Comparison of the morphology and histopathology of large nonpedunculated colorectal polyps in the rectum and colon: implications for endoscopic treatment.

BACKGROUND AND AIMS: The risk of cancer in large nonpedunculated colorectal polyps ≥20 mm (LNPCPs) in the rectum relative to the remainder of the colon is unknown. We aimed to describe differences between rectal and colonic LNPCPs to better inform treatment decisions. METHODS: Patients with LNPCPs referred to tertiary centers for endoscopic resection within a prospective, multicenter, observational cohort were evaluated. Data recorded were participant demographics, LNPCP location, morphology, resection modality, and histopathologic data. Multiple logistic regression analysis was used to identify those variables independently associated with rectal versus nonrectal location in the colon. RESULTS: Patients with LNPCPs referred for endoscopic resection between July 2008 and July 2021 were included. Rectal LNPCPs (n = 618) were larger (median size, 40 mm vs 30 mm; P < .001) and more likely to be granular (79% vs 50%, P < .001) with a nodular component (53% vs 17%, P < .001) compared with nonrectal LNPCPs (n = 2787). Rectal LNPCPs were more likely to have tubulovillous histopathology (72% vs 47%, P < .001) and contain cancer (15% vs 6%, P < .001). After adjusting for the other features independently associated with location, cancer was more common in the rectum compared with the colon (odds ratio, 1.77; 95% confidence interval, 1.25-2.53). CONCLUSIONS: This study suggests that compared with LNPCPs in the rest of the colon, rectal LNPCPs are more likely to be larger and contain more advanced pathology. These findings have implications for curative endoscopic resection techniques particularly where early cancer is present. (Clinical trial registration numbers: NCT01368289 and NCT02000141.).

Infection control in ERCP using a duodenoscope with a disposable cap (ICECAP): rationale for and design of a randomized controlled trial.

BACKGROUND: Endoscopic retrograde cholangio-pancreatography (ERCP) is commonly performed in the management of pancreatic and biliary disease. Duodenoscopes are specialized endoscopes used to perform ERCP, and inherent to their design, a high rate of persistent bacterial contamination exists even after automated reprocessing and disinfection. Consequently, in recent years, ERCP has been associated with infection transmission, leading to several fatal patient outbreaks. Due to increasing fears over widespread future duodenoscope-related outbreaks, regulatory bodies have called for alterations in the design of duodenoscopes. A duodenoscope has recently been developed that employs a disposable cap. This novel design theoretically eliminates the mechanism behind persistent bacterial contamination and infection transmission. However, there are no data demonstrating persistent bacterial contamination rates, technical success rates, or clinical outcomes associated with these duodenoscopes. METHODS: A parallel arm randomized controlled trial will be performed for which 520 patients will be recruited. The study population will consist of consecutive patients undergoing ERCP procedures for any indication at a high-volume tertiary care centre in Calgary, Alberta, Canada. Patients will be randomized to an intervention group, that will undergo ERCP with a novel duodenoscope with disposable cap, or to a control group who will undergo ERCP with a traditional duodenoscope. Co-primary outcomes will include persistent bacterial contamination rates (post automated reprocessing) and ERCP technical success rates. Secondary outcomes include clinical success rates, overall and specific early and late adverse event rates, 30-day mortality and healthcare utilization rates, procedure and reprocessing times, and ease of device use. DISCUSSION: The ICECAP trial will answer important questions regarding the use of a novel duodenoscope with disposable cap. Specifically, persistent bacterial contamination, technical performance, and relevant clinical outcomes will be assessed. Given the mortality and morbidity burden associated with ERCP-related infectious outbreaks, the results of this study have the capacity to be impactful at an international level. TRIAL REGISTRATION: This trial was registered on clinicaltrials.gov (NCT04040504) on July 31, 2019.

Diagnostic yield of small histological cores obtained with a new EUS-guided fine needle biopsy system.

BACKGROUND: As endoscopic ultrasound-guided tissue acquisition techniques evolve, there is increasing interest in obtaining optimal histological samples to improve diagnostic accuracy. In this study, we aimed to assess the tissue acquisition success rate and test performance characteristics of a novel endoscopic ultrasound-guided fine needle biopsy (EUS-FNB) system. METHODS: We performed a retrospective review of consecutive patients undergoing EUS-guided tissue sampling of solid lesions using the SharkCore fine needle system in a tertiary referral facility. At least two passes were submitted for histology and diagnostic accuracy was evaluated. Comparison standard was based on final surgical pathology or minimum six-month clinical follow-up. RESULTS: Seventy-nine patients underwent 85 EUS-FNB procedures. Of the 85 histology specimens, 78 (91.7%) were adequate for diagnostic examination (includes six atypical/suspicious for adenocarcinoma). The sensitivity, specificity, and accuracy for diagnosis of malignancy with FNB were 87.1, 100, and 90.6%, respectively. Cytology was simultaneously sent in 43 cases with the same needle in addition to histology. Out of the 14 cases that were atypical/suspicious for adenocarcinoma or non-diagnostic on cytology, 11 cases (78.6%) achieved definite diagnoses on histology. The overall sensitivity, specificity, and accuracy for diagnosis of malignancy combining histology and cytology were 90.3, 100, and 92.9%, respectively. No complications were reported after the procedures. CONCLUSION: In this initial experience with a new EUS-guided FNB system, obtaining small cores to submit for histological analysis was safe, technically feasible, and highly accurate. Most of the histological cores obtained via FNB yielded a definite diagnosis including in cases with equivocal cytomorphology. Further study is required to confirm these findings.

