Outcomes of ABO-incompatible liver transplantation in end-stage liver disease patients co-infected with hepatitis B and human immunodeficiency virus.

BACKGROUND: Human immunodeficiency virus (HIV)-positive patients coinfected with hepatitis B virus (HBV) are eligible for liver transplantation (LT) in Africa and Southeast Asia, particularly China. However, the outcome of HIV-HBV coinfected patients referred for ABO-incompatible LT (ABOi-LT) is unknown. AIM: To clarify the outcome of ABOi-LT for HIV-HBV coinfected patients with end-stage liver disease (ESLD). METHODS: We report on two Chinese HIV-HBV coinfected patients with ESLD who underwent A to O brain-dead donor LT and reviewed the literature on HIV-HBV coinfected patients treated with ABO-compatible LT. The pretransplantation HIV viral load was undetectable, with no active opportunistic infections. Induction therapy consisted of two sessions of plasmapheresis and a single dose of rituximab in two split doses, followed by an intraoperative regimen of intravenous immunoglobulin, methylprednisolone, and basiliximab. Post-transplant maintenance immunosuppressive agents consisted of tacrolimus and mycophenolate mofetil, and prednisone. RESULTS: At the intermediate-term follow-up, patients showed undetectable HIV viral load, CD4(+) T cell counts greater than 150 cells/µL, no HBV recurrence, and stable liver function. A liver allograft biopsy showed no evidence of acute cellular rejection. Both patients survived at 36-42 mo of follow-up. CONCLUSION: This is the first report of ABOi-LT in HIV-HBV recipients with good intermediate-term outcomes, suggesting that ABOi-LT may be feasible and safe for HIV-HBV coinfected patients with ESLD.

Reconstructing the portal vein through a posterior pancreatic tunnel: New choice for portal vein thrombosis during liver transplantation.

BACKGROUND: Thrombectomy and anatomical anastomosis (TAA) has long been considered the optimal approach to portal vein thrombosis (PVT) in liver transplantation (LT). However, TAA and the current approach for non-physiological portal reconstructions are associated with a higher rate of complications and mortality in some cases. AIM: To describe a new choice for reconstructing the portal vein through a posterior pancreatic tunnel (RPVPPT) to address cases of unresectable PVT. METHODS: Between August 2019 and August 2021, 245 adult LTs were performed. Forty-five (18.4%) patients were confirmed to have PVT before surgery, among which seven underwent PV reconstruction via the RPVPPT approach. We retrospectively analyzed the surgical procedure and postoperative complications of these seven recipients that underwent PV reconstruction due to PVT. RESULTS: During the procedure, PVT was found in all the seven cases with significant adhesion to the vascular wall and could not be dissected. The portal vein proximal to the superior mesenteric vein was damaged in one case when attempting thrombolectomy, resulting in massive bleeding. LT was successfully performed in all patients with a mean duration of 585 min (range 491-756 min) and mean intraoperative blood loss of 800 mL (range 500-3000 mL). Postoperative complications consisted of chylous leakage (n = 3), insufficient portal venous flow to the graft (n = 1), intra-abdominal hemorrhage (n = 1), pulmonary infection (n = 1), and perioperative death (n = 1). The remaining six patients survived at 12-17 mo follow-up. CONCLUSION: The RPVPPT technique might be a safe and effective surgical procedure during LT for complex PVT. However, follow-up studies with large samples are still warranted due to the relatively small number of cases.

Topological approach of liver segmentation based on 3D visualization technology in surgical planning for split liver transplantation.

BACKGROUND: Split liver transplantation (SLT) is a complex procedure. The left-lateral and right tri-segment splits are the most common surgical approaches and are based on the Couinaud liver segmentation theory. Notably, the liver surface following right tri-segment splits may exhibit different degrees of ischemic changes related to the destruction of the local portal vein blood flow topology. There is currently no consensus on preoperative evaluation and predictive strategy for hepatic segmental necrosis after SLT. AIM: To investigate the application of the topological approach in liver segmentation based on 3D visualization technology in the surgical planning of SLT. METHODS: Clinical data of 10 recipients and 5 donors who underwent SLT at Shenzhen Third People's Hospital from January 2020 to January 2021 were retrospectively analyzed. Before surgery, all the donors were subjected to 3D modeling and evaluation. Based on the 3D-reconstructed models, the liver splitting procedure was simulated using the liver segmentation system described by Couinaud and a blood flow topology liver segmentation (BFTLS) method. In addition, the volume of the liver was also quantified. Statistical indexes mainly included the hepatic vasculature and expected volume of split grafts evaluated by 3D models, the actual liver volume, and the ischemia state of the hepatic segments during the actual surgery. RESULTS: Among the 5 cases of split liver surgery, the liver was split into a left-lateral segment and right tri-segment in 4 cases, while 1 case was split using the left and right half liver splitting. All operations were successfully implemented according to the preoperative plan. According to Couinaud liver segmentation system and BFTLS methods, the volume of the left lateral segment was 359.00 ± 101.57 mL and 367.75 ± 99.73 mL, respectively, while that measured during the actual surgery was 397.50 ± 37.97 mL. The volume of segment IV (the portion of ischemic liver lobes) allocated to the right tri-segment was 136.31 ± 86.10 mL, as determined using the topological approach to liver segmentation. However, during the actual surgical intervention, ischemia of the right tri-segment section was observed in 4 cases, including 1 case of necrosis and bile leakage, with an ischemic liver volume of 238.7 mL. CONCLUSION: 3D visualization technology can guide the preoperative planning of SLT and improve accuracy during the intervention. The simulated operation based on 3D visualization of blood flow topology may be useful to predict the degree of ischemia in the liver segment and provide a reference for determining whether the ischemic liver tissue should be removed during the surgery.

