Ulnar-sided wrist pain. II. Clinical imaging and treatment

Pain at the ulnar aspect of the wrist is a diagnostic challenge for hand surgeons and radiologists due to the small and complex anatomical structures involved. In this article, imaging modalities including radiography, arthrography, ultrasound (US), computed tomography (CT), CT arthrography, magnetic resonance (MR) imaging, and MR arthrography are compared with regard to differential diagnosis. Clinical imaging findings are reviewed for a more comprehensive understanding of this disorder. Treatments for the common diseases that cause the ulnar-sided wrist pain including extensor carpi ulnaris (ECU) tendonitis, flexor carpi ulnaris (FCU) tendonitis, pisotriquetral arthritis, triangular fibrocartilage complex (TFCC) lesions, ulnar impaction, lunotriquetral (LT) instability, and distal radioulnar joint (DRUJ) instability are reviewed

Somatic Mutations in UBA1 and Severe Adult-Onset Autoinflammatory Disease

BACKGROUND Adult-onset inflammatory syndromes often manifest with overlapping clinical features. Variants in ubiquitin-related genes, previously implicated in autoinflammatory disease, may define new disorders. METHODS We analyzed peripheral-blood exome sequence data independent of clinical phenotype and inheritance pattern to identify deleterious mutations in ubiquitin-related genes. Sanger sequencing, immunoblotting, immunohistochemical testing, flow cytometry, and transcriptome and cytokine profiling were performed. CRISPR-Cas9–edited zebrafish were used as an in vivo model to assess gene function. RESULTS We identified 25 men with somatic mutations affecting methionine-41 (p.Met41) in UBA1, the major E1 enzyme that initiates ubiquitylation. (The gene UBA1 lies on the X chromosome.) In such patients, an often fatal, treatment-refractory inflammatory syndrome develops in late adulthood, with fevers, cytopenias, characteristic vacuoles in myeloid and erythroid precursor cells, dysplastic bone marrow, neutrophilic cutaneous and pulmonary inflammation, chondritis, and vasculitis. Most of these 25 patients met clinical criteria for an inflammatory syndrome (relapsing polychondritis, Sweet’s syndrome, polyarteritis nodosa, or giant-cell arteritis) or a hematologic condition (myelodysplastic syndrome or multiple myeloma) or both. Mutations were found in more than half the hematopoietic stem cells, including peripheral-blood myeloid cells but not lymphocytes or fibroblasts. Mutations affecting p.Met41 resulted in loss of the canonical cytoplasmic isoform of UBA1 and in expression of a novel, catalytically impaired isoform initiated at p.Met67. Mutant peripheral-blood cells showed decreased ubiquitylation and activated innate immune pathways. Knockout of the cytoplasmic UBA1 isoform homologue in zebrafish caused systemic inflammation. CONCLUSIONS Using a genotype-driven approach, we identified a disorder that connects seemingly unrelated adult-onset inflammatory syndromes. We named this disorder the VEXAS (vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic) syndrome. (Funded by the NIH Intramural Research Programs and the EU Horizon 2020 Research and Innovation Program.

Humor creation during efforts to find humorous cognitive reappraisals of threatening situations

© 2019, The Author(s). This interdisciplinary study examined the structure of humor creation in the specific context of efforts to positively reappraise stressful situations for effective coping. In a sample of n = 101 participants, a performance test was used to assess the quantity (fluency, number of generated ideas that qualified as humor) and quality (rated funniness) of humor creation in cognitive reappraisal. Linguistic mechanisms were identified and quantified using cognitive-linguistic methods of corpus analysis, and their employment was correlated with humor production performance on the level of the individual. Almost all individuals were able to come up with reappraisal ideas that qualified as humorous. Depressive symptoms, a negative mood state, and high perceptions of threat did not compromise the participants’ capability to create humor. Individuals who were more serious-minded as a trait produced ideas that were rated as less funny, but their basic ability to create humor was unaffected. Metonymy (a contiguity-based principle of meaning extension) emerged as by far the most prominent semantic mechanism in the creation of humorous re-interpretations. Furthermore, its use was related to good humor creation performance in terms of quantity and quality, which is in line with its assumed importance in the extension of meaning in general and the creation of humor in particular. Further effective linguistic mechanisms and conceptual phenomena were identified. The empirical data may be valuable for the development of interventions involving the creation of humorous ideas for cognitive reappraisal.Published online, no volume/issue numberingstatus: Published onlin

