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The increased utilization of shoulder arthroplasty, including revision procedures, combined with rises in life expectancy, is expected to translate into a substantial increase in periprosthetic humeral fractures. The evaluation and management of these fractures needs to be updated to consider fractures that complicate anatomic and reverse arthroplasties and contemporary short-stem and stemless implants. Although conservative treatment is successful in a large proportion of these fractures, several surgical reconstructive techniques are required for the management of all fracture types. Surgical options include internal fixation, graft augmentation, standard revision procedures, and occasionally complex reconstructions including modular segmental prosthesis and allograft prosthetic composites. Most studies on the outcomes of periprosthetic humeral fractures have analyzed small samples and have typically reported on anatomic total shoulders with a standard-length humeral implant. Additional research is required to optimize the management of periprosthetic postoperative humeral fractures in the era of reverse arthroplasty, short stems, and stemless arthroplasty.

The history of humeral component design has evolved from prostheses with relatively long stems and limited anatomic head options to a contemporary platform with short stems and stemless implants with shared instrumentation and the ability to provide optimal shoulder reconstruction for both anatomic and reverse configurations. Contemporary humeral components aim to preserve the bone, but they are potentially subject to malalignment. Modern components are expected to favorably load the humerus and minimize adverse bone reactions. Although there will likely continue to be further refinements in humeral component design, the next frontiers in primary shoulder arthroplasty will revolve around designing an optimal plan, including adequate soft tissue tension and providing computer-assisted tools for the accurate execution of the preoperative plan in the operating room.

FLT3-ITD mutations are detected in approximately 25% of newly diagnosed adult acute myeloid leukemia (AML) patients and confer an adverse prognosis. The FLT3-ITD allelic ratio has clear prognostic value. Nevertheless, there are numerous manuscripts with contradictory results regarding the prognostic relevance of the length and insertion site (IS) of the FLT3-ITD fragment. We aimed to assess the prognostic impact of these variables on the complete remission (CR) rates, overall survival (OS) and relapse-free survival (RFS) of AML patients with FLT3-ITDmutations. We studied the FLT3-ITD length of 362 adult AML patients included in the PETHEMA AML registry. We tried to validate the thresholds of ITD length previously published (i.e., 39 bp and 70 bp) in intensively treated AML patients (n = 161). We also analyzed the mutational profile of 118 FLT3-ITD AML patients with an NGS panel of 39 genes and correlated mutational status with the length and IS of ITD. The AUC of the ROC curve of the ITD length for OS prediction was 0.504, and no differences were found when applying any of the thresholds for OS, RFS or CR rate. Only four out of 106 patients had ITD IS in the TKD1 domain. Our results, alongside previous publications, confirm that FLT3-ITD length lacks prognostic value and clinical applicability.

The location (proximal vs. distal) of elbow medial ulnar collateral ligament (MUCL) tears impacts clinical outcomes of nonoperative treatment. The purposes of our study were to (1) determine whether selective releases of the MUCL could be performed under ultrasound (US) guidance without disrupting overlying soft tissues, (2) assess the difference in medial elbow stability for proximal and distal releases of the MUCL using stress US and a robotic testing device, and (3) elucidate the flexion angle that resulted in the greatest amount of medial elbow laxity after MUCL injury.Sixteen paired, fresh-frozen elbow specimens were used. Valgus laxity was evaluated with both US and robotic-assisted measurements before and after selective MUCL releases. A percutaneous US-guided technique was used to perform proximal MUCL releases in 8 elbows and to perform distal MUCL releases in their matched pairs. The robot was used to determine the elbow flexion angle at which the maximum valgus displacement occurred for both proximally and distally released specimens. Open dissection was then performed to assess the accuracy of the percutaneous releases.Percutaneous US-guided releases were successfully performed in 15 of 16 specimens. The proximal release resulted in greater valgus angle displacement (11° ± 2°) than the distal release (8° ± 2°) between flexion angles of 30° and 70° (P .0001 at 30°, P .0001 at 40°, P = .001 at 50°, P = .005 at 60°, and P = .020 at 70°). Valgus displacement between release locations did not reach the level of statistical significance between 80° and 120° (P = .051 at 80°, P = .131 at 90°, P = .245 at 100°, P = .400 at 110°, and P = .532 at 120°). When we compared the values for the mean increase in US delta gap (stressed - supported state) from before to after MUCL release, the proximally released elbows had larger increases than the distally released elbows (5.0 mm proximal vs. 3.7 mm distal, P = .032). After MUCL release, maximum mean valgus displacement occurred at 49° of flexion.US-guided selective releases of the MUCL can be performed reliably without violating the overlying musculature. Valgus instability is not of greater magnitude for distal releases when compared with proximal releases. This findings suggests there must be alternative factors to explain the difference in clinical prognosis between distal and proximal tears. The observed flexion angle for maximum valgus laxity could have important implications for elbow positioning during US or fluoroscopic stress examination, as well as surgical repair or reconstruction of the MUCL.

Background: Evaluation of MRD is standard in patients with AML. However, the role of decentralized MRD assessment for risk stratification in AML remains largely unknown, and so it does which methodological aspects are critical to empower the evaluation of MRD with prognostic significance, particularly if using MFC. Aim: To evaluate the role of decentralized MRD assessment using MFC for risk stratification and putative treatment individualization of patients with AML. Methods: This study was performed on 1,076 AML patients in complete remission (CR) after 7+3 induction chemotherapy, in whom MRD was evaluated by MFC in local laboratories over a period of 20 years in the PETHEMA group. We conducted a survey of technical aspects of MFC based MRD testing in the laboratories of the 60 participating Hospitals, to determine the impact of methodological heterogeneity in the prognostic value of MFC. Results: We first investigated the most effective MRD cutoff to stratify patients' risk at first remission. Patients were segmented into progressively higher cutoffs, starting at 0.01% followed by 0.05%, 0.1%, 0.5% and 1%. Our results showed that 0.1% reached higher statistical significance to discriminate patients with different relapse-free survival (RFS, HR: 0.77; P = .001) and overall survival (OS, HR: 0.73; P = .001). In multivariate analyses together with patients' age, WBC, genetic risk and post-consolidation therapy, MRD status was selected as an independent prognostic factor for OS. To further define the utility of "real-world" MRD assessment using MFC in risk stratification of AML, recursive partitioning was performed using the prognostic and treatment related factors selected in the multivariate Cox model for OS. Of the four variables evaluated, hematopoietic stem cell transplantation (HSCT, regardless of autologous or allogeneic source) vs no transplant emerged as the best single discriminator for OS, followed by genetic risk, age and MRD status. There were two branching points defined by MRD status; the first in patients ≤60 years with intermediate genetic risk who were not transplanted and the second in patients with adverse genetics who were not transplanted, in whom Forty-nine of the 60 hospitals (82%) responded to the survey on questions regarding the measurement of MRD using MFC in the PETHEMA LMA 1999, 2007 and 2010 protocols, providing information corresponding to 966 of the 1,076 (90%) patients regarding the number of markers, preparation of samples, instruments, approach (ie, LAIP, DfN or LAIP+DfN), number of cells to define a cluster, etc. The survey revealed significant heterogeneity intra- and inter-protocols that reflected improvement in MFC assessment of MRD over time, in the absence of harmonization nor standardization at the national level. Accordingly, we investigated if the heterogeneity in methodological, interpretation and reporting aspects of MFC based MRD testing were hampering its ability to predict outcome independently of other patient and treatment related factors. Strikingly, our results showed that except for the denominator used to calculate MRD burden (ie, total nucleated cells vs leukocytes), lack of standardization in all other parameters had an impact on the ability of MFC to predict outcomes in AML (Figure). Namely, panels with ≤4 markers or ≤2 combinations failed to identify patients with significantly different RFS according to MRD status, and MFC-based MRD monitoring was prognostic only when >500,000 cells were measured. Only MRD assessment using patient-specific panels was predictive of outcome. Conclusions: We report here one of the largest studies investigating the role of MRD monitoring using MFC. Our results confirmed that detection of MRD identifies patients in CR/CRi with inferior survival, but uncovered that decentralized MRD testing lacks significance when compared to other baseline risk factors and in the context of risk-adapted post-consolidation strategies. Thus, while this study demonstrated that "real-world" decentralized assessment of MRD using MFC does provide prognostic information in AML patients at first remission, our results question its readiness for risk stratification towards clinical decisions outside trials, at least until adequate standardization of this technique is achieved. Figure Disclosures Paiva: SkylineDx: Consultancy; Takeda: Consultancy, Honoraria, Research Funding; Roche: Research Funding; Adaptive: Honoraria; Amgen: Honoraria; Janssen: Consultancy, Honoraria; Karyopharm: Consultancy, Honoraria; Kite: Consultancy; Celgene: Consultancy, Honoraria, Research Funding, Speakers Bureau; Sanofi: Consultancy, Honoraria, Research Funding. Alonso Dominguez:Celgene: Research Funding; Incyte: Research Funding; Pfizer: Research Funding. Martinez-Lopez:Janssen: Speakers Bureau; Altum: Membership on an entity's Board of Directors or advisory committees, Patents & Royalties; Hosea: Membership on an entity's Board of Directors or advisory committees, Patents & Royalties; Roche: Speakers Bureau; Amgen: Speakers Bureau; Takeda: Speakers Bureau; Vivia Biotech: Honoraria; Novartis: Research Funding; BMS: Research Funding, Speakers Bureau; Incyte: Research Funding, Speakers Bureau. Sossa:Astellas: Honoraria; Roche: Honoraria; Takeda: Honoraria; Novo: Honoraria. San-Miguel:Roche, AbbVie, GlaxoSmithKline, and Karyopharm: Consultancy, Membership on an entity's Board of Directors or advisory committees; Bristol-Myers Squibb, Celgene, Novartis, Takeda, Amgen, MSD, Janssen, and Sanofi: Consultancy, Membership on an entity's Board of Directors or advisory committees.

