TreEAT trial: Protocol for a randomized controlled trial investigating the efficacy and safety of early introduction of tree nuts for the prevention of tree nut allergy in infants with peanut allergy.

INTRODUCTION: Children with peanut allergy are at increased risk of developing tree nut allergies, which can be severe and for most lifelong. Introduction of peanut in the first year of life can reduce the risk of peanut allergy; however, prevention strategies for tree nut allergies have not been established. We aimed to test the efficacy and safety of a novel strategy, a supervised multi-nut oral food challenge (OFC) compared with standard care for tree nut allergy prevention in infants at high risk of developing tree nut allergy, TreEAT. METHODS AND ANALYSIS: TreEAT is a 2-armed, open-label, randomized, controlled trial (RCT). Infants (n = 212) aged 4-11 months with peanut allergy will be randomized 1:1 at peanut allergy diagnosis to either a hospital-based multi-tree nut (almond, cashew, hazelnut, and walnut) OFC using multi-nut butter or standard care (home introduction of individual tree nuts). All infants will be assessed at age 18 months, with questionnaires and SPT to peanut and tree nuts. Peanut and tree nut OFCs will be performed as required to determine the allergy status for each nut. The primary outcome is tree nut allergy at age 18 months. Secondary outcomes include peanut allergy resolution, proportion, and severity of adverse events related to tree nut ingestion, number and frequency of tree nuts ingested, quality of life and parental anxiety, and allergy-related healthcare visits from randomization to 18 months of age. Analyses will be performed on an intention-to-treat basis. ETHICS AND DISSEMINATION: TreEAT was approved by the Royal Children's Hospital Human Research Ethics Committee (#70489). Outcomes will be presented at scientific conferences and disseminated through publication. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov ID: NCT04801823.

Effects of an Amino Acid-Based Formula Supplemented with Two Human Milk Oligosaccharides on Growth, Tolerability, Safety, and Gut Microbiome in Infants with Cow's Milk Protein Allergy.

This open-label, non-randomized, multicenter trial (Registration: NCT03661736) aimed to assess if an amino acid-based formula (AAF) supplemented with two human milk oligosaccharides (HMO) supports normal growth and is well tolerated in infants with a cow's milk protein allergy (CMPA). Term infants aged 1-8 months with moderate-to-severe CMPA were enrolled. The study formula was an AAF supplemented with 2'-fucosyllactose (2'-FL) and lacto-N-neotetraose (LNnT). Infants were fed the study formula for 4 months and were offered to remain on the formula until 12 months of age. Tolerance and safety were assessed throughout the trial. Out of 32 infants (mean age 18.6 weeks; 20 (62.5%) male), 29 completed the trial. During the 4-month principal study period, the mean weight-for-age Z score (WAZ) increased from -0.31 at the baseline to +0.28 at the 4-months' follow-up. Linear and head growth also progressed along the WHO child growth reference, with a similar small upward trend. The formula was well tolerated and had an excellent safety profile. When comparing the microbiome at the baseline to the subsequent visits, there was a significant on-treatment enrichment in HMO-utilizing bifidobacteria, which was associated with a significant increase in fecal short-chain fatty acids. In addition, we observed a significant reduction in the abundance of fecal Proteobacteria, suggesting that the HMO-supplemented study formula partially corrected the gut microbial dysbiosis in infants with CMPA.

Probiotic peanut oral immunotherapy versus oral immunotherapy and placebo in children with peanut allergy in Australia (PPOIT-003): a multicentre, randomised, phase 2b trial.

