Citations

AbstractIn hemophilia B (HB), factor IX gene (F9) genotyping is used for molecular confirmation of affected individuals, for carrier testing, to facilitate the identification of those at risk for anaphylaxis/inhibitors (associated with large deletions), and to assist in assigning disease severity. Owing to test costs, optimal test utilization involves pre/post-test counseling and appropriate patient and test selection (e.g., mutation screening [F9MS] vs. known mutation [F9KM] testing). This article aims to review the trends and outcomes of F9-genotyping orders and describe the spectrum of variants identified in a sample of individuals in our reference laboratory. We performed a retrospective review of consecutive orders submitted to the Special Coagulation DNA Diagnostic Laboratory, Mayo Clinic, between 2012 and 2015. A total of 133 orders (38%) were identified for men: 118 (88%) were F9MS and 15 (12%) were F9KM. Thirteen orders (10%) were cancelled. A total of 209 orders were identified for women: 178 (85%) were F9MS and 31 (15%) were F9KM. Thirty-seven orders (18%) were cancelled and 30% of the tests performed yielded negative results. A total of 164 samples (47%) were received without clinical information. Seventeen previously unreported variants were identified. F9 genotyping provides useful information for HB management; however, 18% of our orders were cancelled and almost half were received without relevant clinical information, thus reaffirming the need for ongoing scrutiny of submitted orders. Optimal patient and test selection is important as is the accurate interpretation of variants identified. Most of the pathogenic variants identified were point mutations, with very few large deletions, consistent with the literature.

Abstract Bile duct injury ( BDI ) during laparoscopic cholecystectomy remains a serious iatrogenic surgical complication. BDI most often occurs as a result of misidentification of the anatomy; however, clinical evidence on its precise mechanism and surgeons’ perceptions is scarce. Surgeons from Japan, Korea, Taiwan, and the USA, etc. ( n = 614) participated in a questionnaire regarding their BDI experience and near‐misses; and perceptions on landmarks, intraoperative findings, and surgical techniques. Respondents voted for a Delphi process and graded each item on a five‐point scale. The consensus was built when ≥80% of overall responses were 4 or 5. Response rates for the first‐ and second‐round Delphi were 60.6% and 74.9%, respectively. Misidentification of local anatomy accounted for 76.2% of BDI . Final consensus was reached on: (1) Effective retraction of the gallbladder, (2) Always obtaining critical view of safety, and (3) Avoiding excessive use of electrocautery/clipping as vital procedures; and (4) Calot's triangle area and (5) Critical view of safety as important landmarks. For (6) Impacted gallstone and (7) Severe fibrosis/scarring in Calot's triangle, bail‐out procedures may be indicated. A consensus was reached among expert surgeons on relevant landmarks and intraoperative findings and appropriate surgical techniques to avoid BDI .

Abstract BACKGROUND The safety of Pipeline TM Embolization Device (PED; Medtronic Inc, Dublin, Ireland) in posterior circulation aneurysms is still controversial. OBJECTIVE To study complications associated with the treatment of posterior circulation aneurysms by conducting a subgroup analysis from the International Retrospective Study of PED registry. METHODS Data from 91 consecutive patients with 95 posterior circulation aneurysms at 17 centers between July 2008 to February 2013 were analyzed. The primary endpoint was defined as any complication leading to neurological morbidity or death. The outcome predictors were calculated using Kaplan–Meier and Cox regression methods. RESULTS The mean aneurysm size was 13.8 mm. Aneurysm types were saccular (36.8%), fusiform (29.5%), dissecting (28.4%), and others (5.3%). The median follow-up was 21.1 mo. Twelve (13.2%) patients encountered a primary endpoint event. In multivariate analysis for the primary endpoint, use of ≥3 PEDs and fusiform shape compared with other shapes had hazard ratios (HRs) of 7.77 (95% confidence interval [CI], 2.48-25.86; P = .0007) and 3.48 (95% CI, 1.06-13.39; P = .0488), respectively. The multivariate HR of aneurysm size for neurological morbidity after PED implantation was 1.11 (95% CI, 1.04-1.18; P = .0015), and HRs of ruptured aneurysm and age for neurological mortality were 8.1 (95% CI, 1.31-41.26; P = .0197) and 1.07 (95% CI, 1.02-1.15; P = .0262), respectively. Basilar artery aneurysm had an HR of 3.54 (95% CI, 1.12-14.18, P = .0529) in the univariate analysis for major outcomes. CONCLUSION PED implantation may be considered for the treatment of posterior circulation aneurysms, especially of saccular or dissecting type. Our major complications appear to be comparable to those reported previously after clipping and coiling in the literature. Neurointerventionists should consider the shape, size, rupture, and location of complex posterior circulation aneurysms as well as age and PED number before the PED placement.

