Coexistence of Chiari 2 malformation and moyamoya syndrome in a 17-year-old girl.

A 17-year-old female with Chiari 2 malformation developed cerebral infarction with angiographically typical bilateral moyamoya vessels manifesting as sudden onset of moderate left hemiparesis. Magnetic resonance imaging revealed multiple infarcts in the right frontal lobe, agenesis of the corpus callosum, upward herniation of the dorsal cerebellum, tectal beak of the midbrain, and downward herniation of the cerebellar vermis. Cerebral angiography demonstrated occlusion of the bilateral internal carotid arteries and basal moyamoya vessels. Single photon emission computed tomography showed significantly reduced regional cerebral blood flow in the right frontoparietal cortex. The cerebral vascular reactivity to acetazolamide was diminished in both cerebral hemispheres. She underwent superficial temporal artery-middle cerebral artery anastomosis combined with encephalo-myo-synangiosis on the right, and on the left 6 months later. Cerebral angiography performed 4 months after the second operation showed good patency of the bypasses and substantial collateral vessels in both cerebral hemispheres. This association may have happened by chance, and a common etiology is uncertain, but a currently undetermined genomic component might have contributed to the disease progression

Pharmacogenetics of warfarin in a paediatric population: time in therapeutic range, initial and stable dosing and adverse effects

Warfarin is used in paediatric populations, but dosing algorithms incorporating pharmacogenetic data have not been developed for children. Previous studies have produced estimates of the effect of polymorphisms in Cytochrome P450 2C9 (CYP2C9) and vitamin K epoxide reductase complex subunit 1 (VKORC1) on stable warfarin dosing, but data on time in therapeutic range, initial dosing and adverse effects are limited. Participants (n=97) were recruited, and routine clinical data and salivary DNA samples were collected from all participants and analysed for CYP2C9*2, *3 and VKORC1-1639 polymorphisms.VKORC1 -1639 was associated with a greater proportion of the first 6 months’ treatment time spent within the target International Normalised Ratio (INR) range, accounting for an additional 9.5% of the variance in the proportion of time. CYP2C9*2 was associated with a greater likelihood of INR values exceeding the target range during the initiation of treatment (odds ratio (OR; per additional copy) 4.18, 95% confidence interval (CI) 1.42, 12.34). CYP2C9*2 and VKORC1-1639 were associated with a lower dose requirement, and accounted for almost 12% of the variance in stable dose. VKORC1-1639 was associated with an increased likelihood of mild bleeding complications (OR (heterozygotes vs homozygotes) 4.53, 95% CI 1.59, 12.93). These data show novel associations between VKORC1-1639 and CYP2C9*2 and INR values in children taking warfarin, as well as replicating previous findings with regard to stable dose requirements. The development of pharmacogenomic dosing algorithms for children using warfarin has the potential to improve clinical care in this population

Catheter-Related Arterial Thrombosis in Neonates and Children: A Systematic Review.

Catheter-related arterial thrombosis (CAT) is increasingly recognized in children. Available data are scarce and based on expert opinions. This systematic review aimed to identify knowledge on paediatric CAT. Among 3,484 publications, 22 met inclusion criteria. Fourteen reported on CAT due to umbilical arterial catheter (UAC), two to extremity indwelling catheter (EIC), one to both and five to cardiac catheter (CC). The overall cumulative incidence of CAT was 21% (95% confidence interval [CI], 13-31) with a relative incidence of 20% (95% CI, 10-33) for UAC and 11% (95% CI, 3-21) for CC-related CAT. The incidence of EIC-related CAT ranged from 3.4 to 63%. Clinical presentation of CAT included symptoms of acute limb ischaemia (79%, 95% CI, 54-97), arterial hypertension (55%, 95% CI, 23-86) and congestive heart failure (28%, 95% CI, 7-53). Underlying conditions of UAC-related CAT included prematurity (70%, 95% CI, 31-98), respiratory distress syndrome (56%, 95% CI, 46-65), asphyxia (41%, 95% CI, 15-69), infection (32%, 95% CI, 13-55), persistent ductus arteriosus (28%, 95% CI, 13-45), meconium aspiration (16%, 95% CI, 8-25) and congenital heart disease (9%, 95% CI, 2-19). Congenital heart disease was the likely condition in EIC- and CC-related CAT. Antithrombotic treatment included thrombolysis (71%, 95% CI, 47-91), heparin (70%, 95% CI, 41-94) and thrombectomy (46%, 95% CI, 10-95) alone or in combination. Complete resolution rate of CAT was 82% (95% CI, 65-96). Long-term complications included arterial hypertension (26%, 95% CI, 0-66) and limb amputation (12%, 95% CI, 1-31). The overall all-cause mortality rate was 7% (95% CI, 2-14). In conclusion, CAT occurs at an increased incidence in neonates and children and is potentially associated with poor outcome. However, limited data are available on paediatric CAT. This systematic review identifies the rationale for further studies on CAT in paediatric patients

Impact of inherited thrombophilia on venous thromboembolism in children: a systematic review and meta-analysis of observational studies

BACKGROUND: The aim of the present study was to estimate the impact of inherited thrombophilia (IT) on the risk of venous thromboembolism (VTE) onset and recurrence in children by a meta-analysis of published observational studies. METHODS AND RESULTS: A systematic search of electronic databases (Medline, EMBASE, OVID, Web of Science, The Cochrane Library) for studies published from 1970 to 2007 was conducted using key words in combination as both MeSH terms and text words. Citations were independently screened by 2 authors, and those meeting the inclusion criteria defined a priori were retained. Data on year of publication, study design, country of origin, number of patients/controls, ethnicity, VTE type, and frequency of recurrence were abstracted. Heterogeneity across studies was evaluated, and summary odds ratios and 95% CIs were calculated with both fixed-effects and random-effects models. Thirty-five of 50 studies met inclusion criteria. No significant heterogeneity was discerned across studies. Although >70% of patients had at least 1 clinical risk factor for VTE, a statistically significant association with VTE onset was demonstrated for each IT trait evaluated (and for combined IT traits), with summary odds ratios ranging from 2.63 (95% CI, 1.61 to 4.29) for the factor II variant to 9.44 (95% CI, 3.34 to 26.66) for antithrombin deficiency. Furthermore, a significant association with recurrent VTE was found for all IT traits except the factor V variant and elevated lipoprotein(a). CONCLUSIONS: The present meta-analysis indicates that detection of IT is clinically meaningful in children with, or at risk for, VTE and underscores the importance of pediatric thrombophilia screening programs

Belgische en Nederlandse stadsgeschiedenis in historische tijdschriften (2020)

Cities, Migration and Global Interdependenc