Real-life Performance of Multiplex Celiac Antibody Test in the Diagnosis of Pediatric Celiac Disease.

OBJECTIVE: Tissue-transglutaminase antibodies (TGA) may be used to diagnose celiac disease (CD) without biopsy in selected cases. We aimed to investigate real-life performance of a CD serology automated analyzer (Bioplex2200), and to explore the correlation between TGA levels and intestinal biopsies in children. METHODS: A retrospective review was performed in 2 pediatric gastroenterological centers, between November 1, 2018 and April 1, 2020 and included patients with both TGA serology testing and duodenal biopsies. Retrieved data included patients' demographics, medical background, TGA levels, and biopsy results. RESULTS: Overall, 538 children were evaluated, 256 with positive TGA (68.4% girls, median age 6.4 years), and 282 with negative TGA (53.9% girls, median age 13.4 years). Among patients with positive TGA, intestinal biopsies confirmed CD in 219 (85.5%). Overall, positive serology with normal histology was found in 14.5% of the cohort, with 52%; 21.6%; 21.1%; and 4.2% in TGA ranges of 1 to 3 times upper limit of normal (ULN); 3 to 5 ULN; 5 to 10 ULN; and above 10 times ULN, respectively, P < 0.001. Area under the receiver-operating characteristic curve (AUC) was 0.963 (95% CI 0.947-0.980). Among patients with positive TGA, 216 (84.4%) had positive anti-endomysial antibodies. In this sub-group, the overall diagnostic performance was inferior, with AUC of 0.737 (95% CI 0.834-0.839). CONCLUSIONS: The Multiplex TGA assay had a very high diagnostic accuracy in real-life. Among patients with positive TGA, adding EMA did not improve the diagnostic performance of the test. False-positive rates differed between different ranges of TGA and were low with TGA above 10 times ULN.

Early effectiveness of BNT162b2 Covid-19 vaccine in preventing SARS-CoV-2 infection in healthcare personnel in six Israeli hospitals (CoVEHPI).

BACKGROUND: Methodologically rigorous studies on Covid-19 vaccine effectiveness (VE) in preventing SARS-CoV-2 infection are critically needed to inform national and global policy on Covid-19 vaccine use. In Israel, healthcare personnel (HCP) were initially prioritized for Covid-19 vaccination, creating an ideal setting to evaluate early real-world VE in a closely monitored population. METHODS: We conducted a prospective study among HCP in 6 hospitals to estimate the effectiveness of the BNT162b2 mRNA Covid-19 vaccine in preventing SARS-CoV-2 infection. Participants filled out weekly symptom questionnaires, provided weekly nasal specimens, and three serology samples - at enrollment, 30 days and 90 days. We estimated VE against PCR-confirmed SARS-CoV-2 infection using the Cox Proportional Hazards model and against a combined PCR/serology endpoint using Fisher's exact test. RESULTS: Of the 1567 HCP enrolled between December 27, 2020 and February 15, 2021, 1250 previously uninfected participants were included in the primary analysis; 998 (79.8%) were vaccinated with their first dose prior to or at enrollment, all with Pfizer BNT162b2 mRNA vaccine. There were four PCR-positive events among vaccinated participants, and nine among unvaccinated participants. Adjusted two-dose VE against any PCR-confirmed infection was 94.5% (95% CI: 82.6%-98.2%); adjusted two-dose VE against a combined endpoint of PCR and seroconversion for a 60-day follow-up period was 94.5% (95% CI: 63.0%-99.0%). Five PCR-positive samples from study participants were sequenced; all were alpha variant. CONCLUSIONS: Our prospective VE study of HCP in Israel with rigorous weekly surveillance found very high VE for two doses of Pfizer BNT162b2 mRNA vaccine against SARS-CoV-2 infection in recently vaccinated HCP during a period of predominant alpha variant circulation. FUNDING: Clalit Health Services.

Anti-tissue transglutaminase titers are associated with endoscopic findings and severity of mucosal damage in children with celiac disease.

