Citations

Abstract Adipose‐derived cellular therapies (AD‐CTs) are increasingly used in orthopedics, yet the field lacks a standardized framework for classifying these heterogeneous products. Although prior efforts have standardized platelet‐rich plasma and bone marrow‐derived mesenchymal stromal cells, AD preparations remain inconsistently defined and poorly characterized. AD‐CTs encompass a range of products including enzymatically derived stromal vascular fraction, culture‐expanded adipose‐derived mesenchymal stromal cells (AD‐MSCs), and mechanically processed adipose tissue (AD‐MPT),each with distinct regulatory, cellular, and structural profiles. Unlike stromal vascular fraction and AD‐MSCs, which can be quantified using conventional assays, the intact extracellular matrix in AD‐MPTs complicates objective characterization. This paper introduces the Mechanical Processing (Harvesting) of Adipose Tissue classification system as a novel framework for standardizing the reporting of AD‐MPT harvesting and processing techniques that provides a structured approach to nomenclature and reporting. The system aims to enhance study comparability, facilitate research replication, and support the responsible advancement of adipose‐based therapies in musculoskeletal medicine.

This Perspective discusses the flaws in the process and methods of institutional external validation in medical education.

Background Level I trauma centers employ various orthopaedic call strategies based on resources and surgeon subspeciality availability. Objective We hypothesize when surgeons fellowship trained in trauma are solely on call that patient outcomes will be improved compared to a combined plan. Methods Retrospective cohort study from two 24-month time periods at an academic level one trauma center. The first cohort consisted of only trauma surgeons taking call. The second cohort consisted of a combination of trauma and other subspecialities taking call. The primary outcome analyzed was time from admission to operating room for hip, femoral shaft, distal femur, tibia shaft, pelvic ring and acetabulum fractures. Secondary outcomes analyzed included length of stay, 90 day incidence of reoperation, mortality, VTE and readmission. Results Eight hundred and fifty seven patients in the trauma cohort and 992 patients in the combined cohort met the inclusion criteria. The time from admission to index surgical procedure was significantly shorter in the trauma cohort (1.7 vs 2.4). Length of stay (8.95 vs 11 days) and 90 day mortality (1.8% vs 3.8%) was improved in the trauma cohort. There was no difference in 90 day rate of VTE, readmission or reoperation. Length of stay and time to OR in pelvic ring injuries and acetabulum fractures were doubled compared to the hybrid group. Conclusions Our findings suggest that when trauma fellowship trained surgeons are the only ones taking call patients have a shorter time from admission to index surgical procedure, length of stay and lower mortality rate.

Abstract Background: Monoclonal B-cell lymphocytosis (MBL), a precursor to chronic lymphocytic leukemia (CLL), is an understudied yet common premalignant condition present in ~8 million adults in the United States. Based on flow cytometry, MBL can be classified into two immunophenotypes: CLL-type (CD5, CD23, and CD20 co-expression) and non-CLL-type (CD5-negative). While the majority of the data to date pertains to CLL-type MBL, the available evidence indicates non-CLL-type MBL is also associated with an increased risk of hematologic malignancies. Clonal hematopoiesis of indeterminate potential (CHIP) is another precursor condition associated with hematologic malignancies. The relationship between non-CLL-type MBL and CHIP and their combined effect remains unknown. Herein, we report findings on these two precursor conditions in the largest screening cohort to date. Methods: Using flow cytometry, we screened for MBL in the Mayo Clinic Biobank participants who were 40 years or older with no prior history of hematologic cancers. Using whole-exome sequencing of whole-blood DNA, CHIP was screened on 291 genes related to myeloid (56 genes) or lymphoid malignancies (235 genes). Incident hematologic malignancies were detected during follow-up using International Classification of Diseases (ICD) codes in the medical record. All diagnoses were manually reviewed for confirmation. Multivariable logistic regression was used to evaluate the association between non-CLL-type MBL and CHIP. Time to incident hematologic malignancy was calculated from date of MBL screening to the earliest date of incident malignancy, withdrawal, death, last medical visit, or study end. Overall survival (OS) was calculated from date of MBL screening to date of death or last known alive. Multivariable Cox regression, adjusted for age, sex and residency, was used to investigate associations between non-CLL-type MBL and CHIP with clinical outcomes; with results reported using hazard ratios (HR) and 95% confidence intervals (CI). Results: In total, 8,802 individuals with MBL screening and CHIP data were analyzed. Non-CLL-type MBL was detected in 249 (2.8%) individuals; 121 (49%) were male, and median age was 78 years (range, 47-95). We identified 757 (8.6%) individuals with CHIP in at least one of the 291 genes tested. The most frequently mutated CHIP genes were DNMT3A, TET2, ASXL1, PPM1D, and TP53. A total of 47 (0.5%) individuals had both non-CLL-type MBL and CHIP; the four genes with the highest number of CHIP variants in these individuals were DNMT3A (n=16), TET2 (n=10), ASXL1 (n=3), and ATM (n=3). An association between non-CLL-type MBL and any CHIP (OR=1.6, 95%CI:1.2-2.3, P=0.006) was observed. When analyzing CHIP in genes related to myeloid malignancies, the association with non-CLL-type MBL was also significant (OR=1.6, 95%CI:1.1-2.3, P=0.012); however, the association was not statistically significant for genes related to lymphoid malignancies (OR=1.6, 95%CI:0.8-3.3, P=0.165). With a median follow-up of 5.4 years, 104 individuals developed incident hematologic malignancies (66 lymphoid and 38 myeloid malignancies). Non-CLL-type MBL (HR=3.5, 95%CI:1.9-6.5, P<0.001) and CHIP (HR=3.2, 95%CI:2.1-5.1, P<0.001) were each associated with increased risk of incident hematologic malignancies. Co-existence of both precursor conditions was associated with a substantially higher risk of incident hematologic malignancies (HR=10.3, 95%CI:4.0-26.2, P<0.001) compared to individuals with neither precursor condition. Among individuals with non-CLL-like MBL, any CHIP was a borderline significant predictor for incident hematologic malignancy (HR=3.6, 95%CI:1.0-12.9, P=0.049). Compared to individuals with no precursor conditions, OS was not significantly different in those with non-CLL-type MBL-only (HR=1.1, 95%CI:0.8-1.5, P=0.40), those with CHIP-only (HR=1.2, 95%CI:0.99-1.4, P=0.06), or those with both CHIP and non-CLL-type MBL (HR=1.3, 95%CI:0.8-2.1, P=0.39). Conclusions: In the largest screening cohort to date evaluating the relationship of CHIP and non-CLL-type MBL, we found that non-CLL-type MBL and CHIP are associated with each other. Individuals with non-CLL-type MBL were more likely to have CHIP variants in DNMT3A, TET2, ASXL1, and ATM. Among individuals with non-CLL-type MBL, the presence of any CHIP was associated with increased risk of developing hematologic malignancy.