Narcolepsy and pregnancy: a retrospective European evaluation of 249 pregnancies

In a retrospective cohort study undertaken in 12 European countries, 249 female narcoleptic patients with cataplexy (n = 216) and without cataplexy (n = 33) completed a self-administrated questionnaire regarding pregnancy and childbirth. The cohort was divided further into patients whose symptoms of narcolepsy started before or during pregnancy (308 pregnancies) and those in whom the first symptoms of narcolepsy appeared after delivery (106 pregnancies). Patients with narcolepsy during pregnancy were older during their first pregnancy (P < 0.001) and had a higher body mass index (BMI) prior to pregnancy (P < 0.01). Weight gain during pregnancy was higher in narcoleptic patients with cataplexy (P < 0.01). More patients with narcolepsy-cataplexy during pregnancy had impaired glucose metabolism and anaemia. Three patients experienced cataplexy during delivery. The rate of caesarean sections was higher in the narcolepsy-cataplexy group compared to the narcolepsy group (P < 0.05). The mean birth weight and gestational age of neonates were within the normal range and did not differ across groups. Neonatal care was affected adversely by symptoms of narcolepsy in 60.1% of those with narcolepsy during pregnancy. This study reports more obstetric complications in patients with narcolepsy-cataplexy during pregnancy; however, these were not severe. This group also had a higher BMI and higher incidence of impaired glucose metabolism during pregnancy. Caesarian section was conducted more frequently in narcolepsy-cataplexy patients, despite cataplexy being a rare event during delivery. Furthermore, symptoms of narcolepsy may render care of the infant more difficult.

A simple presurgical necrotizing enterocolitis-mortality scoring system

OBJECTIVE: To assess the relationship between early laboratory parameters, disease severity, type of management (surgical or conservative) and outcome in necrotizing enterocolitis (NEC). STUDY DESIGN: Retrospective collection and analysis of data from infants treated in a single tertiary care center (1980 to 2002). Data were collected on disease severity (Bell stage), birth weight (BW), gestational age (GA) and pre-intervention laboratory parameters (leukocyte and platelet counts, hemoglobin, lactate, C-reactive protein). RESULTS: Data from 128 infants were sufficient for analysis. Factors significantly associated with survival were Bell stage (P<0.05), lactate (P<0.05), BW and GA (P<0.01, P<0.001, respectively). From receiver operating characteristics curves, the highest predictive value resulted from a score with 0 to 8 points combining BW, Bell stage, lactate and platelet count (P<0.001). At a cutoff level of 4.5 sensitivity and specificity for predicting survival were 0.71 and 0.72, respectively. CONCLUSION: Some single parameters were associated with poor outcome in NEC. Optimal risk stratification was achieved by combining several parameters in a score.

Outcome in neonates with necrotizing enterocolitis and patent ductus arteriosus.

BACKGROUND There is no agreement of the influence of patent ductus arteriosus (PDA) on outcomes in patients with necrotizing enterocolitis (NEC). In this study, we assessed the influence of PDA on NEC outcomes. METHODS A retrospective study of 131 infants with established NEC was performed. Outcomes (death, disease severity, need for surgery, hospitalization duration), as well as multiple clinical parameters were compared between NEC patients with no congenital heart disease (n=102) and those with isolated PDA (n=29). Univariate, multivariate and stepwise logistic regression analyses were performed. RESULTS Birth weight and gestational age were significantly lower in patients with PDA [median (95% CI): 1120 g (1009-1562 g), 28.4 wk (27.8-30.5 wk)] than in those without PDA [median (95% CI): 1580 g (1593-1905 g), 32.4 wk (31.8-33.5 wk); P<0.05]. The risk of NEC-attributable fatality was higher in NEC patients with PDA (35%) than in NEC patients without PDA (14%)[univariate odds ratio (OR)=3.3, 95% CI: 1.8-8.6, P<0.05; multivariate OR=2.4, 95% CI: 0.82-2.39, P=0.111]. Significant independent predictors for nonsurvival within the entire cohort were advanced disease severity stage III (OR=27.9, 95% CI: 7.4-105, P<0.001) and birth weight below 1100 g (OR=5.7, 95% CI: 1.7-19.4, P<0.01). CONCLUSIONS In patients with NEC, the presence of PDA is associated with an increased risk of death. However, when important differences between the two study groups are controlled, only birth weight and disease severity may independently predict mortality.

