The Lipid Intensive Drug Therapy for Sepsis Phase II Pilot Clinical Trial.

OBJECTIVES: Low cholesterol levels in early sepsis patients are associated with mortality. We sought to test if IV lipid emulsion administration to sepsis patients with low cholesterol levels would prevent a decline or increase total cholesterol levels at 48 hours. DESIGN: Phase II, adaptive, randomized pilot clinical trial powered for 48 patients. SETTING: Emergency department or ICU of an academic medical center. PATIENTS: Sepsis patients (first 24 hr) with Sequential Organ Failure Assessment greater than or equal to 4 or shock. INTERVENTIONS: Patients meeting study criteria, including screening total cholesterol levels less than or equal to 100 mg/dL or high-density lipoprotein cholesterol (HDL-C) + low-density lipoprotein cholesterol (LDL-C) less than or equal to 70 mg/dL, were randomized to receive one of three doses of lipid emulsion administered twice in 48 hours or no drug (controls). The primary endpoint was a change in serum total cholesterol (48 hr - enrollment) between groups. MEASUREMENTS AND MAIN RESULTS: Forty-nine patients were enrolled and randomized. Two patients randomized to lipid emulsion were withdrawn before drug administration. Data for 24 control patients and 23 lipid emulsion patients were analyzed. The mean change in total cholesterol from enrollment to 48 hours was not different between groups and was 5 mg/dL (sd 20) for lipid emulsion patients, and 2 mg/dL (sd 18) for control patients (p = 0.62). The mean changes in HDL-C and LDL-C were similar between groups. Mean change in triglycerides was elevated in lipid emulsion patients (61 mg/dL, sd 87) compared with controls (20 mg/dL, sd 70, p = 0.086). The 48-hour change in SOFA score was -2 (interquartile range [IQR] -4, -1) for control patients and -2 (IQR -3, 0) for lipid emulsion patients (p = 0.46). CONCLUSIONS: Administration of IV lipid emulsion to early sepsis patients with low cholesterol levels did not influence change in cholesterol levels from enrollment to 48 hours.

Automated centrifugal microfluidic system for the preparation of adaptor-ligated sequencing libraries.

The intensive workload associated with the preparation of high-quality DNA libraries remains a key obstacle toward widespread deployment of sequencing technologies in remote and resource-limited areas. We describe the development of single-use microfluidic devices driven by an advanced pneumatic centrifugal microfluidic platform, the PowerBlade, to automate the preparation of Illumina-compatible libraries based on adaptor ligation methodology. The developed on-chip workflow includes enzymatic DNA fragmentation coupled to end-repair, adaptor ligation, first DNA cleanup, PCR amplification, and second DNA cleanup. This complex workflow was successfully integrated into simple thermoplastic microfluidic devices that are amenable to mass production with injection molding. The system was validated by preparing, on chip, libraries from a mixture of genomic DNA extracted from three common foodborne pathogens (Listeria monocytogenes, Escherichia coli and Salmonella enterica serovar Typhimurium) and comparing them with libraries made via a manual procedure. The two types of libraries were found to exhibit similar quality control metrics (including genome coverage, assembly, and relative abundances) and led to nearly uniform coverage independent of GC content. This microfluidic technology offers a time-saving and cost-effective alternative to manual procedures and robotic-based automation, making it suitable for deployment in remote environments where technical expertise and resources might be scarce. Specifically, it facilitates field practices that involve mid- to low-throughput sequencing, such as tasks related to foodborne pathogen detection, characterization, and microbial profiling.

Not Your Everyday Duodenal Ulcer: Massive Gastrointestinal Bleed Secondary to Extramedullary Plasma Cell Myeloma.

