revision within 5 years after surgery.

The pattern-recognition receptor nucleotide-binding oligomerization domain--containing protein 1 promotes production of inflammatory mediators in rheumatoid arthritis synovial fibroblasts.

OBJECTIVE: Pattern-recognition receptors (PRRs), such as Toll-like receptors (TLRs) and nucleotide-binding oligomerization domain-containing protein 2 (NOD-2), have been shown to contribute to the pathogenesis of rheumatoid arthritis (RA). The aim of this study was to analyze the expression, regulation, and function of the PRR NOD-1 in RA synovial fibroblasts (RASFs), and to examine its interaction with other PRRs. METHODS: Expression of NOD-1 was analyzed by immunohistochemistry in synovial tissue from RA patients, psoriatic arthritis patients, gout patients, and osteoarthritis (OA) patients. RASFs and human monocyte-derived macrophages (HMDMs) were stimulated with L-alanyl-γ-D-glutamyl-meso-diaminopimelic acid, palmitoyl-3-cysteine-serine-lysine-4, poly(I-C), lipopolysaccharide, heat-inactivated bacteria, tumor necrosis factor α (TNFα), or interleukin-1ß (IL-1ß). Expression levels of IL-6, CCL5, matrix metalloproteinases (MMPs), NODs, and TLRs were measured by real-time reverse transcription-polymerase chain reaction and/or enzyme-linked immunosorbent assay. NOD-1 and NOD-2 were silenced with target-specific small interfering RNA. Phosphorylation of IL-1 receptor-associated kinase 1 (IRAK-1) was measured by Western blotting. RESULTS: Expression of NOD-1 protein was significantly increased in RA synovium compared to OA synovium. The basal expression of NOD-1 was similar in RASFs, OASFs, healthy control peripheral blood mononuclear cells, and healthy control HMDMs. Stimulation of RASFs with TLR-3 up-regulated the expression of NOD-1. Expression of IL-6, CCL5, MMPs, TLR-2, and NOD-2 was significantly up-regulated in RASFs by stimulation with the NOD-1 ligand. A synergistic effect on IL-6 production was observed in cells stimulated with NOD-1 and TLR-2 ligands or NOD-1 and TLR-4 ligands. Silencing of NOD-1, but not NOD-2, decreased the levels of IL-6 in RASFs after stimulation with TLR-2 and IL-1ß, and blocked the phosphorylation of IRAK-1. CONCLUSION: NOD-1 is strongly expressed in different cell types in the synovial tissue of patients with RA. These results indicate that NOD-1, either alone or interacting with other inflammatory mediators, can play an important role in the chronic and destructive inflammation of the joints in RA.

Down-regulation of microRNA-34a* in rheumatoid arthritis synovial fibroblasts promotes apoptosis resistance.

OBJECTIVE: To investigate the expression and effect of the microRNA-34 (miR-34) family on apoptosis in rheumatoid arthritis synovial fibroblasts (RASFs). METHODS: Expression of the miR-34 family in synovial fibroblasts with or without stimulation with Toll-like receptor (TLR) ligands, tumor necrosis factor α (TNFα), interleukin-1ß (IL-1ß), hypoxia, or 5-azacytidine was analyzed by real-time polymerase chain reaction (PCR). Promoter methylation was studied by combined bisulfite restriction analysis. The effects of overexpression and silencing of miR-34a and miR-34a* on apoptosis were analyzed by annexin V/propidium iodide staining. Production of X-linked inhibitor of apoptosis protein (XIAP) was assessed by real-time PCR and immunohistochemistry analysis. Reporter gene assay was used to study the signaling pathways of miR-34a*. RESULTS: Basal expression levels of miR-34a* were found to be reduced in synovial fibroblasts from RA patients compared to osteoarthritis patients, whereas levels of miR-34a, miR-34b/b*, and miR-34c/c* did not differ. Neither TNFα, IL-1ß, TLR ligands, nor hypoxia altered miR-34a* expression. However, we demonstrated that the promoter of miR-34a/34a* was methylated and showed that transcription of the miR-34a duplex was induced upon treatment with demethylating agents. Enforced expression of miR-34a* led to an increased rate of FasL- and TRAIL-mediated apoptosis in RASFs. Moreover, levels of miR-34a* were highly correlated with expression of XIAP, which was found to be up-regulated in RA synovial cells. Finally, we identified XIAP as a direct target of miR-34a*. CONCLUSION: Our data provide evidence of a methylation-specific down-regulation of proapoptotic miR-34a* in RASFs. Decreased expression of miR- 34a* results in up-regulation of its direct target XIAP, thereby contributing to resistance of RASFs to apoptosis.

