Gastrointestinal diagnoses in patients with eating disorders: A retrospective cohort study 2010-2020.

BACKGROUND AND AIMS: Gastrointestinal (GI) disorders are common in patients with eating disorders. However, the temporal relationship between GI and eating disorder symptoms has not been explored. We aimed to evaluate GI disorders among patients with eating disorders, their relative timing, and the relationship between GI diagnoses and eating disorder remission. METHODS: We conducted a retrospective analysis of patients with an eating disorder diagnosis who had a GI encounter from 2010 to 2020. GI diagnoses and timing of eating disorder onset were abstracted from chart review. Coders applied DSM-5 criteria for eating disorders at the time of GI consult to determine eating disorder remission status. RESULTS: Of 344 patients with an eating disorder diagnosis and GI consult, the majority (255/344, 74.2%) were diagnosed with an eating disorder prior to GI consult (preexisting eating disorder). GI diagnoses categorized as functional/motility disorders were most common among the cohort (57.3%), particularly in those with preexisting eating disorders (62.5%). 113 (44.3%) patients with preexisting eating disorders were not in remission at GI consult, which was associated with being underweight (OR 0.13, 95% CI 0.04-0.46, p < 0.001) and increasing number of GI diagnoses (OR 0.47 per diagnosis, 95% CI 0.26-0.85, p = 0.01). CONCLUSIONS: Eating disorder symptoms precede GI consult for most patients, particularly in functional/motility disorders. As almost half of eating disorder patients are not in remission at GI consult. GI providers have an important role in screening for eating disorders. Further prospective research is needed to understand the complex relationship between eating disorders and GI symptoms.

Differences in provider recommendations for Black/African American and White patients with irritable bowel syndrome.

BACKGROUND: Health disparities and barriers to equitable care for patients from racial and ethnic minority backgrounds are common. We sought to evaluate disparities in management recommendations among Black/African American (AA) patients seeking care for IBS. METHODS: We assembled a retrospective cohort of patients at two tertiary care centers who were self-identifying as Black/AA and attended a first gastroenterology consult for IBS. These patients were age- and sex-matched to White controls with IBS also attending an initial gastroenterology consult. Retrospective chart review determined patient demographics, income, comorbidities, as well as provider management recommendations including pharmacologic therapies and non-pharmacologic interventions. KEY RESULTS: Among 602 IBS patients ages 14-88 (M ± SD = 43.6 ± 18.6 years) with IBS, those who identified as Black/AA (n = 301) had a lower estimated mean income and were significantly more likely to have a number of specific chronic medical conditions. Black/AA patients were significantly less likely to have implemented dietary changes for symptoms prior to receiving a diagnosis of IBS from a gastroenterologist. Black/AA patients were also less likely to receive a referral to a dietician within 1 year following their diagnosis of IBS (p = 0.01). Black/AA patients were prescribed pharmacologic therapy more often for constipation (41.9% vs. 34.6%, p = 0.01). It was more common for White patients to present at the initial encounter having already initiated a neuromodulator (41.9% vs. 27.9%, p < 0.001). CONCLUSION & INFERENCES: Management recommendations for IBS appear to vary by race, specifically for dietary advice and referrals.

Relationship Between Psychological Trauma and Irritable Bowel Syndrome and Functional Dyspepsia in a Joint Hypermobility Syndrome/Ehlers-Danlos Syndrome Patient Population.

