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Background: Randomized controlled trials (RCTs) evaluating the efficacy of platelet-rich plasma (PRP) for the management of lateral epicondylitis (LE) have been characterized by substantial variability in reported outcomes. The source of this heterogeneity is uncertain., Purpose: To determine the effect of estimated platelet concentration on the efficacy of PRP for the management of LE., Study Design: Systematic review and meta-analysis; Level of evidence, 2., Methods: All RCTs evaluating the efficacy of PRP in managing LE were identified. RCTs were classified according to whether the study documented a platelet concentration factor of PRP representing a greater than 3-fold increase over whole blood or a supraphysiological platelet dose (high-dose vs low-dose PRP). The primary outcome was the mean difference (MD) in the visual analog scale (VAS) score at latest follow-up. Random-effects and mixed-effects meta-analyses were performed, and meta-regression was used to evaluate whether differences in outcomes after treatment with PRP could be explained by differences in the concentration of PRP used., Results: Overall, 13 RCTs with a total of 791 patients were included in this analysis, with 5 that utilized low-dose PRP and 8 that used high-dose PRP. Meta-analysis of VAS scores reported by studies that used high-dose PRP resulted in an MD of -1.31 (95% CI, -1.87 to -0.75) in favor of PRP over all alternative treatment strategies ( P < .001). Meta-analysis of VAS scores reported by studies that used low-dose PRP resulted in an MD of 0.08 (95% CI, -0.51 to 0.68), suggesting no difference in the effect between PRP and all alternative treatment strategies ( P = .79). The platelet concentration factor of PRP used in each RCT was found to be strongly predictive of the VAS score at final follow-up in meta-regression ( P < .001), with 58.5% of the heterogeneity in the outcomes of PRP between studies explained by the platelet concentration factor alone., Conclusion: The platelet concentration of PRP may play a significant role in the outcomes of patients with LE. A direct linear relationship was observed between the platelet concentration factor of PRP used and the magnitude of patient-reported symptom relief after the management of LE with PRP. Clinicians should ensure a supraphysiological platelet concentration when preparing PRP for the management of LE., Competing Interests: One or more of the authors has declared the following potential conflict of interest or source of funding: J.S.D. has received royalties, consulting fees, and research support from Arthrex; has received royalties from Linvatec, Thieme, and Wolters Kluwer–Lippincott Williams & Wilkins; has received support for education from Gotham Surgical; and holds stock or stock options in ViewFi. R.J.W. has received consulting fees from Arthrex, JRF Ortho, and Lipogems; has received royalties from Arthrex and Smith & Nephew; has received research support from Histogenics; and holds stock or stock options in BICMD, CyMedica, Engage Surgical, Gramercy Extremity Orthopedics, Pristine Surgical, and RecoverX. S.A.R. has received consulting fees from DJ Orthopedics, Norvartis, and Teladoc; has received speaking fees from Smith & Nephew and Terumo; and holds stock or stock options in Jannu Therapeutics and Ortho RTI. S.A.R. is also an associate editor for The American Journal of Sports Medicine. AOSSM checks author disclosures against the Open Payments Database (OPD). AOSSM has not conducted an independent investigation on the OPD and disclaims any liability or responsibility relating thereto.

Purpose: To review the existing literature to (1) determine the diagnostic efficacy of artificial intelligence (AI) models for detecting scaphoid and distal radius fractures and (2) compare the efficacy to human clinical experts., Methods: PubMed, OVID/Medline, and Cochrane libraries were queried for studies investigating the development, validation, and analysis of AI for the detection of scaphoid or distal radius fractures. Data regarding study design, AI model development and architecture, prediction accuracy/area under the receiver operator characteristic curve (AUROC), and imaging modalities were recorded., Results: A total of 21 studies were identified, of which 12 (57.1%) used AI to detect fractures of the distal radius, and nine (42.9%) used AI to detect fractures of the scaphoid. AI models demonstrated good diagnostic performance on average, with AUROC values ranging from 0.77 to 0.96 for scaphoid fractures and from 0.90 to 0.99 for distal radius fractures. Accuracy of AI models ranged between 72.0% to 90.3% and 89.0% to 98.0% for scaphoid and distal radius fractures, respectively. When compared to clinical experts, 13 of 14 (92.9%) studies reported that AI models demonstrated comparable or better performance. The type of fracture influenced model performance, with worse overall performance on occult scaphoid fractures; however, models trained specifically on occult fractures demonstrated substantially improved performance when compared to humans., Conclusions: AI models demonstrated excellent performance for detecting scaphoid and distal radius fractures, with the majority demonstrating comparable or better performance compared with human experts. Worse performance was demonstrated on occult fractures. However, when trained specifically on difficult fracture patterns, AI models demonstrated improved performance., Clinical Relevance: AI models can help detect commonly missed occult fractures while enhancing workflow efficiency for distal radius and scaphoid fracture diagnoses. As performance varies based on fracture type, future studies focused on wrist fracture detection should clearly define whether the goal is to (1) identify difficult-to-detect fractures or (2) improve workflow efficiency by assisting in routine tasks., Competing Interests: Conflicts of Interest No benefits in any form have been received or will be received related directly to this article., (Copyright © 2024 American Society for Surgery of the Hand. Published by Elsevier Inc. All rights reserved.)

