Trends in utilization, demographics, and costs of platelet-rich plasma injections: a ten-year nationwide investigation.

INTRODUCTION: Platelet-Rich Plasma (PRP) has become one of the most popular biologic treatments in orthopedic surgery. Despite this, its utilization over the last decade has not been investigated. METHODS: We conducted a search using Current Procedural Terminology codes to identify patients who received PRP injections between 2010 and 2019 using the PearlDiver database. The purpose was to 1) determine annual trends of PRP injections of the ankle, hip, knee, shoulder, and elbow for cartilaginous, tendinous, ligamentous, meniscal/labral, and miscellaneous pathologies; 2) compare baseline demographics of patients receiving these injections; and 3) analyze costs. RESULTS: A total of 23,716 patients who received PRP injections were identified; 54.4% were female. The incidence of PRP injections was between 1.6 and 4.3 per 100,000 orthopedic patients. The most common anatomic locations targeted for PRP therapy was the knee (36.7%), followed by the shoulder/elbow (30.5%), then the ankle (19.6%) and hip (13.6%). Subgroup analysis revealed that most common use of PRP was for knee cartilaginous pathologies, followed by shoulder/elbow tendinous pathologies. The number of injections used in the knee significantly increased between 2010 and 2019 (p< 0.001), and trended toward significantly increasing in the shoulder/elbow (p = 0.055). Average annual costs for PRP injections ranged from $711.65 for ankles and $1,711.63 for hips; costs significantly changed for 3 of the 4 anatomic locations. By 2019, average PRP injection costs for each area clustered around $1000. CONCLUSION: Between 2010 and 2019, there was an increase in usage of PRP injections in the knee (cartilaginous pathologies) and the shoulder/elbow (tendinous pathologies). PRP costs demonstrated early variability but clustered around $1000 by 2019. Further studies into drivers of prices and cost-effectiveness of PRP are needed to provide clarity into the true costs to patients and healthcare providers.

Sourcing and development of tissue for transplantation in reconstructive surgery: A narrative review.

The wealth of allogeneic and xenogeneic tissue products available to plastic and reconstructive surgeons has allowed for the development of novel surgical solutions to challenging clinical problems, often obviating the need to inflict donor site morbidity. Allogeneic tissue used for reconstructive surgery enters the tissue industry through whole body donation or reproductive tissue donation and has been regulated by the FDA as human cells, tissues, and cellular and tissue-based products (HCT/Ps) since 1997. Tissue banks offering allogeneic tissue can also undergo voluntary regulation by the American Association of Tissue Banks (AATB). Tissue prepared for transplantation is sterilized and can be processed into soft tissue or bone allografts for use in surgical reconstruction, whereas non-transplant tissue is prepared for clinical training and drug, medical device, and translational research. Xenogeneic tissue, which is most often derived from porcine or bovine sources, is also commercially available and is subject to strict regulations for animal breeding and screening for infectious diseases. Although xenogeneic products have historically been decellularized for use as non-immunogenic tissue products, recent advances in gene editing have opened the door to xenograft organ transplants into human patients. Herein, we describe an overview of the modern sourcing, regulation, processing, and applications of tissue products relevant to the field of plastic and reconstructive surgery.

Effect of CCR2 Knockout on Tendon Biomechanical Properties in a Mouse Model of Delayed Rotator Cuff Repair.

BACKGROUND: The high incidence of incomplete or failed healing after rotator cuff repair (RCR) has led to an increased focus on the biologic factors that affect tendon-to-bone healing. Inflammation plays a critical role in the initial tendon-healing response. C-C chemokine receptor type 2 (CCR2) is a chemokine receptor linked to the recruitment of monocytes in early inflammatory stages and is associated with an increase in pro-inflammatory macrophages. The purpose of this study was to evaluate the role of CCR2 in tendon healing following RCR in C57BL/6J wildtype (WT) and CCR2-/- knockout (CCR2KO) mice in a delayed RCR model. METHODS: Fifty-two 12-week-old, male mice were allocated to 2 groups (WT and CCR2KO). All mice underwent unilateral supraspinatus tendon (SST) detachment at the initial surgical procedure, followed by a delayed repair 2 weeks later. The primary outcome measure was biomechanical testing. Secondary measures included histology, gene expression analysis, flow cytometry, and gait analysis. RESULTS: The mean load-to-failure was 1.64 ± 0.41 N in the WT group and 2.50 ± 0.42 N in the CCR2KO group (p = 0.030). The mean stiffness was 1.43 ± 0.66 N/mm in the WT group and 3.00 ± 0.95 N/mm in the CCR2KO group (p = 0.008). Transcriptional profiling demonstrated 7 differentially expressed genes (DEGs) when comparing the CCR2KO and WT groups (p < 0.05) and significant differences in Type-I and Type-II interferon pathway scores (p < 0.01). Flow cytometry demonstrated significant differences between groups for the percentage of macrophages present (8.1% for the WT group compared with 5.8% for the CCR2KO group; p = 0.035). Gait analysis demonstrated no significant differences between groups. CONCLUSIONS: CCR2KO may potentially improve tendon biomechanical properties by decreasing macrophage infiltration and/or by suppressing inflammatory mediator pathways in the setting of delayed RCR. CLINICAL RELEVANCE: CCR2 may be a promising target for novel therapeutics that aim to decrease failure rates following RCR.

