Citations

Abstract Background: Pancreatic cancer (PC) ranks among the top causes of cancer mortality. Risk stratification is an important step toward prevention and early detection. Prior work has shown that ABO blood type (non-O) and first-degree family history of PC are associated with increased PC risk. Individuals with first-degree family history of PC have a 2- to 3-fold increased risk, but it is unclear if ABO blood type plays a role in the familial aggregation of PC. We investigated PC risk among first-degree relatives (FDRs) of PC probands based on the probands' serologic blood type (O vs non-O). Methods: A total of 702 probands sequentially enrolled in the Mayo Clinic Pancreas Research Registry from 2000-2016 with serologic ABO blood type provided information on family history of cancer for 5,178 FDRs. FDRs were grouped based on their related probands' blood type as type O (n=242; 1,768 FDRs) vs non-O (n=460; 3,410 FDRs). Standardized incidence ratios (SIRs) and 95% confidence intervals (CIs) were calculated by comparing the number of PC cases observed among FDRs to those expected using data from the Surveillance, Epidemiology and End Results (SEER) Program as the reference population. SIRs for PC risk were calculated separately for FDRs of probands with type O vs FDRs of probands with non-O blood, and stratified by sex of FDRs and relationship to proband (parent, sibling, or offspring). Results: Compared to the SEER reference, PC risk was nearly 2-fold higher among FDRs of PC probands (SIR=1.76; 95%CI: 1.35-2.26). When stratified by probands' ABO type, risk for PC was higher among FDRs of probands with non-O blood (SIR=1.94; 95%CI: 1.41-2.60), compared to FDRs of probands with O blood (SIR=1.42; 95%CI: 0.83-2.28). Parents of probands with non-O blood had increased PC risk (SIR=3.28; 95%CI: 2.18-4.74, n=920), but not parents of probands with O blood (SIR=1.75; 95%CI: 0.75-3.45, n=484), p-value for between-group difference=0.10. Among FDRs of probands with O blood, female FDRs had increased PC risk (SIR=2.12; 95%CI: 1.06-3.79), but male FDRs did not (SIR=0.86; 95%CI: 0.31-1.88). Higher PC risk was observed among female FDRs of probands with non-O blood (SIR=2.28; 95%CI: 1.44-3.41) than male FDRs of probands with non-O blood (SIR=1.62; 95%CI: 1.00-2.48). Mothers of probands with O blood had increased PC risk (SIR=2.89; 95%CI: 1.05-6.28) compared to fathers (SIR=0.79; 95%CI: 0.09-2.84). Both mothers (SIR=3.60; 95%CI: 1.96-6.03) and fathers (SIR=2.95; 95%CI: 1.61-4.95) of probands with non-O blood had increased PC risk. No major findings were observed among probands' siblings or offspring. Conclusions: PC risk is greater among FDRs of PC probands with non-O blood than among FDRs of probands with type O. PC risk is higher among parents of probands with non-O blood, and female FDRs and mothers of probands with non-O blood. Possible clustering of non-O blood type in families may contribute to increased PC risk. Citation Format: Aarti Kolluri, Samuel O. Antwi, Sarah E. Fagan, Kari G. Chaffee, Brendan T. Broderick, William R. Bamlet, Ann L. Oberg, Robert R. McWilliams, Gloria M. Petersen. Risk of pancreatic cancer is increased among first-degree relatives of pancreatic cancer probands who have non-O ABO blood type [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 1239.

