EUS-guided liver palpation as a screening tool for advanced fibrosis and cirrhosis in patients with suspected metabolic dysfunction-associated steatotic liver disease: a pilot study.

BACKGROUND AND AIMS: Endoscopic liver "palpation" can be performed by indenting the liver surface under EUS. Indentation depth is measured with the use of sonographic calipers. We hypothesized that fibrotic livers are more difficult to indent, and that indentation can accurately predict liver fibrosis staging. We compared EUS-guided liver palpation and conventional screening modalities in patients with suspected metabolic dysfunction-associated steatotic liver disease. METHODS: This was a cross-sectional pilot study. Consecutive patients at 3 hospitals from 2021 to 2023 underwent EUS-guided palpation with liver biopsy. Liver palpation was compared with fibrosis-4 index (FIB-4), aspartate transaminase to platelet ratio index (APRI), nonalcoholic fatty liver disease fibrosis score (NFS), and transient elastography in predicting fibrosis staging on histology. Area under the receiver operating characteristic curve analysis was performed. RESULTS: Seventy-three patients were included. Mean age was 49.1 years, and 71.2% were female. Mean body mass index was 41.1 kg/m.2 Indentation depth was negatively correlated with fibrosis stage (Kruskal-Willis test, P < .0001). EUS palpation demonstrated c-statistics of 0.79 and 0.95 in discriminating advanced fibrosis and cirrhosis, respectively. EUS liver palpation was superior to NFS in predicting advanced fibrosis (P = .0057) and superior to APRI and NFS in predicting cirrhosis (P = .0099 and P = .045, respectively). EUS palpation was not significantly different from FIB-4. EUS palpation was superior to transient elastography in predicting cirrhosis (P = .045). When optimal cutoffs were used, indentation measurement ≤3.5 mm yielded 100% predictive value for ruling in advanced fibrosis, and ≥4.0 mm yielded 100% predictive value for ruling out cirrhosis. CONCLUSIONS: EUS liver palpation is a novel, accurate, and easy-to-use screening tool for advanced fibrosis and cirrhosis in patients with metabolic dysfunction-associated steatotic liver disease.

Can genetics help predict efficacy of bariatric surgery? An analysis of microRNA profiles.

BACKGROUND: There is significant variability in weight loss after bariatric surgery. We hypothesize that part of this variability may be predetermined by genetic differences associated with metabolic homeostasis. MicroRNA (miRNA) are short pieces of RNA that regulate gene expression and are readily detectable in serum. They are implicated in numerous metabolic processes, including weight homeostasis. In this pilot study, we briefly review the role of miRNA, and assess the feasibility of using them in the clinical setting of obesity treatment. OBJECTIVES: To evaluate the feasibility of using miRNA to predict weight loss after bariatric surgery. SETTING: Academic medical center. METHODS: Serum was collected from patients at the initial bariatric surgery consultation. Weight loss data were collected 6 to 12 months postoperatively. Individuals experiencing the least and the greatest amount of percentage of excess weight lost at 6 months were analyzed to assess for genetic differences in miRNA expression. RESULTS: The median percentage of excess weight lost was 51% (range, 34%-63%) for those who lost the least and 87% (range, 82%-111%) for those who lost the most weight. Groups were similar in age, sex, diabetic status, and type of surgery. In total, of the 119 miRNA detected in the serum of the patients, 6 demonstrated potential for discriminating between the high and low weight loss groups. These miRNA have previously been implicated in regulation of fatty acid biosynthesis, adipocyte proliferation, type 2 diabetes, and obesity. CONCLUSIONS: In this pilot study, we demonstrated the feasibility of identifying genetic differences between high and low weight loss groups by identifying distinct serum miRNA. In the near future, these biomarkers could facilitate informed decisions about surgery. In addition, these miRNA could open new genetic pathways that describe the pathophysiology of obesity, and provide targets for future treatment.

Resident participation in laparoscopic Roux-en-Y gastric bypass: a comparison of outcomes from the ACS-NSQIP database.