BACKGROUND: Oral immunotherapy is effective at inducing desensitisation to allergens and induces sustained unresponsiveness (ie, clinical remission) in a subset of patients, but causes frequent reactions. We aimed to investigate whether addition of a probiotic adjuvant improved the efficacy or safety of peanut oral immunotherapy. METHODS: PPOIT-003, a multicentre, randomised, phase 2b trial, was conducted in three tertiary hospitals in Australia (Adelaide [SA], Melbourne [VIC], and Perth [WA]) in children aged 1-10 years, weighing more than 7 kg, with peanut allergy confirmed by a double-blind placebo-controlled food challenge (cumulative 4950 mg dose of peanut protein) and positive peanut skin prick test (≥3 mm) or peanut-specific IgE (≥0·35 kU/L). Children were randomly assigned (2:2:1) to receive probiotic and peanut oral immunotherapy (PPOIT), placebo probiotic and peanut oral immunotherapy (OIT), or placebo probiotic and placebo OIT (placebo) for 18 months, and were followed up until 12 months after completion of treatment. Oral immunotherapy consisted of increasing doses of peanut protein (commercially available food-grade 12% defatted peanut flour [50% peanut protein]) until a 2000 mg daily maintenance dose was reached. The probiotic adjuvant was a daily dose of 2 × 1010 colony-forming units of the probiotic Lactobacillus rhamnosus ATCC 53103. Placebo immunotherapy comprised maltodextrin, brown food colouring, and peanut essence, and placebo probiotic was maltodextrin. Dual primary outcomes were 8-week sustained unresponsiveness, defined as no reaction to a cumulative dose of 4950 mg peanut protein at treatment completion and 8 weeks after treatment completion, in the PPOIT versus placebo groups and the PPOIT versus OIT groups, analysed by intention to treat. Safety endpoints were adverse events during the treatment phase, and peanut ingestion and reactions in the 12-month post-treatment period. This study is registered with the Australian New Zealand Clinical Trials Registry, 12616000322437. FINDINGS: Between July 4, 2016, and Sept 21, 2020, 201 participants were enrolled and included in the intention-to-treat analysis. 36 (46%) of 79 children in the PPOIT group and 42 (51%) of 83 children in the OIT group achieved sustained unresponsiveness compared with two (5%) of 39 children in the placebo group (risk difference 40·44% [95% CI 27·46 to 53·42] for PPOIT vs placebo, p<0·0001), with no difference between PPOIT and OIT (-5·03% [-20·40 to 10·34], p=0·52). Treatment-related adverse events were reported in 72 (91%) of 79 children in the PPOIT group, 73 (88%) of 83 children in the OIT group, and 28 (72%) of 39 children in the placebo group. Exposure-adjusted incidence of adverse events was 10·58 in the PPOIT group, 11·36 in the OIT, and 2·09 in the placebo group (ratio 0·92 [95% CI 0·85 to 0·99] for PPOIT vs OIT, p=0·042; 4·98 [4·11-6·03] for PPOIT vs placebo, p<0·0001; 5·42 [4·48-6·56] for OIT vs placebo, p<0·0001), with differences seen primarily in gastrointestinal symptoms and in children aged 1-5 years. During the 12-month post-treatment period, 60 (85%) of 71 participants in the PPOIT group, 60 (86%) of 70 participants in the OIT group, and six (18%) of 34 participants in the placebo group were eating peanut; rescue epinephrine use was infrequent (two [3%] of 71 in the PPOIT group, four [6%] of 70 in the OIT group, and none in the placebo group). INTERPRETATION: Both PPOIT and OIT were effective at inducing sustained unresponsiveness. Addition of a probiotic did not improve efficacy of OIT, but might offer a safety benefit compared with OIT alone, particularly in preschool children. FUNDING: National Health and Medical Research Council Australia and Prota Therapeutics.

Skin Prick Test Predictive Values for the Outcome of Cashew Challenges in Children.

BACKGROUND: Cashew is a common cause of tree nut allergy in children. To date there have been few studies of diagnostic tests for cashew allergy, and positive predictive values (PPVs) for cashew as well as other tree nuts are largely extrapolated from studies of peanut allergy. How relevant these cutoffs are for cashew has not been formally explored. OBJECTIVE: We aimed to establish skin prick test (SPT) wheal sizes that correlated to 95% PPV for a positive food challenge for cashew. METHODS: We included all cashew oral food challenges (OFCs) conducted as part of the HealthNuts (n = 108; age, 4-6 years) and SchoolNuts (n = 37; age, 10-14 years) studies, both recruited from the community (population cohort). A second cohort of all cashew OFCs conducted at the Royal Children's Hospital (RCH) allergy center (n = 343) (2011-2016) and a private allergy clinic based at RCH (n = 43) was included via electronic medical record review (clinic cohort). The 95% PPV for cashew SPT was calculated for both cohorts. RESULTS: Among the population cohort (n = 145), 62% of cashew OFCs were positive compared with 20% of the clinic cohort (n = 386). The SPT cutoff for 95% PPV derived from the population cohort was 10 mm (95% confidence interval [CI], 7.5-12.0). For the clinic cohort, the 95% PPV was 14 mm (95% CI, 9.5-unknown). An SPT wheal size of 8 mm had a PPV of 89% (95% CI, 79-95) in the population cohort and 62% (95% CI, 45-78) in the clinic cohort. CONCLUSION: A higher SPT wheal size may be more appropriate than the commonly used 8 mm cutoff to guide clinical decisions around when to perform OFC for cashew.

