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Background: Clinically used general anesthetics, alone or in combination, are damaging to the developing mammalian brain. In addition to causing widespread apoptotic neurodegeneration in vulnerable brain regions, exposure to general anesthesia at the peak of synaptogenesis causes learning and memory deficiencies later in life. In vivo rodent studies have suggested that activation of the intrinsic (mitochondria-dependent) apoptotic pathway is the earliest warning sign of neuronal damage, suggesting that a disturbance in mitochondrial integrity and function could be the earliest triggering events.Methods: Because proper and timely mitochondrial morphogenesis is critical for brain development, the authors examined the long-term effects of a commonly used anesthesia combination (isoflurane, nitrous oxide, and midazolam) on the regional distribution, ultrastructural properties, and electron transport chain function of mitochondria, as well as synaptic neurotransmission, in the subiculum of rat pups.Results: This anesthesia, administered at the peak of synaptogenesis, causes protracted injury to mitochondria, including significant enlargement of mitochondria (more than 30%, P < 0.05), impairment of their structural integrity, an approximately 28% increase in their complex IV activity (P < 0.05), and a twofold decrease in their regional distribution in presynaptic neuronal profiles (P < 0.05), where their presence is important for the normal development and functioning of synapses. Consequently, the authors showed that impaired mitochondrial morphogenesis is accompanied by heightened autophagic activity, decrease in mitochondrial density (approximately 27%, P < 0.05), and long-lasting disturbances in inhibitory synaptic neurotransmission. The interrelation of these phenomena remains to be established.Conclusion: Developing mitochondria are exquisitely vulnerable to general anesthesia and may be important early target of anesthesia-induced developmental neurodegeneration. [ABSTRACT FROM AUTHOR]

Purpose: We aimed to characterize the incidence of complications regarding olecranon osteotomy, looking more specifically at the type of osteotomy and the fixation construct used to repair the osteotomy., Methods: In accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, a comprehensive search was performed. A study was included if it was an adult clinical study, a transverse or chevron olecranon osteotomy was performed, and the study explicitly states the fixation construct used to repair the osteotomy. A quality assessment was performed in each study prior to data extraction., Results: We included 39 studies with a total of 1,445 patients. Most studies included patients who were being treated primarily for a distal humerus fracture. The overall incidence of delayed union was 27/643 (4.2%), with a higher rate in transverse osteotomy than in chevron osteotomy (5/49 (10.2%) vs 22/595 (3.7%)). Nonunion occurred in 43/811 (5.4%) of patients, with a higher rate in transverse osteotomy (6/73 (8.2%) vs. 37/712 (5.2%)). Implant failure or loss of reduction occurred in 44/746 (5.9%) of patients, with a higher rate in transverse osteotomy (11/49 (22.4%) vs 33/688 (4.8%)). The removal of implants occurred in 236/1078 (21.9%) of all patients, with the highest rate in those studies that used plate fixation 44/99 (44.4%)., Conclusions: Compared with chevron osteotomy, patients who underwent transverse osteotomy had a higher incidence of delayed union, nonunion, and implant failure or loss of reduction requiring revision surgery. The incidence of implant removal indicates that patients should be informed that nearly half of the osteotomy fixed with a plate was removed after implantation., Type of Study/level of Evidence: Therapeutic III., (© 2023 The Authors.)

