Factors associated with successful weight loss after liraglutide treatment for obesity.

AIM: To identify patient factors, including gastrointestinal functions, that are predictive or associated with weight loss in response to once-daily 3 mg liraglutide administered subcutaneously (SQ) or placebo in obesity. METHODS: One hundred and thirty-six obese adults (87% female) were randomized in a placebo-controlled, 16-week trial of liraglutide, escalated to 3 mg administered SQ daily. Gastrointestinal functions were measured at baseline and 16 weeks: gastric emptying of solids (GET1/2 ); fasting and postprandial gastric volumes; kcal ingested during ad libitum buffet meal and the nutrient drink test. GET1/2 was also measured at 5 weeks. A multiple variable regression model examined variables associated with weight loss of more than 4 kg at 16 weeks. A parsimonious model using backward selection identified the final model. RESULTS: Weight loss of more than 4 kg at 16 weeks occurred in 71% of liraglutide- and 16% of placebo-treated patients. In all participants combined, parameters univariately associated with a weight loss of more than 4 kg were GET1/2 at 5 and 16 weeks, weight loss at 5 weeks and kcal intake during the buffet meal at 16 weeks. The final parsimonious model (area under the receiver operator characteristics [AUROC] curve = 0.832) identified that factors associated with more than 4-kg weight loss were GET1/2 at 5 weeks (OR = 2.505; 95% CI: 1.57-3.997) per 50 minutes and kcal intake during ad libitum meal at 16 weeks (OR = 0.721; 95% CI: 0.602-0.864) per 100 kcal. Among only the 60 liraglutide-treated subjects, kcal intake at 16 weeks was associated with 4-kg weight loss (AUROC = 0.757). CONCLUSIONS: Slower GET1/2 and weight loss at 5 weeks predicted a weight loss of more than 4 kg at 16 weeks in all participants. Among liraglutide-treated adults, weight loss of more than 4 kg was associated with ad libitum meal kcal intake at 16 weeks.

Sural nerve biopsy utility by masked assessment of individual histologic preparations.

BACKGROUND AND AIMS: Comprehensive study of sural nerve biopsy utility based on individual histopathologic preparations is lacking. We aimed to quantify the value of different histologic preparations in diagnosis. METHODS: One hundred consecutive sural nerves were studied by standard histological preparations plus graded teased nerve fibers (GTNF), immunohistochemistry, and epoxy-semithin morphometry. Three examiners scored the individual preparations separately by a questionnaire of neuropathic and interstitial abnormalities, masked to the biopsy number, versus a gold-standard of all preparations. Multivariate modeling was utilized to determine best approach versus the gold-standard. RESULTS: Highest confidence (range 8-9 of 10) and inter-rater reliability (99%) for fiber abnormalities came from GTNF, and interstitial abnormalities from paraffin stains (range 7-8, 99%). Vasculitic neuropathy associated with GTNF axonal degeneration (moderate to severe 79%) with OR 3.8, 95% CI (1.001-14.7), p = .04, but not significantly with the other preparations. Clinicopathologic diagnoses associated with teased fiber abnormalities in chronic inflammatory demyelinating polyradiculoneuropathy, 80% (8/10); amyloidosis, 50% (1/2); adult-onset polyglucosan disease 100% (1/1). GTNF and paraffin stains significantly correlated with fiber density determined by morphometric analysis (GTNF: OR 9.9, p < .0001, paraffin: OR 3.8, p = .03). GTNF combined with paraffin sections had highest accuracy for clinicopathologic diagnoses and fiber density with 0.86 C-stat prediction versus morphometric analysis. Pathological results lead to initiation or changes of immunotherapy in 70% (35/50; initiation n = 22, reduction n = 9, escalation n = 4) with the remaining having alternative intervention or no change. INTERPRETATION: Nerve biopsy paraffin stains combined with GTNF have highest diagnostic utility, confidence, inter-rater reliability, improving accuracy for a pathologic diagnosis aiding treatment recommendations. Immunostains and epoxy preparations are also demonstrated useful supporting consensus guidelines. This study provides class II evidence for individual nerve preparation utility.

Impact of Bile Acid Diarrhea in Patients With Diarrhea-Predominant Irritable Bowel Syndrome on Symptoms and Quality of Life.

