ABSTRACT
Spinal muscular atrophy (SMA) is a motor neuron disease caused by deficiency of the ubiquitous survival motor neuron (SMN) protein. To define the mechanisms of selective neuronal dysfunction in SMA, we investigated the role of SMN-dependent U12 splicing events in the regulation of motor circuit activity. We show that SMN deficiency perturbs splicing and decreases the expression of a subset of U12 intron-containing genes in mammalian cells and Drosophila larvae. Analysis of these SMN target genes identifies Stasimon as a protein required for motor circuit function. Restoration of Stasimon expression in the motor circuit corrects defects in neuromuscular junction transmission and muscle growth in Drosophila SMN mutants and aberrant motor neuron development in SMN-deficient zebrafish. These findings directly link defective splicing of critical neuronal genes induced by SMN deficiency to motor circuit dysfunction, establishing a molecular framework for the selective pathology of SMA.
Subject(s)
Disease Models, Animal , Drosophila Proteins/metabolism , Drosophila melanogaster/metabolism , Membrane Proteins/metabolism , Muscular Atrophy, Spinal/metabolism , RNA, Small Nuclear/metabolism , RNA-Binding Proteins/metabolism , Zebrafish Proteins/metabolism , Animals , Animals, Genetically Modified , Drosophila Proteins/genetics , Drosophila melanogaster/embryology , Humans , Membrane Proteins/genetics , Mice , NIH 3T3 Cells , Zebrafish , Zebrafish Proteins/geneticsABSTRACT
BACKGROUND & AIMS: Guidelines recommend use of risk stratification scores for patients presenting with gastrointestinal bleeding (GIB) to identify very-low-risk patients eligible for discharge from emergency departments. Machine learning models may outperform existing scores and can be integrated within the electronic health record (EHR) to provide real-time risk assessment without manual data entry. We present the first EHR-based machine learning model for GIB. METHODS: The training cohort comprised 2546 patients and internal validation of 850 patients presenting with overt GIB (ie, hematemesis, melena, and hematochezia) to emergency departments of 2 hospitals from 2014 to 2019. External validation was performed on 926 patients presenting to a different hospital with the same EHR from 2014 to 2019. The primary outcome was a composite of red blood cell transfusion, hemostatic intervention (ie, endoscopic, interventional radiologic, or surgical), and 30-day all-cause mortality. We used structured data fields in the EHR, available within 4 hours of presentation, and compared the performance of machine learning models with current guideline-recommended risk scores, Glasgow-Blatchford Score, and Oakland Score. Primary analysis was area under the receiver operating characteristic curve. Secondary analysis was specificity at 99% sensitivity to assess the proportion of patients correctly identified as very low risk. RESULTS: The machine learning model outperformed the Glasgow-Blatchford Score (area under the receiver operating characteristic curve, 0.92 vs 0.89; P < .001) and Oakland Score (area under the receiver operating characteristic curve, 0.92 vs 0.89; P < .001). At the very-low-risk threshold of 99% sensitivity, the machine learning model identified more very-low-risk patients: 37.9% vs 18.5% for Glasgow-Blatchford Score and 11.7% for Oakland Score (P < .001 for both comparisons). CONCLUSIONS: An EHR-based machine learning model performs better than currently recommended clinical risk scores and identifies more very-low-risk patients eligible for discharge from the emergency department.
ABSTRACT
BACKGROUND AND AIM: Idiopathic myointimal hyperplasia of the mesenteric veins (IMHMV) is an uncommon cause of colonic ischemia for which surgical treatment is typically curative. We describe clinical, radiologic, and endoscopic findings in IMHMV patients to provide clinicians with a framework for pre-surgical identification of this rare disease. METHODS: We performed a systematic review of seven databases for IMHMV cases and identified additional cases from Yale New Haven Hospital records. To identify features specifically associated with colonic ischemia due to IMHMV, we performed multivariate logistic regression analysis incorporating data from a large cohort of patients with biopsy-proven ischemic colitis. RESULTS: A total of 124 patients with IMHMV were identified (80% male, mean age 53 years, 56% Caucasian). Presenting symptoms were most commonly abdominal pain (86%) and diarrhea (68%). The most affected areas were the sigmoid colon (91%) and rectum (61%). Complications associated with diagnostic delay occurred in 29% of patients. Radiologic vascular abnormalities including non-opacification of the inferior mesenteric vein were observed in 35% of patients. Of the patients, 97% underwent curative surgical resection. Compared with non-IMHMV colonic ischemia, IMHMV was significantly associated with younger age, male sex, absence of rectal bleeding on presentation, rectal involvement, and mucosal ulcerations on endoscopy. CONCLUSION: IMHMV is a rare, underreported cause of colonic ischemia that predominantly involves the rectosigmoid. Our findings suggest younger age, rectal involvement, and absence of rectal bleeding as clinical features to help identify select patients presenting with colonic ischemia as having higher likelihood of IMHMV and therefore consideration of upfront surgical management.
