Perioperative outcome of laparoscopic left lateral liver resection is improved by using a bioabsorbable staple line reinforcement material in a porcine model

Hypothesis Laparoscopic liver surgery is significantly limited by the technical difficulty encountered during transection of substantial liver parenchyma, with intraoperative bleeding and bile leaks. This study tested whether the use of a bioabsorble staple line reinforcement material would improve outcome during stapled laparoscopic left lateral liver resection in a porcine model. Study design A total of 20 female pigs underwent stapled laparoscopic left lateral liver resection. In group A (n = 10), the stapling devices were buttressed with a bioabsorbable staple line reinforcement material. In group B (n = 10), standard laparoscopic staplers were used. Operative data and perioperative complications were recorded. Necropsy studies and histopathological analysis were performed at 6 weeks. Data were compared between groups with the Student's t-test or the chi-square test. Results Operating time was similar in the two groups (64 +/- 11 min in group A versus 68 +/- 9 min in group B, p = ns). Intraoperative blood loss was significantly higher in group B (185 +/- 9 mL versus 25 +/- 5 mL, p <0.05). There was no mortality. There was no morbidity in the 6-week follow-up period; however, two animals in group B had subphrenic bilomas (20%) at necropsy. At necropsy, methylene blue injection via the main bile duct revealed leakage from the biliary tree in four animals in group B and none in group A (p <0.05). Histopathological examination of the resection site revealed minor abnormalities in group A while animals in group B demonstrated marked fibrotic changes and damaged vascular and biliary endothelium. Conclusion Use of a bioabsorbable staple line reinforcement material reduces intraoperative bleeding and perioperative bile leaks during stapled laparoscopic left lateral liver resection in a porcine model

Proteoliposomal formulations of an HIV-1 gp41-based miniprotein elicit a lipid-dependent immunodominant response overlapping the 2F5 binding motif

The HIV-1 gp41 Membrane Proximal External Region (MPER) is recognized by broadly neutralizing antibodies and represents a promising vaccine target. However, MPER immunogenicity and antibody activity are influenced by membrane lipids. To evaluate lipid modulation of MPER immunogenicity, we generated a 1-Palmitoyl-2-oleoylphosphatidylcholine (POPC)-based proteoliposome collection containing combinations of phosphatidylserine (PS), GM3 ganglioside, cholesterol (CHOL), sphingomyelin (SM) and the TLR4 agonist monophosphoryl lipid A (MPLA). A recombinant gp41-derived miniprotein (gp41-MinTT) exposing the MPER and a tetanus toxoid (TT) peptide that favors MHC-II presentation, was successfully incorporated into lipid mixtures (>85%). Immunization of mice with soluble gp41-MinTT exclusively induced responses against the TT peptide, while POPC proteoliposomes generated potent anti-gp41 IgG responses using lower protein doses. The combined addition of PS and GM3 or CHOL/SM to POPC liposomes greatly increased gp41 immunogenicity, which was further enhanced by the addition of MPLA. Responses generated by all proteoliposomes targeted the N-terminal moiety of MPER overlapping the 2F5 neutralizing epitope. Our data show that lipids impact both, the epitope targeted and the magnitude of the response to membrane-dependent antigens, helping to improve MPER-based lipid carriers. Moreover, the identification of immunodominant epitopes allows for the redesign of immunogens targeting MPER neutralizing determinants