Cirrhosis and Portal Hypertension Worsen Bowel Preparation for Screening Colonoscopy.

BACKGROUND: Colonoscopy is a diagnostic and therapeutic procedure that reduces colorectal cancer incidence and mortality but requires adequate bowel cleansing for high-quality examination. Past studies have suggested cirrhosis as a risk factor for worse bowel preparation. METHODS: We carried out a match-controlled retrospective study evaluating patients with and without cirrhosis who underwent outpatient screening colonoscopies to assess the effect of cirrhosis and portal hypertension complications on preparation quality and endoscopic measures. We also did a subgroup analysis excluding patients with obesity. RESULTS: We examined 1464 patients with cirrhosis and matched controls. Cirrhotic patients had lower mean Boston Bowel Preparation Scale (BBPS) scores and slower cecal intubation times. We found a single point increase in the Model for End-stage Liver Disease (MELD) score, as well as ascites, hepatic encephalopathy, and variceal hemorrhage were all associated with a longer cecal intubation time. Subgroup analysis excluding patients with obesity again found a significantly lower BBPS score and longer cecal intubation time while also finding a 24% drop in polyp detection. CONCLUSIONS: Patients with cirrhosis have worse BBPS scores and longer cecal intubation times. Nonobese cirrhotic patients additionally have a lower polyp detection rate. Portal hypertension complications were associated with worsened preparation quality and longer cecal intubation times. Each incremental increase in MELD score lengthened cecal intubation time. These findings support a more aggressive bowel preparation strategy for patients with cirrhosis, especially patients with severe disease or portal hypertension complications.

Top Tips for Direct Percutaneous Endoscopic Jejunostomy (DPEJ) Tube Placement.

Direct percutaneous endoscopic jejunostomy (DPEJ) provides post-pyloric enteral access in patients unable to meet long-term nutritional needs per os in situations where gastric feeding is neither tolerated nor feasible. Specific conditions associated with feeding intolerance due to due to nausea, vomiting, or ileus include gastric outlet obstruction, gastroparesis, or complications of acute or chronic pancreatitis; infeasibility may be due to high aspiration risk or prior gastric surgery. Since performing DPEJ is not an ACGME requirement for GI fellows or early career gastroenterologists, not all trainees are taught this technique. Hence, provider expertise for teaching and performing this technique varies widely across centers. In this article, we provide top tips for successful performance of DPEJ.

Safety of Percutaneous Endoscopic Jejunostomy Placement Compared With Surgical and Radiologic Jejunostomy Placement: A Nationwide Inpatient Assessment.

BACKGROUND AND AIMS: We compared the safety and outcomes of percutaneous jejunostomy tubes placed endoscopically (PEJ), fluoroscopically by interventional radiology (IR-jejunostomy), and open jejunostomy placed surgically (surgical jejunostomy). METHODS: Using the Nationwide Readmissions Database, we identified hospitalized patients who underwent a jejunostomy from 2016 to 2019. Selected patients were divided into 3 cohorts: PEJ, IR-jejunostomy, and surgical jejunostomy. Adjusted odds ratios (OR) for adverse events were calculated using multivariable logistic regression analysis. RESULTS: A total of 6022 (65.2±9.8 y) surgical jejunostomy patients, 3715 (63.6±11.0 y) endoscopic jejunostomy patients, and 14,912 (64.8±11.6 y) IR-jejunostomy patients were identified. Compared with surgery, PEJ patients were 32% less likely to experience postprocedure complications (OR: 0.68; 95% CI: 0.58-0.79, P<0.001) while IR-jejunostomy patients were 17% less likely to experience complications (OR: 0.83; 95% CI: 0.73-0.94, P<0.001); test of proportion showed that endoscopy had significantly fewer total adverse events compared with IR (P<0.001). For individual complications, compared with surgery, the odds of intestinal perforation using PEJ and IR, respectively, were 0.26 (95% CI: 0.14-0.49, P<0.001) and 0.31 (95% CI: 0.21-0.47, P<0.001), for postprocedure infection 0.32 (95% CI: 0.20-0.50; P<0.001) and 0.61 (95% CI: 0.45-0.83; P=0.001); and for hemorrhage requiring blood transfusion 0.71 (95% CI: 0.56-0.91; P=0.005) and 0.75 (95% CI: 0.61-0.91; P=0.003). CONCLUSIONS: Endoscopic placement of percutaneous jejunostomy tubes (PEJ) in inpatients is associated with significantly lower risks of adverse events and mortality compared with IR and surgical jejunostomy.