Variation within genes has important implications for all biological traits. We identified 3899 single nucleotide polymorphisms (SNPs) that were present within 313 genes from 82 unrelated individuals of diverse ancestry, and we organized the SNPs into 4304 different haplotypes. Each gene had several variable SNPs and haplotypes that were present in all populations, as well as a number that were population-specific. Pairs of SNPs exhibited variability in the degree of linkage disequilibrium that was a function of their location within a gene, distance from each other, population distribution, and population frequency. Haplotypes generally had more information content (heterozygosity) than did individual SNPs. Our analysis of the pattern of variation strongly supports the recent expansion of the human population.

The present study examined a role for GDNF in adaptations to drugs of abuse. Infusion of GDNF into the ventral tegmental area (VTA), a dopaminergic brain region important for addiction, blocks certain biochemical adaptations to chronic cocaine or morphine as well as the rewarding effects of cocaine. Conversely, responses to cocaine are enhanced in rats by intra-VTA infusion of an anti-GDNF antibody and in mice heterozygous for a null mutation in the GDNF gene. Chronic morphine or cocaine exposure decreases levels of phosphoRet, the protein kinase that mediates GDNF signaling, in the VTA. Together, these results suggest a feedback loop, whereby drugs of abuse decrease signaling through endogenous GDNF pathways in the VTA, which then increases the behavioral sensitivity to subsequent drug exposure.

The mesolimbic dopamine (DA) system has been implicated in drug reward, locomotor sensitization, and responding for reward-related stimuli [termed conditioned reinforcers (CR)]. Here, we investigated the effect of brain-derived neurotrophic factor (BDNF), which enhances the survival and function of dopaminergic neurons, on stimulant-induced locomotor sensitization and responding for CR. In experiment 1, BDNF was infused into the nucleus accumbens (NAc) or ventral tegmental area over 2 weeks via chronically implanted minipumps (1-2.5 microgram/d), and the psychomotor stimulant effects of cocaine (5-15 mg/kg, i.p.) were studied. We found that BDNF enhanced the initial stimulant effects of cocaine and seemed to facilitate the development of sensitization to repeated cocaine doses. In experiment 2, we studied the effects of intra-NAc BDNF infusions on responding for CR. BDNF-treated rats showed twice as many CR responses compared with controls when saline was first administered. BDNF enhanced responding on the CR lever more than four times that seen in control animals after a cocaine injection (10 mg/kg, i.p.). The enhanced response to cocaine in BDNF-treated animals persisted for more than a month after the BDNF infusions had stopped, indicating long-lasting changes in the mesolimbic DA system caused by BDNF administration. In experiment 3, we examined locomotor sensitization to cocaine in heterozygous BDNF knock-out mice and found that the development of sensitization was delayed compared with wild-type littermates. These results demonstrate the profound effects of BDNF on the enhancement of both cocaine-induced locomotion and facilitation of CR and suggest a possible role for BDNF in long-term adaptations of the brain to cocaine.

Levels of tyrosine hydroxylase (TH), the rate-limiting enzyme in catecholamine biosynthesis, are known to be upregulated in specific brain regions by chronic administration of drugs of abuse. Chronic morphine administration increases TH levels in the locus coeruleus and ventral tegmental area, whereas chronic cocaine administration increases TH levels in the ventral tegmental area only. While such upregulation of TH has been related to behavioral effects of the drugs, the mechanism underlying these adaptations has remained controversial. To study the possibility that upregulation of TH occurs at the transcriptional level, we investigated the effect of chronic morphine or cocaine treatment on the activity of the TH gene promoter (9.0 kb), coupled to the LacZ reporter gene, in transgenic mice. These TH9.0-LacZ mice have been shown to exhibit correct tissue-specific expression and regulation of the reporter gene. We show here that chronic (but not acute) exposure of the TH9.0-LacZ mice to morphine increases the expression of beta-galactosidase (which is encoded by the LacZ gene) in the locus coeruleus by twofold compared with sham-treated mice. In contrast, beta-galactosidase expression in the ventral tegmental area was decreased 20-25% by chronic morphine and unaffected by chronic cocaine administration. Similar results were obtained after analysis of TH mRNA levels in these brain regions by in situ hybridization. These results suggest that chronic morphine upregulates TH expression via transcriptional mechanisms in the locus coeruleus but by post-transcriptional mechanisms in the ventral tegmental area.