Fisetin has been shown to be beneficial for brain injury and age-related brain disease via different mechanisms. The purpose of this study was to determine the presence of senescent cells and the effects of fisetin on cellular senescence in the brain and other vital organs in old sheep, a more translational model. Female sheep 6–7 years old (N = 6) were treated with 100 mg/kg fisetin or vehicle alone on two consecutive days a week for 8 weeks. All vital organs were harvested at the time of sacrifice. Histology, immunofluorescence staining, and RT-Q-PCR were performed on different regions of brain tissues and other organs. Our results indicated that fisetin treatment at the current regimen did not affect the general morphology of the brain. The presence of senescent cells in both the cerebral brain cortex and cerebellum and non-Cornu Ammonis (CA) area of the hippocampus was detected by senescent-associated β-galactosidase (SA-β-Gal) staining and GL13 (lipofuscin) staining. The senescent cells detected were mainly neurons in both gray and white matter of either the cerebral brain cortex, cerebellum, or non-CA area of the hippocampus. Very few senescent cells were detected in the neurons of the CA1-4 area of the hippocampus, as revealed by GL13 staining and GLB1 colocalization with NEUN. Fisetin treatment significantly decreased the number of SA-β-Gal⁺ cells in brain cortex white matter and GL13⁺ cells in the non-CA area of the hippocampus, and showed a decreasing trend of SA-β-Gal⁺ cells in the gray matter of both the cerebral brain cortex and cerebellum. Furthermore, fisetin treatment significantly decreased P16⁺ and GLB1⁺ cells in neuronal nuclear protein (NEUN)⁺ neurons, glial fibrillary acidic protein (GFAP)⁺ astrocytes, and ionized calcium binding adaptor molecule 1 (IBA1)⁺ microglia cells in both gray and white matter of cerebral brain cortex. Fisetin treatment significantly decreased GLB1⁺ cells in microglia cells, astrocytes, and NEUN⁺ neurons in the non-CA area of the hippocampus. Fisetin treatment significantly decreased plasma S100B. At the mRNA level, fisetin significantly downregulated GLB1 in the liver, showed a decreasing trend in GLB1 in the lung, heart, and spleen tissues, and significantly decreased P21 expression in the liver and lung. Fisetin treatment significantly decreased TREM2 in the lung tissues and showed a trend of downregulation in the liver, spleen, and heart. A significant decrease in NRLP3 in the liver was observed after fisetin treatment. Finally, fisetin treatment significantly downregulated SOD1 in the liver and spleen while upregulating CAT in the spleen. In conclusion, we found that senescent cells were widely present in the cerebral brain cortex and cerebellum and non-CA area of the hippocampus of old sheep. Fisetin treatment significantly decreased senescent neurons, astrocytes, and microglia in both gray and white matter of the cerebral brain cortex and non-CA area of the hippocampus. In addition, fisetin treatment decreased senescent gene expressions and inflammasomes in other organs, such as the lung and the liver. Fisetin treatment represents a promising therapeutic strategy for age-related diseases.

Background: Meniscal extrusion often persists after a medial meniscus root repair. If the meniscus is extruded, the function of the meniscus as a load-sharing device and secondary knee stabilizer is compromised. Hypothesis: It was hypothesized that repairing the meniscotibial ligament (MTL) would decrease meniscal extrusion in the settings of both an isolated MTL tear and a repaired medial meniscus root while also improving medial compartment contact mechanics. Study Design: Controlled laboratory study. Methods: Ten fresh-frozen cadaveric knees (mean age, 50.5 years) were tested in 5 conditions: intact, MTL deficiency, MTL deficiency + posterior medial meniscus root deficiency, MTL deficiency + posterior medial meniscus root repair, and MTL tenodesis + posterior medial meniscus root repair. Specimens were mounted to a load frame that applied a 1000-N axial load. Joint contact pressures were measured using thin pressure sensors, and the peak and mean pressures were analyzed. Ultrasound was used to measure meniscal extrusion. Results: The MTL tear in isolation resulted in significant meniscal extrusion compared with the intact state ( P = 0.035) without a detectable difference in medial compartment pressures. The addition of a root tear to the MTL tear state resulted in significantly more extrusion ( P = 0.001) and significant increases in medial compartment pressure ( P = .030) compared to the MTL tear state. Root repair alone restored extrusion, mean contact pressure, and peak contact pressure back to the intact state ( P > .05). Conclusion: This study showed that MTL disruption led to increased meniscal extrusion in a cadaveric model. Unlike the root tear state, MTL disruption did not change contact mechanics. Furthermore, root repair alone was sufficient in restoring intact biomechanics and extrusion. Clinical Relevance: This study may help clinicians understand the origin of medial meniscus root tears and aid in the decision-making process for whether to add an MTL tenodesis in the setting of root repair.

