Systematic Review of the Effectiveness of Lumbar Medial Branch Thermal Radiofrequency Neurotomy, Stratified for Diagnostic Methods and Procedural Technique.

OBJECTIVE: To determine the effectiveness of lumbar medial branch thermal radiofrequency neurotomy based on different selection criteria and procedural techniques. DESIGN: Comprehensive systematic review. METHODS: A comprehensive literature search was conducted, and all authors screened and evaluated the studies. The Grades of Recommendation, Assessment, Development, and Evaluation system was used to assess all eligible studies. OUTCOME MEASURES: The primary outcome measure assessed was the success rate of the procedure, defined by varying degrees of pain relief following neurotomy. Data are stratified by number of diagnostic blocks and degree of pain relief, as well as procedural technique with perpendicular or parallel placement of electrodes. RESULTS: Results varied by selection criteria and procedural technique. At six months, 26% of patients selected via single medial branch block with 50% pain relief and treated via perpendicular technique achieved at least 50% pain relief; 49% of patients selected via dual medial branch blocks with 50% pain relief and treated via parallel technique achieved at least 50% pain relief. The most rigorous patient selection and technique-two diagnostic medial branch blocks with 100% pain relief and parallel electrode placement-resulted in 56% of patients experiencing 100% relief of pain at six months. CONCLUSIONS: This comprehensive systematic review found differences in the effectiveness of lumbar medial branch radiofrequency neurotomy when studies were stratified by patient selection criteria and procedural technique. The best outcomes are achieved when patients are selected based on high degrees of pain relief from dual medial branch blocks with a technique employing parallel electrode placement.

Description of the SAGhE Cohort: A Large European Study of Mortality and Cancer Incidence Risks after Childhood Treatment with Recombinant Growth Hormone.

BACKGROUND: The long-term safety of growth hormone treatment is uncertain. Raised risks of death and certain cancers have been reported inconsistently, based on limited data or short-term follow-up by pharmaceutical companies. PATIENTS AND METHODS: The SAGhE (Safety and Appropriateness of Growth Hormone Treatments in Europe) study assembled cohorts of patients treated in childhood with recombinant human growth hormone (r-hGH) in 8 European countries since the first use of this treatment in 1984 and followed them for cause-specific mortality and cancer incidence. Expected rates were obtained from national and local general population data. The cohort consisted of 24,232 patients, most commonly treated for isolated growth failure (53%), Turner syndrome (13%) and growth hormone deficiency linked to neoplasia (12%). This paper describes in detail the study design, methods and data collection and discusses the strengths, biases and weaknesses consequent on this. CONCLUSION: The SAGhE cohort is the largest and longest follow-up cohort study of growth hormone-treated patients with follow-up and analysis independent of industry. It forms a major resource for investigating cancer and mortality risks in r-hGH patients. The interpretation of SAGhE results, however, will need to take account of the methods of cohort assembly and follow-up in each country.

A novel homozygous mutation of the IGFALS gene in a female adolescent: indirect evidence for a contributing role of the circulating IGF-I pool in the pubertal growth spurt.

BACKGROUND: Mutations of the IGFALS gene have been reported since 2004 in 24 patients, but only 5 of these are females. CASE REPORT: We describe a 14.7-year-old female of a consanguineous Moroccan family with growth retardation and normal-onset but slow progression of puberty without manifest pubertal height gain. RESULTS: At age 3.2 years, the patient's height was 85.5 cm (-2.9 SDS) and her weight 9.9 kg (-2.9 SDS) with a head circumference of 44.5 cm (-3.3 SDS). Serum IGF-I and IGFBP-3 concentrations were low with normal basal and stimulated growth hormone (GH) levels. An IGF-I generation test confirmed a lack of response to GH administration. While onset of puberty occurred at a normal age, no significant pubertal growth acceleration was observed despite progression of breast development. Sequencing of the IGFALS gene revealed a novel homozygous frameshift mutation (c.1291delT) with a stop codon (p.W431GfsX10) leading to undetectable serum levels of acid-labile subunit. CONCLUSION: We report the phenotype of an adolescent girl with primary IGF-I deficiency due to a novel homozygous mutation of the IGFALS gene, who presented with growth delay, normal pubertal onset with slow progression and no pubertal growth acceleration indirectly suggesting a contributing role of the circulating IGF-I pool in the pubertal growth spurt.

Insulin sensitivity modulates the growth response during the first year of high-dose growth hormone treatment in short prepubertal children born small for gestational age.

AIM: To study the relationship between insulin sensitivity and growth response in short children born small for gestational age (SGA) treated with growth hormone (GH). METHODS: Randomized, open-label, 24-month intervention study in 40 short prepubertal SGA children [age (mean ± SD) 5.3 ± 1.5 years], who either remained untreated (n = 20) or were treated with GH (66 µg/kg/day; n = 20). Changes in fasting glucose, insulin, quantitative insulin sensitivity check index (QUICKI), IGF-1 and leptin after 1 and 2 years were studied. RESULTS: Mean height SDS increased from -3.3 ± 0.7 to -2.3 ± 0.7 after 1 year, and to -1.9 ± 0.7 after 2 years of treatment. QUICKI decreased significantly (p = 0.008) in the first year of GH treatment and stabilized in the second year. Baseline QUICKI was positively associated (r = 0.40; p < 0.05) with the change in height SDS in the first year. CONCLUSION: Higher insulin sensitivity at the start of GH therapy is associated with greater first-year growth response to GH, and could be a promising parameter in selecting prepubertal short SGA children for GH treatment. However, this finding needs to be confirmed in larger studies.

