Obesity Is Associated with Altered Rectal Sensitivity in Chronic Constipation.

BACKGROUND: Defecation dysfunction may contribute to chronic constipation (CC), but the impact of obesity on anorectal physiology in CC remains unclear. We aimed to evaluate the relationship between obesity and anorectal function on physiologic testing in patients presenting with CC. METHODS: This was a retrospective cohort study of consecutive adults who underwent high resolution anorectal manometry (HRAM) at a tertiary center for CC. Patient demographics, clinical history, surgical/obstetric history, medications, and HRAM results were reviewed. Patients were classified into obese (BMI > 30 kg/m2) vs non-obese (BMI < 30 kg/m2) groups at the time of HRAM. Fisher-exact/student t-test for univariate analyses and general linear regression for multivariable analysis were performed. RESULTS: 383 adults (mean 50.3 years; 85.8% female) with CC were included. On HRAM, patients with obesity had lower anal sphincter resting tone (37.3 vs 48.5 mmHg, p = 0.005) and maximum squeeze pressure (104.8 mmHg vs 120.0 mmHg, p = 0.043). No significant differences in dyssynergia (61% vs 53%, p = 0.294) and failed balloon expulsion (18% vs 25%, p = 0.381) were found between obese and non-obese groups. On balloon distention testing, the maximum tolerated (163.5 vs 147.6 mL, p = 0.042) and urge sensation (113.9 vs 103.7 mL, p = 0.048) volumes were significantly increased among patients with obesity. After adjusting for potential confounders, obesity remained independently associated with increased maximum tolerated volume (ß-coefficient 13.7, p = 0.049). CONCLUSION: Obesity was independently associated with altered rectal sensitivity among patients with CC. Altered rectal sensation may play an important role in CC among patients with obesity. Anorectal physiology testing should be considered to understand the pathophysiology and guide management.

Isolation of Toxoplasma gondii in cell culture: an alternative to bioassay.

Toxoplasma gondii is an apicomplexan protozoan parasite that can infect mammals and birds. The infection can cause acute toxoplasmosis and death in susceptible hosts. Bioassay using cats and mice has been the standard for the isolation of T. gondii from infected hosts for the past several decades. However, bioassay is labor-intensive, expensive, and involves using laboratory animals. To search alternative approaches and o work towards replacement of animal experiments, we summarized the key literature and conducted four experiments to isolate T. gondii in vitro by cell culture. A few heart tissue samples from animals with the highest antibody titers in a given collection were used for T. gondii isolation. These experiments included samples from five out of 51 wild ducks, four of 46 wild turkeys, six of 24 white-tailed deer, as well as from six kangaroos that had died with acute toxoplasmosis in a zoo. These experiments resulted in three isolates from five chronically infected wild ducks (60%), four isolates from four chronically infected wild turkeys (100%), one isolate from six chronically infected white-tailed deer (17%), and four isolates from six kangaroos with acute toxoplasmosis (67%). In addition, five isolates from the five chronically infected wild ducks were obtained by bioassay in mice, showing a 100% success rate, which is higher than the 60% rate by direct cell culture. These T. gondii isolates were successfully propagated in human foreskin fibroblast (HFF) or Vero cells, and genotyped by multilocus PCR-RFLP markers. The results showed that it is practical to isolate T. gondii directly in cell culture. Although the cell culture approach may not be as sensitive as the bioassay, it does provide an alternative that is simple, cost-effective, ethically more acceptable, and less time-sensitive to isolate T. gondii. In this paper we propose a procedure that may be applied and further optimized for isolation of T. gondii.

Prospective evaluation of an emergency department protocol to prevent hospitalization in mild acute pancreatitis: Outcomes and predictors of discharge.