Human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) have advanced our ability to study the basic function of the heart and model cardiac diseases. Due to the complexities in stem cell culture and differentiation protocols, many researchers source their hiPSC-CMs from collaborators or commercial biobanks. Generally, the field has assumed the health of frozen cardiomyocytes is unchanged if the cells adhere to the substrate and commence beating. However, very few have investigated the effects of cryopreservation on hiPSC-CM's functional and transcriptional health at the cellular and molecular level. Here we review methods and challenges associated with cryopreservation, and examine the effects of cryopreservation on the functionality (contractility and calcium handling) and transcriptome of hiPSC-CMs from six healthy stem cell lines. Utilizing protein patterning methods to template physiological cell aspect ratios (7:1, length:width) in conjunction with polyacrylamide (PA) hydrogels, we measured changes in force generation and calcium handling of single hiPSC-CMs. We observed that cryopreservation altered the functionality and transcriptome of hiPSC-CMs towards larger sizes and contractile force as assessed by increased spread area and volume, single cell traction force microscopy and delayed calcium dynamics. hiPSC-CMs are broadly used for basic science research, regenerative medicine, and testing biological therapeutics. This study informs the design of experiments utilizing hiPSC-CMs to avoid confounding functional changes due to cryopreservation with other treatments., (Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Purpose: This biomechanical study compared fixation constructs used in radioscapholunate (RSL) arthrodesis. We hypothesized that plates and screws, pin plate, and headless screws would all provide similarly stable fixation constructs., Methods: We chose 27 fresh-frozen cadaveric extremities, 14 of which were matched pairs and randomized them into 3 groups to match age, body mass index, and sex. An RSL arthrodesis was simulated with plates and screws, pin plates, or headless compression screws via a standard dorsal approach to the wrist. Specimens were mounted into a custom jig and cycled through an arc of 120° for 5,000 cycles to simulate 6 weeks range of motion (ROM). A 9-mm stroke differential variable reluctance transducer recorded continuous displacement, and gross hardware failure in the form of screw or pin cutout was investigated after the simulation., Results: Greater distraction across the RSL articulation was observed in the headless screws compared with the plate-and-screws and pin-plate constructs, with no difference between the plates and screws and pin plates. Greater average displacement was observed in the headless screws compared with the plate-and-screws and pin-plate constructs, with no difference between the pin plates and plates and screws. Gross hardware failure was observed least in plates and screws followed by pin plates., Conclusions: Plate-and-screw and pin-plate constructs are biomechanically superior in resisting RSL distraction compared with headless compression screws for RSL arthrodesis over 6 weeks of simulated ROM in the absence of healing., Clinical Relevance: The results of this study demonstrated negligible arthrodesis site distraction in the plate-and-screws and pin-plate constructs when 6 weeks of ROM was simulated. When translated to a clinical scenario, these findings may allow earlier discontinuation of external immobilization after surgery., (Copyright © 2020 American Society for Surgery of the Hand. Published by Elsevier Inc. All rights reserved.)

Background: The incidence of various open shoulder procedures has changed over time. In addition, various fellowships provide overlapping training in open shoulder surgery. There is a lack of information regarding the relationship between surgeon training and open shoulder procedure type and incidence in early career orthopedic surgeons., Methods: The American Board of Orthopaedic Surgery Part-II database was queried from 2002 to 2016 for reported open shoulder procedures. The procedures were categorized as follows: arthroplasty, revision arthroplasty, open instability, trauma, and open rotator cuff. We evaluated procedure trends as well as their relationship to surgeon fellowship categorized by Sports, Shoulder/Elbow, Hand, Trauma, and "Other" fellowship as well as no fellowship training. We additionally evaluated complication data as it related to procedure, fellowship category, and volume., Results: Over the 2002-2016 study period, there were increasing cases of arthroplasty, revision arthroplasty, and trauma (P < .001). There were decreasing cases in open instability and open rotator cuff (P < .001). Those with Sports training reported the largest overall share of open shoulder cases. Those with Shoulder/Elbow training reported an increasing overall share of arthroplasty cases and higher per candidate case numbers. The percentage of early career orthopedic surgeons reporting 5 or more arthroplasty cases was highest among Shoulder/Elbow candidates (P < .001). Across all procedures, those without fellowship training were least likely to report a complication (odds ratio [OR], 0.76; 95% confidence interval, 0.67-0.86; P < .001). Shoulder/Elbow candidates were least likely to report an arthroplasty complication (OR, 0.84, P = .03) as was any surgeon reporting 5 or more arthroplasty cases (OR, 0.81; 95% confidence interval, 0.70-0.94; P = .006)., Conclusion: The type and incidence of open shoulder surgery procedures continues to change. Among early career surgeons, those with more specific shoulder training are now performing the majority of arthroplasty-related procedures, and early career volume inversely correlates with complications., (Copyright © 2020 Journal of Shoulder and Elbow Surgery Board of Trustees. Published by Elsevier Inc. All rights reserved.)