Abstract Background Toxoplasmosis is routinely diagnosed through detection of Toxoplasma gondii–specific antibodies. However, the imperfect specificity of T. gondii serologic assays is a well-recognized limitation. The new BioPlex 2200 (Bio-Rad Laboratories) T. gondii, rubella, and cytomegalovirus (ToRC) IgM multiplex flow immunoassay (MFI) received FDA clearance in May 2017. We evaluated the clinical performance of the new T. gondii IgM and existing IgG portion of this MFI. Methods Three hundred prospectively collected consecutive, residual sera, submitted for T. gondii serologic testing as part of routine clinical care, and an archived set of 52 residual sera previously positive for anti–T. gondii IgM and IgG with the predicate ADVIA Centaur Toxoplasma IgM and IgG assays (Siemens) were evaluated. Performance of the BioPlex 2200 T. gondii IgM and IgG MFIs was assessed by calculating positive (PPA) and negative percent agreement (NPA) compared to the Centaur tests. Results Among prospective specimens, the BioPlex 2200 T. gondii IgM and IgG MFIs demonstrated a PPA of 0% (0/7) and 82.3% (28/34) and NPA of 99.3% (288/290) and 95.8% (251/262), respectively, with the Centaur assays. Chart review of the 7 Centaur T. gondii IgM-positive samples revealed that these were likely falsely positive. Among archived samples, the BioPlex 2200 T. gondii IgM and IgG MFIs showed PPAs of 90.4% (47/52) and 100% (52/52), respectively. Conclusions The BioPlex 2200 T. gondii IgM and IgG MFIs demonstrated excellent concordance with the Centaur assays. The T. gondii IgM MFI may provide higher specificity in low-prevalence populations.

OBJECTIVES: We assessed the adherence to neuroimaging guidelines and the diagnostically relevant yield of neuroimaging in newly presenting early life epilepsy (ELE). METHODS: There were 775 children with a new diagnosis of epilepsy (<3 years old at onset) who were recruited through the ELE study at 17 US pediatric epilepsy centers (2012–2015) and managed prospectively for 1 year. The data were analyzed to assess the proportion of children who underwent neuroimaging, the type of neuroimaging, and abnormalities. RESULTS: Of 725 children (93.5%) with neuroimaging, 714 had an MRI (87% with seizure protocols) and 11 had computed tomography or ultrasound only. Etiologically relevant abnormalities were present in 290 individuals (40%) and included: an acquired injury in 97 (13.4%), malformations of cortical development in 56 (7.7%), and other diffuse disorders of brain development in 51 (7.0%). Neuroimaging was abnormal in 160 of 262 (61%) children with abnormal development at diagnosis versus 113 of 463 (24%) children with typical development. Neuroimaging abnormalities were most common in association with focal seizure semiology (40%), spasms (47%), or unclear semiology (42%). In children without spasms or focal semiology with typical development, 29 of 185 (16%) had imaging abnormalities. Pathogenic genetic variants were identified in 53 of 121 (44%) children with abnormal neuroimaging in whom genetic testing was performed. CONCLUSIONS: Structural abnormalities occur commonly in ELE, and adherence to neuroimaging guidelines is high at US pediatric epilepsy centers. These data support the universal adoption of imaging guidelines because the yield is substantially high, even in the lowest risk group.

Background Management of scapholunate (SL) ligament disruption is a challenging problem. The reduction and association of the scaphoid and lunate (RASL) procedure has been described with varying results. This study assessed the outcomes of the RASL procedure. Purpose The objective of this study was to assess the outcomes of patients undergoing the RASL procedure at our institution in regard to pain relief, range of motion, radiographic and functional outcomes, complications, and reoperations. Materials and Methods Twelve patients with symptomatic chronic SL instability underwent the RASL procedure. The mean age was 35 years. The mean time from injury to surgery was 40 weeks. The mean follow-up was 89 months. Outcomes included visual analog score for pain, wrist range of motion, grip strength, and Mayo Wrist Scores. Preoperative and postoperative radiographs were reviewed. Results Pain scores improved in 10 wrists. Range of motion and grip strength worsened. The average Mayo Wrist Score was 63.3. The mean SL diastasis and angle improved, but seven wrists developed progressive degenerative changes, with two requiring a salvage procedure. Symptomatic progressive screw lucency occurred in eight wrists requiring screw removal. Conclusion The RASL procedure can improve SL widening but has a high rate of early failure and reoperation. Following reoperation, long-term follow-up demonstrates reasonable long-term durability in some cases. Level of Evidence This is a Level IV, therapeutic case study.

