Risk factors for prolonged recovery from concussion in young patients.

OBJECTIVES: For young patients sustaining concussion, assessing recovery is vital in determining safe return to play. Identifying risk factors may aid clinicians in recognising patients at risk for prolonged recovery. The study objective is to identify risk factors for prolonged (>28 days) and extended (>90 days) recovery (defined as symptom duration) and analyse how these risk factors differ between the two groups. METHODS: We retrospectively analysed electronic health record data (n=4937) among patients aged 10-18 years collected at Nationwide Children's Hospital Sports Medicine concussion clinics between 1 July 2012 and 30 June 2019. Data collected included patient demographics, comorbidities (eg, prior psychiatric diagnoses, prior concussions) and injury characteristics (eg, loss of consciousness, injury setting). We examined patient risk factors for prolonged (>28 days) and/or extended (>90 days) recovery using modified Poisson regression models. RESULTS: Factors associated with increased risk of prolonged recovery from concussion included prior concussions (adjusted risk ratio (ARR) 1.19, 95% CI 1.02 to 1.38) for two concussions (ARR 1.36, 95% CI 1.14 to 1.61), for >3, and higher initial symptom score (ARR 2.57, 95% CI 2.34 to 2.83) for postconcussion symptom (PCS) scores 21-60 (ARR 2.89, 95% CI 2.54 to 3.29), for PCS>60. Risk factors for extended recovery included history of concussion (ARR 1.50, 95% CI 1.09 to 2.06) for two concussions (ARR 1.75, 95% CI 1.17 to 2.62), for >3 and older age (15-18 years, ARR 1.11, 95% CI 1.05 to 1.18). Additionally, comorbid attention deficit hyperactivity disorder increased risk of prolonged recovery (ARR 1.14, 95% CI 1.01 to 1.29) while anxiety increased risk for extended recovery (ARR 1.47, 95% CI 1.10 to 1.95). CONCLUSION: Overall, risk factors for prolonged recovery differ somewhat from risk factors for extended recovery. For patients who present to clinic with concussion, mental health is an important consideration which may impact the timeline for symptom recovery.

Treatment of Extensor Tendon Disruption After Total Knee Arthroplasty: A Systematic Review.

BACKGROUND: Patellar or quadriceps tendon ruptures after total knee arthroplasty constitute a devastating complication with historically poor outcomes. With advances in soft tissue reconstruction and repair techniques, treatment has become more nuanced. Numerous graft options for reconstruction and suture techniques for repair have been described but there is no consensus regarding optimal treatment. METHODS: A search of PubMed, MEDLINE, Embase, and Scopus was conducted. Articles meeting inclusion criteria were reviewed. Type of intervention performed, type of injury studied, outcome measures, and complications were recorded. Quantitative and qualitative analyses were performed. RESULTS: Twenty-eight articles met inclusion criteria. The complication rate after repair of patellar tendon (63.16%) was higher than the complication rate after repair of quadriceps tendon (25.37%). However, the complication rate for patellar and quadriceps tendon tears after autograft, allograft, or mesh reconstruction was similar (18.8% vs 19.2%, respectively). The most common complication after extensor mechanism repair or reconstruction was extension lag of 30° or greater (45.33%). This was followed by re-rupture and infection (25.33% and 22.67%, respectively). Early ruptures had a higher overall complication rate than late injuries. CONCLUSION: Extensor mechanism disruption after total knee arthroplasty is a complication with high morbidity. Reconstruction of patellar tendon rupture has a much lower complication rate than repair. Our findings support the recommendation of patellar tendon reconstruction in both the early and late presentation stages. Quadriceps rupture can be treated with repair in early ruptures or with reconstruction in the late rupture or in the case of revision surgery.

Analysis of the roles of microporosity and BMP-2 on multiple measures of bone regeneration and healing in calcium phosphate scaffolds.

Osteoinductive agents, such as BMP-2, are known to improve bone formation when combined with scaffolds. Microporosity (<20 µm) has also been shown to influence bone regeneration in calcium phosphate (CaP) scaffolds. However, many studies use only the term "osteoconductive" to describe the effects of BMP-2 and microporosity on bone formation, and do not assess the degree of healing that occurred. The objective of this study was to quantify the influence of BMP-2 and microporosity on bone regeneration and healing in biphasic calcium phosphate scaffolds using multiple measures including bone volume fraction, radial distribution, and specific surface area. These measures were quantitatively compared by analyzing microcomputed tomography data and used to formally define and assess healing. A custom image segmentation program was used to segment >100 samples, with 900 images each, that were implanted in porcine mandibular defects for 3, 6, 12 and 24 weeks. The assessment of healing presented in this work demonstrates the level of detail possible in evaluating scaffold-guided bone regeneration. The analysis shows that BMP-2 and microporosity accelerate healing up to 4-fold. BMP-2 and microporosity were shown to have different and complementary roles in bone formation that effect the time needed for a defect to heal.

Morphologic and transcriptomic comparison of adipose- and bone-marrow-derived porcine stem cells cultured in alginate hydrogels.

