Radiation Therapy as an Alternative Treatment for Desmoid Fibromatosis.

AIM: To determine the outcome after radiation therapy for desmoid fibromatosis. MATERIALS AND METHODS: A retrospective review of 50 patients treated between 1988 and 2016 in a specialised bone and soft tissue tumour clinic. RESULTS: The median age at the time of radiation therapy was 36.8 years (range 15.1-69.0) and the median follow-up time was 51 months. Forty-three patients underwent radiation therapy as the definitive treatment with a median dose of 56 Gy (range 30-58.8 Gy). The median dose for the seven patients treated with postoperative radiation therapy was 50.4 Gy (range 48-56 Gy). Eleven patients (22%) developed progressive disease after radiation therapy at a median time of 41 months (range 12-113 months). The recurrences were within the radiation therapy field in four patients and outside the field in seven patients. One patient developed a radiation-induced malignancy 20 years after treatment. CONCLUSIONS: Radiation therapy is an alternative treatment in the management of desmoid fibromatosis. It should be considered in patients for whom surgical resection is not feasible, or as adjuvant therapy after surgery with involved margins where any further recurrences would cause significant morbidity.

Prebiotic-supplemented partially hydrolysed cow's milk formula for the prevention of eczema in high-risk infants: a randomized controlled trial.

BACKGROUND: Prevention guidelines for infants at high risk of allergic disease recommend hydrolysed formula if formula is introduced before 6 months, but evidence is mixed. Adding specific oligosaccharides may improve outcomes. OBJECTIVE: To evaluate whether partially hydrolysed whey formula containing oligosaccharides (0.8 g/100 ml) (pHF-OS) can prevent eczema in high-risk infants [ISRCTN65195597]. METHODS: We conducted a parallel-group, multicentre, randomized double-blind controlled trial of pHF-OS vs standard cow's milk formula. Infants with a family history of allergic disease were randomized (stratified by centre/maternal allergy) to active (n = 432) or control (n = 431) formula until 6 months of age if formula was introduced before 18 weeks. Primary outcome was cumulative incidence of eczema by 12 months in infants randomized at 0-4 weeks (375 pHF-OS, 383 control). Secondary outcomes were cumulative incidence of eczema by 12 or 18 months in all infants randomized, immune markers at 6 months and adverse events. RESULTS: Eczema occurred by 12 months in 84/293 (28.7%) infants allocated to pHF-OS at 0-4 weeks of age, vs 93/324 (28.7%) control (OR 0.98 95% CI 0.68, 1.40; P = 0.90), and 107/347 (30.8%) pHF-OS vs 112/370 (30.3%) control in all infants randomized (OR 0.99 95% CI 0.71, 1.37; P = 0.94). pHF-OS did not change most immune markers including total/specific IgE; however, pHF-OS reduced cow's milk-specific IgG1 (P < 0.0001) and increased regulatory T-cell and plasmacytoid dendritic cell percentages. There was no group difference in adverse events. CONCLUSION: pHF-OS does not prevent eczema in the first year in high-risk infants. The immunological changes found require confirmation in a separate cohort.

Exposures influencing total IgA level in colostrum.

Immunoglobulin A (IgA) is a predominant immunoglobulin present in human breast milk and is known to play an important role in infant gut immunity maturation. Breast milk composition varies between populations, but the environmental and maternal factors responsible for these variations are still unclear. We examined the relationship between different exposures and levels of IgA in colostrum. The objective of this study was to examine whether exposures analysed influence levels of IgA in colostrum. The present study used 294 colostrum samples from the MecMilk International cohort, collected from women residing in London, Moscow and Verona. Samples were analysed in automated Abbott Architect Analyser. We found an inverse correlation between time postpartum and colostrum total IgA level (r=-0.49, P<0.001). Adjusting for maternal parity, smoking, fresh fruit and fish consumption and allergen sensitization, multiple regression model showed that IgA levels were influenced by colostrum collection time (P<0.0001) and country of collection (P<0.01). Mode of delivery influence did not appear to be significant in univariate comparisons, once adjusted for the above maternal characteristics it showed a significant influence on total IgA (P=0.01). We conclude that the concentration of IgA in colostrum drops rapidly after birth and future studies should always consider this factor in analysis. IgA concentration varied significantly between countries, with the highest level detected in Moscow and lowest in Verona. Mode of delivery effect should be confirmed on larger cohorts. Further work is needed to determine ways to correct for IgA decline over time in colostrum, and to find the cause of variations in IgA levels between the countries.

