Minutes-duration optical flares with supernova luminosities.

In recent years, certain luminous extragalactic optical transients have been observed to last only a few days1. Their short observed duration implies a different powering mechanism from the most common luminous extragalactic transients (supernovae), whose timescale is weeks2. Some short-duration transients, most notably AT2018cow (ref. 3), show blue optical colours and bright radio and X-ray emission4. Several AT2018cow-like transients have shown hints of a long-lived embedded energy source5, such as X-ray variability6,7, prolonged ultraviolet emission8, a tentative X-ray quasiperiodic oscillation9,10 and large energies coupled to fast (but subrelativistic) radio-emitting ejecta11,12. Here we report observations of minutes-duration optical flares in the aftermath of an AT2018cow-like transient, AT2022tsd (the 'Tasmanian Devil'). The flares occur over a period of months, are highly energetic and are probably nonthermal, implying that they arise from a near-relativistic outflow or jet. Our observations confirm that, in some AT2018cow-like transients, the embedded energy source is a compact object, either a magnetar or an accreting black hole.

Colorectal cancer statistics, 2020.

Colorectal cancer (CRC) is the second most common cause of cancer death in the United States. Every 3 years, the American Cancer Society provides an update of CRC occurrence based on incidence data (available through 2016) from population-based cancer registries and mortality data (through 2017) from the National Center for Health Statistics. In 2020, approximately 147,950 individuals will be diagnosed with CRC and 53,200 will die from the disease, including 17,930 cases and 3,640 deaths in individuals aged younger than 50 years. The incidence rate during 2012 through 2016 ranged from 30 (per 100,000 persons) in Asian/Pacific Islanders to 45.7 in blacks and 89 in Alaska Natives. Rapid declines in incidence among screening-aged individuals during the 2000s continued during 2011 through 2016 in those aged 65 years and older (by 3.3% annually) but reversed in those aged 50 to 64 years, among whom rates increased by 1% annually. Among individuals aged younger than 50 years, the incidence rate increased by approximately 2% annually for tumors in the proximal and distal colon, as well as the rectum, driven by trends in non-Hispanic whites. CRC death rates during 2008 through 2017 declined by 3% annually in individuals aged 65 years and older and by 0.6% annually in individuals aged 50 to 64 years while increasing by 1.3% annually in those aged younger than 50 years. Mortality declines among individuals aged 50 years and older were steepest among blacks, who also had the only decreasing trend among those aged younger than 50 years, and excluded American Indians/Alaska Natives, among whom rates remained stable. Progress against CRC can be accelerated by increasing access to guideline-recommended screening and high-quality treatment, particularly among Alaska Natives, and elucidating causes for rising incidence in young and middle-aged adults.

ßII-Spectrin Is Required for Synaptic Positioning during Retinal Development.

Neural circuit assembly is a multistep process where synaptic partners are often born at distinct developmental stages, and yet they must find each other and form precise synaptic connections with one another. This developmental process often relies on late-born neurons extending their processes to the appropriate layer to find and make synaptic connections to their early-born targets. The molecular mechanism responsible for the integration of late-born neurons into an emerging neural circuit remains unclear. Here, we uncovered a new role for the cytoskeletal protein ßII-spectrin in properly positioning presynaptic and postsynaptic neurons to the developing synaptic layer. Loss of ßII-spectrin disrupts retinal lamination, leads to synaptic connectivity defects, and results in impaired visual function in both male and female mice. Together, these findings highlight a new function of ßII-spectrin in assembling neural circuits in the mouse outer retina.SIGNIFICANCE STATEMENT Neurons that assemble into a functional circuit are often integrated at different developmental time points. However, the molecular mechanism that guides the precise positioning of neuronal processes to the correct layer for synapse formation is relatively unknown. Here, we show a new role for the cytoskeletal scaffolding protein, ßII-spectrin in the developing retina. ßII-spectrin is required to position presynaptic and postsynaptic neurons to the nascent synaptic layer in the mouse outer retina. Loss of ßII-spectrin disrupts positioning of neuronal processes, alters synaptic connectivity, and impairs visual function.

Canagliflozin Mitigates Acute Kidney Injury Secondary to Resuscitative Endovascular Balloon Occlusion of the Aorta in a Porcine Model of Hemorrhagic Shock.

