The Prevalence of IgE-Mediated Food Allergy and Other Allergic Diseases in the First 10 Years: The Population-Based, Longitudinal HealthNuts Study.

BACKGROUND: There are limited longitudinal data on the population prevalence of allergic conditions during childhood, and few studies have incorporated the reference standard oral food challenge to confirm food allergy. OBJECTIVE: To describe the population prevalence of IgE-mediated food allergy, eczema, asthma, and rhinitis at ages 6 and 10 years in Melbourne, Australia. METHODS: The HealthNuts study recruited 5,276 1-year-old infants in Melbourne, Australia, with repeat assessments at ages 6 and 10 years. At ages 6 and 10 years, carers completed a questionnaire on symptoms and doctor diagnosis of allergic conditions (International Study of Asthma and Allergies in Children). Children were invited to attend a clinic assessment including skin prick test, lung function tests, and oral food challenges when indicated. To minimize the impact of attrition bias, prevalence estimates among participants at ages 6 and 10 years were weighted to reflect characteristics of the whole cohort at recruitment. RESULTS: In total, 4,455 and 4,065 families participated at ages 6 and 10 years, respectively (84% and 77% of the original cohort). Of those, 73% and 55% of participants ages 6 and 10 years, respectively, completed clinical assessments. Overall, 36.5% (95% CI, 34.8-38.2) and 38.2% (95% CI, 36.5-40.1%) of 6- and 10-year-olds had at least one current allergic disease, and around one third of those had two or more allergic diseases. Food allergy occurred in 6.4% (95% CI, 5.6-7.2) of 6-year olds and 6.3% (95% CI, 5.5-7.2) of 10-year-olds. Among infants with challenge-confirmed food allergy in infancy, 45% had persistent disease at age 10 years. The prevalence of current diagnosed asthma at ages 6 and 10 years were 12.1% (95% CI, 10.9-13.3) and 13.1% (95% CI, 11.9-14.4), respectively, current eczema decreased slightly from 15.3% (95% CI, 14.1-19.7) at age 6 years to 12.9% (95% CI, 11.7-14.2) at age 10 years, and current rhinitis increased from 15.1% (95% CI, 13.9-16.5) at age 6 years to 25.0% (95% CI, 23.4-26.7) at age 10 years. CONCLUSIONS: Allergic diseases affect 40% of primary school-age children; one third have multiple allergic diagnoses. Challenge-confirmed food allergy prevalence remains high, and 45% of infants with food allergy have persistent disease to age 10 years.

Preparing Patients for Oral Immunotherapy (PPOINT): International Delphi consensus for procedural preparation and consent.

BACKGROUND: Despite the promise of oral immunotherapy (OIT) to treat food allergies, this procedure is associated with potential risk. There is no current agreement about what elements should be included in the preparatory or consent process. OBJECTIVE: We developed consensus recommendations about the OIT process considerations and patient-specific factors that should be addressed before initiating OIT and developed a consensus OIT consent process and information form. METHODS: We convened a 36-member Preparing Patients for Oral Immunotherapy (PPOINT) panel of allergy experts to develop a consensus OIT patient preparation, informed consent process, and framework form. Consensus for themes and statements was reached using Delphi methodology, and the consent information form was developed. RESULTS: The expert panel reached consensus for 4 themes and 103 statements specific to OIT preparatory procedures, of which 76 statements reached consensus for inclusion specific to the following themes: general considerations for counseling patients about OIT; patient- and family-specific factors that should be addressed before initiating OIT and during OIT; indications for initiating OIT; and potential contraindications and precautions for OIT. The panel reached consensus on 9 OIT consent form themes: benefits, risks, outcomes, alternatives, risk mitigation, difficulties/challenges, discontinuation, office policies, and long-term management. From these themes, 219 statements were proposed, of which 189 reached consensus, and 71 were included on the consent information form. CONCLUSION: We developed consensus recommendations to prepare and counsel patients for safe and effective OIT in clinical practice with evidence-based risk mitigation. Adoption of these recommendations may help standardize clinical care and improve patient outcomes and quality of life.

Predicting One-year Recurrence of HCC based on Gadoxetic Acid-enhanced MRI by Machine Learning Models.

