Evaluation and nonsurgical management of rotator cuff calcific tendinopathy.

Rotator cuff calcific tendinopathy is a common finding that accounts for about 7% of patients with shoulder pain. There are numerous theories on the pathogenesis of rotator cuff calcific tendinopathy. The diagnosis is confirmed with radiography, MRI or ultrasound. There are numerous conservative treatment options available and most patients can be managed successfully without surgical intervention. Nonsteroidal anti-inflammatory drugs and multiple modalities are often used to manage pain and inflammation; physical therapy can help improve scapular mechanics and decrease dynamic impingement; ultrasound-guided needle aspiration and lavage techniques can provide long-term improvement in pain and function in these patients

Hand Surgery Patient Perspectives on Medical Cannabis: A Survey of Over 600 Patients

Purpose: Medical cannabis (MC) has been proposed as a potential addition to multimodal pain man- agement regimens in orthopedics. This study evaluates hand and upper-extremity patient perspectives of MC as a treatment for common orthopedic and musculoskeletal pain conditions. This study also aims to identify the proportion of patients already using MC, perceived barriers to MC use, and opinions on insurance coverage and legality of cannabis. Methods: An anonymous cross-sectional survey study was conducted of all patients at least 18 years old presenting from October 2020 to January 2021 to a hand and upper-extremity outpatient clinic. The survey collected information regarding opinion on MC, including use, legality, and willingness to use MC in the future. Medical cannabis was legal in the states where the study was conducted. Results: A total of 679 patients completed the survey (response rate 72.5%). Sixty-eight patients (10.0%) reported currently using MC. Of the 623 patients (90.0%) who reported not currently using MC, 504 (80.9%) would consider using MC for chronic pain, while the remaining 119 (19.1%) would not consider the use of MC for chronic pain. Age was not associated with whether a patient would consider using MC (P ¼ .16) or was already using MC (P ¼ .10). The most identified barrier to MC use was cost, reported as either expensive or not affordable by 477 patients (70.5%). Conclusions: This study found that most patients presenting for hand and upper-extremity complaints would consider using MC (80.9%), and most perceive it as a safe treatment option for common orthopedic conditions. Moreover, 10% of patients reported already using MC. One of the major barriers to MC use is the cost. Most (90.9%) patients support policies for legalization and insurance coverage of MC. Type of study/level of evidence: Therapeutic Level III

Blocking UBE2N abrogates oncogenic immune signaling in acute myeloid leukemia.

Dysregulation of innate immune signaling pathways is implicated in various hematologic malignancies. However, these pathways have not been systematically examined in acute myeloid leukemia (AML). We report that AML hematopoietic stem and progenitor cells (HSPCs) exhibit a high frequency of dysregulated innate immune-related and inflammatory pathways, referred to as oncogenic immune signaling states. Through gene expression analyses and functional studies in human AML cell lines and patient-derived samples, we found that the ubiquitin-conjugating enzyme UBE2N is required for leukemic cell function in vitro and in vivo by maintaining oncogenic immune signaling states. It is known that the enzyme function of UBE2N can be inhibited by interfering with thioester formation between ubiquitin and the active site. We performed in silico structure-based and cellular-based screens and identified two related small-molecule inhibitors UC-764864/65 that targeted UBE2N at its active site. Using these small-molecule inhibitors as chemical probes, we further revealed the therapeutic efficacy of interfering with UBE2N function. This resulted in the blocking of ubiquitination of innate immune- and inflammatory-related substrates in human AML cell lines. Inhibition of UBE2N function disrupted oncogenic immune signaling by promoting cell death of leukemic HSPCs while sparing normal HSPCs in vitro. Moreover, baseline oncogenic immune signaling states in leukemic cells derived from discrete subsets of patients with AML exhibited a selective dependency on UBE2N function in vitro and in vivo. Our study reveals that interfering with UBE2N abrogates leukemic HSPC function and underscores the dependency of AML cells on UBE2N-dependent oncogenic immune signaling states