A Quality Improvement Study on Colonoscopy Wait Times in Underinsured Patients Following the COVID-19 Pandemic.

INTRODUCTION: The coronavirus disease 2019 (COVID-19) pandemic limited access to colonoscopy. To advance colorectal cancer health equity, we conducted a quality improvement study on colonoscopy wait times in 2019-2023 for underinsured (Medicaid, uninsured) compared to insured patients at an academic medical center providing colonoscopy for surrounding Federally Qualified Health Centers. METHODS: Retrospective chart reviews were performed on adult outpatient colonoscopies in the pre-intervention period (2019-2021). In 2022, an institutional grant funded bilingual patient navigation to reduce colonoscopy wait times. Post-intervention data was collected prospectively from May 2022 to May 2023 in two phases. Multivariable regression analyses were conducted for colonoscopy wait times as a primary outcome. RESULT: Analysis of 3403 screening/surveillance and 1896 diagnostic colonoscopies revealed significantly longer colonoscopy wait times for underinsured compared to insured patients after 2019. For screening/surveillance colonoscopies, wait time differences between underinsured and insured patients in the second post-intervention phase were reduced by 34.21 days (95% CI: 11.07 - 57.35) compared to the post-pandemic period and by 56.36 days (95% CI: 34.16 - 78.55) compared to the first post-intervention phase. For diagnostic colonoscopies, wait time differences in the second post-intervention phase were reduced by 27.57 days (95% CI: 9.96 - 45.19) compared to the post-pandemic period and by 20.40 days (95% CI: 1.02 - 39.77) compared to the first post-intervention phase. CONCLUSION: Colonoscopy wait times were significantly longer for underinsured compared to insured patients following the COVID-19 pandemic. This disparity was partially ameliorated by patient navigation. Monitoring outpatient colonoscopy wait times in underinsured patients is important for advancing health equity.

Gender-Specific Attitudes of Internal Medicine Residents Toward Gastroenterology.

BACKGROUND AND AIMS: Female representation among gastroenterology (GI) fellows has remained around 30%, yet women comprise over 50% of internal medicine (IM) residents. We aim to identify the gender-specific barriers of IM residents toward pursuing GI. METHODS: We surveyed IM residents in the Northeast by emailing 168 IM programs a survey link to be distributed to their residents. A 4-point Likert barrier scale and bivariate analysis were performed with "yes" and "no," where "yes" was analyzed as "somewhat of a barrier" and above. Females received a third table assessing female-specific barriers. Significance was set at < 0.05. RESULTS: Of 215 survey responses, 56.3% (n = 121) were female. Response rate could not be determined due to resident identity protection and inconsistent responses of survey dissemination from programs. Females had significantly greater concerns about fertility, maternity leave, radiation exposure, work-life balance, stress, and burnout compared to males (p < 0.05). For females, 48.7% felt a lack of gender diversity in GI, 54.6% felt a lack of female GI mentors, and 43.7% felt there is a lack of respect as a female in GI. No gender differences existed in motivation to pursue GI, exposure to GI, and access to GI mentors, or GI-related research. CONCLUSIONS: Our study reveals that female IM trainees had greater concerns surrounding fertility, radiation exposure, and maternity leave compared to male IM trainees. Lack of gender diversity and lack of female GI mentors were noted barriers for female IM trainees. Addressing these barriers may help increase female representation in GI.

Metagenomic and bile acid metabolomic analysis of fecal microbiota transplantation for recurrent Clostridiodes difficile and/or inflammatory bowel diseases.

Background: Fecal microbiota transplantation (FMT) is an effective treatment of recurrent Clostridioides difficile infections (rCDI), but has more limited efficacy in treating either ulcerative colitis (UC) or Crohn's disease (CD), two major forms of inflammatory bowel diseases (IBD). We hypothesize that FMT recipients with rCDI and/or IBD have baseline fecal bile acid (BA) compositions that differ significantly from that of their healthy donors and that FMT will normalize the BA compositions. Aim: To study the effect of single colonoscopic FMT on microbial composition and function in four recipient groups: 1.) rCDI patients without IBD (rCDI-IBD); 2.) rCDI with IBD (rCDI+IBD); 3.) UC patients without rCDI (UC-rCDI); 4.) CD patients without rCDI (CD-rCDI). Methods: We performed 16S rRNA gene sequence, shotgun DNA sequence and quantitative bile acid metabolomic analyses on stools collected from 55 pairs of subjects and donors enrolled in two prospective single arm FMT clinical trials (Clinical Trials.gov ID NCT03268213, 479696, UC no rCDI ≥ 2x IND 1564 and NCT03267238, IND 16795). Fitted linear mixed models were used to examine the effects of four recipient groups, FMT status (Donor, pre-FMT, 1-week post-FMT, 3-months post-FMT) and first order Group*FMT interactions on microbial diversity and composition, bile acid metabolites and bile acid metabolizing enzyme gene abundance. Results: The pre-FMT stools collected from rCDI ± IBD recipients had reduced α-diversity compared to the healthy donor stools and was restored post-FMT. The α-diversity in the pre-FMT stools collected from UC-rCDI or CD-rCDI recipients did not differ significantly from donor stools. FMT normalized some recipient/donor ratios of genus level taxa abundance in the four groups. Fecal secondary BA levels, including some of the secondary BA epimers that exhibit in vitro immunomodulatory activities, were lower in rCDI±IBD and CD-rCDI but not UC-rCDI recipients compared to donors. FMT restored secondary BA levels. Metagenomic baiE gene and some of the eight bile salt hydrolase (BSH) phylotype abundances were significantly correlated with fecal BA levels. Conclusion: Restoration of multiple secondary BA levels, including BA epimers implicated in immunoregulation, are associated with restoration of fecal baiE gene counts, suggesting that the 7-α-dehydroxylation step is rate-limiting.

