Feasibility and diagnostic accuracy of a gated SPECT early-imaging protocol: a multicenter study of the Myoview Imaging Optimization Group.

The aim of this study was to investigate whether early (time 1, or T1) myocardial tetrofosmin imaging is feasible and as accurate in detecting coronary artery disease as is standard delayed (time 2, or T2) imaging. METHODS: One hundred twenty patients (100 men and 20 women; mean age +/- SD, 61 +/- 10 y) with anginal symptoms underwent tetrofosmin gated SPECT. Stress/rest T1 imaging was performed at 15 min and T2 at 45 min after injection. Image quality was visually evaluated using a 4-point scale (from 0 = poor to 3 = optimal). Myocardial perfusion analysis was performed on a 20-segment model using quantitative perfusion SPECT software, and reversible ischemia was scored as a summed difference score (SDS). Coronary angiography was performed within 1 mo on all patients, and stenosis of more than 50% of the diameter was considered significant. RESULTS: Overall, quality was scored as optimal or good for 94% of T1 images and 95% of T2 images (P = not statistically significant). Heart, lung, liver, and subdiaphragmatic counts did not differ for stress and rest T1 and T2 imaging. A good linear relationship was seen between T1 and T2 SDS (r = 0.69; P < 0.0001), and Bland-Altman analysis showed good agreement between the 2 conditions. In terms of global diagnostic accuracy, areas under the receiver-operating-characteristic curve were comparable between T1 and T2 (0.80 vs. 0.81, P = not statistically significant). Discrepancies between T1 and T2 SDS were observed in 44% of patients (T1 - T2 SDS > 2). Linear regression analysis showed a good correlation between T1 and T2 SDS (r = 0.67; P < 0.0001), whereas the Bland-Altman method showed a shift in the mean value of the difference of +2.67 +/- 2.73. In patients with a T1 - T2 SDS of more than 2, areas under the receiver-operating-characteristic curves were significantly higher for T1 than for T2 images (0.79 vs. 0.70, P < 0.001). CONCLUSION: T1 imaging is feasible and as accurate as T2 imaging in identifying coronary artery disease. However, in a discrete subset of patients, early acquisition strengthens the clinical message of defect reversibility by permitting earlier, more accurate identification of more severe myocardial ischemia.     

Prevalence and clinical correlates of white coat hypertension in chronic kidney disease.

BACKGROUND: The role of white coat hypertension (WCH) in the poor control of blood pressure (BP) in chronic kidney disease (CKD) is ill defined. METHODS: We measured systolic clinical (CBP) and ambulatory blood pressure (ABP) in 290 consecutive patients with non-dialysis CKD [glomerular filtration rate (GFR) <60 ml/min/1.73 m(2)]. We defined normotension (NOR) if CBP and daytime ABP <130 mmHg, sustained hypertension (SH) when both BP >or=130 mmHg, WCH if only daytime ABP <130 mmHg, and masked hypertension (MH) when only CBP <130 mmHg. RESULTS: NOR patients were 15.5%, WCH 31.7%, SH 46.9% and MH 5.9%. Due to the high prevalence of WCH, achievement of BP target (<130 mmHg) was more than doubled by daytime ABP than CBP (47.2 vs 21.4%). WCH was characterized by prevalence of diabetes (31.5%), left ventricular hypertrophy (LVH; 50.0%) and CBP values (146 +/- 12 mmHg) lower than in SH (41.9%, 71.3% and 158 +/- 18 mmHg) but greater than in NOR (17.8%, 37.8% and 118 +/- 7 mmHg). Among patients with CBP >or=130 mmHg, the independent risk of having SH rather than WCH increased in the presence of higher CBP [Odds ration (OR) 1.61, 95% confidence intervals (CI) 1.29-2.02], LVH (OR 1.94, 95% CI 1.03-3.63) and proteinuria (OR 3.12, 95% CI 1.31-7.43). In the WCH group, 24 h, daytime and nighttime ABP were 118 +/- 7/68 +/- 8, 120 +/- 7/71 +/- 8 and 112 +/- 12/63 +/- 9 mmHg, respectively. CONCLUSIONS: In CKD, WCH is highly prevalent and can be predicted in the absence of higher CBP, LVH and proteinuria. In these patients, pursuing a low BP target may not be safe because of the risk of cardio-renal hypoperfusion especially at nighttime.     

Behavioural and emotional profiles of children and adolescents with disorders of arousal

Disorders of arousals are common sleep disorders characterized by complex motor behaviours that arise episodically out of slow‐wave sleep. Psychological distress has long been associated with disorders of arousal, but this link remains controversial, especially in children and adolescents. The aim of this multi‐centre study was to characterize behavioural and emotional problems in a sample of children/adolescents with disorders of arousal, and to explore their relationship with the severity of nocturnal episodes. The parents of 41 children/adolescents with a diagnosis of disorders of arousal (11.5 ± 3.3 years old, 61% males) and of a group of 41 age‐ and gender‐matched control participants filled in the Child Behavior Checklist, along with the Sleep Disturbance Scale for Children and the Paris Arousal Disorders Severity Scale. Multilevel t‐tests revealed significantly higher total scores and sub‐scores of the Child Behavior Checklist for the patient group compared with the control group. Thirty‐four percent of the patients obtained pathological total scores, and 12% of them borderline scores. The severity of emotional/behavioural problems in the patient group was positively correlated with the severity of the nocturnal episodes. Interestingly, children/adolescents with disorders of arousal also obtained higher excessive daytime sleepiness and insomnia symptoms sub‐scores at the Sleep Disturbance Scale for Children. These results confirmed the hypothesis that behavioural/emotional problems are surprisingly common in children/adolescents with disorders of arousal. Further studies are warranted to investigate the causal relationship between pathological manifestations, subtler sleep abnormalities, and diurnal emotional/behavioural problems in children/adolescents with disorders of arousal.     

Congenital X-linked neutropenia with myelodysplasia and somatic tetraploidy due to a germline mutation in SEPT6

Septins play key roles in mammalian cell division and cytokinesis but have not previously been implicated in a germline human disorder. A male infant with severe neutropenia and progressive dysmyelopoiesis with tetraploid myeloid precursors was identified. No known genetic etiologies for neutropenia or bone marrow failure were found. However, next-generation sequencing of germline samples from the patient revealed a novel, de novo germline stop-loss mutation in the X-linked gene SEPT6 that resulted in reduced SEPT6 staining in bone marrow granulocyte precursors and megakaryocytes. Patient skin fibroblast-derived induced pluripotent stem cells (iPSCs) produced reduced myeloid colonies, particularly of the granulocyte lineage. CRISPR/Cas9 knock-in of the patient's mutation or complete knock-out of SEPT6 was not tolerated in non-patient-derived iPSCs or human myeloid cell lines, but SEPT6 knock-out was successful in an erythroid cell line and resulting clones revealed a propensity to multinucleation. In silico analysis predicts that the mutated protein hinders the dimerization of SEPT6 coiled-coils in both parallel and antiparallel arrangements, which could in turn impair filament formation. These data demonstrate a critical role for SEPT6 in chromosomal segregation in myeloid progenitors that can account for the unusual predisposition to aneuploidy and dysmyelopoiesis.