ABSTRACT Microbiota-modulating strategies, including probiotic administration, have been tested for the treatment of chronic gastrointestinal diseases despite limited information regarding their mechanisms of action. We previously demonstrated that patients with active celiac disease have decreased duodenal expression of elafin, a human serine protease inhibitor, and supplementation of elafin by a recombinant Lactococcus lactis strain prevents gliadin-induced immunopathology in the NOD/DQ8 mouse model of gluten sensitivity. The commensal probiotic strain Bifidobacterium longum NCC2705 produces a serine protease inhibitor (Srp) that exhibits immune-modulating properties. Here, we demonstrate that B. longum NCC2705, but not a srp knockout mutant, attenuates gliadin-induced immunopathology and impacts intestinal microbial composition in NOD/DQ8 mice. Our results highlight the beneficial effects of a serine protease inhibitor produced by commensal B. longum strains. IMPORTANCE Probiotic therapies have been widely used to treat gastrointestinal disorders with variable success and poor mechanistic insight. Delivery of specific anti-inflammatory molecules has been limited to the use of genetically modified organisms, which has raised some public and regulatory concerns. By examining a specific microbial product naturally expressed by a commensal bacterial strain, we provide insight into a mechanistic basis for the use of B. longum NCC2705 to help treat gluten-related disorders.

We report a 9-year-old Chinese girl with congenital thrombotic thrombocytopenic purpura found to be a compound heterozygote for 2 pathogenic variants in the ADAMTS13 gene, including a novel variation. The girl suffered from recurrent, life-threatening episodes of thrombocytopenia and hemolysis, and laboratory testing showed ADAMST13 enzyme activity of <5%. Sequencing of the ADAMTS13 gene revealed a previously reported missense variant, c.1787C>T (p.Ala596Val), and a novel duplication defined as c.1007_1025dup19 (p.Asp343Leufs*53); the duplication is predicted to result in a premature stop codon and protein truncation. We propose that this novel variant is partly responsible for the patient’s early-onset and severe phenotype.

Gallbladder cancer is a rare malignancy in most countries. The racial and sociodemographic factors associated with its incidence and survival are poorly defined. We aimed to investigate population-based gallbladder cancer incidence and survival trends on the basis of clinical characteristics and sociodemographic factors in the USA. Gallbladder cancer incidence and survival data from 2001 to 2012 were obtained from 18 registries of the Surveillance, Epidemiology, and End Results database. Incidence rates and Joinpoint trends were calculated by demographic subgroup. Survival trends were assessed using Cox proportional hazard models. A total of 7769 patients were identified. The overall gallbladder cancer incidence rates did not significantly change during the 2001–2012 period. Incidence rates were three times higher in Hispanics and 1.6 times higher in Blacks compared with Whites. Over the time period, incidence rates significantly increased among Blacks and decreased among Hispanics. Male sex [hazard ratio (HR): 1.10, 95% confidence interval (CI): 1.03–1.17], older age (HR: 1.73, 95% CI: 1.53–1.96), and single and divorced statuses (HR: 1.19, 95% CI: 1.09–1.30 and 1.12, 95% CI: 1.01–1.24) were independently associated with shorter overall survival, whereas higher education (HR: 0.89, 95% CI: 0.82–0.97) and higher income (HR: 0.89, 95% CI: 0.82–0.96) were associated with longer survival. Furthermore, overall survival has improved in all races/ethnicities except for Hispanics and Blacks. The overall incidence rates for gallbladder cancer were stable during 2001–2012. Hispanics have the highest incidence rates, but the incidence rates in Blacks are on the rise.