BACKGROUND: There is frequent overlap between and the connective tissue diseases Joint Hypermobility Syndrome/Ehlers-Danlos Syndrome (JHS/EDS) and disorders of the gut-brain interaction (DGBIs). AIMS: Because not all JHS/EDS patients develop DGBIs, we sought to determine whether secondary environmental triggers may lead to development of irritable bowel syndrome (IBS) and functional dyspepsia (FD) in patients with JHS/EDS. METHODS: We sent electronic surveys to 253 patients from a JHS/EDS support group, with responses collected over one year. IBS and FD were diagnosed by the Rome IV criteria, with additional validated assessments of adverse childhood experiences (ACEs) and traumatic stressors according to DSM-V criteria. We compared clinical and psychological characteristics of JHS/EDS patients with and without DGBIs using univariable and multivariable analyses. RESULTS: We enrolled 193 JHS/EDS patients, of whom 67.9% met Rome IV criteria for IBS. The IBS and JHS/EDS overlap group reported significantly more traumatic exposures (P < 0.001) and were more likely to have experienced greater than 3 ACEs (P < 0.001) than JHS/EDS patients without IBS. FD was found in 35.2% of patients and was associated with significantly more traumatic exposures (P < 0.001) and were more likely to have experienced greater than 3 ACEs (P < 0.001) than JHS/EDS patients without FD. CONCLUSIONS: We found that JHS/EDS patients with IBS and FD overlap reported significantly more traumatic exposures and ACEs compared to JHS/EDS patients without overlapping IBS or FD. JHS/EDS patients may have increased susceptibility to DGBIs, with traumatic life experiences and/or ACEs acting a secondary environmental trigger driving the subsequent development of DGBIs.

Unrecognized Functional Dyspepsia Among Those With Refractory Chronic Constipation: Analysis of a Tertiary Cohort.

BACKGROUND AND AIMS: Patients with functional constipation (FC) are frequently dissatisfied with current treatment options which may be related to persistent, unaddressed symptoms. We hypothesized that refractory FC may actually represent functional dyspepsia (FD) overlap. Among adults presenting with refractory FC, we sought to (1) identify the prevalence of concurrent FD and (2) identify the symptoms and presentations most frequently associated with concurrent FD and FC. METHODS: We assembled a retrospective cohort of 308 patients sequentially presenting to a tertiary neurogastroenterology clinic for evaluation of refractory FC, defined as having failed first-line therapy. Using Rome IV criteria, trained raters identified the presence and characteristics of concurrent FD in addition to demographics, presenting complaints, and psychological comorbidities. RESULTS: Among 308 patients presenting with refractory FC (average of 3.0 ± 2.3 constipation treatments tried unsuccessfully), 119 (38.6%) had concurrent FD. Aside from meeting FD criteria, the presence of concurrent FD was associated with patient complaints of esophageal symptoms (Odds ratio = 3.1; 95% confidence interval, 1.80-5.42) and bloating and distension (Odds ratio = 2.67; 95% confidence interval, 1.50-4.89). Patients with concurrent FD were more likely to have a history of an eating disorder (21.0% vs 12.7%) and were also more likely to present with current avoidant/restrictive food intake disorder-related symptoms (31.9% vs 21.7%). CONCLUSION: Almost 40% of adult patients referred for refractory FC met criteria for concurrent FD in a tertiary-level cohort. The presence of both FC and FD was associated with greater esophageal symptoms and bloating/distention. Determining presence of concurrent FD may represent an additional therapeutic opportunity in refractory patients who may attribute symptoms to FC alone.

Psychiatric comorbidities among adult patients with disorders of gut-brain interaction: Prevalence and relationships to treatment outcomes.

BACKGROUND: Little is known about the impact of psychiatric comorbidity on pharmacologic treatment outcomes, including neuromodulators (medications targeting the gut-brain axis), among adult patients with disorders of gut-brain interaction (DGBI). Accordingly, we aimed to examine associations between psychiatric comorbidity and DGBI pharmacologic treatment outcomes. METHODS: In a retrospective study of consecutively referred new patients (N = 410; ages 18-90; 73% female) to a tertiary neurogastroenterology clinic in 2016 with follow-up through 2018, relationships between psychiatric illness (any psychiatric illness, anxiety disorders, depressive disorders) and pharmacologic treatment selection (any medication, neuromodulating medication) and treatment outcomes, respectively, were examined using multivariable logistic regression, adjusting for demographics, gastrointestinal (GI) diagnoses, and pre-existing neuromodulator use. KEY RESULTS: Anxiety disorders (35%) were the most common psychiatric comorbidity, followed by depressive disorders (29%). Patients with anxiety disorders were more likely to be prescribed a neuromodulator by their gastroenterologist (OR = 1.72 [95% CI 1.10-2.75]) yet less likely to respond to neuromodulators (OR = 0.43 [0.21-0.90]) or any GI medication (OR = 0.24 [0.12-0.50]) in fully adjusted analyses. In contrast, depressive disorders were not associated with neuromodulator prescription or response. CONCLUSIONS AND INFERENCES: Anxiety disorders are common among patients with DGBI and significantly reduce the likelihood of GI pharmacologic treatment response to any medication prescribed, including neuromodulators.

