Notes

Analyzing PACS Consumption Styles by Means of Procedure Exploration: Steps In the direction of a More Comprehensive Workflows Examination inside Radiology.
In this large prospective study of women, no associations of ACEi or ARB use with colorectal cancer risk were observed.

Choice of drug in the large population of aging women who will be prescribed ACEi and ARB should be made without factoring in any benefit on colorectal cancer risk.
Choice of drug in the large population of aging women who will be prescribed ACEi and ARB should be made without factoring in any benefit on colorectal cancer risk.
Stomach cancer incidence and mortality rates are declining across circumpolar nations, but the burden may not be distributed equally across subpopulations, including Indigenous peoples. Our objective was to examine stomach cancer incidence and mortality trends across circumpolar populations.

Cancer incidence and mortality data from 1999-2016 were obtained from the Canadian Cancer Registry, Canadian Vital Statistics, CDC WONDER, NORDCAN, Northwestern Russian cancer registries, and National Cancer Reports. The direct method was used to calculate 10-year rolling age-standardized incidence and mortality rates to the world (WHO 2000-2025) and 2011 Canadian standard populations. Standardized incidence rate ratios (SRR) were calculated. Data were stratified by sex, year, and region. U.S. data were broken down by race [White; American Indian/Alaska Native (AIAN)]. Race data were not available from non-U.S. cancer registries.

Most populations showed declining incidence and mortality rates over time. Incidence ragions, addressing disparities could benefit from coordinated international action.
Inflammatory bowel disease (IBD) has been associated with hepatobiliary cancer, but existing evidence is poor. We evaluated risk of death from hepatocellular carcinoma (HCC), intrahepatic cholangiocarcinoma (ICC), and extrahepatic cholangiocarcinoma (ECC) among patients with IBD.

This Swedish/Danish population-based cohort study (1969-2017) followed patients with IBD and 110 matched population comparators from their diagnosis/match date until death, emigration, or end of follow-up.

Among the 97,496 patients with ulcerative colitis/963,026 comparators, we found 66/390 HCC-deaths, 120/173 ICC-deaths, and 91/220 ECC-deaths (median follow-up 10 years); the 10-year-mortality was 0.5‰ (per mille) for HCC, 0.6‰ for ICC, and 0.4‰ for ECC, which decreased to 0.3‰, 0.4‰, and 0.2‰, respectively, in 2003-2017. Overall hazard ratios (HR) were 1.83 [95% confidence interval (CI), 1.41-2.38] for HCC-, 7.33 (95% CI, 5.81-9.25) for ICC-, and 4.46 (95% CI, 3.49-5.70) for ECC-deaths. A total of 22/66 HCC-deaths, 87/120 ICC-deaths, and 55/91 ECC-deaths occurred among patients with ulcerative colitis with primary sclerosing cholangitis (PSC), corresponding to 10-year-mortality of 6.7‰, 26.2‰, and 17.2‰, respectively. Among 47,399 patients with Crohn's disease (median follow-up 11 years), 10-year-mortality from HCC (
= 28), ICC (
= 28), and ECC (
= 24) were 0.3‰, 0.1‰, and 0.3‰, respectively, and corresponding HRs were 1.96 (95% CI, 1.31-2.93), 3.33 (95% CI, 2.19-5.09), and 3.10 (95% CI, 1.97-4.87). One of 28 HCC-deaths, 14/28 ICC-deaths (10-year-mortality 19‰), and 12/24 ECC-deaths (10-year-mortality 14‰) occurred after PSC.

Risk of HCC-, ICC-, and ECC-deaths was low in patients with IBD and decreased over time. However, a large proportion of deaths occurred after PSC.

Guidelines on specific surveillance strategies for patients with IBD with PSC, but not those without PSC, are needed.
Guidelines on specific surveillance strategies for patients with IBD with PSC, but not those without PSC, are needed.The recent U.S. Supreme Court case of Kahler v. Kansas determined that the Kansas mens rea laws were sufficient to stand as the state's only insanity defense statute. ABBV-744 clinical trial In this issue of The Journal, Landess and Holoyda describe the legal reasoning that led to this decision and the persistent concerns about the wisdom of the decision. This commentary is meant to serve as a mirror image to Landess and Holoyda's article, as it focuses on the impact of Kahler on severely mentally ill individuals faced with criminal charges in the four mens rea states Montana, Idaho, Utah, and Kansas. The authors assert that the absence of a traditional insanity defense disrupts the criminal justice process, adds the pressure of greater numbers of individuals pushed into the competency-to-stand-trial and competency-restoration systems, resurrects the guilty but mentally ill verdict from the condemnation of history, and forces people with serious mental iillness into prisons without any evidence that the prisons are up to the task of adequately caring for them.Mutations in IFN and MHC signaling genes endow immunotherapy resistance. Patients with colorectal cancer infrequently exhibit IFN and MHC signaling gene mutations and are generally resistant to immunotherapy. In exploring the integrity of IFN and MHC signaling in colorectal cancer, we found that optineurin was a shared node between the two pathways and predicted colorectal cancer patient outcome. Loss of optineurin occurs in early-stage human colorectal cancer. Immunologically, optineurin deficiency was shown to attenuate IFNGR1 and MHC-I expression, impair T-cell immunity, and diminish immunotherapy efficacy in murine cancer models and patients with cancer. Mechanistically, we observed that IFNGR1 was S-palmitoylated on Cys122, and AP3D1 bound with and sorted palmitoylated IFNGR1 to lysosome for degradation. Unexpectedly, optineurin interacted with AP3D1 to prevent palmitoylated IFNGR1 lysosomal sorting and degradation, thereby maintaining IFNγ and MHC-I signaling integrity. Furthermore, pharmacologically targeting IFNGR1 palmitoylation stabilized IFNGR1, augmented tumor immunity, and sensitized checkpoint therapy. Thus, loss of optineurin drives immune evasion and intrinsic immunotherapy resistance in colorectal cancer. SIGNIFICANCE Loss of optineurin impairs the integrity of both IFNγ and MHC-I signaling pathways via palmitoylation-dependent IFNGR1 lysosomal sorting and degradation, thereby driving immune evasion and intrinsic immunotherapy resistance in colorectal cancer. Our work suggests that pharmacologically targeting IFNGR1 palmitoylation can stabilize IFNGR1, enhance T-cell immunity, and sensitize checkpoint therapy in colorectal cancer.See related commentary by Salvagno and Cubillos-Ruiz, p. 1623.This article is highlighted in the In This Issue feature, p. 1601.
Website: https://www.selleckchem.com/products/abbv-744.html