Around one third of humeral fractures and 2–6% of all fractures occur to the distal part of the humerus. There is a bimodal distribution differentiating between young male patients with high-energy and elderly female patients with low-energy trauma related to osteoporosis. The AO classification and Dubberley subclassification are used in daily routine. Most fractures are diagnosed on radiographs. For further evaluation, three-dimensional computed tomography is recommended, especially for comminuted or complex fractures. Owing to the long immobilization and resultant poor functional outcome, conservative treatment is followed for inoperable patients. The operative approach and osteosynthesis depend on the fracture pattern. In A1 avulsion fractures, open reduction and screw fixation are recommended. In A2/A3 fractures, a triceps-sparing approach following a 90° double-plate construction (radial dorsal/ulnar lateral) with locking plates is favored. Partial articular B1/B2 fractures are exposed via a medial or lateral approach using unilateral locking plates to stabilize the medial/lateral column. Coronal shear fractures (B3) are classified after Dubberley and are treated via an extended Kocher approach and headless compression screws in anteroposterior direction. If there is a further posterior comminution or a lateral column fragment, stabilization is needed for the lateral/medial column with a precontoured locking plate. In solely articular fracture patterns, a dorsal approach with either a 90° or 180° double-plate construction is advised. If a reconstruction is not possible owing to fracture complexity or bone quality, total elbow arthroplasty is a viable option. However, lifelong limitation in weight-bearing up to 5 kg, limited longevity, and the potential for complicated revision surgery should be considered.

Both clinical outcomes and early rates of failure will not be associated with glenoid retroversion. All patients who underwent an anatomic total shoulder arthroplasty with minimal, noncorrective reaming between 2006 and 2016 with minimum 2-year follow-up were reviewed. Measurements for retroversion, inclination, and posterior subluxation were obtained from magnetic resonance imaging or computerized tomography. A regression analysis was performed to assess the association between retroversion, inclination and subluxation, and their effect on patient reported outcomes (PROs). Clinical failures and complications were reported. One hundred fifty-one anatomic total shoulder arthroplasties (90% follow-up) with a mean follow-up of 4.6 years (range, 2-12 years) were assessed. The mean preoperative retroversion was 15.6° (range, 0.2-42.1), the mean posterior subluxation was 15.1% (range, −3.6 to 44.1%), and the mean glenoid inclination was 13.9° (range, −11.3 to 44.3). All median outcome scores improved significantly from pre- to post-operatively (P < .001). The median satisfaction was 10/10 (1st quartile = 7 and 3rd quartile = 10). Linear regression analysis found no significant association between retroversion and any postoperative PRO. A total of 5 (3.3%) failures occurred due to glenoid implant loosening (3 patients) and Cutibacterium acnes infection (2 patients) with no association between failure causation and increased retroversion or inclination. No correlation could be found between the Walch classification and postoperative PROs. Anatomic total shoulder replacement with minimal and noncorrective glenoid reaming demonstrates reliable increases in patient satisfaction and clinical outcomes at a mean of 4.6-year follow-up in patients with up to 40° of native retroversion. Higher values of retroversion were not associated with early deterioration of clinical outcomes, revisions, or failures. Long-term studies are needed to see if survivorship and outcomes hold up over time.

Reverse total shoulder arthroplasty (RTSA) is the standard of care for patients with glenohumeral osteoarthritis and rotator cuff deficiency. Preoperative RTSA planning based on medical images and patient-specific instruments has been established over the last decade. This study aims to determine the effects of using augmented reality-assisted intraoperative navigation (ARIN) for baseplate positioning in RTSA compared to preoperative planning. It is hypothesized that ARIN will decrease deviation between preoperative planning and postoperative baseplate positioning. Moreover, ARIN will decrease deviation between the (senior) more (>50 RTSAs/yr) and less experienced (junior) surgeon (5-10 RTSAs/yr). Preoperative CT scans of 16 fresh-frozen cadaveric shoulders were obtained. Baseplate placements were planned using a validated software. The data were then converted and uploaded to the augmented reality system (NextAR; Medacta International). Each of the 8 RTSAs were implanted by a senior and a junior surgeon, with 4 RTSAs using ARIN and 4 without. A postoperative CT scan was performed in all cases. The scanned scapulae were segmented, and the preoperative scan was laid over the postoperative scapula by the nearest iterative point cloud analysis. The deviation from the planned entry point and trajectory was calculated regarding the inclination, retroversion, medialization (reaming depth) and lateralization, anteroposterior position, and superoinferior position of the baseplate. Data are reported as mean ± standard deviation (SD) or mean and 95% confidence interval (CI). P values < .05 were considered statistically significant. The use of ARIN yielded a reduction in the absolute difference between planned and obtained inclination from 9° (SD: 4°) to 3° (SD: 2°) (P = .011). Mean difference in planned-obtained inclination between surgeons was 3° in free-hand surgeries (95% CI: -4 to 10; P = .578), whereas this difference reduced to 1° (95% CI: -6 to 7, P = .996) using ARIN. Retroversion, medialization (reaming depth) and lateralization, anteroposterior position, and superoinferior position of the baseplate were not affected by using ARIN. Surgical duration was increased using ARIN for both the senior (10 minutes) and junior (18 minutes) surgeon. The implementation of ARIN leads to greater accuracy of glenoid component placement, specifically with respect to inclination. Further studies have to verify if this increased accuracy is clinically important. Furthermore, ARIN allows less experienced surgeons to achieve a similar level of accuracy in component placement comparable to more experienced surgeons. However, the potential advantages of ARIN in RTSA are counterbalanced by an increase in operative time.