Digital Rectal Exams Are Infrequently Performed Prior to Anorectal Manometry.

BACKGROUND: Digital rectal examination should be performed prior to anorectal manometry; however, real-world data is lacking. AIMS: Characterize real world rates of digital rectal and their sensitivity for detecting dyssynergia compared to anorectal manometry and balloon expulsion test. METHODS: A retrospective single-center study was conducted to examine all patients who underwent anorectal manometry for chronic constipation between 2021 and 2022 at one tertiary center with motility expertise. Primary outcomes consisted of the rate of digital rectal exam prior to anorectal manometry; and secondary outcomes included the sensitivity of digital rectal exam for dyssynergic defecation. RESULTS: Only 42.3% of 142 patients had digital rectal examinations prior to anorectal manometry. Overall sensitivity for detecting dyssynergic defecation was 46.4%, but significantly higher for gastroenterology providers (p = .004), and highest for gastroenterology attendings (82.6%). CONCLUSIONS: Digital rectal examination is infrequently performed when indicated for chronic constipation. Sensitivity for detecting dyssynergic defecation may be impacted by discipline and level of training.

Identifying Visceral Kaposi Sarcoma (KS): A Responsibility to Avoid Anchoring on the Diagnosis of a Crohn's Flare.

The initial evaluation of reported inflammatory bowel disease (IBD) should include an assessment for immunosuppression which can broaden the differential diagnosis to include opportunistic infection as well as other processes. Here we present an exceedingly rare case of a patient with a self-reported history of Crohn's disease presenting with frequent diarrhea presumed to be a Crohn's flare, however, after further workup was found to have extensive visceral Kaposi sarcoma (KS).

Longitudinal and Circumferential Distributions of Dysplasia and Early Neoplasia in Barrett's Esophagus: A Pooled Analysis of Three Prospective Studies.

INTRODUCTION: Studies have shown that dysplasia in Barrett's esophagus (BE) has a predilection for the right hemisphere. There is limited information on the longitudinal distribution. The aim was to determine both the longitudinal and circumferential distributions of dysplasia and early neoplasia from 3 prospective studies. METHODS: This is a pooled analysis from 3 prospective studies of patients with treatment-naive BE. Both circumferential and longitudinal locations (for BE segments greater than 1 cm) of dysplastic and early neoplastic lesions were recorded. RESULTS: A total of 177 dysplastic and early neoplastic lesions from 91 patients were included in the pooled analysis; of which 59.3% (n = 105) were seen on high-definition white light endoscopy, 29.4% (n = 52) on advanced imaging, and 11.2% (n = 20) with random biopsies. The average Prague score was C3M5. Of 157 lesions within BE segments greater than 1 cm, 49 (34.8%) lesions were in the proximal half, whereas 92 lesions (65.2%) were in the distal half (P < 0.001). The right hemisphere of the esophagus contained 55% (86/157) of the total lesions compared with 45% (71/157) for the left hemisphere (P = 0.02). This was because of the presence of high-grade dysplasia being concentrated in the right hemisphere compared with the left hemisphere (60% vs 40%, P = 0.002). DISCUSSION: In this pooled analysis of prospective studies, both low-grade dysplasia and high-grade dysplasia are more frequently found in the distal half of the Barrett's segment. This study confirms that the right hemisphere is a hot spot for high-grade dysplasia. Careful attention to these locations is important during surveillance endoscopy.

Escalation of Immunosuppressive Therapy for Inflammatory Bowel Disease Is Not Associated With Adverse Outcomes After Infection With Clostridium difficile.