The actions of neonicotinoid insecticides on nicotinic acetylcholine subunits Ldα1 and Ldα8 of Leptinotarsa decemlineata and assembled receptors.

The insect nicotinic acetylcholine receptor (nAChR) is a pentameric channel protein and also a target for neonicotinoids. There are few reported studies on the molecular interactions of Leptinotarsa decemlineata nAChRs with neonicotinoids. In this study, we analyzed the response of acetylcholine and neonicotinoids (thiamethoxam [TMX], imidacloprid [IMI], and clothianidin [CLO]) on hybrid receptors constructed by nAChR α1 and α8 subunits of L. decemlineata (Ldα1 and Ldα8) co-expressed with rat ß2 subunit (rß2) at different capped RNA (cRNA) ratios in Xenopus oocytes. In addition, we evaluated the expression changes of Ldα1 and Ldα8 after median lethal dose of TMX treatment for 72 h by quantitative polymerase chain reaction (qPCR). The resulting functional nAChRs Ldα1/rß2 and Ldα1/Ldα8/rß2 showed different pharmacological characteristics. The neonicotinoids tested showed lower agonist affinity on Ldα1/Ldα8/rß2 compared to Ldα1/rß2 at same ratios of subunit cRNAs. The sensitivities of neonicotinoids tested for Ldα1/rß2 and Ldα1/Ldα8/rß2 at cRNA ratios of 5:1, 1:1 and 5:5:1, 1:1:1, respectively, were lower than those for nAChRs at ratios of 1:5 and 1:1:5, respectively, whereas the values of maximum response (Imax ) varied. For Ldα1/Ldα8/rß2, a reduction of Lda8 cRNA resulted in increased sensitivity to IMI and decreased sensitivity to TMX. The expression of Ldα1 and Ldα8 significantly decreased in adults by 82.12% and 47.02%, respectively, while Ldα8 was significantly upregulated by 2.44 times in 4th instar larvae after exposure to TMX. We infer that Ldα1 and Ldα8 together play an important role in the sensitivity of L. decemlineata to neonicotinoids.

Synthesis of N-aryl ß-amino acid derivatives via Cu(ii)-catalyzed asymmetric 1,4-reduction in air.

In the presence of the inexpensive and stable stoichiometric reductant polymethylhydrosiloxane (PMHS) as well as certain amounts of appropriate alcohol and base additives, the non-precious metal copper-catalyzed asymmetric 1,4-hydrosilylation of ß-aryl or ß-alkyl-substituted N-aryl ß-enamino esters was well realized to afford a diverse range of N-aryl ß-amino acid esters in high yields and excellent enantioselectivities (26 examples, 90-98% ee). This approach tolerated the handling of both catalyst and reactants in air without special precautions. The chiral products obtained have been successfully converted to the corresponding enantiomerically enriched ß-lactam and unprotected ß-amino acid ester, which highlighted the synthetic utility of the developed catalytic procedure.

A supramolecularly tunable chiral diphosphine ligand: application to Rh and Ir-catalyzed enantioselective hydrogenation.

A supramolecularly tunable chiral bisphosphine ligand bearing two pyridyl-containing crown ethers, (-) or (+)-Xyl-P16C6-Phos, was fabricated and utilized in the Rh-catalyzed asymmetric hydrogenation of α-dehydroamino acid esters and Ir-catalyzed asymmetric hydrogenation of quinolines in high yields with excellent enantioselectivities (90-99% ee). Up to a 22% enhancement in enantioselectivity was achieved by the addition of certain amounts of alkali ions (Li+, Na+ or K+), which could be selectively recognized and effectively complexed by the crown ethers on the chiral Xyl-P16C6-Phos.

Copper(II)-catalyzed enantioselective hydrosilylation of halo-substituted alkyl aryl and heteroaryl ketones: asymmetric synthesis of (R)-fluoxetine and (S)-duloxetine.

A set of reaction conditions has been established to facilitate the non-precious copper-catalyzed enantioselective hydrosilylation of a number of structurally diverse ß-, γ- or ε-halo-substituted alkyl aryl ketones and α-, ß- or γ-halo-substituted alkyl heteroaryl ketones under air to afford a broad spectrum of halo alcohols in high yields and good to excellent enantioselectivities (up to 99% ee). The developed procedure has been successfully applied to the asymmetric synthesis of antidepressant drugs (R)-fluoxetine and (S)-duloxetine, which highlighted its synthetic utility.

Copper(II)-catalyzed hydrosilylation of ketones using chiral dipyridylphosphane ligands: highly enantioselective synthesis of valuable alcohols.

In the presence of PhSiH(3) as the reductant, the combination of enantiomeric dipyridylphosphane ligands and Cu(OAc)(2)·H(2)O, which is an easy-to-handle and inexpensive copper salt, led to a remarkably practical and versatile chiral catalyst system. The stereoselective formation of a selection of synthetically interesting ß-, γ- or δ-halo alcohols bearing high degrees of enantiopurity (up to 99.9% enantiomeric excess (ee)) was realized with a substrate-to-ligand molar ratio (S/L) of up to 10,000. The present protocol also allowed the hydrosilylation of a diverse spectrum of alkyl aryl ketones with excellent enantioselectivities (up to 98% ee) and exceedingly high turn-over rates (up to 50,000 S/L molar ratio in 50 min reaction time) in air, under very mild conditions, which offers great opportunities for the preparation of various physiologically active targets. The synthetic utility of the chiral products obtained was highlighted by the efficient conversion of optically enriched ß-halo alcohols into the corresponding styrene oxide, ß-amino alcohol, and ß-azido alcohol, respectively.