Single-center US Research Articles

Abstract A068: Evaluate the performance of FibraChek™ for non-invasive detection of hepatic fibrosis and hepatocellular carcinoma

Abstract Metabolic dysfunction-associated steatotic liver disease (MASLD), fibrosis, and cirrhosis are risk factors for hepatocellular carcinoma (HCC). Blood-based assays to date have limited accuracy for detecting MASLD and cirrhosis, and thus have not been widely adopted in the clinical setting. The identification and validation of a multiplex molecular signature associated with liver disease may address this unmet need. This prospective single-center US study evaluated the performance of the non-invasive Liver FibraChek Dx serum assay for detecting MASLD. The study algorithm analyzes weighted values of five serum biomarkers (AST, ALT, taurocholic acid, L-tyrosine, and platelet count) plus age to derive a risk score. Samples comprised 14 MASLD cases, 19 HCC cases, and 12 healthy controls. Liver status was confirmed by tissue biopsy. Wilcoxon rank sum tests determined the association between the risk score and confirmed liver histology. Diagnostic performance was assessed using ROC curves. The probability of identifying MASLD and/or HCC by Liver FibraChek Dx, in conjunction with other patient parameters, was demonstrated by an AUROC of 0.890 (95% CI: 0.776-1.000), with 93.9% sensitivity, 75.0% specificity, 91.1% positive predictive value, 81.8% negative predictive value, and 88.9% accuracy. Risk scores associated with the biomarker panel enabled accurate discrimination of liver disease from healthy controls. The non-invasive multiplex Liver FibraChek Dx test can effectively and accurately detect and classify hepatic fibrosis risk in peripheral blood samples and may have utility in diagnosing and monitoring liver pathogenesis. Citation Format: Fernando Siguencia, Michitaka Matsuda, Vijay Pandyarajan, Sunao Tanaka, Steven M Smith, Ekihiro Seki, Charles J Rosser, Hideki Furuya. Evaluate the performance of FibraChek™ for non-invasive detection of hepatic fibrosis and hepatocellular carcinoma [abstract]. In: Proceedings of the AACR Special Conference: Liquid Biopsy: From Discovery to Clinical Implementation; 2024 Nov 13-16; San Diego, CA. Philadelphia (PA): AACR; Clin Cancer Res 2024;30(21_Suppl):Abstract nr A068.

Demographics, Types of Patient-Reported Allergic Diseases, and Anaphylaxis in Mastocytosis: A Single-Center US Experience

BackgroundPatients with mastocytosis are at increased risk of anaphylaxis. Idiopathic anaphylaxis and venom induced allergy are commonly reported in mastocytosis, however the incidence of other allergies has been less well studied. ObjectiveWe sought to characterize the true prevalence of allergic disease including food, venom, contrast, and drug allergy compared to the number of patients that simply avoid potential triggers. We also gathered demographic information. MethodsWe performed a retrospective study of 259 consecutive pediatric and adult patients with a confirmed diagnosis of either cutaneous or systemic mastocytosis who received care through the University of Michigan Health system from 1/1/2018 to 3/17/2021. ResultsMastocytosis was more prevalent in non-Hispanic white population. As compared to the general population, patients had similar rates of atopy and allergies with a slight increase in reported asthma prevalence. Overall prevalence of anaphylaxis was 28% and the great majority occurred in SM, with most common trigger being hymenoptera venoms. Most patients reported drug allergies preemptively in order to avoid exposure, particularly to NSAIDs. We also saw an increase in contrast-induced anaphylaxis compared to prior literature, and a lower prevalence of venom allergy as compared to European cohorts. ConclusionOur study characterizes the rate of common atopic conditions as well as allergies in a large cohort of patients with mastocytosis in the US. Anaphylaxis in CM is rare. Hymenoptera venoms were the most common trigger for anaphylaxis while drug allergies were overreported preemptively in order to avoid potential exposures due to concern for having a reaction.

Emergency Anesthesiology Encounters, Care Practices, and Outcomes for Patients with Firearm Injuries: A 9-Year Single-Center US Level 1 Trauma Experience.

