Fluoxetine restrains allergic inflammation by targeting an FcɛRI-ATP positive feedback loop in mast cells.

There is a clinical need for new treatment options addressing allergic disease. Selective serotonin reuptake inhibitors (SSRIs) are a class of antidepressants that have anti-inflammatory properties. We tested the effects of the SSRI fluoxetine on IgE-induced function of mast cells, which are critical effectors of allergic inflammation. We showed that fluoxetine treatment of murine or human mast cells reduced IgE-mediated degranulation, cytokine production, and inflammatory lipid secretion, as well as signaling mediated by the mast cell activator ATP. In a mouse model of systemic anaphylaxis, fluoxetine reduced hypothermia and cytokine production. Fluoxetine was also effective in a model of allergic airway inflammation, where it reduced bronchial responsiveness and inflammation. These data show that fluoxetine suppresses mast cell activation by impeding an FcɛRI-ATP positive feedback loop and support the potential repurposing of this SSRI for use in allergic disease.

Clinical and radiographic outcomes following anatomic total shoulder arthroplasty utilizing an inset glenoid component at 2-year minimum follow-up: a dual center study.

BACKGROUND: Anatomic total shoulder arthroplasty (aTSA) is a successful and reproducible treatment for patients with painful glenohumeral arthritis. However, long-term outcomes using traditional onlay glenoid components have been tempered by glenoid loosening. Inset components have been proposed to minimize glenoid loosening by reducing edge-loading and opposite-edge lift-off forces with humeral translation. Successful short- and long-term outcomes have been reported while using inset glenoid implants. The current study is the largest study presenting a minimum of 2-year follow-up data following aTSA with an all-polyethylene inset glenoid component (Shoulder Innovations, Holland, MI, USA). METHODS: A dual center, retrospective review of patients undergoing aTSA using an Inset glenoid component by 2 fellowship-trained shoulder surgeons at 2 separate institutions from August, 2016, to August, 2019, was performed. Minimum follow-up was 2 years. Range of motion (ROM), visual analog scale (VAS) pain scores, Single Assessment Numeric Evaluation (SANE), and American Shoulder and Elbow Surgeons (ASES) scores were obtained. Radiographic outcomes, including central peg lucency and glenoid loosening, were assessed by 3 independent reviewers on the postoperative Grashey and axillary radiographs obtained at the final follow-up. RESULTS: Seventy-five shoulders were included for the final analysis. The mean age of the entire cohort was 64 (±11.4) years. Twenty-one (28%) glenoids were type A1, 10 (13.3%) were type A2, 13 (17.3%) were type B1, 22 (29.3%) were type B2, 6 (8%) were type B3, and 3 (4%) were type D. At a minimum follow-up of 24 months (mean: 28.7 months), a significant improvement in ROM in all planes was observed. Significant improvements in VAS (5.1-0.9, P < .001), SANE (39.5-91.2, P < .001), and ASES (43.7-86.6, P < .001) scores were observed. There were 4 (5.3%) cases of central peg lucency about the inset glenoid component and one (1.3%) case of glenoid loosening. No revisions were performed for glenoid loosening. CONCLUSION: At a minimum of 2 years postoperatively, there were significant improvements in ROM, VAS, SANE, and ASES scores with very low rates of central peg lucency and glenoid loosening in patients undergoing aTSA with an inset glenoid component. Further work is needed to determine the long-term benefit of this novel implant.

Targeting Mast Cells in Allergic Disease: Current Therapies and Drug Repurposing.

The incidence of allergic disease has grown tremendously in the past three generations. While current treatments are effective for some, there is considerable unmet need. Mast cells are critical effectors of allergic inflammation. Their secreted mediators and the receptors for these mediators have long been the target of allergy therapy. Recent drugs have moved a step earlier in mast cell activation, blocking IgE, IL-4, and IL-13 interactions with their receptors. In this review, we summarize the latest therapies targeting mast cells as well as new drugs in clinical trials. In addition, we offer support for repurposing FDA-approved drugs to target mast cells in new ways. With a multitude of highly selective drugs available for cancer, autoimmunity, and metabolic disorders, drug repurposing offers optimism for the future of allergy therapy.

Comparative Analysis of Contemporary Fixed Tibial Inserts: A Systematic Review and Network Meta-analysis of Randomized Controlled Trials.

Background: Multiple options are available for the tibial insert in total knee arthroplasty (TKA). A systematic review (SR) and network meta-analysis (NMA) to compare available randomized controlled trials (RCTs) could assist with decision making. We aim to show that designs with increased conformity may improve function and satisfaction without an increase in complications though posterior stabilized (PS) inserts will likely have more flexion. Methods: A search of MEDLINE, EMBASE, and the Cochrane Library was performed. Studies were limited to RCTs evaluating cruciate retaining (CR), PS, anterior stabilized (AS), medial pivot (MP), bicruciate retaining (BR), and bicruciate stabilizing (BCS) inserts. Mean differences (MD) were used for patient reported outcome measures (PROMs) and odds ratios (OR) for reoperation rates and MUA. A systematic review was performed for satisfaction. Results: 27 trials were identified. The NMA showed no difference from a statistical or clinical standpoint for PROMs evaluated. There was a statistical difference for increased flexion for PS knees (3 degrees p 0.04). There were no differences in the MUA or reoperation rates. There was insufficient information to determine if a specific insert improved satisfaction. Discussion: The results of this NMA show no statistical or clinical difference in PROMs. There was higher flexion for PS knees though the amount was not clinically significant. There was insufficient data for conclusions on patient satisfaction. Therefore, the surgeon should evaluate the clinical situation to determine the best insert rather than choose and insert based on functional scores, patient satisfaction, or complication rates.

Hip and Knee Bracing: Categorization, Treatment Algorithm, and Systematic Review.

Hip and knee braces or orthoses are often used to provide support after surgery and to prevent or reduce the severity of injuries. The braces are used for stabilization, immobilization, mechanical correction, and rehabilitation. Hip braces consist of stabilization and unloader variations, whereas knee braces are composed of knee sleeves and patellofemoral, prophylactic, unloader, and functional braces. Indications vary widely and depend on the type of brace. Hip braces can treat osteoarthritis to instability after total hip arthroplasty. Knee brace indications range from mild arthralgias to instability and osteoarthritis. Although braces are routinely used clinically, high-level evidence is sparse for their use. With this review, the different types and uses of hip and knee braces have been defined, and their indications exemplified in hopes of spurring future research.