OBJECTIVE: We investigated the potential of acute canagliflozin administration to mitigate acute kidney injury (AKI) and attenuate deleterious pro-inflammatory cytokine release in a clinically relevant swine model of severe renal ischemia reperfusion injury (IRI) induced by hemorrhage and aortic occlusion. BACKGROUND: Long-term canagliflozin use attenuates renal function decline and reduces AKI in diabetes mellitus and heart failure patients. Whilst several reports indicate prophylactic SGLT2 inhibition prevents AKI in IRI, the efficacy of acute administration on IRI and inflammation is not known. METHODS: Female swine (n=16) underwent controlled hemorrhage of 25% blood volume, followed by 90 min of aortic occlusion at the level of the renal ostia (via Resuscitative Endovascular Balloon Occlusion of the Aorta). A single 300 mg dose of oral canagliflozin or vehicle (saline) was delivered 5 mins into aortic occlusion. Hemodynamic monitoring, markers of renal function (serum creatinine, blood urea nitrogen, proteinuria and urinary neutrophil gelatinase-associated lipocalin) and serum cytokine concentrations (including interleukins: IL-1RA, IL-6, IL-8, IL-10, IL-18; and Tumor necrosis factor alpha) were analyzed after IRI, and during a 6h critical care phase. RESULTS: Compared to controls, animals receiving canagliflozin had less severe AKI, improved creatinine clearance, reduced proteinuria, and significantly lower tubular damage as evidenced by histopathology and urinary NGAL. Furthermore, the pro-inflammatory cytokine IL-6 was markedly attenuated without reduction in anti-inflammatory cytokines (IL-1RA and IL-10). CONCLUSIONS: A single dose of canagliflozin administered shortly into ischemic insult mitigates AKI and attenuates harmful pro-inflammatory cytokine release following trauma or surgery. These findings suggest a potential novel therapeutic role for canagliflozin in mitigating the effects of renal IRI worthy of further investigation.

Cold Snare Resection in the Colorectum: When to Choose it, When to Avoid it, and How to Do it.

Cold snaring is now the preferred resection method for the majority of colorectal polyps encountered during colonoscopy. A key advantage of cold resection over resection utilizing electrocautery is a substantially lower risk of delayed hemorrhage. Cold snare resection is preferred for all lesions ≤ 10 mm and for non-dysplastic sessile serrated lesions of any size, but should be avoided when lesions have a significant risk of submucosal invasion or fibrosis. Cold snare resection can be considered for certain lesions 11-19 mm in size and some lateral spreading lesions ≥ 20 mm. This review discusses tips and techniques to optimize cold snare resection.

Hematopoietic stem cell gene therapy for the treatment of SYNGAP1-related non-specific intellectual disability.

BACKGROUND: Synaptic Ras GTPase activating protein 1 (SYNGAP1)-related non-specific intellectual disability is a neurodevelopmental disorder caused by an insufficient level of SynGAP1 resulting in a dysfunction of neuronal synapses and presenting with a wide array of clinical phenotypes. Hematopoietic stem cell gene therapy has the potential to deliver therapeutic levels of functional SynGAP1 to affected neurons upon transduction of hematopoietic stem and progenitor cells with a lentiviral vector. METHODS: As a novel approach toward the treatment of SYNGAP1, we have generated a lentiviral vector expressing a modified form of SynGAP1 for transduction of human CD34+ hematopoietic stem and progenitor cells. The gene-modified cells were then transplanted into adult immunodeficient SYNGAP1+/- heterozygous mice and evaluated for improvement of SYNGAP1-related clinical phenotypes. Expression of SynGAP1 was also evaluated in the brain tissue of transplanted mice. RESULTS: In our proof-of-concept study, we have demonstrated significant improvement of SYNGAP1-related phenotypes including an improvement in motor abilities observed in mice transplanted with the vector transduced cells because they displayed decreased hyperactivity in an open field assay and an increased latency to fall in a rotarod assay. An increased level of SynGAP1 was also detected in the brains of these mice. CONCLUSIONS: These early-stage results highlight the potential of this stem cell gene therapy approach as a treatment strategy for SYNGAP1.

Association of Endoscopist Colonoscopy Quality Measures With Follow-Up Colonoscopy Outcomes After Positive Stool Tests (Multitarget Stool DNA or Fecal Immunochemical Test): Retrospective Cross-Sectional Analysis of Data From the New Hampshire Colonoscopy Registry.