Clinical and radiographical results after double flip button stabilization of acute grade III and IV acromioclavicular joint separations.

INTRODUCTION: Persistent horizontal instability after acute acromioclavicular (AC) joint separation may provoke unsatisfactory results of conservative treatment. HYPOTHESIS: the arthroscopically assisted double flip button stabilization of acute horizontally unstable grade III and IV AC joint disruptions results in full functional restoration and stable radiological reposition. MATERIALS: 21 patients treated for an acute grade III or IV AC joint separation were enrolled. Clinical assessment at least 2-year postoperative included the constant score (CS) and the simple shoulder test. A panorama stress view, bilateral axial view and an AC view were obtained for radiographic evaluation. RESULTS: 19 individuals (mean 37 years; 17 men) with 16 Rockwood type III and 3 type IV injuries were available for examination 24­51 months postoperatively. The mean CS was 90.2 points (SD 6.5) with no statistically significant difference between CS and age-adjusted normative values. The mean Simple Shoulder Test scored 11.5 points (range 8­12). Loss of reduction of more than 2 mm in the coronal plane stress views was present in 6 patients (32 %) with no associated loss of functional outcome. Two of four reported complications in four patients were treated surgically (one open revision with graft augmentation for coracoid implant break out, one arthroscopic capsular release for persistent glenohumeral stiffness). CONCLUSION: Arthroscopically assisted double flip button stabilization for acute grade III and IV AC joint separation restores fully horizontal stability and age-expected shoulder function, resulting in high patient satisfaction, despite a loss of reduction observed radiographically in approximately one-third of patients. LEVEL OF EVIDENCE: IV.

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. By using statistical and machine learning models, we observed that the T cell response highly correlated with a compound titer of antibodies against the Receptor Binding Domain (RBD), S and N. However, while serum antibodies decayed over time, the cellular phenotype of these individuals remained stable over four months. Our computational analysis demonstrates that in young adults, asymptomatic and paucisymptomatic SARS-CoV-2 infections can induce robust and long-lasting CD4 T cell responses that exhibit slower decays than antibody titers. These observations imply that next-generation COVID-19 vaccines should be designed to induce stronger cellular responses to sustain the generation of potent neutralizing antibodies.

Altered expression of microRNA-203 in rheumatoid arthritis synovial fibroblasts and its role in fibroblast activation.

OBJECTIVE: MicroRNA (miRNA) are recognized as important regulators of a variety of fundamental biologic processes. Previously, we described increased expression of miR-155 and miR-146a in rheumatoid arthritis (RA) and showed a repressive effect of miR-155 on matrix metalloproteinase (MMP) expression in RA synovial fibroblasts (RASFs). The present study was undertaken to examine alterations in expression of miR-203 in RASFs and analyze its role in fibroblast activation. METHODS: Differentially expressed miRNA in RASFs versus osteoarthritis synovial fibroblasts (OASFs) were identified by real-time polymerase chain reaction (PCR)-based screening of 260 individual miRNA. Transfection of miR-203 precursor was used to analyze the function of miR-203 in RASFs. Levels of interleukin-6 (IL-6) and MMPs were measured by real-time PCR and enzyme-linked immunosorbent assay. RASFs were stimulated with IL-1ß, tumor necrosis factor α (TNFα), lipopolysaccharide (LPS), and 5-azacytidine (5-azaC). Activity of IκB kinase 2 was inhibited with SC-514. RESULTS: Expression of miR-203 was higher in RASFs than in OASFs or fibroblasts from healthy donors. Levels of miR-203 did not change upon stimulation with IL-1ß, TNFα, or LPS; however, DNA demethylation with 5-azaC increased the expression of miR-203. Enforced expression of miR-203 led to significantly increased levels of MMP-1 and IL-6. Induction of IL-6 by miR-203 overexpression was inhibited by blocking of the NF-κB pathway. Basal expression levels of IL-6 correlated with basal expression levels of miR-203. CONCLUSION: The current results demonstrate methylation-dependent regulation of miR-203 expression in RASFs. Importantly, they also show that elevated levels of miR-203 lead to increased secretion of MMP-1 and IL-6 via the NF-κB pathway and thereby contribute to the activated phenotype of synovial fibroblasts in RA.