Esophageal Eosinophilia Is Common Among Relatives of Eosinophilic Esophagitis Patients.

BACKGROUND & AIMS: Familial clustering of eosinophilic esophagitis (EoE) has been described, and we report on the biopsy-assessed prevalence of esophageal eosinophilia (EE) in first-degree family members. The aim was to determine the prevalence of EE in first-degree adult relatives (FDRs) of EoE patients. METHODS: Index EoE patients diagnosed by EE (>15 eosinophils per high-power field) and proton pump inhibitor nonresponsiveness were identified and family trees were constructed. Adult FDRs were invited to undergo upper endoscopy with esophageal biopsies and to complete reflux, dysphagia, and allergy/atopy questionnaires. Questionnaire information was gathered only for those who responded as per institutional review board purview. Records from other children and adult FDRs with prior EoE diagnoses also were obtained when permission was obtained. Simple and multivariable logistic regression models were used to evaluate the unadjusted and odds ratios of EoE for demographic and clinical variables. RESULTS: A total of 239 FDRs from 37 index EoE patients were identified. Seventy-one of 239 adult (age, >18 y) FDRs completed endoscopy and questionnaires and 18 of 71 FDRs had EE. An additional 17 FDRs were confirmed to have EE after external medical record retrieval, resulting in a total of 35 of 239 (14.6%) FDRs with EE. Significantly more male FDRs had EE compared with female FDRs (P = .027). Proton pump inhibitors, dysphagia, gastroesophageal reflux disease, asthma, and reflux symptoms predicted EE in FDRs. FDRs who had EE reported hay fever, allergic eye symptoms, and food allergy more frequently than those without EE (P = .03, P = .001, and P = .02, respectively). Specifically, younger age, higher serum eosinophils, being male, and having food allergies all were associated with higher odds of EoE (P = .0211, P = .0031, P = .0362, and P = .0089, respectively). CONCLUSIONS: The prevalence of esophageal eosinophilia is extremely high and male-predominant in first-degree relatives of EoE patients. Symptoms of hay fever, allergic eye symptoms, and food allergy were predictors of EE in FDRs. Dysphagia did not predict esophageal eosinophilia. Family members of EoE patients are at risk for EE, particularly those who have atopic symptoms.

High-throughput methods for measuring DNA thermodynamics.

Understanding the thermodynamics of DNA motifs is important for prediction and design of probes and primers, but melt curve analyses are low-throughput and produce inaccurate results for motifs such as bulges and mismatches. Here, we developed a new, accurate and high-throughput method for measuring DNA motif thermodynamics called TEEM (Toehold Exchange Energy Measurement). It is a refined framework of comparing two toehold exchange reactions, which are competitive strand displacement between oligonucleotides. In a single experiment, TEEM can measure over 1000 ΔG° values with standard error of roughly 0.05 kcal/mol.

Safety of endoscopist-directed nurse-administered balanced propofol sedation in patients with severe systemic disease (ASA class III).

