Nonsyndromic craniosynostosis: diagnosis and contemporary surgical management

Contemporary surgical management of nonsyndromic craniosynostosis requires the combined expertise of a pediatric craniofacial surgeon and pediatric neurosurgeon. The goals of surgical intervention are the release of the affected suture, which allows for unrestricted development of the visceral components (eg, brain, eyes) and three-dimensional reconstruction of the skeletal components, which establishes a more normal anatomic position and contour. Surgeon who care for infants with these cranial and orbital malformations must maintain a thorough understanding of the three-dimensional anatomy, characteristic dysmorphology associated with the different types of synostosis, and the complex interplay that exists between surgical intervention and ongoing skeletal growth.     

The Determination of Hemoglobin in Blood Banks

The accuracy of the copper sulfate method of determining hemoglobin was investigated under usual blood bank conditions. In our hands this method was found to be grossly inaccurate. Using the cyanmethemoglobin technic, it was demonstrated that 83.9 per cent of females and 80.4 per cent of males rejected as having a low hemoglobin by the copper sulfate method, actually had hemoglobin values above minimum requirements for blood donors. Detailed instruction as to technics and pitfalls of the copper sulfate method was ineffectual in correcting errors as encountered by a large nursing staff carrying out the procedure. Donors found to have acceptable hemoglobin values by the copper sulfate method appeared to be safely accepted as donors; cyanmethemoglobin duplicate checks did not reveal any discrepancies in this group.     

Patient subgroup analyses of the treatment effect of subcutaneous interferon β-1a on development of multiple sclerosis in the randomized controlled REFLEX study

The REFLEX study (NCT00404352) established that subcutaneous (sc) interferon (IFN) β-1a reduced the risks of McDonald MS (2005 criteria) and clinically definite multiple sclerosis (CDMS) in patients with a first clinical demyelinating event suggestive of MS. The aim of this subgroup analysis was to assess the treatment effect of sc IFN β-1a in patient subgroups defined by baseline disease and demographic characteristics (age, sex, use of steroids at the first event, classification of first event as mono- or multifocal, presence/absence of gadolinium-enhancing lesions, count of <9 or ≥9 T2 lesions), and by diagnosis of MS using the revised McDonald 2010 MS criteria. Patients were randomized to the serum-free formulation of IFN β-1a, 44 μg sc three times weekly or once weekly, or placebo, for 24 months or until diagnosis of CDMS. Treatment effects of sc IFN β-1a on McDonald 2005 MS and CDMS in the predefined subgroups were similar to effects found in the intent-to-treat population. McDonald 2010 MS was retrospectively diagnosed in 37.7 % of patients at baseline. Both regimens of sc IFN β-1a significantly reduced the risk versus placebo of McDonald 2005 MS and CDMS, irrespective of McDonald 2010 status at baseline (risk reductions between 29 and 51 %). The effect of sc IFN β-1a was not substantially influenced by baseline patient demographic and disease characteristics, or baseline presence/absence of McDonald 2010 MS.     

Systematic comparison of adeno‐associated virus and biotinylated dextran amine reveals equivalent sensitivity between tracers and novel projection targets in the mouse brain

As an anterograde neuronal tracer, recombinant adeno‐associated virus (AAV) has distinct advantages over the widely used biotinylated dextran amine (BDA). However, the sensitivity and selectivity of AAV remain uncharacterized for many brain regions and species. To validate this tracing method further, AAV (serotype 1) was systematically compared with BDA as an anterograde tracer by injecting both tracers into three cortical and 15 subcortical regions in C57BL/6J mice. Identical parameters were used for our sequential iontophoretic injections, producing injections of AAV that were more robust in size and in density of neurons infected compared with those of BDA. However, these differences did not preclude further comparison between the tracers, because the pairs of injections were suitably colocalized and contained some percentage of double‐labeled neurons. A qualitative analysis of projection patterns showed that the two tracers behave very similarly when injection sites are well matched. Additionally, a quantitative analysis of relative projection intensity for cases targeting primary motor cortex (MOp), primary somatosensory cortex (SSp), and caudoputamen (CP) showed strong agreement in the ranked order of projection intensities between the two tracers. A detailed analysis of the projections of two brain regions (SSp and MOp) revealed many targets that have not previously been described in the mouse or rat. Minor retrograde labeling of neurons was observed in all cases examined, for both AAV and BDA. Our results show that AAV has actions equivalent to those of BDA as an anterograde tracer and is suitable for analysis of neural circuitry throughout the mouse brain. J. Comp. Neurol. 522:1989–2012, 2014. © 2014 Wiley Periodicals, Inc.     

Adherence to surveillance guidelines after radical cystectomy: A population-based analysis

