Faculty Bibliography

INTRODUCTION/BACKGROUND:Since 2001, device-assisted enteroscopy (DAE) has revolutionized the diagnostic and therapeutic capabilities for managing small bowel pathology. Though commonly performed, there have been no recent large studies to assess the use, yield, and risks of DAE and none that include all 3 DAE modalities. We hypothesized that DAE is safe with high diagnostic and therapeutic yields achieved within reasonable procedure duration and here we present a large retrospective multicenter US study evaluating the use, yield, and complications of DAE. METHODS:After obtaining institutional review board approval, electronic records were used to identify all DAE's performed for luminal small bowel evaluation in adult patients at 4 US referral centers (Duke University Medical Center, New York University Langone Medical Center, Louisiana State University Health Sciences Center, and University of Massachusetts Medical Center) from January 1, 2014 to January 1, 2019. Electronic medical records were reviewed to collect and analyze a variety of procedure-related outcomes. Using the data pooled across centers, descriptive statistics were generated for the patient and procedure-related characteristics and outcomes; relationships between characteristics and outcomes were explored. RESULTS:A total of 1787 DAE's were performed over this 5-year period (392 at Duke University Medical Center, 887 at Louisiana State University Health Sciences Center, 312 at New York University Langone Medical Center, and 195 at University of Massachusetts Medical Center). Of these, there were 1017 (57%) double-balloon, 391 (29%) single-balloon, and 378 (21%) spiral enteroscopies. The mean age of patients undergoing DAE was 66 years and 53% of examinations were performed on women; 18% of patients in the cohort underwent >1 DAE over this time span. A total of 53% of examinations were performed for suspected small bowel bleeding, 31% were directly guided by video capsule endoscopy findings and 8% were performed for abnormal imaging. A total of 85% of examinations used an antegrade approach and DAE took a mean of 45 minutes to complete; 76% of examinations revealed abnormal findings, with vascular, inflammatory, and neoplastic findings seen in 49%, 17%, and 15% of the cohort, respectively. Older age was significantly associated with any abnormal finding, including arteriovenous malformations (P<0.0001); 50% of examinations included a therapeutic maneuver, most commonly argon plasma coagulation/cautery (43%). There were complications in 16 examinations (0.9%) including 2 perforations (0.1%), 6 cases with bleeding (0.3%) and 1 episode of pancreatitis (0.1%). CONCLUSIONS:DAE is most commonly performed to evaluate suspected small bowel bleeding and is commonly directed by video capsule findings. DAE is safe, has a high diagnostic yield, with 76% of examinations showing abnormal findings, and frequently features therapeutic maneuvers. Advancing age is associated with abnormal findings on DAE.

OBJECTIVELumboperitoneal (LP) shunts have a role not only in pseudotumor cerebri, but also in patients with slit-like ventricles who are treated with CSF shunting on a chronic basis. Hesitation to utilize LP shunts is based on previous conventional beliefs including the tendency for overdrainage, difficulties accessing the shunt to tap or revise, and risk of progressive cerebellar tonsillar herniation. The authors hypothesized that the use of horizontal-vertical (HV) valves may reduce the risk of these complications, particularly overdrainage and development of Chiari malformation.METHODSAll pediatric cases involving patients treated with an LP shunt at the Children's Hospital of Michigan were reviewed in this retrospective case series. A total of 143 patients with hydrocephalus were treated with LP shunts from 1997-2015 (follow-up range 8 months-8 years, median 4.2 years). Patients with pseudotumor cerebri underwent placement of an LP shunt as a primary procedure. In patients with slit ventricles from chronically treated hydrocephalus or repeated shunt malfunctions from proximal catheter obstruction, a lumbar drain was inserted to assess candidacy for conversion to an LP shunt. In patients who tolerated the lumbar drain and demonstrated communication of the ventricles with the spinal cisterns, treatment was converted to an LP shunt. All patients included in the series had undergone initial shunt placement between birth and age 16 years.RESULTSIn 30% of patients (n = 43), LP shunts were placed as the initial shunt treatment; in 70% (n = 100), treatment was converted to LP shunts from ventriculoperitoneal (VP) shunts. The patients' age at insertion of or conversion to an LP shunt ranged from 1 to 43 years (median 8.5 years). Of the patients with clear pre-LP and post-LP shunt follow-up imaging, none were found to develop an acquired Chiari malformation. In patients with pre-existing tonsillar ectopia, no progression was noted on follow-up MRIs of the brain in these patients after LP shunt insertion. In our LP shunt case series, no patient presented with acute deterioration from shunt malfunction.CONCLUSIONSConversion to an LP shunt may minimize acute deterioration from shunt malfunction and decrease morbidity of repeated procedures in patients with chronically shunt-treated hydrocephalus and small ventricles. In comparison to previously published case series of LP shunt treatment, the use of LP shunts in conjunction with HV valves may decrease the overall risk of cerebellar tonsillar herniation. The use of an LP shunt may be an alternative in the management of slit ventricles when VP shunting repeatedly fails.

