When physicians consider which analgesia to use postsurgery, the primary goal is to relieve pain with minimal adverse side effects. Bupivacaine, a commonly used analgesic, has been formulated into an aqueous suspension of multivesicular liposomes that provide long-lasting analgesia for up to 72 hours, while avoiding the adverse side effects of opioids. The increased efficacy of liposomal extended-release bupivacaine, compared to bupivacaine hydrochloride, has promoted its usage in a variety of surgeries including hemorrhoidectomy, bunionectomy, inguinal hernia repair, total knee arthroplasty, and augmentation mammoplasty. However, like other bupivacaine formulations, the liposomal extended-release bupivacaine does have some side effects. In this brief review, we provide an update of the current knowledge in the use of bupivacaine for postsurgical analgesia.

In the United States, one-third of population is affected by obesity and almost 29 million people are suffering from type 2 diabetes. Obese people have elevated serum levels of insulin, insulin-like growth factor 1 (IGF1), and interleukin-17 (IL-17). Insulin and IGF1 are known to enhance IL-17-induced expression of inflammatory cytokines and chemokines, which may contribute to the chronic inflammatory status observed in obese people. We have previously demonstrated that insulin/IGF1 signaling pathway crosstalks with IL-17-activated nuclear factor-κB pathway through inhibiting glycogen synthase kinase 3β (GSK3β) activity. However, it is unclear whether GSK3α also plays a role and whether this crosstalk can be manipulated by AZD5363, a novel pan-Akt inhibitor that has been shown to increase glycogen synthase kinase 3 activity through reducing phosphorylation of GSK3α and GSK3β. In this study, we investigated IL-17-induced expression of C-X-C motif ligand 1 (Cxcl1), C-C motif ligand 20 (Ccl20), and interleukin-6 (Il-6) in wild-type, GSK3α−/−, and GSK3β−/− mouse embryonic fibroblast cells as well as in mouse prostate tissues by real-time quantitative PCR. We examined the proteins involved in the signaling pathways by Western blot analysis. We found that insulin and IGF1 enhanced IL-17-induced expression of Cxcl1, Ccl20, and Il-6, which was associated with increased phosphorylation of GSK3α and GSK3β in the presence of insulin and IGF1. AZD5363 inhibited the synergy between IL-17 and insulin/IGF1 through reducing phosphorylation of GSK3α and GSK3β by inhibiting Akt function. These findings imply that the cooperative crosstalk of IL-17 and insulin/IGF1 in initiating inflammatory responses may be alleviated by AZD5363.

Study Design: Systematic review. Objective: Spinal cord injuries (SCIs) resulting in motor deficits can be devastating injuries resulting in millions of health care dollars spent per incident. Nonsteroidal anti-inflammatory drugs (NSAIDs) are a potential class of drugs that could improve motor function after an SCI. This systematic review utilizes PRISMA guidelines to evaluate the effectiveness of NSAIDs for SCI. Methods: PubMed/MEDLINE, CINAHL, PsycINFO, Embase, and Scopus were reviewed linking the keywords of “ibuprofen,” “meloxicam,” “naproxen,” “ketorolac,” “indomethacin,” “celecoxib,” “ATB-346,” “NSAID,” and “nonsteroidal anti-inflammatory drug” with “spinal.” Results were reviewed for relevance and included if they met inclusion criteria. The SYRCLE checklist was used to assess sources of bias. Results: A total of 2960 studies were identified in the PubMed/MEDLINE database using the above-mentioned search criteria. A total of 461 abstracts were reviewed in Scopus, 340 in CINAHL, 179 in PsycINFO, and 7632 in Embase. A total of 15 articles met the inclusion criteria. Conclusions: NSAIDs’ effectiveness after SCI is largely determined by its ability to inhibit Rho-A. NSAIDs are a promising therapeutic option in acute SCI patients because they appear to decrease cord edema and inflammation, increase axonal sprouting, and improve motor function with minimal side effects. Studies are limited by heterogeneity, small sample size, and the use of animal models, which might not replicate the therapeutic effects in humans. There are no published human studies evaluating the safety and efficacy of these drugs after a traumatic cord injury. There is a need for well-designed prospective studies evaluating ibuprofen or indomethacin after adult spinal cord injuries.

Cystic fibrosis (CF) is a relatively common disease seen in Whites of northern European descent. Classically, it was a lethal disease and uncommon for the orthopedic practitioner to interact with CF patients. Recent pharmaceutical breakthroughs targeting the CF transmembrane conductance regulator (CFTR) gene have significantly prolonged patient life expectancy. This makes it increasingly likely that orthopedic surgeons will encounter CF patients in their clinic. In this article, the authors discuss pertinent musculoskeletal manifestations of the CF population, including the increased risk of decreased bone mineral density and bone mineral content, muscle deconditioning, spinal kyphosis, fractures, and elevated systemic inflammation predisposing these individuals to CF-related arthralgia. The diagnoses are grouped into subspecialties (arthroplasty, pediatrics, spine, sports, and trauma) most likely to evaluate the patient. Additionally, the authors review treatment options for these conditions and discuss the need for these patients to be seen in the perioperative period by their CF care team for patient optimization due to their diminished pulmonary function. Interspersed with this literature review, the authors present 2 unique cases. The first case details a patient with pain over her spine due to multilevel spinous process bursitis caused by a high-frequency chest wall oscillation system, which masquerades as an infection. The second case is a non-contact midsubstance rectus femoris tear in an athlete. These cases highlight the need for increased vigilance for uncommon diagnoses in the CF patient population. [ Orthopedics . 2021;44(3):e440–e445.]

Glycine is a nonessential amino acid that is reversibly converted from serine intracellularly by serine hydroxymethyltransferase. Glyphosate and its degradation product, aminomethylphosphonic acid (AMPA), are analogs to glycine, thus they may inhibit serine hydroxymethyltransferase to decrease intracellular glycine synthesis. In this study, we found that glyphosate and AMPA inhibited cell growth in eight human cancer cell lines but not in two immortalized human normal prostatic epithelial cell lines. AMPA arrested C4-2B and PC-3 cancer cells in the G1/G0 phase and inhibited entry into the S phase of the cell cycle. AMPA also promoted apoptosis in C4-2B and PC-3 cancer cell lines. AMPA upregulated p53 and p21 protein levels as well as procaspase 9 protein levels in C4-2B cells, whereas it downregulated cyclin D3 protein levels. AMPA also activated caspase 3 and induced cleavage of poly (adenosine diphosphate [ADP]-ribose) polymerase. This study provides the first evidence that glyphosate and AMPA can inhibit proliferation and promote apoptosis of cancer cells but not normal cells, suggesting that they have potentials to be developed into a new anticancer therapy.