The impact of corticosteroid use on inpatients with inflammatory bowel disease and positive polymerase chain reaction for Clostridium difficile.

BACKGROUND/AIMS: Optimal management of inflammatory bowel disease (IBD) with concomitant Clostridium difficile infection (CDI) is controversial, especially when CDI diagnosis is made by polymerase chain reaction (PCR) testing, which may reflect colonization without infection. METHODS: We performed a multicenter review of all inpatients with IBD and PCR diagnosed CDI. Outcomes included length of stay, 30- and 90-day readmission, colectomy during admission and within 3 months, intensive care unit (ICU) admission, CDI relapse and death for patients who received corticosteroid (CS) after CDI diagnosis versus those that did not. Propensity-adjusted regression analysis of outcomes based on CS usage was performed. RESULTS: We identified 177 IBD patients with CDI, 112 ulcerative colitis and 65 Crohn's disease. For IBD overall, CS after CDI diagnosis was associated with prolonged hospitalization (5.5 days: 95% confidence interval [CI], 1.5-9.6 days; P=0.008), higher colectomy rate within 3 months (odds ratio [OR], 5.5; 95% CI, 1.1-28.2; P=0.042) and more frequent ICU admissions (OR, 7.8; 95% CI, 1.5-41.6; P=0.017) versus no CS. CS use post-CDI diagnosis in UC patients was associated with prolonged hospitalization (6.2 days: 95% CI, 0.4- 12.0 days; P=0.036) and more frequent ICU admissions (OR, 7.4; 95% CI, 1.1-48.7; P=0.036). CONCLUSIONS: CS use among IBD inpatients with CDI diagnosed by PCR is associated with poorer outcomes and would seem to reinforce the importance of C. difficile toxin assay to help distinguish colonization from infection. This adverse effect appears more prominent among those with UC.

Longitudinal microbiome analysis of single donor fecal microbiota transplantation in patients with recurrent Clostridium difficile infection and/or ulcerative colitis.

BACKGROUND: Studies of colonoscopic fecal microbiota transplant (FMT) in patients with recurrent CDI, indicate that this is a very effective treatment for preventing further relapses. In order to provide this service at Stony Brook University Hospital, we initiated an open-label prospective study of single colonoscopic FMT among patients with ≥ 2 recurrences of CDI, with the intention of monitoring microbial composition in the recipient before and after FMT, as compared with their respective donor. We also initiated a concurrent open label prospective trial of single colonoscopic FMT of patients with ulcerative colitis (UC) not responsive to therapy, after obtaining an IND permit (IND 15642). To characterize how FMT alters the fecal microbiota in patients with recurrent Clostridia difficile infections (CDI) and/or UC, we report the results of a pilot microbiome analysis of 11 recipients with a history of 2 or more recurrences of C. difficile infections without inflammatory bowel disease (CDI-only), 3 UC recipients with recurrent C. difficile infections (CDI + UC), and 5 UC recipients without a history of C. difficile infections (UC-only). METHOD: V3V4 Illumina 16S ribosomal RNA (rRNA) gene sequencing was performed on the pre-FMT, 1-week post-FMT, and 3-months post-FMT recipient fecal samples along with those collected from the healthy donors. Fitted linear mixed models were used to examine the effects of Group (CDI-only, CDI + UC, UC-only), timing of FMT (Donor, pre-FMT, 1-week post-FMT, 3-months post-FMT) and first order Group*FMT interactions on the diversity and composition of fecal microbiota. Pairwise comparisons were then carried out on the recipient vs. donor and between the pre-FMT, 1-week post-FMT, and 3-months post-FMT recipient samples within each group. RESULTS: Significant effects of FMT on overall microbiota composition (e.g., beta diversity) were observed for the CDI-only and CDI + UC groups. Marked decreases in the relative abundances of the strictly anaerobic Bacteroidetes phylum, and two Firmicutes sub-phyla associated with butyrate production (Ruminococcaceae and Lachnospiraceae) were observed between the CDI-only and CDI + UC recipient groups. There were corresponding increases in the microaerophilic Proteobacteria phylum and the Firmicutes/Bacilli group in the CDI-only and CDI + UC recipient groups. At a more granular level, significant effects of FMT were observed for 81 genus-level operational taxonomic units (OTUs) in at least one of the three recipient groups (p<0.00016 with Bonferroni correction). Pairwise comparisons of the estimated pre-FMT recipient/donor relative abundance ratios identified 6 Gammaproteobacteria OTUs, including the Escherichia-Shigella genus, and 2 Fusobacteria OTUs with significantly increased relative abundance in the pre-FMT samples of all three recipient groups (FDR < 0.05), however the magnitude of the fold change was much larger in the CDI-only and CDI + UC recipients than in the UC-only recipients. Depletion of butyrate producing OTUs, such as Faecalibacterium, in the CDI-only and CDI + UC recipients, were restored after FMT. CONCLUSION: The results from this pilot study suggest that the microbial imbalances in the CDI + UC recipients more closely resemble those of the CDI-only recipients than the UC-only recipients.