BACKGROUND & AIMS: Bile acid diarrhea (BAD) affects approximately a quarter of patients with irritable bowel syndrome with diarrhea (IBS-D). We aimed to compare the demographics, bowel and somatic symptoms, and quality of life of patients with IBS-D, with or without BAD. METHODS: On one occasion, patients with IBS-D (positive for Rome III criteria) completed the following questionnaires: bowel disease questionnaire, Hospital Anxiety and Depression inventory, general quality of life (Symptom Checklist-90), and IBS-specific quality of life. A fasting serum C4 level higher than 52.5 ng/mL was used as a biomarker for BAD. Statistical analysis included a multiple variable logistic model to identify strong predictors of BAD in IBS-D. RESULTS: Among 219 patients (79% female) with IBS-D, 44 had BAD; the BAD group was significantly older and had a higher body mass index than the patients without BAD. Patients with BAD had more severe bowel dysfunction and impact on IBS-specific quality of life (need of toilet proximity) compared with patients with IBS-D without BAD. Patients with BAD were more likely than other IBS-D groups to receive antidiarrheals, bile acid binders, and antacid secretory agents. The severity of diarrhea and need of toilet proximity were predictors of BAD in IBS-D (P < .01). Patients with BAD were more likely to have a depression score higher than 8 on the Hospital Anxiety and Depression inventory. CONCLUSIONS: There is a greater impact on bowel and somatic symptoms and quality of life in IBS-D with BAD compared with IBS-D without BAD. Screening for BAD in IBS-D is especially relevant, with more severe and frequent diarrhea along with urgency.

Comparative Outcomes of Cap Assisted Endoscopic Resection and Endoscopic Submucosal Dissection in Dysplastic Barrett's Esophagus.

BACKGROUND & AIMS: Endoscopic resection is an important component of the endoscopic treatment of Barrett's esophagus (BE) with dysplasia and intramucosal adenocarcinoma. Endoscopic resection can be performed by cap-assisted endoscopic mucosal resection (cEMR) or endoscopic submucosal dissection (ESD). We compared the histologic outcomes of ESD vs cEMR, followed by ablation. METHODS: We queried a prospectively maintained database of all patients undergoing cEMR and ESD followed by ablation at our institution from January 2006 to March 2020 and abstracted relevant demographic and clinical data. Our primary outcomes included the rate of complete remission of dysplasia (CRD): absence of dysplasia on surveillance histology, and complete remission of intestinal metaplasia (CRIM): absence of intestinal metaplasia. Our secondary outcome included complication rates. RESULTS: We included 537 patients in the study: 456 underwent cEMR and 81 underwent ESD. The cumulative probabilities of CRD at 2 years were 75.8% and 85.6% in the cEMR and ESD groups, respectively (P < .01). Independent predictors of CRD were as follows: ESD (hazard ratio [HR], 2.38; P < .01) and shorter BE segment length (HR, 1.11; P < .01). The cumulative probabilities of CRIM at 2 years were 59.3% and 50.6% in the cEMR and ESD groups, respectively (P > .05). The only independent predictor of CRIM was a shorter BE segment (HR, 1.16; P < .01). CONCLUSIONS: BE patients with dysplasia or intramucosal adenocarcinoma undergoing ESD reach CRD at higher rates than those treated with cEMR, although CRIM rates at 2 years and complication rates were similar between the 2 groups.

Budesonide Maintenance in Microscopic Colitis: Clinical Outcomes and Safety Profile From a Population-Based Study.

INTRODUCTION: Outcomes and safety of budesonide maintenance therapy in microscopic colitis (MC) are not well known. METHODS: Adult residents of Olmsted County, Minnesota, diagnosed with MC (2002-2019) and treated with budesonide were identified using the Rochester Epidemiology Project. Response was assessed at 12 ± 4 weeks after initiation of therapy and defined as complete (resolution of diarrhea), partial (≥50% improvement in the number of bowel movements), nonresponse (<50% improvement), and intolerance (discontinued because of side effects). For safety outcomes, cases (budesonide maintenance) and MC controls (no budesonide therapy) were matched by sex and age at diagnosis (±2 years). RESULTS: A total of 450 patients were identified, of whom 162 (36.0%) were treated with budesonide for induction of clinical remission (median age 67 [23-91] years and 126 women [77.8%] ). Clinical outcomes for induction were as follows: 130 (80.2%) complete response, 22 (13.6%) partial response, 8 (4.9%) no response, and 2 (1.2%) intolerance. After induction, 96 (63.2%) had recurrence after discontinuation, of whom 27 (28.1%) required further budesonide induction treatment without maintenance, 56 (58.3%) required long-term budesonide maintenance, and 13 (13.5%) were treated with other therapies. Of those receiving budesonide maintenance, all responded (55 [98.2%] complete and 1 [1.8%] partial). No patient stopped maintenance from adverse events. The median duration of follow-up was 5.6 years (0.3-18.9). There was no significant difference between cases and controls in the incidence of osteopenia/osteoporosis, diabetes mellitus, hypertension, glaucoma, or cataracts. DISCUSSION: The long-term use of budesonide in MC seems to be effective and generally well tolerated with limited adverse effects.

