Mortality and Causes of Death From Sickle Cell Disease in The Netherlands, 1985-2017.

In the Netherlands, between 1985 and 2007 secular changes in the health care of patients with sickle cell disease (SCD) have taken place, such as penicillin prophylaxis, vaccination programs and stroke prevention. We investigated the number and causes of death in a cohort of 298 SCD patients, established in 2007, before introduction of neonatal screening, to determine preventable deaths. All patients were diagnosed with SCD before the age of 18 (median age at diagnosis 5.1 y). Their vital status was determined up to January 2017. After a total follow-up period of 4565 patient years and a median time of follow-up of 15 years for all patients, 230 patients (77%) were still alive, 45 patients (15%) were lost to follow-up and a total of 23 patients (8%) had died. Estimated survival to 18 years was 92% with a global mortality rate of 0.48 deaths/100 patient years. Leading causes of death were infection (35%) followed by neurologic complications (22%) and death in the course of a painful episode (13%). Nine of the 20 known causes of death were preventable. These results strongly suggest the benefit of comprehensive care measures for patients with SCD in the Netherlands to further prevent morbidity and mortality.

New reference charts for testicular volume in Dutch children and adolescents allow the calculation of standard deviation scores.

AIM: Accurate calculations of testicular volume standard deviation (SD) scores are not currently available. We constructed LMS-smoothed age-reference charts for testicular volume in healthy boys. METHODS: The LMS method was used to calculate reference data, based on testicular volumes from ultrasonography and Prader orchidometer of 769 healthy Dutch boys aged 6 months to 19 years. We also explored the association between testicular growth and pubic hair development, and data were compared to orchidometric testicular volumes from the 1997 Dutch nationwide growth study. RESULTS: The LMS-smoothed reference charts showed that no revision of the definition of normal onset of male puberty - from nine to 14 years of age - was warranted. In healthy boys, the pubic hair stage SD scores corresponded with testicular volume SD scores (r = 0.394). However, testes were relatively small for pubic hair stage in Klinefelter's syndrome and relatively large in immunoglobulin superfamily member 1 deficiency syndrome. CONCLUSION: The age-corrected SD scores for testicular volume will aid in the diagnosis and follow-up of abnormalities in the timing and progression of male puberty and in research evaluations. The SD scores can be compared with pubic hair SD scores to identify discrepancies between cell functions that result in relative microorchidism or macroorchidism.

The independent functioning of the orchidopexied congenital undescended testis as assessed by positron emission tomography/computed tomography.

Fertility after orchidopexied undescended testes (UDT) is impaired. Although fertility parameters are known to be more favorable in unilateral cases than in bilateral cases, the exact contribution of the unilateral orchidopexied UDT to fertility is unknown. We used testicular (18)F-fluoro-2-deoxyglucose ((18)F-FDG)-uptake assessed by positron emission tomography/computed tomography (PET/CT) to investigate the function of the orchidopexied unilateral congenital UDT, compared to its normally descended counterpart. We hypothesize that the contribution of the orchidopexied unilateral congenital UDT to fertility in adulthood is low. Eleven men who underwent orchidopexy for congenital UDT at the age of 1.9 ± 1.4 (range, 4.5 months -4.0) years were seen in follow-up at the age of 24.1 ± 2.3 (20.6-28.0) years. All underwent physical examination, testicular ultrasonography and PET/CT. Testicular (18)F-FDG-uptake was expressed as the peak Standardized Uptake Value (SUVpeak). The mean SUVpeak of the orchidopexied UDT was 2.74 ± 0.48 (2.13-3.47), which was significantly lower than its counterpart (P = 0.021). Besides, there was no correlation between the testicular volume and the SUVpeak. The orchidopexied congenital UDT has been shown to be less metabolically active than its contralateral counterpart. Nevertheless, we suggest that the operated testes function to some degree.

Natural course of undescended testes after inguinoscrotal surgery.

PURPOSE: The purpose of the study is to study the natural course of undescended testes after inguinoscrotal surgery. METHODS: From 2003-2010, 24 boys were observed with 26 undescended testes after inguinoscrotal surgery; 12 had previously undergone inguinal hernia repair and 12 orchidopexy. Spontaneous descent was awaited and (re-)orchidopexy would only be performed in case of non-descent at puberty. The boys were assessed annually for testis position and for testis volume as measured by ultrasound. RESULTS: At the end of the study period, 19 testes had reached scrotal position; of these, 13 (68%) had descended spontaneously and 6 (32%) had been (re-)orchidopexied. No difference was found in the rate of spontaneous descent after previous orchidopexy or inguinal hernia repair (P=0.419). CONCLUSION: Spontaneous descent of undescended testes after inguinoscrotal surgery occurs regularly. In this study, it was observed in two out of every three cases.

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.

Mortality and causes of death in children with sickle cell disease in the Netherlands, before the introduction of neonatal screening.

This study analyzed the mortality and causes of death in sickle cell disease patients in the Netherlands, to provide a baseline for monitoring the effect of the recently introduced neonatal screening programme and to indicate areas of improvement in the care for these patients. All children (<18 years) diagnosed with sickle cell disease in a tertiary hospital from 1985 to 2007 were included. Vital status was determined up to March 2008. A total of 298 children were included: 189 (63%) patients had HbSS, 17 (6%) HbSß(0) thalassaemia, 72 (24%) HbSC and 20 (7%) HbSß(+) thalassaemia. Twelve patients (4%) died during a total follow-up of 3896 patient years. All known deaths were sickle cell disease-related. Meningitis/sepsis (n=4; 33%), stroke (n=3; 25%) and death during a visit to the country of origin (n=3; 25%) were the most common causes of death. The overall mortality rate was 0·27 deaths/100 patient years [95% confidence interval (CI): 0·15-0·43]. The estimated survival at the age of 18 years was 97·3% (95% CI: 95-99%). This report confirms that the burden of mortality in sickle cell disease is increasingly shifting to adults. It is recommended that compliance to antibiotic prophylaxis, thorough counselling and support for patients travelling abroad and specialized peri-operative care should receive continuous attention.