We aimed to assess the correlation between clinical findings, serology, endoscopic findings, and histology in children diagnosed with celiac disease. Medical records of children diagnosed with celiac disease (2010-2017) at the Schneider Children's Hospital were reviewed retrospectively. Correlation between serologic measures anti-tissue transglutaminase (anti-tTG)/anti-endomysial antibodies (EMA) and other variables including mucosal damage, endoscopic findings (scalloping of duodenal folds), and clinical findings (abdominal pain, diarrhea, and anemia) was assessed. Out of 686 patients, 432 patients fulfilled the inclusion criteria (females 262, 61%; median age 6.0; interquartile range 4.0-9.0 years). Distribution of histopathology findings was Marsh IIIa 4%, Marsh IIIb 25%, and Marsh IIIc 71% with 313 (73%) patients having anti-tTG titer of ≥ 10 times the upper normal limit. Anti-tTG titer (but not EMA) positively correlated with Marsh grades, scalloping of duodenal folds and anemia. Anti-tTG ≥ 10 times the upper normal limit was associated with Marsh IIIc changes with an adjusted odds ratio of 4.5 (95% confidence interval, 1.7-12.1). Diarrhea and abdominal pain were not associated with serologic, endoscopic, or histologic markers of disease severity.Conclusion: Anti-tTG titers correlated with macroscopic and microscopic mucosal damage, with anemia but not with diarrhea or abdominal pain in children with celiac disease. What is Known: • Tissue transglutaminase antibody titers were shown to correlate with the degree of mucosal damage in patients with celiac disease. • There is a limited evidence regarding the association of celiac serologies with endoscopic and clinical measures. What is New: • Higher titers of tissue transglutaminase but not anti-endomysial antibodies are associated with more severe histologic and endoscopic damage and with the presence of anemia. • Symptoms do not correlate with the severity of mucosal damage such as scalloping of duodenal folds and histopathology changes according to Marsh classification or with serologic markers.

Increased serum C-reactive protein levels are associated with shorter survival and development of second cancers in chronic lymphocytic leukemia.

BACKGROUND: Chronic lymphocytic leukemia (CLL) is characterized by a heterogeneous clinical course, ranging from stable to more aggressive disease. Herein, we determined the prognostic significance of serum C-reactive protein (CRP) levels in patients with CLL Methods: A retrospective cohort study reviewing the records of 107 consecutive treatment naïve patients with CLL and a control group comprised of apparently healthy individuals attending for periodic health examinations. RESULTS: The median CRP level of patients with CLL was 0.19 mg/dL (0-2.9). In univariate analysis, high-CRP levels (≥0.4 mg/dL) were significantly associated with an increased risk of mortality (HR = 3.97, 95%CI 1.64-9.62, p = .002) and development of second solid cancers (HR = 4.54, 95%CI 1.57-13.11, p = .005), compared to low-CRP values (<0.4 mg/dL). In multivariate analysis, high-CRP retained statistical significance for all-cause mortality (HR = 2.81, 95%CI 1.04-7.57, p = .04) and the development of second solid malignancies (HR = 4.54, 95%CI 1.57-13.11, p = .005). Moreover, when compared to an apparently healthy population, CLL patients with high CRP levels had more than an eightfold risk of cancer. CONCLUSIONS: Elevated baseline CRP levels are associated with shorter survival and development of second cancers in patients with CLL. We suggest that increased CRP in patients with CLL may justify a more rigorous search for second cancers. KEY MESSAGES Elevated CRP levels are associated with a shorter overall survival in CLL. Elevated CRP levels are associated with an increased risk of second cancers in CLL. Increased CRP in patients with CLL may justify a more rigorous search for second cancers.

Celiac disease screening assays for children younger than 3 years of age: the performance of three serological tests.