A multinational case-control study on childhood brain tumours, anthropogenic factors, birth characteristics and prenatal exposures: A validation of interview data.

Little is known about the aetiology of childhood brain tumours. We investigated anthropometric factors (birth weight, length, maternal age), birth characteristics (e.g. vacuum extraction, preterm delivery, birth order) and exposures during pregnancy (e.g. maternal: smoking, working, dietary supplement intake) in relation to risk of brain tumour diagnosis among 7-19 year olds. The multinational case-control study in Denmark, Sweden, Norway and Switzerland (CEFALO) included interviews with 352 (participation rate=83.2%) eligible cases and 646 (71.1%) population-based controls. Interview data were complemented with data from birth registries and validated by assessing agreement (Cohen's Kappa). We used conditional logistic regression models matched on age, sex and geographical region (adjusted for maternal age and parental education) to explore associations between birth factors and childhood brain tumour risk. Agreement between interview and birth registry data ranged from moderate (Kappa=0.54; worked during pregnancy) to almost perfect (Kappa=0.98; birth weight). Neither anthropogenic factors nor birth characteristics were associated with childhood brain tumour risk. Maternal vitamin intake during pregnancy was indicative of a protective effect (OR 0.75, 95%-CI: 0.56-1.01). No association was seen for maternal smoking during pregnancy or working during pregnancy. We found little evidence that the considered birth factors were related to brain tumour risk among children and adolescents.

Sciatic neuropathy after body contouring surgery in massive weight loss patients

To date, obesity affects a substantial population in industrialised countries. Due to the increased awareness of obesity-related morbidity, efficient dietary regimens and the recent successes with bariatric surgery, there is now a high demand for body contouring surgery to correct skin abundancies after massive weight loss. The known risks for this type of surgery are mainly wound-healing complications, and, more rarely, thromboembolic or respiratory complications. We present two female patients (23 and 39 years of age) who, in spite of standard positioning and precautions, developed sciatic neuropathy after combined body contouring procedures, including abdominoplasty and inner thigh lift. Complete functional loss of the sciatic nerve was found by clinical and electroneurographic examination on the left side in patient one and bilaterally in patient two. Full nerve conductance recovery was obtained after 6 months in both patients. Although the occurrence of spontaneous neuropathies after heavy weight loss is well documented, this is the first report describing the appearance of such a phenomenon following body contouring surgery. One theoretical explanation may be the compression of the nerve during the semirecumbent positioning combined with hip flexion and abduction, which was required for abdominal closure and simultaneous access to the inner thighs. We advise to avoid this positioning and to include the risk of sciatic neuropathy in the routine preoperative information of patients scheduled for body contouring surgery after heavy weight loss.

Petrology and geochronology of "muscovite age standard" B4M

Muscovite B4M, distributed in 1961 as an age standard, was ground under ethanol. Five grain size fractions were obtained and characterized by X-ray diffraction. They display a mixing trend between a phengitic (enriched in the fraction <0.2 µm) and a muscovitic component (predominant in the fraction >20 µm). High-pressure phengite is preserved as a relict in retrograde muscovite. Electron microprobe analyses of the distributed mineral separate reveal at least four white mica populations based on Si, Al, Mg, Na, Fe and F. Rb/K ratios vary by one order of magnitude. Rb–Sr analyses link the mineralogical heterogeneity to variable Rb/Sr and 87Sr/86Sr ratios. The grain size fractions define no internal isochron. Relict fine-grained phengite gives older ages than coarse-grained retrograde greenschist facies muscovite. The inverse grain size–age relationship also characterizes 39Ar/40Ar analyses. Cl/K anticorrelates with step ages: Cl-rich coarse muscovite is younger than Cl-poor fine relict phengite. Sr and Ar preserve a similar isotopic inheritance despite peak metamorphism reaching 635±20 °C. A suitable mineral standard requires that its petrological equilibrium first be demonstrated. Relicts and retrograde reaction textures are a guarantee of isotopic disequilibrium and heterogeneous ages within single crystal at the micrometre scale.

