Hepatic encephalopathy (HE) is a serious neurological complication of acute and chronic liver failure. Expression of the neurosteroid/bile acid receptor TGR5 has been demonstrated in the brain and is thought to be neuroprotective. However, it is unknown how TGR5 signaling can influence the progression and associated neuroinflammation of HE. HE was induced in C57Bl/6 mice via intraperitoneal injection of azoxymethane (AOM) and tissue was collected throughout disease progression. TGR5 expression was elevated in the frontal cortex following AOM injection in mice. The cellular localization of TGR5 was found in both neurons and microglia in the cortex of C57Bl/6 mice. Central infusion of the TGR5 agonist, betulinic acid, prior to AOM injection delayed neurological decline, increased cortical cyclic adenosine monophosphate concentrations, reduced microglia activation and proliferation, and reduced proinflammatory cytokine production. Betulinic acid treatment in vitro reduced the neuronal expression of CCL2, a chemokine previously demonstrated to contribute to HE pathogenesis. Lastly, treatment of the microglia cell line EOC-20 with conditioned media from betulinic acid-treated primary neurons decreased phagocytic activity and cytokine production. Together, these data identify that activation of TGR5, which is upregulated during HE, alleviates neuroinflammation and improves outcomes of AOM-treated mice through neuron and microglia paracrine signaling.

Background:Free flap reconstruction cases of the head and neck are often complex, long and have a multitude of risks. One of the greatest risks is intraoperative blood loss and need for transfusion. The purpose of this study was to examine basic patient and procedure characteristics in head and neck free flap reconstruction pre- and postoperatively that may help to predict severity of blood loss.Methods:A retrospective chart analysis of 67 free flap reconstructions for head and neck defects was performed. Patient characteristics, surgical variables, length of stay, and postoperative complications were reviewed and compared between the transfused and nontransfused patients. Characteristics between transfused and nontransfused patients were analyzed using two-tailed t tests and Fisher’s exact tests.Results:Of the 67 procedures, 19 reconstructions (28.4%) required a transfusion. Transfused patients were found to have a lower preoperative hemoglobin and elevated coagulation labs. The average length of stay was also statistically longer for transfused patients. There was no statistical difference in patient characteristics, length of surgery, type of free flap, or complication rate in the transfused versus nontransfused patients.Conclusions:Our study demonstrates that head and neck microsurgical resection and reconstruction presents patients with a transfusion risk of over 28%. We found that patients with a lower preoperative hemoglobin and abnormal coagulation levels are at a higher risk for receiving a transfusion. We also have demonstrated that patients who received a transfusion had a statistically significant longer length of stay.

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Background: Immediate fat grafting to the pedicled myocutaneous latissimus dorsi (LD) flap has recently gained in popularity as a means to supplement volume for breast reconstruction. The aim of this study is to compare complication rates of the immediately fat-grafted LD to free tissue transfer in the obese population. Methods: In this retrospective cohort, 82 patients (149 breasts) from 2015 to 2019 were included. Patients underwent either unilateral or bilateral breast reconstruction with either LD with immediate fat grafting or abdominal-based free tissue transfer. Included patients had a body mass index ≥ 30 kg/m2 at the time of surgery. Complication data were recorded as minor, major, and medical complications. Procedure characteristics and postoperative data were also studied. Results: Minor complication rates between the LD with immediate fat grafting and free tissue transfer cases were similar (26.9% versus 26%, respectively). The free tissue transfer group had a significantly higher rate of major complications (20.3% versus 3.8%; P = 0.048) and medical complications (10.6% versus zero). Finally, the LD with immediate fat grafting group had significantly shorter operating room times, hospital length of stay, and fewer donor-site revisions. Conclusions: LD with immediate fat grafting offers the benefit of a totally autologous reconstruction without the risks of abdominal-based microvascular free tissue transfer or an implant. Favorable complication rates, shorter operative times, and shorter hospital length of stay make this reconstructive option a safe alternative to free tissue transfer in the obese population.