Baseline Features and Reasons for Nonparticipation in the Colonoscopy Versus Fecal Immunochemical Test in Reducing Mortality From Colorectal Cancer (CONFIRM) Study, a Colorectal Cancer Screening Trial.

Importance: The Colonoscopy Versus Fecal Immunochemical Test in Reducing Mortality From Colorectal Cancer (CONFIRM) randomized clinical trial sought to recruit 50 000 adults into a study comparing colorectal cancer (CRC) mortality outcomes after randomization to either an annual fecal immunochemical test (FIT) or colonoscopy. Objective: To (1) describe study participant characteristics and (2) examine who declined participation because of a preference for colonoscopy or stool testing (ie, fecal occult blood test [FOBT]/FIT) and assess that preference's association with geographic and temporal factors. Design, Setting, and Participants: This cross-sectional study within CONFIRM, which completed enrollment through 46 Department of Veterans Affairs medical centers between May 22, 2012, and December 1, 2017, with follow-up planned through 2028, comprised veterans aged 50 to 75 years with an average CRC risk and due for screening. Data were analyzed between March 7 and December 5, 2022. Exposure: Case report forms were used to capture enrolled participant data and reasons for declining participation among otherwise eligible individuals. Main Outcomes and Measures: Descriptive statistics were used to characterize the cohort overall and by intervention. Among individuals declining participation, logistic regression was used to compare preference for FOBT/FIT or colonoscopy by recruitment region and year. Results: A total of 50 126 participants were recruited (mean [SD] age, 59.1 [6.9] years; 46 618 [93.0%] male and 3508 [7.0%] female). The cohort was racially and ethnically diverse, with 748 (1.5%) identifying as Asian, 12 021 (24.0%) as Black, 415 (0.8%) as Native American or Alaska Native, 34 629 (69.1%) as White, and 1877 (3.7%) as other race, including multiracial; and 5734 (11.4%) as having Hispanic ethnicity. Of the 11 109 eligible individuals who declined participation (18.0%), 4824 (43.4%) declined due to a stated preference for a specific screening test, with FOBT/FIT being the most preferred method (2820 [58.5%]) vs colonoscopy (1958 [40.6%]; P < .001) or other screening tests (46 [1.0%] P < .001). Preference for FOBT/FIT was strongest in the West (963 of 1472 [65.4%]) and modest elsewhere, ranging from 199 of 371 (53.6%) in the Northeast to 884 of 1543 (57.3%) in the Midwest (P = .001). Adjusting for region, the preference for FOBT/FIT increased by 19% per recruitment year (odds ratio, 1.19; 95% CI, 1.14-1.25). Conclusions and Relevance: In this cross-sectional analysis of veterans choosing nonenrollment in the CONFIRM study, those who declined participation more often preferred FOBT or FIT over colonoscopy. This preference increased over time and was strongest in the western US and may provide insight into trends in CRC screening preferences.

Excess SeqA leads to replication arrest and a cell division defect in Vibrio cholerae.

Although most bacteria contain a single circular chromosome, some have complex genomes, and all Vibrio species studied so far contain both a large and a small chromosome. In recent years, the divided genome of Vibrio cholerae has proven to be an interesting model system with both parallels to and novel features compared with the genome of Escherichia coli. While factors influencing the replication and segregation of both chromosomes have begun to be elucidated, much remains to be learned about the maintenance of this genome and of complex bacterial genomes generally. An important aspect of replicating any genome is the correct timing of initiation, without which organisms risk aneuploidy. During DNA replication in E. coli, newly replicated origins cannot immediately reinitiate because they undergo sequestration by the SeqA protein, which binds hemimethylated origin DNA. This DNA is already methylated by Dam on the template strand and later becomes fully methylated; aberrant amounts of Dam or the deletion of seqA leads to asynchronous replication. In our study, hemimethylated DNA was detected at both origins of V. cholerae, suggesting that these origins are also subject to sequestration. The overproduction of SeqA led to a loss of viability, the condensation of DNA, and a filamentous morphology. Cells with abnormal DNA content arose in the population, and replication was inhibited as determined by a reduced ratio of origin to terminus DNA in SeqA-overexpressing cells. Thus, excessive SeqA negatively affects replication in V. cholerae and prevents correct progression to downstream cell cycle events such as segregation and cell division.

Identification of borinic esters as inhibitors of bacterial cell growth and bacterial methyltransferases, CcrM and MenH.

