Essential features of Chiari II malformation in MR imaging: an interobserver reliability study—part 1

Purpose

Brain MR imaging is essential in the assessment of Chiari II malformation in clinical and research settings concerning spina bifida. However, the interpretation of morphological features of the malformation on MR images may not always be straightforward. In an attempt to select those features that unambiguously characterize the Chiari II malformation, we investigated the interobserver reliability of all its well-known MR features.

Methods

Brain MR images of 79 children [26 presumed to have Chiari II malformation, 36 presumed to have no cerebral abnormalities, and 17 children in whom some Chiari II malformation features might be present; mean age 10.6 (SD 3.2; range, 6-16) years] were blindly and independently reviewed by three observers. They rated 33 morphological features of the Chiari II malformation as present, absent, or indefinable in three planes (sagittal, axial, and coronal). The interobserver reliability was assessed using κ statistics.

Results

Twenty-three of the features studied turned out to be unreliable, whereas the interobserver agreement was almost perfect (κ value?>?0.8) for nine features (eight in the sagittal plane and one in the axial plane, but none in the coronal plane).

Conclusions

This study presents essential features of the Chiari II malformation on MR images by ruling out the unreliable features. Using these features may improve the assessment of Chiari II malformation in clinical and research settings.     

Effect of e-learning and repeated performance feedback on spirometry test quality in family practice: a cluster trial

PURPOSE Spirometry has become an indispensable tool in primary care to exclude, diagnose, and monitor chronic respiratory conditions, but the quality of spirometry tests in family practices is a reason for concern. Aim of this study was to investigate whether a combination of e-learning and bimonthly performance feedback would improve spirometry test quality in family practices in the course of 1 year.METHODS Our study was a cluster trial with 19 family practices allocated to intervention or control conditions through minimization. Intervention consisted of e-learning and bimonthly feedback reports to practice nurses. Control practices received only the joint baseline workshop. Spirometry quality was assessed by independent lung function technicians. Two outcomes were defined, with the difference between rates of tests with 2 acceptable and repeatable blows being the primary outcome and the difference between rates of tests with 2 acceptable blows being the secondary outcome. We used multilevel logistic regression analysis to calculate odds ratios (ORs) for an adequate test in intervention group practices.RESULTS We analyzed 1,135 tests. Rate of adequate tests was 33% in intervention and 30% in control group practices (OR = 1.3; P=.605). Adequacy of tests did not differ between groups but tended to increase with time: OR = 2.2 (P = .057) after 3 and OR = 2.0 (P = .086) in intervention group practices after 4 feedback reports. When ignoring test repeatability, these differences between the groups were slightly more pronounced: OR = 2.4 (P = .033) after 3 and OR=2.2 (P = .051) after 4 feedback reports.CONCLUSIONS In the course of 1 year, we observed a small and late effect of e-learning and repeated feedback on the quality of spirometry as performed by family practice nurses. This intervention does not seem to compensate the lack of rigorous training and experience in performing spirometry tests in most practices.     

Impact of infant and preschool pertussis vaccinations on memory B-cell responses in children at 4 years of age

Whooping cough, caused by Bordetella pertussis, is reemerging in the vaccinated population. Antibody levels to pertussis antigens wane rapidly after both whole-cell (wP) and acellular pertussis (aP) vaccination and protection may largely depend on long-term B- and T-cell immunity. We studied the effect of wP and aP infant priming at 2, 3, 4 and 11 months according to the Dutch immunization program on pertussis-specific memory B-cell responses before and after a booster vaccination with either a high- or low-pertussis dose vaccine at 4 years of age.Purified B-cells were characterized by FACS-analysis and after polyclonal stimulation, memory B-cells were detected by ELISPOT-assays specific for pertussis toxin, filamentous haemagglutinin and pertactin.Before and after the booster, higher memory B-cell responses were measured in aP primed children compared with wP primed children. In contrast with antibody levels, no dose-effect was observed on the numbers of memory B-cell responses. In aP primed children a fifth high-dose aP vaccination tended to induce even lower memory B-cell responses than a low-dose aP booster. In both wP and aP primed children, the number of memory B-cells increased after the booster and correlated with the pertussis-specific antibody concentrations and observed affinity maturation.This study indicates that aP vaccinations in the first year of life induce higher pertussis-specific memory B-cell responses in children 4 years of age compared with Dutch wP primary vaccinations. Since infant aP vaccinations have improved protection against whooping cough in children despite waning antibody levels, this suggests that an enhanced memory B-cell pool induction may have an important role in protection. However, the pertussis-dose of the preschool booster needs to be considered depending on the vaccine used for priming to optimize long-term protection against whooping cough.     