Cannabidiol for Functional Dyspepsia With Normal Gastric Emptying: A Randomized Controlled Trial.

INTRODUCTION: Cannabidiol (CBD), a CBR2 agonist with limited psychic effects, antagonizes CB1/CB2 receptors. Allelic variation CNR1 (gene for CBR1) rs806378 and FAAH rs324420 were associated with altered gut motility and sensation. This study aimed to compare the pharmacodynamics and clinical effects of a 4-week treatment with pharmaceutical-grade CBD vs placebo and assess the interactions of FAAH and CNR1 gene variants on the effects of CBD in patients with functional dyspepsia (FD). METHODS: We performed a randomized, double-blinded, placebo-controlled (1:1 ratio) study of CBD b.i.d. (20 mg/kg/d according to the US Food and Drug Administration escalation guidance) in FD patients with nondelayed gastric emptying (GE) at baseline. Symptoms were assessed by validated daily symptom diary (0-4 scale for upper abdominal pain, nausea, and bloating), weekly assessment of adequate relief, Leuven Postprandial Distress Scale (8 symptoms, adjectival scores rated 0-4 for severity), and quality of life (Short-Form Nepean Dyspepsia Index [average of 10 dimensions each on a 5-point scale]). After the 4-week treatment, all patients underwent measurements of GE of solids, gastric volumes, and Ensure nutrient satiation test. Statistical analysis compared 2 treatments for all endpoints and the effects of CBD in association with FAAH rs324420 and CNR1 rs806378. RESULTS: CBD and placebo effects on physiological functions and patient response outcomes were not significantly different. There were borderline CBD treatment-by-genotype interactions: rs806378 CNR1 with Leuven Postprandial Distress Scale ( P = 0.06) and GE solids ( P = 0.12). DISCUSSION: Approved doses of CBD used off-label do not relieve FD with normal baseline GE of solids or alter gastric motor functions and satiation. CBD treatment-by-gene interactions suggest potential benefits for postprandial distress with CNR1 rs806378 T allele.

Effects of Colesevelam on Bowel Symptoms, Biomarkers, and Colonic Mucosal Gene Expression in Patients With Bile Acid Diarrhea in a Randomized Trial.

BACKGROUND & AIMS: Approximately one-third of patients with IBS-diarrhea (IBS-D) have increased bile acid (BA) synthesis or excretion. An open-label study showed benefits of colesevelam on bowel functions, consistent with luminal BA sequestration by colesevelam. We compared the effects of colesevelam vs placebo on symptoms and gene expression patterns in the sigmoid colon mucosa in patients with BA diarrhea associated with IBS-D. METHODS: We performed a double-blind, parallel-group study of 30 adults with IBS-D and evidence of increased BA synthesis or fecal excretion, from December 2017 through December 2018 at a single center. Patients were randomly assigned (1:1) to groups given colesevelam (3 tablets, 625 mg each) or matching placebo, orally twice daily for 4 weeks. Stool diaries documented bowel functions for 8 days before and 28 days during colesevelam or placebo. Stool and fasting serum samples were collected for analyses of fecal BAs and serum levels of C4 and FGF19. We measured colonic transit by scintigraphy, mucosal permeability by in vivo excretion of saccharide probes, and mRNA levels in rectosigmoid biopsies. All measurements were made at baseline and on the last days of treatment. The primary endpoints were change in total fecal BA concentration and stool consistency. RESULTS: Compared with placebo, colesevelam was associated with significant changes in sequestered fecal total BA excretion (P < .001) and serum levels of C4 and FGF19 (both P < .001), and with a mean increase in fecal level of deoxycholic acid (10%; P = .07) compared to placebo. Colesevelam decreased colon mucosal expression of NR1H4 and P2RY4 and increased expression of GPBAR1, compared with baseline. Stool frequency and consistency, colonic transit, and permeability did not differ significantly between groups. Colesevelam was well tolerated. CONCLUSIONS: In a randomized trial, we found that colesevelam increases delivery of total and secondary BAs to stool, hepatic BA synthesis, and colonic mucosal expression of genes that regulate BA, farnesoid X, and GPBAR1 receptors. Larger studies are needed to determine the effects on clinical responses. ClinicalTrials.gov no: NCT03270085.

