Follow Up Imaging in Hepatocellular Cancer Ultrasound Screening Exams With Poor Visualization Scores.

OBJECTIVES: The Ultrasound Liver Imaging Reporting and Data Systems (LI-RADS) provides standardized terminology and reporting for ultrasound (US) examinations performed for hepatocellular cancer (HCC) screening. However, there are no recommendations regarding follow up imaging for visualization scores with suboptimal visualization. Therefore, the aim of this study is to examine follow up imaging practices in the setting of US studies scored as B (moderate limitations) and C (severe limitations). METHODS: A single center retrospective analysis of studies from 2017 to 2021 with HCC US screening visualization scores of B and C was performed. Follow up imaging with US, CT, or MRI within 6 months with visualization score B or C on initial US were included. RESULTS: Five hundred and sixty HCC US studies with suboptimal imaging were reviewed. Of those with follow up imaging, patients with a visualization score of B underwent US in more than half (58%) of the cases while those with visualization score of C underwent more CT/MRI studies (62.5%, P = .12) Patients with visualization score of B had more MRI exams performed (55%) while patients with a visualization score of C underwent more CT exams (70%, P = .16). CONCLUSIONS: Currently, there are no guidelines instructing follow up imaging on HCC screening ultrasounds with poor visualization, and the data suggests that providers have taken a heterogeneous approach. This suggests a need for society recommendations on how to approach HCC screening ultrasounds in patients with suboptimal studies.

Is the SIRS Criteria a Good Predictor of Blood stream Infection in Cirrhosis? A Single-Center Retrospective Analysis.

Introduction: Cirrhosis-associated immune dysfunction (CAID) is a chronic vasodilatory state with hyperdynamic circulation and alterations in thermoregulation that may make patients more susceptible to and mask underlying infection. This study aims to determine whether SIRS criteria are an accurate tool for predicting bloodstream infection (BSI) in cirrhosis. Methods: In our retrospective chart review, study population included patients with cirrhosis that were 18 years or older. For all study patients, model for end-stage liver disease (MELD) scores and values for each SIRS variable at the time of admission and blood culture data were recorded. Univariable and multivariable logistic regression analysis was performed to identify any associations between dichotomized SIRS variables that fulfill SIRS positivity and BSI. Results: Significantly more patients without BSI met positivity criteria for WBC counts (30% vs 13% p < .001). In the analysis of the SIRS variables as continuous variables in prediction of BSI, the AUC curves generated were all unsatisfactory with the temperature (36-38°C) and WBC count (4 × 103 to 12 × 103 mcL) at the time of admission having the highest areas under the ROC curve (0.52 and 0.55, respectively). Looking at the SIRS variables dichotomized (according to whether fulfilling SIRS criteria or not) in univariable logistic regression, only WBC counts meeting SIRS criteria were significantly associated with BSI OR 0.37 (0.18-0.77); p = .008, but this was an inverse association. This association was true even in the multivariable model OR 0.38 (0.18-0.80); p = .01. Conclusion: Our study shows that SIRS criteria are a poor predictor of BSI among patients with cirrhosis.

Effect of small bowel transit time on accuracy of video capsule endoscopy in evaluating suspected small bowel bleeding.

BACKGROUND: Obscure small bowel bleeding is defined as gastrointestinal bleeding (GIB) that is unidentifiable with esophagogastroduodenoscopy and a colonoscopy with video capsule endoscopy (VCE) being the next gold standard step for evaluation. Small bowel transit time (SBTT) is a metric of a VCE study that is defined as the time the capsule takes to travel through the small intestine. AIM: To determine if SBTT within the VCE study, correlates to overall detection of obscure small bowel bleeds. Furthermore, we attempted to identify any existing correlation between SBTT and re-bleeding after a negative VCE study. METHODS: This is a single center retrospective analysis of VCE studies performed for overt and occult GIB at Einstein Medical Center, Philadelphia, between 2015 and 2019. Inclusion criteria primarily consisted of patients 18 years or older who had a VCE study done as part of the workup for a GIB. Patients with incomplete VCEs, poor preparation, or with less than 6 mo of follow up were excluded. A re-bleeding event was defined either as overt or occult within a 6-mo timeframe. Overt re-bleeding was defined as Visible melena or hematochezia with > 2 gm/dL drop in hemoglobin defined an overt re-bleeding event; whereas an unexplained > 2 gm/dL drop in hemoglobin with no visible bleeding defined an occult re-bleed. RESULTS: Results indicated that there was a significant and positive point biserial correlation between SBTT of 220 min and detection of a bleeding focus with a statistically significant p value of 0.008. However, the area under the curve was negligible when trying to identify a threshold time for SBTT to discriminate between risk of re-bleeding events after a negative VCE. CONCLUSION: In terms of SBTT and association with accuracy of VCE finding a bleeding focus, 220 min was found to be adequate transit time to accurately find a bleeding focus, when present. It was found that no threshold SBTT could be identified to help predict re-bleeding after a negative VCE.

FANCM suppresses DNA replication stress at ALT telomeres by disrupting TERRA R-loops.

Cancer cells maintain their telomeres by either re-activating telomerase or adopting the homologous recombination (HR)-based Alternative Lengthening of Telomere (ALT) pathway. Among the many prominent features of ALT cells, C-circles (CC) formation is considered to be the most specific and quantifiable biomarker of ALT. However, the molecular mechanism behind the initiation and maintenance of CC formation in ALT cells is still largely unknown. We reported previously that depletion of the FANCM complex (FANCM-FAAP24-MHF1&2) in ALT cells induced pronounced replication stress, which primarily takes place at their telomeres. Here, we characterized the changes in ALT associated phenotypes in cells deficient of the FANCM complex. We found that depletion of FAAP24 or FANCM, but not MHF1&2, induces a dramatic increase of CC formation. Most importantly, we identified multiple DNA damage response (DDR) and DNA repair pathways that stimulate the dramatic increase of CC formation in FANCM deficient cells, including the dissolvase complex (BLM-TOP3A-RMI1/2, or BTR), DNA damage checkpoint kinases (ATR and Chk1), HR proteins (BRCA2, PALB2, and Rad51), as well as proteins involved in Break-Induced Replication (BIR) (POLD1 and POLD3). In addition, FANCD2, another Fanconi Anemia (FA) protein, is also required for CC formation, likely through promoting the recruitment of BLM to the replication stressed ALT telomeres. Finally, we demonstrated that TERRA R-loops accumulate at telomeres in FANCM deficient ALT cells and downregulation of which attenuates the ALT-associated PML bodies (APBs), replication stress and CC formation. Taken together, our data suggest that FANCM prevents replisomes from stalling/collapsing at ALT telomeres by disrupting TERRA R-loops.