Firearm injuries cause significant morbidity and mortality. Patients with firearm injuries require urgent/emergency operative procedures but the literature incompletely describes how anesthesia care and outcomes differ between high acuity trauma patients with and without firearm injuries. Our objective was to examine anesthesia care, resource utilization, and outcomes of patients with acute firearm injuries compared to nonfirearm injuries. We conducted a retrospective cross-sectional study of patients ≥18 years admitted to a regional Level 1 trauma center between 2014 and 2022 who required operative management within the first 2 hours of hospital arrival. We examined clinical characteristics, anesthesiology care practices, and intra- and postoperative outcomes of patients with firearm injuries compared to patients with nonfirearm injuries. Over the 9-year study period, firearm injuries accounted for the largest yearly average increase in trauma admissions (firearm 10.1%, blunt 3.2%, other 1.3%, motor-vehicle crash 0.9%). Emergency anesthesiology care within 2 hours of arrival was delivered to 4.7% of injured patients (2124; 541 firearm [25.4%] and 1583 [74.5%] nonfirearm). Patients with firearm injuries were younger (30 [23-40] years vs 41 [29-56] years; P < .0001), male (90% vs 75%; P < .0001), direct admissions from scene (78% vs 62%; P < .0001), had less polytrauma (10% vs 22%; P < .0001), arrived after hours (73% vs 63%; P < .0001), and received earlier anesthesiology care (0.4 [0.3-0.7] vs 0.9 [0.5-1.5] hours after arrival; P < .0001). Patients with firearm injuries more often received invasive arterial (83% vs 77%; P < .0001) and central venous (14% vs 10%; P = .02) cannulation, blood products (3 [0-11] vs 0 [0-7] units; P < .0001), tranexamic acid (30% vs 22%; P < .001), as well as had higher estimated blood loss (500 [200-1588] mL vs 300 [100-1000] mL; P < .0001), and were transferred to the intensive care unit (ICU) more frequently (83% vs 77%; P < .001) than patients with nonfirearm injuries. Intraoperative mortality was comparable (6% firearm vs 4% nonfirearm) but postoperative mortality was lower for patients with firearm injuries who survived the intraoperative course (6% vs 14%; P < .0001). Comparatively, more patients with firearm injuries were discharged to home, or to jail (P < .001). Over the study period, anesthesiologists increasingly cared for patients with firearm injuries, who often present outside of daytime hours and require urgent operative intervention. Operating room readiness and high-intensity resuscitation capacity, such as access to hemostatic control measures, are critical to achieving intraoperative survival and favorable postoperative outcomes, particularly for patients with firearm injuries.

Impact of Portable Normothermic Machine Perfusion for Liver Transplantation From Adult Deceased Donors.

To assess how liver allografts preserved using portable normothermic machine perfusion (NMP) compare against those that underwent ischemic cold storage (ICS) in the setting of donation after brain death (DBD) and donation after circulatory death (DCD) liver transplantation (LT). Compared with conventional ICS, NMP may offer more homeostatic preservation, permit physiological assessment of organ function, and provide opportunities for graft improvement/modification. We report a single-center US experience of liver NMP. A single-center, retrospective analysis of collected data on 541 adult whole LTs from 469 DBD donors [NMP (n = 58) vs ICS (n = 411)] and 72 DCD donors [NMP (n = 52) vs ICS (n = 20)] between January 2016 and December 2022. In DBD LT, male sex [odds ratio (95% CI): 1.83 (1.08-3.09)] and >10% macrosteatosis of the donor liver [1.85 (1.10-3.10)] were statistically significant independent risk factors of early allograft dysfunction (EAD). Donor age >40 years and cold ischemia time >7 hours were independent risk factors of reperfusion syndrome (RPS). One-year, 3-year, and 5-year incidences of ischemic cholangiopathy (IC) did not differ significantly in DBD cases between the NMP and ICS cohorts. In DCD LT, NMP was an independent protective factor against EAD [0.11 (0.03-0.46)] and RPS [0.04 (0.01-0.25)]. The incidence of IC in the DCD cases at 1-year and 3-year time points was significantly lower in the NMP cohort (1.9% compared with 20% in the ICS group). Compared with conventional ICS, NMP can significantly reduce the incidence of EAD, RPS, and IC after DCD LT.

Adherence to guideline-directed hepatocellular carcinoma screening: A single-center US experience.

The American Association for the Study of Liver Disease recommends screening patients with cirrhosis for hepatocellular carcinoma (HCC) using imaging with or without alpha-fetoprotein every six months. Unfortunately, screening rates remain inadequate. To assess root causes of screening failure in a subspecialty hepatology clinic. The authors identified patients with cirrhosis seen in a subspecialty hepatology clinic and determined whether they underwent appropriate screening, defined as two cross-sectional images between five and seven months apart. The authors characterized the primary driver of screening failure. Finally, other hepatologists were surveyed to determine provider perceptions of screening failure causes. 1034 patients were identified with an average age of 61 years and a mean MELD of 8.1 ± 3.8. Hepatitis C virus was the most common cirrhosis etiology. 489 (47%) underwent appropriate screening. No demographic or clinical differences were detected between those who underwent appropriate screening and those who did not. The most common etiologies of screening failure, in descending order, were: radiology unable to schedule timely imaging, provider did not order imaging, patient canceled follow up appointment, appointments scheduled too far apart, lost to follow up, no-show to radiology appointment, and provider canceled appointment. Hepatologists surveyed believed the most common cause of screening failure was no-show to radiology. Rates of screening were poor even in a subspecialty hepatology clinic. Screening failure was mostly due to systemic factors such as radiology availability and time between hepatology appointments rather than individual error.