BACKGROUND: As clinical outcome data are increasingly tied to hospital reimbursement, balancing quality care with training of surgical residents has become critical. We used the ACS-NSQIP database to determine impact of resident participation in laparoscopic gastric bypass on 30-day morbidity and mortality. METHODS: We queried the ACS-NSQIP database from 1/2005 to 12/2012 for laparoscopic gastric bypass, dividing cases between those with or without resident involvement. Univariate and multivariate analyses of intraoperative and postoperative outcomes were assessed. A sub-analysis was performed to address whether different resident training levels affected outcomes. RESULTS: A total of 43,477 laparoscopic gastric bypass cases were available for analysis; 22,189 had resident involvement (resident = R), and 21,288 did not (no resident = NR). Preoperative characteristics were similar between groups. On multivariate analysis, procedures with resident assistance had increased risk of the following complications: superficial site infection (R = 2.1 vs. 1.5 %, p < 0.001), renal failure (R = 0.4 vs. NR = 0.3 %, p = 0.002), urinary tract infection (R = 1.1 vs. 0.9 %, p = 0.027), and sepsis (R = 0.8 vs. NR = 0.6 %, p = 0.019). Increased operative time in the resident group (29 min, p < 0.0001) demonstrated direct linear association with resident trainee level. There was no statistical difference in the incidences of the following: pulmonary embolism, deep venous thrombosis, deep surgical site infection, organ space infection, pneumonia, unplanned intubation, mechanical ventilation >48 h, septic shock, cardiac arrest, return to the operating room, or mortality. CONCLUSION: Resident participation in laparoscopic gastric bypass was associated with statistically significant, but clinically insignificant increase in incidence of superficial site infection, renal failure, readmission rate, and length of stay. Therefore, although resident participation in laparoscopic gastric bypass is associated with significantly increased operative time, it does not lead to increased mortality and has no clinically significant effect on morbidity.

Colonic perforation in graft versus host disease: a case report.

Graft versus host disease (GVHD) is a phenomenon that occurs after allogeneic bone marrow transplants. Gastrointestinal (GI) manifestations of acute GVHD are common, but severe GI GVHD complications, such as bowel perforation, occur rarely and necessitate surgical intervention. To our knowledge, there are no recorded cases of colonic perforation resulting from GVHD with negative cultures for infectious agents such as cytomegalovirus. We present a case of large bowel perforation due to GVHD.

New class of Son-of-sevenless (Sos) alleles highlights the complexities of Sos function.

The guanine nucleotide exchange factor (GEF) Son-of-sevenless (Sos) encodes a complex multidomain protein best known for its role in activating the small GTPase RAS in response to receptor tyrosine kinase (RTK) stimulation. Much less well understood is SOS's role in modulating RAC activity via a separate GEF domain. In the course of a genetic modifier screen designed to investigate the complexities of RTK/RAS signal transduction, a complementation group of 11 alleles was isolated and mapped to the Sos locus. Molecular characterization of these alleles indicates that they specifically affect individual domains of the protein. One of these alleles, SosM98, which contains a single amino acid substitution in the RacGEF motif, functions as a dominant negative in vivo to downregulate RTK signaling. These alleles provide new tools for future investigations of SOS-mediated activation of both RAS and RAC and how these dual roles are coordinated and coregulated during development.

Functional dissection of eyes absent reveals new modes of regulation within the retinal determination gene network.

The retinal determination (RD) gene network encodes a group of transcription factors and cofactors necessary for eye development. Transcriptional and posttranslational regulation of RD family members is achieved through interactions within the network and with extracellular signaling pathways, including epidermal growth factor receptor/RAS/mitogen-activated protein kinase (MAPK), transforming growth factor beta/DPP, Wingless, Hedgehog, and Notch. Here we present the results of structure-function analyses that reveal novel aspects of Eyes absent (EYA) function and regulation. We find that the conserved C-terminal EYA domain negatively regulates EYA transactivation potential, and that GROUCHO-SINE OCULIS (SO) interactions provide another mechanism for negative regulation of EYA-SO target genes. We have mapped the transactivation potential of EYA to an internal proline-, serine-, and threonine-rich region that includes the EYA domain 2 (ED2) and two MAPK phosphorylation consensus sites and demonstrate that activation of the RAS/MAPK pathway potentiates transcriptional output of EYA and the EYA-SO complex in certain contexts. Drosophila S2 cell two-hybrid assays were used to describe a novel homotypic interaction that is mediated by EYA's N terminus. Our data suggest that EYA requires homo- and heterotypic interactions and RAS/MAPK signaling responsiveness to ensure context-appropriate RD gene network activity.