Should the standard dimethyl sulfoxide concentration be reduced? Results of a European Group for Blood and Marrow Transplantation prospective noninterventional study on usage and side effects of dimethyl sulfoxide.

BACKGROUND Dimethyl sulfoxide (DMSO) is essential for the preservation of liquid nitrogen-frozen stem cells, but is associated with toxicity in the transplant recipient. STUDY DESIGN AND METHODS In this prospective noninterventional study, we describe the use of DMSO in 64 European Blood and Marrow Transplant Group centers undertaking autologous transplantation on patients with myeloma and lymphoma and analyze side effects after return of DMSO-preserved stem cells. RESULTS While the majority of centers continue to use 10% DMSO, a significant proportion either use lower concentrations, mostly 5 or 7.5%, or wash cells before infusion (some for selected patients only). In contrast, the median dose of DMSO given (20 mL) was much less than the upper limit set by the same institutions (70 mL). In an accompanying statistical analysis of side effects noted after return of DMSO-preserved stem cells, we show that patients in the highest quartile receiving DMSO (mL and mL/kg body weight) had significantly more side effects attributed to DMSO, although this effect was not observed if DMSO was calculated as mL/min. Dividing the myeloma and lymphoma patients each into two equal groups by age we were able to confirm this result in all but young myeloma patients in whom an inversion of the odds ratio was seen, possibly related to the higher dose of melphalan received by young myeloma patients. CONCLUSION We suggest better standardization of preservation method with reduced DMSO concentration and attention to the dose of DMSO received by patients could help reduce the toxicity and morbidity of the transplant procedure.

Age-specific and sex-specific weight gain norms to monitor antiretroviral therapy in children in low-income and middle-income countries.

BACKGROUND Viral load and CD4% are often not available in resource-limited settings for monitoring children's responses to antiretroviral therapy (ART). We aimed to construct normative curves for weight gain at 6, 12, 18, and 24 months following initiation of ART in children, and to assess the association between poor weight gain and subsequent responses to ART. DESIGN Analysis of data from HIV-infected children younger than 10 years old from African and Asian clinics participating in the International epidemiologic Databases to Evaluate AIDS. METHODS The generalized additive model for location, scale, and shape was used to construct normative percentile curves for weight gain at 6, 12, 18, and 24 months following ART initiation. Cox proportional models were used to assess the association between lower percentiles (< 50th) of weight gain distribution at the different time points and subsequent death, virological suppression, and virological failure. RESULTS Among 7173 children from five regions of the world, 45% were underweight at baseline. Weight gain below the 50th percentile at 6, 12, 18, and 24 months of ART was associated with increased risk of death, independent of baseline characteristics. Poor weight gain was not associated with increased hazards of virological suppression or virological failure. CONCLUSION Monitoring weight gain on ART using age-specific and sex-specific normative curves specifically developed for HIV-infected children on ART is a simple, rapid, sustainable tool that can aid in the identification of children who are at increased risk of death in the first year of ART.