Metabolic monitoring and management among clozapine users.

OBJECTIVE: To assess, among clozapine users, the rates of monitoring, presence and treatment of metabolic syndrome and its components. METHODS: A chart review was conducted of all clozapine users who were followed up in community mental health clinics at two Metro South Health Hospitals over a 1-year period. Metabolic syndrome was diagnosed according to the International Diabetes Federation criteria. RESULTS: We included 251 clozapine users. Only 43.4% (109/251) had data collected for all five metabolic syndrome parameters. Among these people, 45.0% (49/109) met criteria for metabolic syndrome, while 61.2% (30/49) of those with metabolic syndrome were offered appropriate treatments. Correspondence with primary care providers occurred in only 18.7% ( n = 47). Non-pharmacological interventions, such as motivational interviewing and education about healthy lifestyle alternatives, occurred in 49.8% ( n = 125). CONCLUSIONS: There is growing awareness of the importance of metabolic monitoring, however, there remain specific gaps in the collaborative work among mental health services, primary care providers and clozapine users, to ensure appropriate physical health interventions.

Correction: Duodenal neuroendocrine tumors: Short-term outcomes of endoscopic submucosal dissection performed in the Western setting.

[This corrects the article DOI: 10.1055/a-2181-0320.].

Duodenal neuroendocrine tumors: Short-term outcomes of endoscopic submucosal dissection performed in the Western setting.

Background and study aims Endoscopic resection (ER) is recommended for the management of duodenal neuroendocrine tumors (D-NETs) confined to the submucosal layer, without lymph node or distant metastasis. While this is accepted practice for lesions < 10 mm, consensus for larger lesions remains unclear. Although endoscopic submucosal dissection (ESD) has been proposed as the preferred ER technique for DNETs ≥10 mm, there are limited data on efficacy and safety, particularly in the Western setting. Patients and methods We performed a retrospective analysis of patients with D-NETs who underwent ESD between 2012 and 2022 in three tertiary referral centers in Australia, France, and Belgium. Results Fourteen patients with 15 D-NETs were evaluated. Median patient age was 64 years (interquartile range [IQR] 58-70 years). All D-NETs were confined to the duodenal bulb. Median D-NET size was 10 mm (IQR 7-12 mm) and specimen size was 15 mm (IQR 15-20 mm). Median procedure time was 60 minutes (IQR 25-90 minutes). The rate of en bloc resection was 100%. Intra-procedural perforation occurred in four patients (26.7%), with all closed endoscopically without long-term sequelae. There were no episodes of clinically significant bleeding. No local recurrence, lymph node or distant metastasis was observed at a median follow-up of 19.9 months (IQR 10.3-49.3 months). Conclusions In experienced hands, ESD for D-NETs can achieve a 100% en bloc resection rate. There were no cases of local recurrence or distant metastatic spread, indicating that ESD may be a viable option for patients with D-NETs 10 to 15 mm that are not surgical candidates.

Effect of Disposable Elevator Cap Duodenoscopes on Persistent Microbial Contamination and Technical Performance of Endoscopic Retrograde Cholangiopancreatography: The ICECAP Randomized Clinical Trial.

