Can Surgeons Reliably Identify Non-cirrhotic Liver Disease During Laparoscopic Bariatric Surgery?

INTRODUCTION: Identification of liver disease during bariatric operations is an important task given the patients risk for occult fatty liver disease. Surgeon's accuracy of assessing for liver disease during an operation is poorly understood. The objective was to measure surgeons' performance on intra-operative visual assessment of the liver in a simulated environment. METHODS: Liver images from 100 patients who underwent laparoscopic bariatric surgery and pre-operative ultrasound elastography between July 2020 and July 2021 were retrospectively evaluated. The perception of 15 surgeons regarding the degree of hepatic steatosis and fibrosis was collected in a simulated clinical environment by survey and compared to results determined by ultrasonographic exam. RESULTS: The surgeons' ability to correctly identify the class of steatosis and fibrosis was poor (accuracy 61% and 59%, respectively) with a very weak correlation between the surgeon's predicted class and its true class (r = 0.17 and r = 0.12, respectively). When liver disease was present, surgeons completely missed its presence in 26% and 51% of steatosis and fibrosis, respectively. Digital image processing demonstrated that surgeons subjectively classified steatosis based on the "yellowness" of the liver and fibrosis based on texture of the liver, despite neither correlating with the true degree of liver disease. CONCLUSION: Laparoscopic visual assessment of the liver surface for identification of non-cirrhotic liver disease was found to be an inaccurate method during laparoscopic bariatric surgery. While validation studies are needed, the results suggest the clinical need for alternative approaches.

Differential neutralization of human immunodeficiency virus (HIV) replication in autologous CD4 T cells by HIV-specific cytotoxic T lymphocytes.

Defining the antiviral efficacy of CD8 T cells is important for immunogen design, and yet most current assays do not measure the ability of responses to neutralize infectious virus. Here we show that human immunodeficiency virus (HIV)-specific cytotoxic T-lymphocyte (CTL) clones and cell lines derived from infected persons and targeting diverse epitopes differ by over 1,000-fold in their ability to retard infectious virus replication in autologous CD4 T cells during a 7-day period in vitro, despite comparable activity as assessed by gamma interferon (IFN-gamma) enzyme-linked immunospot (ELISPOT) assay. Cell lines derived from peripheral blood mononuclear cells stimulated in vitro with peptides representing targeted Gag epitopes consistently neutralized HIV better than Env-specific lines from the same person, although ineffective inhibition of virus replication is not a universal characteristic of Env-specific responses at the clonal level. Gag-specific cell lines were of higher avidity than Env-specific lines, although avidity did not correlate with the ability of Gag- or Env-specific lines to contain HIV replication. The greatest inhibition was observed with cell lines restricted by the protective HLA alleles B*27 and B*57, but stimulation with targeted Gag epitopes resulted in greater inhibition than did stimulation with targeted Env epitopes even in non-B*27/B*57 subjects. These results assessing functional virus neutralization by HIV-specific CD8 T cells indicate that there are marked epitope- and allele-specific differences in virus neutralization by in vitro-expanded CD8 T cells, a finding not revealed by standard IFN-gamma ELISPOT assay currently in use in vaccine trials, which may be of critical importance in immunogen design and testing of candidate AIDS vaccines.

Genetic characterization of human immunodeficiency virus type 1 in elite controllers: lack of gross genetic defects or common amino acid changes.

Despite reports of viral genetic defects in persons who control human immunodeficiency virus type 1 (HIV-1) in the absence of antiviral therapy, the extent to which such defects contribute to the long-term containment of viremia is not known. Most previous studies examining for such defects have involved small numbers of subjects, primarily focused on subjects expressing HLA-B57, or have examined single viral genes, and they have focused on cellular proviral DNA rather than plasma viral RNA sequences. Here, we attempted viral sequencing from 95 HIV-1 elite controllers (EC) who maintained plasma viral loads of <50 RNA copies/ml in the absence of therapy, the majority of whom did not express HLA-B57. HIV-1 gene fragments were obtained from 94% (89/95) of the EC, and plasma viral sequences were obtained from 78% (61/78), the latter indicating the presence of replicating virus in the majority of EC. Of 63 persons for whom nef was sequenced, only three cases of nef deletions were identified, and gross genetic defects were rarely observed in other HIV-1 coding genes. In a codon-by-codon comparison between EC and persons with progressive infection, correcting for HLA bias and coevolving secondary mutations, a significant difference was observed at only three codons in Gag, all three of which represented the historic population consensus amino acid at the time of infection. These results indicate that the spontaneous control of HIV replication is not attributable to shared viral genetic defects or shared viral polymorphisms.