The differential for gastrointestinal (GI) bleeding is broad, ranging from peptic ulcers and Helicobacter pylori infection to variceal hemorrhage and neoplasms. The rarer causes of GI bleeds are frequently overlooked and as such can ultimately be more dangerous. Extramedullary multiple myeloma, an atypical plasma cell dyscrasia arising outside of the bone marrow, involves the GI tract in <5% of cases and often presents with nonspecific symptoms. We describe a rare case of such GI involvement of a plasma cell tumor, with subsequent transmural duodenal ulceration involving the gastroduodenal artery, ultimately resulting in a fatal GI bleed.

Factors associated with bleeding after ultrasound-assisted catheter-directed thrombolysis for the treatment of pulmonary embolism.

Ultrasound-assisted catheter directed thrombolysis (US-CDT) is frequently used for the treatment of pulmonary embolism. Due to the variety of thrombolytic and anticoagulant dosing utilized in practice, patients with pulmonary embolism who undergo US-CDT may be at an increased risk of bleeding. The primary objective of this study was to determine factors associated with major bleeding occurring with US-CDT. Secondary outcomes included in-hospital mortality and ventilator-free days. This multicentre retrospective cohort study evaluated inpatients diagnosed with pulmonary embolism and treated with US-CDT and systemic anticoagulation. A total of 173 patients were included. Most patients receiving US-CDT had a submassive pulmonary embolism with a median Pulmonary Embolism Severity Index (PESI) score of 85. Major bleeding events occurred in 37 of the 173 patients (21%). In-hospital mortality occurred in four (11%) of the patients who experienced major bleeding and three (2%) patients who did not experience major bleeding (P = 0.04). Factors associated with a higher risk of major bleeding included female sex and anticoagulation strategy. The odds of major bleeding were 3.3 times higher for women than for men (odds ratio = 3.32, 95% confidence interval 1.29-8.54). In addition, for each second increase in goal aPTT the odds of major bleeding increased by 5% (odds ratio = 1.05, 95% confidence interval 1.02-1.09). In patients with pulmonary embolism treated with US-CDT, major bleeding may be underestimated. In this analysis, major bleeding was associated with female sex and higher goal aPTT levels. In addition, bleeding with US-CDT was associated with a higher risk of in-hospital mortality.

Effectiveness and Safety of Beta-Lactam Antibiotics with and without Therapeutic Drug Monitoring in Patients with Pseudomonas aeruginosa Pneumonia or Bloodstream Infection.

This objective of this study was to compare clinical outcomes in hospitalized patients with Pseudomonas aeruginosa pneumonia (PNA) or bloodstream infection (BSI) receiving beta-lactam antibiotic (BLA) infusions with and without the guidance of therapeutic drug monitoring (TDM). A retrospective, parallel cohort study was conducted at two academic medical centers between December 2015 and January 2020, UF Shands Gainesville, which uses BLA TDM for select patients (BLA TDM), and UF Health Jacksonville, which does not use BLA TDM (No-BLA TDM). All hospitalized adult patients with respiratory or blood culture positive for P. aeruginosa who met diagnosis criteria for lower respiratory tract infection with a positive P. aeruginosa respiratory culture and who received ≥48 h of intravenous BLA with in vitro susceptibility within 72 h of positive culture collection were included. The primary outcome was a composite of presumed treatment failure defined as the presence of any of the following from index-positive P. aeruginosa culture collection to the end of BLA therapy: all-cause mortality, escalation of and/or additional antimicrobial therapy for P. aeruginosa infection after 48 h of treatment with susceptible BLA due to worsening clinical status, or transfer to a higher level of care (i.e., the intensive care unit [ICU]). Analyses were adjusted for possible confounding with inverse probability of treatment weighting (IPTW). Two-hundred patients were included (BLA TDM, n = 95; No-BLA TDM, n = 105). In IPTW-adjusted analysis of the primary composite endpoint, BLA TDM demonstrated a significant decrease in presumed treatment failure compared to No-BLA TDM (adjusted odds ratio [aOR] 0.037, 95% confidence interval [CI] [0.013 to 0.107]; P < 0.001). BLA TDM had more 30-, 60- and 90-day infection-related readmissions ([aOR], 11.301, 95% CI (3.595 to 35.516); aOR 10.389, 95% CI [2.496 to 43.239], and aOR 24.970, 95% CI [6.703 to 93.028]) in IPTW analyses. For both unadjusted and IPTW-adjusted cohorts, there was no significant difference in hospital and ICU length of stay, adverse effects while on BLA, or microbiological eradication between BLA TDM and No-BLA TDM. In hospitalized adult patients with P. aeruginosa PNA or BSI, the use of TDM-guided BLA infusions decreased the odds of presumed treatment failure compared to patients receiving BLA infusions without TDM guidance. Future studies should evaluate BLA TDM impact on readmission.

