Special Populations in Orthobiologics: Athletic, Elderly, and Pediatrics Populations.

This section is devoted to a review of the literature regarding the usage of orthobiologics in the special populations of elite athletes, the elderly, and pediatrics. The prospect of these regenerative options is encouraging to help provide alternative options that may enhance recovery and healing of acute and degenerative pathologic conditions. The goal is to provide the readers an overview of the existing literature highlighting areas with growing research and others that are still lacking.

Adaptive Cycling.

Adaptive athletes have globally embraced the sport of adaptive cycling, and participation is expanding rapidly on local, national, and international levels. With a diverse array of events supporting adaptive cyclist participation, there is a need to create more awareness about the history and classes of adaptive cycling, adaptive cycle technology, and injuries and medical concerns specific to this group of adaptive athletes. This communication aims to review the major aspects of adaptive cycling, from the technological aspects of both the cycles and adaptations of the athlete to injuries and medical concerns specific to adaptive cyclists.

Use of Platelet-Rich Plasma for the Treatment of Acetabular Labral Tear of the Hip: A Pilot Study.

OBJECTIVE: This study aims to assess whether ultrasound-guided injection of platelet-rich plasma can safely and effectively treat symptoms associated with acetabular hip labral tears. DESIGN: Institutional review board approval was gained for a prospective study of eight patients (N = 8), who have previously failed conservative management, to receive ultrasound-guided injection of platelet-rich plasma at the site of hip labrum tear. We assessed pain reduction and functional ability at baseline and then 2, 6, and 8 wks after injection, using the visual analog scale and Harris Hip Score, respectively. RESULTS: Statistically significant differences in Harris Hip Score were seen 2 wks (86.5 ± 10.8, P < 0.01), 6 wks (88.0 ± 10.7) P < 0.01), and 8 wks (92.1 ± 11.6, P < 0.01) after injection as compared with baseline (76.0 ± 13.4). Corresponding improvements were seen in visual analog scale 2 wks (1.0, P < 0.01 at rest, 2.5, P < 0.01 with activity), 6 (0.9, P < 0.01 at rest, 2.3, P < 0.01 with activity), and 8 wks (0.5, P < 0.01 at rest, 1.3, P < 0.01 with activity) compared with baseline (3.8 at rest, 5.4 with activity). CONCLUSIONS: Ultrasound-guided injection of platelet-rich plasma holds promise as an emerging, minimally invasive technique toward symptom relief, reducing pain, and improving function in patients with hip labral tears.

Adolescent Pitcher Recovery from Partial Ulnar Collateral Ligament Tear after Platelet-Rich Plasma.

Platelet-rich plasma (PRP), as a regenerative treatment for partial ulnar collateral ligament (UCL) tears, is validated to lead to faster clinical recovery and return to play in adult athletes. However, studies examining such a role of PRP in younger pediatric and adolescent athletes are scarce. A 14-year-old adolescent throwing athlete, a right-handed pitcher, presented with chronic right medial elbow pain discovered to be secondary to a partial UCL tear, as identified on both ultrasound and magnetic resonance imaging. A single ultrasound-guided injection of PRP to the pathologic site of the partial UCL tear, in concert with our standardized rehabilitation protocol for throwing athletes after UCL injuries, enabled the boy to heal and return to throwing at full pitching distance without pain and without complications. This emphasizes the utility of PRP as a regenerative treatment option in an adolescent throwing athlete.

Factors associated with outcome after superior hypogastric plexus neurolysis in cancer patients.

OBJECTIVE: Superior hypogastric plexus neurolysis (SHP-N) has been shown in uncontrolled studies to provide intermediate-term benefit in a majority of patients with pain secondary to genitourinary, gynecologic, and colorectal cancers. The purpose of this is to determine factors associated with treatment outcome. MATERIALS AND METHODS: Patients who underwent SHP-N after a positive prognostic block were identified based on diagnostic classification and procedural codes from databases at 2 large teaching hospitals. A host of demographic, clinical, and treatment factors were examined for their association with treatment success, which was defined as ≥50% pain relief lasting ≥1 month. RESULTS: A total of 53.1% of 32 patients with sufficient medical records for analysis experienced a positive outcome. Those with a positive outcome were older (mean age 59.6 y, SD 13.1 vs. 47.8, SD 15.6; P=0.03), less likely to have pelvic pain (36.8% success rate, P=0.04), and more likely to have bladder cancer (88.9% success rate; P=0.01) than those with a negative outcome. In stratified analysis, female were more likely to have positive outcome if they did not have pelvic pain compared to those that did (P=0.008). This difference was not significant for males. DISCUSSION: Selecting patients based on demographic and clinical variables may improve treatment outcomes for SHP-N. Larger, prospective studies are needed to confirm our results and better refine selection criteria better.

Differences in fat and muscle mass associated with a functional human polymorphism in a post-transcriptional BMP2 gene regulatory element.