Subject(s)
Colitis, Ischemic , Mesenteric Veins , Humans , Male , Middle Aged , Female , Hyperplasia/pathology , Mesenteric Veins/diagnostic imaging , Mesenteric Veins/surgery , Mesenteric Veins/pathology , Delayed Diagnosis/adverse effects , Colitis, Ischemic/pathology , Ischemia/pathologyABSTRACT
BACKGROUND: Hospital-based specialty-trained physicians have become more prevalent with emerging data suggesting benefit in consult and procedure volume, reduced complication rates, and increased practice productivity. Interest in gastroenterology (GI) hospitalist programs has increased in recent years. However, little is known regarding the types of GI hospitalist models that currently exist. AIMS: To characterize the infrastructure of GI hospitalist models across the USA. METHODS: A 50-question survey was distributed to the GI Hospitalist Special Interest Group of the American Society for Gastrointestinal Endoscopy. Information on demographics, hospital infrastructure, and compensation were collected. RESULTS: 31 of 33 (94%) GI hospitalists completed the questionnaire. Respondents were mostly male (65%), white (48%) or Asian (42%). Most GI hospitalists spent at least half of their clinical time dedicated to the inpatient consultation service (73%), during which they had no other clinical duties. Most services had endoscopy suites with dedicated inpatient endoscopy rooms (66%), over 4 h allotted for procedures (83%), and were available on weekends (62%). Over half of GI hospitalists reported having outpatient duties, the most common being performance of direct access endoscopy (69%). Outside of clinical responsibilities, GI hospitalists were most frequently involved in clinical education or fellowship program leadership (48%). Most GI hospitalists were salaried with an incentive-based bonus based on work relative value units. CONCLUSION: GI hospitalist programs are varied throughout the USA but key commonalities exist between most programs.
Subject(s)
Gastroenterology , Hospitalists , Humans , Male , United States , Female , Scope of Practice , Surveys and Questionnaires , HospitalsABSTRACT
BACKGROUND: Microangiopathic hemolytic anemia (MAHA) is a rare paraneoplastic syndrome that has been reported in patients with gastric signet ring cell carcinoma (SRCC). Clinical and prognostic features of MAHA in this setting have been poorly described. MATERIALS AND METHODS: We conducted a systematic review in 8 databases of gastric SRCC complicated by MAHA and performed a case-control study assessing factors associated with survival in patients with gastric SRCC and MAHA in our pooled cohort compared with age-, sex-, and stage-matched cases of gastric SRCC from the Surveillance, Epidemiology, and End Results (SEER) database. Descriptive analyses were performed and multivariable Cox-proportional hazards regression modeling was used to determine factors associated with overall survival. RESULTS: All identified patients (n = 47) were symptomatic at index presentation, commonly with back/bone pain, and dyspnea. Microangiopathic hemolytic anemia was the first manifestation of gastric SRCC in 94% of patients. Laboratory studies were notable for anemia (median 7.7 g/dL), thrombocytopenia (median 45.5 × 103/µL), and hyperbilirubinemia (median 2.3 mg/dL). All patients with MAHA had metastatic disease at presentation, most often to the bone, bone marrow, and lymph nodes. Median survival in patients with gastric SRCC and MAHA was significantly shorter than a matched SEER-derived cohort with metastatic gastric SRCC (7 weeks vs 28 weeks, P < .01). In multivariate analysis, patients with MAHA were at significantly increased risk of mortality (HR 3.28, 95% CI 2.11-5.12). CONCLUSION: Microangiopathic hemolytic anemia is a rare, late-stage complication of metastatic gastric SRCC and is associated with significantly decreased survival compared with metastatic gastric SRCC alone.