Evaluation of glycemic control in critically ill patients with bacteremia: a retrospective, single-center cohort study.

Dysglycemia is a common complication in hospitalized patients and has been suggested to play a significant role in the pathology and virulence of patients with bacteremia. The literature evaluating this relationship in critically ill patients, however, is limited. This retrospective, single-center cohort study aimed to investigate the relationship of glycemic control with 28-day intensive care unit (ICU)-free days in critically ill patients with bacteremia. Glycemic control was evaluated and determined based on time in targeted blood glucose range (TIR) of 70-140 mg/dL. Using a threshold of 80%, patients were then categorized into 2 groups: TIR-lo (<80%) and TIR-hi (≥80%). Unadjusted data identified a significant difference in ICU-free days (TIR-lo 21.29 days vs TIR-hi 24.08 days, p=0.007). However, due to an excess of zero ICU-free days, a zero-inflated Poisson model was used for analysis and demonstrated that patients in the TIR-lo group were 2.57 times more likely to have zero ICU-free days (p=0.033), which was attributed to mortality. Of the survivors, no difference was seen with TIR status and the number of ICU-free days (p=0.780). These findings demonstrate that glycemic control may increase the likelihood of being liberated from the ICU within a 28-day period, which the authors attributed to increased survival. However, of the patients who left the ICU, glycemic control was not associated with a significant difference in the number of ICU-free days.

Effect of desmopressin acetate on acute spontaneous intracranial hemorrhage in patients on antiplatelet therapy.

PURPOSE: To evaluate the impact of desmopressin acetate (DDAVP) on poor outcomes, hematoma expansion, and adverse events in patients diagnosed with a non-traumatic, antiplatelet-associated intracranial hemorrhage (ICH). METHODS: This was a multicenter, retrospective, propensity-matched cohort study comparing DDAVP to control in patients diagnosed with a non-traumatic ICH previously on antiplatelet therapy. Notable exclusion criteria included admission to trauma service, subarachnoid hemorrhages, confounding coagulopathic factors, and hematoma evacuation. Poor outcome, defined as discharge to hospice or in-patient mortality, was the primary outcome. Secondary outcomes included intracranial hematoma expansion and occurrence of adverse events, which included hyponatremia and thromboembolic events. RESULTS: A total of 49 patients receiving DDAVP were compared to 107 controls in the unmatched cohort. Thirty-seven patients treated with DDAVP and 55 controls were included in the propensity-matched analysis, which was adjusted for age, ethnicity, history of diabetes, receipt of platelet transfusion, and thromboembolism prophylaxis. Poor outcome (16.2% DDAVP vs 29% control, p = 0.13), rates of hematoma expansion (11.8% DDAVP vs 11.1% control, p = 0.99), and adverse events (21.6% DDAVP vs 20% control, p = 0.99) were statistically similar between the matched groups. CONCLUSIONS: DDAVP administration in patients with spontaneous antiplatelet-associated ICH was not associated with a reduction in poor outcomes, hematoma expansion, or an increase in adverse events. Use of DDAVP in this patient population appears to be safe. Larger prospective studies are warranted to evaluate DDAVP utility in this patient population.

Impact of Clinical Sepsis Phenotypes on Mortality and Fluid Status in Critically Ill Patients.