Six and eight weeks injection frequencies of bevacizumab are non-inferior to the current four weeks injection frequency for quality of life in neovascular age-related macular degeneration: a randomized controlled trial

Quality of Life Research - Patients with neovascular age-related macular degeneration (nARMD) will not deteriorate on visual acuity and retinal thickness when treated with bevacizumab injection...     

Five‐year follow‐up after live donor nephrectomy – cross‐sectional and longitudinal analysis of a prospective cohort within the era of extended donor eligibility criteria

To establish the outcome of live kidney donors 5 years after donation, we investigated the risk for progressive renal function decline and quality of life (QoL). Data on estimated glomerular filtration rate (eGFR), creatinine, hypertension, QoL and survival were assessed in a prospective cohort of 190 donors, who donated between 2008 and 2010. Data were available for >90%. The mean age predonation was 52.8 ± 11.5 years, 30 donors having pre‐existent hypertension. The mean follow‐up was 5.1 ± 0.9 years. Eight donors had died due to non‐donation‐related causes. After 5 years, the mean eGFR was 60.2 (95% CI 58.7–62.7) ml/min/1.73 m², with a median serum creatinine of 105.1 (95% CI 102.5–107.8) μmol/l. eGFR decreased to 33.6% and was longitudinally lower among men than women and declining with age (P < 0.001), without any association on QoL. Donors with pre‐existent and new‐onset hypertension demonstrated no progressive decline of renal function overtime compared to nonhypertensives. No donors were found with proteinuria, microalbuminuria or at risk for end‐stage renal disease. After an initial decline postdonation, renal function remained unchanged overtime. Men and ageing seem to affect renal function overtime, while decreased renal function did not affect QoL. These data support further stimulation of living kidney donation programmes as seen from the perspective of donor safety.     

A community-based evaluation of sudden death associated with therapeutic levels of methadone

Background

Published case reports have associated the therapeutic use of methadone with the occasional occurrence of sudden cardiac death. Because of the established utility of this drug and with the eventual goal of enhancing safety of use, we performed a community-based study to evaluate this association.

Methods

During a 4-year period, we prospectively evaluated all patients who consecutively had sudden cardiac death and underwent investigation by the medical examiner in the metropolitan area of Portland, Ore. Case subjects of interest were those with a therapeutic blood level of methadone (<1 mg/L), and case comparison subjects were those with no methadone identified. Patients with recreational drug use or any drug overdose were excluded from either group. Detailed autopsies were conducted, including the detection and quantification of all substances in the blood.

Results

A total of 22 sudden cardiac death cases with therapeutic levels of methadone (mean 0.48 ± 0.22 mg/L; range 0.1-0.9 mg/L) were identified (mean age 37.0 ± 10 years, 68% were male) and compared with 106 consecutive sudden cardiac death cases without evidence of methadone (mean age 42 ± 13 years, 69% were male). The most common indication for methadone use was pain control (n = 12, 55%). Among cases receiving methadone therapy, sudden death-associated cardiac abnormalities were identified in only 23% (n = 5), with no clear cause of sudden cardiac death in the remaining 77% (n = 17). Among cases with no methadone, sudden death-associated cardiac abnormalities were identified in 60% (n = 64, P = .002).

Conclusion

The significantly lower prevalence of cardiac disease in the case group implicates methadone, even at therapeutic levels, as a likely cause of sudden death. These findings point toward an association between methadone and occurrence of sudden death in the community. Clinical safeguards and further prospective studies specifically designed to enhance safety of methadone use are warranted.     