Operative vaginal delivery as an independent risk factor for maternal postpartum infectious morbidity

A recent study from the United Kingdom suggested that a single dosage of adjunctive amoxicillin/clavulanic acid with operative vaginal delivery reduces maternal infectious morbidity by 40% (from 19% to 11%). However, 89% of their study population received an episiotomy. This study aimed to evaluate whether operative vaginal delivery is an independent risk factor for composite maternal postpartum infectious morbidity in a population with a low episiotomy rate. This was a retrospective cohort study of patients with viable singleton vaginal deliveries after ≥34 weeks gestation at a single perinatal center (2013-2018). The patients were categorized by the mode of delivery: spontaneous vaginal delivery or operative vaginal delivery (forceps or vacuum-assisted). The primary outcome was a composite of maternal infectious morbidity up to 6 weeks after delivery, defined as (1) endometritis, (2) perineal wound morbidity (infection, breakdown, or dehiscence), or (3) culture-proven urinary tract infection. The patient characteristics and outcomes were compared between the groups using appropriate tests. Multivariable models were used to estimate the association between operative vaginal delivery and study outcomes compared with spontaneous vaginal delivery, with adjustment for selected confounders. Of 14,647 deliveries meeting the inclusion criteria, 732 (5.0%) were operative vaginal deliveries: 354 (48%) forceps and 378 (52%) vacuums. Overall, 210 (1.4%) patients developed the morbidity composite. Patients having an operative vaginal delivery were more likely to be nulliparous, have labor inductions, develop intrapartum chorioamnionitis, receive an episiotomy, and sustain a third- or fourth-degree laceration. After adjusting for confounding factors, no significant association was observed between operative vaginal delivery and composite morbidity (adjusted odds ratio, 1.4 [0.8-2.4]) or any of its individual components. Administration of postpartum antibiotics and documented fever were also similar between groups. There was also no significant association between instrument (forceps vs vacuum) and the maternal infection composite. In this single-center US cohort, operative vaginal delivery was not an independent risk factor for maternal composite postpartum infectious morbidity.

Chronic Granulomatous Disease: an Updated Experience, with Emphasis on Newly Recognized Features

PurposeChronic granulomatous disease (CGD) is an uncommon, inborn error of immunity. We updated our large, single-center US experience with CGD and describe some newly recognized features.MethodsWe retrospectively reviewed 26 patients seen from November 2013 to December 2019. Serious infections required intravenous antibiotics or hospitalization.ResultsThere were 21 males and 5 females. The most frequent infectious agents at presentation were aspergillus (4), serratia (4), burkholderia (2), Staphylococcus aureus (2), and klebsiella (2). The most common serious infections at presentation were pneumonia (6), lymphadenitis (6), and skin abscess (3). Our serious infection rate was 0.2 per patient-year from December 2013 through November 2019, down from 0.62 per patient-year from the previous study period (March 1985–November 2013). In the last 6 years, four patients were evaluated for human stem cell transplantation, two were successfully transplanted, and we had no deaths. Several patients had unusual infections or autoimmune manifestations of disease, such as pneumocystis pneumonia, basidiomycete/phellinus fungal pneumonia, and retinitis pigmentosa. We included one carrier female with unfavorable Lyonization in our cohort.ConclusionWe update of a large US single-center experience with CGD and describe some recently identified features of the illness.

P-208: Ongoing trials investigating in-class transition (iCT) from parenteral to oral proteasome inhibitor (PI)-based treatment with ixazomib in multiple myeloma (MM)

P-208: Ongoing trials investigating in-class transition (iCT) from parenteral to oral proteasome inhibitor (PI)-based treatment with ixazomib in multiple myeloma (MM)