BACKGROUND: Sepsis is associated with high rates of in-hospital mortality, despite being the focus of medical research and public health initiatives for several years. The primary objective of this study was to determine the influence of septic phenotypes on rates of in-hospital mortality throughout intensive care unit (ICU) admission. PATIENTS AND METHODS: Retrospective, single-center cohort study. Medical ICU of an academic medical center. Medical ICU patients admitted between January 2016 and August 2019 with a "sepsis alert" were screened for admitting diagnosis of "sepsis" or "septic shock." Patients were classified into one of four clinical sepsis phenotypes: multi-organ failure (MOF), respiratory dysfunction (RD), neurologic dysfunction (ND), or other patients (OP). RESULTS: An analysis of 320 patients was completed. In-hospital mortality was different between groups (P < 0.001). Patients with the MOF phenotype had the highest rate of mortality (48.4%), followed by the ND phenotype (39.7%), RD phenotype (20.8%), and OP phenotype (13.7%). There were differences in volume balances between phenotypes at 48 h (P = 0.001), 72 h (P < 0.001), and 96 h (P < 0.001) after hospital presentation, with the MOF and ND phenotypes having the largest volume balances at these time points. Ventilator-free days (P < 0.001) and ICU length of stay (LOS) (P = 0.030) were different between groups. There was no difference in hospital LOS (P = 0.479). CONCLUSIONS: This data supports the presence of marked intra-disease differences in septic patient presentation and correlation with clinical outcomes including mortality. Additionally, significantly more positive fluid balances were observed between survivors and non-survivors in some patient subsets. Using pragmatic clinical variables readily available to providers to classify patients into septic phenotypes has the propensity to guide treatment strategies in the future.

Clinical factors associated with adverse outcomes in the acute period of management of submassive pulmonary embolism.

The majority of patients with intermediate-to-severe submassive pulmonary embolism are hemodynamically stable upon presentation. There is a lack of evidence for the clinical relevance and safety of initially employed therapies in this population. The objective of current analysis was to determine predictors associated with adverse outcomes in submassive pulmonary embolism patients. This was a single-center, retrospective chart review identifying patient characteristics and clinical factors associated with adverse outcomes within the management of patients presenting to the emergency department for submassive pulmonary embolism. A total of 122 admissions for submassive pulmonary embolism were included. Among these patients, 41% (n = 50) of admissions had an adverse outcomes. Fluid volume was associated with adverse events in an incremental manner (odds ratio 2.1, 95% confidence interval, 1.4-3.2). These findings demonstrate a significant incidence of adverse events in patients with submassive pulmonary embolism and an incremental increase in likelihood of adverse events with each liter of fluid.

Comparison of Weight-Based Dosing versus Fixed Dosing of 23.4% Hypertonic Saline for Intracranial Pressure Reduction in Patients with Severe Traumatic Brain Injury.

CONTEXT: Hypertonic saline (HTS) is a pharmacologic therapy used in patients with severe traumatic brain injuries to decrease intracranial pressure (ICP) associated with cerebral edema. AIMS: The purpose of this study was to compare ICP reduction between fixed doses of 23.4% HTS and weight-based doses. SETTING AND DESIGN: This was a retrospective study that included adult patients at a level 1 trauma center who had nonpenetrating traumatic brain injury, an ICP monitor, and received at least one dose of 23.4% HTS. SUBJECTS AND METHODS: Doses were classified as either high weight-based (>0.6 ml/kg), low weight-based (<0.6 ml/kg), or standard fixed dose (30 ml). Only doses given within 5 days post-injury were evaluated. Percent reduction in ICP was compared pre- and post-dose between dosing groups, and each dose was evaluated as a separate episode. STATISTICAL ANALYSIS: The primary and secondary endpoints for the study were analyzed using mixed-model, repeated-measures analysis of covariance. RESULTS: A total of 97 doses of HTS were evaluated. The primary endpoint of ICP reduction showed a 42.5% decrease in ICP after the administration of a high weight-based dose, a 36.7% reduction after a low weight-based dose, and a 31.5% reduction after a fixed dose. There was no significant relationship between dose group and percent change in ICP (P = 0.25). A sub-analysis of doses received within 48 h postinjury found a significant relationship between both dose group and percent change in ICP, and initial ICP and percent change in ICP (P = 0.04, and <0.0001 respectively). CONCLUSIONS: Our data did not show a significant difference between fixed- and weight-based doses of 23.4% HTS for ICP reduction.

