AKT Hyperphosphorylation and T Cell Exhaustion in Down Syndrome.

Down syndrome (DS) is associated with increased susceptibility to infections, auto-immunity, immunodeficiency and haematological malignancies. The exact underlying immunological pathophysiology is still unclear. The immunophenotype and clinical characteristics of DS resemble those of Activated PI3K Delta Syndrome (APDS), in which the PI3K/AKT/mTOR pathway is overactivated. We hypothesized that T cell exhaustion and the hyperactivation of the AKT signalling pathway is also present in immune cells of children with DS. In this observational non-interventional cohort study we collected blood samples of children with DS (n=22) and healthy age-matched controls (n=21) for flowcytometric immunophenotyping, phospho-flow AKT analysis and exhaustion analysis of T cells. The median age was 5 years (range 1-12y). Total T and NK cells were similar for both groups, but absolute values and transitional B cells, naive memory B cells and naive CD4+ and CD8+ T cells were lower in DS. pAKT and AKT were increased for CD3+ and CD4+ T cells and CD20+ B cells in children with DS. Total AKT was also increased in CD8+ T cells. Children with DS showed increased expression of inhibitory markers Programmed cell dealth-1 (PD-1), CD244 and CD160 on CD8+ T cells and increased PD-1 and CD244+ expression on CD4+ T cells, suggesting T cell exhaustion. Children with DS show increased pAKT and AKT and increased T cell exhaustion, which might contribute to their increased susceptibility to infections, auto immunity and haematological malignancies.

Serum and Prostatic Tissue Concentrations of Cefazolin, Ciprofloxacin and Fosfomycin after Prophylactic Use for Transurethral Resection of the Prostate.

The optimal drug of choice, its time of administration and duration of antibiotic prophylaxis in patient undergoing a TURP procedure are still matters of debate. In this study, we evaluated the concentrations of cefazolin, ciprofloxacin and fosfomycin in the human prostate in a cohort of men undergoing TURP. We compared prostate tissue concentrations to the serum concentrations and MICs of common uropathogens, to determine the appropriateness of the current presurgical prophylactic antibiotics and to gain supportive data about the suitability of fosfomycin for antibiotic prophylaxis in men undergoing urological procedures of the prostate. After a single intravenous dose of cefazoline or an oral dose of ciprofloxacin prior to TURP, concentrations in serum and prostate tissue of well above the MIC (EUCAST breakpoint) of common uropathogens (Enterobacterales) were reached, and both antibiotics seem potentially effective in preventing postsurgical infections. A single dose of oral and intravenous administration of fosfomycin both led to serum concentrations above the MIC for uncomplicated urinary tract infections (8 µg/mL). The MIC for other infections (32 µg/mL) was only reached after a single dose of intravenous fosfomycin. We were unable to detect fosfomycin concentrations in prostate tissue.

Neisseria Mucosa: A New Urinary Tract Pathogen?

The most common complication of vesicoureteral reflux is urinary tract infection. We report a case of a urinary tract infection in a child with severe vesicoureteral reflux, caused by Neisseria mucosa, usually considered to be a commensal inhabitant of the oro- or nasopharynx.

Long-term testicular volume after orchiopexy at diagnosis of acquired undescended testis.

PURPOSE: We studied long-term outcomes of orchiopexy at diagnosis of acquired undescended testes using ultrasound to determine testicular volume. MATERIALS AND METHODS: Patients who had undergone orchiopexy for acquired undescended testis at diagnosis were recruited to assess testicular volume. Testis volume was measured by ultrasound and compared with recently developed normative values for testicular size. For young adults (older than 18 years) volumes were grouped and compared to normative values reported in the literature. In all unilateral cases testicular volume was compared with its counterpart. RESULTS: A total of 155 patients 5.1 to 26.6 years old (181 acquired undescended testes) were included in the study. Mean ± SD followup was 6.6 ± 3.8 years (range 1.4 to 15.5). For all patients 18 years old or younger (125 patients, 143 testes) operated testis volume was 0.1 to 12.7 ml (mean ± SD 2.5 ± 2.9), which was significantly smaller than the normative values (50th percentile) for the same age (p <0.001). Mean ± SD testis volume in young adults (38 testes) was 8.1 ± 3.7 ml, compared to a mean volume of 13.4 ml reported in the literature (p <0.001). In unilateral cases the mean volume of the testes fixed by orchiopexy differed significantly from their counterparts (3.4 ± 3.3 ml vs 4.6 ± 4.6 ml, p <0.001). CONCLUSIONS: The long-term volumes at diagnosis of acquired undescended testes after orchiopexy were significantly less than the normative values at all ages. In unilateral cases the volumes were also significantly less compared to the contralateral testes.

Orchidopexy in late childhood often associated with previously normal testicular position.

INTRODUCTION: The aim of this study was to determine retrospectively, the prevalence of acquired undescended testis (UDT) in boys who underwent late orchidopexies, that is, performed after the age of 2 years. METHODS: We included all patients who were 2 years or older when they underwent orchidopexy (ORP) for UDT at the Juliana Children's Hospital during 1996 to 2009. Previous testis position from birth until the date of ORP was obtained from youth health care records. RESULTS: We identified 660 boys who underwent ORP after the age of 2 years for undescended testis. For 421 of these 660 boys, the previous testicular position could be retrieved from the health records. In 143 of these 421 boys (34%), the operated testis had never been scrotal (congenital UDT), whereas in the other 278 boys (66%), a previous scrotal position had been documented twice or more (acquired UDT). CONCLUSION: Our results show that two-thirds of the boys that underwent ORP after the age of 2 had previously normal descended testes. This finding may offer an additional explanation for the discrepancy between the incidence of congenital UDT and the high rate of ORP in mid and late childhood.