Background Although literature exists regarding hip and knee arthroplasty outcomes in patients with skin allergy to metals, there is minimal information about skin allergy implications on shoulder arthroplasty outcomes. The purpose of this study was to determine the results, complications, and failure rate among patients with a self-reported metal allergy undergoing shoulder arthroplasty. Methods Fifty-two shoulder arthroplasties were performed at our Institution in 43 patients with self-reported metal allergies. Forty primary and 12 revision shoulder arthroplasties were performed using anatomic (30) and reverse (22) components. Retrospective chart review was performed to determine metal allergy history, implant composition, pain, motion, and complications. Radiographs were reviewed to determine mechanical failure rates. Average follow-up time was 65 months. Results Allergies reported included nickel (37), cobalt chrome (4), copper (2), zinc (1), titanium (1), gold (1), and nonspecific metal allergy (8); 8 patients reported multiple metal allergies. All components implanted in patients with nickel allergies contained nickel. At most recent follow-up, pain was rated as none or mild in 88% of shoulders. Active elevation improved from 80° to 141° and external rotation from 24° to 52°. Two revisions were performed for glenoid loosening (3.8%); both were revision cases with substantial glenoid bone loss. One patient with mild pain had a radiographically loose glenoid component 12 years after anatomic shoulder arthroplasty. Conclusion Results from this study suggest that shoulder arthroplasty in patients with self-reported metal allergy provides satisfactory pain relief and improved range of motion with low revision rates.

Background Despite good reported outcomes with open reduction and internal fixation of intra-articular distal humerus fractures, complication rates remain high. The objective of this work is to identify factors associated with reoperation. Methods Sixty-three patients treated with open reduction and internal fixation for intra-articular ( Arbeitsgemeinschaft für Osteosynthesefragen type C) distal humerus fractures between 2004 and 2010 were identified using an institutional trauma registry, 62 of which were followed for a minimum of six months. Age, gender, fracture subclassification, open fracture presence, Injury Severity Score, time to definitive surgery, length of postoperative immobilization, and type of approach were recorded. Multivariate analysis was utilized to identify factors independently associated with reoperation. Results Complications requiring reoperation developed in 25 (40.3%) elbows. The most common reasons were wound dehiscence or infection in nine elbows (14.5%) and symptomatic hardware in six (9.6%). During multivariate analysis, only olecranon osteotomy remained an independent predictor for reoperation ( P = 0.043). Discussion Despite improved internal fixation techniques, a high proportion of elbows require reoperation after open reduction and internal fixation for distal humerus fractures. Higher complication rates in fractures fixed through an olecranon osteotomy may reflect additional reoperations due to nonunion of the osteotomy or need to remove hardware from the ulna. Level of evidence Prognostic Level III.

Background:While a large volume of literature has focused on risk factors for anterior shoulder instability, the rates of recurrence are inconsistent and require additional population-based epidemiologic data.Purpose/Hypothesis:The purpose was to report the effect of patient age on the number of instability events before physician consultation, rate of surgical stabilization, recurrent instability, and progression to osteoarthritis in patients Study Design:Descriptive epidemiologic study.Methods:An established geographic database of more than 500,000 patients was used to identify patients Results:The study population consisted of 654 patients with a mean follow-up of 11.1 years (range, 2.0-25.2 years). This resulted in 118 patients (18%) ≤15 years of age at initial instability; 250 (38%), 16 to 20 years; 110 (17%), 21 to 25 years; 80 (12%), 26 to 30 years; and 96 (15%), 31 to 40 years. Of patients ≤15 years old at initial instability 47% had 3+ instability events, compared with 12% of patients aged 31 to 40 years ( P < .001). At 10 years of follow-up, patients ≤15 and 16 to 20 years old demonstrated the highest recurrent instability rates of 38.8% and 47.1% after nonoperative management, respectively. Patients 16 to 20 years old demonstrated the highest rates of both surgical intervention (40.4%) and recurrence after surgery (24.8%). Patients 31 to 40 years of age were significantly more likely to develop clinically symptomatic osteoarthritis (15.6%) than all other age groups.Conclusion:In a US epidemiologic population of patients

The ideal analgesic modality for total shoulder arthroplasty (TSA) remains controversial. We hypothesized that a multimodal analgesic pathway incorporating continuous interscalene blockade (ISB) provides better analgesic efficacy than both single-injection ISB and local infiltration analgesia.This single-center, parallel, unblinded, randomized clinical trial evaluated 129 adults undergoing primary TSA. Patients were allocated to single-injection ISB, continuous ISB, or local infiltration analgesia. The primary outcome was the Overall Benefit of Analgesia Score (range, 0 [best] to 28 [worst]) on postoperative day 1. Additional outcomes included pain scores, opioid consumption, quality of life, and postoperative complications in the first 24 hours, at 3 months, and at 1 year.We analyzed 125 patients (42 with single-injection ISB, 41 with continuous ISB, and 42 with local infiltration analgesia). The Overall Benefit of Analgesia Score was significantly improved in the continuous group (median [25th percentile, 75th percentile], 0 [0, 2]) compared with the single-injection group (2 [1, 4]; P = .002) and local infiltration analgesia group (3 [2, 4]; P.001). Pain scores were significantly lower in the continuous group compared with the local infiltration analgesia group (P.001 for all time points) and after 12 hours from ward arrival compared with the single-injection group (median [25th percentile, 75th percentile], 1.0 [0.0, 2.8] vs. 2.5 [0.0, 4.0]; P = .016). After postanesthesia recovery discharge, opioid consumption (oral morphine equivalents) was significantly lower in the continuous group (median [25th percentile, 75th percentile], 7.5 mg [0.0, 25.0 mg]) than in the local infiltration analgesia group (30 mg [15.0, 52.5 mg]; P.001) and single-injection group (17.6 mg [7.5, 45.5 mg]; P = .010). No differences were found across groups for complications, 3-month outcomes, and 1-year outcomes.Continuous ISB provides superior analgesia compared with single-injection ISB and local infiltration analgesia in the first 24 hours after TSA.

Introduction Cutibacterium acnes is a recognized culprit for implant-associated infections, but positive cultures do not always indicate clinically relevant infection. Studies have shown a correlation between the β-hemolytic phenotype of C. acnes and its infectious capacity, but correlation with genetic phylotype has not been performed in literature. The purpose of this study is to evaluate β-hemolysis phenotype, genetic phylotype, and mid-term clinical outcomes of C. acnes isolated from orthopedic surgical sites. Methods Fifty-four C. acnes isolates previously obtained from surgical wounds of patients undergoing hip, knee, shoulder, or spine implant removal were re-cultured. There were 21 females and 33 males with an average age of 59 years (range, 18–84). Twenty-four were from clinically infected sites whereas 30 were considered contaminants. De novo β-hemolysis was analyzed and a retrospective chart review was performed to evaluate clinical outcomes at 7.1 years (range, 0.1–12.8). Results On Brucella agar with 5% rabbit blood, 46% of contaminant and 43% of infectious isolates were hemolytic. Type II phylotype was significantly more nonhemolytic regardless of infectious or contaminant status (p Conclusion The β-hemolytic profile of C. acnes did not correlate with phylotype or clinically relevant orthopedic infection.