AIM/OBJECTIVE:To investigate challenges, risk factors, prognostic indicators, and treatment outcomes associated with Budd-Chiari syndrome (BCS) at a tertiary care center. METHODS:A retrospective cohort study was conducted at the University of Pennsylvania in patients with a diagnosis of BCS or hepatic vein thrombosis. All patients receiving care at the University of Pennsylvania, and who had at least 2 clinical encounters in the University of Pennsylvania Health system from January 1, 2008 to September 10, 2013 were eligible for study inclusion. Data were extracted from the electronic medical record of each patient, and recorded in a secure Research Electronic Data Capture database. Logistic regression analyses were applied to identify predictors of outcome of liver transplant (LT) or death. RESULTS:Between January 1, 2008 and September 10, 2013, forty-seven patients were identified. Median age was 42.4 years. Thirty-one (66.0%) were women. A majority were Caucasian (68.1%). At diagnosis, 43 (91.5%) patients had ascites, 27 (57.4%) patients had a hematologic disorder associated with a hypercoagulable state and 26 (55.3%) had cirrhosis. Forty (85.1%) patients were on anticoagulation (AC), 30 (63.8%) of whom were maintained on warfarin. Two patients (4.3%) underwent thrombolytic therapy. A transjugular intrahepatic portosystemic shunt (TIPS) was placed in 21 (44.7%) patients, 19 (90.5%) of whom were also on AC. Twenty-one (44.7%) received AC alone. Over a median of 974 d, 8 (17.0%) patients received LT, and 10 (21.3%) died. The median time from listing to death was 26 mo [interquartile range (IQR) = 16, 65)]. TIPS with AC was utilized more frequently in younger patients (P = 0.02). Age, cirrhosis and chronic kidney disease (CKD) were significant predictors of LT or death. CONCLUSION/CONCLUSIONS:AC alone was employed as frequently as TIPS with AC, though the latter was used more frequently in younger patients with polycythemia vera. There were no significant differences in treatment outcome regardless of the therapeutic intervention employed. Significant predictors of poor prognosis included age, cirrhosis and CKD.

OBJECTIVE:Rho-associated protein kinases (ROCKs) have been implicated in the pathogenesis of cardiovascular and renal disorders. We recently showed that ROCKs could regulate the differentiation of murine Th17 cells and the production of interleukin-17 (IL-17) and IL-21, two cytokines associated with systemic lupus erythematosus (SLE). The goal of this study was to assess ROCK activation in human Th17 cells and to evaluate ROCK activity in SLE patients. METHODS:An enzyme-linked immunosorbent assay (ELISA)-based ROCK activity assay was used to evaluate ROCK activity in human cord blood CD4+ T cells differentiated under Th0 or Th17 conditions. We then performed a cross-sectional analysis of 28 SLE patients and 25 healthy matched controls. ROCK activity in peripheral blood mononuclear cell (PBMC) lysates was determined by ELISA. Cytokine and chemokine profiles were analyzed by ELISA. RESULTS:Human cord blood CD4+ T cells differentiated under Th17 conditions expressed higher levels of ROCK activity than did CD4+ T cells stimulated under Th0 conditions. Production of IL-17 and IL-21 was inhibited by the addition of a ROCK inhibitor. SLE PBMCs expressed significantly higher levels of ROCK activity than did healthy control PBMCs (1.25 versus 0.56; P = 0.0015). Sixteen SLE patients (57%) expressed high levels of ROCK (optical density at 450 nm >1). Disease duration, lymphocyte count, and azathioprine use were shown to be significant independent predictors of ROCK activity in multivariable analyses. CONCLUSION/CONCLUSIONS:Consistent with previous results in the murine system, increased ROCK activation was associated with Th17 cell differentiation. Moreover, enhanced ROCK activity was observed in a subgroup of SLE patients. These data support the concept that the ROCK pathway could represent an important therapeutic target for SLE.