BACKGROUND AND AIMS: The safety of endoscopist-directed nurse-administered propofol sedation (EDNAPS) has been demonstrated in low-risk patients (American Society of Anesthesiologists [ASA] class I and II). There are limited data regarding the safety of EDNAPS for endoscopic procedures in ASA class III patients. The purpose of this study was to determine the safety of EDNAPS for routine outpatient endoscopy in this population. METHODS: We retrospectively reviewed all outpatient EGDs and colonoscopies performed with EDNAPS at the University of Utah from January 2015 to November 2018. Exclusion criteria were inpatient procedures, combined procedures, ASA IV or higher, use of continuous or bilevel positive airway pressure at the start of the procedure, or procedures performed by a nongastroenterologist. Major adverse events were defined as intubation or death. Minor adverse events were defined as hypoxia, hypotension, bradycardia, or need for airway interventions. Patients were stratified by procedure type and ASA I/II status and were compared with patients with ASA III status and matched according to age, gender, and the involvement of a fellow in a 3 to 1 fashion. RESULTS: The final sample size was 18,910 colonoscopy procedures (17,205 patients) and 9178 EGD procedures (6827 patients). In both colonoscopy and EGD procedures, there were no major adverse events such as intubation, need for resuscitation, or death. The rates of any airway intervention, jaw thrust, oral nasal airway, or use of positive pressure ventilation were low in both procedure types and not different between ASA I/II and ASA III patients. CONCLUSION: EDNAPS is safe in both ASA I/II and ASA class III patients undergoing routine outpatient endoscopy.

A comparison of ventilation with a non-invasive ventilator versus standard O2 with a nasal cannula for colonoscopy with moderate sedation using propofol.

The aim of this study was to test the effects of CPAP on moderately sedated patients undergoing colonoscopy. Our hypothesis was that CPAP can reduce the incidence and duration of obstructive apnea and hemoglobin oxygen desaturation in patients undergoing procedural sedation for colonoscopy. Two groups of consenting adult patients scheduled to undergo routine colonoscopy procedures and sedated with propofol and fentanyl were monitored in this study: control and intervention. Patients in the intervention group were connected via a facemask to a ventilator that delivered supplemental oxygen (100%) through a standard air-cushion mask. The mask had a built-in leak to facilitate CO2 clearance during CPAP. Patients in the control group received 2-10 L/min of oxygen via nasal cannula or non-rebreather mask. Subjects in the control group were collected in a prior study and used as historical controls. The primary outcome measures were the number of apneic events and the cumulative duration of apneic events. An apneic event was defined as a period longer than 10 s without respiration. The secondary outcome was the area under the curve (AUC) for the arterial oxygen saturation less than 90% versus time during sedative and analgesic administration (time (s) below threshold multiplied by percent below threshold). A desaturation event was defined as a period of time during which arterial oxygen saturation was less than 90%. 29 patients were enrolled in the intervention group and 156 patients were previously enrolled in the control group as part of an earlier study. The median number of apneic events in the control group was 7 compared to 0 in the intervention group. The intervention group experienced apnea less than 1% of the total procedure time compared to 17% in the control group (p < 0.001). There were no desaturation events observed in the 29 patients in the intervention group. In contrast, 27 out of 156 patients in the control group experienced a desaturation event. Average AUC of patients in the control group was 70%-s (time (s) * oxygen saturation below < 90%) (95% CI 32.34-108.60%) whereas the average AUC in intervention group patients was 0%-s (% time (s) * oxygen saturation < 90%) (95% CI 0-0%), p = 0.01. This preliminary study found that CPAP via a tight-fitting mask may be an effective tool to reduce the incidence and duration of obstructive apneic events as well as hemoglobin oxygen desaturation during lower endoscopy procedures that use propofol and fentanyl for sedation.Clinical Trial Registration ClinicalTrials.gov ID: NCT02623270. https://clinicaltrials.gov/ct2/show/NCT02623270 .

Continuously tunable nucleic acid hybridization probes.