ObjectivesSurveillance after radical cystectomy is recommended to detect tumor recurrence and treatment complications. We evaluated adherence to National Comprehensive Cancer Network (NCCN) guidelines using a large population-based database.Methods and materialsThe Surveillance, Epidemiology, and End Results–Medicare database was used to identify patients aged ≥66 years diagnosed with nonmetastatic bladder cancer who had undergone radical cystectomy between 2000 and 2007. Medicare claims information identified recommended surveillance tests for 2 years after cystectomy as outlined in the NCCN guidelines. Adherence was defined as receipt of urine cytology and imaging of the chest, abdomen, and pelvis in each year. We evaluated the effect of patient and provider characteristics on adherence, controlling for demographic and disease characteristics.ResultsOf 3,757 patients who had undergone radical cystectomy, 2,990 (80%) were alive after 2 years. Adherence to all recommended investigations was 17% for the first and the second years following surgery. Among patients surviving 2 years, only 9% had complete surveillance in both years. In either year, adherence was less likely in patients with advanced pathologic stage (III/IV) (adjusted odds ratio [AOR] = 0.74, 95% CI: 0.60–0.91) and unmarried patients (AOR = 0.82, 95% CI: 0.68–0.99). Adherence was more likely in patients treated by high-volume surgeons (AOR = 2.00, 95% CI: 1.70–2.36) and those who saw a medical oncologist (AOR = 1.52, 95% CI: 1.27–1.82). We also observed significant geographic variability in adherence.ConclusionPatterns of surveillance after radical cystectomy deviate considerably from NCCN recommendations. Despite increased utilization of radiographic imaging investigations, the omission of urine cytology significantly contributed to the low rate of overall adherence to surveillance guidelines. Uniform adherence to surveillance guidelines was observed in patients treated by high-volume surgeons. This suggests an important opportunity for quality improvement in bladder cancer care.     

Patient- and Provider-Reported Information about Transplantation and Subsequent Waitlisting

Because informed consent requires discussion of alternative treatments, proper consent for dialysis should incorporate discussion about other renal replacement options including kidney transplantation (KT). Accordingly, dialysis providers are required to indicate KT provision of information (KTPI) on CMS Form-2728; however, provider-reported KTPI does not necessarily imply adequate provision of information. Furthermore, the effect of KTPI on pursuit of KT remains unclear. We compared provider-reported KTPI (Form-2728) with patient-reported KTPI (in-person survey of whether a nephrologist or dialysis staff had discussed KT) in a prospective ancillary study of 388 hemodialysis initiates. KTPI was reported by both patient and provider for 56.2% of participants, by provider only for 27.8%, by patient only for 8.3%, and by neither for 7.7%. Among participants with provider-reported KTPI, older age was associated with lack of patient-reported KTPI. Linkage with the Scientific Registry for Transplant Recipients showed that 20.9% of participants were subsequently listed for KT. Patient-reported KTPI was independently associated with a 2.95-fold (95% confidence interval [95% CI], 1.54 to 5.66; P=0.001) higher likelihood of KT listing, whereas provider-reported KTPI was not associated with listing (hazard ratio, 1.18; 95% CI, 0.60 to 2.32; P=0.62). Our findings suggest that patient perception of KTPI is more important for KT listing than provider-reported KTPI. Patient-reported and provider-reported KTPI should be collected for quality assessment in dialysis centers because factors associated with discordance between these metrics might inform interventions to improve this process.     

Renal Outcomes in Patients with Type 1 Diabetes and Macroalbuminuria

Macroalbuminuria, defined as urine albumin excretion rate (AER)≥300 mg/d, has long been considered a stage of irreversible kidney damage that leads reliably to GFR loss. We examined the long-term renal outcomes of persons with type 1 diabetes who developed incident macroalbuminuria during the Diabetes Control and Complications Trial (DCCT)/Epidemiology of Diabetes Interventions and Complications (EDIC) study. One hundred fifty-nine participants developed incident macroalbuminuria and were subsequently followed for a median duration of 9 years (maximum of 25 years). At the time of macroalbuminuria diagnosis, mean (SD) age was 37 (9) years, mean (SD) duration of diabetes was 17 (5) years, median AER was 524 mg/d, and mean (SD) eGFR was 108 (20) ml/min per 1.73 m². Ten years after macroalbuminuria diagnosis, the cumulative incidence of a sustained reduction in AER to <300 mg/d was 52%, mostly but not entirely under treatment with renin-angiotensin system inhibitors. The cumulative incidence of impaired GFR (sustained eGFR<60 ml/min per 1.73 m²) 10 years after macroalbuminuria diagnosis was 32%, including 16% who developed ESRD. Lower hemoglobin A1c and BP and regression to AER<300 mg/d were associated with reduced risk of developing impaired GFR. In conclusion, people with type 1 diabetes who develop macroalbuminuria are at high risk of progressive kidney disease. However, through at least 10 years of follow-up, AER could often be controlled, and GFR frequently remained in the normal range.Macroalbuminuria, defined as urine albumin excretion rate (AER)≥300 mg/d, has long been considered a stage of irreversible kidney damage that leads reliably to GFR loss.¹ In early published type 1 diabetes cohorts, macroalbuminuria was associated with a 15-year cumulative incidence of ESRD as high as 75%.^2,3 However, contemporary long-term renal outcomes of macroalbuminuria have not been fully characterized.The Diabetes Control and Complications Trial (DCCT) and its observational follow-up, the Epidemiology of Diabetes Interventions and Complications (EDIC) study, present a valuable opportunity to examine macroalbuminuria and its long-term clinical outcomes. In DCCT/EDIC, the onset of macroalbuminuria can be defined with confidence using frequent longitudinal measurements of AER, participants have been followed for up to 25 years after the diagnosis of macroalbuminuria, and outcomes were meticulously recorded using standardized methods. Previous work in this cohort has shown that most cases of impaired GFR are preceded by macroalbuminuria,⁴ which is associated with a 50-fold higher risk of developing impaired GFR (eGFR<60 ml/min per 1.73 m²).⁵ Here, we extend these studies by comprehensively evaluating the long-term renal outcomes of incident macroalbuminuria in the DCCT/EDIC cohort and examining the risk factors for its progression to impaired GFR.