Improvement in outcomes after implantation of a novel polyurethane meniscal scaffold for the treatment of medial meniscus deficiency

© 2014, Springer-Verlag Berlin Heidelberg. Purpose: Meniscal injury resulting in segmental loss of meniscal tissue is a major risk factor for the development of osteoarthritis. Tissue engineering strategies have provided scaffolds for meniscal regeneration in order to establish a treatment option for patients with limited opportunities for meniscal reconstruction. The purpose of this study was to assess the clinical and magnetic resonance imaging (MRI) results 2 years after implantation of a polyurethane scaffold for chronic segmental medial meniscus deficiency following partial medial meniscectomy. Methods: Eighteen patients were treated with arthroscopic implantation of an ActiFit® (Orteq Sports Medicine) polyurethane meniscal scaffold for meniscus deficiency of the medial meniscus. Patients were followed up at 6, 12, and 24 months. Clinical outcome was assessed using patient-reported outcome scores (KOOS, KSS, UCLA activity scale, VAS for pain). Radiological outcome was assessed using MRI at 6, 12, and 24 months by evaluating scaffold morphology, scaffold integration, and additional joint injury, as well as joint inflammation. Results: Eighteen patients with a median age of 32.5 years (range 17–49) were enrolled. Statistically significant improvements were present in all patients, but one at 2 years compared to baseline in all categories. Complete resorption of the scaffold occurred in one patient representing a failure to treatment. MRI showed abnormal signal intensity of the scaffold when compared to residual meniscal tissue but without synovitis or joint inflammation. Extrusion of the scaffold was present in four patients. No correlation between scaffold extrusion and clinical outcome was observed. Conclusion: Arthroscopic implantation of a polyurethane meniscal scaffold in patients with chronic segmental medial meniscus deficiency is not only a safe procedure but leads to good clinical results at a 2-year follow-up. Scaffold extrusion did not appear to affect clinical outcome. Level of evidence: IV

Somatic Mutations in UBA1 Define a Distinct Subset of Relapsing Polychondritis Patients With VEXAS

Objective Somatic mutations in UBA1 cause a newly defined syndrome known as VEXAS (vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic syndrome). More than 50% of patients currently identified as having VEXAS met diagnostic criteria for relapsing polychondritis (RP), but clinical features that characterize VEXAS within a cohort of patients with RP have not been defined. We undertook this study to define the prevalence of somatic mutations in UBA1 in patients with RP and to create an algorithm to identify patients with genetically confirmed VEXAS among those with RP. Methods Exome and targeted sequencing of UBA1 was performed in a prospective observational cohort of patients with RP. Clinical and immunologic characteristics of patients with RP were compared based on the presence or absence of UBA1 mutations. The random forest method was used to derive a clinical algorithm to identify patients with UBA1 mutations. Results Seven of 92 patients with RP (7.6%) had UBA1 mutations (referred to here as VEXAS-RP). Patients with VEXAS-RP were all male, were on average ≥45 years of age at disease onset, and commonly had fever, ear chondritis, skin involvement, deep vein thrombosis, and pulmonary infiltrates. No patient with VEXAS-RP had chondritis of the airways or costochondritis. Mortality was greater in VEXAS-RP than in RP (23% versus 4%; P = 0.029). Elevated acute-phase reactants and hematologic abnormalities (e.g., macrocytic anemia, thrombocytopenia, lymphopenia, multiple myeloma, myelodysplastic syndrome) were prevalent in VEXAS-RP. A decision tree algorithm based on male sex, a mean corpuscular volume >100 fl, and a platelet count <200 ×103/μl differentiated VEXAS-RP from RP with 100% sensitivity and 96% specificity. Conclusion Mutations in UBA1 were causal for disease in a subset of patients with RP. This subset of patients was defined by disease onset in the fifth decade of life or later, male sex, ear/nose chondritis, and hematologic abnormalities. Early identification is important in VEXAS given the associated high mortality rate