BACKGROUND: While acute pancreatitis (AP) contributes significantly to hospitalizations and costs, most cases are mild with minimal complications. In 2016, we piloted an observation pathway in the emergency department (ED) for mild AP and showed reduced admissions and length of stay (LOS) without increased readmissions or mortality. After 5 years of implementation, we evaluated outcomes of the ED pathway and identified predictors of successful discharge. METHODS: We reviewed a prospectively enrolled cohort of patients with mild AP presenting to a tertiary care center ED between 10/2016 and 9/2021, evaluating LOS, charges, imaging, and 30-day readmission, and assessed predictors of successful ED discharge. Patients were divided into two main groups: successfully discharged via the ED pathway ("ED cohort") and admitted to the hospital ("admission cohort"), with subgroups to compare outcomes, and multivariate analysis to determine predictors of discharge. RESULTS: Of 619 AP patients, 419 had mild AP (109 ED cohort, 310 admission cohort). The ED cohort was younger (age 49.3 vs 56.3,p < 0.001), had lower Charlson Comorbidity Index (CCI) (1.30 vs 2.43, p < 0.001), shorter LOS (12.3 h vs 116 h, p < 0.001), lower charges (mean $6768 vs $19886, p < 0.001) and less imaging, without differences in 30-day readmissions. Increasing age (OR: 0.97; p < 0.001), increasing CCI (OR: 0.75; p < 0.001) and biliary AP (OR: 0.10; p < 0.001) were associated with decreased ED discharge, while idiopathic AP had increased ED discharge (OR: 7.8; p < 0.001). CONCLUSIONS: After appropriate triage, patients with mild AP (age <50, CCI <2, idiopathic AP) can safely discharge from the ED with improved outcomes and cost savings.

Universal Constraints on Linguistic Event Categories: A Cross-Cultural Study of Child Homesign.

Languages carve up conceptual space in varying ways-for example, English uses the verb cut both for cutting with a knife and for cutting with scissors, but other languages use distinct verbs for these events. We asked whether, despite this variability, there are universal constraints on how languages categorize events involving tools (e.g., knife-cutting). We analyzed descriptions of tool events from two groups: (a) 43 hearing adult speakers of English, Spanish, and Chinese and (b) 10 deaf child homesigners ages 3 to 11 (each of whom has created a gestural language without input from a conventional language model) in five different countries (Guatemala, Nicaragua, United States, Taiwan, Turkey). We found alignment across these two groups-events that elicited tool-prominent language among the spoken-language users also elicited tool-prominent language among the homesigners. These results suggest ways of conceptualizing tool events that are so prominent as to constitute a universal constraint on how events are categorized in language.

Acquisition of turn-taking in sign language conversations: An overview of language modality and turn structure.

The task of transitioning from one interlocutor to another in conversation - taking turns - is a complex social process, but typically transpires rapidly and without incident in conversations between adults. Cross-linguistic similarities in turn timing and turn structure have led researchers to suggest that it is a core antecedent to human language and a primary driver of an innate "interaction engine." This review focuses on studies that have tested the extent of turn timing and turn structure patterns in two areas: across language modalities and in early language development. Taken together, these two lines of research offer predictions about the development of turn-taking for children who are deaf or hard of hearing (DHH) acquiring sign languages. We introduce considerations unique to signed language development - namely the heterogenous ecologies in which signed language acquisition occurs, suggesting that more work is needed to account for the diverse circumstances of language acquisition for DHH children. We discuss differences between early sign language acquisition at home compared to later sign language acquisition at school in classroom settings, particularly in countries with national sign languages. We also compare acquisition in these settings to communities without a national sign language where DHH children acquire local sign languages. In particular, we encourage more documentation of naturalistic conversations between DHH children who sign and their caregivers, teachers, and peers. Further, we suggest that future studies should consider: visual/manual cues to turn-taking and whether they are the same or different for child or adult learners; the protracted time-course of turn-taking development in childhood, in spite of the presence of turn-taking abilities early in development; and the unique demands of language development in multi-party conversations that happen in settings like classrooms for older children versus language development at home in dyadic interactions.

Opioid-Associated Anorectal Dysfunction in Chronic Constipation.