Abstract Large-scale genome-wide association studies (GWAS) have identified approximately 35 loci associated with epithelial ovarian cancer (EOC) risk. The majority of GWAS-identified disease susceptibility variants are located in noncoding regions, and causal genes underlying these associations remain largely unknown. Here, we performed a transcriptome-wide association study to search for novel genetic loci and plausible causal genes at known GWAS loci. We used RNA sequencing data (68 normal ovarian tissue samples from 68 individuals and 6,124 cross-tissue samples from 369 individuals) and high-density genotyping data from European descendants of the Genotype-Tissue Expression (GTEx V6) project to build ovarian and cross-tissue models of genetically regulated expression using elastic net methods. We evaluated 17,121 genes for their cis-predicted gene expression in relation to EOC risk using summary statistics data from GWAS of 97,898 women, including 29,396 EOC cases. With a Bonferroni-corrected significance level of P < 2.2 × 10−6, we identified 35 genes, including FZD4 at 11q14.2 (Z = 5.08, P = 3.83 × 10−7, the cross-tissue model; 1 Mb away from any GWAS-identified EOC risk variant), a potential novel locus for EOC risk. All other 34 significantly associated genes were located within 1 Mb of known GWAS-identified loci, including 23 genes at 6 loci not previously linked to EOC risk. Upon conditioning on nearby known EOC GWAS-identified variants, the associations for 31 genes disappeared and three genes remained (P < 1.47 × 10−3). These data identify one novel locus (FZD4) and 34 genes at 13 known EOC risk loci associated with EOC risk, providing new insights into EOC carcinogenesis. Significance: Transcriptomic analysis of a large cohort confirms earlier GWAS loci and reveals FZD4 as a novel locus associated with EOC risk. Cancer Res; 78(18); 5419–30. ©2018 AACR.

AbstractParenteral nutrition (PN) is a complex therapeutic modality provided to neonates, children, and adults for various indications. Surveys have shown that current electronic health record (EHR) systems are in need of functionality enhancement for safe and optimal delivery of PN. This is a consensus statement from the American Society for Parenteral and Enteral Nutrition, the Academy of Nutrition and Dietetics, and the American Society of Health‐System Pharmacists outlining some of the key challenges to prescribing, order review/verification, compounding, and administration of PN using EHRs today and is a call to action for clinicians and vendors to optimize their EHRs regarding the PN build and workflow.

Abstract Background Current American College of Gastroenterology (ACG) guidelines suggest that Helicobacter pylori serologic testing may be helpful to rule out H. pylori in areas with low disease prevalence. However, even in low prevalence regions, the positive predictive value of a positive serologic result remains low. Additionally, both the ACG and the American Gastroenterological Association recommend that this noninvasive testing be avoided entirely for patients 55 years and older. Methods The objective of this multicenter retrospective study was to assess H. pylori seroprevalence rates among symptomatic patients and serologic test utilization at the local, state, and national level. Submitted specimens were presumed to be collected from patients with upper gastrointestinal symptoms suspicious for an H. pylori etiology. Results for H. pylori IgG serologic tests performed between 2005 and 2014 were collected from 5 medical centers. Data were evaluated in the context of professional practice guidelines, with a focus on patients ages 55 years and older. Results Nationwide seropositivity among symptomatic individuals is approximately 25%, and 4 of 5 centers reported decreasing seropositivity rates over this 10-year period. State-specific seropositivity among symptomatic patients ranged from 12.4% in the state of Washington to 33.9% in Mississippi. Conclusions We demonstrate that for 48 states >25% of all H. pylori serologic testing was performed in individuals ≥55 years. Despite recommendations to avoid serologic evaluation for H. pylori infection, this study indicates that serology continues to be used at high rates across age-groups.