Aiming at one-stage corrective surgery for extended thoracic aortic dilatation.

Definitive treatment of extended thoracic aortic dilatation is a major surgical challenge. Histopathology of resected thoracic aortic wall may reveal undiagnosed aortitis affecting outcome. We sought to investigate the benefit of thorough histopathology after one-stage corrective surgery for the treatment of extended thoracic aortic dilatation. Five patients underwent one-stage corrective surgery using the hybrid open arch repair by the frozen elephant trunk together with endovascular aortic grafting. A representative sample of the resected aortic arch was procured for histology. T- and B-lymphocytes, plasma cells, macrophages, and immunoglobulin G4 (IgG4) positivity were evaluated by immunohistochemistry. The mean preoperative maximum aortic diameter was 54 mm (range, 41-79 mm). The mean follow-up was 18 months (range, 1-24 months). As confirmed by computed tomography (CT) upon follow-up, complete thrombosis of the false lumen at the level of the frozen elephant trunk was achieved in all patients with dissection. One patient was operated due to atherosclerotic dilatation of the thoracic aorta, and postoperative CT showed successful exclusion of the atherosclerotic dilatation; this 75-year-old man was diagnosed with IgG4-positive aortitis and experienced unexpected blindness after surgery without evidence of emboli or long-term neurological impairment upon repeated brain CT. The hybrid open arch repair by the frozen elephant trunk and simultaneous endovascular repair is a feasible choice for one-stage surgery through sternotomy aiming at definitive treatment of extended thoracic aortic pathology. However, systematic evaluation of inflammation may reveal concealed aortitis affecting postoperative outcome and need for long-term surveillance.

HMGB1 neutralization is associated with bacterial translocation during acetaminophen hepatotoxicity.

BACKGROUND: Acetaminophen (APAP) hepatotoxicity is associated with a high rate of gram-negative enteric bacterial infection; however, the underlying mechanism is still unknown. APAP overdose induces massive hepatocyte necrosis, necrotic tissue releases high mobility group B1 (HMGB1) and exogenous HMGB1 is able to induce gut bacterial translocation (BT) in normal mice; therefore, it is possible that HMGB1 mediates gut BT in APAP hepatotoxicity. This study aims to test this hypothesis by using anti-HMGB1 neutralizing antibody to treat APAP overdose for 24-48 hours. METHODS: Male C57BL/6 mice were intraperitoneally (i.p.) injected with a single dose of APAP (350 mg/kg dissolved in 1 mL sterile saline). 2 hrs after APAP injection, the APAP challenged mice were randomized to receive treatment with either anti-HMGB1 antibody (400 µg per dose) or non-immune (sham) IgG every 24 h for a total of 2 doses. RESULTS: 24 and 48 hrs after APAP challenge, anti-HMGB1 treatment instead of sham IgG therapy significantly decreased serum HMGB1 concentrations and reduced BT by 85%; serum HMGB1 levels were positively correlated with the amount of BT; anti-HMGB1 therapy decreased hepatic BT at 48 h, which was associated with better recovered liver structure and better restored hepatic immune system that was shown by enhanced hepatic mRNA expression of TNF-α, IL-6 and extensive proliferation of inflammatory and reticuloendothelial cells; however, anti-HMGB1 treatment did not decrease gut mucosal permeability as compared to the sham IgG therapy at either 24 or 48 hrs. CONCLUSION: HMGB1 neutralization is associated with bacterial translocation during APAP hepatotoxicity.

Immunoglobulin G4-positive ascending thoracic aortitis may be prone to dissection.

OBJECTIVE: Immunoglobulin (Ig) G4-positive aortitis may determine outcome after surgery for ascending aorta. We evaluated IgG4 expression of dilated ascending aortic wall. METHODS: The study consisted of 91 patients who underwent ascending aortic surgery. For histology, hematoxylin-eosin, elastase-van Gieson, and periodic acid-Schiff stainings were performed. The amount of T and B lymphocytes, plasma cells, macrophages, cell proliferation, and IgG4 positivity were determined by immunohistochemistry. RESULTS: The aortic wall in 12 patients had IgG4 positivity that was always confined to the adventitia. Adventitial plasma cells were numerous in all but 2 of these patients (P < .0001). Aortitis was revealed in 2 patients (17%) with IgG4-positive staining of the aorta and in 6 patients (8%) with IgG4 negativity. IgG4 staining was significantly associated with total aortic wall inflammation (area under the curve, 0.865; standard error, 0.043; P = .000; 95% confidence interval, 0.779-0.950). The mean diameter of the ascending aorta was 69 ± 4.7 mm and 56 ± 1.1 mm in patients with IgG4 positivity and negativity, respectively (P < .004). Approximately half of the patients with IgG4 positivity had dissection (42%), compared with only 15 of 79 (19%) of the remaining patients (P = not significant). Two patients with IgG4 positivity had to undergo reoperation because of immediate postoperative dissection. Seven patients died, including 4 patients (33%) with IgG4 positivity; the remaining 3 patients (4%) were IgG4 negative (P < .005). CONCLUSIONS: IgG4-positive ascending aortic wall was frequent in our study cohort (13%) and revealed aortic inflammation associated with dilatation.

Ringer's lactate improves liver recovery in a murine model of acetaminophen toxicity.

BACKGROUND: Acetaminophen (APAP) overdose induces massive hepatocyte necrosis. Liver regeneration is a vital process for survival after a toxic insult. Since hepatocytes are mostly in a quiescent state (G0), the regeneration process requires the priming of hepatocytes by cytokines such as TNF-α and IL-6. Ringer's lactate solution (RLS) has been shown to increase serum TNF-α and IL-6 in patients and experimental animals; in addition, RLS also provides lactate, which can be used as an alternative metabolic fuel to meet the higher energy demand by liver regeneration. Therefore, we tested whether RLS therapy improves liver recovery after APAP overdose. METHODS: C57BL/6 male mice were intraperitoneally injected with a single dose of APAP (300 mg/kg dissolved in 1 mL sterile saline). Following 2 hrs of APAP challenge, the mice were given 1 mL RLS or Saline treatment every 12 hours for a total of 72 hours. RESULTS: 72 hrs after APAP challenge, compared to saline-treated group, RLS treatment significantly lowered serum transaminases (ALT/AST) and improved liver recovery seen in histopathology. This beneficial effect was associated with increased hepatic tissue TNF-α concentration, enhanced hepatic NF-κB DNA binding and increased expression of cell cycle protein cyclin D1, three important factors in liver regeneration. CONCLUSION: RLS improves liver recovery from APAP hepatotoxicity.