Rheumatoid arthritis has been associated with poor clinical outcomes in hemiarthroplasty and unconstrained total shoulder arthroplasty. The reverse shoulder arthroplasty can be utilized to address the shortcomings of hemiarthroplasty and unconstrained total shoulder arthroplasty in the inflammatory arthritis patient population. The objective of the present study was to retrospectively review clinical and radiographic outcomes of patients who underwent reverse shoulder arthroplasty for rheumatoid arthritis and other inflammatory arthropathies and provide a comprehensive analysis to identify factors that may alter patient outcomes. We identified 91 primary reverse shoulder arthroplasties performed between 2006 and 2013 in patients with inflammatory arthritis. Seventy-five had at least two years of follow up with an average follow-up of 4.0 years. The average age at the time of surgery was 70 years old. Peri-operative use of steroids, biologics, and methotrexate were reviewed. Outcomes evaluated included revision and reoperation rates, complications, American Shoulder and Elbow Surgeons (ASES) scores, simple shoulder test (SST) scores, component loosening, and scapular notching. The two and five year implant revision-free survival was 99%. The two and five year re-operation-free survival was 97%. Eighteen (24%) glenoid components required augmentation with corticocancellous autograft from the humeral head. There were two cases of glenoid loosening with gross changes in position. Patients experienced significant pain relief with a 92% satisfaction rate. Shoulder elevation and external rotation improved from 65 and 21 degrees pre-operatively to 138 and 45 degrees post-operatively, respectively (p

Introduction Upper extremity lymphedema can complicate mastectomy, lymph node dissection, and radiation. The purpose of this study is to present the outcomes of shoulder arthroplasty in patients with lymphedema. Methods The 19 shoulders with a shoulder arthroplasty and lymphedema on the surgical side (6 anatomic, 12 reverse, 1 hemiarthroplasty) were followed for four years (1–10 years). There were 2 males and 17 females; average age was 67.8 (48–86) years. Breast carcinoma was the most common reason for lymphedema (75%). A dedicated lymphedema questionnaire could be completed for 14 shoulders. Results Pain improved from moderate or severe preoperatively to no or mild in 18 shoulders. Motion improved in elevation (55° preoperatively, 107° at last follow-up), external rotation (14°, 43°), and internal rotation (sacrum, L5). Complications included an acromion stress fracture with a deep infection (1), deep infection (1), superficial infection (1), and glenoid loosening (1). Lymphedema worsened in nine cases, but worsening was permanent in only four. Currently, lymphedema treatment is being performed by 93% of survey respondents. No patients reported lymphangitis or lymphangiosarcoma. Conclusion Shoulder arthroplasty for an upper extremity with lymphedema provides substantial improvements in pain and motion; however, infection is a concerning complication. Fifty percent of the patients will experience worsening of their lymphedema and in 20% worsening may be permanent.

Since its first description, the concept of reverse shoulder arthroplasty (RSA) has evolved. The term lateralization remains unclear and is used to describe implants that lateralize on the glenoid side, the humeral side, or both. The objective of this study was to provide a clear definition of lateralization and to measure the lateralization achieved by the most commonly used implants. Twenty-eight different configurations with 22 different implants were analyzed. Glenoid, humeral, and global lateralization was measured on digitized templates. Implant lateralization was normalized to the lateral offset of the Delta III. Each implant was defined as a combination of one of two glenoid categories (medialized glenoid (MG), lateralized glenoid (LG), and one of four humeral categories (medialized humerus (MH), minimally lateralized humerus (LH), lateralized humerus (LH+). In addition, implants were separated in categories of 5-mm increments for global offset (medialized RSA (M-RSA), minimally lateralized RSA (ML-RSA), lateralized RSA (L-RSA), highly lateralized RSA (HL-RSA), and very highly lateralized RSA (VHL-RSA). The global lateral offset of the Delta III was 13.1 mm; global lateral offset of all designs in this study varied between 13.1 and 35.8 mm. Regarding their global lateral offset, five implants are M-RSA (lateral offset

Background The early results of reverse shoulder arthroplasty (RSA) were influenced to some extent by the use of first-generation implants and surgeons’ learning curves, resulting in relatively high reoperation rates. The purpose of this study was to quantify the burden of and identify the indications for reoperation after primary RSA using contemporary implants and techniques. Methods A retrospective review of 1649 primary RSAs implanted consecutively between 2009 and 2015 at a single institution was conducted. All arthroplasties were performed by 5 fellowship-trained shoulder surgeons at a tertiary referral center. Demographic characteristics, indications for primary RSA, and reoperations were analyzed and categorized for trends associated with each type of reoperation performed. Results A total of 39 reoperations (2.37%) were performed for a variety of indications. Overall, only a few patients with infection or instability required reoperation (0.55%). The most common indications for reoperation were related to the humeral component (1.03%); the majority of humeral component complications were related to a specific design flaw of 1 implant system. RSAs performed for proximal humeral fracture sequelae more commonly underwent reoperation owing to instability or humeral component–related issues; all 4 cases of aseptic humeral stem loosening occurred in the setting of proximal humeral fracture sequela treatment. Only 0.36% of all primary RSAs required reoperation because of glenoid complications. Conclusions Primary RSA performed with contemporary implants and surgical techniques seems to be associated with a very low rate of reoperation. The most common reasons for reoperation were humeral component fracture for 1 particular implant, humeral loosening, dislocation, infection, and glenoid failure, each occurring at a rate under 1%.

Objectives This study aimed to compare differences in patient characteristics and clinical outcomes of nonagenarians undergoing transcatheter aortic valve replacement (TAVR) versus patients younger than 90 years of age and to test the predictive accuracy of the logistic EuroSCORE (European System for Cardiac Operative Risk Evaluation), the EuroSCORE II, and the STS-PROM (Society of Thoracic Surgeons Predicted Risk of Mortality) for mortality after TAVR in nonagenarians. Background The prevalence of severe aortic valve stenosis is increasing due to the rising life expectancy. However, there are limited data evaluating outcomes in patients older than 90 years of age. Moreover, the predictive accuracy of risk scores for mortality has not been evaluated in nonagenarian patients undergoing transfemoral TAVR. Methods The CENTER (Cerebrovascular EveNts in Patients Undergoing TranscathetER Aortic Valve Implantation) collaboration (N = 12,381) is an international collaboration consisting of 3 national registries, 6 local or multicenter registries, and 1 prospective clinical study, selected through a systematic online search. The primary endpoint of this study was the difference in 30-day all-cause mortality and stroke after TAVR in nonagenarians versus patients younger than 90 years of age. Secondary endpoints included differences in baseline characteristics, in-hospital outcomes, and the differences in predictive accuracy of the logistic EuroSCORE, the EuroSCORE II, and STS-PROM. Results A total of 882 nonagenarians and 11,499 patients younger than 90 years of age undergoing transfemoral TAVR between 2007 and 2018 were included. Nonagenarians had considerably fewer comorbidities than their counterparts. Nevertheless, rates of 30-day mortality (9.9% vs. 5.4%; relative risk [RR]: 1.8; 95% confidence interval [CI]: 1.4 to 2.3; p = 0.001), in-hospital stroke (3.0% vs. 1.9%; RR: 1.5; 95% CI: 1.0 to 2.3; p = 0.04), major or life-threatening bleeding (8.1% vs. 5.5%; RR: 1.6; 95% CI: 1.1 to 2.2; p = 0.004), and new-onset atrial fibrillation (7.9% vs. 5.2%; RR: 1.6; 95% CI: 1.1 to 2.2; p = 0.01) were higher in nonagenarians. The STS-PROM adequately estimated mortality in nonagenarians, with an observed-expected mortality ratio of 1.0. Conclusions In this large, global, patient-level analysis, mortality after transfemoral TAVR was 2-fold higher in nonagenarians compared with patients younger than 90 years of age, despite the lower prevalence of baseline comorbidities. Moreover, nonagenarians had a higher risk of in-hospital stroke, major or life-threatening bleeding, and new-onset atrial fibrillation. The STS-PROM was the only surgical risk score that accurately predicted the risk of mortality in nonagenarians.