Treatment strategies for periprosthetic infections after primary elbow arthroplasty.

BACKGROUND: The goal of this study was to investigate the outcome of different surgical procedures (debridement and retention vs 1- or 2-stage exchange) together with a well-defined antimicrobial regimen. MATERIALS AND METHODS: A total of 236 consecutive patients underwent 262 primary elbow arthroplasties between January 1994 and December 2007. We observed 20 episodes of periprosthetic infections in 19 patients and placed them into 3 groups according to the occurrence of infection after index surgery. A total of 9 early infections (<3 months), 1 delayed infection (3-24 months), and 10 late infections (>24 months) were observed. The treatment among those 3 groups was compared, and the outcome was assessed with a mean follow-up of 60.2 months. RESULTS: In the group with early infections (n = 9), 8 cases were treated by irrigation and debridement and 1 case was treated by a 2-stage exchange without recurrence of infection. The mean Mayo Elbow Performance Score improved from 48.3 points (range, 30-75 points) to 91.7 points (range, 85-100 points). The delayed infection was treated by 1-stage exchange without recurrence of infection. For late infections (n = 10), 3 cases presented recurrence of infection after debridement and irrigation, and the mean Mayo Elbow Performance Score remained nearly unchanged, from 60 points (range, 45-80 points) to 65 points (range, 50-80 points). Eradication of infection could be achieved by staged revision and in 3 cases by debridement. CONCLUSION: Both debridement with retention and staged reimplantation are highly successful for appropriate indications. Staged revisions are successful even against biofilm-active microorganisms, but a prosthesis-free interval of at least 3 months is recommended.

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. We hypothesized that (1) arthroscopic revision RCR would lead to improved outcomes, (2) the clinical results would be dependent on tendon integrity and (3) tear pattern, tendon involvement, and repair technique would influence clinical and structural results. STUDY DESIGN: Case series; Level of evidence 4. METHODS: During a 40-month period, 100 patients who underwent arthroscopic revision RCR were prospectively enrolled in this multicenter study. Outcomes were evaluated preoperatively, at 6 months (6M), and at 24 months (24M) using the Constant score (CS), the Oxford Shoulder Score (OSS), and the Subjective Shoulder Value (SSV). Tendon integrity at 2 years was analyzed using magnetic resonance imaging. A total of 13 patients (13%) were lost to follow-up, and 14 patients (14%) had a symptomatic retear before the 24M follow-up. RESULTS: All clinical scores improved significantly during the study period (CS: preoperative, 44 ± 16; 6M, 58 ± 22; 24M, 69 ± 19 points; OSS: preoperative, 27 ± 8; 6M, 36 ± 11; 24M, 40 ± 9 points; SSV: preoperative, 43% ± 18%; 6M, 66% ± 24%; 24M, 75% ± 22%) (P < .01). At 2 years, a retear rate of 51.8% (43/83) and a surgical revision rate of 12.6% (11/87) were observed. Mean full-thickness tear size decreased from 5.00 ± 1.61 cm2 to 3.25 ± 1.92 cm2 (P = .041). Although the Sugaya score improved from 4.5 ± 0.9 to 3.7 ± 1.4 (P = .043), tendon integrity did not correlate with better outcome scores. Previous open RCR, involvement of the subscapularis, chondral lesions of Outerbridge grade ≥2, and medial cuff failure were correlated with poorer SSV scores at 2 years (P≤ .047). Patients with traumatic retears had better CS and OSS scores at 2 years (P≤ .039). CONCLUSION: Although arthroscopic revision RCR improved shoulder function, retears were frequent but usually smaller. Patients with retears, however, did not necessarily have poorer shoulder function. Patient satisfaction at 2 years was lower when primary open RCR was performed, when a subscapularis tear or osteoarthritis was present, and when the rotator cuff retear was located at the musculotendinous junction. Patients with traumatic retears showed better functional improvement after revision.