In silico-designed nucleic acid probes and primers often do not achieve favorable specificity and sensitivity tradeoffs on the first try, and iterative empirical sequence-based optimization is needed, particularly in multiplexed assays. We present a novel, on-the-fly method of tuning probe affinity and selectivity by adjusting the stoichiometry of auxiliary species, which allows for independent and decoupled adjustment of the hybridization yield for different probes in multiplexed assays. Using this method, we achieved near-continuous tuning of probe effective free energy. To demonstrate our approach, we enforced uniform capture efficiency of 31 DNA molecules (GC content, 0-100%), maximized the signal difference for 11 pairs of single-nucleotide variants and performed tunable hybrid capture of mRNA from total RNA. Using the Nanostring nCounter platform, we applied stoichiometric tuning to simultaneously adjust yields for a 24-plex assay, and we show multiplexed quantitation of RNA sequences and variants from formalin-fixed, paraffin-embedded samples.

Confined Thalamic Deep Brain Stimulation in Refractory Essential Tremor.

BACKGROUND: Thalamic ventral intermediate nucleus (VIM) deep brain stimulation (DBS) is an effective therapy for medication-refractory essential tremor (ET). However, 13-40% of patients with an initially robust tremor efficacy lose this benefit over time despite reprogramming attempts. At our institution, a cohort of ET patients with VIM DBS underwent implantation of a second anterior (ventralis oralis anterior; VOA) DBS lead to permit "confined stimulation." We sought to assess whether confined stimulation conferred additional tremor capture compared to VIM or VOA stimulation alone. METHODS: Seven patients participated in a protocol-based programming session during which a video-recorded Fahn-Tolosa-Marin Part A (FTM-A) tremor rating scale was used in the following 4 DBS states: off stimulation, VIM stimulation alone, VOA stimulation alone, and dual lead (confined) stimulation. RESULTS: The average (SD) baseline FTM-A off score was 17.6 (4.0). VIM stimulation alone lowered the average FTM-A total score to 6.9 (4.0). Confined stimulation further attenuated the tremor, reducing the total score to 5.7 (2.8). CONCLUSIONS: Confined thalamic DBS can provide additional symptomatic benefits in patients with unsatisfactory tremor control from VIM or VOA stimulation alone.

Population-based familial aggregation of eosinophilic esophagitis suggests a genetic contribution.

BACKGROUND: Prior familial clustering studies have observed an increased risk of eosinophilic esophagitis (EoE) mostly among first-degree relatives, suggesting a genetic contribution to EoE, and twin studies have suggested a powerful contribution from environmental factors. OBJECTIVE: This study sought to clarify the contribution of genetic factors to EoE through estimation of familial aggregation and risk of EoE in extended relatives. METHODS: The Utah Population Database, a population-based genealogy resource linked to electronic medical records for health care systems across the state of Utah, was used to identify EoE cases and age, sex, and birthplace-matched controls at a 5:1 ratio. Logistic regression was used to determine the odds of EoE among relatives of EoE probands compared with the odds of EoE among relatives of controls. RESULTS: There were 4,423 EoE cases and 24,322 controls. The population-attributable risk of EoE was 31% (95% CI, 28% to 34%), suggesting a relatively strong genetic contribution. Risks of EoE were significantly increased among first-degree relatives (odds ratio [OR], 7.19; 95% CI, 5.65-9.14), particularly first-degree relatives of EoE cases diagnosed <18 years of age (OR, 16.3; 95% CI, 9.4-28.3); second-degree relatives (OR, 1.99; 95% CI, 1.49-2.65); and first cousins (OR, 1.35; 95% CI, 1.03-1.77), providing evidence of a genetic contribution. However, spouses of EoE probands were observed to be at increased risk of EoE (OR, 2.86; 95% CI, 1.31-6.25), suggesting either positive assortative mating or a shared environmental contribution to EoE. CONCLUSIONS: This study supports a significant genetic contribution to EoE as evidenced by increased risk of EoE in distant relatives.

Filling the Void: A Review of Intragastric Balloons for Obesity.