Subject(s)
Anemia, Hemolytic , Carcinoma, Signet Ring Cell , Stomach Neoplasms , Anemia, Hemolytic/complications , Carcinoma, Signet Ring Cell/complications , Carcinoma, Signet Ring Cell/pathology , Case-Control Studies , Humans , Prognosis , Stomach Neoplasms/pathologyABSTRACT
BACKGROUND & AIMS: Glycogenic hepatopathy (GH) in type 1 diabetes-mellitus (T1DM) is characterized by hepatomegaly and perturbations of liver chemistries (LC) that have not been well studied. Furthermore, misdiagnosis with other hepatic complications of T1DM, such as nonalcoholic fatty liver disease, has been described. We perform a systematic review of biopsy-proven GH reports in T1DM patients to identify LC patterns. METHODS: A systematic review identified reports of biopsy-proven GH in patients with T1DM. We excluded GH with other liver diseases, Mauriac syndrome, or GH without T1DM. Two reviewers screened and extracted studies and assessed their methodological quality. LC elevation magnitude, AST-to-ALT ratio, R-ratio to designate hepatocellular, cholestatic or mixed pattern of hepatic injury, and evolution of transaminases after glycemic control were analyzed. RESULTS: A total of 192 patients were included, with median age of 20 years, 73% adults, 66% females, median duration of T1DM before diagnosis 10 years, median adult body mass index 21 kg/m2 , median HbA1c 12%, at least one episode of diabetic ketoacidosis 70%, and hepatomegaly 92%. ALT and AST showed moderate-to-severe elevation in 78% and 76%, respectively, AST/ALT >1 in 71% and hepatocellular to mixed pattern of hepatic injury in 81%. Transaminase improvement with glycemic control was the rule, regardless of other factors in multilinear regression analysis. CONCLUSION: GH tends to have AST-predominant elevation with a median of 13 times the upper normal limit and R-ratio >2, which may distinguish it from other etiologies of AST-predominant LC elevation, and in the appropriate clinical context, may obviate invasive tests.
Subject(s)
Diabetes Mellitus, Type 1 , Liver Diseases , Adult , Diabetes Mellitus, Type 1/complications , Female , Glycogen , Hepatomegaly/etiology , Humans , Male , Young AdultABSTRACT
BACKGROUND & AIMS: Although transient elastography (TE) is used to determine liver stiffness as a surrogate to hepatic fibrosis, the normal range in children is not well defined. We performed a systematic review and individual participant data (IPD) meta-analysis to determine the range of liver stiffness in healthy children and evaluate the influence of important biological parameters. METHODS: We pooled data from 10 studies that examined healthy children using TE. We divided 1702 children into two groups: ≥3 years (older group) and < 3 years of age (younger group). Univariate and multivariate linear regression models predicting liver stiffness were conducted. RESULTS: After excluding children with obesity, diabetes, or abnormal liver tests, 652 children were analysed. Among older children, mean liver stiffness was 4.45 kPa (95% confidence interval 4.34-4.56), and increased liver stiffness was associated with age, sedation status, and S probe use. In the younger group, the mean liver stiffness was 4.79 kPa (95% confidence interval 4.46-5.12), and increased liver stiffness was associated with sedation status and Caucasian race. In a subgroup analysis, hepatic steatosis on ultrasound was significantly associated with increased liver stiffness. We define a reference range for normal liver stiffness in healthy children as 2.45-5.56 kPa. CONCLUSIONS: We have established TE-derived liver stiffness ranges for healthy children and propose an upper limit of liver stiffness in healthy children to be 5.56 kPa. We have identified increasing age, use of sedation, probe size, and presence of steatosis on ultrasound as factors that can significantly increase liver stiffness.
