Citations

Key Points Serum glycerol-3-phosphate (G3P) levels were significantly associated with higher fibroblast growth factor 23 levels in ESKD. Pathway and mediation analyses identified the pentose phosphate pathway as the top mediator of the relationship between serum G3P and fibroblast growth factor 23. The role of G3P in ESKD provides new insights into potential therapeutic targets for CKD-mineral and bone disorder. Background Fibroblast growth factor 23 (FGF23) is a key regulator of mineral metabolism that is independently associated with mortality in patients with ESKD. Glycerol-3-phosphate (G3P), a byproduct of glycolysis that can be derived from injured kidneys, stimulates FGF23 production. We aimed to determine if serum G3P is associated with FGF23 levels in patients with ESKD and identify potential molecular pathways that mediate their relationship. Methods We conducted a cross-sectional study of 99 nondiabetic patients with ESKD on hemodialysis. We used linear regression to examine the association between G3P terciles and log-transformed C-terminal FGF23 levels, adjusting for demographics, coronary artery disease, serum calcium, phosphorus, and parathyroid hormone. Mann–Whitney U tests compared 247 serum metabolite levels between the first and third FGF23 terciles; significant metabolites ( P < 0.01) were selected for pathway enrichment analyses. Top pathway scores were used in mediation analyses. Results The median age of participants was 54 years (interquartile range [IQR], 44–63), 38% were women, 71% self-identified as Black, and 27% had coronary artery disease. The median FGF23 level was 777 (interquartile range, 222–1310) RU/ml. In adjusted analyses, compared with participants with the lowest G3P tercile, those with the highest G3P tercile had a 95% higher FGF23 level (95% Confidence Interval, 6% to 260%; P = 0.04). Of the 27 metabolites significantly associated with FGF23 levels, pathway enrichment analysis identified the pentose phosphate pathway as the top hit (impact score=0.33, false discovery rate-adjusted P value = 0.01). The pentose phosphate pathway mediated the relationship between G3P and FGF23, resulting in a 62% change in the β coefficient. Conclusions In nondiabetic patients with ESKD on hemodialysis, serum G3P positively correlated with serum C-terminal FGF23, and this relationship was mediated by the pentose phosphate pathway. Exploring the pentose phosphate pathway could yield critical mechanistic insights into the regulation of FGF23, enhancing our understanding of its broader biologic functions.

We aimed to describe outcomes, including shoulder motion, deltoid strength and Disabilities of Arm, Shoulder and Hand scores, in 19 patients with terrible triad shoulder injuries (anterior shoulder dislocation, rotator cuff tear or greater tuberosity fracture, and axillary nerve injury) who required axillary nerve reconstruction. The type of nerve surgery (grafting vs. nerve transfer), demographic factors and injury characteristics were not significantly associated with outcomes. The mean postoperative abduction and Disabilities of Arm, Shoulder and Hand score were 95° and 28, respectively. Patients with rotator cuff tears had a higher Disabilities of Arm, Shoulder and Hand score (more disability) than those with isolated greater tuberosity fractures. We conclude that spontaneous recovery of the axillary nerve may not occur in patients with a terrible triad injury. Functional outcomes after axillary nerve repair are poor with respect to motion, strength and patient-reported outcomes compared with reported results for axillary nerve reconstruction in the absence of rotator cuff injury. Level of evidence: IV

AbstractNonsteroidal anti‐inflammatory drugs (NSAIDs) are a valuable class of medications for orthopedic surgeons and often play a pivotal role in pain control. However, there are many common stipulations resulting in avoidance of its use in the treatment of musculoskeletal disease. This review summarizes the mechanism of action of NSAIDs as well as provides an overview of commonly used NSAIDs and the differences between them. It provides a concise summary on the osseous effects of NSAIDs with regard to bone healing and heterotopic ossification. Most of all, it serves as a guide or reference for orthopedic providers when counseling patients on the risks and benefits of NSAID use, as it addresses the common stipulations encountered: “It irritates my stomach,” “I have a history of bariatric surgery,” “I'm already on a blood thinner,” “I've had a heart attack,” and “I've got kidney problems” and synthesizes both current research and society recommendations regarding safe use and avoidance of NSAIDs.

ABSTRACT P/Q‐type voltage‐dependent calcium channel CACNA1A mutations cause dominantly inherited migraine, episodic ataxia, and cerebellar atrophy in humans and cause recessively inherited ataxia, episodic dyskinesia, cerebellar atrophy, and absence epilepsy in mice. The basis of these species differences and the disease mechanism(s) are not understood. To address this question and to identify required P/Q function in vivo , we created a germline Cacna1a null mutation (designated Cacna1a Fcrtm1 ) by gene targeting. Null mice develop dystonia and late‐onset cerebellar degeneration in a specific pattern. This indicates a requirement for P/Q function for survival in a subset of cerebellar neurons. Homozygous null mice completely lack P/Q‐type channel activity, and they also lack ω‐CTx‐MVIIC receptors, indicating that a single gene encodes P/Q channel activity. An increase of L‐and N‐type current densities is detected in P/Q‐null granule cells. Heterozygous Cacna1a Fcrtm1 /+ mice are phenotypically normal, despite having a 50% reduction in current density, indicating that reduced current density is not itself sufficient to cause the pathophysiology of spontaneous mouse mutants with ataxia and seizures.