Pure varus posteromedial rotatory instability of the elbow: Radiographic findings, treatment, and outcomes.

INTRODUCTION: Although varus posteromedial rotatory instability (VPMRI) is a subtle elbow injury that involves anteromedial coronoid facet (AMCF) fracture and ligamentous injuries, treatment options and outcomes of VPMRI remains controversial. The aim of this study was to investigate radiographic findings, treatments, and outcomes of a large series of VPMRI. METHODS: We retrospectively reviewed 91 pure VPMRI cases with AMCF fracture (O'Driscoll classification anteromedial type) which were treated at 6 hospitals. Clinical and radiographic outcomes were investigated with a mean follow-up period of 46.8 months using the Mayo elbow performance score (MEPS), and the Quick Disabilities of the Arm, Shoulder and Hand (Quick-DASH) score, and serial plain radiographs. RESULTS: In AMCF fracture, there were 4 cases of subtype 1, 67 cases of subtype 2, and 20 cases of subtype 3. On MRI, complete tears of lateral collateral ligament and medial collateral ligament were observed in 83.1 % (59/71 cases) and 33.8 % (24/71 cases). Operative treatment was performed in 68 cases (74.7 %) including both side fixation in 40 cases (58.8 %), medial side fixation only in 17 cases (25.0 %), and lateral side fixation only in 11 cases (16.2 %). Nonoperative treatment was performed in 23 cases (25.3 %). The mean final MEPS and Quick-DASH scores were 93.7 and 7.9. The overall complication and reoperation rates were 22.0 % and 15.4 %. No significant differences regarding final clinical scores and range of motions were observed between the operative group and the nonoperative group, but significant differences were observed regarding number (p = 0.019) and displacement (p = 0.002) of coronoid fragment, and complication rate (p < 0.001) between the two groups. CONCLUSION: Depending on the pattern of coronoid fragment and the degree of ligamentous injuries, operative treatment of unstable VPMRI using various fixation techniques including coronoid fixation and ligament repair yielded satisfactory final clinical outcomes. However, surgeons should be aware of the high complication and reoperation rates after operative treatment. Stable VPMRI with AMCF fracture involving minimal displacement or small number of fragments can be treated nonoperatively.

miR-141/200c contributes to ethanol-mediated hepatic glycogen metabolism.

OBJECTIVE: Hepatic glucose metabolism is profoundly perturbed by excessive alcohol intake. miR-141/200c expression is significantly induced by chronic ethanol feeding. This study aimed at identifying the role of miR-141/200c in glucose homeostasis during chronic ethanol exposure. METHODS: WT and miR-141/200c KO mice were fed a control or an ethanol diet for 30 days, followed by a single binge of maltose dextrin or ethanol, respectively. Untargeted metabolomics analysis of hepatic primary metabolites was performed along with analyses for liver histology, gene expression, intracellular signaling pathways, and physiological relevance. Primary hepatocytes were used for mechanistic studies. RESULTS: miR-141/200c deficiency rewires hepatic glucose metabolism during chronic ethanol feeding, increasing the abundance of glucose intermediates including G6P, an allosteric activator for GS. miR-141/200c deficiency replenished glycogen depletion during chronic ethanol feeding accompanied by reduced GS phosphorylation in parallel with increased expression of PP1 glycogen targeting subunits. Moreover, miR-141/200c deficiency prevented ethanol-mediated increases in AMPK and CaMKK2 activity. Ethanol treatment reduced glycogen content in WT-hepatocytes, which was reversed by dorsomorphin, a selective AMPK inhibitor, while KO-hepatocytes displayed higher glycogen content than WT-hepatocytes in response to ethanol treatment. Furthermore, treatment of hepatocytes with A23187, a calcium ionophore activating CaMKK2, lowered glycogen content in WT-hepatocytes. Notably, the suppressive effect of A23187 on glycogen deposition was reversed by dorsomorphin, demonstrating that the glycogen depletion by A23187 is mediated by AMPK. KO-hepatocytes exhibited higher glycogen content than WT-hepatocytes in response to A23187. Finally, miR-141/200c deficiency led to improved glucose tolerance and insulin sensitivity during chronic ethanol feeding. CONCLUSIONS: miR-141/200c deficiency replenishes ethanol-mediated hepatic glycogen depletion through the regulation of GS activity and calcium signaling coupled with the AMPK pathway, improving glucose homeostasis and insulin sensitivity. These results underscore miR-141/200c as a potential therapeutic target for the management of alcohol intoxication.