INTRODUCTION: The role of anorectal and defecatory dysfunction in opioid-related constipation is unclear. We aimed to evaluate the relationship between opioid use and rectal sensation, defecatory function, and balloon expulsion on anorectal physiology testing. METHODS: This was a retrospective cohort study of consecutive adults undergoing high-resolution anorectal manometry (HRAM) at a tertiary center for constipation. Clinical characteristics, medication use, and HRAM findings were obtained. Statistical analyses were performed using Fisher-exact/student t-test for univariate analyses and logistic/general linear regression for multivariable analyses to compare patients with no opioid use, recent (< 3 months) use, and distant (> 3 months) use. RESULTS: 424 patients (49.8 ± 17.2 years; 85.6% female) were included. Compared to those without opioid history, patients with recent use had increased volumes for first rectal sensation (70.4 mL vs 59.4, p = 0.043), urge (120.5 mL vs 101.5, p = 0.017), and maximal tolerance (170.2 mL vs 147.2, p = 0.0018), but not patients with distant use. Recent opioid use was associated with increased risk of dyssynergic defecation (DD) (61.8% vs 46.4%, p = 0.035), but not failed balloon expulsion. On multivariable models controlling for potential confounders, recent opioid use, but not distant use, remained independently correlated with increased volumes for first rectal sensation (ß-coefficient 9.78, p = 0.019), urge (ß-coefficient 16.7, p = 0.0060), and maximal tolerance (ß-coefficient 22.9, p = 0.0032), and higher risk for DD (aOR = 2.18, p = 0.026). CONCLUSION: Recent opioid use was an independent risk factor for rectal hyposensitivity and DD on HRAM in patients with constipation, but that effect may decrease with discontinuation of use. Anorectal physiology testing should be considered in patients with opioid-associated constipation.

In recurrent C difficile infection, oral FMT capsules have a pooled cure rate of 82% (low-quality evidence).

SOURCE CITATION: Du C, Luo Y, Walsh S, Grinspan A. Oral fecal microbiota transplant capsules are safe and effective for recurrent Clostridioides difficile infection: a systematic review and meta-analysis. J Clin Gastroenterol. 2021;55:300-8. 33471490.

In adults with severe acute GI bleeding, tranexamic acid did not reduce death due to bleeding at 5 days.

SOURCE CITATION: The HALT-IT Trial Collaborators. Effects of a high-dose 24-h infusion of tranexamic acid on death and thromboembolic events in patients with acute gastrointestinal bleeding (HALT-IT): an international randomised, double-blind, placebo-controlled trial. Lancet. 2020;395:1927-36. 32563378.

The communicative importance of agent-backgrounding: Evidence from homesign and Nicaraguan Sign Language.

Some concepts are more essential for human communication than others. In this paper, we investigate whether the concept of agent-backgrounding is sufficiently important for communication that linguistic structures for encoding this concept are present in young sign languages. Agent-backgrounding constructions serve to reduce the prominence of the agent - the English passive sentence a book was knocked over is an example. Although these constructions are widely attested cross-linguistically, there is little prior research on the emergence of such devices in new languages. Here we studied how agent-backgrounding constructions emerge in Nicaraguan Sign Language (NSL) and adult homesign systems. We found that NSL signers have innovated both lexical and morphological devices for expressing agent-backgrounding, indicating that conveying a flexible perspective on events has deep communicative value. At the same time, agent-backgrounding devices did not emerge at the same time as agentive devices. This result suggests that agent-backgrounding does not have the same core cognitive status as agency. The emergence of agent-backgrounding morphology appears to depend on receiving a linguistic system as input in which linguistic devices for expressing agency are already well-established.

Effect of Aspiration Therapy on Obesity-Related Comorbidities: Systematic Review and Meta-Analysis.

BACKGROUND/AIMS: Aspiration therapy (AT) involves endoscopic placement of a gastrostomy tube with an external device that allows patients to drain 30% of ingested calories after meals. Its efficacy for inducing weight loss has been shown. This study aimed to assess the effect of AT on obesity-related comorbidities. METHODS: A meta-analysis of studies that assessed AT outcomes was conducted through December 2018. Primary outcomes were changes in comorbidities at 1 year following AT. Secondary outcomes were the amount of weight loss at up to 4 years and pooled serious adverse events (SAEs). RESULTS: Five studies with 590 patients were included. At 1 year, there were improvements in metabolic conditions: mean difference (MD) in systolic blood pressure: -7.8 (-10.7 - -4.9) mm Hg; MD in diastolic blood pressure: -5.1 (-7.0 - 3.2) mm Hg; MD in triglycerides: -15.8 (-24.0 - -7.6) mg/dL; MD in high-density lipoprotein: 3.6 (0.7-6.6) mg/dL; MD in hemoglobin A1c (HbA1c): -1.3 (-1.8 - -0.8) %; MD in aspartate transaminase: -2.7 (-4.1 - -1.3) U/L; MD in alanine transaminase: -7.5 (-9.8 - -5.2) U/L. At 1 (n=218), 2 (n=125), 3 (n=46), and 4 (n=27) years, the patients experienced 17.8%, 18.3%, 19.1%, and 18.6% total weight loss (TWL), corresponding to 46.3%, 46.2%, 48.0%, and 48.7% excess weight loss (EWL) (p<0.0001 for all). Subgroup analysis of 2 randomized controlled trials (n=225) showed that AT patients lost more weight than did controls by 11.6 (6.5-16.7) %TWL and 25.6 (16.0-35.3) %EWL and experienced greater improvement in HbA1c and alanine transaminase by 1.3 (0.8-1.8) % and 9.0 (3.9-14.0) U/L. The pooled SAE rate was 4.1%. CONCLUSION: Obesity-related comorbidities significantly improved at 1 year following AT. Additionally, a subgroup of patients who continued to use AT appeared to experience significant weight loss that persisted up to at least 4 years.