Off-the-Shelf Nipple Engineering: Neonipple Formation via Implantation of Scaffolded Decellularized Ovine Xenograft.

BACKGROUND: Nipple reconstruction is widely regarded as the final step in postmastectomy breast reconstruction. While grafts, local flaps, or combination approaches have been used in nipple reconstruction, none has been able to achieve reliable long-term projection preservation. In response, we have sought to bioengineer neonipples in situ via the implantation of processed, decellularized cartilage xenografts placed within 3-dimensional-printed polylactic acid (PLA) scaffolds. MATERIALS AND METHODS: External nipple scaffolds were designed in-house and 3-dimensional-printed with PLA filament. Decellularized ovine xenograft infill was prepared and processed by mincing or zesting. All nipple scaffolds were placed subcutaneously on the dorsa of Sprague-Dawley rats and explanted after 1, 3, and 6 months for analysis. RESULTS: Explanted nipple scaffolds demonstrated gross maintenance of scaffold shape, diameter, and projection with accompanying increases in tissue volume. Histologic analyses revealed preservation of native cartilage architecture after 6 months without evidence of degradation. Analysis of formed tissue within the scaffolds revealed a progressive invasion of fibrovascular tissue with identifiable vascular channels and adipose tissue after 6 months in vivo. Confined compression testing revealed equilibrium moduli of both minced and zested samples that were within the expected range of previously reported human nipple tissue, while these data revealed no differences in the mechanical properties of the neotissue between time points or processing techniques. CONCLUSIONS: These preliminary data support potential use of decellularized allograft to foster healthy tissue ingrowth within a PLA scaffold, thereby offering a novel solution to current limitations in nipple reconstruction.

The effects of feed restriction, time of day, and time since feeding on behavioral and physiological indicators of hunger in broiler breeder hens.

Broiler breeder chickens are commercially feed restricted to slow their growth and improve their health and production, however, there is research demonstrating that this leads to chronic hunger resulting in poor welfare. A challenge in these studies is to account for possible daily rhythms or the effects of time since last meal on measures relating hunger. To address this, we used 3 feed treatments: AL (ad libitum fed), Ram (restricted, fed in the morning), and Rpm (restricted, fed in the afternoon) to control for diurnal effects. We then conducted foraging motivation tests and collected home pen behavior and physiological samples at 4 times relative to feeding throughout a 24-h period. The feed treatment had the largest influence on the data, with AL birds weighing more, having lower concentrations of plasma NEFA, and mRNA expression of AGRP and NPY alongside higher expression of POMC in the basal hypothalamus than Ram or Rpm birds (P < 0.001). R birds were more successful at and had a shorter latency to complete the motivation test, and did more walking and less feeding than AL birds in the home pen (P < 0.01). There was little effect of time since last meal on many measures (P > 0.05) but AGRP expression was highest in the basal hypothalamus shortly after a meal (P < 0.05), blood plasma NEFA was higher in R birds just before feeding (P < 0.001) and glucose was higher in Ram birds just after feeding (P < 0.001), and the latency to complete the motivation test was shortest before the next meal (P < 0.05). Time of day effects were mainly found in the difference in activity levels in the home pen when during lights on and lights off periods. In conclusion, many behavioral and physiological hunger measures were not significantly influenced by time of day or time since the last meal. For the measures that do change, future studies should be designed so that sampling is balanced in such a way as to minimize bias due to these effects.

World trauma education: hemorrhage control training for healthcare providers in India.