Endoscopic bariatric therapies are predicted to become much more widely used in North America for obese patients who are not candidates for bariatric surgery. Of all the endoscopic bariatric therapies, intragastric balloons (IGBs) have the greatest amount of clinical experience and published data supporting their use. Three IGBs are FDA approved and are now commercially available in the USA (Orbera, ReShape Duo, and Obalon) with others likely soon to follow. They are generally indicated for patients whose BMI ranges from 30 to 40 mg/kg2 and who have failed to lose weight with diet and exercise. IGBs have been shown to be safe, effective, and relatively straightforward to place and remove. Accommodative symptoms commonly occur within the initial weeks post-placement; however, major complications are rare. Gastric ulceration can occur in up to 10% of patients, while balloon deflation with migration and bowel obstruction occurs in <1% of patients. The effectiveness of the Orbera and ReShape Duo IGBs ranges from 25 to 50% EWL (excess weight loss) after 6 months of therapy. The use of IGBs is likely to grow dramatically in the USA, and gastroenterologists and endoscopists should be familiar with their indications/contraindications, efficacy, placement/removal, and complications.

Regional Variability of Repeat Esophagogastroduodenoscopy Use in the National Veteran Population.

BACKGROUND: Esophagogastroduodenoscopy (EGD) procedures are performed frequently to evaluate gastrointestinal disease and symptoms. AIM: To determine regional practice variability of repeat EGDs in a national population. METHODS: The study sample included US Veterans with an outpatient index EGD from 1/1/2008 to 12/2010. We determined risk of repeat endoscopy from 1/2008 to 10/1/2014. A logistic regression model was used to assess the association between the odds of repeated EGD and patient demographics, ICD diagnostic codes, and geographic region. Multivariable logistic regression was performed to obtain the adjusted odds ratio and predicted probabilities of repeat EGDs by region. RESULTS: A total of 202,086 patients had an index endoscopy from 1/2008 to 12/2010. Unique patients with an index endoscopy were predominantly male (93.2%), white (72.8%), and on average 61 years. A total of 58,469 patients (28.9%) had one or more repeat EGDs, accounting for 103,253 repeat procedures through 10/2014. ICD-9-CM codes associated with increased risk of repeat procedures were Barrett's esophagus (OR 3.6, 95% CI 3.5-3.7), dysphagia (OR 1.3, 95% CI 1.2-1.3), ulcer (OR 1.3, 95% CI 2.2-2.4), stricture (OR 1.8, 95% CI 1.7-1.9), and esophageal varices (OR 2.8, 95% CI 2.7-3.0). There was a significant difference in the probability of repeat EGD by VA region, with the Midwest region having the highest probability (31.2%) and Southeast the lowest probability (27.3%). This difference would account for 400 more EGD procedures per 10,000 Veterans, after adjusting for patient demographics and diagnosis codes. CONCLUSIONS: Regional practice variability accounts for a substantial volume of repeat EGD procedures, regardless of patient characteristics and associated diagnoses.

Risk of Autoimmunity in EoE and Families: A Population-Based Cohort Study.

OBJECTIVES: Recent genome-wide association studies have suggested possible genetic associations between eosinophilic esophagitis (EoE) and genes associated with autoimmunity. No studies to date have looked at potential genetic association of EoE with specific autoimmune diseases by evaluating such diagnoses within family members. Investigate the risk of specific autoimmune disease within EoE probands and their extended family members. METHODS: The Utah Population Database offers a unique opportunity to link medical records from over 85% of Utah's population to genealogy records representing Utah. We searched for associations of specific autoimmune diseases in probands diagnosed with EoE and their extended family members (e.g., first cousins). Comparisons were made to age- and sex-matched controls and their respective families at a 5:1 ratio. RESULTS: Excess risk for multiple autoimmune conditions was detected in subjects with a diagnosis of EoE. Celiac, Crohn's, ulcerative colitis (UC), rheumatoid arthritis, IgA deficiency, CVID, multiple sclerosis (MS), and Hashimoto's thyroiditis were found at increased risk in first-degree relatives of EoE subjects. UC, systemic sclerosis, and MS had nominally significant associations within second-degree family members of EoE subjects; and, in reverse analysis, probands and their families with the above three conditions were at an increased risk for EoE suggesting shared genetic factors with EoE. CONCLUSIONS: Patients with EoE have an increased risk of multiple autoimmune diseases. Possible shared genetic etiologies were observed between EoE and UC, systemic sclerosis, and MS. Practitioners should be aware of these comorbid associations and query all EoE patients and family members for symptoms of these diseases.