Patterns of Carriage of Prescribed Adrenaline Autoinjectors in 10- to 14-Year-Old Food-Allergic Students: A Population-Based Study.

BACKGROUND: Adolescence is well recognized as a period of increased risk for severe and fatal food-induced anaphylaxis. Current Australian adrenaline autoinjector (AAI) prescription guidelines therefore suggest that consideration be given to AAI prescription in all adolescents with a food allergy. To date, however, few studies have assessed the AAI carriage behavior of adolescents prescribed AAI devices. OBJECTIVE: To determine the carriage behavior of prescribed AAI devices in a population-based sample of young Australian adolescents. METHODS: Students aged 10 to 14 years (and their parents) from randomly selected schools in metropolitan Melbourne completed self-administered questionnaires regarding the history and management of food allergy, including prescription and carriage of AAI device in different domains of school and social life. RESULTS: A total of 9816 students completed the questionnaire (46% response): 620 students were assessed to have likely IgE-mediated food allergy and 234 (38%) of these had been prescribed an AAI. Most students (93%; 95% CI, 89%-96%) who were prescribed AAIs reported that they provided their AAI and anaphylaxis action plan to their school. Adherence to AAI carriage in other domains of social life was poor, with 49% (95% CI, 42%-56%) never carrying their AAI in 1 or more locations. Carriage of the AAI device was particularly poor when students were independent of parental supervision: 32% (95% CI, 25%-39%) never carried it when they were by themselves, 28% (95% CI, 22%-36%) never carried it while out with friends, and 36% (95% CI, 30%-43%) never carried their AAI to sporting activities. CONCLUSIONS: Carriage of AAI devices is suboptimal in young adolescents prescribed AAIs, particularly when young adolescents are independent of parental supervision.

Formula and breast feeding in infant food allergy: A population-based study.

AIM: To determine whether infant-feeding practices, including duration of exclusive breastfeeding and use of partially hydrolysed formula, modify the risk of developing infant food allergy. METHODS: In an observational population-based study, 1 year olds were recruited from community immunisation clinics in Melbourne, Australia. Parent-reported data on infant-feeding practices and potential confounders were collected prior to infant skin prick testing for four food allergens. Sensitised infants attended hospital-based oral food challenges to establish food allergy status. Multiple logistic regression was used to investigate associations between breastfeeding and formula-feeding and infant food allergy adjusting for possible confounding variables. RESULTS: A total of 5276 (74% response) infants participated. Of the 4537 for whom food allergy status was determined, 515 (11.3%) were food allergic (challenge-proven in the context of skin prick testing positive (≥2 mm)). After adjusting for confounding variables, there was no association between duration of exclusive breastfeeding and food allergy. Use of partially hydrolysed formula did not reduce the risk of food allergy compared with cow's milk formula in the general population (adjusted odds ratios 1.03 (confidence interval 0.67-1.50)). CONCLUSION: Duration of exclusive breastfeeding and use of partially hydrolysed formula were not associated with food allergy at 1 year of age in this large population-based study. These findings have implications for population-based infant-feeding guidelines and do not support the use of partially hydrolysed formula for food allergy prevention.

Administration of a probiotic with peanut oral immunotherapy: A randomized trial.