Advances in bioengineering, material chemistry, and developmental biology have led to the design of three-dimensional (3D) culture systems that better resemble the surrounding structure and chemistry of the in situ niches of cells in tissues. This study was designed to characterize and compare porcine adipose-derived stem cells (ADSC) and bone-marrow-derived stem cells (BMSC) induced to differentiate toward osteogenic and adipogenic lineages in vitro by using a 3D alginate hydrogel. The morphology and gene expression of the two cell populations during differentiation were analyzed. Both ADSC and BMSC showed morphological evidence of osteogenic and adipogenic differentiation. Expression patterns of genes characteristic of the onset of osteogenic differentiation (ALP, COL1A1, SPARC, SPP1) were low at the beginning of culture and generally increased during the period of differentiation up to 28 days in culture. Expression of genes associated with adipogenic differentiation (ACSL1, ADFP, ADIPOQ, CD36, DBI, DGAT2, PPARG, SCD) was consistently increased in ADSC cultured in alginate hydrogel relative to the start of differentiation. However, adipogenic gene expression of BMSC cultured in alginate hydrogel was more limited when compared with that of ADSC. Evaluation of cell numbers (via the MTT staining assay) suggested a greater viability of BMSC under osteogenic conditions in alginate hydrogels than under adipogenic conditions, whereas ADSC had greater viability under adipogenic conditions than under osteogenic conditions. This study thus provides an important initial evaluation of ADSC and BMSC seeded and differentiated toward the osteogenic and adipogenic cell lineages in a 3D alginate hydrogel in vitro.

The effect of BMP-2 on micro- and macroscale osteointegration of biphasic calcium phosphate scaffolds with multiscale porosity.

It is well established that scaffolds for applications in bone tissue engineering require interconnected pores on the order of 100 microm for bone in growth and nutrient and waste transport. As a result, most studies have focused on scaffold macroporosity (>100 microm). More recently researchers have investigated the role of microporosity in calcium phosphate -based scaffolds. Osteointegration into macropores improves when scaffold rods or struts contain micropores, typically defined as pores less than approximately 50 microm. We recently demonstrated multiscale osteointegration, or growth into both macropores and intra-red micropores (<10 microm), of biphasic calcium phosphate (BCP) scaffolds. The combined effect of BMP-2, a potent osteoinductive growth factor, and multiscale porosity has yet to be investigated. In this study we implanted BCP scaffolds into porcine mandibular defects for 3, 6, 12 and 24 weeks and evaluated the effect of BMP-2 on multiscale osteointegration. The results showed that given this in vivo model BMP-2 influences osteointegration at the microscale, but not at the macroscale, but not at the macroscale. Cell density was higher in the rod micropores for scaffolds containing BMP-2 compared with controls at all time points, but BMP-2 was not required for bone formation in micropores. In contrast, there was essentially no difference in the fraction of bone in macropores for scaffolds with BMP-2 compared with controls. Additionally, bone in macropores seemed to have reached steady-state by 3 weeks. Multiscale osteointegration results in bone-scaffold composites that are fully osteointegrated, with no 'dead space'. These composites are likely to contain a continuous cell network as well as the potential for enhanced load transfer and improved mechanical properties.

Multiscale osteointegration as a new paradigm for the design of calcium phosphate scaffolds for bone regeneration.

The role of macropore size (>100 microm) and geometry in synthetic scaffolds for bone regeneration has been studied extensively, but successful translation to the clinic has been slow. Significantly less attention has been given to porosity at the microscale (0.5-10 microm). While some have shown that microporosity in calcium phosphate (CaP)-based scaffolds can improve rate and extent of bone formation in macropores, none has explored microporosity as an additional and important space for bone ingrowth. Here we show osteointegration of biphasic calcium phosphate (BCP) scaffolds at both the macro and micro length scales. Bone, osteoid, and osteogenic cells fill micropores in scaffold rods and osteocytes are embedded in mineralized matrix in micropores, without the addition of growth factors. This work further highlights the importance of considering design parameters at the microscale and demonstrates the possibility for a bone-scaffold composite with no "dead space." Embedded osteocytes distributed throughout microporous rods may form a mechanosensory network, which would not be possible in scaffolds without microporosity. Multiscale osteointegration has the potential to greatly improve overall performance of these scaffolds through an improvement of mechanical properties, load transfer, and stability in the long and short term, and represents a new paradigm for scaffold design.

Decreased bone turnover with balanced resorption and formation prevent cortical bone loss during disuse (hibernation) in grizzly bears (Ursus arctos horribilis).

Disuse uncouples bone formation from resorption, leading to increased porosity, decreased bone geometrical properties, and decreased bone mineral content which compromises bone mechanical properties and increases fracture risk. However, black bear bone properties are not adversely affected by aging despite annual periods of disuse (i.e., hibernation), which suggests that bears either prevent bone loss during disuse or lose bone and subsequently recover it at a faster rate than other animals. Here we show decreased cortical bone turnover during hibernation with balanced formation and resorption in grizzly bear femurs. Hibernating grizzly bear femurs were less porous and more mineralized, and did not demonstrate any changes in cortical bone geometry or whole bone mechanical properties compared to active grizzly bear femurs. The activation frequency of intracortical remodeling was 75% lower during hibernation than during periods of physical activity, but the normalized mineral apposition rate was unchanged. These data indicate that bone turnover decreases during hibernation, but osteons continue to refill at normal rates. There were no changes in regional variation of porosity, geometry, or remodeling indices in femurs from hibernating bears, indicating that hibernation did not preferentially affect one region of the cortex. Thus, grizzly bears prevent bone loss during disuse by decreasing bone turnover and maintaining balanced formation and resorption, which preserves bone structure and strength. These results support the idea that bears possess a biological mechanism to prevent disuse osteoporosis.