Lipid intensive drug therapy for sepsis pilot: A Bayesian phase I clinical trial.

OBJECTIVES: Cholesterol may be protective in sepsis. Patients with early sepsis may have critically low cholesterol levels that are associated with poor outcomes. The study objective was to test the safety of a fish oil-containing lipid injectable emulsion for stabilizing early cholesterol levels in sepsis. METHODS: Phase I Bayesian optimal interval design trial of adult patients with septic shock (Sequential Organ Failure Assessment score ≥4 or vasopressor dependence). Using sequential dose escalation, participants received 2 doses of 1.0 to 1.6 g/kg of lipid emulsion (Smoflipid 20% lipid emulsion) within 48 hours of enrollment. Cholesterol levels, function, and organ failure were assessed serially during the first 7 days of hospital admission. MEASUREMENTS AND MAIN RESULTS: A total of 10 patients with septic shock were enrolled. One patient withdrew for social reasons. Another patient had an unrelated medical complication and received 1 drug dose. Of 9 patients, mean age was 58 years (SD 16), median Sequential Organ Failure Assessment was 8, and 28-day mortality was 30%. No serious adverse events related to lipid infusion occurred. The six occurrences of non-serious adverse events possibly related to lipid infusion included hyperglycemia (1), elevated triglycerides (3), anemia (1), and vascular access redness/pain (1) for all doses. The mean change in total cholesterol levels from enrollment was -7 (SD 16.6) at 48 hours and 14 (SD 25.2) at 7 days. CONCLUSIONS: Fish oil-containing lipid emulsion administration during early septic shock was safe. Further studies are needed to assess effects on cholesterol levels, function, and organ failure. CLINICAL TRIAL REGISTRATION: NCT03405870.

Spontaneous Pneumomediastinum, Pneumoperitoneum, and Pneumoretroperitoneum After Endoscopic Cryoablation Without Frank Perforation.

Perforation after endoscopic cryoablation is a rare but serious complication. We present a middle-aged male patient who presented for an elective session of endoscopic cryoablation for his Barrett esophagus with high-grade dysplasia. After cryoablation, the patient complained of abdominal pain, and his abdomen became distended and tympanic. Computed tomography showed pneumomediastinum, pneumoperitoneum, and pneumoretroperitoneum but no evidence of extraluminal contrast extravasation. The patient was treated with antibiotics and had no complications. To our knowledge, this is the first described case of pneumomediastinum, pneumoperitoneum, and pneumoretroperitoneum without frank perforation after endoscopic cryoablation.

LIPid Intensive Drug therapy for Sepsis Pilot (LIPIDS-P): Phase I/II clinical trial protocol of lipid emulsion therapy for stabilising cholesterol levels in sepsis and septic shock.