A Multicenter Study Into Causes of Severe Acute Liver Injury.

The differential diagnosis of an increase in alanine aminotransferase (ALT) level and/or aspartate aminotransferase (AST) level of ≥1000 IU/L often is stated to include 3 main etiologies: ischemic hepatitis, acute viral hepatitis (typically hepatitis A and hepatitis B), and drug-induced (more specifically, acetaminophen/paracetamol) liver injury (DILI).1 Unfortunately, there are a paucity of studies examining the most common causes of acute liver injury (ALI) and those that have been published have been small,2 single-center,2 or examined less severe increases in ALT or AST levels.3,4 We conducted a multicenter study of all patients with an ALT and/or AST level ≥1000 IU/L. Our study had 3 main goals: (1) to determine the most common causes of an ALT and/or AST level ≥1000 IU/L, along with their relative frequencies; (2) to determine differences in etiology based on hospital type (liver transplant center, community hospital, Veterans Affairs hospital); and (3) to confirm or disprove the differential heuristic that ischemic hepatitis, acute viral hepatitis, and acetaminophen toxicity are the most common etiologies.

Regression of Peripheral Subclinical Enthesopathy in Therapy-Naive Patients Treated With Ustekinumab for Moderate-to-Severe Chronic Plaque Psoriasis: A Fifty-Two-Week, Prospective, Open-Label Feasibility Study.

OBJECTIVE: To investigate whether sonographically determined subclinical enthesopathy in patients with moderate-to-severe psoriasis regresses with the use of ustekinumab therapy for skin disease. METHODS: Seventy-three patients with moderate-to-severe psoriasis, who were not treated with systemic therapy and did not have symptoms of psoriatic arthritis (PsA), and 23 healthy volunteers were screened by ultrasound for subclinical enthesitis. Subsequently, 23 patients with psoriasis whose ultrasound results showed inflammatory changes were treated with ustekinumab for 52 weeks. The evolution of sonographic abnormalities of the upper and lower limb entheses was assessed using an extensive gray-scale and power Doppler (PD) ultrasound protocol at weeks 0, 12, 24, and 52. For each parameter, a gray-scale or PD ultrasound score of >0 was determined to be abnormal, and a summative score based on the Glasgow Ultrasound Enthesitis Scoring System was calculated. RESULTS: Of all the patients with psoriasis screened using ultrasound, 49.3% had at least 1 inflammatory entheseal abnormality. Mean ± SD inflammation scores were higher in the patients with psoriasis compared with the healthy volunteers (9.9 ± 6.6 versus 1.0 ± 1.4). With treatment, the mean inflammation scores decreased significantly by 42.2% from week 0 to week 24 (-4.2 [95% confidence interval -6.3, -2.1]; P < 0.001) and by 47.5% by week 42 (-4.7 [95% confidence interval -7.1, -2.3]; P = 0.001). Entheseal structural abnormalities did not change significantly during treatment. CONCLUSION: Within 12 weeks of treatment, interleukin-12 (IL-12)/IL-23 inhibition for psoriasis appears to suppress subclinical enthesopathy, and the suppression is maintained through week 52. Further longitudinal studies are needed to determine whether therapy initiated for skin disease may prevent the development of PsA.

Successful endoscopic treatment of an intraductal papillary neoplasm of the bile duct.