INTRODUCTION: Negative colonoscopies following positive stool tests could result from stool test characteristics or from the quality of endoscopist performance. We used New Hampshire Colonoscopy Registry data to examine the association between endoscopist detection rates and polyp yield in colonoscopies performed for positive fecal immunochemical test (FIT) or multitarget stool DNA (mt-sDNA) test to evaluate the degree to which positive stool tests followed by negative colonoscopy ("false positives") vary with endoscopist quality. In addition, we investigated the frequency of significant polyps in the subgroup of highest quality colonoscopies following positive stool tests. METHODS: We compared the frequencies of negative colonoscopies and of specific polyps following positive stool tests across quartiles of endoscopist adenoma detection rate (ADR) and clinically significant serrated polyp detection rate (CSSDR). RESULTS: Our sample included 864 mt-sDNA+ and 497 FIT+ patients. We found a significantly lower frequency of negative colonoscopies following positive stool tests among endoscopists with higher ADR and CSSDR, particularly in the 2 highest quartiles. In addition, detection of any adenoma after a positive stool test for endoscopists in the fourth ADR quartile was 63.3% (FIT+) and 62.8% (mt-sDNA+). Among endoscopists in the fourth CSSDR quartile, sessile serrated lesions were found in 29.2% of examinations following a positive mt-sDNA and in 13.5% following FIT+ examinations. DISCUSSION: The frequency of negative colonoscopies after positive stool tests was significantly higher in examinations performed by endoscopists with low ADR and CSSDR. Our results also suggest a benchmark target of at least 40% for ADR in patients with mt-sDNA+ or FIT+ tests and 20% for sessile serrated lesions in mt-sDNA+ patients.

From starvation to time-restricted eating: a review of fasting physiology.

We have long known that subjects with obesity who fast for several weeks survive. Calculations that assume the brain can only use glucose indicated that all carbohydrate and protein sources would be consumed by the brain within several weeks yet subjects with obesity who fasted for several weeks survived. This anomaly led to the determination of the metabolic role of ketone bodies. Subsequent studies transformed our understanding of ketone bodies and illustrated the value of challenging the norm and adapting theory to evidence. Although prolonged fasting is no longer a treatment for obesity, the early studies of starvation provided valuable insights about macronutrient metabolism and ketone body adaptations that fasting elicits. Intermittent fasting and its variants such as time-restricted eating are fasting models that are far less regimented than starvation and severe calorie restriction; yet they produce metabolic benefits. The mechanisms that produce the metabolic changes that intermittent fasting elicits are relatively unknown. In this article, we review the physiology of starvation, starvation adaptation diets, diet-induced ketosis, and intermittent fasting. Understanding the premise and physiology that these regimens induce is necessary to draw parallels and provoke thoughts on the mechanisms underlying the metabolic benefits of intermittent fasting and its variants.

Does Olfactory Training Improve Brain Function and Cognition? A Systematic Review.

Olfactory training (OT), or smell training,consists of repeated exposure to odorants over time with the intended neuroplastic effect of improving or remediating olfactory functioning. Declines in olfaction parallel declines in cognition in various pathological conditions and aging. Research suggests a dynamic neural connection exists between olfaction and cognition. Thus, if OT can improve olfaction, could OT also improve cognition and support brain function? To answer this question, we conducted a systematic review of the literature to determine whether there is evidence that OT translates to improved cognition or altered brain morphology and connectivity that supports cognition. Across three databases (MEDLINE, Scopus, & Embase), 18 articles were identified in this systematic review. Overall, the reviewed studies provided emerging evidence that OT is associated with improved global cognition, and in particular, verbal fluency and verbal learning/memory. OT is also associated with increases in the volume/size of olfactory-related brain regions, including the olfactory bulb and hippocampus, and altered functional connectivity. Interestingly, these positive effects were not limited to patients with smell loss (i.e., hyposmia & anosmia) but normosmic (i.e., normal ability to smell) participants benefitted as well. Implications for practice and research are provided.

Cognitive Dysfunction in Non-CNS Metastatic Cancer: Comparing Brain Metastasis, Non-CNS Metastasis, and Healthy Controls.