Outcomes of Next-Day Versus Non-next-Day Colonoscopy After an Initial Inadequate Bowel Preparation.

BACKGROUND: Inadequate bowel preparation is the most common cause of failed colonoscopy, and repeat failure occurs in more than 20 % of follow-up attempts. Limited data suggest that next-day follow-up may reduce the risk for repeat inadequate preparation. OBJECTIVE: Evaluate differences in prep quality with next-day follow-up after initial inadequate preparation. DESIGN: Retrospective study. SETTING: Academic center. PATIENTS: Outpatient screening and surveillance colonoscopies between 7/2002 and 6/2007. INTERVENTION: Comparison of next-day versus any other day ("non-next-day") repeat colonoscopy outcomes. MAIN OUTCOME MEASUREMENTS: Aronchick scale, polyp and adenoma detection rates. RESULTS: Of 20,798 initial colonoscopies, 857 (4.1 %) had inadequate preparation. 460 (54 %) were lost to follow-up. One hundred and fourteen (13 %) had next-day and 283 (33 %) had non-next-day colonoscopy with mean follow-up of 8.8 months. On follow-up examination, 29.8 % of next-day and 23.3 % of non-next-day colonoscopies had inadequate bowel preparation (p = 0.48). The adenoma detection rate for the next-day group improved from 3.5 to 38.6 % on follow-up, compared to 20.5 and 36.8 % in the non-next-day group. There was no significant difference between groups in detection of total adenoma (p = 0.73) or advanced adenomas (p = 0.20) on follow-up examinations. LIMITATIONS: Retrospective design, differences in baseline colonoscopy characteristics. CONCLUSION: The results confirm the need for repeat examination after a colonoscopy with inadequate bowel prep, as there was substantial increase in adenoma detection on follow-up. There were no differences in outcomes between next-day versus non-next-day colonoscopy. These data support repeating after inadequate colonoscopy within 1 year as convenient for patient and physician.

Eosinophilic esophagitis in adults is associated with IgG4 and not mediated by IgE.