Virtual Tai Chi program for patients with irritable bowel syndrome with constipation: Proof-of-concept feasibility trial.

BACKGROUND: Satisfaction with current treatment options for irritable bowel syndrome with constipation (IBS-C) is low, with many patients turning to complementary treatments. Tai Chi is a mind-body medicine practice with proven efficacy in other functional disorders. As a proof-of-concept, we tested the feasibility and preliminary clinical outcomes associated with a Tai Chi program designed for IBS-C. METHODS: A total of 27 IBS-C patients participated in a single-arm trial of 8 sessions of Tai Chi delivered weekly over 7 weeks via live videoconferencing in group format. Clinical improvement was assessed via change in IBS Symptom Severity Score (IBS-SSS) from baseline to 4 weeks posttreatment (week 11) with secondary outcomes exploring symptom ratings, IBS-related quality of life (IBS-QOL), GI-specific anxiety, abdominal distention, and psychological factors. KEY RESULTS: Despite substantial dropout (n = 7; 26%), the treatment protocol had moderate to excellent feasibility for other criteria. Treatment satisfaction was excellent. Exit interviews confirmed high satisfaction with the program among completers, but a high burden of data collection was noted. One participant experienced an adverse event (mild, exacerbation of sciatica). There was a significant improvement in intra-individual IBS-SSS between baseline and posttreatment (average change -66.5, 95% CI -118.6 to -14.3, p = 0.01). Secondary outcomes were notable for improvements in other IBS symptom scoring measures, IBS-QOL, measured abdominal diameter, and leg strength. CONCLUSIONS AND INFERENCES: Our data provide preliminary evidence of the feasibility of a Tai Chi intervention for IBS-C, show promise for improving outcomes, and identify more streamlined data collection as an area for further program improvement.

Waldenström macroglobulinaemia presenting as tingling ulcers on the feet.

A 56-year-old man presented with tingling ulcers on the feet. On further skin examination, papules on the knees were observed. Biopsies revealed extravascular eosinophilic deposits of IgM, and Waldenström macroglobulinaemia was diagnosed. The skin manifestations have resolved with chemotherapy. Peripheral neuropathy and storage papules are rare manifestations of Waldenström's macroglobulinaemia.

Pre- and postoperative urodynamic findings in patients after a bulbourethral composite suspension with intraoperative urodynamically controlled sling tension adjustment for postprostatectomy incontinence.