Limited research has compared cognition of people with non-central nervous system metastatic cancer (NCM) vs. metastatic brain cancer (BM). This prospective cross-sectional study was comprised 37 healthy controls (HC), 40 NCM, and 61 BM completing 10 neuropsychological tests. The NCM performed below HCs on processing speed and executive functioning tasks, while the BM group demonstrated lower performance across tests. Tasks of processing speed, verbal fluency, and verbal memory differentiated the clinical groups (BM < NCM). Nearly 20% of the NCM group was impaired on at least three neuropsychological tests whereas approximately 40% of the BM group demonstrated the same level of impairment.

Organometallic Bridge Diversification of Bicyclo[1.1.1]pentanes.

Bicyclo[1.1.1]pentane (BCP) derivatives have attracted significant recent interest in drug discovery as alkyne, tert-butyl and arene bioisosteres, where their incorporation is frequently associated with increased compound solubility and metabolic stability. While strategies for functionalisation of the bridgehead (1,3) positions are extensively developed, platforms allowing divergent substitution at the bridge (2,4,5) positions remain limited. Recent reports have introduced 1-electron strategies for arylation and incorporation of a small range of other substituents, but are limited in terms of scope, yields or practical complexity. Herein, we show the synthesis of diverse 1,2,3-trifunctionalised BCPs through lithium-halogen exchange of a readily accessible BCP bromide. When coupled with medicinally relevant product derivatisations, our developed 2-electron "late stage" approach provides rapid and straightforward access to unprecedented BCP structural diversity (>20 hitherto-unknown motifs reported). Additionally, we describe a method for the synthesis of enantioenriched "chiral-at-BCP" bicyclo[1.1.1]pentanes through a novel stereoselective bridgehead desymmetrisation.

Association between Colonoscopy Sedation Type and Polyp Detection: A Registry-based Cohort Study.

BACKGROUND: Colorectal cancer is a leading cause of cancer-related death. Adenomas and serrated polyps are precursors of colorectal cancer, with serrated polyps being more difficult to detect during colonoscopy. The relationship between propofol use and polyp detection remains unclear. The authors investigated the association of propofol-based versus mild-moderate sedation on adenoma and serrated polyp detection during colonoscopy. METHODS: This retrospective cohort study used observational data from the New Hampshire Colonoscopy Registry. Patients aged greater than 50 yr with screening or surveillance colonoscopies between January 1, 2015, and February 28, 2020, were included. Exclusions were diagnostic examinations, no sedation, missing pathology data, and poor bowel preparation. Multivariate logistic regression was used to evaluate differences in polyp detection between propofol and moderate sedation in the full sample while adjusting for covariates. Propensity score adjustment and clustering at the endoscopist level were used in a restricted sample analysis that included endoscopists and facilities with between 5% and 95% propofol sedation use. RESULTS: A total of 54,063 colonoscopies were analyzed in the full sample and 18,998 in the restricted sample. Serrated polyp prevalence was significantly higher using propofol (9,957 of 29,312; 34.0% [95% CI, 33.4 to 34.5%]) versus moderate sedation (6,066 of 24,751; 24.5% [95% CI, 24.0 to 25.1%]) in the full sample and restricted samples (1,410 of 4,661; 30.3% [95% CI, 28.9 to 31.6%] vs. 3,690 of 14,337; 25.7% [95% CI, 25.0 to 26.5%]). In the full sample multivariate logistic regression, propofol was associated with higher neoplasm (adjusted odds ratio, 1.25 [95% CI, 1.21 to 1.29]), adenoma (odds ratio, 1.07 [95% CI, 1.03 to 1.11]), and serrated polyp detection (odds ratio, 1.51 [95% CI, 1.46 to 1.57]). In the restricted sample using inverse probability of treatment weighted propensity score adjustment and clustering at the endoscopist level, an attenuated but statistically significant effect size was observed for serrated polyps (odds ratio, 1.13 [95% CI, 1.07 to 1.19]), but not for adenomas (odds ratio, 1.00 [95% CI, 0.95 to 1.05]) or any neoplastic lesion (odds ratio, 1.03 [95% CI, 0.98 to 1.08]). CONCLUSIONS: Propofol sedation during colonoscopy may be associated with improved detection of serrated polyps, but not adenomas.

Expert endoscopist assessment of colorectal polyp size using virtual scale endoscopy, visual or snare-based estimation: a prospective video-based study.