Importance: Infection transmission following endoscopic retrograde cholangiopancreatography (ERCP) can occur due to persistent contamination of duodenoscopes despite high-level disinfection to completely eliminate microorganisms on the instrument. Objective: To determine (1) contamination rates after high-level disinfection and (2) technical performance of duodenoscopes with disposable elevator caps compared with those with standard designs. Design, Setting, and Participants: In this parallel-arm multicenter randomized clinical trial at 2 tertiary ERCP centers in Canada, all patients 18 years and older and undergoing ERCP for any indication were eligible. Intervention: The intervention was use of duodenoscopes with disposable elevator caps compared with duodenoscopes with a standard design. Main Outcomes and Measures: Coprimary outcomes were persistent microbial contamination of the duodenoscope elevator or channel, defined as growth of at least 10 colony-forming units of any organism or any growth of gram-negative bacteria following high-level disinfection (superiority outcome), and technical success of ERCP according to a priori criteria (noninferiority outcome with an a priori noninferiority margin of 7%), assessed by blinded reviewers. Results: From December 2019 to February 2022, 518 patients were enrolled (259 disposable elevator cap duodenoscopes, 259 standard duodenoscopes). Patients had a mean (SD) age of 60.7 (17.0) years and 258 (49.8%) were female. No significant differences were observed between study groups, including in ERCP difficulty. Persistent microbial contamination was detected in 11.2% (24 of 214) of standard duodenoscopes and 3.8% (8 of 208) of disposable elevator cap duodenoscopes (P = .004), corresponding to a relative risk of 0.34 (95% CI, 0.16-0.75) and number needed to treat of 13.6 (95% CI, 8.1-42.7) to avoid persistent contamination. Technical success using the disposable cap scope was noninferior to that of the standard scope (94.6% vs 90.7%, P = .13). There were no differences between study groups in adverse events and other secondary outcomes. Conclusions and Relevance: In this randomized clinical trial, disposable elevator cap duodenoscopes exhibited reduced contamination following high-level disinfection compared with standard scope designs, without affecting the technical performance and safety of ERCP. Trial Registration: ClinicalTrials.gov Identifier: NCT04040504.

Distinct regulatory role for RFL, the rice LFY homolog, in determining flowering time and plant architecture.

Activity of axillary meristems dictates the architecture of both vegetative and reproductive parts of a plant. In Arabidopsis thaliana, a model eudicot species, the transcription factor LFY confers a floral fate to new meristems arising from the periphery of the reproductive shoot apex. Diverse orthologous LFY genes regulate vegetative-to-reproductive phase transition when expressed in Arabidopsis, a property not shared by RFL, the homolog in the agronomically important grass, rice. We have characterized RFL by knockdown of its expression and by its ectopic overexpression in transgenic rice. We find that reduction in RFL expression causes a dramatic delay in transition to flowering, with the extreme phenotype being no flowering. Conversely, RFL overexpression triggers precocious flowering. In these transgenics, the expression levels of known flowering time genes reveal RFL as a regulator of OsSOC1 (OsMADS50), an activator of flowering. Aside from facilitating a transition of the main growth axis to an inflorescence meristem, RFL expression status affects vegetative axillary meristems and therefore regulates tillering. The unique spatially and temporally regulated RFL expression during the development of vegetative axillary bud (tiller) primordia and inflorescence branch primordia is therefore required to produce tillers and panicle branches, respectively. Our data provide mechanistic insights into a unique role for RFL in determining the typical rice plant architecture by regulating distinct downstream pathways. These results offer a means to alter rice flowering time and plant architecture by manipulating RFL-mediated pathways.

Impairment of metabolic capacities in copper and calcium contaminated wild yellow perch (Perca flavescens).

This study examined variations in resting oxygen consumption rate (ROCR), post-exercise oxygen consumption rate, relative scope for activity (RSA), liver and muscle aerobic and anaerobic capacities (using citrate synthase (CS) and lactate dehydrogenase, respectively, as indicators), and tissue biosynthetic capacities (using nucleoside diphosphate kinase (NDPK) as an indicator), in wild yellow perch from four lakes varying in copper (Cu) and cadmium (Cd) contamination. Liver Cu and Cd concentrations largely reflected environmental contamination and were positively correlated with liver protein concentrations and NDPK activities. Our results suggest that metal contamination leads to an upregulation of liver protein metabolism, presumably at least in part for the purpose of metal detoxification. In contrast, muscle NDPK activities decreased with increasing liver Cd concentrations and NDPK activities. There was a 25% decrease in ROCR for a doubling of liver Cu concentrations and a 42% decrease in RSA for a doubling of liver Cd concentrations in the range studied. Cu contamination was also associated with lower muscle CS activities. Our results support previous findings of impaired aerobic capacities in the muscle of metal-contaminated fish, and demonstrate that this impairment is also reflected in aerobic capacities of whole fish. The evidence presented suggests that mitochondria may be primary targets for inhibition by Cu, and that Cd may reduce gill respiratory capacity. Muscle aerobic and anaerobic capacities were inversely related. This work indicates that metal exposure of wild yellow perch leads to a wide range of disturbances in metabolic capacities.

Prevalence of vitamin D deficiency and response to oral vitamin D supplementation in patients receiving home parenteral nutrition.