Management of Coagulopathy Associated with CTL019 CAR T-Cell Therapy

Introduction: CTL019 (tisagenlecleucel) is an anti-CD19 chimeric antigen receptor (CAR) T-cell therapy that has demonstrated high durable response rates and a manageable safety profile in pediatric/young adult patients (pts) with relapsed or refractory (r/r) B-cell acute lymphoblastic leukemia (B-ALL). CTL019-associated cytokine-release syndrome (CRS), a systemic inflammatory response caused by elevated serum cytokine levels, occurred in 81% of pts treated in 2 multicenter trials (Maude et al, Haematologica . 2017;120(s2): [abstract P517]). Coagulopathy has been associated with CRS and macrophage activation syndrome (MAS) in previous reports of CTL019 from a single-center US study, and similar coagulopathy has been reported in cases of MAS/hemophagocytic lymphohistiocytosis associated with other events such as infections or chemotherapy. Here, we outline the treatment guidelines established and US and global multicenter experience with CTL019-associated coagulopathy in 97 pts treated with CTL019.Methods: Pooled data from 2 single-arm, multicenter phase II trials of CTL019 in pediatric/young adult pts with r/r B-ALL (ELIANA, NCT02435849 and ENSIGN, NCT02228096) were used to further characterize coagulopathy during CTL019-associated CRS.Results: Maximal grades 1-2, 3, and 4 CRS occurred in 36, 19, and 24 pts, respectively. Median lowest fibrinogen levels were 3.5 g/L and 3.3 g/L in pts with maximal grade 1-2 and 3 CRS, respectively, while median lowest fibrinogen level in pts with maximal grade 4 CRS was 1.2 g/L. 3%, 11%, and 25% of pts with maximal grades 1-2, 3, and 4 CRS, respectively, had lowest reported fibrinogen levels of ≥ 1 to < 1.5 g/L. Very low fibrinogen levels (<1 g/L) were observed in 33% of pts with maximal grade 4 CRS, with 2 pts having unmeasurable levels of fibrinogen, but not in any pt with maximal grade 1-3 CRS. Very low fibrinogen levels (<1 g/L) could occur before maximal CRS grade (n=1), during maximal CRS grade (n=6), or at the time of CRS improvement (n=1). Near the time of very low fibrinogen levels (<1 g/L) onset, only 1 pt had concurrent grade 3 increased INR and aPTT; the other 7 pts had grade 0-2 increased INR and aPTT.Given that hypofibrinogenemia was the most notable coagulopathy, cryoprecipitate was the mainstay of treatment in the US. In addition, administration of large volumes of fresh frozen plasma can be problematic in pts with CRS, fluid overload, and capillary leak. Guidelines for fibrinogen concentrate (FC) use were developed for the ELIANA global trial for CTL019-associated coagulopathy since cryoprecipitate is not readily available in Japan and some European countries. FC was available at 7/25 sites and administered to 3/7 pts with grade 4 CRS, and none of 8 pts with grades 1-3 CRS, out of 20 infused pts. Cryoprecipitate was available in 18/25 sites and administered to 12/17 pts with grade 4 CRS, 2/15 pts with grade 3 CRS, and none of 32 pts with grades 1-2 CRS, out of 77 infused pts.In pediatric pts with r/r B-ALL, the risk of bleeding from CTL019-associated hypofibrinogenemia can be increased by co-morbid thrombocytopenia and the use of anticoagulants, including those used in veno-venous hemofiltration (CVVH). Within 1 day of onset of very low fibrinogen levels (<1 g/L), 5/8 pts had concurrent grade 3 or 4 decreased platelets. 1 fatal case (1/97 infused pts=1%) of intra-parenchymal cranial hemorrhage was seen during resolving CRS with grade 3 hypofibrinogenemia, ongoing thrombocytopenia, and CVVH with citrate.Conclusions: Clinical recommendations and guidelines were developed for the use of FC and cryoprecipitate for the treatment of CTL019-associated coagulopathy with hypofibrinogenemia. During CTL019-associated coagulopathy, fibrinogen levels were disproportionately low as compared with INR/PTT. Hypofibrinogenemia was observed more frequently in pts with higher CRS grades, could be seen either during or when CRS was improving or resolution, and was effectively managed by FC or cryoprecipitate replacement. Rarely, fatal bleeding can be seen. Frequent monitoring of fibrinogen, INR/PTT, platelets, and signs of clinical bleeding, as well as appropriate fibrinogen replacement are needed in pts with grade 3 and 4 CRS associated with CAR T-cell therapies. DisclosuresBüchner:Novartis Pharmaceuticals Corporation: Consultancy; Pfizer: Consultancy. Grupp:Novartis Pharmaceuticals Corporation: Consultancy, Other: grant; Jazz Pharmaceuticals: Consultancy; Adaptimmune: Consultancy; University of Pennsylvania: Patents & Royalties. Maude:Novartis Pharmaceuticals: Consultancy, Other: Medical Advisory Boards. Hiramatsu:Novartis Pharmaceuticals Corporation: Other: Clinical trials . Wood:Novartis Pharmaceuticals Corporation: Employment, Equity Ownership. Awasthi:Novartis Pharmaceuticals Corporation: Employment. Yi:Novartis Pharmaceuticals Corporation: Employment.

Severe Acute Respiratory Syndrome-Coronavirus-2 Transmission in an Urban Community: The Role of Children and Household Contacts.

This is a single center US retrospective study of infection patterns among household sick contacts of children with confirmed Severe Acute Respiratory Syndrome – Coronavirus 2 (SARS-CoV-2) infection in an urban setting. A household sick contact (HHSC) was identified in fewer than half (42%) of patients and no child-to-adult transmission was identified.