BACKGROUND: Coadministration of a bacterial adjuvant with oral immunotherapy (OIT) has been suggested as a potential treatment for food allergy. OBJECTIVE: To evaluate a combined therapy comprising a probiotic together with peanut OIT. METHODS: We performed a double-blind, placebo-controlled randomized trial of the probiotic Lactobacillus rhamnosus CGMCC 1.3724 and peanut OIT (probiotic and peanut oral immunotherapy [PPOIT]) in children (1-10 years) with peanut allergy. The primary outcome was induction of sustained unresponsiveness 2 to 5 weeks after discontinuation of treatment (referred to as possible sustained unresponsiveness). Secondary outcomes were desensitization, peanut skin prick test, and specific IgE and specific IgG4 measurements. RESULTS: Sixty-two children were randomized and stratified by age (≤5 and >5 years) and peanut skin test wheal size (≤10 and >10 mm); 56 reached the trial's end. Baseline demographics were similar across groups. Possible sustained unresponsiveness was achieved in 82.1% receiving PPOIT and 3.6% receiving placebo (P < .001). Nine children need to be treated for 7 to achieve sustained unresponsiveness (number needed to treat, 1.27; 95% CI, 1.06-1.59). Of the subjects, 89.7% receiving PPOIT and 7.1% receiving placebo were desensitized (P < .001). PPOIT was associated with reduced peanut skin prick test responses and peanut-specific IgE levels and increased peanut-specific IgG4 levels (all P < .001). PPOIT-treated participants reported a greater number of adverse events, mostly with maintenance home dosing. CONCLUSION: This is the first randomized placebo-controlled trial evaluating the novel coadministration of a probiotic and peanut OIT and assessing sustained unresponsiveness in children with peanut allergy. PPOIT was effective in inducing possible sustained unresponsiveness and immune changes that suggest modulation of the peanut-specific immune response. Further work is required to confirm sustained unresponsiveness after a longer period of secondary peanut elimination and to clarify the relative contributions of probiotics versus OIT.

The natural history and clinical predictors of egg allergy in the first 2 years of life: a prospective, population-based cohort study.

BACKGROUND: There is a paucity of data examining the natural history of and risk factors for egg allergy persistence, the most common IgE-mediated food allergy in infants. OBJECTIVE: We aimed to assess the natural history of egg allergy and identify clinical predictors for persistent egg allergy in a population-based cohort. METHODS: The HealthNuts study is a prospective, population-based cohort study of 5276 infants who underwent skin prick tests to 4 allergens, including egg. Infants with a detectable wheal were offered hospital-based oral food challenges (OFCs) to egg, irrespective of skin prick test wheal sizes. Infants with challenge-confirmed raw egg allergy were offered baked egg OFCs at age 1 year and follow-up at age 2 years, with repeat OFCs to raw egg. RESULTS: One hundred forty infants with challenge-confirmed egg allergy at age 1 year participated in the follow-up. Egg allergy resolved in 66 (47%) infants (95% CI, 37% to 56%) by 2 years of age; however, resolution was lower in children with baked egg allergy at age 1 year compared with baked egg tolerance (13% and 56%, respectively; adjusted odds ratio, 5.27; 95% CI, 1.36-20.50; P = .02). In the subgroup of infants who were tolerant to baked egg at age 1 year, frequent ingestion of baked egg (≥5 times per month) compared with infrequent ingestion (0-4 times per month) increased the likelihood of tolerance (adjusted odds ratio, 3.52; 95% CI, 1.38-8.98; P = .009). Mutation in the filaggrin gene was not associated with the resolution of either egg allergy or egg sensitization at age 2 years. CONCLUSION: Phenotyping of egg allergy (baked egg tolerant vs allergic) should be considered in the management of this allergy because it has prognostic implications and eases dietary restrictions. Randomized controlled trials for egg oral immunotherapy should consider stratifying at baseline by the baked egg subphenotype to account for the differential rate of tolerance development.

Vitamin D insufficiency is associated with challenge-proven food allergy in infants.

BACKGROUND: Epidemiological evidence has shown that pediatric food allergy is more prevalent in regions further from the equator, suggesting that vitamin D insufficiency may play a role in this disease. OBJECTIVE: To investigate the role of vitamin D status in infantile food allergy. METHODS: A population sample of 5276 one-year-old infants underwent skin prick testing to peanut, egg, sesame, and cow's milk or shrimp. All those with a detectable wheal and a random sample of participants with negative skin prick test results attended a hospital-based food challenge clinic. Blood samples were available for 577 infants (344 with challenge-proven food allergy, 74 sensitized but tolerant to food challenge, 159 negative on skin prick test and food challenge). Serum 25-hydroxyvitamin D levels were measured by using liquid chromatography tandem mass spectrometry. Associations between serum 25-hydroxyvitamin D and food allergy were examined by using multiple logistic regression, adjusting for potential risk and confounding factors. RESULTS: Infants of Australian-born parents, but not of parents born overseas, with vitamin D insufficiency (≤50 nmol/L) were more likely to be peanut (adjusted odds ratio [aOR], 11.51; 95% CI, 2.01-65.79; P=.006) and/or egg (aOR, 3.79; 95% CI, 1.19-12.08; P=.025) allergic than were those with adequate vitamin D levels independent of eczema status. Among those with Australian-born parents, infants with vitamin D insufficiency were more likely to have multiple food allergies (≥2) rather than a single food allergy (aOR, 10.48; 95% CI, 1.60-68.61 vs aOR, 1.82; 95% CI, 0.38-8.77, respectively). CONCLUSIONS: These results provide the first direct evidence that vitamin D sufficiency may be an important protective factor for food allergy in the first year of life.