INTRODUCTION: Sepsis is a life-threatening, dysregulated response to infection. Both high-density lipoprotein and low-density lipoprotein cholesterol should protect against sepsis by several mechanisms; however, for partially unknown reasons, cholesterol levels become critically low in patients with early sepsis who experience poor outcomes. An anti-inflammatory lipid injectable emulsion containing fish oil is approved by the Food and Drug Administration as parenteral nutrition for critically ill patients and may prevent this decrease in serum cholesterol levels by providing substrate for cholesterol synthesis and may favourably modulate inflammation. This LIPid Intensive Drug therapy for Sepsis Pilot clinical trial is the first study to attempt to stabilise early cholesterol levels using lipid emulsion as a treatment modality for sepsis. METHODS AND ANALYSIS: This is a two-centre, phase I/II clinical trial. Phase I is a non-randomised dose-escalation study using a Bayesian optimal interval design in which up to 16 patients will be enrolled to evaluate the safest and most efficacious dose for stabilising cholesterol levels. Based on phase I results, the two best doses will be used to randomise 48 patients to either lipid injectable emulsion or active control (no treatment). Twenty-four patients will be randomised to one of two doses of the study drug, while 24 control group patients will receive no drug and will be followed during their hospitalisation. The control group will receive all standard treatments mandated by the institutional sepsis alert protocol. The phase II study will employ a permuted blocked randomisation technique, and the primary endpoint will be change in serum total cholesterol level (48 hours - enrolment). Secondary endpoints include change in cholesterol level from enrolment to 7 days, change in Sequential Organ Failure Assessment score over the first 48 hours and 7 days, in-hospital and 28-day mortality, lipid oxidation status, inflammatory biomarkers, and high-density lipoprotein function. ETHICS AND DISSEMINATION: Investigators are trained and follow good clinical practices, and each phase of the study was reviewed and approved by the institutional review boards of each institution. Results of each phase will be disseminated through presentations at national meetings and publication in peer-reviewed journals. If promising, data from the pilot study will be used for a larger, multicentre, phase II clinical trial. TRIAL REGISTRATION NUMBER: NCT03405870.

A case-report of successful use of thromboelastography to manage anticoagulation therapy in a patient with concomitant catastrophic antiphospholipid syndrome and heparin-induced thrombocytopenia.

: Catastrophic antiphospholipid syndrome (CAPS) is a severe but rare form of antiphospholipid syndrome (APS) that results in multiple thrombosis of multiple organs within a week . Similarly, heparin-induced thrombocytopenia (HIT) has been associated with severe and life-threatening thrombosis, both conditions mediated by an autoimmune disorder resulting in a highly thrombotic state . Both conditions requiring aggressive therapeutic anticoagulation when coinciding CAPS complicated by HIT presents a therapeutic challenge. Current recommendations advocate for the use of anti-Xa activity monitoring in the setting of APS because of the common laboratory interaction with commercially available tests, such as prothrombin and activated partial thromboplastin times . With the recommendations to utilize direct thrombin inhibitors (DTI) in the presence of HIT this precludes the possibility of anti-Xa monitoring making for a monitoring predicament. The current case presents a patient where thromboelastography (TEG) was utilized to direct anticoagulation in the setting of concurrent CAPS and HIT without complication.

Intravenous Acetaminophen-Induced Hypotension: A Review of the Current Literature.

Objective: Recent literature suggests that intravenous (IV) administration may cause hypotension in hospitalized patients; data further suggest that this effect is most pronounced in the critically ill. The purpose of this review is to identify and evaluate current literature that addresses the incidence and implications of IV acetaminophen-induced hypotension. Data Sources: A literature search of MEDLINE, Cochrane, and EMBASE databases was performed (2002-2019) using the following terms: acetaminophen, paracetamol, intravenous, and hypotension. Abstracts and peer-reviewed publications were reviewed. Study Selection and Data Extraction: Relevant English-language studies conducted in humans evaluating the hemodynamic effects of IV acetaminophen were considered. Data Synthesis: A majority of the 19 studies included in this review identified a statistically significant drop in hemodynamic variables after the administration of 500 to 1000 mg IV acetaminophen as measured by changes in systolic blood pressure, diastolic blood pressure, or mean arterial pressure. Of the trials reporting vasopressor use, the authors found a significant increase in vasopressor requirements following IV acetaminophen administration. Relevance to Patient Care and Clinical Practice: This review represents the first comprehensive review of IV acetaminophen-induced hypotension. The findings raise the question of whether IV acetaminophen is an appropriate choice for inpatient pain or temperature management in the critically ill. Conclusions: Available evidence indicates that the administration of IV acetaminophen may be harmful in the critically ill. Additional monitoring is likely required when using IV acetaminophen in this specific population, particularly if a patient is hemodynamically unstable prior to administration.