Factors affecting breast milk composition and potential consequences for development of the allergic phenotype.

There is conflicting evidence on the protective role of breastfeeding in relation to allergic sensitization and disease. The factors in breast milk which influence these processes are still unclear and under investigation. We know that colostrum and breast milk contain a variety of molecules which can influence immune responses in the gut-associated lymphoid tissue of a neonate. This review summarizes the evidence that variations in colostrum and breast milk composition can influence allergic outcomes in the infant, and the evidence that maternal and environmental factors can modify milk composition. Taken together, the data presented support the possibility that maternal dietary interventions may be an effective way to promote infant health through modification of breast milk composition.

Nitrogen cycle feedbacks as a control on euxinia in the mid-Proterozoic ocean.

Geochemical evidence invokes anoxic deep oceans until the terminal Neoproterozoic ~0.55 Ma, despite oxygenation of Earth's atmosphere nearly 2 Gyr earlier. Marine sediments from the intervening period suggest predominantly ferruginous (anoxic Fe(II)-rich) waters, interspersed with euxinia (anoxic H(2)S-rich conditions) along productive continental margins. Today, sustained biotic H(2)S production requires NO(3)(-) depletion because denitrifiers outcompete sulphate reducers. Thus, euxinia is rare, only occurring concurrently with (steady state) organic carbon availability when N(2)-fixers dominate the production in the photic zone. Here we use a simple box model of a generic Proterozoic coastal upwelling zone to show how these feedbacks caused the mid-Proterozoic ocean to exhibit a spatial/temporal separation between two states: photic zone NO(3)(-) with denitrification in lower anoxic waters, and N(2)-fixation-driven production overlying euxinia. Interchange between these states likely explains the varying H(2)S concentration implied by existing data, which persisted until the Neoproterozoic oxygenation event gave rise to modern marine biogeochemistry.

A systematic review of the clinical effectiveness and cost-effectiveness of Pharmalgen® for the treatment of bee and wasp venom allergy.