Angiotensin Converting Enzyme Inhibitor and Angiotensin II Receptor Blocker Use Among Outpatients Diagnosed With COVID-19

Coronavirus disease 2019 (COVID-19) is a viral pandemic precipitated by the severe acute respiratory syndrome coronavirus 2. Since previous reports suggested that viral entry into cells may involve angiotensin converting enzyme 2, there has been growing concern that angiotensin converting enzyme inhibitor (ACEI) and angiotensin II receptor blocker (ARB) use may exacerbate the disease severity. In this retrospective, single-center US study of adult patients diagnosed with COVID-19, we evaluated the association of ACEI/ARB use with hospital admission. Secondary outcomes included: ICU admission, mechanical ventilation, length of hospital stay, use of inotropes, and all-cause mortality. Propensity score matching was performed to account for potential confounders. Among 590 unmatched patients diagnosed with COVID-19, 78 patients were receiving ACEI/ARB (median age 63 years and 59.7% male) and 512 patients were non-users (median age 42 years and 47.1% male). In the propensity matched population, multivariate logistic regression analysis adjusting for age, gender and comorbidities demonstrated that ACEI/ARB use was not associated with hospital admission (OR 1.2, 95%CI 0.5 to 2.7, p = 0.652). CAD and CKD/end stage renal disease [ESRD] remained independently associated with admission to hospital. All-cause mortality, ICU stay, need for ventilation, and inotrope use was not significantly different between the 2 study groups. In conclusion, among patients who were diagnosed with COVID-19, ACEI/ARB use was not associated with increased risk of hospital admission.

Tu1489 ENDOSCOPIC SUBMUCOSAL DISSECTION OF DUODENAL LESIONS: A SINGLE CENTER EXPERIENCE

Endoscopic submucosal dissection (ESD) has revolutionized the approach and treatment of gastrointestinal lesions, particularly the colon and stomach. In these locations, this technique has been proven to be safe with efficacy ad low recurrence rate. However, ESD in the duodenum is less common due to technical challenges with duodenal lesions. We herein present a single center US series of ESD for duodenal lesions. We performed a retrospective review of prospectively collected data on patients who underwent ESD of lesions in the duodenum between 01/2016 and 10/2019. Baseline data was collected for age, sex, prior EMR attempts, lesion location, and procedural related data. Primary outcomes included technical success, defined as successful en-bloc complete resection, R0 resection rate and intra/post procedural adverse event rates. Secondary outcomes included local recurrence rate. Mean with standard deviations were calculated for continuous data, while percentages were calculated for categorical data. Ten consecutive patients underwent duodenal ESD by an experienced endoscopist Table 1]. Mean age was 63 +/- 9 years, 50% were female. The duodenal bulb was the most common site for ESD (60%). Mean lesion diameter was 26.4 (+/- 28) mm. En-bloc resection and R0 resection rates were 100% and 100% respectively. 80% of post ESD defects were successfully closed, with an endoscopic suturing device being the most commonly employed method of closure (75%). Mean procedure time was 110 +/- 39.8 minutes. There were no intraprocedural complications encountered. The most common pathology was neuroendocrine tumor (60%). Two patients (20%) had post procedural bleeding within one week, both required repeat EGD with hemostasis. None of the patients with endoscopic suturing for defect closure had post-procedural bleeding. Sixty percent of patients presented for follow up at mean 165 (+/- 66) days with no evidence of recurrence on endoscopic or histologic evaluation. Duodenal ESD can be performed safely and effectively with a low serious adverse event rate and low risk of recurrence. Duodenal defect closure is important to prevent complications such as delayed perforation and hemorrhage.

Practical applications and learning curve for EUS-guided hepaticoenterostomy: results of a large single-center US retrospective analysis.

Background and study aims Endoscopic ultrasound-guided hepaticoenterostomy (EUS-HE) is an effective method of endoscopic biliary drainage in cases where endoscopic retrograde cholangiopancreatography has failed or is deemed impossible. Indications for EUS-HE have expanded, resulting in increased interest by endoscopists to learn the procedure; however, few data exist on breadth of application or experience needed to develop proficiency. We describe utilization of EUS-HE for biliary decompression at a large tertiary referral center along with procedural learning curve. Patients and methods Retrospective evaluation of 60 consecutive patients who underwent attempted EUS-HE by one endoscopist from February 2016 through June 2018. Procedures were divided into chronological and summative experience quartiles. We compared procedural success rate, procedural utilization, and procedure duration over time. Results Sixty patients underwent attempted EUS-HE during the study period: 35 with surgically altered anatomy, 23 with malignant biliary obstruction, 35 outpatients, 35 females; median age, 66 years. The procedure was technically successful in 53 patients. Success rates by summative experience quartile were 80 %, 80 %, 93.3 % and 100 % respectively. Beginning at patient number 40, the remaining cases had a success rate of 100 %. Utilization increased from eight cases in the first chronological quartile to 28 in the fourth. There was no significant reduction in procedure duration over time. Conclusion For an experienced endoscopist, EUS-HE could be performed effectively and safely after the experience of 40 cases. Limitations of this study include a single endoscopist and heterogeneous patient population with variable anatomy that may affect procedural success. Future studies should include data from multiple centers and endoscopists.