Iatrogenic Gallstone Pancreatitis Complicated by Cholangitis: Post-Cholecystectomy Clip as a Nidus for Common Bile Duct Stone Formation.

Cholecystectomy is one of the most common surgical procedures in clinical practice. Laparoscopic cholecystectomy has become the gold standard for the management of symptomatic gallstone disease due to its minimally invasive nature and safety with quoted complication rates of under 5%. Surgical clip migration into the bile duct with resultant stone formation is a rare complication of laparoscopic cholecystectomy. Here we present a case of cholangitis in addition to gallstone pancreatitis as a result of surgical clip migration into the bile duct leading to stone formation.

Successful Endoscopic Reduction of an Ileocolonic Intussusception in an Adult With Peutz-Jeghers Syndrome.

Peutz-Jeghers syndrome (PJS) is a rare autosomal dominant disorder characterized by hamartomatous polyps throughout the gastrointestinal tract, mostly causing gastrointestinal bleeding and recurrent intestinal obstructions. Few intussusception related to PJS occurs reportedly in adults. Unlike pediatric cases almost all reported cases end up with surgical resection. Here we present a case of PSJ-related intussusception in an adult patient treated successfully with endoscopic approach, with no surgical intervention required.

Setting minimum standards for training in EUS and ERCP: results from a prospective multicenter study evaluating learning curves and competence among advanced endoscopy trainees.

BACKGROUND AND AIMS: Minimum EUS and ERCP volumes that should be offered per trainee in "high quality" advanced endoscopy training programs (AETPs) are not established. We aimed to define the number of procedures required by an "average" advanced endoscopy trainee (AET) to achieve competence in technical and cognitive EUS and ERCP tasks to help structure AETPs. METHODS: American Society for Gastrointestinal Endoscopy (ASGE)-recognized AETPs were invited to participate; AETs were graded on every fifth EUS and ERCP examination using a validated tool. Grading for each skill was done using a 4-point scoring system, and learning curves using cumulative sum analysis for overall, technical, and cognitive components of EUS and ERCP were shared with AETs and trainers quarterly. Generalized linear mixed-effects models with a random intercept for each AET were used to generate aggregate learning curves, allowing us to use data from all AETs to estimate the average learning experience for trainees. RESULTS: Among 62 invited AETPs, 37 AETs from 32 AETPs participated. Most AETs reported hands-on EUS (52%, median 20 cases) and ERCP (68%, median 50 cases) experience before starting an AETP. The median number of EUS and ERCPs performed per AET was 400 (range, 200-750) and 361 (range, 250-650), respectively. Overall, 2616 examinations were graded (EUS, 1277; ERCP-biliary, 1143; pancreatic, 196). Most graded EUS examinations were performed for pancreatobiliary indications (69.9%) and ERCP examinations for ASGE biliary grade of difficulty 1 (72.1%). The average AET achieved competence in core EUS and ERCP skills at approximately 225 and 250 cases, respectively. However, overall technical competence was achieved for grade 2 ERCP at about 300 cases. CONCLUSION: The thresholds provided for an average AET to achieve competence in EUS and ERCP may be used by the ASGE and AETPs in establishing the minimal standards for case volume exposure for AETs during their training. (Clinical trial registration number: NCT02509416.).

Burkitt's lymphoma masquerading as a Crohn's flare.

Sporadic Burkitt's lymphoma can have a variety of clinical manifestations, including a constellation of gastrointestinal symptoms that can masquerade as other conditions and lead to a delay in diagnosis. Here we review a case of Burkitt's lymphoma in a patient with a history of Crohn's disease, initially thought to be a Crohn's flare on initial presentation. This case highlights the importance of keeping a broad differential and ruling out Crohn's mimics in the process of treating a presumed exacerbation of inflammatory bowel disease.