Aims Shoulder arthroplasty using short humeral components is becoming increasingly popular. Some such components have been associated with relatively high rates of adverse radiological findings. The aim of this retrospective review was to evaluate the radiological humeral bone changes and mechanical failure rates with implantation of a short cementless humeral component in anatomical (TSA) and reverse shoulder arthroplasty (RSA). Patients and Methods A total of 100 shoulder arthroplasties (35 TSA and 65 RSA) were evaluated at a mean of 3.8 years (3 to 8.3). The mean age at the time of surgery was 68 years (31 to 90). The mean body mass index was 32.7 kg/m2 (17.3 to 66.4). Results Greater tuberosity stress shielding was noted in 14 shoulders (two TSA and 12 RSA) and was graded as mild in nine, moderate in two, and severe in three. Medial calcar resorption was noted in 23 shoulders (seven TSA and 16 RSA), and was graded as mild in 21 and moderate in two. No humeral components were revised for loosening or considered to be loose radiologically. Nine shoulders underwent reoperation for infection (n = 3), fracture of the humeral tray (n = 2), aseptic glenoid loosening (n = 1), and instability (n = 3). No periprosthetic fractures occurred. Conclusion Implantation of this particular short cementless humeral component at the time of TSA or RSA was associated with a low rate of adverse radiological findings on the humeral side at mid-term follow-up. Our data do not raise any concerns regarding the use of a short stem in TSA or RSA. Cite this article: Bone Joint J 2019;101-B:610–614.

Some companies have begun to take a stand on controversial social and political issues. These initiatives, which are defined as ‘corporate activism’, are part of a complex context that is characterised by distrust in public institutions and governments. This article analyses the impact of corporate activism on the financial returns of companies that have implemented it. Our contribution to the empirical research of corporate activism is to identify two variables not previously studied that have an influence on whether that impact is positive or negative. To this end, a wide sample of corporate activism cases were analysed using an event analysis approach to identify the effect of two key variables: (a) the controversial nature of the sector and (b) the type of activism. The results show that corporate activism actions have positive effects when the sector is not perceived as controversial, and negative when the type of activism is based on social rights. The findings provide managerial implications for marketing professionals and broaden the possibilities of corporate activism as long-term strategy.

Background: There are limited data on the incidence of capitellar osteochondritis dissecans (OCD) in the United States (US) population. Purpose: To determine the incidence of symptomatic capitellar OCD in a representative US subpopulation and identify changes in its incidence over time and to investigate the relationship between the incidence of capitellar OCD and patient sex and age. Study Design: Descriptive epidemiology study. Methods: A retrospective review was performed of patients aged ≤24 years from Olmsted County, Minnesota, with symptomatic capitellar OCD over a 25-year period (1995-2019). Patients with acute osteochondral injuries, Panner disease, and hereditary arthropathy were excluded. Poisson regression was utilized to identify the predictors of a capitellar OCD diagnosis. Incidence rates (per 100,000) were assessed for changes over time. Age groups of younger (10-15 years) versus older (16-24 years) patients were compared. Results: A total of 45 patients (78% male) were identified. The mean age was 14.5 years (range, 10-24 years); 31 patients were in the younger group, and 14 patients were in the older group. Sport participation was seen in 89%of patients; 90% were overhead athletes, and 58% were throwing athletes. The incidence of capitellar OCD was 6.0 per 100,000 overall, 9.5 per 100,000 for male patients, and 2.6 per 100,000 for female patients. The incidence was highest for male patients in the younger group (15.3/100,000) and lowest for female patients in the older group (0.8/100,000). The estimated incidence rate ratio for younger versus older patients was 3.3 ( P < .001), and the incidence rate ratio for male versus female patients was 3.5 ( P < .001). There were no changes in the incidence of capitellar OCD over time as a continuous or 5-year categorical variable ( P = .290 and P = .460, respectively). Overall, 82% of patients were treated surgically. There were no significant changes in surgical rates over time. Conclusion: In this US subpopulation, the overall incidence of symptomatic capitellar OCD between the ages of 10 and 24 years was 6.0 per 100,000 over the 25-year period studied, which is higher than previously reported US estimates. Incidence rates and treatment strategies did not change significantly over time.

Dietary supplements, based on essential polyunsaturated fatty acids, help in normalizing the circulating lipids in overweight people. These fatty acids are abundant in fish oils and certain vegetable seed oils. In this context, the fatty acid profile of 9 commercial flaxseed trademarks was analyzed. Regarding fatty acid composition, α-linolenic acid represented more than 60% of the total fatty acids. In addition, sample 3 displayed the highest oxidative stability; thus, it was selected to be used in a pilot nutritional intervention study. The objective was to assess the hypolipidemic effects of flaxseed together with an isocaloric fish-rich diet. Two groups of women aged 25-70 years presenting high levels of circulating cholesterol (> 200 mg dL-1) and triglycerides (>150 mg dL-1) participated. Group F consumed flaxseed, while group D did not. At the end of intervention, participants from group F presented significantly reduced total cholesterol and lower systolic and diastolic pressure as compared to group D. Triacylglycerols decreased in both groups with respect to initial values, suggesting a role of diet. The flaxseed trademark is an influencing variable in its fatty acid composition and flaxseed supplementation combined with a fish-rich diet can help to reduce blood lipid parameters.

Poorly controlled Paget's disease leads to excessive blood loss following total hip arthroplasty. The effect in shoulder arthroplasty is unknown. The authors reviewed 3 patients with Paget's disease involving the proximal humerus, comparing them with 17 patients with Paget's disease but no humeral involvement. The 3 patients had an estimated blood loss of 1400 mL, 1100 mL, and 350 mL, compared with an average of 280 mL in the control group. The first 2 cases required 4 units of packed red blood cells intraoperatively, and both were not managed with bisphosphonates. Paget's disease of the humerus leads to more intraoperative blood loss and higher blood transfusion requirements, particularly in cases not managed with bisphosphonates. [ Orthopedics . 2021;44(4):e614–e619.]

Distal humeral fractures in adults are challenging injuries. They often require surgical intervention in form of internal fixation or total elbow arthroplasty which is being increasingly used in physiologically elderly patients with comminuted fractures. Careful preoperative evaluation including type of fracture, quality of bone, pre-existing conditions and functional demand help in deciding optimal treatment. CT scans including 2D and 3D reconstructions are almost mandatory in proper planning of the surgical treatment. In most cases with a healthy physiologically young patient, ORIF is the treatment of choice. Biomechanical studies have shown that parallel plating resists rotational deformity to a greater degree than 90/90 plating allowing supracondylar union. Accurate realignment of articular fragments and compression at the supracondylar area is key to the success of the internal fixation. Main cause of failure of fixation is the nonunion or malunion in the supracondylar area. The principles described by O'Driscoll et al. allow for rigid fixation of the distal articular fragments and compression at the supracondylar level which is vital to healing and the prevention of hardware failure, and nonunion. Olecranon osteotomy improves the expodure of distal humeral articular surface but has its own share of problems and should be avoided if possible. Irritation of ulnar nerve is a common complication so it should be isolated, kept under vision throughout and if necessary, transposed anteiriorly. Nonunion or malunion of supracondylar fractures can be treated by revision ORIF or total elbow arthroplasty (TEA). Supracondylar shortening, bone grafting and contracture release are important elements of treatment of nonunions. In unreconstructable distal humerus fractures, where open reduction and internal fixation is not possible due to the small size of the fragments, severe comminution and/or poor bone quality, TEA is the treatment of choice. Triceps can be left intact as the excision of fractured fragments usually provide enough space to carry out the operation. Sometimes, the decision to perform TEA is only made after exposing the fracture so the surgeon should be comfortable in performing TEA if ORIF is not possible; and necessary instruments and implants should be available on the shelf. In spite of satisfactory outcome, overall complication rate after TEA remains high and makes surgical efficiency and technical competence of utmost importance.

Introduction The elbow is a rare location for primary and metastatic tumors in the upper extremity. The goal of reconstruction is to provide painless motion and stability for hand function. Total elbow arthroplasty (TEA) is commonly utilized, with either off-the-self components, modular segmental endoprosthesis, or allograft-prosthesis composites (APC). The purpose of this study was to analyze and compare commonly utilized elbow reconstructions and report outcomes of (1) patient function and (2) implant survival and complications. Methods We reviewed 33 patients (18 females and 15 males) undergoing elbow arthroplasty for reconstruction of an underlying oncologic process including linked TEA (n = 22, 67%), APC (n = 9, 27%), and endoprosthesis (n = 2, 6%). The most common indication was metastatic disease (n = 17, 52%), with 24 patients (73%) presenting with a pathologic fracture. Results Five-year implant survival was following elbow reconstruction was 88%. The mean most recent Mayo Elbow Performance Score and Musculoskeletal Tumor Society Score were 84 ± 18 and 78 ± 15%. Postoperative complications occurred in 15 elbows (45%), most commonly periprosthetic fracture (n = 5, 15%), leading to reoperation in six elbows (18%). Conclusion Although elbow arthroplasty is associated with a high incidence of complications, it provides a stable platform for upper extremity function in patients with oncologic processes of the elbow.