Endoscopic Ultrasound-Directed Transgastric ERCP (EDGE): a Single-Center US Experience with Follow-up Data on Fistula Closure

Endoscopic ultrasound-directed transgastric ERCP (EDGE) by creating an anastomosis from the gastric pouch or jejunum to the excluded stomach allows performance of ERCP in Roux-en-Y gastric bypass (RYGB) anatomy. Concern for persistent fistula following stent removal and sparse data limit adoption. Retrospective review of consecutive patients undergoing EDGE over a 2-year period. Nineteen RYGB patients underwent EDGE; three had previously failed ERCP by the device-assisted method. Indications for ERCP were choledocholithiasis (8), recurrent acute pancreatitis (6), benign post-surgical stricture (3), elevated bilirubin, and papillary stenosis (1 each). EDGE was technically successful in all 19 patients with jejunogastric anastomosis in 11 patients and gastrogastric in 8 using a 15-mm lumen-apposing metal stent. Stent malposition occurred in six and was managed by rescue maneuvers. ERCP was performed in the same session in four patients; the remainder were delayed after a mean of 48days. Diagnostic endoscopic ultrasound (EUS) was performed in four patients. No severe adverse events occurred; clinical success was 100%. Stents were removed after a mean dwell time of 182days. Argon plasma coagulation (APC) was used to promote fistula closure in 12 patients. Upper GI series to assess fistula closure was obtained in 11 patients after a mean of 182days following stent removal. One persistent fistula was identified and closed endoscopically. EDGE is an effective modality for performing ERCP in patients with RYGB anatomy and can be performed via gastrogastric or jejunogastric approaches. Persistent fistula is uncommon and can be managed endoscopically. APC may promote fistula closure.

Standardized high-sensitivity flow cytometry testing for paroxysmal nocturnal hemoglobinuria in children with acquired bone marrow failure disorders: A single center US study.

Paroxysmal nocturnal hemoglobinuria (PNH) is a rare, acquired hematopoietic stem cell disorder that has not been well-documented in children, particularly those with acquired bone marrow failure disorders (ABMFD)-acquired aplastic anemia (AAA) and myelodysplastic syndrome (MDS). Therefore, we sought to determine the prevalence of PNH populations in children with ABMFD. PNH testing was performed in children with an ABMFD diagnosis using high sensitivity (≥0.01%) fluorescent aerolysin (FLAER)-based assay according to 2010 International Clinical Cytometry Society (ICCS) PNH Consensus Guidelines and 2012 Practical PNH Guidelines. FLAER/CD64/CD15/CD24/CD14/CD45 and CD235a/CD59 panels were used for white blood cell and red blood cell testing, respectively. Thirty-seven patients with ABMFD (34 AAA, 3 MDS) were included (17M/20F, age 2-18years, median 9years). PNH populations were identified in 17 of 37 (46%) patients. Of the 17 patients with PNH populations identified, 7 were PNH clones (>1% PNH population), and 10 had minor PNH population or rare cells with PNH phenotype (≤1% PNH population). This is the first study to use a standardized high-sensitivity FLAER-based flow cytometry assay and the recommended cutoff of 0.01% to identify cells with PNH phenotype in pediatric patients with ABMFD in the United States. The identification of a PNH population in 46% of ABMFD supports the recommendation for high sensitivity PNH testing in children with these disorders. As a less sensitive assay using a cutoff of ≥ 1% PNH population would have missed 10 (27%) patients with minor PNH population or rare cells with PNH phenotype. © 2017 International Clinical Cytometry Society.

Transplantation for acute alcoholic hepatitis.

Transplantation for acute alcoholic hepatitis.