BACKGROUND AND AIMS: The optimum serological test for celiac disease (CD) in young children is not known. The objective of our study was to compare the performance of three serological tests (IgA + IgG DGP, IgA TTG, and IgA + IgG EMA) for children younger than 3 years of age. METHODS: We identified all subjects younger than 3 years of age (n = 6,074) that were tested for CD serology and included those with biopsy data. Patients were classified as group 1 (n = 47): patients with confirmed CD or group 2 (n = 12): patients with normal biopsy findings. RESULTS: There was statistically significant difference between group 1 and group 2 with regard to number of patients with positive IgA TTG (97.87% vs. 50%, P < 0.001), IgA + IgG DGP (100% vs. 77.78%, P = 0.007), and IgA + IgG EMA (95.65% vs. 9.09%, P < 0.001). There was a significantly positive correlation between Marsh-Oberhuber score on the small duodenal biopsies and all tests. Analysis of sensitivity and specificity showed that manufacturer's levels had high sensitivity for all tests (IgA TTG 97%, IgA + IgG DGP 100%, IgA + IgG EMA 96%), however specificity was low for IgA + IgG DGP (44%) and IgA TTG (50%) but not for IgA + IgG EMA (91%). CONCLUSIONS: For children younger than 3 years of age, IgA + IgG EMA is highly sensitive and specific. Use of IgA + IgG DGP or IgA TTG as a single serological marker is insufficient for definite diagnosis of CD in this age group. Based on our results, it might be reasonable to postpone the biopsy for asymptomatic children with negative EMA.

Use of the six-minute walk test poststroke: is there a practice effect?

OBJECTIVES: To determine whether a practice effect occurs across 2 trials of the six-minute walk test (6MWT) among community-dwelling people within 1 year poststroke and to identify characteristics distinguishing people who show a practice effect from those who do not. DESIGN: Secondary analysis of scores on 2 trials of the 6MWT administered approximately 30 minutes apart at baseline in a randomized controlled trial. SETTING: General community. PARTICIPANTS: People (N=91) living in the community with a residual walking deficit within the first year of a first or recurrent stroke. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURE: Distance walked on the 6MWT. RESULTS: Mean 6MWT scores +/- SD for trials 1 and 2 were 196+/-119m and 197+/-126m, respectively (n=83). The mean difference in 6MWT performance across trials was 0+/-35m (95% confidence interval [CI], -7 to 8m). The Pearson correlation coefficient between 6MWT distances was .96 (P<.001), and the intraclass correlation coefficient was .98 (95% CI, .97-.99). The Bland-Altman plot showed no clear pattern. Participants whose improvement was equal to or greater than the minimal detectable change of 29m between trials (14%) did not significantly differ from those in the rest of the study sample; however, they tended to be younger (P=.05) and more likely to have a mild or moderate gait deficit (P=.06). CONCLUSIONS: Findings do not support a practice effect across 2 trials of the 6MWT in individuals within 1 year poststroke. Thus, a practice walk does not appear necessary. Further research is recommended to evaluate the influence of young age, acute stroke, and mild-to-moderate gait deficit on practice effects.

Harmonization of the Bayer ADVIA Centaur and Abbott AxSYM automated B-type natriuretic peptide assay in patients on hemodialysis.

There are two fully automated high-throughput clinical instruments for brain natriuretic peptide (BNP) assays, the Bayer ADVIA Centaur assay, and the Abbott AxSYM assay. Although both recommend a cut-off value of 100 pg/mL, we are unaware of previous studies that have compared the unadjusted results of the two methods, required for proper evaluation of patients undergoing this test on different platforms. From 43 hemodialysis patients, 80 paired samples were collected by venipuncture into plastic evacuated tubes containing EDTA. The Bayer assay yielded lower values than the Abbott assay, with linear regression of 0.53 x Abbott assay (95% confidence interval, 0.50-0.56) being forced through 0, demonstrating an r(2)-value of 0.954. Regression for the Abbott assay was 1.79 x Bayer assay (95% CI, 1.69-1.89). The cut-off values for abnormal BNP results analyzed on the Abbott system are not identical to those on the Bayer system, and this needs to be taken into account when comparing studies on the clinical utility of these systems.

Outcome of IgM- and IgG-seropositive cases of varicella zoster in pregnancy.

OBJECTIVE: To study the outcome of IgG- and IgM-seropositive cases of varicella zoster virus (VZV) in pregnancy. STUDY DESIGN: The VZV immune status of 120 pregnant women who had been exposed to VZV and did not recall a history of VZV infection was determined, and 109 were VZV immune. Eleven women were both IgG and IgM seropositive, and the outcomes of their pregnancies were studied. RESULTS: Nine of the 11 VZV IgM-, IgG-seropositive pregnant women were asymptomatic, without fetal damage. CONCLUSION: The majority of the women were asymptomatic, but no statement about the relative risk of being affected by the virus can be made.