Material differentiation by dual energy CT: initial experience

The aim of this study was to assess the feasibility of a differentiation of iodine from other materials and of different body tissues using dual energy CT. Ten patients were scanned on a SOMATOM Definition Dual Source CT (DSCT; Siemens, Forchheim, Germany) system in dual energy mode at tube voltages of 140 and 80 kVp and a ratio of 1:3 between tube currents. Weighted CT Dose Index ranged between 7 and 8 mGy, remaining markedly below reference dose values for the respective body regions. Image post-processing with three-material decomposition was applied to differentiate iodine or collagen from other tissue. The results showed that a differentiation and depiction of contrast material distribution is possible in the brain, the lung, the liver and the kidneys with or without the underlying tissue of the organ. In angiographies, bone structures can be removed from the dataset to ease the evaluation of the vessels. The differentiation of collagen makes it possible to depict tendons and ligaments. Dual energy CT offers a more specific tissue characterization in CT and can improve the assessment of vascular disease. Further studies are required to draw conclusions on the diagnostic value of the individual applications.     

Adjuvant capecitabine-containing chemotherapy benefit and homologous recombination deficiency in early-stage triple-negative breast cancer patients

Background The addition of adjuvant capecitabine to standard chemotherapy of early-stage triple-negative breast cancer (TNBC) patients has improved survival in a few randomised trials and in meta-analyses. However, many patients did not benefit. We evaluated the BRCA1-like DNA copy number signature, indicative of homologous recombination deficiency, as a predictive biomarker for capecitabine benefit in the TNBC subgroup of the FinXX trial.Methods Early-stage TNBC patients were randomised between adjuvant capecitabine-containing (TX + CEX: capecitabine-docetaxel, followed by cyclophosphamide-epirubicin-capecitabine) and conventional chemotherapy (T + CEF: docetaxel, followed by cyclophosphamide-epirubicin-fluorouracil). Tumour BRCA1-like status was determined on low-coverage, whole genome next-generation sequencing data using an established DNA comparative genomic hybridisation algorithm.Results For 129/202 (63.9%) patients the BRCA1-like status could be determined, mostly due to lack of tissue. During a median follow-up of 10.7 years, 35 recurrences and 32 deaths occurred. Addition of capecitabine appears to improve recurrence-free survival more among 61 (47.3%) patients with non-BRCA1-like tumours (HR 0.23, 95% CI 0.08–0.70) compared to 68 (52.7%) patients with BRCA1-like tumours (HR 0.66, 95% CI 0.24–1.81) (P-interaction = 0.17).Conclusion Based on our data, patients with non-BRCA1-like TNBC appear to benefit from the addition of capecitabine to adjuvant chemotherapy. Patients with BRCA1-like TNBC may also benefit. Additional research is needed to define the subgroup within BRCA1-like TNBC patients who may not benefit from adjuvant capecitabine.Subject terms: Breast cancer, Translational research, Predictive markers, Breast cancer     

Chronic health conditions and school performance among children and youth

PurposeChronic health conditions are common and increasing among U.S. children and youth. We examined whether chronic health conditions are associated with low school performance.MethodsThis retrospective cohort study of 22,730 children and youth (grades 2–11) in San Jose, California, was conducted from 2007 through 2010. Health conditions were defined as chronic if reported in each of the first 2 years, and school performance was measured using standardized English language arts (ELA) and math assessments.ResultsChronic health conditions were independently associated with low ELA and math performance, irrespective of ethnicity, socioeconomic status, or grade level. Adjusted odds ratios for the association between any chronic health condition and low (“basic or below”) performance were 1.25 (95% confidence interval [CI], 1.16–1.36; P < .001) for ELA and 1.28 (95% CI, 1.18–1.38; P < .001) for math, relative to students without reported health conditions. Further adjustment for absenteeism had little effect on these results. The strongest associations were found for ADHD, autism, and seizure disorders, whereas a weak association was found for asthma before but not after adjusting for absenteeism, and no associations were found for cardiovascular disorders or diabetes.ConclusionsChronic neurodevelopmental and seizure disorders, but not cardiovascular disorders or diabetes, were independently associated with low school performance among children and youth.     