Risk Factors Associated with Incomplete Endoscopic Mucosal Resection of Colonic Polyps

Introduction: Risk factors for incomplete endoscopic mucosal resection (EMR) of large colonic polyps are uncertain. We aimed to characterize the rates and risk factors of incomplete resections (IR) at a single US center. We hypothesize that polyp size > 40mm predicts IR and resections initiated by endoscopists specializing in colonic EMR protect against IR. Methods: Using an electronic endoscopic database, we identified patients who underwent EMR with at least one follow up colonoscopy from 2006-2015 at our institution. Patients with IBD were excluded. The primary outcome (IR) was defined as cases which the provider noted residual polyp at the end of the first resection attempt. Polyp characteristics and the endoscopist first performing EMR (specialist (SE) vs. non-specialist endoscopist) were noted. Univariate and multivariate analysis was used to identify factors associated with IR. Clinical outcomes were recorded. Results: 258 patients with 289 polyps underwent EMR with at least one follow up colonoscopy. 39/258 (15%) had IR. Age, gender, polyp location, and follow up were similar between complete resections (CR) and IR (Table 1). SE as the sole EMR provider achieved CR in fewer colonoscopies than non-SE± subsequent SE referral (mean 2.4 vs. 3, p< 0.0001). On univariate and multivariate logistic regressions, polyp > 40 mm (odds ratio [OR] = 2.3; 95% confidence interval [CI] = 1.1-14.9), piecemeal removal (OR = 7.5, CI 1.8-31.9), and difficulty lifting the polyp (OR = 3.1, CI 1.1-8.9) were associated with IR. Resections performed by SE alone were protective against IR (OR 0.31, CI 0.15-0.65). Based on our regression model, the probability of IR in piecemeal resections of polyps>40 mm with and without difficulty lifting (and started by a non-SE) is 88% and 56%,respectively. When SE are the sole EMR provider, the probability of IR drops to 41% and 11%, respectively, (Figure 1). Of the IR patients, 12 (28%) were referred for surgery, 2 of which were for adenocarcinoma and 1 of which were for high grade dysplasia. 16 (41%) achieved CR after a mean of 2 more colonoscopies (range 1-4), 7(18%) are actively undergoing further EMR, and 4 were lost to follow-up.Figure 1Table 1: Demographics, endoscopic findings and pathology of patients with complete and incomplete resections.Conclusion: In this single center US experience, IR of large colon polyps occurred infrequently. Polyps > 40mm, piecemeal resections and difficulty lifting were risk factors for IR. Primary resections by specialist endoscopists reduce the risk of IR and the number of procedures to achieve CR.

Blood Donor Demographics and Transfusion Recipient Survival-No Country for Old Men?

Blood for transfusion is a drugor,more specifically, a biological medicine.1 The US Food and Drug Administration regulatesbloodforpurity,potency,andsafetyunder theFood,Drug, and Cosmetic Act of 1938. Regulatory authorities in most developed countries prescribe blood collection, storage, testing, labeling, and intended use. Facilities for blood component “manufacture” are licensed and inspected for compliance with current good manufacturing practices. Where blood differs from small-molecule pharmaceuticals and recombinant biologics is in its unit-to-unit heterogeneity (batch variability). Although blood donors are qualified as suppliers of “raw material” by rigorous selection and testing standards, each donor is biologically distinct. Therefore, every unit of blood is considered its own batch. Despite the acknowledged batch variability, unit-to-unit differences are not expected to be so significant as to affect transfusion outcomes. However, the association of donor characteristics with transfusion outcomes has not been carefully investigated. In this issue of JAMA Internal Medicine, Chasse and colleagues2 report the association of blood donor age and sex with recipient survival after red blood cell (RBC) transfusion. Their longitudinal cohort study links blood donor data routinely collectedby theCanadianBloodServices toRBC recipient clinical information gathered from databases containing the short-term and long-term patient outcomes from 4 academichospitals.The investigatorspredeterminedprimaryand secondary exposures (donor age and donor sex) and the primaryoutcome (recipient survival). The studyperiod spanned 7years and included80755blooddonors, 30503patients, and 187 960 RBC units. The investigators constructed a robust model supported by generally accepted statistical principles. Yet, evenwith rigorous analyses and sensitivity testing, their study remainsobservational andsubject to the risksofbiasand confounding. The findings should be consideredhypotheses, not evidence of causality. Theobservation that donordemographic factorsmight be associatedwith transfusionoutcome isnotnew.More than50 yearsago, the riskof transfusion-transmittedhepatitiswascorrelated with donor sex, age, socioeconomic status, and ethnicity.3 All of these associations were eventually found to be related to the donor’s risk of infectionwith hepatitis B or C viruses.However, the findingsbyChasse andcolleagues,2 particularly the primary exposure that transfused RBCs from youngerdonors areassociatedwithan increasedmortality risk of6%to8%,with thegreatest risk inmale recipients, arehardly expectedor intuitive.Whyshouldoldmenbe safer donors but more vulnerable recipients? The only other published study4 ofRBCdonor age and recipientmortality, a large,matched cohort investigation from the Danish and Swedish ScandinavianDonationsandTransfusions (SCANDAT)2database, found noassociationbetweendonor ageandpatient 30-dayor 1-year mortality afterRBCorplasma transfusion. The studies arenot precisely comparable. Patients in the SCANDAT2analysis had a lower RBC exposure. Similarly, in a single-center US study,5 noassociationwas foundbetweendonorageandrecipientoutcomeafterplasma transfusion ina largedatabase-linkedstudy of coronary artery bypass surgery.However, the absenceof an obvious mechanism or of confirmatory studies does not refute the findings byChasse and colleagues2 but indicates that verification is necessary before such findings canbe actedon. With the secondary exposure, Chasse and colleagues2 founda strongassociationbetween femaleRBCdonors and recipientmortality. The transfusionof each additional RBCunit from a female donor compared with a male donor was associated with an increased risk of death of 8%. Numerous biological differencesdistinguishblood fromfemaleandmaledonors, from lower hemoglobin levels and different protein concentrations to the frequency of HLA, platelet, and granulocyte alloantibodies. None of these factors are used in routine blood donor screening to determine the safety of RBC transfusion. However, plasma from female donors is routinely avoided, as are single-donor platelet concentrates from multiparous women who have not been screened for HLA alloantibodies, because of their association with transfusionrelated acute lung injury (TRALI). Still, the risk of TRALI, especially from blood components that contain minimal amounts of plasma, cannot explain an 8% mortality difference. Other genetic factors appear to be involved in the documented differences in donor RBC in vivo survival and ex vivo storage, although neither of these examples of batch variability has been associated with donor sex,6,7 nor have such differences been shown to affect survival of blood component recipients. Several featuresof the studybyChasseandcolleagues2deserve emphasis. Of course, the specific conclusions are tantalizingandclearlymerit furtherexploration.Moregenerally, this study highlights the need to further investigatewhich demographic and genetic donor factors aside from blood groups might influence the safety and efficacy of the different blood components. Such researchhasbeenovershadowedby theunderstandable focus on pathogen transmission. Perhaps the most significant message may be recognition, as the authors point out, that to perform such studies one has to be able to track blood from “vein to vein.” Themost efficient way to do thisona large scale is byexploitingexistingdatabases, thebest example of which is the previously cited SCANDAT database, a collaboration between Sweden and Denmark.4 Related article page 1307 Association of Blood Donor Age and SexWith Recipient Survival Original Investigation Research