BACKGROUND: Each year in the UK, there are between two and nine deaths from anaphylaxis caused by bee and wasp venom. Anaphylactic reactions can occur rapidly following a sting and can progress to a life-threatening condition within minutes. To avoid further reactions in people with a history of anaphylaxis to bee and wasp venom, the use of desensitisation, through a process known as venom immunotherapy (VIT), has been investigated and is in use in the UK. VIT consists of subcutaneous injections of increasing amounts of purified bee and/or wasp venom extract. Pharmalgen® products (ALK Abelló) have had UK marketing authorisation for VIT (as well as diagnosis) of allergy to bee venom (using Pharmalgen Bee Venom) and wasp venom (using Pharmalgen Wasp Venom) since March 1995. OBJECTIVE: This review assessed the clinical effectiveness and cost-effectiveness of Pharmalgen in providing immunotherapy to individuals with a history of type 1 [immunoglobulin E (IgE)-mediated] systemic allergic reaction to bee and wasp venom. DATA SOURCES: A comprehensive search strategy using a combination of index terms (e.g. Pharmalgen) and free-text words (e.g. allerg$) was developed and used to interrogate the following electronic databases: EMBASE, MEDLINE, The Cochrane Library. REVIEW METHODS: Papers were included if they studied venom immunotherapy using Pharmalgen (PhVIT) in patients who had previously experienced a systemic reaction to a bee and/or a wasp sting. Comparators were any alternative treatment options available in the NHS without VIT. Included outcomes were systemic reactions, local reactions, mortality, anxiety related to the possibility of future allergic reactions, health-related quality of life (QoL) and adverse reactions (ARs) to treatment. Cost-effectiveness outcomes included cost per quality-adjusted life-years (QALYs) gained. Because of the small number of published randomised controlled trials (RCTs), no meta-analyses were conducted. A de novo economic model was developed to assess the cost-effectiveness of PhVIT plus high-dose antihistamine (HDA) plus adrenaline auto-injector (AAI) plus avoidance advice in relation to two comparators. RESULTS: A total of 1065 citations were identified, of which 266 full-text papers were obtained. No studies were identified that compared PhVIT with any of the outlined comparators. When these criteria were widened to include different protocols and types of PhVIT administration, four RCTs and five quasi-experimental studies were identified for inclusion. The quality of included studies was poor, and none was conducted in the UK. Eight studies reported re-sting data (systemic reactions ranged from 0.0% to 36.4%) and ARs (systemic reactions ranged from 0.0% to 38.1% and none was fatal). No included studies reported quality of life. No published economic evidence relevant to the decision problem was identified. The manufacturer of PhVIT did not submit any clinical effectiveness or cost-effectiveness evidence to the National Institute for Health and Clinical Excellence in support of PhVIT. The results of the Assessment Group's (AG) base-case analysis show that the comparison of PhVIT + HDA + AAI versus AAI + HDA yields an incremental cost-effectiveness ratio (ICER) of £18,065,527 per QALY gained; PhVIT + HDA + AAI versus avoidance advice only yields an ICER of £7,627,835 per QALY gained. The results of the sensitivity analyses and scenario analyses showed that the results of the base-case economic evaluation were robust for every plausible change in parameter made. The results of the 'High Risk of Sting Patients' subgroup analysis show that PhVIT + HDA + AAI dominates both AAI + HDA and avoidance advice only (i.e. is less expensive and more effective). The 'VIT Anxiety QoL Improvement' subgroup analysis shows that PhVIT + HDA + AAI versus HDA + AAI has an ICER of £23,868 per QALY gained, and PhVIT + HDA + AAI versus avoidance advice only yields an ICER of £25,661 per QALY gained. LIMITATIONS: This review is limited to the use of Pharmalgen in the treatment of hymenoptera venom allergy and therefore does not assess the effectiveness of VIT in general. CONCLUSIONS: The current use of PhVIT in clinical practice in the NHS appears to be based on limited and poor-quality clinical effectiveness research. Available evidence indicates that sting reactions following the use of PhVIT are low and that the ARs related to treatment are minor and easily treatable. The results of the AG's de novo economic evaluation demonstrate that PhVIT + AAI + HDA compared with AAI + HDA and with avoidance advice only yields ICERs in the range of £8-20M per QALY gained. Two subgroups ('High Risk of Sting Patients' and 'VIT Anxiety QoL Improvement') were considered in the economic evaluation and the AG concludes that the use of PhVIT + AAI + HDA may be cost-effective in both groups. Future research should focus on clearly identifying groups of patients most likely to benefit from treatment and ensure that clinical practice is focussed on these groups. Furthermore, given the paucity of UK data in this area it would be informative if data could be collected routinely when VIT is administered in the NHS (e.g. rates of systemic adverse reactions to VIT, rates of systemic reactions to bee/wasp stings). FUNDING: The National Institute for Health Research Health Technology Assessment programme.

Essential fatty acids and phospholipase A2 in autistic spectrum disorders.

A health questionnaire based on parental observations of clinical signs of fatty acid deficiency (FAD) showed that patients with autism and Asperger's syndrome (ASP) had significantly higher FAD scores (6.34+/-4.37 and 7.64+/-6.20, respectively) compared to controls (1.78+/-1.68). Patients with regressive autism had significantly higher percentages of 18:0,18:2n-6 and total saturates in their RBC membranes compared to controls, while 24:0, 22:5n-6, 24:1 and the 20:4n-6/20:5n-3 ratio were significantly higher in both regressive autism and ASP groups compared to controls. By comparison, the 18:1n-9 and 20:4n-6 values were significantly lower in patients with regressive autism compared to controls while 22:5n-3, total n-3 and total dimethyl acetals were significantly lower in both regressive autism and ASP groups compared to controls. Storage of RBC at -20 degrees C for 6 weeks resulted in significant reductions in highly unsaturated fatty acid levels in polar lipids of patients with regressive autism, compared to patients with classical autism or ASP, or controls. Patients diagnosed with both autism and ASP showed significantly increased levels of EPA ( approximately 200%) and DHA ( approximately 40%), and significantly reduced levels of ARA ( approximately 20%), 20:3n-6 and ARA/EPA ratio in their RBC polar lipids, when supplemented with EPA-rich fish oils, compared to controls and non-supplemented patients with autism. Patients with both regressive autism and classical autism/Asperger's syndrome had significantly higher concentrations of RBC type IV phospholipase A2 compared to controls. However, patients with autism/ASP, who had taken EPA supplements, had significantly reduced PLA2 concentrations compared to unsupplemented patients with classical autism or ASP.