Background Rotator cuff fatty infiltration (FI) is one of the most important parameters to predict the outcome of certain shoulder conditions. The primary objective of this study was to define a new computed tomography (CT)–based quantitative 3-dimensional (3D) measure of muscle loss (3DML) based on the rationale of the 2-dimensional (2D) qualitative Goutallier score. The secondary objective of this study was to compare this new measurement method to traditional 2D qualitative assessment of FI according to Goutallier et al and to a 3D quantitative measurement of fatty infiltration (3DFI). Materials and methods 102 CT scans from healthy shoulders (46) and shoulders with cuff tear arthropathy (21), irreparable rotator cuff tears (18), and primary osteoarthritis (17) were analyzed by 3 experienced shoulder surgeons for subjective grading of fatty infiltration according to Goutallier, and their rotator cuff muscles were manually segmented. Quantitative 3D measurements of fatty infiltration (3DFI) were completed. The volume of muscle fibers without intramuscular fat was then calculated for each rotator cuff muscle and normalized to the patient’s scapular volume to account for the effect of body size (NVfibers). 3D muscle mass (3DMM) was calculated by dividing the NVfibers value of a given muscle by the mean expected volume in healthy shoulders. 3D muscle loss (3DML) was defined as 1 – (3DMM). The correlation between Goutallier grading, 3DFI, and 3DML was compared using a Spearman rank correlation. Results Interobserver reliability for the traditional 2D Goutallier grading was moderate for the infraspinatus (ISP, 0.42) and fair for the supraspinatus (SSP, 0.38), subscapularis (SSC, 0.27) and teres minor (TM, 0.27). 2D Goutallier grading was found to be significantly and highly correlated with 3DFI (SSP, 0.79; ISP, 0.83; SSC, 0.69; TM, 0.45) and 3DML (SSP, 0.87; ISP, 0.85; SSC, 0.69; TM, 0.46) for all 4 rotator cuff muscles (P Conclusion The Goutallier score has been helping surgeons by using 2D CT scan slices. However, this grading is associated with suboptimal interobserver agreement. The new measures we propose provide a more consistent assessment that correlates well with Goutallier’s principles. As 3DML measurements incorporate atrophy and fatty infiltration, they could become a very reliable index for assessing shoulder muscle function. Future algorithms capable of automatically calculating the 3DML of the cuff could help in the decision process for cuff repair and the choice of anatomic or reverse shoulder arthroplasty.

Experimental analyses of post-traumatic knee arthrofibrosis utilize a rabbit model as a gold standard. However, a rodent model of arthrofibrosis offers many advantages including reduced cost and comparison with other models of organ fibrosis. This study aimed to characterize the biomechanical, histological, and molecular features of a novel post-traumatic model of arthrofibrosis in rats. 48 rats were divided into two equal groups. An immobilization procedure was performed on the right hind limbs of experimental rats. One group was immobilized for 4 weeks and the other for 8 weeks. Both groups were remobilized for 4 weeks. Limbs were studied biomechanically via assessment of torque versus degree of extension, histologically via whole knee specimen, and molecularly via gene expression of posterior capsular tissues. Significant differences were observed between experimental and control limbs at 4 N-cm of torque in the 4-week (knee extension: 115° ± 8° vs. 169° ± 17°, respectively; p=0.007) and 8-week immobilization groups (knee extension: 99° ± 12° vs. 174° ± 9°, respectively; p=0.008). Histologically, in each group experimental limbs demonstrated increased posterior capsular thickness and total area of tissue when compared to control limbs (p

Background Persistent infection rate after 2-stage reimplantation complicating elbow arthroplasty has been reported to be as high as 25%. The purposes of this retrospective study were to determine the infection eradication rates, complications and outcomes in a cohort of patients treated with two-stage reimplantation for deep periprosthetic joint infection (PJI) following total elbow arthroplasty (TEA) and to determine possible associated risk factors for treatment failure. Methods Between 2000 and 2017, 52 elbows underwent a two-stage reimplantation for PJI after TEA. There were 22 males and 30 females with a mean age of 61 (range, 25–82) years. The most common bacterium was Staphylococcus epidermidis (28 elbows). Mayo Elbow Performance Scores were calculated at the latest follow-up. Mean follow-up time was 6 years (range, 2–14 years). Results PJI was eradicated in 36 elbows (69%). The remaining 16 elbows were considered treatment failures secondary to recurrent infection. The risk of persistent infection was 3.3 times higher in elbows with retained cement (p 0.04), and 3.5 times higher when the infecting organism was Staphylococcus epidermidis (p 0.06). Conclusion Two-stage reimplantation for PJI after TEA was successful in eradicating deep infection in 69% of cases. The eradication of PJI after TEA still needs to be improved substantially.

Aims The purpose of this study was to report bone adaptive changes after anatomical total shoulder arthroplasty (TSA) using a standard-length hydroxyapatite (HA)-coated humeral component, and to report on a computer-based analysis of radiographs to determine changes in peri-implant bone density objectively. Methods A total of 44 TSAs, performed between 2011 and 2014 using a cementless standard-length humeral component proximally coated with HA, were included. There were 23 males and 21 females with a mean age of 65 years (17 to 65). All shoulders had good quality radiographs at six weeks and five years postoperatively. Three observers graded bone adaptive changes. All radiographs were uploaded into a commercially available photographic software program. The grey value density of humeral radiological areas was corrected to the grey value density of the humeral component and compared over time. Results Stress shielding was graded as mild in 14 shoulders and moderate in three; the greater tuberosity was the predominant site for stress shielding. The mean metaphyseal and diaphyseal fill-fit ratios were 0.56 (SD 0.1) and 0.5 (SD 0.07), respectively. For shoulders with no radiologically visible stress shielding, the mean decrease in grey value in zones 1 and 7 was 20%, compared with 38% in shoulders with radiologically visible stress shielding. Conclusion The rate of moderate stress shielding was 7%, five years after implantation of a cementless standard-length HA-coated humeral component. Clinical observation of stress shielding identified on radiographs seems to represent a decrease in grey value of 25% or more. Cite this article: Bone Joint J 2021;103-B(5):958–963.

Innate immune cellular effectors are actively consumed during systemic inflammation, but the systemic traffic and the mechanisms that support their replenishment remain unknown. Here, we demonstrate that acute systemic inflammation induces the emergent activation of a previously unrecognized system of rapid migration of granulocyte-macrophage progenitors and committed macrophage-dendritic progenitors, but not other progenitors or stem cells, from bone marrow (BM) to regional lymphatic capillaries. The progenitor traffic to the systemic lymphatic circulation is mediated by Ccl19/Ccr7 and is NF-κB independent, Traf6/IκB-kinase/SNAP23 activation dependent, and is responsible for the secretion of pre-stored Ccl19 by a subpopulation of CD205+/CD172a+ conventional dendritic cells type 2 and upregulation of BM myeloid progenitor Ccr7 signaling. Mature myeloid Traf6 signaling is anti-inflammatory and necessary for lymph node myeloid cell development. This report unveils the existence and the mechanistic basis of a very early direct traffic of myeloid progenitors from BM to lymphatics during inflammation., eLife digest When the body becomes infected with disease-causing pathogens, such as bacteria, the immune system activates various mechanisms which help to fight off the infection. One of the immune system’s first lines of defense is to launch an inflammatory response that helps remove the pathogen and recruit other immune cells. However, this response can become overactivated, leading to severe inflammatory conditions that damage healthy cells and tissues. A second group of cells counteract this over inflammation and are different to the ones involved in the early inflammatory response. Both types of cells – inflammatory and anti-inflammatory – develop from committed progenitors, which, unlike stem cells, are already destined to become a certain type of cell. These committed progenitors reside in the bone marrow and then rapidly travel to secondary lymphoid organs, such as the lymph nodes, where they mature into functioning immune cells. During this journey, committed progenitors pass from the bone marrow to the lymphatic vessels that connect up the different secondary lymphoid organs, and then spread to all tissues in the body. Yet, it is not fully understood what exact route these cells take and what guides them towards these lymphatic tissues during inflammation. To investigate this, Serrano-Lopez, Hegde et al. used a combination of techniques to examine the migration of progenitor cells in mice that had been treated with lethal doses of a bacterial product that triggers inflammation. This revealed that as early as one to three hours after the onset of infection, progenitor cells were already starting to travel from the bone marrow towards lymphatic vessels. Serrano-Lopez, Hegde et al. found that a chemical released by an “alarm” immune cell already residing in secondary lymphoid organs attracted these progenitor cells towards the lymphatic tissue. Further experiments showed that the progenitor cells travelling to secondary lymphoid organs were already activated by bacterial products. They then follow the chemical released by alarm immune cells ready to respond to the immune challenge and suppress inflammation. These committed progenitors were also found in the inflamed lymph nodes of patients. These findings suggest this rapid circulation of progenitors is a mechanism of defense that contributes to the fight against severe inflammation. Altering how these cells migrate from the bone marrow to secondary lymphoid organs could provide a more effective treatment for inflammatory conditions and severe infections. However, these approaches would need to be tested further in the laboratory and in clinical trials.