Subject(s)
Elasticity Imaging Techniques , Fatty Liver , Adolescent , Child , Humans , Liver/diagnostic imaging , Liver Cirrhosis/diagnostic imaging , Reference ValuesABSTRACT
Recent studies have reported higher rates of hepatocellular carcinoma (HCC) in individuals treated with direct-acting antivirals (DAAs). However, making definitive conclusions has been challenging because of the heterogeneous populations and methodologies of these reports. We investigated whether DAA use is associated with higher rates of incident HCC compared to treatment with interferon (IFN)-based regimens. We performed a retrospective, population-based cohort study using the Electronically Retrieved Cohort of HCV Infected Veterans (ERCHIVES) database. In a cohort of 17,836 persons, sustained virological response (SVR) was achieved by 66.6% and 96.2% of the IFN and DAA groups, respectively. Among all treated persons, risk of HCC was not higher in the DAA group compared to the IFN group (hazard ratio, 1.07; 95% confidence interval, 0.55, 2.08). Among persons with cirrhosis who achieved SVR, neither the HCC incidence rate nor HCC-free survival were significantly different in the DAA group compared to the IFN group (21.2 vs. 22.8 per 1,000 person-years; P = 0.78 and log-rank P = 0.17, respectively). Untreated persons with cirrhosis had a significantly higher HCC incidence rate (45.3 per 1,000 person-years) compared to those treated with either IFN or DAAs (P = 0.03). Both groups of treated persons had significantly lower probability of HCC development compared to untreated persons (log-rank, P = 0.0004). CONCLUSION: DAA treatment is not associated with a higher risk of HCC in persons with cirrhosis with chronic HCV infection in the short term. Previously reported higher rates of HCC associated with DAA treatment may be explained by both the presence of relatively fewer baseline HCC risk factors in persons treated with IFN as well as selection bias, given that DAA regimens were used to treat persons at higher risk for developing HCC. (Hepatology 2018;67:2244-2253).
Subject(s)
Antiviral Agents/therapeutic use , Carcinoma, Hepatocellular/epidemiology , Hepatitis C, Chronic/drug therapy , Liver Neoplasms/epidemiology , Carcinoma, Hepatocellular/chemically induced , Carcinoma, Hepatocellular/complications , Cohort Studies , Female , Hepatitis C, Chronic/complications , Humans , Incidence , Interferons/therapeutic use , Liver Neoplasms/chemically induced , Liver Neoplasms/complications , Male , Middle Aged , Retrospective Studies , Sustained Virologic Response , Time FactorsABSTRACT
BACKGROUND: Cerebrospinal fluid ascites is a rare complication of ventriculoperitoneal shunting and is the result of infection and subsequent peritonitis in the majority of cases. Sterile cerebrospinal fluid ascites in which no known infectious etiology is identified, is even more unusual. CASE PRESENTATION: A 26-year-old female with Loeys-Dietz syndrome and congenital hydrocephalus treated with a ventriculoperitoneal shunt, was evaluated after developing new-onset ascites of unclear etiology after abdominal surgery for repair of an aortic aneurysm requiring multiple therapeutic paracenteses. Her serum ascites albumin gradient (SAAG) was greater than 1.1, suggestive of a portal hypertensive etiology. Gram stain as well as multiple cultures of her ascites fluid were both negative. Extensive investigation including hepatic venous portal gradient measurement and liver biopsy revealed no evidence of hepatic disease or portal hypertension. She was ultimately found to have sterile cerebrospinal fluid ascites which was treated successfully with a peritoneovenous shunt. CONCLUSION: Sterile cerebrospinal fluid ascites is a rare clinical entity that has only been reported approximately 50 times in the medical literature. In this report, we also highlight it as a rare cause of high SAAG ascites. Moreover, we describe the use of a peritoneovenous shunt as a novel therapeutic option in the management of this condition.
Subject(s)
Ascites/etiology , Ventriculoperitoneal Shunt/adverse effects , Adult , Ascites/diagnosis , Ascites/therapy , Ascitic Fluid/metabolism , Female , Humans , Hydrocephalus/therapy , Loeys-Dietz Syndrome , Peritoneovenous Shunt , Serum Albumin/metabolismABSTRACT
At the post-transcriptional level, expression of protein-coding genes is controlled by a series of RNA regulatory events including nuclear processing of primary transcripts, transport of mature mRNAs to specific cellular compartments, translation and ultimately, turnover. These processes are orchestrated through the dynamic association of mRNAs with RNA binding proteins and ribonucleoprotein (RNP) complexes. Accurate formation of RNPs in vivo is fundamentally important to cellular development and function, and its impairment often leads to human disease. The survival motor neuron (SMN) protein is key to this biological paradigm: SMN is essential for the biogenesis of various RNPs that function in mRNA processing, and genetic mutations leading to SMN deficiency cause the neurodegenerative disease spinal muscular atrophy. Here we review the expanding role of SMN in the regulation of gene expression through its multiple functions in RNP assembly. We discuss advances in our understanding of SMN activity as a chaperone of RNPs and how disruption of SMN-dependent RNA pathways can cause motor neuron disease.