A randomised controlled trial of a self-management plan for patients with newly diagnosed angina.

BACKGROUND: There are approximately 1.8 million patients with angina in the United Kingdom, many of whom report a poor quality of life, including raised levels of anxiety and depression. AIM: To evaluate the effect of a cognitive behavioural disease management programme, the Angina Plan, on psychological adjustment in patients newly diagnosed with angina pectoris. DESIGN OF STUDY: Randomised controlled trial. SETTING: Patients from GP practices in a Northern UK city (York) between April 1999 and May 2000. METHOD: Recruited patients were randomised to receive the Angina Plan or to a routine, practice nurse-led secondary prevention educational session. RESULTS: Twenty of the 25 practices invited to join the study supplied patients' names; 142 patients attended an assessment clinic and were randomised There were no significant differences in any baseline measures. At the six month post-treatment follow-up, 130 (91%) patients were reassessed. When compared with the educational session patients (using analysis of covariance adjusted for baseline scores in an intention-to-treat analysis) Angina Plan patients showed a greater reduction in anxiety (P = 0.05) and depression (P = 0.01), the frequency of angina (reduced by three episodes per week, versus a reduction of 0.4 per week, P = 0.016) the use of glyceryl trinitrate (reduced by 4.19 fewer doses per week versus a reduction of 0.59 per week, P = 0.018), and physical limitations (P<0.001: Seattle Angina Questionnaire). They were also more likely to report having changed their diet (41 versus 21, P<0.001) and increased their daily walking (30 versus 2, P<0.001). There was no significant difference between the groups on the other sub-scales of the Seattle Angina Questionnaire or in any of the medical variables measured. CONCLUSION: The Angina Plan appears to improve the psychological, symptomatic, and functional status of patients newly diagnosed with angina.

Lipiodol avidity of hepatic breast carcinoma metastases.

Lipiodol is taken up by hepatocellular carcinomas and is used for diagnosis and therapy. This is the first report of lipiodol uptake by liver metastases from breast cancer.

Fluconazole prophylaxis against fungal colonization and infection in preterm infants.

BACKGROUND: Invasive fungal infection is associated with substantial morbidity and mortality in preterm infants. We evaluated the efficacy of prophylactic fluconazole in preventing fungal colonization and invasive infection in extremely-low-birth-weight infants. METHODS: We conducted a prospective, randomized, double-blind clinical trial over a 30-month period in 100 preterm infants with birth weights of less than 1000 g. The infants were randomly assigned during the first five days of life to receive either intravenous fluconazole or placebo for six weeks. We obtained weekly surveillance cultures from all patients. RESULTS: The 50 infants randomly assigned to fluconazole and the 50 control infants were similar in terms of birth weight, gestational age at birth, and base-line risk factors for fungal infection. During the six-week treatment period, fungal colonization was documented in 30 infants in the placebo group (60 percent) and 11 infants in the fluconazole group (22 percent; difference in risk, 0.38; 95 percent confidence interval, 0.18 to 0.56; P=0.002). Invasive fungal infection with positive growth of fungal isolates from the blood, urine, or cerebrospinal fluid developed in 10 infants in the placebo group (20 percent) and none of the infants in the fluconazole group (difference in risk, 0.20; 95 percent confidence interval, 0.04 to 0.36; P=0.008). The sensitivities of the fungal isolates to fluconazole did not change during the study, and no adverse effects of the fluconazole therapy were documented. CONCLUSIONS: Prophylactic administration of fluconazole during the first six weeks of life is effective in preventing fungal colonization and invasive fungal infection in infants with birth weights of less than 1000 g.