Increasing the accuracy of peanut allergy diagnosis by using Ara h 2.

BACKGROUND: Measurement of whole peanut-specific IgE (sIgE) is often used to confirm sensitization but does not reliably predict allergy. Ara h 2 is the dominant peanut allergen detected in 90% to 100% of patients with peanut allergy and could help improve diagnosis. OBJECTIVES: We sought to determine whether Ara h 2 testing might improve the accuracy of diagnosing peanut allergy and therefore circumvent the need for an oral food challenge (OFC). METHODS: Infants from the population-based HealthNuts study underwent skin prick tests to determine peanut sensitization and subsequently underwent a peanut OFC to confirm allergy status. In a stratified random sample of 200 infants (100 with peanut allergy and 100 with peanut tolerance), whole peanut sIgE and Ara h 2 sIgE levels were quantified by using fluorescence enzyme immunoassay. RESULTS: By using the previously published 95% positive predictive value of 15 kU(A)/L for whole peanut sIgE, a corresponding specificity of 98% (95% CI, 93% to 100%) was found in this study cohort. At the equivalent specificity of 98%, the sensitivity of Ara h 2 sIgE is 60% (95% CI, 50% to 70%), correctly identifying 60% of subjects with true peanut allergy compared with only 26% correctly identified by using whole peanut sIgE. We report that when using a combined approach of plasma sIgE testing for whole peanut followed by Ara h 2 for the diagnosis of peanut allergy, the number of OFCs required is reduced by almost two thirds. CONCLUSION: Ara h 2 plasma sIgE test levels provide higher diagnostic accuracy than whole peanut plasma sIgE levels and could be considered a new diagnostic tool to distinguish peanut allergy from peanut tolerance, which might reduce the need for an OFC.

Can early introduction of egg prevent egg allergy in infants? A population-based study.

BACKGROUND: Infant feeding guidelines have long recommended delaying introduction of solids and allergenic foods to prevent allergy in high-risk infants, despite a paucity of evidence. OBJECTIVE: We aimed to determine whether confirmed egg allergy in 12-month-old infants is associated with (1) duration of breast-feeding and (2) ages of introducing egg and solids. METHODS: In a population-based cross-sectional study (HealthNuts) parents reported on infant feeding and potential confounding factors before skin prick testing for egg white. Egg-sensitized infants were then offered an egg oral food challenge. Multiple logistic regression was used to investigate associations between diet and egg allergy adjusted for possible confounding factors. RESULTS: A total of 2589 infants (73% response) participated. Compared with introduction at 4 to 6 months, introducing egg into the diet later was associated with higher risks of egg allergy (adjusted odds ratios [ORs], 1.6 [95% CI, 1.0-2.6] and 3.4 [95% CI, 1.8-6.5] for introduction at 10-12 and after 12 months, respectively). These findings persisted even in children without risk factors (OR, 3.3 [95% CI, 1.1-9.9]; 10-12 months). At age 4 to 6 months, first exposure as cooked egg reduced the risk of egg allergy compared with first exposure as egg in baked goods (OR, 0.2 [95% CI, 0.06-0.71]). Duration of breast-feeding and age at introduction of solids were not associated with egg allergy. CONCLUSIONS: Introduction of cooked egg at 4 to 6 months of age might protect against egg allergy. Changes in infant feeding guidelines could have a significant effect on childhood egg allergy and possibly food allergy more generally.

Stone forming risk factors in patients with type Ia glycogen storage disease.