Population-Based Assessment of Aortic-Related Outcomes in Aortic Dissection, Intramural Hematoma, and Penetrating Aortic Ulcer.

BACKGROUND: The aim of the study was to analyze aortic-related outcomes after diagnosis of aortic dissection (AD), intramural hematoma (IMH), and penetrating aortic ulcer (PAU) from a population-based approach. METHODS: Retrospective review of an incident cohort of AD, IMH, and PAU patients in Olmsted County, Minnesota from 1995 to 2015. Primary end point was aortic death. Secondary end points were subsequent aortic events (aortic intervention, new dissection, or rupture not present at presentation) and first-time diagnosis of an aortic aneurysm. Outcomes were compared with randomly selected population referents matched for age and sex in a 3:1 ratio using Cox proportional hazards regression adjusting for comorbidities. RESULTS: Among 133 patients (77 AD, 21 IMH, and 35 PAU), 57% were males, and mean age was 71.8 years (standard deviation, 14). Median follow-up was 10 years. Of 73 deaths among AD/IMH/PAU patients, 23 (32%) were aortic-related. Estimated freedom from aortic death was 84%, 80%, and 77% at 5, 10, and 15 years. There were no aortic deaths among population referents (adjusted hazard ratio [HR] for aortic death in AD/IMH/PAU, 184.7; 95% confidence interval [95% CI], 10.3-3,299.2; P < 0.001). Fifty (38%) AD/IMH/PAU patients had a subsequent aortic event (aortic intervention, new dissection, or rupture), whereas there were 8 (2%) aortic events among population referents (all elective aneurysm repairs; adjusted HR for any aortic event and aortic intervention in AD/IMH/PAU patients, 33.3; 95% CI, 15.3-72.0; P < 0.001 and 31.5; 95% CI, 14.5-68.4; P < 0.001, respectively). After excluding aortic events/interventions ≤14 days of diagnosis, AD/IMH/PAU patients remained at increased risk of any aortic event (adjusted HR, 10.8; 95% CI, 3.9-29.8; P < 0.001) and aortic intervention (adjusted HR, 9.6; 95% CI, 3.4-26.8; P < 0.001). Among those subjects with available follow-up imaging, the risk of first-time diagnosis of aortic aneurysm was significantly increased for AD/IMH/PAU patients when compared with population referents (adjusted HR, 10.9; 95% CI, 5.4-21.7; P < 0.001 and 8.3; 95% CI, 4.1-16.7; P < 0.001 for thoracic and abdominal aneurysms, respectively) and remained increased when excluding aneurysms that formed within 14 days of AD/IMH/PAU (adjusted HR, 6.2; 95% CI, 1.8-21.1; P = 0.004 and 2.8; 95% CI, 1.0-7.6; P = 0.040 for thoracic and abdominal aneurysms, respectively). CONCLUSIONS: AD/IMH/PAU patients have a substantial risk of aortic death, any aortic event, aortic intervention, and first-time diagnosis of aortic aneurysm that persists even when the acute phase (≤14 days after diagnosis) is uncomplicated. Advances in postdiagnosis treatment are necessary to improve the prognosis in these patients.

Cardiovascular morbidity and mortality after aortic dissection, intramural hematoma, and penetrating aortic ulcer.

OBJECTIVE: The nonaortic cardiovascular morbidity and mortality of patients with aortic dissection (AD), intramural hematoma (IMH), and penetrating aortic ulcer (PAU) is unknown. We aimed to define the rates of cardiovascular (CV) events in a cohort of patients with newly diagnosed AD, IMH, and PAU. METHODS: We performed a retrospective review of all Olmsted County, Minnesota, residents diagnosed with AD, IMH, and PAU from 1995 to 2015. The primary outcome was nonaortic CV death. The secondary outcome was a first-time nonfatal CV event (myocardial infarction, heart failure [HF], or stroke). The outcomes were compared with age- and sex-matched population referents using Cox proportional hazards regression, with adjustment for comorbidities. RESULTS: A total of 133 patients (77 with AD, 21 with IMH, 35 with PAU; 57% male) with a mean age of 71.8 ± 14.1 years were identified. The median follow-up was 10 years. Compared with the population referents, the patients with AD/IMH/PAU had an increased risk of CV death (adjusted hazard ratio [HR], 2.4; 95% confidence interval [CI], 1.4-4.2; P = .003) and an increased risk of any first-time nonfatal CV event (adjusted HR, 3.0; 95% CI, 1.9-4.8; P < .001), mainly resulting from an increased risk of first-time HF (adjusted HR, 2.7; 95% CI, 1.7-4.3; P < .001). When excluding events within 14 days of the diagnosis, the patients with AD/IMH/PAU remained at increased risk of CV death (adjusted HR, 2.6; 95% CI, 1.4-4.7; P = .002), any first-time nonfatal CV event (adjusted HR, 2.6; 95% CI, 1.5-4.4, P <.001), and first-time HF (adjusted HR 2.5, 95% CI 1.5-4.3; P < .001). CONCLUSIONS: Compared with the population referents, the patients with AD/IMH/PAU had a two- to threefold risk of nonaortic CV death, any first-time nonfatal CV event, and first-time HF. These data implicate the need for long-term cardiovascular management for patients with AD/IMH/PAU.