UNLABELLED: The purpose of this study was to document vitamin D status in home parenteral nutrition (HPN) patients and determine if oral vitamin D supplementation has a substantial effect. METHODS: A retrospective chart review of eligible adults enrolled in the Southern Alberta Home Parenteral Nutrition program (n = 15) for a minimum of 6 months was conducted. Serum measurements of 25OHD were recorded and patients were categorized by vitamin D status as follows: sufficient; insufficient; deficient with respective levels of 25OHD ≥75 nmol/L, 27.5-75 nmol/L, and ≤27.5 nmol/L; and mixed. RESULTS: Five of 15 patients had insufficient vitamin D status throughout the study period; all had short bowel syndrome. Nine were in the mixed category; 1 was consistently sufficient, and no one was consistently deficient. Patient demographics were similar between the insufficient and mixed groups. There were no significant differences in health outcomes between the insufficient and mixed vitamin D status groups. The median (interquartile range) dose and duration of vitamin D3 supplementation for the insufficient group was 5000 IU/d (4,000-7,143) for 1,175 (1,145-1,578) total days compared to 3,000 IU/d (1,000-7,143) for 1,529 (111-1,980) days for the mixed group. CONCLUSIONS: Most patients receiving HPN had insufficient vitamin D status. When prescribed high doses of oral vitamin D, patients did not consistently achieve appropriate 25OHD levels. Alternate routes of vitamin D supplementation in patients receiving HPN should be considered. Large multicenter prospective studies are needed to best characterize the relationship between vitamin D dosing for HPN patients and vitamin D status.

Hyperglycemia in hospitalized patients receiving parental nutrition is associated with increased morbidity and mortality: a review.

Parenteral Nutrition (PN) is a valuable life saving intervention which can improve the nutritional status of hospitalized malnourished patients. PN is associated with complications including the development of hyperglycemia. This paper aims to provide a descriptive systematic review regarding the effects of PN-induced hyperglycemia in hospitalized patients, either in the intensive care unit or ward, while formulating and complementing existing guidelines on the administration of PN and glucose monitoring in hospitalized patients. Medline and Pubmed were searched for relevant articles describing complications arising from the development of hyperglycemia in patients receiving PN; four relevant studies were identified in the search. These articles had different glycemic targets and patient populations, and their protocols varied with regards to glycemic control. However, there was consistency regarding the association between hyperglycemia and mortality in patients receiving PN. These studies highlight the need for guidelines regarding monitoring and initiation of therapy in hyperglycemic patients. Unfortunately, all the currently available studies are retrospective in design; a large, prospective, randomized controlled trial regarding glycemic control in patients receiving PN is required for the development of standardized protocols.

Metabolic adaptation and oxaloacetate homeostasis in P. fluorescens exposed to aluminum toxicity.

Microbial systems are known to elaborate intricate metabolic strategies in an effort to fend the toxic impact of numerous metals. In this study, we show that the exposure of Pseudomonas fluorescens to aluminum (Al) resulted in a metabolic shift aimed at diverting oxaloacetate towards the biogenesis of an aluminophore. This metabolic alteration was characterized by uncoupling of two gluconeogenic enzymes, namely pyruvate carboxylase (PC) and phosphoenolpyruvate carboxykinase (PEPCK). While PC displayed a sharp increase in activity and expression, PEPCK was severely diminished. Malic enzyme (ME) and NAD kinase (NADK), two enzymes involved in maintaining a reductive environment, were markedly increased in the Al-stressed cells. Hence, Al-exposed Pseudomonas fluorescens evoked a metabolic response aimed at generating oxaloacetate and promoting an intracellular reductive environment.

Adaptation of Pseudomonas fluorescens to Al-citrate: involvement of tricarboxylic acid and glyoxylate cycle enzymes and the influence of phosphate.

The degradation of Aluminum-citrate by Pseudomonas fluorescens necessitated a major restructuring of the various enzymatic activities involved in the TCA and glyoxylate cycles. While a six-fold increase in fumarase (FUM EC 4.2.1.2) activity was observed in cells subjected to Al-citrate compared to control cells, citrate synthase (CS EC 4.1.3.7) activity experienced a two-fold increase. On the other hand, in the Al-stressed cells malate synthase (MS EC 4.1.3.2) activity underwent a five-fold decrease in activity. This modulation of enzymatic activities appeared to be evoked by Al stress, as the incubation of Al-stressed cells in control media led to the complete reversal of these enzymatic profiles. These observations were further confirmed by 1H NMR and 13C NMR spectroscopy. No significant variations were observed in the activities of other glyoxylate and TCA cycle enzymes, like isocitrate lyase (ICL EC 4.1.3.1), malate dehydrogenase (MDH EC 1.1.1.37), and succinate dehydrogenase (SDH EC 1.3.99.1). This reconfiguration of the metabolic pathway appears to favour the production of a citrate-rich aluminophore that is involved in the sequestration of Al.