Uncovered Self-Expanding Metal Stent (SEMS) Four Years After Placement for Long-Term Treatment of a Benign Colonic Obstruction.

Self-expanding metal stents (SEMS) have emerged as an alternative to surgery in the treatment of malignant colorectal obstructions. There is limited data about their use for benign colonic obstructions, especially in regards to safety and long-term patency. We present a case in which long-term SEMS placement proved to be a durable option for over 4 years in a patient with a benign colonic stricture.

Acute Mesenteric Ischemia Caused by Rare Cardiac Tumor Embolus.

Acute mesenteric ischemia (AMI) is a rare vascular emergency associated with a high mortality rate. The most common cause of AMI is cardiac emboli from thrombi associated with atrial fibrillation or following myocardial infarction. We present a case of AMI caused by a unique source of emboli, confirmed as an embolization of a cardiac sarcoma to the small bowel by matching biopsies obtained from the superior mesenteric artery (SMA) and the embolic source.

Determination of nuclear localization signal sequences for Krüppel-like factor 8.

Transcription factor proteins function in the nucleus to regulate gene expression. Many transcription factors are critical regulators of tumor progression. Conversely, many oncogenic and tumor suppressor proteins are transcription factors or other types of nuclear proteins. Because of their critical physiological and pathological roles, these tumor regulators are tightly regulated not only in the protein expression but also in their subcellular localization. This chapter is focused on experimental strategies and method details for the identification and characterization of nuclear localization signal sequences for nuclear proteins using the Krüppel-like transcription factor 8 as an example.

A unique sequence in the N-terminal regulatory region controls the nuclear localization of KLF8 by cooperating with the C-terminal zinc-fingers.

Krüppel-like factor 8 (KLF8) transcription factor plays a critical role in cell cycle progression, oncogenic transformation, epithelial to mesenchymal transition and invasion. However, its nuclear localization signal(s) (NLS) has not been identified. KLF8 shares with other KLFs monopartite NLSs (mNLS) and C(2)H(2) zinc fingers (ZFs), both of which have been shown to be the NLSs for some other KLFs. In this report, using PCR-directed mutagenesis and immunofluorescent microscopy, we show that disruption of the mNLSs, deletion of any single ZF, or mutation of the Zn(2+)-binding or DNA-contacting motifs did not affect the nuclear localization of KLF8. Deletion of >1.5 ZFs from C-terminus, however, caused cytoplasmic accumulation of KLF8. Surprisingly, deletion of amino acid (aa) 151-200 region almost eliminated KLF8 from the nucleus. S165A, K171E or K171R mutation, or treatment with PKC inhibitor led to partial cytoplasmic accumulation. Co-immunoprecipitation demonstrated that KLF8 interacted with importin-beta and this interaction required the ZF motif. Deletion of aa 1-150 or 201-261 region alone did not alter the nuclear localization. BrdU incorporation and cyclin D1 promoter luciferase assays showed that the KLF8 mutants defective in nuclear localization could not promote DNA synthesis or cyclin D1 promoter activation as the wild-type KLF8 did. Taken together, these results suggest that KLF8 has two NLSs, one surrounding S165 and K171 and the other being two tandem ZFs, which are critical for the regulation of KLF8 nuclear localization and its cellular functions.