Effects of NK1 receptors on gastric motor functions and satiation in healthy humans: results from a controlled trial with the NK1 antagonist aprepitant.

Aprepitant, an NK1 receptor antagonist, is approved for the treatment of chemotherapy-induced or postoperative emesis by blocking NK1 receptors in the brain stem vomiting center. The effects of NK1 receptors on gastric functions and postprandial symptoms in humans are unclear; a single, crossover study did not show a significant effect of aprepitant on gastrointestinal transit. Our aim was to compare, in a randomized, double-blind, placebo-controlled, parallel-group study (12 healthy volunteers per group), the effects of aprepitant vs. placebo on gastric emptying of solids (by scintigraphy) with a 320-kcal meal, gastric volumes (GVs; fasting and accommodation by single photon emission-computed tomography ), satiation [maximum tolerated volume (MTV)], and symptoms after a dyspeptogenic meal of Ensure. Aprepitant (125 mg on day 1, followed by 80 mg on days 2-5) or placebo, one tablet daily, was administered for 5 consecutive days. Statistical analysis was by unpaired rank sum test, adjusted for sex difference and body mass index. To assess treatment effects on symptoms, we incorporated MTV in the model. Aprepitant increased fasting, postprandial, and accommodation GV and tended to increase volume to fullness and MTV by ~200 kcal. However, aprepitant increased aggregate symptoms, nausea, and pain scores after ingestion the MTV of Ensure. There was no significant effect of aprepitant on gastric half-emptying time of solids. We conclude that NK1 receptors are involved in the control of GV and in determining postprandial satiation and symptoms. Further studies of the pharmacodynamics and therapeutic role of NK1 receptor antagonists in patients with gastroparesis and dyspepsia are warranted.NEW & NOTEWORTHY Aprepitant increases fasting, postprandial, and accommodation gastric volumes. Aprepitant increases volume to fullness and maximum tolerated volume during a nutrient drink test. NK1 receptors are involved in the control of gastric volume and in determining postprandial satiation and symptoms.

Incidence and Prevalence of Crohn's Disease and Ulcerative Colitis in Olmsted County, Minnesota From 1970 Through 2010.

BACKGROUND & AIMS: The incidence and prevalence of inflammatory bowel diseases (IBD) continue to increase worldwide. We sought to update incidence rates of Crohn's disease (CD) and ulcerative colitis (UC) in a well-defined United States population, calculating values for Olmsted County, Minnesota through 2010. We also calculated prevalence values. METHODS: The resources of the Rochester Epidemiology Project were used to identify county residents who were diagnosed with IBD (CD or UC), based on previously set criteria. Those with new diagnoses of CD or UC between 1970 and 2010 were identified as incidence cases, and those meeting diagnostic criteria on January 1, 2011, were identified as prevalence cases. Incidence rates were estimated (adjusted for age and sex to the US white population in 2010). Trends in incidence based on age at diagnosis, sex, and year of diagnosis were evaluated by Poisson regression. RESULTS: The incidence cohort included 410 patients with CD (51% female) and 483 individuals with UC (56% male). Median age of diagnosis was 29.5 years for persons with CD (range, 4-93 years) and 34.9 years for UC (range, 1-91 years). From 2000 through 2010, the adjusted annual incidence rate for CD was 10.7 cases per 100,000 person-years (95% confidence interval [CI], 9.1-12.3 person-years) and for UC was 12.2 per 100,000 (95% CI, 10.5-14.0 person-years). On January 1, 2011, there were 380 residents with CD, with an adjusted prevalence of 246.7 cases per 100,000 persons (95% CI, 221.7-271.8 cases per 100,000 persons), and 435 residents with UC, with an adjusted prevalence of 286.3 (95% CI, 259.1-313.5 cases per 100,000 persons). Male sex was significantly associated with a higher incidence rate of UC, and younger age was significantly associated with a higher incidence rate of CD. CONCLUSIONS: Estimated incidence rates for UC and CD in Olmsted County are among the highest in the United States. Extrapolating the adjusted prevalence to the most recent US Census, there could be approximately 1.6 million persons in the United States with IBD.

