Faculty Bibliography

OBJECTIVE:The purpose of this study was to perform a network meta-analysis of level I and II evidence comparing different management techniques to define the optimum treatment method for humeral shaft fractures (HSFs). DATA SOURCES/METHODS:A systematic review of the literature using Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines of MEDLINE, Embase, and Cochrane Library was screened from 2010 to 2023. STUDY SELECTION/METHODS:Inclusion criteria were evidence level I or II studies comparing nonoperative and/or operative repair techniques including open reduction internal fixation plate osteosynthesis (ORIF-Plate), minimally invasive percutaneous plating (MIPO), and intramedullary nail (IMN) fixation for the management of HSFs (OTA/AO 12A, B, C). DATA EXTRACTION/METHODS:The risk of bias and methodologic quality of evidence were assessed according to the guidelines designed by the Cochrane Statistical Methods Group and Cochrane Methods Bias Group. DATA SYNTHESIS/RESULTS:Network meta-analysis was conducted with a frequentist approach with a random-effects model using the netmeta package version 0.9-6 in R. RESULTS:A total of 25 studies (1908 patients) were included. MIPO resulted in the lowest complication rate (2.1%) when compared with ORIF-Plate (16.1%) [odds ratio (OR), 0.13; 95% confidence interval (CI), 0.04-0.49]. MIPO resulted in the lowest nonunion rate (0.65%) compared with all management techniques (OR, 0.28; 95% CI, 0.08-0.98), whereas Non-Op resulted in the highest (15.87%) (OR, 3.48; 95% CI, 1.98-6.11). MIPO demonstrated the lowest rate of postoperative radial nerve palsy overall (2.2%) and demonstrated a significantly lower rate compared with ORIF-Plate (OR, 0.22; 95% CI, 0.07-0.71, P = 0.02). IMN resulted in the lowest rate of deep infection (1.1%) when compared with ORIF-Plate (8.6%; P = 0.013). MIPO resulted in a significantly lower Disabilities of the Arm, Shoulder, and Hand score (3.86 ± 5.2) and higher American Shoulder and Elbow Surgeons score (98.2 ± 1.4) than ORIF-Plate (19.5 ± 9.0 and 60.0 ± 5.4, P < 0.05). CONCLUSION/CONCLUSIONS:The results from this study support that surgical management results in better postoperative functional outcomes, leads to higher union rates, reduces fracture healing time, reduces revision rate, and decreases malunion rates in patients with HSFs. In addition, MIPO resulted in statistically higher union rates, lowest complication rate, lowest rate of postoperative radial nerve palsy, and lower intraoperative time while resulting in better postoperative Disabilities of the Arm, Shoulder, and Hand and American Shoulder and Elbow Surgeons scores when compared with nonoperative and operative (ORIF and IMN) treatment modalities. LEVEL OF EVIDENCE/METHODS:Therapeutic Level II. See Instructions for Authors for a complete description of levels of evidence.

Aortic stiffening is an inevitable manifestation of chronological aging, yet the mechano-molecular programs that orchestrate region- and layer-specific adaptations along the length and through the wall of the aorta are incompletely defined. Here, we show that the decline in passive cyclic distensibility is more pronounced in the ascending thoracic aorta (ATA) compared to distal segments of the aorta and that collagen content increases in both the medial and adventitial compartments of the ATA during aging. The single-cell RNA sequencing of aged ATA tissues reveals altered cellular senescence, remodeling, and inflammatory responses accompanied by enrichment of T-lymphocytes and rarefaction of vascular smooth muscle cells, compared to young samples. T lymphocyte clusters accumulate in the adventitia, while the activation of mechanosensitive Piezo-1 enhances vasoconstriction and contributes to the overall functional decline of ATA tissues. These results portray the immuno-mechanical aging of the ATA as a process that culminates in a stiffer conduit permissive to the accrual of multi-gerogenic signals priming to disease development.

Melanosomal pH is important for the synthesis of melanin as the rate-limiting enzyme, tyrosinase, is very pH-sensitive. The soluble adenylyl cyclase (sAC) signaling pathway was recently identified as a regulator of melanosomal pH in melanocytes; however, the melanosomal proteins critical for sAC-dependent regulation of melanosomal pH were undefined. We now systematically examine four well-characterized melanosomal membrane proteins to determine whether any of them are required for sAC-dependent regulation of melanosomal pH. We find that OA1, OCA2, and SLC45A2 are dispensable for sAC-dependent regulation of melanosomal pH. In contrast, TPC2 activity is required for sAC-dependent regulation of melanosomal pH and melanin synthesis. In addition, activation of TPC2 by NAADP-AM rescues melanosomal pH alkalinization and reduces melanin synthesis following pharmacologic or genetic inhibition of sAC signaling. These studies establish TPC2 as a critical melanosomal protein for sAC-dependent regulation of melanosomal pH and pigmentation.

Infection and chronic post-traumatic osteomyelitis of the tibia after open fracture are complex problems that cause significant morbidity and threaten the viability of a limb. Therefore, it is of utmost importance for the orthopaedic surgeon to understand both patient and treatment factors that modify the risk of developing these disastrous complications. Infection risk is largely based on severity of open injury in addition to inherent patient factors. Orthopaedic surgeons can work to mitigate this risk with prompt antibiotic administration, thorough and complete debridement, expedient fracture stabilization, and early wound closure. In the case osteomyelitis does occur, the surgeon should use a systematic multidisciplinary approach for eradication.

BACKGROUND/UNASSIGNED:Individuals with type 1 diabetes (T1D) generally have normal or even higher HDL (high-density lipoprotein)-cholesterol levels than people without diabetes yet are at increased risk for atherosclerotic cardiovascular disease (CVD). Human HDL is a complex mixture of particles that can vary in cholesterol content by >2-fold. To investigate if specific HDL subspecies contribute to the increased atherosclerosis associated with T1D, we created mouse models of T1D that exhibit human-like HDL subspecies. We also measured HDL subspecies and their association with incident CVD in a cohort of people with T1D. METHODS/UNASSIGNED: RESULTS/UNASSIGNED: CONCLUSIONS/UNASSIGNED:Our results suggest that the balance between APOB lipoproteins and the larger HDL subspecies contributes to atherosclerosis progression and incident CVD in the setting of T1D and that larger HDLs exert atheroprotective effects on endothelial cells rather than by promoting macrophage cholesterol efflux.

Although the mechanism for activation of latent TGFβ1 and TGFβ3 is understood to involve the binding of the TGFβ propeptide (LAP) to both an integrin and an insoluble substrate, the activation of latent TGFβ2 has been unclear because the TGFβ2 LAP does not have the classical integrin binding sequence found in the other two TGFβ isoform LAPs. To assess the potential requirement for covalent linkage with a matrix or cell surface protein for the activation of latent TGFβ2, we generated mice in which the TGFβ2 Cys residue predicted to be involved in binding was mutated to Ser (Tgfb2^C24S