Arthrofibrosis is characterized by excessive extracellular matrix deposition in patients with total knee arthroplasties (TKAs) and causes undesirable joint stiffness. The pathogenesis of arthrofibrosis remains elusive and currently there are no diagnostic biomarkers for the pathological formation of this connective tissue. Fibrotic soft tissues are known to have elevated levels of plasminogen activator inhibitor-1 (PAI-1) (encoded by SERPINE1), a secreted serine protease inhibitor that moderates extracellular matrix remodeling and tissue homeostasis. The 4G/5G insertion/deletion (rs1799889) is a well-known SERPINE1 polymorphism that directly modulates PAI-1 levels. Homozygous 4G/4G allele carriers typically have higher PAI-1 levels and may predispose patients to soft tissue fibrosis (e.g., liver, lung, and kidney). Here, we examined the genetic contribution of the SERPINE1 rs1799889 polymorphism to musculoskeletal fibrosis in arthrofibrotic (n = 100) and non-arthrofibrotic (n = 100) patients using Sanger Sequencing. Statistical analyses revealed that the allele frequencies of the SERPINE1 rs1799889 polymorphism are similar in arthrofibrotic and non-arthrofibrotic patient cohorts. Because the fibrosis related SERPINE1 rs1799889 polymorphism is independent of arthrofibrosis susceptibility in TKA patients, the possibility arises that fibrosis of joint connective tissues may involve unique genetic determinants distinct from those linked to classical soft tissue fibrosis.

16S ribosomal RNA (rRNA) gene PCR followed by next-generation sequencing (NGS) was compared to culture of sonicate fluid derived from total elbow arthroplasty for periprosthetic joint infection (PJI) diagnosis. Sonicate fluids collected from 2007 to 2019 from patients who underwent revision of a total elbow arthroplasty were retrospectively analyzed at a single institution. PCR amplification of the V1-V3 region of the 16S rRNA gene was performed, followed by NGS using an Illumina MiSeq. Results were compared to those of sonicate fluid culture using McNemar's test of paired proportions. Forty-seven periprosthetic joint infections and 58 non-infectious arthroplasty failures were studied. Sensitivity of targeted NGS was 85%, compared to 77% for culture (P = 0.045). Specificity and positive and negative predictive values of targeted NGS were 98, 98 and 89%, respectively, compared to 100, 100 and 84%, respectively, for culture. 16S rRNA gene-based targeted metagenomic analysis of sonicate fluid was more sensitive than culture.

Objectives: Distal biceps tendon tears, although rare, significantly impair patient’s elbow mobility and function. There is a paucity of literature reporting outcomes of partial thickness tears to inform management strategies. Therefore, the authors sought to identify magnetic resonance imaging (MRI) confirmed partial thickness distal biceps tears and report on (1) demographics and treatment strategies, (2) outcomes and complications, and (3) any identifiable risk factors for progression to surgery or full thickness tear. Methods: Patients who experienced a partial thickness distal biceps tear confirmed on MRI from 1996 to 2016 were identified by a musculoskeletal radiologist through an institutional image database. Patients were included if they had complete medical records and at least one visit of clinical follow-up. Patients with inflammatory arthritis and enthesitis, polytrauma, or incidental findings without clinical assessment were excluded. Medical records were reviewed to confirm the diagnosis and obtain study details. Multivariate logistic regression models were created using baseline characteristics, injury details and physical exam findings in order to predict operative intervention. Results: Overall, 111 patients (22F, 89M, age: 53.6 years ± 13) were identified and included. Baseline injury characteristics and patient demographics including weakness in elbow flexion, forearm supination, and patient reported sensation at time of injury were all found to be statistically different between treatment groups (Table 1). Patients were followed to a mean of 10 years of clinical follow up. Within the cohort, 57 patients were treated non-operatively, while 54 were treated operatively. Patients who received surgical intervention were more likely to report missing time from work and greater loss of productivity due to missed time (Table 2); however, almost 90% of patients returned to work without restrictions, regardless of treatment modality (88% vs 88%, Table 2). For surgical patients, there were 5 re-operations (9%), 3 re-ruptures (6%), and overall, 31% of the operatively treated cohort experienced a complication. Results of the final multivariate logistic regression model are included in Table 3; final model variables included age at initial consult, tenderness to palpation tendon insertion on exam, and supination weakness. Of these, supination weakness at initial consult was found to be a statistically significant predictor for surgical intervention (p=.001, OR=24.8). Conclusions: Operative patients tended to be male with more profound supination weakness; these patients tended to report increased loss of productivity due to time missed after treatment. At 10 year clinical follow up 31% experienced some complication and 9% underwent a re-operation. However, patients demonstrated uniform ability to return to work without modification and no statistical differences in functional outcomes, regardless of treatment modality. Patients who suffer from a partial distal biceps tear should be counseled that operative management represents a balance of returning function with potential complications and increased loss of productivity. [Table: see text][Table: see text][Table: see text]

Objectives: Distal biceps tendon tears, although rare, significantly impair patient’s elbow mobility and function. There is a paucity of contemporary literature reporting long term outcomes of distal biceps (DB) injuries. Therefore, the authors sought to identify magnetic resonance imaging (MRI) confirmed distal bicep tears and report on (1) patient demographics and injury characteristics of all patients with distal bicep pathology, (2) outcomes of all patients with non-operatively managed DB pathology, and (3) outcomes of all patients with operatively managed DB pathology. Methods: Patients with an MRI-confirmed distal biceps rupture from 1996 to 2016 were identified through an institutional image database. Patients from the initial search were then cross-referenced with the [REDACTED]1 to ensure record availability. Patients were included if they had complete medical records and ≥5 years of clinical follow-up. Patients with inflammatory arthritis and enthesitis, polytrauma, or incidental findings without clinical assessment were excluded. Medical records were reviewed to confirm the diagnosis of distal biceps tears and obtain further subject details. Results: A total of 158 patients (22 female, 136 male) with a mean age 51.5 years (44.8-61.2) were identified and included. Baseline patient demographics including BMI, smoking status, dominant-handedness, laborer occupation, and gender were gathered (Table 1). Patients had a mean clinical follow-up of almost 14 years (Table 1, range 8.4 -17.8). Outcomes of the 52 non-operative and 106 operatively managed patients, included severe complications, functional outcomes, and health-related productivity loss are reported in Table 2. There were 7 re-operations (4%), 5 re-ruptures (3%), and overall 35% of the operatively treated cohort experienced a complication. Conclusions: Patients with distal bicep pathology tended to be a male laborer in their 50s without clinically significantly associated risk factors. The majority of patients regained full ROM, and 83% were able to return to work without modifications, irregardless of operative or non-operative management. At long term follow up, patients treated operatively were more likely to report missing time from work and averaged more days missed than their non-operatively treated counterparts. Additionally, operative patients had no statistically significant gains functional outcomes, and were subject to potential post-operative complications. Surgeon bias may play a role in deciding treatment for distal biceps tears. As such, careful patient selection for surgical intervention for distal biceps pathology should be employed; surgeons should consider restricting surgical intervention to patients who have significant clinical symptoms or fail non-operative management. [Table: see text][Table: see text]

Innate immune cellular effectors are actively consumed during systemic inflammation but the systemic traffic and the mechanisms that support their replenishment remain unknown. Here we demonstrate that acute systemic inflammation induces the emergent activation of a previously unrecognized system of rapid migration of granulocyte-macrophage progenitors and committed macrophage-dendritic progenitors, but not other progenitors or stem cells, from bone marrow (BM) to lymphatic capillaries. The progenitor traffic to the systemic lymphatic circulation is mediated by Ccl19/Ccr7 and is NFκB independent, Traf6/IκB-kinase/SNAP23 activation which is responsible for the secretion of pre-stored Ccl19 by a subpopulation of CD205+/CD172a+ conventional dendritic cells type 2 (cDC2) and upregulation of BM myeloid progenitor Ccr7 signaling. The consequence of this progenitor traffic is anti-inflammatory with promotion of early survival and initiation of replenishment of lymph node cDC.