Low Risk of Pneumonia From Pneumocystis jirovecii Infection in Patients With Inflammatory Bowel Disease Receiving Immune Suppression.

BACKGROUND & AIMS: Use of immunosuppressants and inflammatory bowel disease (IBD) may increase the risk of pneumonia caused by Pneumocystis jirovecii (PJP). We assessed the risk of PJP in a population-based cohort of patients with IBD treated with corticosteroids, immune-suppressive medications, and biologics. METHODS: We performed a population-based cohort study of residents of Olmsted County, Minnesota, diagnosed with Crohn's disease (n = 427) or ulcerative colitis (n = 510) from 1970 through 2011. Records of patients were reviewed to identify all episodes of immunosuppressive therapies and concomitant PJP prophylaxis through February 2016. We reviewed charts to identify cases of PJP, cross-referenced with the Rochester Epidemiology Project database (using diagnostic codes for PJP) and the Mayo Clinic and Olmsted Medical Center databases. The primary outcome was risk of PJP associated with the use of corticosteroids, immune-suppressive medications, and biologics by patients with IBD. RESULTS: Our analysis included 937 patients and 6066 patient-years of follow-up evaluation (median, 14.8 y per patient). Medications used included corticosteroids (520 patients; 55.5%; 555.4 patient-years of exposure), immunosuppressants (304 patients; 32.4%; 1555.7 patient-years of exposure), and biologics (193 patients; 20.5%; 670 patient-years of exposure). Double therapy (corticosteroids and either immunosuppressants and biologics) was used by 236 patients (25.2%), with 173 patient-years of exposure. Triple therapy (corticosteroids, immunosuppressants, and biologics) was used by 70 patients (7.5%) with 18.9 patient-years of exposure. There were 3 cases of PJP, conferring a risk of 0.2 (95% CI, 0.01-1.0) to corticosteroids, 0.1 (95% CI, 0.02-0.5) cases per 100 patient-years of exposure to immunosuppressants, 0.3 (95% CI, 0.04-1.1) cases per 100 patient-years of exposure to biologics, 0.6 (95% CI, 0.01-3.2) cases per 100 patient-years of exposure to double therapy, and 0 (95% CI, 0.0-19.5) cases per 100 patient-years of exposure to triple therapy. Primary prophylaxis for PJP was prescribed to 37 patients, for a total of 24.9 patient-years of exposure. CONCLUSIONS: In a population-based cohort of patients with IBD treated with corticosteroids, immunosuppressants, and biologics, there were only 3 cases of PJP, despite the uncommon use of PJP prophylaxis. Routine administration of PJP prophylaxis in these patients may not be warranted, although it should be considered for high-risk groups, such as patients receiving triple therapy.

Gastric Motor Dysfunction in Patients With Functional Gastroduodenal Symptoms.

OBJECTIVES: The pathophysiology of dyspeptic symptoms is complex. The aim of this study was to evaluate the association of gastric emptying (GE), gastric accommodation (GA), and respiratory sinus arrhythmia (RSA, to assess vagal dysfunction) in a large cohort with functional gastroduodenal symptoms. METHODS: We reviewed demographic, clinical features, and results of gastric motor and vagal function studies of 1,287 patients (74.0% females, mean age 43.1±15.4 years) who had undergone both single photon emission computed tomography GA and scintigraphic GE. Accommodation was based on postprandial to fasting gastric volume ratio (VR). Electrocardiograms were available and analyzed for RSA in 300 patients. RESULTS: There were 29.8% patients with normal GE and GA, 21.9% with abnormal GA only, 27.1% with abnormal GE only, and 21.1% with abnormal GA and GE. There were numerical differences in GA among patients with normal, accelerated, and delayed GE (P=0.062, by χ2). Increased GA (VR >3.85) was more prevalent in patients with delayed GE compared to accelerated GE (14.0% vs. 6.8%, P=0.004). Decreased VRs (median 2.9) were observed with accelerated GE compared to normal GE (median 3.1, P<0.05). Nausea and vomiting were more prevalent (in contrast to the less prevalent bloating) in patients with delayed compared to accelerated or normal GE (all P<0.05). In patients with diminished RSA, there was higher prevalence of reduced GA (41.5%) compared to those with preserved RSA (29.2%, P=0.031). Multivariable analysis showed associations of the main abdominal symptoms with gender, body mass index, gastric emptying, diabetes, and prior abdominal surgery. CONCLUSIONS: Patients with symptoms of functional gastroduodenal disorders may have one or more gastric motor dysfunctions and reduced RSA; among the patients with abnormal gastric motor functions, vomiting suggests delayed GE, whereas reduced RSA is associated with reduced GA.