BACKGROUND & AIMS: Eosinophilic esophagitis is usually triggered by foods, by unclear mechanisms. We evaluated the roles of IgE and IgG4 in the development of eosinophilic esophagitis. METHODS: We performed a prospective, randomized, double-blind, placebo-controlled trial of adults with eosinophilic esophagitis given an antibody against IgE (omalizumab, n = 16) or placebo (n = 14) every 2-4 weeks for 16 weeks, based on weight and serum level of IgE. Endoscopy was performed, esophageal biopsy specimens were collected, and symptoms were assessed at baseline and at 16 weeks. Maximum numbers of eosinophils/high-power field were determined. Homogenates of esophageal biopsy specimens from 11 subjects with eosinophilic esophagitis and 8 without (controls) were assessed for IgM, IgA, and IgG subclasses. In a retrospective analysis, we performed immunofluorescence analysis of IgG4 in fixed esophageal tissues from 2 patients with eosinophilic esophagitis who underwent esophagectomy and 47 consecutive autopsies (controls). We also performed immunofluorescence analysis of IgG4 in esophageal mucosal biopsy specimens from 24 subjects with eosinophilic esophagitis and 9 without (controls). Finally, sera were collected from 15 subjects with eosinophilic esophagitis and from 41 without (controls), and assayed for total and food-reactive IgG4. RESULTS: Omalizumab did not alter symptoms of eosinophilic esophagitis or eosinophil counts in biopsy samples compared with placebo. Homogenates of esophageal tissues from patients with eosinophilic esophagitis had a 45-fold increase in IgG4 compared with controls (P < 3 × 10(-5)), but no significant increases in other IgG subclasses, IgM, or IgA. Sparse stromal deposits resembling immune complexes were found in 2 of 5 eosinophilic esophagitis biopsy specimens based on ultrastructural analysis. Esophagectomy samples from 2 patients with eosinophilic esophagitis contained 180 and 300 IgG4 plasma cells/maximal high-power field, mainly in the deep lamina propria; these levels were greater than in tissues from controls. Fibrosis essentially was exclusive to the lamina propria. Granular extracellular IgG4 was detected in biopsy specimens from 21 of 24 patients with eosinophilic esophagitis, but in none of the specimens from 9 controls (P = 6 × 10(-6)). The total serum level of IgG4 increased only slightly in patients with eosinophilic esophagitis, compared with controls. Subjects with eosinophilic esophagitis had increased serum levels of IgG4 that reacted with milk, wheat, egg, and nuts-the 4 foods that most commonly trigger this condition (P ≤ 3 × 10(-4) for each food). CONCLUSIONS: In a prospective trial, omalizumab did not reduce symptoms of eosinophilic esophagitis or tissue eosinophil counts compared with placebo. This finding, along with observed granular deposits of IgG4, abundant IgG4-containing plasma cells, and serum levels of IgG4 reactive to specific foods, indicate that, in adults, eosinophilic esophagitis is IgG4-associated, and not an IgE-induced allergy. ClinicalTrials.gov number: NCT 00123630.

Extracellular Eosinophil Granule Protein Deposition in Ringed Esophagus with Sparse Eosinophils.

BACKGROUND: Eosinophilic esophagitis (EoE) remains difficult to classify because of varying presentations. Not uncommonly, patients present with symptoms of esophageal dysfunction and have esophageal changes on endoscopy resembling EoE but without >15 eosinophils/HPF. Patients with low numbers of eosinophils in esophageal biopsy specimens may have esophageal changes and symptomatic disease brought about by eosinophil granule protein deposition without recognizable intact cells. AIM: To determine whether extracellular eosinophil granule protein deposition is present in the esophagi of patients with low eosinophil numbers who have clinical symptoms and characteristic endoscopic esophageal changes of EoE including ringed esophagus (RE). METHODS: Esophageal biopsy specimens were studied from eight EoE patients with >15 eosinophils per high power field (HPF) and nine patients with RE (<15 eosinophils/HPF). The specimens were analyzed for eosinophil granule proteins, major basic protein 1 (eMBP1) and eosinophil-derived neurotoxin (EDN), by indirect immunofluorescence. RESULTS: Both EoE and RE showed positive EDN and eMBP1 extracellular deposition; control esophagus showed minimal or none. Comparing EoE and RE, extracellular EDN and eMBP1 were similar except that EDN in EoE was greater in the distal esophagus. CONCLUSIONS: This study highlights the importance of assessing eosinophil granule protein deposition in esophageal disease with potential eosinophil involvement. Persistent/progressive esophageal changes may be brought about by eosinophil granule proteins despite low numbers of intact cells. The meaning of "resolution" in EoE may need to be redefined based on numbers of esophageal eosinophils, extracellular eosinophil granule protein deposition, and subsequent clinical course of patients.

The optimal pallidal target in deep brain stimulation for dystonia: a study using a functional atlas based on nonlinear image registration.