A classic morphogen, bone morphogenetic protein 2 (BMP2) regulates the differentiation of pluripotent mesenchymal cells. High BMP2 levels promote osteogenesis or chondrogenesis and low levels promote adipogenesis. BMP2 inhibits myogenesis. Thus, BMP2 synthesis is tightly controlled. Several hundred nucleotides within the 3' untranslated regions of BMP2 genes are conserved from mammals to fishes indicating that the region is under stringent selective pressure. Our analyses indicate that this region controls BMP2 synthesis by post-transcriptional mechanisms. A common A to C single nucleotide polymorphism (SNP) in the BMP2 gene (rs15705, +A1123C) disrupts a putative post-transcriptional regulatory motif within the human ultra-conserved sequence. In vitro studies indicate that RNAs bearing the A or C alleles have different protein binding characteristics in extracts from mesenchymal cells. Reporter genes with the C allele of the ultra-conserved sequence were differentially expressed in mesenchymal cells. Finally, we analyzed MRI data from the upper arm of 517 healthy individuals aged 18-41 years. Individuals with the C/C genotype were associated with lower baseline subcutaneous fat volumes (P = 0.0030) and an increased gain in skeletal muscle volume (P = 0.0060) following resistance training in a cohort of young males. The rs15705 SNP explained 2-4% of inter-individual variability in the measured parameters. The rs15705 variant is one of the first genetic markers that may be exploited to facilitate early diagnosis, treatment, and/or prevention of diseases associated with poor fitness. Furthermore, understanding the mechanisms by which regulatory polymorphisms influence BMP2 synthesis will reveal novel pharmaceutical targets for these disabling conditions.

Glycosylated foldamers to probe the carbohydrate-carbohydrate interaction.

The synthesis of a triglycosylated helical foldamer based on a combination of cyclopentyl- and pyrrolidinyl-based amino acids is described. This structure is stable in water, maintaining as it does a series of carbohydrate units in proximity to one another, and represents the basis of a new approach to the study of carbohydrate-carbohydrate interactions.

Nuclear factor-kappaB-dependent mechanisms in breast cancer cells regulate tumor burden and osteolysis in bone.

A central mediator of a wide host of target genes, the nuclear factor-kappaB (NF-kappaB) family of transcription factors, has emerged as a molecular target in cancer and diseases associated with bone destruction. To evaluate how NF-kappaB signaling in tumor cells regulates processes associated with osteolytic bone tumor burden, we stably infected the bone-seeking MDA-MB-231 breast cancer cell line with a dominant-negative mutant IkappaB that prevents phosphorylation of IkappaBalpha and associated nuclear translocation of NF-kappaB. Blockade of NF-kappaB signaling in MDA-MB-231 cells by the mutant IkappaB decreased in vitro cell proliferation, expression of the proinflammatory, bone-resorbing cytokine interleukin-6, and in vitro bone resorption by tumor/osteoclast cocultures while reciprocally up-regulating production of the proapoptotic enzyme caspase-3. Suppression of NF-kappaB transcription in these breast cancer cells also reduced incidence of in vivo tumor-mediated osteolysis after intratibial injection of tumor cells in female athymic nude mice. Immunohistochemistry showed that the cancerous lesions formed in bone by MDA-MB-231 cells express both interleukin-6 and the p65 subunit of NF-kappaB at the bone-tumor interface. NF-kappaB signaling in breast cancer cells therefore promotes bone tumor burden and tumor-mediated osteolysis through combined control of tumor proliferation, cell survival, and bone resorption. These findings imply that NF-kappaB and its associated genes may be relevant therapeutic targets in osteolytic tumor burden.

NFkappaB: a pivotal transcription factor in prostate cancer metastasis to bone.

Prostate cancers frequently metastasize to bone and this accounts for substantial morbidity. We investigated the potential role of the transcription factor NFkappaB as a central regulator of prostate cancer metastasis using the prostate adenocarcinoma cell line, PC-3, in a series of in vitro studies. Wild type PC-3 cells (PC-3.WT) have high basal levels of NFkappaB signaling, otherwise absent in PC-3 cells stably expressing a mutant form of the inhibitory kappa B (IkappaB) protein alpha (PC-3.mIkappaB). Although PC-3.WT cells in co-culture with rat bone marrow cells enhance bone resorption, no increase was observed in co-cultures with PC-3.mIkappaB cells. Similarly, although PC-3.WT cells were invasive in a chicken chorioallantoic membrane extravasation model, PC-3.mIkappaB cells lose this capacity to invade. NFkappaB reciprocally regulated genes involved in cellular invasion, with upregulation of MMP-9 and downregulation of its inhibitor, TIMP-1 in PC-3.WT cells, whereas MMP-9 was downregulated and TIMP-1 was upregulated in PC-3.mIkappaB cells. Finally, high basal gene and protein expression of the osteoclast-activating cytokine IL-6, observed in PC-3.WT cells, was absent in PC-3.mIkappaB cells. These in vitro experiments suggest NFkappaB as an important target to prevent prostate cancer bone metastasis and provide a rationale for further study of this transcription factor in metastatic disease.