Cholera Vaccination in Urban Haiti

Successful and sustained efforts have been made to curtail the major cholera epidemic that occurred in Haiti in 2010 with the promotion of hygiene and sanitation measures, training of health personnel and establishment of treatment centers nationwide. Oral cholera vaccine (OCV) was introduced by the Haitian Ministry of Health as a pilot project in urban and rural areas. This paper reports the successful OCV pilot project led by GHESKIO Centers in the urban slums of Port-au-Prince where 52,357 persons received dose 1 and 90.8% received dose 2; estimated coverage of the at-risk community was 75%. This pilot study demonstrated the effort, community mobilization, and organizational capacity necessary to achieve these results in a challenging setting. The OCV intervention paved the way for the recent launching of a national cholera vaccination program integrated in a long-term ambitious and comprehensive plan to address Haiti''s critical need in water security and sanitation.     

Familial steroid-sensitive nephrotic syndrome in Southern Israel: clinical and genetic observations

Reports on genetically informative steroid-responsive (sensitive) idiopathic nephrotic syndrome (SSNS) families are lacking. We studied an extended SSNS Bedouin (B) family with a high rate of consanguinity. The clinical presentation and steroid response of its 11 affected individuals were similar to those of sporadic SSNS (spontaneous remission towards puberty and minimal change disease by kidney biopsy). Genome-wide linkage analysis, using a 382 microsatellite-markers mapping set and additional markers adjacent to 80 candidate genes of the index family, did not support linkage to any chromosomal locus. Retrospective analysis of all additional children with SSNS treated by our institution in the past 20 years (n = 96, 50% of them of Jewish origin) revealed another five non-related B families with 2–3 first-degree cousins affected with SSNS in each. The overall familial SSNS rate among the B population (excluding the index family) was 28%, compared with 4% among Jews (Js) (OR 1.8–64, P < 0.005). There were more Bs with simple SSNS than there were Js (71% and 40%, respectively; OR 3.58, 95% CI 1.41–9.23, P < 0.01). In summary, SSNS in this index family was not linked to any of the presently known chromosomal loci nor predicted to be caused by mutation in any one of a list of genes associated with nephrotic syndrome (NS). The presence of other B families affected by SSNS supports the role for susceptibility genes enrichment, exposing highly consanguineous populations to an increased incidence of SSNS. An erratum to this article can be found at     

Selective increase of dark phase water intake in neuropeptide-Y Y2 and Y4 receptor knockout mice

Neuropeptide-Y (NPY) is involved in the regulation of ingestive behaviour and energy homeostasis. Since deletion of the NPY Y2 and Y4 receptor gene increases and decreases food intake, respectively, we examined whether water intake during the light and dark phases is altered in Y2 and Y4 receptor knockout mice. The water consumption of mice staying in their home cages was measured by weighing the water bottles at the beginning and end of the light phase during 4 consecutive days. Control, Y2 and Y4 receptor knockout mice did not differ in their water intake during the light phase. However, during the dark phase Y2 and Y4 receptor knockout mice drank significantly more (46-63%, P<0.05) water than the control mice. The total daily water intake over 24 h was also enhanced. The enhanced water intake during the dark phase was not altered by the beta-adrenoceptor antagonist propranolol or the angiotensin AT1 receptor antagonist telmisartan (each injected intraperitoneally at 10 mg/kg). These data indicate that NPY acting via Y2 and Y4 receptors plays a distinctive role in the regulation of nocturnal water consumption. While beta-adrenoceptors and angiotensin AT1 receptors do not seem to be involved, water intake in Y2 and Y4 receptor knockout mice may be enhanced because presynaptic autoinhibition of NPY release and inhibition of orexin neurons in the central nervous system are prevented.     