OBJECTIVES: To compare pre- and postoperative urodynamic findings in patients with a bulbourethral composite suspension and intraoperative urodynamically controlled sling tension adjustment. METHODS AND PATIENTS: All data were prospectively collected from 10 patients (mean age 66 years) who successfully underwent bulbourethral composite suspension for moderate to severe postprostatectomy incontinence. Patients were evaluated preoperatively and 3-6 months postoperatively by urodynamic measurements, including urethra pressure profiles (UPPs) and pressure flow studies (PFSs). Clinical outcome was evaluated by patient-reported pad use and questionnaires (ICIQ-UI SF and I-QOL). Intraoperatively sling tension was adjusted under repeated urodynamic measurements of abdominal leak point pressure. Data were evaluated using the Kruskal-Wallis Wilcoxon test. RESULTS: Sling implantation was successful in all patients. Pre- to postoperative pad use decreased significantly (P < .005). Five patients were pad-free, 3 used 1 pad, and 2 used 2 pads per day. Continence and quality of life improved significantly (ICIQ-UI SF: pre-op 17 vs post-op 4.9; I-QOL: pre-op 66 vs post-op 91; P < .05 for both). Urodynamic parameters during the filling phase remained unchanged. UPPs revealed a significant increase of the maximal urethral closure pressure (pre-op 40 cm H(2)O vs post-op 58 cm H(2)O) and functional length (pre-op 31 mm vs post-op 40 mm; P < .05 for both). Postoperatively, urodynamic maximal flow rates were slightly reduced from 16 mL/s to 12 mL/s (P = .4). PFSs revealed an unobstructed voiding in all patients. CONCLUSIONS: According to the present evaluation, a bulbourethral composite suspension with intraoperative urodynamically controlled sling tension adjustment improves continence without causing prolonged clinically or urodynamically significant voiding obstruction.

Is galectin-1 a trigger for trophoblast cell fusion?: the MAP-kinase pathway and syncytium formation in trophoblast tumour cells BeWo.

Galectin-1 (gal-1), a member of the mammalian ß-galactoside-binding proteins, exerts biological effects by recognition of glycan ligands, including those involved in cell adhesion and growth regulation. In a previous study, we demonstrated that gal-1 induces cell differentiation processes on the membrane of choriocarcinoma cells BeWo, including the receptor tyrosine kinases, REarranged during transfection, janus kinase 2 and vascular endothelial growth factor receptor 3. Within this study, we examined which mitogen-activated protein kinases (MAPK) and serine/threonine kinases were phoshorylated by gal-1. Out of a number of 21 different MAPKs and other serine/threonine kinases, the stimulation of BeWo cells with gal-1 showed a significant alteration of signal intensity in extracellular-regulated kinases 1/2 (ERK1/2), Akt-3, Akt-pan and glycogen synthase kinase-α/ß (GSK-3α/ß). We demonstrated that gal-1 significantly inhibited ERK1/2, Akt-3/pan and GSK-3α/ß phosphorylation in BeWo cells and in addition induced Elk1 transcription factor activation. In contrast to gal-1 effects, MAPK inhibitor U0126 reduced syncytium formation of BeWo cells. The results of our data showed that phosphorylation of MAP kinases are involved in gal-1-induced signal transduction processes in BeWo cells. Additional results obtained with MAPK inhibitor U0126 close the gap between syncytium formation induced by gal-1 and MAPK activation in trophoblast cells. Furthermore, we demonstrated that gal-1 induces the activation of Elk1, a transcription factor that is activated by MAPK pathways.

The role of galectin-1 in trophoblast differentiation and signal transduction.

Galectins are proteins with the ability to bind ß-galactosides through a conserved carbohydrate recognition domain. Galectin-1 exerts its biological effects by binding glycan ligands on proteins involved in cell adhesion and growth regulation. Galectin-1 inhibits trophoblast cell proliferation and induces syncytium formation. Its down-regulation in the syncytiotrophoblast has been associated with early pregnancy loss. In the choriocarcinoma-derived BeWo cells the galectin-1 induced growth inhibition is apoptosis-independent, but rather appears to be mediated by binding to cell surface receptors, such as the receptor tyrosine kinases REarranged during Transfection (RET) and Janus Kinase (JAK) 2 as well as vascular endothelial growth factor receptor 3. On the syncytiotrophoblast and extravillous trophoblast galectin-1 binds the Thomsen-Friedenreich disaccharide on mucin-1. The cell differentiation processes induced by binding to these receptors ultimately lead to the inhibition of proliferation and syncytium formation.

Beta-lactam and aminoglycoside resistance rates and mechanisms among Pseudomonas aeruginosa in French general practice (community and private healthcare centres).