Long-term mortality and causes of death in isolated GHD, ISS, and SGA patients treated with recombinant growth hormone during childhood in Belgium, The Netherlands, and Sweden: preliminary report of 3 countries participating in the EU SAGhE study.

CONTEXT: The long-term mortality in adults treated with recombinant GH during childhood has been poorly investigated. Recently released data from the French part of the European Union Safety and Appropriateness of GH treatments in Europe (EU SAGhE) study have raised concerns on the long-term safety of GH treatment. OBJECTIVE: To report preliminary data on long-term vital status and causes of death in patients with isolated GH deficiency or idiopathic short stature or born small for gestational age treated with GH during childhood, in Belgium, The Netherlands, and Sweden. DESIGN: Data were retrieved from national registries of GH-treated patients and vital status from National Population Registries. Causes of death were retrieved from a National Cause of Death Register (Sweden), Federal and Regional Death Registries (Belgium), or individual patient records (The Netherlands). PATIENTS: All patients diagnosed with isolated GH deficiency or idiopathic short stature or born small for gestational age started on recombinant GH during childhood from 1985-1997 and who had attained 18 yr of age by the end of 2010 were included. Vital status was available for approximately 98% of these 2,543 patients, corresponding to 46,556 person-years of observation. MAIN OUTCOME MEASURE: Vital status, causes of death, age at death, year of death, duration of GH treatment, and mean GH dose during treatment were assessed. RESULTS: Among 21 deaths identified, 12 were due to accidents, four were suicides, and one patient each died from pneumonia, endocrine dysfunction, primary cardiomyopathy, deficiency of humoral immunity, and coagulation defect. CONCLUSIONS: In these cohorts, the majority of deaths (76%) were caused by accidents or suicides. Importantly, none of the patients died from cancer or from a cardiovascular disease.

Growth hormone treatment and fat redistribution in children born small for gestational age.

OBJECTIVE: To determine whether in children born small for gestational age (SGA) high-dose growth hormone (GH) treatment is not only associated with catch-up of growth and with gain of lean mass, but also with a more central fat distribution. STUDY DESIGN: Short children who were SGA (n = 25; age [mean +/- SD], 5.3 +/- 1.5 years) were randomly assigned to remain untreated (n = 14) or to receive GH (n = 11; sc 66 mug/Kg/d). Growth status and body composition were assessed at the study's start, after 1 year, and after 2 years with anthropometry and absorptiometry. RESULTS: Children who were treated with GH gained more height and weight than children who were untreated and developed a less adipose body composition (all P < .0001), as expected. However, these changes were also accompanied by a relatively more centripetal distribution of fat mass (0-2 year change in ratio of trunk fat to limb fat; 0.26 +/- 0.23 versus 0.02 +/- 0.15; P < .0001). CONCLUSION: In children who are SGA, catch-up growth induced by exogenous GH in high doses is accompanied by a less adipose body composition and a more central fat distribution.

Determinants of early atherosclerosis in obese children and adolescents.

CONTEXT: Obesity in childhood is associated with an increased mortality due to cardiovascular (CV) diseases in adulthood, independent of adult weight. Recent studies in children indicate that the atherosclerosis process starts at an early age and is linked to obesity. OBJECTIVE: The aim of the study was to investigate determinants of increased carotid intima-media thickness (IMT), an early marker of atherosclerosis, in obese children. DESIGN: A total of 104 obese children [age, 12.7 +/- 0.2 yr; body mass index (BMI)-z-score, 2.8 +/- 0.7] underwent an oral glucose tolerance test. Fasting levels of glucose, insulin, C-reactive protein and adhesion molecules (sICAM, sVCAM, sE-selectin), lipid profile, adiponectin, and resistin were determined. IMT was measured by ultrasound. Insulin resistance was estimated by the homeostatic model assessment index. Baseline measurements of blood parameters were obtained from 93 nonobese children (age, 13.0 +/- 0.2 yr; BMI-z-score, -0.2 +/- 0.9), and IMT was measured in 23 other control children with similar characteristics. RESULTS: Univariate analysis showed a significant positive correlation between IMT and relative BMI, the degree of systolic hypertension, fasting insulin levels, homeostatic model assessment-R index, and resistin concentrations, whereas an inverse correlation with adiponectin levels was found. No correlation was obtained between IMT and classical CV risk factors such as positive familial history of type 2 diabetes or precocious CV disease, visceral obesity, or the lipid profile. C-reactive protein and adhesion molecule levels were not associated with IMT in our obese population. When controlled for sex, Tanner stage, and relative BMI, only adiponectin levels remained an independent determinant of IMT. CONCLUSION: Adiponectin more than conventional CV risk factors and inflammation status may be related to early atherosclerosis in obese children.

Neonatal cholestatic jaundice as the first symptom of a mutation in the hepatocyte nuclear factor-1beta gene (HNF-1beta).

This report describes the phenotype of a novel de novo heterozygous frameshift mutation in the hepatocyte nuclear factor-1beta gene (HNF-1beta or TCF2) manifest as a neonatal paucity of intrahepatic bile ducts. HNF-1beta mutations should be considered in neonates with cholestatic jaundice associated with renal malformation or diabetes mellitus.

Techniques Used to Determine Extreme Wave Heights from the NESS Data Set.

The objective of the present paper is to explore the application of different extreme value procedures to a selected grid point in the NESS (North European Storm Study) data set. For the purpose of the present benchmark study, each of the participants was invited to submit estimates of a significant wave height with a high return period at a given grid point in the North Sea, together with a detailed description and a rationale of the approach used in deriving extreme wave heights. Submissions from five industry groups were received, compared, and benchmarked against one another. This analysis leads to a number of conclusions regarding the actual use and misuse of extreme value techniques in the fields of engineering and oceanography.