On the variety of cell death pathways in the Lurcher mutant mouse

Apoptosis as well as autophagy have been implicated in the death of cerebellar Purkinje cells (PCs) in the Lurcher (Lc/+) mutant mouse and at least two different apoptotic pathways participate in the transsynaptic death of granule cells (GC) and inferior olivary (IO) neurones. The relative contribution of these pathways can only be assessed from their momentary involvement at any stage of the complete course of neurodegeneration. Here we used quantitative labelling for activated caspase-3 (Casp-3) and Fluoro-Jade B (FJ-B) to investigate the spatio-temporal pattern of neuronal death from P6 to P67 in Lc/+ mutants. Activated Casp-3 was present only in narrow time intervals (P14 to P22 in PCs; P14 to P28 in GCs) and in small subpopulations of PCs, GCs, and IO neurones. FJ-B positive PCs were detected during a broader period (P14 to P28), and outnumbered Casp-3 labelled PCs by a factor exceeding eight. Nevertheless, FJ-B labelling was restricted to PCs and never found in either GC or IO neurones. In conclusion, we present the first complete time course and extent of Casp-3 activation in Lc/+ mutants and show that the majority of dying neurones in Lc/+ mutants undergo Casp-3 independent cell death. The cellular overload produced by the initial gene defect in Lc/+ mutants apparently activates a variety of apoptotic and non-apoptotic pathways within the same neuronal population. Moreover, we present the first evidence for the ability of FJ-B to selectively label a discrete population of dying PCs, implying a higher selectivity of FJ-B than previously supposed.     

Clinical impact of CCM mutation detection in familial cavernous angioma

Introduction and background A 3-year-old Bosnian girl with a large symptomatic brainstem and multiple supratentorial cavernous angiomas, who underwent neurosurgical treatment, is presented. As multiple cavernomas are more common in familial cases, genetic analyses and neuroradiological imaging were performed in the patient and her parents to see whether there was any evidence for inheritance. This information is important for genetic counseling and provision of medical care for at-risk relatives. Currently, no recommendation is available on how to manage these cases.Results Genetic analyses demonstrated a novel CCM1 frameshift mutation (c.1683_1684insA; p.V562SfsX6) in the child and the asymptomatic 27-year-old mother. Sensitive gradient-echo magnetic resonance imaging of the mother revealed multiple supratentorial lesions, whereas analogous imaging of the father showed no pathological findings.Conclusion This case exemplifies that seemingly sporadic cases with multiple lesions might well be hereditary and that presymptomatic genetic testing of family members may identify relatives for whom clinical and neuroradiological monitoring is indicated.     

Valproic acid induced encephalopathy--19 new cases in Germany from 1994 to 2003--a side effect associated to VPA-therapy not only in young children.

Valproic acid (VPA) is a broad-spectrum antiepileptic drug and is usually well-tolerated. Rare serious complications may occur in some patients, including haemorrhagic pancreatitis, bone marrow suppression, VPA-induced hepatotoxicity and VPA-induced encephalopathy. The typical signs of VPA-induced encephalopathy are impaired consciousness, sometimes marked EEG background slowing, increased seizure frequency, with or without hyperammonemia. There is still no proof of causative effect of VPA in patients with encephalopathy, but only of an association with an assumed causal relation. We report 19 patients with VPA-associated encephalopathy in Germany from the years 1994 to 2003, none of whom had been published previously.     

Could metabolic liver function tests predict mortality on waiting list for liver transplantation? A study on 560 patients

Ecochard M, Boillot O, Guillaud O, Roman S, Adham M, Mion F, Dumortier J. Could metabolic liver function tests predict mortality on waiting list for liver transplantation? A study on 560 patients.
Clin Transplant 2011: 25: 755–765. © 2010 John Wiley & Sons A/S. Abstract: Background: Allocation of graft in liver transplantation (LT) depends mainly on Model for End Stage Liver Disease (MELD) score. We studied the prognostic ability of three metabolic liver function tests in 560 cirrhotic patients listed for transplantation, in comparison with MELD and Child–Turcotte–Pugh (CTP) scores. Methods: Indocyanine green retention rate (ICG), aminopyrine breath test (ABT), and galactose elimination capacity were performed at the time of listing in addition to standard biological parameters. Seventy‐three patients died on waiting list, 438 were transplanted, and 73 died after LT. Cox regression analysis and receiver operating characteristic curves with c‐statistics were calculated after stratification according to CTP and MELD score. Results: For the mortality before transplantation, c‐statistics showed that ICG and ABT had a slightly better prognostic ability (0.73 and 0.68, respectively) than MELD score (0.66), and similar to CTP score (0.70). ABT’s prognostic ability remained significant once the MELD score (below and above 20) had already been taken into account. Only ICG had a prognostic ability to predict the survival after LT, even after stratification according to MELD and CTP score. Conclusions: Our results strongly support that ABT and ICG may be useful in the ranking of the patients in LT list, adding prognosis information in association with MELD score.