Long-term follow-up of patients with Bartter syndrome type I and II

BACKGROUND: Little information is available on a long-term follow-up in Bartter syndrome type I and II. METHODS: Clinical presentation, treatment and long-term follow-up (5.0-21, median 11 years) were evaluated in 15 Italian patients with homozygous (n = 7) or compound heterozygous (n = 8) mutations in the SLC12A1 (n = 10) or KCNJ1 (n = 5) genes. RESULTS: Thirteen new mutations were identified. The 15 children were born pre-term with a normal for gestational age body weight. Medical treatment at the last follow-up control included supplementation with potassium in 13, non-steroidal anti-inflammatory agents in 12 and gastroprotective drugs in five patients. At last follow-up, body weight and height were within normal ranges in the patients. Glomerular filtration rate was <90 mL/min/1.73 m(2) in four patients (one of them with a pathologically increased urinary protein excretion). In three patients, abdominal ultrasound detected gallstones. The group of patients with antenatal Bartter syndrome had a lower renin ratio (P < 0.05) and a higher standard deviation score (SDS) for height (P < 0.05) than a previously studied group of patients with classical Bartter syndrome. CONCLUSIONS: Patients with Bartter syndrome type I and II tend to present a satisfactory prognosis after a median follow-up of more than 10 years. Gallstones might represent a new complication of antenatal Bartter syndrome.

Diffusion-weighted MR imaging of the placenta in fetuses with placental insufficiency

PURPOSE: To evaluate diffusion-weighted magnetic resonance (MR) imaging of the human placenta in fetuses with and fetuses without intrauterine growth restriction (IUGR) who were suspected of having placental insufficiency. MATERIALS AND METHODS: The study was approved by the local ethics committee, and written informed consent was obtained. The authors retrospectively evaluated 1.5-T fetal MR images from 102 singleton pregnancies (mean gestation ± standard deviation, 29 weeks ± 5; range, 21-41 weeks). Morphologic and diffusion-weighted MR imaging were performed. A region of interest analysis of the apparent diffusion coefficient (ADC) of the placenta was independently performed by two observers who were blinded to clinical data and outcome. Placental insufficiency was diagnosed if flattening of the growth curve was detected at obstetric ultrasonography (US), if the birth weight was in the 10th percentile or less, or if fetal weight estimated with US was below the 10th percentile. Abnormal findings at Doppler US of the umbilical artery and histopathologic examination of specimens from the placenta were recorded. The ADCs in fetuses with placental insufficiency were compared with those in fetuses of the same gestational age without placental insufficiency and tested for normal distribution. The t tests and Pearson correlation coefficients were used to compare these results at 5% levels of significance. RESULTS: Thirty-three of the 102 pregnancies were ultimately categorized as having an insufficient placenta. MR imaging depicted morphologic changes (eg, infarction or bleeding) in 27 fetuses. Placental dysfunction was suspected in 33 fetuses at diffusion-weighted imaging (mean ADC, 146.4 sec/mm(2) ± 10.63 for fetuses with placental insufficiency vs 177.1 sec/mm(2) ± 18.90 for fetuses without placental insufficiency; P < .01, with one false-positive case). The use of diffusion-weighted imaging in addition to US increased sensitivity for the detection of placental insufficiency from 73% to 100%, increased accuracy from 91% to 99%, and preserved specificity at 99%. CONCLUSION: Placental dysfunction associated with growth restriction is associated with restricted diffusion and reduced ADC. A decreased ADC used as an early marker of placental damage might be indicative of pregnancy complications such as IUGR.

Addition of bevacizumab to chemotherapy in acute myeloid leukemia at older age: a randomized phase 2 trial of the Dutch-Belgian Cooperative Trial Group for Hemato-Oncology (HOVON) and the Swiss Group for Clinical Cancer Research (SAKK)

An urgent need for new treatment modalities is emerging in elderly patients with acute myeloid leukemia (AML). We hypothesized that targeting VEGF might furnish an effective treatment modality in this population. Elderly patients with AML were randomly assigned in this phase 2 study (n = 171) to receive standard chemotherapy (3 + 7) with or without bevacizumab at a dose of 10 mg/kg intravenously at days 1 and 15. In the second cycle, patients received cytarabine 1000 mg/m(2) twice daily on days 1-6 with or without bevacizumab. The complete remission rates in the 2 arms were not different (65%). Event-free survival at 12 months was 33% for the standard arm versus 30% for the bevacizumab arm; at 24 months, it was 22% and 16%, respectively (P = .42). The frequencies of severe adverse events (SAEs) were higher in the bevacizumab arm (n = 63) compared with the control arm (n = 28; P = .043), but the percentages of death or life-threatening SAEs were lower in the bevacizumab arm (60% vs 75% of SAEs). The results of the present study show that the addition of bevacizumab to standard chemotherapy does not improve the therapeutic outcome of older AML patients. This trial is registered as number NTR904 in The Nederlands Trial Register (www.trialregister.nl).

