Prenatal diagnosis of mosaic tetrasomy 12p/trisomy 12p by fluorescent in situ hybridization in amniotic fluid cells: A case report of Pallister-Killian syndrome

A prenatally detected case of a rare mosaic tetrasomy 12p/trisomy 12p is reported, presenting as the well‐known accessory isochromosome 12p and a supernumerary single 12p marker in 17/24 and 6/24 clones of cultured amniotic fluid cells, respectively. The chromosomal nature of both marker chromosomes was investigated in cultured amniotic fluid cells by fluorescent in situ hybridization with various probes: the 12‐centromeric probes pa12H8 and D12Z3, a whole chromosome 12 paint, and the chromosome 12p‐specific paint M28. DNA analysis revealed a maternal origin of the extra 12p material. After counselling, the parents requested termination of pregnancy. Inspection and autopsy of the fetus revealed many of the dysmorphisms and internal structural abnormalities of the Pallister–Killian syndrome. Copyrigh

Exploring copy number variants in deceased fetuses and neonates with abnormal vertebral patterns and cervical ribs

Background: Cervical patterning abnormalities are rare in the general population, but one variant, cervical ribs, is particularly common in deceased fetuses and neonates. The discrepancy between the incidence in the general population and early mortality is likely due to indirect selection against cervical ribs. The cause for the co-occurrence of cervical ribs and adverse outcome remains unidentified. Copy number variations resulting in gain or loss of specific genes involved in development and patterning could play a causative role. Methods: Radiographs of 374 deceased fetuses and infants, including terminations of pregnancies, stillbirths and neonatal deaths, were assessed. Copy number profiles of 265 patients were determined using single nucleotide polymorphism array. Results: 274/374 patients (73.3%) had an abnormal vertebral pattern, which was associated with congenital abnormalities. Cervical ribs were present in 188/374 (50.3%) and were more common in stillbirths (69/128 [53.9%]) and terminations of pregnancies (101/188 [53.7%]), compared to live births (18/58, 31.0%). Large (likely) deleterious copy number variants and aneuploidies were prevalent in these patients. None of the rare copy number variants were recurrent or overlapped with candidate genes for vertebral patterning. Conclusions: The large variety of copy number variants in deceased fetuses and neonates with similar abnormalities of the vertebral pattern probably reflects the etiological heterogeneity of vertebral patterning abnormalities. This genetic heterogeneity corresponds with the hypothesis that cervical ribs can be regarded as a sign of disruption of critical, highly interactive stages of embryogenesis. The vertebral pattern can probably provide valuable information regarding fetal and neonatal outcome

A randomised, blinded, trial of clopidogrel versus aspirin in patients at risk of ischaemic events (CAPRIE). CAPRIE Steering Committee

Many clinical trials have evaluated the benefit of long-term use of antiplatelet drugs in reducing the risk of clinical thrombotic events. Aspirin and ticlopidine have been shown to be effective, but both have potentially serious adverse effects. Clopidogrel, a new thienopyridine derivative similar to ticlopidine, is an inhibitor of platelet aggregation induced by adenosine diphosphate. METHODS: CAPRIE was a randomised, blinded, international trial designed to assess the relative efficacy of clopidogrel (75 mg once daily) and aspirin (325 mg once daily) in reducing the risk of a composite outcome cluster of ischaemic stroke, myocardial infarction, or vascular death; their relative safety was also assessed. The population studied comprised subgroups of patients with atherosclerotic vascular disease manifested as either recent ischaemic stroke, recent myocardial infarction, or symptomatic peripheral arterial disease. Patients were followed for 1 to 3 years. FINDINGS: 19,185 patients, with more than 6300 in each of the clinical subgroups, were recruited over 3 years, with a mean follow-up of 1.91 years. There were 1960 first events included in the outcome cluster on which an intention-to-treat analysis showed that patients treated with clopidogrel had an annual 5.32% risk of ischaemic stroke, myocardial infarction, or vascular death compared with 5.83% with aspirin. These rates reflect a statistically significant (p = 0.043) relative-risk reduction of 8.7% in favour of clopidogrel (95% Cl 0.3-16.5). Corresponding on-treatment analysis yielded a relative-risk reduction of 9.4%. There were no major differences in terms of safety. Reported adverse experiences in the clopidogrel and aspirin groups judged to be severe included rash (0.26% vs 0.10%), diarrhoea (0.23% vs 0.11%), upper gastrointestinal discomfort (0.97% vs 1.22%), intracranial haemorrhage (0.33% vs 0.47%), and gastrointestinal haemorrhage (0.52% vs 0.72%), respectively. There were ten (0.10%) patients in the clopidogrel group with significant reductions in neutrophils (< 1.2 x 10(9)/L) and 16 (0.17%) in the aspirin group. INTERPRETATION: Long-term administration of clopidogrel to patients with atherosclerotic vascular disease is more effective than aspirin in reducing the combined risk of ischaemic stroke, myocardial infarction, or vascular death. The overall safety profile of clopidogrel is at least as good as that of medium-dose aspirin

Saccular Abdominal Aortic Aneurysms Patient Characteristics, Clinical Presentation, Treatment, and Outcomes in the Netherlands

Objective: The aim of this was to analyze differences between saccularshaped abdominal aortic aneurysms (SaAAAs) and fusiform abdominal aortic aneurysms (FuAAAs) regarding patient characteristics, treatment, and outcome, to advise a threshold for intervention for SaAAAs.Background: Based on the assumption that SaAAAs are more prone to rupture, guidelines suggest early elective treatment. However, little is known about the natural history of SaAAAs and the threshold for intervention is not substantiated.Methods: Observational study including primary repairs of degenerative AAAs in the Netherlands between 2016 and 2018 in which the shape was registered, registered in the Dutch Surgical Aneurysm Audit (DSAA). Patients were stratified by urgency of surgery; elective versus acute (symptomatic/ruptured). Patient characteristics, treatment, and outcome were compared between SaAAAs and FuAAAs.Results: A total of 7659 primary AAA-patients were included, 6.1% (n = 471) SaAAAs and 93.9% (n = 7188) FuAAAs. There were 5945 elective patients (6.5% SaAAA) and 1714 acute (4.8% SaAAA). Acute SaAAApatients were more often female (28.9% vs 17.2%, P = 0.007) compared with acute FuAAA-patients. SaAAAs had smaller diameters than FuAAAs, in elective (53.0mm vs 61 mm, P = 0.000) and acute (68mm vs 75 mm, P = 0.002) patients, even after adjusting for sex. In addition, 25.2% of acute SaAAA-patients presented with diameters <55mm and 8.4% <45 mm, versus 8.1% and 0.6% of acute FuAAA-patients (P = 0.000). Postoperative outcomes did not significantly differ between shapes in both elective and acute patients.Conclusions: SaAAAs become acute at smaller diameters than FuAAAs in DSAA patients. This study therefore supports the current idea that SaAAAs should be electively treated at smaller diameters than FuAAAs. The exact diameter threshold for elective treatment of SaAAAs is difficult to determine, but a diameter of 45mm seems to be an acceptable threshold.Vascular Surger