Subject(s)
Gene Expression Regulation , Motor Neuron Disease/metabolism , Motor Neurons/metabolism , Ribonucleoproteins/metabolism , SMN Complex Proteins/metabolism , Animals , Humans , Models, Genetic , Motor Neuron Disease/genetics , RNA Splicing , RNA Stability , Ribonucleoproteins/genetics , SMN Complex Proteins/geneticsABSTRACT
BACKGROUND: Clinical activity and quality of life (QOL) indices assess disease activity in Crohn's disease (CD) and ulcerative colitis (UC). However, a paucity of data exists on the validity of these indices according to disease characteristics. AIMS: To examine the correlation between QOL and clinical activity indices and endoscopic disease activity according to disease characteristics. METHODS: We used a prospective registry to identify CD and UC patients ≥18 years old with available information on Short Inflammatory Bowel Disease Questionnaire scores (SIBDQ), Harvey-Bradshaw Index (HBI) and simple endoscopic scores for CD (SES-CD), and Simple Clinical Colitis Activity Index (SCCAI) and Mayo endoscopic score for UC. We used Spearman rank correlations to calculate correlations between indices and Fisher transformation to compare correlations across disease characteristics. RESULTS: Among 282 CD patients, we observed poor correlation between clinical activity and QOL indices to SES-CD with no differences in correlation according to disease characteristics. Conversely, among 226 UC patients, clinical activity and QOL had good correlation to Mayo endoscopic score (r = 0.55 and -0.56, respectively) with better correlations observed with left-sided versus extensive colitis (r = 0.73 vs. 0.45, p = 0.005) and shorter duration of disease (r = 0.61 vs. 0.37, p = 0.04). CONCLUSIONS: Our data suggest good correlation between SCCAI and endoscopic disease activity in UC, particularly in left-sided disease. Poor correlations between HBI or SIBDQ and SES-CD appear to be consistent across different disease phenotypes.
Subject(s)
Colitis, Ulcerative/physiopathology , Crohn Disease/physiopathology , Quality of Life , Registries , Adult , Colitis, Ulcerative/pathology , Crohn Disease/pathology , Endoscopy, Digestive System , Female , Humans , Male , Middle Aged , Phenotype , Reproducibility of Results , Severity of Illness Index , Surveys and Questionnaires , Young AdultABSTRACT
Spinal muscular atrophy (SMA) is caused by mutations of the survival motor neuron 1 (SMN1) gene, retention of the survival motor neuron 2 (SMN2) gene and insufficient expression of full-length survival motor neuron (SMN) protein. Quinazolines increase SMN2 promoter activity and inhibit the ribonucleic acid scavenger enzyme DcpS. The quinazoline derivative RG3039 has advanced to early phase clinical trials. In preparation for efficacy studies in SMA patients, we investigated the effects of RG3039 in severe SMA mice. Here, we show that RG3039 distributed to central nervous system tissues where it robustly inhibited DcpS enzyme activity, but minimally activated SMN expression or the assembly of small nuclear ribonucleoproteins. Nonetheless, treated SMA mice showed a dose-dependent increase in survival, weight and motor function. This was associated with improved motor neuron somal and neuromuscular junction synaptic innervation and function and increased muscle size. RG3039 also enhanced survival of conditional SMA mice in which SMN had been genetically restored to motor neurons. As this systemically delivered drug may have therapeutic benefits that extend beyond motor neurons, it could act additively with SMN-restoring therapies delivered directly to the central nervous system such as antisense oligonucleotides or gene therapy.
