Early urodynamic findings after complete primary repair of exstrophy.

INTRODUCTION: Detrusor contraction in bladder exstrophy (BE) patients following reconstruction is poorly understood as there are few published studies assessing urodynamic findings in this population. Understanding the ability of the detrusor to contract in BE patients early after closure may be able to inform the longer-term management and potential for the development of future continence in this population. OBJECTIVE: We sought to evaluate early detrusor contraction using urodynamic studies (UDS) in children who had previously undergone complete primary repair of bladder exstrophy (CPRE). We hypothesized that a majority of children with BE would display the presence of normal detrusor contractile function after CPRE. STUDY DESIGN: A retrospective review of our prospectively collected database was performed for all patients with a diagnosis of classic BE who underwent primary CPRE between 2013 and 2017. From this cohort we identified patients with at least one post-operative UDS at 3 years of age or older who had undergone an initial CPRE. Our primary outcome was the presence of a detrusor contraction demonstrated on UDS. RESULTS: There were 50 children (31 male, 19 female) with CBE who underwent CPRE between 2013 and 2017.There were 26 (13 male, 13 female) who met inclusion criteria. Median age was 3.5 (IQR: 3.2-4.7) years at the time of UDS Sixteen of the 26 (61.5%) generated a sustained detrusor contraction generating a void, with a median peak voiding pressure of 38 cm H20 (IQR: 28-51). The median bladder capacity reached was 48 ml, which represented a median of 30% of expected bladder capacity. The median post void residual (PVR) for the entire cohort was 26 ml (IQR: 9, 47) or 51% (IQR: 20%-98%) of their actual bladder capacity, while the median PVR for those children with a sustained detrusor contraction was 18 ml (IQR: 5, 46) or 33% (IQR: 27%, 98%) of their actual bladder capacity. Intraoperative bladder width and bladder dome to bladder neck length did not correlate with the presence of voiding via a detrusor contraction (p = 0.64). DISCUSSION: We present the first study assessing early UDS finding of detrusor contraction in BE patients after CPRE. In our cohort, 61.5% of patients were able to generate a sustained detrusor contraction on UDS which is a higher percentage than has been reported in previous series. A difference in initial surgical management may account for these findings. CONCLUSION: At short term follow up, the majority of children in our cohort were able to produce sustained detrusor contractions sufficient to generate a void per urethra with a modest post void residual volume. Long-term follow-up and repeated UDS will be needed to track detrusor contractility rates, bladder capacities, compliance, post void residuals and ultimately continence rates over time.

Autoimmune markers in lymphoid malignancies.

Chronic immune stimulation such as Helicobacter pylori (hp) infection, Sjögren's syndrome or coeliac disease may initiate non-Hodgkin lymphoma (NHL). The opposite (appearance of autoimmunity) has also been reported. The aim of this study was to describe the pattern of these immune markers in patients with lymphoid malignancies. Sera from 96 patients with NHL (median age 72, range 38-88, F/M 41/55) were analysed with ELISA to determine the frequency of antibodies against guinea pig (gp) and human recombinant (hr) transglutaminase type 2 (Tg2), and hr factor XIII subunit a* (part of the Tg-family), extractable nuclear antigen (ENA), and hp. As hp antibodies decrease in younger age cohorts a sex- and age-matched control group of 768 persons was used. The control population for transglutaminase antibodies consisted of 59 blood donors, (median 42 years, range 19-65) was analysed with a commercial kit. Gp-Tg2-IgG positivity was documented in 72% and hr-Tg2-IgG positivity in 15% (5% positive controls for both; P < 0.001 and ns, respectively). For IgA 3% had gp-Tg2 and 4% hr-Tg2 (5% in controls: ns for both). Anti-FXIII-IgA positivity was found in 22% (5% in controls; P = 0.03). Unspecific anti-ENA-IgG positivity was found in 24% (P < 0.001), while only 2% had specific ENA autoantibodies. Moreover, 36% were positive for anti-hp-IgG, while controls were positive in 54% (P < 0.001). The frequency of unspecific autoantibodies was increased. No differences could be noted in specific autoantibodies (hr-Tg2-IgA). In contrast, fewer than expected were anti-hp-positive. A defective immune response, similar to that in autoimmune diseases, could contribute to the pathogenesis of lymphoid malignancies.

Antibodies against transglutaminases, peptidylarginine deiminase and citrulline in rheumatoid arthritis--new pathways to epitope spreading.

OBJECTIVE: The findings of the involvement of tissue transglutaminase (tTg) in the pathogenesis of coeliac disease (CD) have stimulated progress in the field of auto-immune diseases. Another calcium-dependent cysteine enzyme, peptidylarginine deiminase type 4 (PAD4), seems to be involved in the pathogenesis of rheumatoid arthritis (RA). There are obvious similarities between Tgs and PADs. METHODS: Using enzyme-linked immuno-sorbent assays, we have measured the occurrence of antibodies against guinea pig (gp) and human recombinant (hr) tTg, PAD and citrulline in 59 controls and 184 RA-patients, of whom 71 were treated with methotrexate (mtx). RESULTS: In addition to the expected antibodies against citrulline (62%), sera from the 113 RA-patients without mtx treatment contained significantly increased frequencies of IgG anti-PAD (35%), IgA anti-gp-tTg (34%), IgA anti-hr tTg (20%), IgG anti-gp-tTg (13%) and IgA anti-hr-FXIII (15%) compared to controls. In sera from the mtx-treated RA-patients the expression of antibodies was reduced. In patients not treated with methotrexate there was a statistically significant correlation between, on one hand, IgG anti-PAD and on the other hand, IgG anti-citrulline, IgA anti-gp-tTg, IgA anti-hr-tTg, IgG anti-gp-tTg, IgG anti-hr-tTg, or IgA anti-hr-FXIII. In the mtx-treated group these correlations were less pronounced. CONCLUSION: In addition to the expected antibodies against citrulline, sera from RA-patients contained antibodies against PAD and against Tgs of at least two kinds, indicating that the specificity for anti-tTg in CD is far from complete. Most of the patients displayed more than one antibody, a possible indication of epitope spreading. MTX-treatment reduced the expression of antibodies.