PURPOSE: Patients with type Ia glycogen storage disease have an increased recurrent nephrolithiasis rate. We identified stone forming risk factors in patients with type Ia glycogen storage disease vs those in stone formers without the disease. MATERIALS AND METHODS: Patients with type Ia glycogen storage disease were prospectively enrolled from our metabolic clinic. Patient 24-hour urine parameters were compared to those in age and gender matched stone forming controls. RESULTS: We collected 24-hour urine samples from 13 patients with type Ia glycogen storage disease. Average +/- SD age was 27.0 +/- 13.0 years and 6 patients (46%) were male. Compared to age and gender matched hypocitraturic, stone forming controls patients had profound hypocitraturia (urinary citrate 70 vs 344 mg daily, p = 0.009). When comparing creatinine adjusted urinary values, patients had profound hypocitraturia (0.119 vs 0.291 mg/mg creatinine, p = 0.005) and higher oxalate (0.026 vs 0.021 mg/mg creatinine, p = 0.038) vs other stone formers. CONCLUSIONS: Patients with type Ia glycogen storage disease have profound hypocitraturia, as evidenced by 24-hour urine collections, even compared to other stone formers. This may be related to a recurrent nephrolithiasis rate greater than in the overall population. These findings may be used to support different treatment modalities, timing and/or doses to prevent urinary lithiasis in patients with type Ia glycogen storage disease.

Impact of long-term potassium citrate therapy on urinary profiles and recurrent stone formation.

PURPOSE: Potassium citrate therapy has become one of the cornerstones of medical stone management. We elucidated the long-term effects of potassium citrate on urinary metabolic profiles and its impact on stone formation rates. MATERIALS AND METHODS: We performed a retrospective cohort study in patients treated at the Comprehensive Kidney Stone Center at our institution between 2000 and 2006. Patients with pre-therapy and post-therapy 24-hour urinary profiles available who remained on potassium citrate for at least 6 months were included in the analysis. RESULTS: Of the 1,480 patients with 24-hour urinary profiles 503 met study inclusion criteria. Mean therapy duration was 41 months (range 6 to 168). Overall a significant and durable change in urinary metabolic profiles was noted as soon as 6 months after the onset of therapy. These changes included increased urinary pH (5.90 to 6.46, p <0.0001) and increased urinary citrate (470 to 700 mg a day, p <0.0001). The stone formation rate also significantly decreased after the initiation of potassium citrate from 1.89 to 0.46 stones per year (p <0.0001). There was a 68% remission rate and a 93% decrease in the stone formation rate. CONCLUSIONS: Potassium citrate provides a significant alkali and citraturic response during short-term and long-term therapy with the change in urinary metabolic profiles sustained as long as 14 years of treatment. Moreover, long-term potassium citrate significantly decreases the stone formation rate, confirming its usefulness in patients with recurrent nephrolithiasis.

Magnetic resonance imaging findings in a population-based cohort of children with cerebral palsy.

The purpose of this study was to investigate the frequency and spectrum of magnetic resonance imaging (MRI) abnormalities in a population of children with cerebral palsy (CP) who were born in the years 2000 and 2001 in Victoria, Australia. In 2000 and 2001, 221 children (126 males, 95 females; mean age 6y [SD 7mo], range 5-7y) with CP, excluding those with CP due to postneonatal causes (6% of all cases), were identified through the Victorian Cerebral Palsy Register. All medical records were systematically reviewed and all available brain imaging was comprehensively evaluated by a single senior MRI radiologist. MRI was available for 154 (70%) individuals and abnormalities were identified in 129 (84%). The study group comprised 88% with a spastic motor type CP; the distribution was hemiplegia in 33.5%, diplegia in 28.5%, and quadriplegia in 37.6% of children. Overall, pathological findings were most likely to be identified in children with spastic hemiplegia (92%) and spastic quadriplegia (84%). Abnormalities were less likely to be identified in non-spastic motor types (72%) and spastic diplegia (52%). The most common abnormalities identified on MRI were periventricular white matter injury (31%), focal ischaemic/haemorrhagic lesions (16%), diffuse encephalopathy (14%), and brain malformations (12%). Dual findings were seen in 3% of patients. This is the first study to document comprehensively the neuroimaging findings of all children identified with CP born over a consecutive 24-month period in a large geographical area.

Maternal pulmonary edema during fetoscopic surgery.

Minimally invasive fetal surgery uses small endoscopes placed percutaneously through the mother's abdominal wall in order to operate on a fetus, placenta or umbilical cord. We report a case of postoperative pulmonary edema in a mother who underwent minimally invasive fetal surgery for the treatment of twin reverse arterial perfusion sequence. The procedure involves ultrasound and fetoscopic guidance to interrupt umbilical vessel blood flow to one twin. Saline irrigation is used during the procedure to facilitate surgical exposure. We hypothesize that the pulmonary edema resulted from irrigating fluid (totaling net 8 L) absorbed i.v. through myometrial venous channels accessed by passage of the operating trocars.

