Trigger Finger Release Using Wide-Awake Local Anesthesia No Tourniquet Versus Local Anesthesia With a Tourniquet: A Systematic Review and Meta-analysis.

Trigger finger release (TFR) is a common hand surgery, historically performed using a tourniquet. Recently, wide-awake local anesthesia no tourniquet (WALANT) has gained popularity due to ostensible advantages such as improved patient pain, satisfaction, lower rate of complications, and decreased cost. This systematic review compares outcomes of WALANT for TFR with local anesthesia with a tourniquet (LAWT). MEDLINE, Embase, CINAHL, Web of Science, Cochrane Central Register of Controlled Trials, and ClinicalTrials.gov were searched. All English-language peer-reviewed randomized and observational studies assessing TFR in adults were included. Quality of evidence was assessed with the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) system. Eleven studies (4 randomized controlled trials, 7 observational) including 1233 patients were identified. In the WALANT group, pain on injection was statistically nonsignificantly lower (mean difference [MD]: -1.69 points, 95% confidence interval [CI] = -4.14 to 0.76, P = .18) and postoperative pain was statistically lower in 2 studies. Patient and physician satisfaction were higher and analgesic use was lower in WALANT. There were no significant differences between groups for functional outcomes or rates of adverse events. Preoperative time was longer (MD: 26.43 minutes, 95% CI = 15.36 to 37.51, P < .01), operative time similar (MD: -0.59 minutes, 95% CI = -2.37 to 1.20, P = .52), postoperative time shorter (MD: -27.72 minutes, 95% CI = -36.95 to -18.48, P < .01), and cost lower (MD: -52.2%, 95% CI = -79.9% to -24.5%) in WALANT versus LAWT. The GRADE certainty of evidence of these results ranges from very low to low. This systematic review does not confirm superiority of WALANT over LAWT for TFR due to moderate to high risk of bias of included studies; further robust trials must be conducted.

Combination of an ACLY inhibitor with a GLP-1R agonist exerts additive benefits on nonalcoholic steatohepatitis and hepatic fibrosis in mice.

Increased liver de novo lipogenesis (DNL) is a hallmark of nonalcoholic steatohepatitis (NASH). A key enzyme controlling DNL upregulated in NASH is ATP citrate lyase (ACLY). In mice, inhibition of ACLY reduces liver steatosis, ballooning, and fibrosis and inhibits activation of hepatic stellate cells. Glucagon-like peptide-1 receptor (GLP-1R) agonists lower body mass, insulin resistance, and steatosis without improving fibrosis. Here, we find that combining an inhibitor of liver ACLY, bempedoic acid, and the GLP-1R agonist liraglutide reduces liver steatosis, hepatocellular ballooning, and hepatic fibrosis in a mouse model of NASH. Liver RNA analyses revealed additive downregulation of pathways that are predictive of NASH resolution, reductions in the expression of prognostically significant genes compared with clinical NASH samples, and a predicted gene signature profile that supports fibrosis resolution. These findings support further investigation of this combinatorial therapy to treat obesity, insulin resistance, hypercholesterolemia, steatohepatitis, and fibrosis in people with NASH.

Inhibition of ATP-citrate lyase improves NASH, liver fibrosis, and dyslipidemia.

Elevated liver de novo lipogenesis contributes to non-alcoholic steatohepatitis (NASH) and can be inhibited by targeting acetyl-CoA carboxylase (ACC). However, hypertriglyceridemia limits the use of pharmacological ACC inhibitors as a monotherapy. ATP-citrate lyase (ACLY) generates acetyl-CoA and oxaloacetate from citrate, but whether inhibition is effective for treating NASH is unknown. Here, we characterize a new mouse model that replicates many of the pathological and molecular drivers of NASH and find that genetically inhibiting ACLY in hepatocytes reduces liver malonyl-CoA, oxaloacetate, steatosis, and ballooning as well as blood glucose, triglycerides, and cholesterol. Pharmacological inhibition of ACLY mirrors genetic inhibition but has additional positive effects on hepatic stellate cells, liver inflammation, and fibrosis. Mendelian randomization of human variants that mimic reductions in ACLY also associate with lower circulating triglycerides and biomarkers of NASH. These data indicate that inhibiting liver ACLY may be an effective approach for treatment of NASH and dyslipidemia.

The Bone Phenotype and Pain Response to Pamidronate in Tyrosine Kinase Inhibitor-Treated Chronic Myelogenous Leukemia.

Tyrosine kinase inhibitors (TKIs) have been linked to bone pain and linear growth attenuation in children with TKI-treated chronic myelogenous leukemia (CML). We describe the skeletal phenotype in an 11-year-old boy with chronic bone pain due to TKI-treated CML, including his response to intravenous (IV) pamidronate. This boy was diagnosed with Philadelphia chromosome-positive CML at 4 years of age. He was treated with imatinib for 3 years, followed by dasatinib for 4 years. At age 11 years, he was seen in a bone health clinic with a 4-year history of leg pains that necessitated regular nonsteroidal anti-inflammatory drugs (NSAIDS) and downward crossing of height percentiles (from the 25th to fifth). The bone volume/tissue volume Z-score was +1.6 for a trans-iliac bone biopsy specimen, with an increase in trabecular number (Z-score, +3.1). Bone formation and resorption parameters on trabecular surfaces were within normal limits. Tibia volumetric bone mineral density (BMD) and bone geometry were normal by peripheral quantitative computed tomography, areal BMD Z-scores were average or above average at multiple skeletal sites by dual-energy x-ray absorptiometry, and tibia length Z-score was reduced (-2.3). Growth- and bone-related biochemical studies were unremarkable except a low serum alkaline phosphatase level. His bone pain resolved completely after 9 months of low-dose IV pamidronate. An increase in trans-iliac trabecular number and shortened tibia were the main skeletal features in this patient. Short-term IV pamidronate was effective for mitigating bone pain, allowing this boy to continue receiving dasatinib without the need for chronic NSAID therapy.