International audience; Design, development, manufacturing, and test activities of the RF power system (RFPS) for Linear IFMIF Prototype Accelerator (LIPAc) were completed in Europe. Installation and commissioning activities were carried out at the International Fusion Materials Irradiation Facility-Engineering Validation and Engineering Design Activities (IFMIF/EVEDA) site in Rokkasho, Japan. Challenging IFMIF requirements led to a number of innovations during design and development. Commissioning required a major effort on calibration and fine setting and led to development of new functionalities. The RFPS was validated under full power and 125-mA deuteron beam loading conditions, in the radio frequency quadrupole (RFQ), demonstrating good performance. This article is an overview about how technical challenges impacted the prototype RFPS design and its functional evolution during commissioning, cavity conditioning, and beam operation of the RFQ.

Next-Generation Sequencing has recently been introduced to efficiently and simultaneously detect genetic variations in acute myeloid leukemia. However, its implementation in the clinical routine raises new challenges focused on the diversity of assays and variant reporting criteria. To overcome this challenge, the PETHEMA group established a nationwide network of reference laboratories aimed to deliver molecular results in the clinics. We report the technical cross-validation results for next-generation sequencing panel genes during the standardization process and the clinical validation in 823 samples of 751 patients with newly diagnosed or refractory/relapse acute myeloid leukemia. Two cross-validation rounds were performed in seven nationwide reference laboratories in order to reach a consensus regarding quality metrics criteria and variant reporting. In the pre-standardization cross-validation round, an overall concordance of 60.98% was obtained with a great variability in selected genes and conditions across laboratories. After consensus of relevant genes and optimization of quality parameters the overall concordance rose to 85.57% in the second cross-validation round. We show that a diagnostic network with harmonized next-generation sequencing analysis and reporting in seven experienced laboratories is feasible in the context of a scientific group. This cooperative nationwide strategy provides advanced molecular diagnostic for acute myeloid leukemia patients of the PETHEMA group.

Three-dimensional (3D) geometry of the normal glenohumeral bone anatomy and relations is poorly documented. Our aims were (1) to determine the 3D geometry of the normal glenohumeral joint (GHJ) with reference to the scapular body plane and (2) to identify spatial correlations between the orientation and direction of the humeral head and the glenoid.Computed tomographies (CTs) of the normal, noninjured GHJ were collected from patients who had undergone CTs in the setting of (1) polytrauma, (2) traumatic head injury, (3) chronic acromioclavicular joint dislocations, and (4) unilateral trauma with a contralateral normal shoulder. We performed 3D segmentation and measurements with a fully automatic software (Glenosys; Imascap). Measurements were made in reference to the scapular body plane and its transverse axis. Geometric measurements included version, inclination, direction, orientation, best-fit sphere radius (BFSR), humeral subluxation, critical shoulder angle, reverse shoulder angle, glenoid area, and glenohumeral distance. Statistical correlations were sought between glenoid and humeral 3D measurements (Pearson correlation).A total of 122 normal GHJs (64 men, 58 women, age: 52 ± 17 years) were studied. The glenoid BFSR was always larger than the humerus BFSR (constant factor of 1.5, standard deviation = 0.2). The mean glenoid version and inclination were -6° ± 4° and 7° ± 5°, respectively. Men and women were found to have significantly different values for inclination (6° vs. 9°, P = .02), but not for version. Humeral subluxation was 59% ± 7%, with a linear correlation with glenoid retroversion (r = -0.70, P.001) regardless of age. There was a significant and linear correlation between glenoid and humeral orientation and direction (r = 0.72 and r = 0.70, P.001).The 3D geometry of the glenoid and humeral head present distinct limits in normal shoulders that can be set as references in daily practice: version and inclination are -6° and 7°, respectively, and humeral posterior subluxation is 59%; interindividual variations, regardless of the size, are relative to the scapular plane. There exists a strong correlation between the position of the humeral head and the glenoid orientation and direction.

Objectives To determine outcomes of radial head replacement (RHR) for acute fractures using 3 different implant designs with or without cement fixation. Design Retrospective. Setting Tertiary referral hospital. Patients/participants One hundred fourteen elbows underwent RHR for an acute radial head fracture using either (1) a nonanatomic design and smooth stem (n = 60), (2) a nonanatomic design with a grit-blasted, ingrowth, curved stem (n = 21), or (3) an anatomic design with a grit-blasted ingrowth straight stem (n = 33). Cemented (25%) or uncemented (75%) fixation was used at the discretion of the treating surgeon. Intervention RHR. Main outcome measurements The primary outcome was implant survivorship free of revision or removal for any reason. All elbows were evaluated clinically (the Mayo Elbow Performance Score and reoperations/complications) and radiographically. Results Fourteen implants (12%) were revised. Of elbows with a minimum 2-year clinical follow-up, the average Mayo Elbow Performance Score was 88. The rate of survivorship free from revision was 92% [95% confidence interval (CI) = 87%-98%] at 2 years, 90% (CI = 84%-96%) at 5 years and 84% (CI = 75%-94%) at 10 years. The differences in survivorship between the 3 implants did not reach statistical significance, but the nonanatomic design with a grit-blasted ingrowth curved stem had a hazard ratio of 4.6 (95% CI = 0.9%-23%) for failure. There were no differences in survivorship between cemented versus uncemented stems. For those elbows with a minimum of 2 years of radiographic follow-up, implant tilt was observed in 10 (16%) elbows and loosening in 16 (26%) elbows. Stress shielding was present in 19 (42%) of well-fixed implants. Conclusions RHR for acute trauma leads to survivorship greater than 80% at 10 years. Radiographic changes (loosening, stress shielding, and implant tilting) can be expected in a substantial portion of elbows at long-term follow-up. Level of evidence Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence.

Background Metabolic syndrome (MetS) is an abnormal physiological condition that has been increasingly identified as a risk factor for complications after orthopedic surgery. Given the lack of information on the effect of MetS in shoulder arthroplasty (SA), this investigation analyzed the rates of postoperative complications and implant survivorship free from reoperation and revision in patients with and without MetS. Methods Between 2007 and 2017, data from 4635 adults who underwent a primary SA were collected and classified based on the presence or absence of MetS. MetS was defined as the existence of type 2 diabetes mellitus and a minimum of 2 of the following diagnoses: hyperlipidemia, hypertension, and body mass index ≥ 30 kg/m2 within 1 year of surgery. Of the 4635 arthroplasties, 714 were performed in patients with MetS (anatomic total shoulder arthroplasty [aTSA] in 289 and reverse shoulder arthroplasty [RSA] in 425) and 3921 were performed in patients without MetS (aTSA in 1736 and RSA in 2185). Demographic characteristics, complications, reoperations, and revision surgery were compared. Results At a mean of follow-up of 4.5 ± 2.3 years, 67 MetS patients (9.4%) and 343 non-MetS patients (8.7%) had sustained at least 1 postoperative complication (P = .851). Rotator cuff failure was the most common complication overall, with 84 cases (1.8%) (15 MetS cases [2.1%] and 69 non-MetS cases [1.8%], P = .851), and in both MetS and non-MetS patients, followed by infection, with 68 cases (1.2%) (10 MetS cases [1.4%] and 58 non-MetS cases [1.2%], P = .913). For aTSAs, the most common complication was rotator cuff failure (84 shoulders, 1.8%); for RSAs, the most common complication was periprosthetic fracture (52 shoulders, 1.1%). In RSAs, the rates of deep infection (1.9% vs. 0.7%, P = .04), instability (3.1% vs. 1.5%, P = .04), and deep venous thrombosis or pulmonary embolism (0.5% vs. 0.3%, P = .03) were found to be significantly higher in patients with MetS than in those without MetS. Reoperations were observed in 36 MetS patients (5%) and 170 non-MetS patients (4.3%) (P = .4). Revisions were performed in 30 MetS patients (4.2%) and 127 non-MetS patients (3.2%) (P = .19). The Kaplan-Meier 5-year rate of survivorship free from reoperation, revision, and prosthetic joint infection was equal between groups. Conclusions A preoperative diagnosis of MetS in patients undergoing primary SA did not significantly increase the risk of postoperative complications, infection, reoperation, or revision following primary SA. However, in the RSA subgroup, complications were significantly more common in patients with MetS. Individual risk factors may be more appropriate than the umbrella diagnosis of MetS prior to aTSA.