Frequency and predictors of hyperkalemia in patients ≥60 years of age with heart failure undergoing intense medical therapy

Hyperkalemia is a concern in heart failure (HF), especially in older patients with co-morbidities. Previous studies addressing this issue have focused mainly on younger patients. This study was aimed at determining the frequency and predictors of hyperkalemia in older patients with HF undergoing intense medical therapy. Frequency and predictors of hyperkalemia were defined in patients (n = 566) participating in the Trial of Intensified versus Standard Medical Therapy in Elderly Patients with Congestive Heart Failure, in which patients ≥60 years of age were randomized to a standard versus an intensified N-terminal brain natriuretic peptide-guided HF therapy. During an 18-month follow-up 76 patients (13.4%) had hyperkalemia (≥5.5 mmol/L) and 28 (4.9%) had severe hyperkalemia (≥6.0 mmol/L). Higher baseline serum potassium (odds ratio [OR] 2.92 per mmol/L), baseline creatinine (OR 1.11 per 10 μmol/L), gout (OR 2.56), New York Heart Association (NYHA) class (compared to NYHA class II, IV OR 3.08), higher dosage of spironolactone at baseline (OR 1.20 per 12.5 mg/day), and higher dose changes of spironolactone (compared to no dose change: 12.5 mg, OR 1.45; 25 mg, OR 2.52; >25 mg, OR 3.24) were independent predictors for development of hyperkalemia (p <0.05 for all comparisons). In conclusion, hyperkalemia is common in patients ≥60 years of age with HF undergoing intense medical therapy. Risk is increased in patients treated with spironolactone, in addition to patient-specific risk factors such as chronic kidney disease, higher serum potassium, advanced NYHA class, and gout. Careful surveillance of serum potassium and cautious use of spironolactone in patients at risk may help to decrease the incidence of potentially hazardous complications caused by hyperkalemia.

Comparison of contrast-enhanced multi-station MR angiography and digital subtraction angiography of the lower extremity arterial disease

PURPOSE: To compare diagnostic accuracy of multi-station, high-spatial resolution contrast-enhanced MR angiography (CE-MRA) of the lower extremities with digital subtraction angiography (DSA) as the reference standard in patients with symptomatic peripheral arterial occlusive disease. MATERIALS AND METHODS: Of 485 consecutive patients undergoing a run-off CE-MRA, 152 patients (86 male, 66 female; mean age, 71.6 years) with suspected peripheral arterial occlusive disease were included into our Institutional Review Board approved study. All patients underwent MRA and DSA of the lower extremities within 30 days. MRA was performed at 1.5 Tesla with a single bolus of 0.1 mmol/kg body weight of gadobutrol administered at a rate of 2.0 mL/s at three stations. Two readers evaluated the MRA images independently for stenosis grade and image quality. Sensitivity and specificity were derived. RESULTS: Sensitivity and specificity ranged from 73% to 93% and 64% to 89% and were highest in the thigh area. Both readers showed comparable results. Evaluation of good and better quality MRAs resulted in a considerable improvement in diagnostic accuracy. CONCLUSION: Contrast-enhanced MRA demonstrates good sensitivity and specificity in the investigation of the vasculature of the lower extremities. While a minor investigator experience dependence remains, it is standardizable and shows good inter-observer agreement. Our results confirm that the administration of Gadobutrol at a standard dose of 0.1 mmol/kg for contrast-enhanced runoff MRA is able to detect hemodynamically relevant stenoses. Use of contrast-enhanced MRA as an alternative to intra-arterial DSA in the evaluation and therapeutic planning of patients with suspected peripheral arterial occlusive disease is well justified. J. Magn. Reson. Imaging 2013;37:1427-1435. © 2012 Wiley Periodicals, Inc.