Subject(s)
Endoribonucleases/antagonists & inhibitors , Motor Neurons/drug effects , Muscular Atrophy, Spinal/physiopathology , Quinazolines/pharmacology , Ribonucleoproteins, Small Nuclear/metabolism , Survival of Motor Neuron 1 Protein/metabolism , Animals , Central Nervous System/drug effects , Central Nervous System/metabolism , Disease Models, Animal , Dose-Response Relationship, Drug , Drug Evaluation, Preclinical , Humans , Mice , Mice, Transgenic , Motor Neurons/physiology , Muscles/drug effects , Muscles/metabolism , Muscular Atrophy, Spinal/drug therapy , Muscular Atrophy, Spinal/genetics , Muscular Atrophy, Spinal/metabolism , Neuromuscular Junction/drug effects , Neuromuscular Junction/physiology , Quinazolines/administration & dosage , Quinazolines/pharmacokinetics , Survival of Motor Neuron 2 Protein/genetics , Survival of Motor Neuron 2 Protein/metabolism , Synaptic TransmissionABSTRACT
Hepatocellular carcinoma (HCC) is one of the leading causes of cancer-related death in the world. Infection with hepatitis C virus (HCV) represents one of the most common risk factors for HCC development, and cases of HCV-related complications have been rising over the last 2 decades. Although the standard for HCV therapy has been interferon (IFN)-based for many years, the therapeutic revolution spurred by the development of direct-acting antivirals (DAAs) promises to usher in a new era in which chronic HCV becomes a rare disease. On the basis of long-term follow-up of patients experiencing IFN-based sustained virological responses (SVRs), it can be expected that rates of HCV-associated HCC will decrease significantly after the widespread adoption of DAAs, but there remains a persistent risk for HCC even among some patients with advanced fibrosis who have achieved SVR. As such, individuals treated for HCV with advanced fibrosis should continue to be screened regularly for HCC after SVR. Furthermore, as the population of SVR patients grows, it will become imperative to accurately identify those individuals at high risk for developing HCC, appropriately allocate resources for screening, and consider cost-effective chemopreventive strategies. Risk factors include preexisting advanced fibrosis/cirrhosis, older age, diabetes mellitus, and ethanol use. In addition, laboratory biomarkers and genetic signatures are currently being identified that not only predict the likelihood of HCC development in SVR patients but also may serve as dynamic indicators of therapeutic response.
Subject(s)
Antiviral Agents/therapeutic use , Carcinoma, Hepatocellular/prevention & control , Hepatitis C, Chronic/drug therapy , Liver Neoplasms/prevention & control , Animals , Carcinoma, Hepatocellular/virology , Humans , Liver Neoplasms/virology , Risk Factors , Risk Reduction BehaviorABSTRACT
Multidrug resistance (MDR) is a serious complication during treatment of opportunistic fungal infections that frequently afflict immunocompromised individuals, such as transplant recipients and cancer patients undergoing cytotoxic chemotherapy. Improved knowledge of the molecular pathways controlling MDR in pathogenic fungi should facilitate the development of novel therapies to combat these intransigent infections. MDR is often caused by upregulation of drug efflux pumps by members of the fungal zinc-cluster transcription-factor family (for example Pdr1p orthologues). However, the molecular mechanisms are poorly understood. Here we show that Pdr1p family members in Saccharomyces cerevisiae and the human pathogen Candida glabrata directly bind to structurally diverse drugs and xenobiotics, resulting in stimulated expression of drug efflux pumps and induction of MDR. Notably, this is mechanistically similar to regulation of MDR in vertebrates by the PXR nuclear receptor, revealing an unexpected functional analogy of fungal and metazoan regulators of MDR. We have also uncovered a critical and specific role of the Gal11p/MED15 subunit of the Mediator co-activator and its activator-targeted KIX domain in antifungal/xenobiotic-dependent regulation of MDR. This detailed mechanistic understanding of a fungal nuclear receptor-like gene regulatory pathway provides novel therapeutic targets for the treatment of multidrug-resistant fungal infections.