BACKGROUND: Deep brain stimulation (DBS) of the globus pallidus internus is established as efficacious for dystonia, yet the optimal target within this structure is not well defined. Published evidence suggests that spatial normalization provides a better estimate of DBS lead location than traditional methods based on standard stereotactic coordinates. METHODS: We retrospectively reviewed our pallidal implanted dystonia population. Patient imaging scans were morphed into an MRI atlas using a nonlinear image registration algorithm. Active contact locations were projected onto the atlas and clusters analyzed for the degree of variance in two groups: (1) good and poor responders and (2) cervical (CD) and generalized dystonia (GD). RESULTS: The average active contact location between CD and GD good responders was distinct but not significantly different. The mean active contact for CD poor responders was significantly different from CD responders and GD poor responders in the dorsoventral direction. CONCLUSIONS: A normalized imaging space is arguably more accurate in visualizing postoperative leads. Despite some separation between groups, this data suggests there was not an optimal pallidal target for common dystonia patients. Degrees of variance overlapped due to a large degree of individual target variation. Patient selection may ultimately be the key to maximizing patient outcomes.

Electron microscopy elucidates eosinophil degranulation patterns in patients with eosinophilic esophagitis.

BACKGROUND: In patients with eosinophilic esophagitis (EoE), eosinophils accumulate and release granule proteins onto esophageal epithelium. However, little is understood about the mechanism of eosinophil degranulation. OBJECTIVE: To determine and quantify eosinophil degranulation patterns, we studied esophageal biopsy specimens from both the proximal and distal esophagi of 9 randomly selected patients with EoE. METHODS: The specimens were fixed in glutaraldehyde, embedded, sectioned, and imaged by means of transmission electron microscopy. Eosinophils and their granules were identified by their distinctive morphology, and all eosinophils and granules were imaged. A total of 1672 images from 18 esophageal specimens were evaluated and graded. Eosinophils were categorized based on membrane integrity and by cytoplasmic vesiculation as evidence of piecemeal degranulation. Granules were categorized based on reversal of staining (eosinophil granule core lightening) and localization within and outside the cells. RESULTS: The results revealed that greater than 98% of eosinophils infiltrating the esophagus in patients with EoE demonstrate morphologic abnormalities ranging from granule changes with reversal of staining to marked cytoplasmic vesiculation to loss of cellular membrane integrity with cytolytic disruption and release of intact membrane-bound granules into the tissues. Approximately 81% of eosinophils showed membrane disruption. Extracellular granules were abundant in at least 70% of the images, and approximately 50% of these granules showed reversal of staining. On the basis of the prominence of tubulovesicular development, piecemeal degranulation appears closely related to the other morphologic changes seen in patients with EoE. CONCLUSION: These findings reveal that eosinophils in esophageal biopsy specimens from patients with EoE are abnormal, with greater than 80% showing cytolysis, and therefore that evaluation by means of light microscopy after hematoxylin and eosin staining might not accurately reflect eosinophil involvement.

Neurologist consistency in interpreting information provided by an interactive visualization software for deep brain stimulation postoperative programming assistance.

INTRODUCTION: Postoperative programming in deep brain stimulation (DBS) therapy for movement disorders can be challenging and time consuming. Providing the neurologist with tools to visualize the electrode location relative to the patient's anatomy along with models of tissue activation and statistical data can therefore be very helpful. In this study, we evaluate the consistency between neurologists in interpreting and using such information provided by our DBS programming assistance software. METHODS: Five neurologists experienced in DBS programming were each given a dataset of 29 leads implanted in 17 patients. For each patient, probabilistic maps of stimulation response, anatomical images, models of tissue activation volumes, and electrode positions were presented inside a software framework called CRAnialVault Explorer (CRAVE) developed in house. Consistency between neurologists in optimal contact selection using the software was measured. RESULTS: With only the efficacy map, the average consistency among the five neurologists with respect to the mode and mean of their selections was 97% and 95%, respectively, while these numbers were 93% and 89%, respectively, when both efficacy and an adverse effect map were used simultaneously. Fleiss' kappa statistic also showed very strong agreement among the neurologists (0.87 when using one map and 0.72 when using two maps). CONCLUSION: Our five neurologists demonstrated high consistency in interpreting information provided by the CRAVE interactive visualization software for DBS postoperative programming assistance. Three of our five neurologists had no prior experience with the software, which suggests that the software has a short learning curve and contact selection is not dependent on familiarity with the program tools.