BACKGROUND AND AIMS: Accurate polyp size estimation during colonoscopy has an impact on clinical decision-making. A laser-based virtual scale endoscope (VSE) is available to allow measuring polyp size using a virtual adaptive scale. This study evaluates video-based polyp size measurement accuracy among expert endoscopists using either VSE or visual assessment (VA) with either snare as reference size or without any reference size information. METHODS: A prospective, video-based study was conducted with 10 expert endoscopists. Video sequences from 90 polyps with known reference size (fresh specimen measured using calipers) were distributed on three different slide sets so that each slide set showed the same polyp only once with either VSE, VA or snare-based information. A slide set was randomly assigned to each endoscopist. Endoscopists were asked to provide size estimation based on video review. RESULTS: Relative accuracies for VSE, VA, and snare-based estimation were 75.1% (95% CI [71.6-78.5]), 65.0% (95% CI [59.5-70.4]) and 62.0% (95% CI [54.8-69.0]), respectively. VSE yielded significantly higher relative accuracy compared to VA (p = 0.002) and to snare (p = 0.001). A significantly lower percentage of polyps 1-5 mm were misclassified as >5 mm using VSE versus VA and snare (6.52% vs. 19.6% and 17.5%, p = 0.004) and a significantly lower percentage of polyps >5 mm were misclassified as 1-5 mm using VSE versus VA and snare (11.4% vs. 31.9% and 14.9%, p = 0.038). CONCLUSIONS: Endoscopists estimate polyp size with the highest accuracy when virtual adaptive scale information is displayed. Using a snare to assist sizing did not improve measurement accuracy compared to displaying visual information alone.

Virtual Interviews in the Post-COVID-19 Emergency Era: Insights from the Gastroenterology Fellowship Applicants and Programs.

BACKGROUND: Virtual interviews are still recommended for fellowship applications, 3 years after the beginning of the COVID-19 pandemic. Improving equity by reducing the cost for the applicants has been the most important reason for continuing virtual interviews. However, some argue that important information may be missed in a virtual setting. Our objective was to assess the perspective of Gastroenterology (GI) fellowship interviewers and applicants toward virtual interviews. METHODS: We designed two different anonymous surveys directed at GI programs and GI applicants who were interviewed for GI fellowship programs from 2020 to 2022 and matched to a GI program. Survey links were emailed to the Program Directors (PDs) and Program Coordinators via the AGA listserv starting in January 2023. A descriptive analysis was performed using Excel, and Fisher's exact tests were performed using R version 4.3.1. RESULTS: Sixty-one applicants and 79 interviewers responded to our survey. More than 80% of applicants strongly agreed (n = 36; 59%) and agreed (n = 14; 23%) that they would prefer in-person interviews if money was not an issue. When applicants were asked about the interview format in order of their preference, "in-person, hybrid, virtual" was the most popular answer (n = 16; 26.2%). Most interviewers (n = 47; 59.5%) do not prefer virtual interviews over in-person interviews. Furthermore, some interviewers were rarely able to judge the applicants' interpersonal (n = 17; 21.5%) and ethical skills (n = 16; 20.3%). These results differed according to the type of interviewer (p = 0.013 and 0.018, respectively). CONCLUSION: Based on our survey, most programs still prefer in-person interviews. Despite the several advantages of virtual interviews, the majority of applicants would prefer an in-person setting if the financial burden was not a factor. Nonetheless, many applicants think that the cost savings outweigh all the disadvantages associated with virtual interviews. The lack of empathy, personal connections, and engagement may impact the ability of interviewers to judge and ultimately rank a candidate. The virtual interview is here to stay, and we need input from the applicants and the interviewers to make the process more productive.

Ferroptosis, Inflammation, and Microbiome Alterations in the Intestine in the Göttingen Minipig Model of Hematopoietic-Acute Radiation Syndrome.

