Efficacy of postoperative analgesia with duloxetine in posthemorrhoidectomy pain: a prospective, randomized, double-blind and placebo-controlled trial.

BACKGROUND: To evaluate the effect of duloxetine when added to a multimodal analgesia regimen on posthemorrhoidectomy pain, opioid consumption, and side effects. METHODS: Prospective, randomized, double-blind placebo-controlled trial. This study included 62 patients who underwent hemorrhoidectomy. The patients were randomly assigned to receive oral duloxetine 60 mg or placebo 2 h before and 24 h after surgery. The primary outcomes were pain intensity - measured on an 11-point visual analog pain scale - and cumulative morphine consumption at 12, 24, and 48 postoperative hours. RESULTS: Fifty-two patients completed the study (25 in the duloxetine group and 27 in the placebo group). Pain scores did not differ between duloxetine and placebo: 4.5; 3.0 - 7.0 vs. 5.0; 3.5 - 7.0, p = 0.68 at 12 h, 3.0; 2.0 - 5.0 vs. 3.0; 2.0 - 5.0, p = 0.56 at 24 h, and 2.5; 1.75 - 3.75 vs. 1.5; 0.5 - 3, p = 0.08 at 48 h. Further, cumulative morphine consumption did not differ between the duloxetine and placebo groups: 4; 1.25 - 10.75 mg vs. 7; 1.0 - 12.0 mg, p = 0.68 at 12 h, 9.5; 2.0 - 17.5 mg vs. 8.0; 4.0 - 18.0 mg; p = 0.80 at 24 h, and 11.0; 2.0 - 27.0 mg vs. 10; 4.0 - 24.0 mg, p = 0.78 at 48 h. Side effects did not differ between the groups. CONCLUSIONS: Compared with placebo, duloxetine did not decrease pain intensity or morphine consumption during the first 48 h postoperatively. TRIAL REGISTRATION: The study was retrospectively registered on the Brazilian Clinical Trials Registry (identifier: RBR-9pdgms, registration date: 08/10/2020).

Vitamin E Attenuates the Progression of Non-Alcoholic Fatty Liver Disease Caused by Partial Hepatectomy in Mice.

BACKGROUND AND AIM: The progression of non-alcoholic fatty liver disease (NAFLD) likely involves a 'multiple hit' mechanism. We hypothesized that partial hepatectomy, a procedure performed frequently in patients with NAFLD, would accelerate the progression of disease. METHODS: C57BL/6JolaHsd mice were fed a choline-deficient L-amino acid-defined diet (CD-AA) or a choline-sufficient L-amino acid-defined control diet (CS-AA). Part of the mice in the CD-AA group received a diet enriched in vitamin E (~20 mg /day). Two weeks after the start of the diet, mice underwent a partial hepatectomy or a sham operation. RESULTS: In the CD-AA group, NAFLD activity scores were significantly higher at 7 days after partial hepatectomy compared to the sham operated mice (3.7 ± 1.3 vs. 1.8 ± 0.7; P<0.05). In addition, TBARS, a measure for oxidative stress, in liver tissue of the CD-AA group were significantly higher at day 1, 3 and 7 after partial hepatectomy compared to the sham operated mice (P<0.05). Vitamin E therapy significantly reduced TBARS level at day 7 after partial hepatectomy compared to the CD-AA diet group (P< 0.05). Vitamin E suppletion reduced NAFLD activity score at day 7 after partial hepatectomy compared to the CD-AA group (2.3 ± 0.8 vs. 3.8 ± 1.0; P<0.05). CONCLUSION: Partial hepatectomy accelerates the progression of NAFLD. Disease progression induced by partial hepatectomy is substantially attenuated by vitamin E.

Diffuse reflectance spectroscopy accurately quantifies various degrees of liver steatosis in murine models of fatty liver disease.

BACKGROUND: A real-time objective evaluation for the extent of liver steatosis during liver transplantation is currently not available. Diffuse reflectance spectroscopy (DRS) rapidly and accurately assesses the extent of steatosis in human livers with mild steatosis. However, it is yet unknown whether DRS accurately quantifies moderate/severe steatosis and is able to distinguish between micro- and macrovesicular steatosis. METHODS: C57BL/6JolaHsd mice were fed wit a choline-deficient L-amino acid-defined diet (CD-AA) or a choline-sufficient L-amino acid-defined control diet (CS-AA) for 3, 8, and 20 weeks. In addition B6.V-Lepob/OlaHsd (ob/ob) mice and their lean controls were studied. A total of 104 DRS measurements were performed in liver tissue ex vivo. The degree of steatosis was quantified from the DRS data and compared with histopathological analysis. RESULTS: When assessed by histology, livers of mice fed with a CD-AA and CS-AA diet displayed macrovesicular steatosis (range 0-74 %), ob/ob mice revealed only microvesicular steatosis (range 75-80 %), and their lean controls showed no steatosis. The quantification of steatosis by DRS correlated well with pathology (correlation of 0.76 in CD-AA/CS-AA fed mice and a correlation of 0.75 in ob/ob mice). DRS spectra did not distinguish between micro- and macrovesicular steatosis. In samples from CD-AA/CS-AA fed mice, the DRS was able to distinguish between mild and moderate/severe steatosis with a sensitivity and specificity of 86 and 81 %, respectively. CONCLUSION: DRS can quantify steatosis with good agreement to histopathological analysis. DRS may be useful for real-time objective evaluation of liver steatosis during liver transplantation, especially to differentiate between mild and moderate/severe steatosis.