OBJECTIVES: The aim of this study was to assess antibiotic resistance rates and mechanisms of beta-lactam and aminoglycoside resistance among isolates of Pseudomonas aeruginosa isolated in the extra-hospital setting (community and private healthcare centres). PATIENTS AND METHODS: During a 4 month period, 226 non-repetitive strains of P. aeruginosa were collected from patients residing in private healthcare centres (73.5%) or at home (26.5%). Resistance rates were evaluated by MIC determination, and beta-lactam and aminoglycoside resistance was analysed by phenotypic tests, PCR amplification, cloning and sequencing. RESULTS: Among the ticarcillin-resistant strains (38.1%), 33.7% overexpressed their chromosomal cephalosporinase, 27.9% produced acquired penicillinases (21 PSE-1, 2 OXA-21 and 1 TEM-2), 4.7% produced extended-spectrum beta-lactamases (ESBLs) (3 TEM-21 and 1 SHV-2a) and 45.3% possessed a non-enzymatic resistance (NER). Thus, 88.4% had a single mechanism of resistance, whereas 11.6% cumulated several mechanisms. No carbapenemases were detected among the 6.6% imipenem-resistant strains. With regard to aminoglycosides, 23.0% of the strains exhibited an acquired resistance to gentamicin (GEN), tobramycin (TOB), amikacin (AMK) or netilmicin (NET). Enzymatic resistance was more frequent (71.2%) than NER (34.6%). Various aminoglycoside modifying enzymes were associated with overlapping phenotypes: 36.5% strains produced AAC(6')-I with either a serine (GEN-TOB-NET) or a leucine (TOB-NET-AMK) at position 119, or both variants (GEN-TOB-NET-AMK); 21.2% expressed ANT(2'')-I (GEN-TOB), 7.7% AAC(3)-II (GEN-TOB-NET), 5.8% AAC(3)-I (GEN) and 1.9% AAC(6')-II (GEN-TOB-NET-AMK) or AACA7 (TOB-NET-AMK). CONCLUSIONS: Antibiotic resistance rates in P. aeruginosa were globally similar in general practice as in French hospitals. This first analysis of resistance mechanisms showed an unexpectedly high frequency of ESBLs and an unusual distribution of aminoglycoside modifying enzymes.

Comparative transcriptome profiling of near-isogenic barley (Hordeum vulgare) lines differing in the allelic state of a major grain protein content locus identifies genes with possible roles in leaf senescence and nitrogen reallocation.

To identify genes involved in the regulation and execution of leaf senescence and whole-plant nitrogen reallocation, near-isogenic barley germplasm divergent in senescence timing and protein concentration of mature grains was contrasted. Barley lines differing in allelic state at a major locus on chromosome six, controlling grain protein concentration, were obtained after four generations of backcrossing. Based on physiological data indicating major differences between low- and high-grain protein germplasm at 14-21 d past anthesis, the flag leaf and kernel transcriptomes of the low-protein parent and one high-protein near-isogenic line were compared at these time points, using the 22-k Barley1 Affymetrix microarray. Our data associate several genes with both known (based on sequence comparisons) and unknown functions with the senescence process. These include leucine-rich repeat transmembrane protein kinases, a glycine-rich RNA-binding protein with homology to AtGRP7 and a 'mother of FT/TF1' gene. Our data also indicate upregulation of genes coding for both plastidial and extraplastidial proteases in germplasm with accelerated leaf senescence. Functional characterization of candidate genes identified by this research may contribute to our understanding of the molecular network underlying leaf senescence and nitrogen reallocation.

Extended-spectrum-beta-lactamase-producing Enterobacteriaceae strains in various types of private health care centers.

During a 2004 survey, 49 extended-spectrum-beta-lactamase-producing enterobacteria were collected in 20 French private health care centers and one local hospital. They included 12 CTX-M-producing Escherichia coli strains (1.8% versus 0.3% in a 1999 survey). Most of them belonged to the same clone and contained a bla(CTX-M-15) gene on similar conjugative plasmids.