Hematopoietic acute radiation syndrome (H-ARS) involves injury to multiple organ systems following total body irradiation (TBI). Our laboratory demonstrated that captopril, an angiotensin-converting enzyme inhibitor, mitigates H-ARS in Göttingen minipigs, with improved survival and hematopoietic recovery, as well as the suppression of acute inflammation. However, the effects of captopril on the gastrointestinal (GI) system after TBI are not well known. We used a Göttingen minipig H-ARS model to investigate captopril's effects on the GI following TBI (60Co 1.79 or 1.80 Gy, 0.42-0.48 Gy/min), with endpoints at 6 or 35 days. The vehicle or captopril (0.96 mg/kg) was administered orally twice daily for 12 days, starting 4 h post-irradiation. Ilea were harvested for histological, protein, and RNA analyses. TBI increased congestion and mucosa erosion and hemorrhage, which were modulated by captopril. GPX-4 and SLC7A11 were downregulated post-irradiation, consistent with ferroptosis at 6 and 35 days post-irradiation in all groups. Interestingly, p21/waf1 increased at 6 days in vehicle-treated but not captopril-treated animals. An RT-qPCR analysis showed that radiation increased the gene expression of inflammatory cytokines IL1B, TNFA, CCL2, IL18, and CXCL8, and the inflammasome component NLRP3. Captopril suppressed radiation-induced IL1B and TNFA. Rectal microbiome analysis showed that 1 day of captopril treatment with radiation decreased overall diversity, with increased Proteobacteria phyla and Escherichia genera. By 6 days, captopril increased the relative abundance of Enterococcus, previously associated with improved H-ARS survival in mice. Our data suggest that captopril mitigates senescence, some inflammation, and microbiome alterations, but not ferroptosis markers in the intestine following TBI.

Functional rescue in an Angelman syndrome model following treatment with lentivector transduced hematopoietic stem cells.

Angelman syndrome (AS) is a rare neurodevelopmental disorder characterized by impaired communication skills, ataxia, motor and balance deficits, intellectual disabilities, and seizures. The genetic cause of AS is the neuronal loss of UBE3A expression in the brain. A novel approach, described here, is a stem cell gene therapy which uses lentivector-transduced hematopoietic stem and progenitor cells to deliver functional UBE3A to affected cells. We have demonstrated both the prevention and reversal of AS phenotypes upon transplantation and engraftment of human CD34+ cells transduced with a Ube3a lentivector in a novel immunodeficient Ube3amat-/pat+ IL2rg-/y mouse model of AS. A significant improvement in motor and cognitive behavioral assays as well as normalized delta power measured by electroencephalogram was observed in neonates and adults transplanted with the gene modified cells. Human hematopoietic profiles observed in the lymphoid organs by detection of human immune cells were normal. Expression of UBE3A was detected in the brains of the adult treatment group following immunohistochemical staining illustrating engraftment of the gene-modified cells expressing UBE3A in the brain. As demonstrated with our data, this stem cell gene therapy approach offers a promising treatment strategy for AS, not requiring a critical treatment window.

Updates on Age to Start and Stop Colorectal Cancer Screening: Recommendations From the U.S. Multi-Society Task Force on Colorectal Cancer.

This document is a focused update to the 2017 colorectal cancer (CRC) screening recommendations from the U.S. Multi-Society Task Force on Colorectal Cancer, which represents the American College of Gastroenterology, the American Gastroenterological Association, and the American Society for Gastrointestinal Endoscopy. This update is restricted to addressing the age to start and stop CRC screening in average-risk individuals and the recommended screening modalities. Although there is no literature demonstrating that CRC screening in individuals under age 50 improves health outcomes such as CRC incidence or CRC-related mortality, sufficient data support the U.S. Multi-Society Task Force to suggest average-risk CRC screening begin at age 45. This recommendation is based on the increasing disease burden among individuals under age 50, emerging data that the prevalence of advanced colorectal neoplasia in individuals ages 45 to 49 approaches rates in individuals 50 to 59, and modeling studies that demonstrate the benefits of screening outweigh the potential harms and costs. For individuals ages 76 to 85, the decision to start or continue screening should be individualized and based on prior screening history, life expectancy, CRC risk, and personal preference. Screening is not recommended after age 85.

Diagnosis and Management of Cancer Risk in the Gastrointestinal Hamartomatous Polyposis Syndromes: Recommendations From the US Multi-Society Task Force on Colorectal Cancer.