Interaction of acute lymphopblastic leukemia cells with C-type lectins DC-SIGN and L-SIGN

The C-type lectins DC-SIGN (CD209) and L-SIGN (CD299) recognize defined carbohydrates expressed on pathogens and cells. Those lectins are expressed on dendritic cells (DC) and/or on liver-sinusoidal endothelial cells. Both cell types modulate immune responses. In acute lymphoblastic leukemia (ALL), aberrant glycosylation of blast cells can alter their interaction with the C-type lectins DC-SIGN and L-SIGN, thereby affecting their immunological elimination. We investigated whether recombinant DC-SIGN and L-SIGN bind to blood or bone marrow cells from B- and T-ALL patients and compared that with binding of peripheral blood lymphocytes from healthy donors. It was found that increased binding of ALL cells to DC-SIGN and L-SIGN was observed compared to cells from healthy donors. Furthermore, L-SIGN bound a higher percentage of leukemic and normal cells than DC-SIGN. B-ALL bone marrow cells showed the highest binding to L-SIGN. DC-SIGN bound equally well to B-ALL and T-ALL cells. Within ALL subtypes, DC-SIGN binding was higher with mature T-ALL. Interestingly, our data demonstrate that increased binding of DC-SIGN and L-SIGN to peripheral leukemic cells from B-ALL patients is associated with poor survival. These data demonstrate that high binding of B-ALL peripheral blood cells to DC-SIGN and L-SIGN correlates with poor prognosis. Apparently, when B-ALL cells enter the blood circulation and are able to interact with DC-SIGN and L-SIGN the immune response is shifted toward tolerance. Additional studies are necessary to ascertain the possible role of these results in terms of disease pathogenesis and their potential as target to eradicate leukemic cells.     

Effect of diet-induced weight loss on lipoprotein(a) levels in obese individuals with and without type 2 diabetes

Aims/hypothesis

Elevated levels of lipoprotein(a) [Lp(a)] are an independent risk factor for cardiovascular disease (CVD), particularly in individuals with type 2 diabetes. Although weight loss improves conventional risk factors for CVD in type 2 diabetes, the effects on Lp(a) are unknown and may influence the long-term outcome of CVD after diet-induced weight loss. The aim of this clinical study was to determine the effect of diet-induced weight loss on Lp(a) levels in obese individuals with type 2 diabetes.

Methods

Plasma Lp(a) levels were determined by immunoturbidimetry in plasma obtained before and after 3–4 months of an energy-restricted diet in four independent study cohorts. The primary cohort consisted of 131 predominantly obese patients with type 2 diabetes (cohort 1), all participants of the Prevention Of Weight Regain in diabetes type 2 (POWER) trial. The secondary cohorts consisted of 30 obese patients with type 2 diabetes (cohort 2), 37 obese individuals without type 2 diabetes (cohort 3) and 26 obese individuals without type 2 diabetes who underwent bariatric surgery (cohort 4).

Results

In the primary cohort, the energy-restricted diet resulted in a weight loss of 9.9% (95% CI 8.9, 10.8) and improved conventional CVD risk factors such as LDL-cholesterol levels. Lp(a) levels increased by 14.8 nmol/l (95% CI 10.2, 20.6). In univariate analysis, the change in Lp(a) correlated with baseline Lp(a) levels (r = 0.38, p < 0.001) and change in LDL-cholesterol (r = 0.19, p = 0.033). In cohorts 2 and 3, the weight loss of 8.5% (95% CI 6.5, 10.6) and 6.5% (95% CI 5.7, 7.2) was accompanied by a median increase in Lp(a) of 13.5 nmol/l (95% CI 2.3, 30.0) and 11.9 nmol/l (95% CI 5.7, 19.0), respectively (all p < 0.05). When cohorts 1–3 were combined, the diet-induced increase in Lp(a) correlated with weight loss (r = 0.178, p = 0.012). In cohort 4, no significant change in Lp(a) was found (?7.0 nmol/l; 95% CI -18.8, 5.3) despite considerable weight loss (14.0%; 95% CI 12.2, 15.7).

Conclusions/interpretation

Diet-induced weight loss was accompanied by an increase in Lp(a) levels in obese individuals with and without type 2 diabetes while conventional CVD risk factors for CVD improved. This increase in Lp(a) levels may potentially antagonise the beneficial cardiometabolic effects of diet-induced weight reduction.