Prostatic Artery Embolization Using Embosphere Microspheres for Prostates Measuring 80–150 cm3: Early Results from a US Trial

Between November 2014 and October 2015, 12 patients with prostates measuring 80–150 cm3 and lower urinary tract symptoms (LUTSs) were enrolled in a prospective single-center US trial to evaluate Embosphere Microspheres for use in prostatic artery embolization (PAE). At 3 months, mean improvements in International Prostate Symptom Score and quality of life score were 18.3 points (range, 5–27) and 3.6 points (range, 1–6), respectively. One-month cystoscopies and anoscopies demonstrated no ischemic injuries. There were no major complications. In this cohort, Embosphere Microspheres, when used for PAE, were safe and effective in reducing LUTSs in the early follow-up period.

Chronic Granulomatous Disease: A Large, Single-center US Experience.

Background:Chronic granulomatous disease (CGD) is an uncommon primary immunodeficiency that can be inherited in an X-linked (XL) or an autosomal recessive (AR) manner. We reviewed our large, single-center US experience with CGD.Methods:We reviewed 27 patients at Ann & Robert H. Lurie Children’s Hospital of Chicago from March 1985 to November 2013. Fisher exact test was used to compare differences in categorical variables, and Student t test was used to compare means for continuous variables. Serious infections were defined as those requiring intravenous antibiotics or hospitalization.Results:There were 23 males and 4 females; 19 were XL and 8 were AR. The average age at diagnosis was 3.0 years; 2.1 years for XL and 5.3 years for AR inheritance (P = 0.02). There were 128 serious infections. The most frequent infectious agents were Staphylococcus aureus (n = 13), Serratia (n = 11), Klebsiella (n = 7), Aspergillus (n = 6) and Burkholderia (n = 4). The most common serious infections were pneumonia (n = 38), abscess (n = 32) and lymphadenitis (n = 29). Thirteen patients had granulomatous complications. Five patients were below the 5th percentile for height and 4 were below the 5th percentile for weight. Average length of follow-up after diagnosis was 10.1 years. Twenty-four patients were compliant and maintained on interferon-γ, trimethoprim-sulfamethoxazole and an azole. The serious infection rate was 0.62 per patient-year. Twenty-three patients are alive (1 was lost to follow-up).Conclusions:We present a large, single-center US experience with CGD. Twenty-three of 27 patients are alive after 3276 patient-months of follow-up (1 has been lost to follow-up), and our serious infection rate was 0.62 per patient-year.