BACKGROUND: Hemorrhage remains a major cause of death around the world. Eighty percent of trauma patients in India do not receive medical care within the first hour. The etiology of these poor outcomes is multifactorial. We describe findings from the first Stop the Bleed (StB) course recently offered to a group of medical providers in southern India. METHODS: A cross-sectional survey of 101 participants who attended StB trainings in India was performed. Pre-training and post-training questionnaires were collected from each participant. In total, 88 healthcare providers' responses were analyzed. Three bleeding control skills were presented: wound compression, wound packing, and tourniquet application. RESULTS: Among participants, only 23.9% had received prior bleeding control training. Participants who reported feeling 'extremely confident' responding to an emergency medical situation rose from 68.2% prior to StB training to 94.3% post-training. Regarding hemorrhage control abilities, 37.5% felt extremely confident before the training, compared with 95.5% after the training. For wound packing and tourniquet application, 44.3% and 53.4%, respectively, felt extremely confident pre-training, followed by 97.7% for both skills post-training. Importantly, 90.9% of StB trainees felt comfortable teaching newly acquired hemorrhage control skills. A significant majority of participants said that confidence in their wound packing and tourniquet skills would improve with more realistic mannequins. CONCLUSION: To our knowledge, this is the first StB training in India. Disparities in access to care, long transport times, and insufficient numbers of prehospital personnel contribute to its significant trauma burden. Dissemination of these critical life-saving skills into this region and the resulting civilian interventions will increase the number of trauma patients who survive long enough to reach a trauma center. Additionally, considerations should be given to translating the course into local languages to increase program reach. LEVEL OF EVIDENCE: Level IV.

Pancreatic PYY but not PPY expression is responsive to short-term nutritional state and the pancreas constitutes the major site of PYY mRNA expression in chickens.

PP-fold peptides such as peptide YY (PYY) and pancreatic polypeptide (PPY) are known to play key roles in vertebrate energy homeostasis. Until recently, no gene sequence was available for avian PYY and therefore a gap in knowledge of regulation of its expression exists in avian species. Here we further evidence the mRNA sequence for chicken PYY and show that the pancreas is the major site of its mRNA expression, with a secondary peak of expression around the distal jejunum, in contrast to mammals where the large intestine is the major site of PYY expression. We also demonstrate that pancreatic PYY expression is responsive to short-term and long-term nutritional state, increasing within hours of feeding, in contrast to intestinal PYY which does not fluctuate to the same extent, and pancreatic PPY which appears to be primarily determined by long-term energy state. Both pancreatic PYY and PPY expression were found to exhibit ontogeny, being evenly distributed throughout the pancreas in young (2wk) chicks but having a decreasing splenic to duodenal gradient by adolescence (12wk).

Hypertension fails to disrupt white matter integrity in young or aged Fisher (F44) Cyp1a1Ren2 transgenic rats.

Hypertension is linked with an increased risk of white matter hyperintensities; however, recent findings have questioned this association. We examined whether hypertension and additional cerebrovascular risk factors impacted on white matter integrity in an inducible hypertensive rat. No white matter hyperintensities were observed on magnetic resonance imaging either alone or in conjunction with ageing and high-fat diet. Aged hypertensive rats that were fed a high-fat diet had moderately reduced fractional anisotropy in the corpus callosum with no overt pathological features. Herein we show that moderate hypertension alone or with additional risk factors has minimal impact on white matter integrity in this model.

Short-term inhibition of 11ß-hydroxysteroid dehydrogenase type 1 reversibly improves spatial memory but persistently impairs contextual fear memory in aged mice.

High glucocorticoid levels induced by stress enhance the memory of fearful events and may contribute to the development of anxiety and posttraumatic stress disorder. In contrast, elevated glucocorticoids associated with ageing impair spatial memory. We have previously shown that pharmacological inhibition of the intracellular glucocorticoid-amplifying enzyme 11ß-hydroxysteroid dehydrogenase type 1 (11ß-HSD1) improves spatial memory in aged mice. However, it is not known whether inhibition of 11ß-HSD1 will have any beneficial effects on contextual fear memories in aged mice. Here, we examined the effects of UE2316, a selective 11ß-HSD1 inhibitor which accesses the brain, on both spatial and contextual fear memories in aged mice using a vehicle-controlled crossover study design. Short-term UE2316 treatment improved spatial memory in aged mice, an effect which was reversed when UE2316 was substituted with vehicle. In contrast, contextual fear memory induced by foot-shock conditioning was significantly reduced by UE2316 in a non-reversible manner. When the order of treatment was reversed following extinction of the original fear memory, and a second foot-shock conditioning was given in a novel context, UE2316 treated aged mice (previously on vehicle) now showed increased fear memory compared to vehicle-treated aged mice (previously on UE2316). Renewal of the original extinguished fear memory triggered by exposure to a new environmental context may explain these effects. Thus 11ß-HSD1 inhibition reverses spatial memory impairments with ageing while reducing the strength and persistence of new contextual fear memories. Potentially this could help prevent anxiety-related disorders in vulnerable elderly individuals.