Outcome at two years of age in a Swiss national cohort of extremely preterm infants born between 2000 and 2008

Background While survival rates of extremely preterm infants have improved over the last decades, the incidence of neurodevelopmental disability (ND) in survivors remains high. Representative current data on the severity of disability and of risk factors associated with poor outcome in this growing population are necessary for clinical guidance and parent counselling. Methods Prospective longitudinal multicentre cohort study of preterm infants born in Switzerland between 240/7 and 276/7 weeks gestational age during 2000–2008. Mortality, adverse outcome (death or severe ND) at two years, and predictors for poor outcome were analysed using multilevel multivariate logistic regression. Neurodevelopment was assessed using Bayley Scales of Infant Development II. Cerebral palsy was graded after the Gross Motor Function Classification System. Results Of 1266 live born infants, 422 (33%) died. Follow-up information was available for 684 (81%) survivors: 440 (64%) showed favourable outcome, 166 (24%) moderate ND, and 78 (11%) severe ND. At birth, lower gestational age, intrauterine growth restriction and absence of antenatal corticosteroids were associated with mortality and adverse outcome (p < 0.001). At 360/7 weeks postmenstrual age, bronchopulmonary dysplasia, major brain injury and retinopathy of prematurity were the main predictors for adverse outcome (p < 0.05). Survival without moderate or severe ND increased from 27% to 39% during the observation period (p = 0.02). Conclusions In this recent Swiss national cohort study of extremely preterm infants, neonatal mortality was determined by gestational age, birth weight, and antenatal corticosteroids while neurodevelopmental outcome was determined by the major neonatal morbidities. We observed an increase of survival without moderate or severe disability.

Percutaneous endoscopic gastrostomy in children on peritoneal dialysis

OBJECTIVE: Insertion of percutaneous endoscopic gastrostomies (PEG) in patients on chronic peritoneal dialysis (PD) has been reported to be contraindicated due to an increased risk of morbidity and mortality. However, no systematic survey on this topic has yet been published. DESIGN: Retrospective multicenter study. SETTING: 23 pediatric dialysis units associated with the working group Arbeitsgemeinschaft für Pädiatrische Nephrologie (APN). DATA SOURCE: A structured questionnaire on clinical details of PD patients who had undergone PEG insertion or open gastrostomy (OG) since 1994 was distributed to all pediatric dialysis units of the APN. RESULTS: 27 PD patients (20 males) from 12 centers in whom PEG insertion was performed after Tenckhoff catheter introduction were evaluated. Age at intervention ranged from 0.25 to 10.9 years (median 1.3 years). Most patients were malnourished, with standard deviation score (SDS) for body weight between -4.2 and -0.6 (median -2.2). Major complications were early peritonitis < 7 days after PEG in 10/27 (37%) patients, episodes of fungal peritonitis in 7/27 (26%) patients, 4 cessations of PD and change to hemodialysis, and 2 associated deaths. However, in 14 patients, no such problems were encountered and, in 4 patients, early peritonitis effectively treated with intraperitoneal antibiotics was the only major complication. Thus, in 18/27 (67%) patients, PD was successfully reinitiated shortly after PEG insertion. Among all participating centers, only two OG procedures were reported during the study period, illustrating a clear preference for the PEG over the OG procedure among members of the APN. CONCLUSION: PEG insertion following PD initiation carries a high risk for fungal peritonitis and potential PD failure; however, complication rates in this largest reported series were lower than previously described. Antibiotic and antifungal prophylaxis, withholding PD for 2 - 3 days, and gastrostomy placement by an experienced endoscopy team are suggested precautions for lowering the risk of associated complications. When gastrostomy placement does not occur prior to or at the time of initiating PD, the risks and benefits of percutaneous versus open placement must be carefully weighed.