OBJECTIVE: Accurate prediction of recurrence risk after resction in patients with Hepatocellular Carcinoma (HCC) may help to individualize therapy strategies. This study aimed to develop machine learning models based on preoperative clinical factors and multiparameter Magnetic Resonance Imaging (MRI) characteristics to predict the 1-year recurrence after HCC resection. METHODS: Eighty-two patients with single HCC who underwent surgery were retrospectively analyzed. All patients underwent preoperative gadoxetic acidenhanced MRI examination. Preoperative clinical factors and MRI characteristics were collected for feature selection. Least Absolute Shrinkage and Selection Operator (LASSO) was applied to select the optimal features for predicting postoperative 1-year recurrence of HCC. Four machine learning algorithms, Multilayer Perception (MLP), random forest, support vector machine, and k-nearest neighbor, were used to construct the predictive models based on the selected features. A Receiver Operating Characteristic (ROC) curve was used to assess the performance of each model. RESULTS: Among the enrolled patients, 32 patients experienced recurrences within one year, while 50 did not. Tumor size, peritumoral hypointensity, decreasing ratio of liver parenchyma T1 value (ΔT1), and α-fetoprotein (AFP) levels were selected by using LASSO to develop the machine learning models. The area under the curve (AUC) of each model exceeded 0.72. Among the models, the MLP model showed the best performance with an AUC, accuracy, sensitivity, and specificity of 0.813, 0.742, 0.570, and 0.853, respectively. CONCLUSION: Machine learning models can accurately predict postoperative 1-year recurrence in patients with HCC, which may help to provide individualized treatment.

Differential anti-viral response to respiratory syncytial virus A in preterm and term infants.

BACKGROUND: Preterm infants are more likely to experience severe respiratory syncytial virus (RSV) disease compared to term infants. The reasons for this are multi-factorial, however their immature immune system is believed to be a major contributing factor. METHODS: We collected cord blood from 25 preterm (gestational age 30.4-34.1 weeks) and 25 term infants (gestation age 37-40 weeks) and compared the response of cord blood mononuclear cells (CBMCs) to RSVA and RSVB stimulation using neutralising assays, high-dimensional flow cytometry, multiplex cytokine assays and RNA-sequencing. FINDINGS: We found that preterm and term infants had similar maternally derived neutralising antibody titres to RSVA and RSVB. Preterm infants had significantly higher myeloid dendritic cells (mDC) RSV infection compared to term infants. Differential gene expression analysis of RSVA stimulated CBMCs revealed enrichment of genes involved in cytokine production and immune regulatory pathways involving IL-10, IL-36γ, CXCL1, CXCL2, SOCS1 and SOCS3 in term infants, while differentially expressed genes (DEGs) in preterm infants were related to cell cycle (CDK1, TTK, ESCO2, KNL1, CDC25A, MAD2L1) without associated expression of immune response genes. Furthermore, enriched genes in term infants were highly correlated suggesting an increased co-ordination of their immune response to RSVA. When comparing DEGs in preterm and term infants following RSVB stimulation, no differences in immune response genes were identified. INTERPRETATION: Overall, our data suggests that preterm infants have a more restricted immunological response to RSVA compared with term infants. While further studies are required, these findings may help to explain why preterm infants are more susceptible to severe RSV disease and identify potential therapeutic targets to protect these vulnerable infants. FUNDING: Murdoch Children's Research Institute Infection and Immunity theme grant.

Transcriptomic changes associated with oral immunotherapy for food allergy.

This review summarizes recent advances in characterizing the transcriptional pathways associated with outcomes following Oral Immunotherapy. Recent technological advances including single-cell sequencing are transforming the ways in which the transcriptional landscape is understood. The application of these technologies is still in its infancy in food allergy but here we summarize current understanding of gene expression changes following oral immunotherapy for food allergy and specific signatures underpinning the different clinical outcomes of desensitization and remission (sustained unresponsiveness). T helper 2A cells have been identified as a cell type which correlates with disease activity and is modified by treatment. Molecular features at study entry may differentiate individuals who achieve more positive outcomes during OIT. Recent findings point to T cell anergy and Type 1 interferon pathways as potential mechanisms supporting redirection of the allergen-specific immune response away from allergy towards remission. Despite these developments in our understanding of immune mechanisms following OIT, there are still significant gaps. Additional studies examining immune signatures associated with long term and well-defined clinical outcomes are required to gain a more complete understanding of the pathways leading to remission of allergy, in order to optimize treatments and gain improved outcomes for patients.

Associations between gender and health-related quality of life in people with IgE-mediated food allergy and their caregivers: A systematic review.