BACKGROUND: Clostridium difficile infection (CDI) is common in patients with inflammatory bowel disease (IBD), often leading to diagnostic confusion and delays in IBD therapy escalation. This study sought to assess outcomes after CDI in IBD patients exposed to new or escalated immunosuppressive therapy. METHODS: This multicenter retrospective cohort study included IBD patients with documented CDI at 4 academic medical centers. Data were abstracted from clinical databases at each institution. Outcomes at 30 and 90 days were compared between patients undergoing new or intensified immunosuppressive therapy and those without therapy escalation. Continuous variables were compared using t tests, and proportions using chi-square tests. Multivariable logistic regression was used to determine the association of individual variables with severe outcomes (including death, sepsis, and/or colectomy) within 90 days. Secondary outcomes included CDI recurrence, rehospitalization, worsening of IBD, and severe outcomes within 30 days. RESULTS: A total of 207 adult patients with IBD and CDI were included, of whom 62 underwent escalation to biologic or corticosteroid therapy (median time to escalation, 13 days). Severe outcomes within 90 days occurred in 21 (15.6%) nonescalated and 1 (1.8%) therapy-escalated patients. Serum albumin <2.5 mg/dL, lactate >2.2 mg/dL, intensive care unit admission, hypotension, and comorbid disease were associated with severe outcomes. Likelihood of severe outcomes was decreased in patients undergoing escalation of IBD therapy after CDI (adjusted odds ratio [aOR], 0.12) and increased among patients aged >65 years (aOR, 4.55). CONCLUSIONS: Therapy escalation for IBD within 90 days of CDI was not associated with worse clinical outcomes. Initiation of immunosuppression for active IBD may therefore be appropriate in carefully selected patients after treatment of CDI.

Identification of molecular motors in the Woods Hole squid, Loligo pealei: an expressed sequence tag approach.

The squid giant axon and synapse are unique systems for studying neuronal function. While a few nucleotide and amino acid sequences have been obtained from squid, large scale genetic and proteomic information is lacking. We have been particularly interested in motors present in axons and their roles in transport processes. Here, to obtain genetic data and to identify motors expressed in squid, we initiated an expressed sequence tag project by single-pass sequencing mRNAs isolated from the stellate ganglia of the Woods Hole Squid, Loligo pealei. A total of 22,689 high quality expressed sequence tag (EST) sequences were obtained and subjected to basic local alignment search tool analysis. Seventy six percent of these sequences matched genes in the National Center for Bioinformatics databases. By CAP3 analysis this library contained 2459 contigs and 7568 singletons. Mining for motors successfully identified six kinesins, six myosins, a single dynein heavy chain, as well as components of the dynactin complex, and motor light chains and accessory proteins. This initiative demonstrates that EST projects represent an effective approach to obtain sequences of interest.

In vivo systems analysis identifies spatial and temporal aspects of the modulation of TNF-α-induced apoptosis and proliferation by MAPKs.

Cellular responses to external stimuli depend on dynamic features of multipathway network signaling; thus, cell behavior is influenced in a complex manner by the environment and by intrinsic properties. Methods of multivariate systems analysis have provided an understanding of these convoluted effects, but only for relatively simplified examples in vitro. To determine whether such approaches could be successfully used in vivo, we analyzed the signaling network that determines the response of intestinal epithelial cells to tumor necrosis factor-α (TNF-α). We built data-driven, partial least-squares discriminant analysis (PLSDA) models based on signaling, apoptotic, and proliferative responses in the mouse small intestinal epithelium after systemic exposure to TNF-α. The extracellular signal-regulated kinase (ERK) signaling axis was a critical modulator of the temporal variation in apoptosis at different doses of TNF-α and of the spatial variation in proliferation in distinct intestinal regions. Inhibition of MEK, a mitogen-activated protein kinase kinase upstream of ERK, altered the signaling network and changed the temporal and spatial phenotypes consistent with model predictions. Our results demonstrate the dynamic, adaptive nature of in vivo signaling networks and identify natural, tissue-level variation in responses that can be deconvoluted only with quantitative, multivariate computational modeling. This study lays a foundation for the use of systems-based approaches to understand how dysregulation of the cellular network state underlies complex diseases.