Subject(s)
Candida glabrata/metabolism , Drug Resistance, Fungal , Fungal Proteins/metabolism , Gene Expression Regulation, Fungal , Receptors, Steroid/metabolism , Saccharomyces cerevisiae/metabolism , Animals , Antifungal Agents/metabolism , Antifungal Agents/pharmacology , Candida glabrata/drug effects , Candida glabrata/genetics , DNA-Binding Proteins/chemistry , DNA-Binding Proteins/genetics , DNA-Binding Proteins/metabolism , Drug Resistance, Fungal/genetics , Fungal Proteins/chemistry , Fungal Proteins/genetics , Gene Expression Regulation, Fungal/genetics , Genes, Fungal/genetics , Mediator Complex , Multigene Family , Pregnane X Receptor , Protein Structure, Tertiary , Saccharomyces cerevisiae/drug effects , Saccharomyces cerevisiae/genetics , Saccharomyces cerevisiae Proteins/chemistry , Saccharomyces cerevisiae Proteins/genetics , Saccharomyces cerevisiae Proteins/metabolism , Trans-Activators/chemistry , Trans-Activators/genetics , Trans-Activators/metabolism , Transcription Factors/metabolism , Transcription, Genetic/genetics , Xenobiotics/metabolismABSTRACT
Background: Colonoscopy withdrawal time (CWT) of at least 6-9 minutes is the minimum time needed for adequate adenoma detection in the general population. The ideal CWT in patients with inflammatory bowel disease (IBD) has not been determined. We aimed to identify the optimal CWT associated with the detection of visible dysplasia in patients with IBD. Methods: This is a retrospective study from 1/1/2017 to 9/1/2022 of adult patients with IBD in endoscopic healing undergoing surveillance via high-definition white light colonoscopy. The primary outcome was the association of CWT with visible dysplasia detection. Results: A total of 259 patients (mean age 56â ±â 14.8 years; 51.3% female, 68% with ulcerative colitis; 8.9% with primary sclerosing cholangitis) underwent 330 colonoscopies. Patients with visible dysplasia were more likely to be older (Pâ <â .001) and have a personal history of visible dysplasia (Pâ <â .001) and invisible dysplasia (Pâ =â .023). The mean CWT was significantly longer in the visible dysplasia group at 26 minutes (interquartile range [IQR] 20-38.5) vs. 21 minutes (IQR 15-28) in procedures without visible dysplasia (Pâ <â .001). On multivariable analysis, increased age (Pâ <â .001), increased CWT (Pâ =â .001), and personal history of visible dysplasia (Pâ =â .013) were independently associated with the detection of visible dysplasia. A CWT of ≥15 minutes (odds ratio [OR] 2.71; 95% confidence interval [CI], 1.11-6.6; Pâ =â .02] and not ≥9 minutes (OR 2.57; 95% CI, 0.33-20.2; Pâ =â .35) is significantly associated with detection of visible dysplasia. Conclusions: For patients with IBD undergoing surveillance via high-definition white light colonoscopy, the mean CWT was independently associated with the detection of visible dysplasia.
ABSTRACT
BACKGROUND: Recent guidelines do not recommend routine use of aspirin for primary cardiovascular prevention (ppASA) and suggest avoidance of ppASA in older individuals due to bleeding risk. However, ppASA is frequently taken without an appropriate indication. Estimates of the incidence of upper gastrointestinal bleeding due to ppASA in the United States are lacking. In this study, we provide national estimates of upper gastrointestinal bleeding incidence, characteristics, and costs in ppASA users from 2016-2020. METHODS: Primary cardiovascular prevention users (patients on long-term aspirin therapy without cardiovascular disease) presenting with upper gastrointestinal bleeding were identified in the Nationwide Emergency Department Sample using International Statistical Classification of Diseases and Related Health Problems, 10th revision codes. Trends in upper gastrointestinal bleeding incidence, etiology, severity, associated Medicare reimbursements, and the impact of ppASA on bleeding outcomes were assessed with regression models. RESULTS: From 2016-2020, adjusted incidence of upper gastrointestinal bleeding increased 29.2% among ppASA users, with larger increases for older patients (increase of 41.6% for age 65-74 years and 36.0% for age ≥75 years). The most common etiology among ppASA users was ulcer disease but increases in bleeding incidence due to angiodysplasias were observed. The proportion of hospitalizations with major complications or comorbidities increased 41.5%, and Medicare reimbursements increased 67.6%. Among patients without cardiovascular disease, ppASA was associated with increased odds of hospital admission, red blood cell transfusion, and endoscopic intervention as compared to no ppASA use. CONCLUSIONS: Considering recent guideline recommendations, the rising incidence, severity, and costs associated with upper gastrointestinal bleeding among patients on ppASA highlights the importance of careful assessment for appropriate ppASA use.