Radiographs and computed tomography scans show similar observer agreement when classifying glenoid morphology in glenohumeral arthritis.

BACKGROUND: Glenohumeral subluxation and glenoid morphology are commonly evaluated in primary osteoarthritis by use of the Walch classification. The reliability of this classification system has been analyzed only by computed tomography (CT). The purpose of this study was to determine the reliability of plain axillary radiographs compared with CT scans. METHODS: Three shoulder surgeons blindly and independently evaluated the radiographs and CT scans of 75 consecutive shoulders with primary glenohumeral osteoarthritis. Each observer classified all shoulders according to Walch in 4 separate sessions, each 6 weeks apart. There were 2 sessions using only radiographs and 2 using only CT scans. The order of shoulders evaluated was randomized. RESULTS: The first reading by the most senior observer based on CT was arbitrarily used as the "gold standard" (A1, 21; A2, 13; B1, 12; B2, 28; C, 1). The average intraobserver agreement for radiographs was 0.66 (substantial; 0.66, 0.59, and 0.74 for each observer). The average intraobserver agreement for CT scans was 0.60 (moderate; 0.53, 0.61, and 0.65). Pairwise comparisons between observers showed higher agreement for radiographs than for CT scans (0.48 vs. 0.39). The average agreement for observations on radiographs and CT scans was 0.42 (moderate; 0.40, 0.37, and 0.50). CONCLUSION: In this study, intraobserver agreement using the Walch classification based on axillary radiographs was substantial and compared favorably with agreement based on CT scans. The Walch classification provides a useful frame of reference when assessing subluxation and glenoid morphology in primary glenohumeral osteoarthritis, but not unlike other classification systems, it does not allow perfect agreement among observers.

The role age plays in the outcomes and complications of shoulder arthroplasty.

BACKGROUND: This investigation used age as a continuous variable to estimate implant survival and the risk of complications. METHODS: Prospectively collected data were used to analyze 5494 consecutive shoulder arthroplasties performed from 1970 to 2012. Patients were a mean age of 67 years. The association between the age at the index procedure and the risk for each outcome was assessed using Cox regression and smoothing spline analysis. RESULTS: Older age was associated with a decreased risk of revision surgery, revision for mechanical failure, and reoperation but with a higher risk for thromboembolic events. Reoperation rates also decreased in a linear fashion with older ages (P < .001). The risk of revision surgery decreased in a linear fashion between the ages of 40 and 85, with a 3% decreased risk of revision per 1-year increase in age (P < .01). This association held true in a multivariate model and when specific procedures were separated out. Compared with patients aged <50 years, patients aged from 50 to 65 years (P < .001) and those >65 years (P < .001) have decreased risks of revision surgery. The risk of a revision surgery in a patient aged >50 years was significantly decreased (~13% reduction in risk for each year; P < .001). There was a subtle association between older age and decreased rates of infection (P = .01). CONCLUSIONS: There is a strong association between older age and decreased rates of revision surgery and reoperation after shoulder arthroplasty, with a striking association with decreased rates of mechanical failure. These are important considerations when counseling younger patients regarding their risks.

Cumulative Length of Bowel Resection in a Population-Based Cohort of Patients With Crohn's Disease.