We present a case of a 76-year-old man with right upper quadrant abdominal pain and weight loss, who was found to have an intraductal papillary neoplasm of the bile duct (IPNB) of the pancreaticobiliary subtype, deemed curatively resectable. The patient declined surgery and opted for endoscopic therapy. He underwent two sessions of endoscopic retrograde cholangiopancreatography (ERCP)-guided radiofrequency ablation (RFA). Ten months later, no evidence of recurrence was identified on repeat ERCP. To our knowledge, this is the first reported case of successful use of RFA as a primary treatment modality for resectable IPNB.

A comparison of an opioid abuse screening tool and prescription drug monitoring data in the emergency department.

OBJECTIVES: This study aimed to: (a) determine the percentage of ED patients receiving prescriptions for opioid pain medications that meet the criteria for "high-risk for abuse potential" on the Screener and Opioid Assessment for Patients with Pain (SOAPP(®)-R), (b) determine the percentage of patients with high-risk behavior on the state prescription drug monitoring program (PDMP) database, (c) compare the SOAPP-R with data from the PDMP, and (d) determine psychometric properties of SOAPP-R for ED patients METHODS: Convenience sample of ED patients who were being considered for discharge with a prescription for an opioid pain medication. Subjects completed SOAPP-R on an electronic tablet and PDMP data was obtained. Scores on SOAPP-R ≥ 18 were defined as "at-risk", and PDMP data showing both ≥ 4 opioid prescriptions and ≥ 4 providers in 12 months was considered the criterion standard for high-risk behavior. RESULTS: 82 patients (88.2%) provided consent. 32.9% (n=27) were determined to be "at-risk" (score ≥ 18) by SOAPP-R. 15.9% (n=13) subjects met PDMP criteria and 53.9% (n=7) of those had SOAPP-R scores ≥ 18 (sensitivity 54%, specificity 71%, positive predictive value 26%, negative predictive value 89%). The association of an at-risk SOAPP-R score and PDMP high-risk criteria was an adjusted odds ratio of 1.39 (95% confidence interval 0.73-3.68). CONCLUSIONS: In our population, about one-third of patients being considered for discharge with an opioid prescription scored "at-risk" on SOAPP-R and 15.9% met the PDMP high-risk criteria. The high negative predictive value of SOAPP-R indicates it may be a useful screening tool for the ED patient population.

Feasibility of tablet computer screening for opioid abuse in the emergency department.

INTRODUCTION: Tablet computer-based screening may have the potential for detecting patients at risk for opioid abuse in the emergency department (ED). Study objectives were a) to determine if the revised Screener and Opioid Assessment for Patients with Pain (SOAPP®-R), a 24-question previously paper-based screening tool for opioid abuse potential, could be administered on a tablet computer to an ED patient population; b) to demonstrate that >90% of patients can complete the electronic screener without assistance in <5 minutes and; c) to determine patient ease of use with screening on a tablet computer. METHODS: This was a cross-sectional convenience sample study of patients seen in an urban academic ED. SOAPP®-R was programmed on a tablet computer by study investigators. Inclusion criteria were patients ages ≥18 years who were being considered for discharge with a prescription for an opioid analgesic. Exclusion criteria included inability to understand English or physical disability preventing use of the tablet. RESULTS: 93 patients were approached for inclusion and 82 (88%) provided consent. Fifty-two percent (n=43) of subjects were male; 46% (n=38) of subjects were between 18-35 years, and 54% (n=44) were >35 years. One hundred percent of subjects completed the screener. Median time to completion was 148 (interquartile range 117.5-184.3) seconds, and 95% (n=78) completed in <5 minutes. 93% (n=76) rated ease of completion as very easy. CONCLUSIONS: It is feasible to administer a screening tool to a cohort of ED patients on a tablet computer. The screener administration time is minimal and patient ease of use with this modality is high.

Value of ultrasound in rheumatologic diseases.

The use of musculoskeletal ultrasound in rheumatology clinical practice has rapidly increased over the past decade. Ultrasound has enabled rheumatologists to diagnose, prognosticate and monitor disease outcome. Although international standardization remains a concern still, the use of ultrasound in rheumatology is expected to grow further as costs fall and the opportunity to train in the technique improves. We present a review of value of ultrasound, focusing on major applications of ultrasound in rheumatologic diseases.