Clinical and molecular analysis of extended-spectrum {beta}-lactamase-producing enterobacteria in the community setting.

During a previous survey, five extended-spectrum beta-lactamase (ESBL)-producing enterobacteria (ESBLE) (two Enterobacter aerogenes isolates expressing TEM-24 b, two Escherichia coli isolates expressing TEM-21 or TEM-24 b, and one Klebsiella pneumoniae isolate expressing SHV-4/TEM-15) responsible for urinary tract infections (UTIs) were found among 1,584 strains collected from community patients. The aim of the present study was to elucidate the route of emergence of these typically nosocomial organisms in the community. Thus, the files of the five patients were analyzed over at least a decade, and potentially related ESBLE from hospitals or clinics were examined. Their enzymes were characterized at a molecular level, and the strains were typed by amplified-primed PCR, enterobacterial repetitive intergenic consensus PCR, and restriction plasmid profile. All patients (C1 to C5) had risk factors for ESBLE acquisition, including past history of hospitalization (2.5 to 23 months before). Four (C1 and C3 to C5) had previously received antibiotics (concomitantly to 35 months earlier), two (C1 and C3) had indwelling urinary catheters and recurrent UTIs, and three (C2, C3, and C5) formerly experienced ESBLE-induced UTIs (2 to 11 months before). The same ESBLE and/or an identical or similar ESBL-encoding plasmid was identified in the hospital ward (C1 to C4) or in a clinic (C5) where the patients had previously resided. Patients C1 and C4, infected with different ESBLE carrying a closely related plasmid, were hospitalized in the same unit. Persistence of ESBLE over at least a 5-year period was demonstrated for patient C3. Thus, community-acquired UTIs in these patients likely resulted from nosocomially acquired ESBLE or an ESBL-encoding plasmid followed by a prolonged digestive carriage.

Extended-spectrum beta-lactamase-producing Enterobacteriaceae in community and private health care centers.

In 1999, 39 of 2,599 isolates of the family Enterobacteriaceae (1.5%) collected by eight private laboratories in the Aquitaine region in France produced an extended-spectrum beta-lactamase (ESBL). Among these were 19 Enterobacter aerogenes isolates; 8 Klebsiella pneumoniae isolates; 6 Escherichia coli isolates; 3 Proteus mirabilis isolates; and 1 isolate each of Serratia marcescens, Morganella morganii, and Providencia stuartii. ESBL producers were isolated from 38 patients, including 33 residents of 11 clinics or nursing homes and 5 ambulatory patients. Seven different ESBLs were characterized. These mainly consisted of TEM-24 (25 isolates) and TEM-21 (9 isolates), but TEM-15 (2 isolates) and TEM-3, TEM-19, SHV-4, and CTX-M-1 (1 isolate each) were also characterized. Seven strains showed the coexistence of different TEM- and/or SHV-encoding genes, including a new SHV-1 variant, SHV-44, defined by the substitution R205L previously reported for SHV-3 in association with S238G. The epidemiology of the ESBL producers was investigated by random amplification of polymorphic DNA, typing by enterobacterial repetitive intergenic consensus PCR, analysis of resistance cotransferred with the ESBL, and analysis of the restriction profiles of the ESBL-encoding plasmids. Of the TEM-24-expressing strains, 18 were E. aerogenes isolates, including 9 from the same clinic, that were representatives of the epidemic clone disseminating in France. Of the TEM-21-producing strains that belonged to different species of the family Enterobacteriaceae (E. coli, K. pneumoniae, and P. mirabilis), 8 were isolated in the same nursing home. Outbreaks due to strain and/or plasmid dissemination in these clinic and nursing home were demonstrated. The presence of ESBL producers in five ambulatory patients probably resulted from nosocomial acquisition. Our data highlight the serious need to monitor patients for ESBL-producing Enterobacteriaceae in general practice.