BACKGROUND & AIMS: Little is known about the cumulative extent of bowel resection among patients with Crohn's disease. METHODS: Using the resources of the Rochester Epidemiology Project, we identified a cohort of 310 incident cases of Crohn's disease from Olmsted County, Minnesota who were diagnosed between 1970 and 2004. Operative and pathology reports were reviewed for bowel resection length. Median bowel resection lengths (with interquartile range [IQR]) were calculated per resection, cumulatively, and as a rate per year of follow-up. RESULTS: One hundred forty-seven patients underwent 1 or more bowel resections. The median follow-up time per patient was 13.6 years (range, 0.2-39 years). Among the 141 patients with resection data available, 211 resections were performed (100 patients with 1 resection, 24 with 2 resections, 9 with 3 resections, 6 with 4 resections, 1 with 5 resections, and 1 patient with 7 resections). The median length of bowel resected was 40 cm (IQR, 22-65 cm) at any resection. The median cumulative length of bowel resected was 64 cm (38-93 cm) during the follow-up period. The median (IQR) rate of bowel resected was 4.2 cm total bowel annually (2.8-7.7 cm). The median length resected was highest for the first resection (52 cm; IQR, 32-71 cm). A mixed regression analysis showed that the length of the first resection was significantly greater than that of the second (P = .002), without significant differences between the second and third or subsequent resections. CONCLUSIONS: In a population-based cohort of patients with Crohn's disease, the median cumulative length of total bowel resected was 64 cm during the follow-up period; the median rate of bowel loss due to resection was 4.2 cm annually.

Hidradenitis Suppurativa in Patients With Inflammatory Bowel Disease: A Population-Based Cohort Study in Olmsted County, Minnesota.

BACKGROUND & AIMS: Patients with inflammatory bowel disease (IBD) may be at higher risk for hidradenitis suppurativa (HS). We studied the risk and clinical characteristics of HS in a population-based cohort of patients with IBD. METHODS: We identified all cases of HS (confirmed by biopsy and/or dermatologic evaluation) in a population-based inception cohort of Olmsted County, Minnesota, residents diagnosed with IBD between 1970 and 2004 and followed up through August 2013. We estimated the incidence rate ratio of HS in patients with IBD compared with the general population, and described the clinical characteristics, risk factors, and management of HS. RESULTS: In 679 IBD patients followed up over a median of 19.8 years, we identified 8 patients with HS (mean age, 44.4 ± 8.3 y; 7 women; 6 obese). Compared with the general population, the incidence rate ratio of HS in IBD was 8.9 (95% confidence interval, 3.6-17.5). The 10- and 30-year cumulative incidence of HS was 0.85% and 1.55%, respectively. Five patients had Crohn's disease, 4 of whom had perianal disease; of 3 patients with ulcerative colitis, 2 had undergone ileal pouch-anal anastomosis. Axillae, groin, and thighs were the most common sites of involvement. Six patients had Hurley stage 2 disease (recurrent abscesses with sinus tracts and scarring, involving widely separated areas), and required a combination of antibiotics and surgery; none of the patients were treated with anti-tumor necrosis factor-α agents. CONCLUSIONS: In this population-based study, patients with IBD were approximately 9 times more likely to develop HS than the general population, with a female predisposition.

Delineation of factors associated with prolonged length of stay after laparoscopic ventral hernia repair leads to a clinical pathway and improves quality of care.

BACKGROUND: Centers for Medicare and Medicaid Services define laparoscopic ventral hernia repair (LVHR) as outpatient procedure. We identified our institutional length of stay (LOS) to be above the National Surgical Quality Improvement Program (NSQIP) benchmark of 1 day [interquartile range (IQR) 2 days]. This study was undertaken to investigate risk factors associated with prolonged hospital stay and design an intervention to decrease median LOS. METHODS: This study analyzed institutional NSQIP data on patients who underwent elective LVHR from 2006 to 2011 to define factors associated with prolonged LOS, defined as LOS > 2 days. Modifiable factors identified in the initial analysis were included in a clinical care pathway to impact LOS. We repeated the NSQIP data analysis after implementation (4/2011-9/2012) to assess the effect of our intervention. Analysis was by univariate, ANOVA and logistic regression models. RESULTS: During the pre-implementation period, 80 patients with a median age of 54 years (31-84) stayed a median of 2 days (IQR 3). On univariate analysis, factors associated with prolonged LOS included operative time, mesh size, amount of narcotics used and female gender. In multivariate analysis, operative time and narcotics used were associated with a prolonged LOS, C statistic = 0.88. Introduction of a clinical pathway focusing on non-narcotic pain relief resulted in a decrease in mean narcotic usage from 223 to 63 mg morphine equivalents/patient (p < 0.0001), decrease in median LOS to 1 day (IQR 2) (p = 0.027), in line with NSQIP benchmarks, a slight decrease in complications and a 10% decrease in hospital cost. CONCLUSION: High narcotic use and long operative times are independent predictors of prolonged LOS in our patient population. Introduction of a standardized clinical care pathway designed to reduce perioperative narcotic use resulted in shorter LOS, improved quality and cost savings for patients undergoing LVHR.