Spinocerebellar ataxia type 7: clinical course, phenotype-genotype correlations, and neuropathology.

Spinocerebellar ataxia type 7 is a neurodegenerative polyglutamine disease characterized by ataxia and retinal degeneration. The longitudinal course is unknown, and relationships between repeat expansion, clinical manifestations, and neuropathology remain uncertain. We followed 16 affected individuals of a 61-member kindred over 27 years with electroretinograms, neurological examinations including the Brief Ataxia Rating Scale, neuroimaging in five, and autopsy in four cases. We identified four stages of the illness: Stage 0, gene-positive but phenotypically silent; Stage 1, no symptoms, but hyperreflexia and/or abnormal electroretinograms; Stage 2, symptoms and signs progress modestly; and Stage 3, rapid clinical progression. CAG repeat length correlated inversely with age of onset of visual or motor signs (r = -0.74, p = 0.002). Stage 3 rate of progression did not differ between cases (p = 0.18). Electroretinograms correlated with Brief Ataxia Rating Scale score and were a biomarker of disease onset and progression. All symptomatic patients developed gait ataxia, extremity dysmetria, dysarthria, dysrhythmia, and oculomotor abnormalities. Funduscopy revealed pale optic discs and pigmentary disturbances. Visual acuity declined to blindness in those with longer CAG expansions. Hyperreflexia was present from Stage 1 onwards. Restless legs syndrome and sensory impairment were common. Neuropathological hallmarks were neuronal loss in cerebellar cortex, deep cerebellar nuclei, inferior olive, and anterior horns of the spinal cord, and axonal loss in spinocerebellar tracts, dorsal nerve roots, and posterior columns. Retinal pathology included photoreceptor degeneration and disruption of retinal pigment epithelium. Spinocerebellar ataxia type 7 evolves through four clinical stages; neuropathological findings underlie the clinical presentation; electroretinograms are a potential biomarker of disease progression.

Atypical case of Wolfram syndrome revealed through targeted exome sequencing in a patient with suspected mitochondrial disease.

BACKGROUND: Mitochondrial diseases comprise a diverse set of clinical disorders that affect multiple organ systems with varying severity and age of onset. Due to their clinical and genetic heterogeneity, these diseases are difficult to diagnose. We have developed a targeted exome sequencing approach to improve our ability to properly diagnose mitochondrial diseases and apply it here to an individual patient. Our method targets mitochondrial DNA (mtDNA) and the exons of 1,600 nuclear genes involved in mitochondrial biology or Mendelian disorders with multi-system phenotypes, thereby allowing for simultaneous evaluation of multiple disease loci. CASE PRESENTATION: Targeted exome sequencing was performed on a patient initially suspected to have a mitochondrial disorder. The patient presented with diabetes mellitus, diffuse brain atrophy, autonomic neuropathy, optic nerve atrophy, and a severe amnestic syndrome. Further work-up revealed multiple heteroplasmic mtDNA deletions as well as profound thiamine deficiency without a clear nutritional cause. Targeted exome sequencing revealed a homozygous c.1672C > T (p.R558C) missense mutation in exon 8 of WFS1 that has previously been reported in a patient with Wolfram syndrome. CONCLUSION: This case demonstrates how clinical application of next-generation sequencing technology can enhance the diagnosis of patients suspected to have rare genetic disorders. Furthermore, the finding of unexplained thiamine deficiency in a patient with Wolfram syndrome suggests a potential link between WFS1 biology and thiamine metabolism that has implications for the clinical management of Wolfram syndrome patients.

Eosinophilic gastrointestinal disorder in coeliac disease: a case report and review.

Eosinophilic gastrointestinal disorder is a rare disorder characterised by eosinophilic infiltration of the gastrointestinal tract. There are various gastrointestinal manifestations with eosinophilic ascites being the most unusual and rare presentation. Diagnosis requires high index of suspicion and exclusion of various disorders associated with peripheral eosinophilia. There are no previous case reports to suggest an association between eosinophilic gastrointestinal disorder and coeliac disease in adults. We report a case of eosinophilic ascites and gastroenteritis in a 30-year-old woman with a known history of coeliac disease who responded dramatically to a course of steroids.