(1) Background: Arthrofibrosis is a common cause of patient debility and dissatisfaction after total knee arthroplasty (TKA). The diversity of molecular pathways involved in arthrofibrosis disease progression suggest that effective treatments for arthrofibrosis may require a multimodal approach to counter the complex cellular mechanisms that direct disease pathogenesis. In this study, we leveraged RNA-seq data to define genes that are suppressed in arthrofibrosis patients and identified adiponectin (ADIPOQ) as a potential candidate. We hypothesized that signaling pathways activated by ADIPOQ and the cognate receptors ADIPOR1 and ADIPOR2 may prevent fibrosis-related events that contribute to arthrofibrosis. (2) Methods: Therefore, ADIPOR1 and ADIPOR2 were analyzed in a TGF&beta, 1 inducible cell model for human myofibroblastogenesis by both loss- and gain-of-function experiments. (3) Results: Treatment with AdipoRon, which is a small molecule agonist of ADIPOR1 and ADIPOR2, decreased expression of collagens (COL1A1, COL3A1, and COL6A1) and the myofibroblast marker smooth muscle &alpha, actin (ACTA2) at both mRNA and protein levels in basal and TGF&beta, 1-induced cells. (4) Conclusions: Thus, ADIPOR1 and ADIPOR2 represent potential drug targets that may attenuate the pathogenesis of arthrofibrosis by suppressing TGF&beta, dependent induction of myofibroblasts. These findings also suggest that AdipoRon therapy may reduce the development of arthrofibrosis by mediating anti-fibrotic effects in joint capsular tissues.

The relative indications of anatomic total shoulder arthroplasty (TSA) and reverse shoulder arthroplasty (RSA) continue to evolve. Some surgeons favor RSA over TSA for elderly patients with primary glenohumeral osteoarthritis (GHOA) and an intact rotator cuff due to fear of a postoperative (secondary) rotator cuff tear in this age group. However, RSA is associated with unique complications and a worse functional arc of motion compared with TSA. Therefore, it is important to understand the clinical outcomes and rates of revision surgery and secondary rotator cuff tears in elderly patients undergoing TSA.Between January 1, 2010, and December 31, 2017, 377 consecutive TSAs were performed for primary GHOA in 340 patients 70 years of age or older. The mean age at surgery was 76.2 years (standard deviation [SD], 4.9). Clinical evaluation included pain, motion, and American Shoulder and Elbow Surgeons score. Radiographs were reviewed for preoperative morphology and postoperative complications. All complications and reoperations were recorded. The average clinical follow-up time was 3.3 years (SD, 2.0). Statistical analyses were performed, and Kaplan-Meier implant survival estimates were calculated. For all analyses, a P value.05 was considered statistically significant.The mean pain visual analog scale and American Shoulder and Elbow Surgeons score at the final follow-up were 1.6 (SD, 2.2) and 78.0 (SD, 17.8), respectively. Forward elevation and external rotation increased from 96° (SD, 30°) and 26° (SD, 20°) preoperatively to 160° (SD, 32°) and 64° (SD, 26°) postoperatively (P.001 for each). The percentage of patients who had internal rotation to L5 or greater increased from 24.8% preoperatively to 71.8% postoperatively (P.001). Revision surgery was performed in 3 shoulders (0.8%), and the 5-year implant survival estimate was 98.9% (95% confidence interval: 97.3%-100%). There were 3 medical (0.8%), 10 minor surgical (2.7%), and 5 major surgical (1.3%) complications. No shoulder had radiographic evidence of humeral component loosening, whereas 7 (2%) had evidence of some degree of glenoid component loosening. In total, there were 5 secondary rotator cuff tears (1.3%), of which 2 (0.5%) required revision surgery.Elderly patients with primary GHOA and an intact rotator cuff have excellent clinical and radiographic outcomes after anatomic TSA, with high implant survival rates and a low incidence of secondary rotator cuff tears in the first 5 postoperative years. Age greater than 70 by itself should not be considered an indication for RSA over TSA.

INTRODUCTION The proximal humerus is a common site of primary and metastatic disease in the upper extremity. Historically, the goal of a hemiarthroplasty reconstruction was to provide a stable platform for hand and elbow function, with limited shoulder function. Techniques utilizing a reverse endoprosthesis (endoprosthetic replacement [EPR]) and allograft-prosthetic composite (APC) have been developed; however, there is a paucity of comparative studies. METHODS A total of 83 (42 females, 41 males) patients undergoing an intraarticular resection of the humerus were reviewed. Reconstructions included 30 reverse and 53 hemiarthroplasty; including hemiarthroplasty EPR (n = 36) and APC (n = 17), and reverse EPR (n = 20) and APC (n = 10). RESULTS Reverse reconstructions had improved forward elevation (85° vs. 44°, p

Background: Acute myeloid leukemia (AML) remains a major clinical challenge due to poor overall survival, which is even more dramatic in elderly patients. TIGIT, an inhibitory receptor that interacts with CD155 and CD112 molecules, is considered as a checkpoint in T and NK cell activation. This receptor shares ligands with the co-stimulatory receptor DNAM-1 and with TACTILE. The aim of this work was to analyze the expression of DNAM-1, TIGIT and TACTILE in NK cells and T cell subsets in AML patients. Methods: We have studied 36 patients at the time of diagnosis of AML and 20 healthy volunteers. The expression of DNAM-1, TIGIT and TACTILE in NK cells and T cells, according to the expression of CD3 and CD56, was performed by flow cytometry. Results: NK cells, CD56&minus, T cells and CD56+ T (NKT-like) cells from AML patients presented a reduced expression of DNAM-1 compared with healthy volunteers. An increased expression of TIGIT was observed in mainstream CD56&minus, T cells. No differences were observed in the expression of TACTILE. Simplified presentation of incredibly complex evaluations (SPICE) analysis of the co-expression of DNAM-1, TIGIT and TACTILE showed an increase in NK and T cells lacking DNAM-1 and co-expressing TIGIT and TACTILE. Low percentages of DNAM-1&minus, TIGIT+TACTILE+ NK cells and DNAM-1&minus, TIGIT+TACTILE+ CD56&minus, T cells were associated with a better survival of AML patients. Conclusions: The expression of DNAM-1 is reduced in NK cells and in CD4+ and CD8+ T cells from AML patients compared with those from healthy volunteers. An increased percentage of NK and T cells lacking DNAM-1 and co-expressing TIGIT and TACTILE is associated with patient survival, supporting the role of TIGIT as a novel candidate for checkpoint blockade.

The reasons for referral and travel patterns are lacking for patients undergoing reverse shoulder arthroplasty (RSA). The purpose of this study was to compare comorbidities, surgical time, cost and complications between local and distant primary RSA patients.Between 2007 and 2015, 1,666 primary RSAs were performed at our institution. Patients were divided into two cohorts, local patients (from within Olmstead county and surrounding counties, 492 RSAs) and those from a distance (1,174 RSAs).Local patients were older (74 vs 71 years, p .001), more likely to have RSA for fracture, had a higher Charlson comorbidity score (3.8 vs 3.2, p .001) and longer hospital stays (2.0 vs 1.8 days, p 0.001) compared to referred patients. Referral patients required longer operative times (95 vs 88 min, p = .002), had higher hospitalization costs ($19,101 vs $18,735, p .001), and had a higher rate of prior surgery (32% vs 24%, p .001). There were no differences between cohorts regarding complications or need for reoperation.Patients traveling from a distance to undergo primary RSA had longer operative times and were more likely to have had prior surgery than local patients. This may demonstrate the referral bias seen at large academic centers and should be considered when reviewing RSA outcomes, hospital performance, and calculating insurance reimbursement.Level IV.