The gastrointestinal hamartomatous polyposis syndromes are rare, autosomal dominant disorders associated with an increased risk of benign and malignant intestinal and extraintestinal tumors. They include Peutz-Jeghers syndrome, juvenile polyposis syndrome, the PTEN hamartoma tumor syndrome (including Cowden's syndrome and Bannayan-Riley-Ruvalcaba syndrome), and hereditary mixed polyposis syndrome. Diagnoses are based on clinical criteria and, in some cases, confirmed by demonstrating the presence of a germline pathogenic variant. The best understood hamartomatous polyposis syndrome is Peutz-Jeghers syndrome, caused by germline pathogenic variants in the STK11 gene. The management is focused on prevention of bleeding and mechanical obstruction of the small bowel by polyps and surveillance of organs at increased risk for cancer. Juvenile polyposis syndrome is caused by a germline pathogenic variant in either the SMAD4 or BMPR1A genes, with differing clinical courses. Patients with SMAD4 pathogenic variants may have massive gastric polyposis, which can result in gastrointestinal bleeding and/or protein-losing gastropathy. Patients with SMAD4 mutations usually have the simultaneous occurrence of hereditary hemorrhagic telangiectasia (juvenile polyposis syndrome-hereditary hemorrhagic telangiectasia overlap syndrome) that can result in epistaxis, gastrointestinal bleeding from mucocutaneous telangiectasias, and arteriovenous malformations. Germline pathogenic variants in the PTEN gene cause overlapping clinical phenotypes (known as the PTEN hamartoma tumor syndromes), including Cowden's syndrome and related disorders that are associated with an increased risk of gastrointestinal and colonic polyposis, colon cancer, and other extraintestinal manifestations and cancers. Due to the relative rarity of the hamartomatous polyposis syndromes, recommendations for management are based on few studies. This U.S Multi-Society Task Force on Colorectal Cancer consensus statement summarizes the clinical features, assesses the current literature, and provides guidance for diagnosis, assessment, and management of patients with the hamartomatous polyposis syndromes, with a focus on endoscopic management.

Performing High-Quality, Safe, Cost-Effective, and Efficient Basic Colonoscopy in 2023: Advice From Two Experts.

Based on published evidence and our expert experience, we provide recommendations to maximize the efficacy, safety, efficiency, and cost-effectiveness of routine colonoscopy. High-quality colonoscopy begins with colon preparation using a split or same-day dose and preferably a low-volume regimen for optimal patient tolerance and compliance. Successful cecal intubation can be achieved by choosing the correct colonoscope and using techniques to facilitate navigation through challenges such as severe angulations and redundant colons. Safety is a primary goal, and complications such as perforation and splenic rupture can be prevented by avoiding pushing through fixed resistance and avoiding loops in proximal colon. Furthermore, barotrauma can be avoided by converting to water filling only (no gas insufflation) in every patient with a narrowed, angulated sigmoid. Optimal polyp detection relies primarily on compulsive attention to inspection as manifested by adequate inspection time, vigorous probing of the spaces between haustral folds, washing and removing residual debris, and achieving full distention. Achieving minimum recommended adenoma detection rate thresholds (30% in men and 20% in women) is mandatory, and colonoscopists should aspire to adenoma detection rate approaching 50% in screening patients. Distal attachments can improve mucosal exposure and increase detection while shortening withdrawal times. Complete resection of polyps complements polyp detection in preventing colorectal cancer. Cold resection is the preferred method for all polyps < 10 mm. For effective cold resection, an adequate rim of normal tissue should be captured in the snare. Finally, cost-effective high-quality colonoscopy requires the procedure not be overused, as demonstrated by following updated United States Multi Society Task Force on Colorectal Cancer postpolypectomy surveillance recommendations.

Higher Serrated Polyp Detection Rates Are Associated With Lower Risk of Postcolonoscopy Colorectal Cancer: Data From the New Hampshire Colonoscopy Registry.

INTRODUCTION: We used New Hampshire Colonoscopy Registry data to examine the association between postcolonoscopy colorectal cancer (PCCRC) and sessile serrated detection rates (SSLDRs). METHODS: We included patients with either a colonoscopy or a CRC diagnosis in the NH State Cancer Registry. PCCRC was any CRC diagnosed ≥ 6 months after index examination. RESULTS: Of 26,901 patients, 162 were diagnosed with PCCRC. The hazard ratio for PCCRC was lowest for patients whose endoscopists had the highest SSLDR quintile (≥6%) (hazard ratio 0.29; 95% confidence interval 0.16-0.50). DISCUSSION: Endoscopists with higher SSLDRs had lower risks of PCCRC. These data validate SSLDR as a clinically relevant quality measure.