Assessment of citrate concentrations in citrus fruit-based juices and beverages: implications for management of hypocitraturic nephrolithiasis.

BACKGROUND AND PURPOSE: Dietary intake of citrate in the form of citrus juices (eg, lemonade, orange juice) will enhance urinary citrate excretion, a valuable benefit for patients with hypocitraturic calcium oxalate nephrolithiasis. While information on citrate concentrations in select citrus juices is available, data on citrate concentrations of commercially available beverages (juice and otherwise) are limited. Using nuclear magnetic resonance spectroscopy (1H NMR), we report citrate concentrations of several beverages to help guide dietary recommendations aimed at increasing urinary citrate excretion and correcting hypocitraturia. METHODS: Citrate concentrations of a squeezed lemon, several fruit juices, and common beverages were measured using 1H NMR. Spectra for each sample were obtained in duplicate; citrate peak was identified, measured, and quantified and compared with the citrate concentration in the juice of 1 medium lemon. RESULTS: Quantitative analysis revealed the highest concentration of citrate was in grapefruit juice (64.7 mmol/L), followed in decreasing concentrations by lemon juice (47.66 mmol/L), orange juice (47.36 mmol/L), pineapple juice (41.57 mmol/L), reconstituted lemonade (38.65 mmol/L), lemonade flavored Crystal Light (38.39 mmol/L), ready to consume not from concentrate lemonade (38.24 mmol/L), cranberry juice (19.87 mmol/L), lemon-flavored Gatorade (19.82 mmol/L), homemade lemonade (17.42 mmol/L), Mountain Dew (8.84 mmol/L), and Diet 7Up (7.98 mmol/L), respectively. CONCLUSIONS: According to 1H NMR, all of the tested "natural" citrus juices have high concentrations of citrate (38.3-67.4 mmol/L), with grapefruit juice having the highest concentration of the beverages chosen. Lemonade flavored Crystal Light had the highest concentration of citrate in the nonjuice category of tested beverages. In patients with mild to moderate hypocitraturia, dietary supplementation with citrus-based juices may be an effective alternative to medical management while not requiring large serving sizes. Further prospective studies are warranted to evaluate the clinical significance of these findings.

Allergy testing and referral in children.

BACKGROUND: Allergic diseases (asthma, atopic dermatitis, allergic rhinitis and food allergy) are the commonest chronic diseases of childhood. General practitioners commonly encounter children with allergic diseases and need to be aware of when referral to a paediatric allergist should be considered. An understanding of what diagnostic tests the allergist may use in confirming the diagnosis is also necessary. OBJECTIVE: This article discusses the criteria for referral to a specialist paediatric allergist and also details the tests that may be used by the allergist as part of the diagnostic work up. DISCUSSION: Management of allergic diseases requires accurate diagnosis and avoidance of offending allergens where possible. The diagnosis of an IgE mediated allergy requires both a history of symptoms on exposure to the allergen and detection of allergen specific IgE. The most commonly employed diagnostic methods in clinical allergy assessment are skin prick testing, RAST and clinical oral food challenge procedures. The use of alternative or unorthodox tests may provide misleading results and delay correct diagnosis and therefore should not be used.

Allergy prevention - Current recommendations and new insights.

BACKGROUND: The prevalence of allergic disease has increased considerably in recent decades and Australia has one of the highest rates of allergic disease in the world. As there is currently no cure for allergic diseases, prevention offers a logical approach to addressing the rising burden of disease. The factors responsible for this escalation in prevalence remain unclear, and strategies for allergy prevention remain limited. OBJECTIVE: This article discusses current recommendations for allergy prevention and highlights new insights into allergic disease. DISCUSSION: History of allergic disease in a first degree relative is currently the only useful indicator for increased risk of developing allergic disease in a child. Prevention strategies should be directed to these high risk individuals. Currently, maternal dietary restriction during pregnancy or lactation and aeroallergen avoidance are not recommended. Breastfeeding is recommended, and where not possible or insufficient, a partially hydrolysed formula should be used in high risk infants. Introduction of solids should be delayed to 4-6 months of age. There is no evidence that delaying solids beyond this age is of benefit. There is currently insufficient evidence to recommend the addition of probiotics for allergy prevention.