As bacteria continue to develop resistance toward current antibiotics, we find ourselves in a continual battle to identify new antibacterial agents and targets. We report herein a class of boron-containing compounds termed borinic esters that have broad spectrum antibacterial activity with minimum inhibitory concentrations (MIC) in the low microgram/mL range. These compounds were identified by screening for inhibitors against Caulobacter crescentus CcrM, an essential DNA methyltransferase from gram negative alpha-proteobacteria. In addition, we demonstrate that borinic esters inhibit menaquinone methyltransferase in gram positive bacteria using a new biochemical assay for MenH from Bacillus subtilis. Our data demonstrate the potential for further development of borinic esters as antibacterial agents as well as leads to explore more specific inhibitors against two essential bacterial enzymes.

Genetic aspects of non-polypoid colorectal neoplasms.

Colorectal cancer is a heterogeneous disease arising through multiple possible pathways. Elucidating the genetic factors controlling molecular phenotype, morphology, histology, and prognosis of different tumor types continues to be a challenge. Non-polypoid colorectal neoplasms provide opportunities for ongoing study of their underlying genetic abnormalities and molecular phenotypes. The varied data from different groups, however, highlight the need for further studies in different populations.

Assessing compliance with national quality measures to improve colorectal cancer care at the VA.

BACKGROUND: The US Department of Veterans Affairs (VA) Office of Quality and Performance's July 2009 report detailed the quality of VA colorectal cancer (CRC) care on the basis of 10 quality indicators (QIs). Of 21 Veterans Integrated Service Networks (VISNs), the authors' VISN ranked last or near last on more than half of the QIs. The aim of this study was to compare a national-level assessment of performance with an institutional-level clinical review. METHODS: The authors reabstracted all patients seen at surgical hospitals within their VISN during the time period of the Office of Quality and Performance report and reanalyzed their performance on the 10 QIs. A number of quality improvement efforts were also implemented to further boost performance, including the creation of a computerized patient record system CRC order set and quarterly surveillance meetings. RESULTS: After reanalysis of the VISN's QI performance for CRC patients during the time period of the OQP report, the VISN performed 18% better than reported and 2% better than the national average. Since that time, a multidisciplinary CRC committee has implemented quality improvement measures that have further improved QI performance. CONCLUSIONS: There is variability between administrative quality assessments and clinically abstracted data. Care must be taken when analyzing QIs at the national level.

A parA homolog selectively influences positioning of the large chromosome origin in Vibrio cholerae.

A Vibrio cholerae deletion mutant lacking VS2773, a parA partitioning gene homolog located in a parAB operon on the large chromosome, displays altered positioning of the large chromosome origin. Deletion of a second parA homolog on the large chromosome (VC2061) does not affect its origin positioning. The origin position of the small chromosome is unchanged by either or both of these deletions, suggesting that VC2773 function is specific to the replicon on which it is carried. VC2773 and VC2772 form a parABS system with inverted repeats found near the large chromosome origin.

Polar localization of replicon origins in the multipartite genomes of Agrobacterium tumefaciens and Sinorhizobium meliloti.

The origins of replication of many different bacteria have been shown to reside at specific subcellular locations, but the mechanisms underlying their positioning and segregation are still being elucidated. In particular, little is known about the replication of multipartite genomes in bacteria. We determined the cellular positions of the origins of the replicons in the alpha proteobacteria Agrobacterium tumefaciens and Sinorhizobium meliloti and found that they are located at the poles of the cells. Our work demonstrates the conserved extreme polar localization of circular chromosome origins in these alpha proteobacteria and is also the first to specify the cellular location of origin regions from the repABC family. The cellular location of a derivative of the RK2 plasmid is distinct from that of the alpha proteobacterium genomic replicon origins but is conserved across bacteria. Colocalization experiments with the genomic replicons of A. tumefaciens revealed that the repABC replicons, although preferentially positioned at the cell pole, colocalize only rarely. For the repABC replicons in this organism, occupying discrete spatial locations may contribute to their coexistence and stable inheritance.

Flat and depressed colorectal neoplasms.

An increasing body of literature is available showing the existence of flat and depressed colorectal neoplasms in Western countries. The appreciation that colorectal neoplasms may present as flat or depressed lesions has important implications, as the risk of adenocarcinoma in depressed lesions has been found to be markedly higher than in flat or protruding lesions of similar size. There is concern that flat or depressed colorectal neoplasms might be easily missed during a colonoscopy and subsequently diagnosed as cancer within a few years after a clearing examination. In this review, we appraise advances in the study of flat and depressed colorectal cancers based on the English literature published in 2000 and subsequently, with emphasis on their epidemiology, diagnosis, and therapy.