OBJECTIVE: Understanding factors that impact health-related quality of life (HRQL) is essential to inform personalised food allergy management. However, there are inconsistencies about the impact of gender on HRQL in food allergy. This review aimed to collate all investigations of the association between gender and total or subdomain HRQL scores of individuals with food allergy and their caregivers. DESIGN: This is a narrative systematic review. We descriptively synthesised and compared HRQL outcomes by participant and parent genders according to statistical and clinical significance. Study quality was assessed using the ROBINS-I, inclusive of all domains. Sensitivity analysis of non-interventional studies was conducted using the ROBINS-E. DATA SOURCES: A systematic search of Medline and Embase databases was conducted on 4 April 2022 and updated on 5 December 2023. ELIGIBILITY CRITERIA: Studies were eligible for inclusion if they reported original data on the association between any sex and/or gender and HRQL, as measured with any validated instrument, in populations with IgE-mediated food allergy. Interventional and non-interventional studies were eligible. RESULTS: A comparison of 34 eligible studies (10 interventional and 24 non-interventional) indicated females with food allergy (62.5% of studies of children, 83.3% of studies of adults) and mothers of children with food allergy (50% of studies of caregivers) experienced poorer self-reported baseline HRQL than their counterparts, notably in domains of physical, emotional or food anxiety-related well-being. Gender differences in child HRQL after food allergen immunotherapy were observed. However, selective reporting in included interventional studies meant the direction of this association could not be determined. The proxy-reported total HRQL of participants was not affected by caregiver gender, nor was caregiver HRQL likely impacted by child gender. CONCLUSIONS: Gender should be considered an important modifier of participant HRQL outcomes in food allergy studies. Purposeful exploration of HRQL in all genders is needed to fully understand the implications of this construct on the lived experience of food allergy. SYSTEMATIC REVIEW REGISTRATION: PROSPERO (CRD42022329901).

Prediction of immunocyte infiltration and prognosis in postoperative hepatitis B virus-related hepatocellular carcinoma patients using magnetic resonance imaging.

Background: The immune microenvironment (IME) is closely associated with prognosis and therapeutic response of hepatitis B virus-related hepatocellular carcinoma (HBV-HCC). Multi-parametric magnetic resonance imaging (MRI) enables non-invasive assessment of IME and predicts prognosis in HBV-HCC. We aimed to construct an MRI prediction model of the immunocyte-infiltration subtypes and explore its prognostic significance. Methods: HBV-HCC patients at the First Affiliated Hospital of Sun Yat-sen University (Guangzhou, China) with radical surgery (between 1 October and 30 December 2021) were prospectively enrolled. Patients with pathologically proven HCC (between 1 December 2013 and 30 October 2019) were retrospectively enrolled. Pearson correlation analysis was used to examine the relationship between the immunocyte-infiltration counts and MRI parameters. An MRI prediction model of immunocyte-infiltration subtypes was constructed in prospective cohort. Kaplan-Meier survival analysis was used to analyse its prognostic significance in the retrospective cohort. Results: Twenty-four patients were prospectively enrolled to construct the MRI prediction model. Eighty-nine patients were retrospectively enrolled to determine its prognostic significance. MRI parameters (relative enhancement, ratio of the apparent diffusion coefficient value of tumoral region to peritumoral region [rADC], T1 value) correlated significantly with the immunocyte-infiltration counts (leukocytes, T help cells, PD1+Tc cells, B lymphocytes). rADC differed significantly between high and low immunocyte-infiltration groups (1.47 ± 0.36 vs 1.09 ± 0.25, P = 0.009). The area under the curve of the MRI model was 0.787 (95% confidence interval 0.587-0.987). Based on the MRI model, the recurrence-free time was longer in the high immunocyte-infiltration group than in the low immunocyte-infiltration group (P = 0.026). Conclusions: MRI is a non-invasive method for assessing the IME and immunocyte-infiltration subtypes, and predicting prognosis in post-operative HBV-HCC patients.

Dysfunction of neurotransmitter metabolism is associated with the severity of depression in first-diagnosed, drug-naïve depressed patients.

BACKGROUND & AIMS: Biochemical changes of neurotransmitters underlying major depressive disorder (MDD) are unknown. This study preliminarily explored the association between neurotransmitters with MDD and the possibility of objective laboratory prediction of neurotransmitter involvement in MDD. METHODS: A total of 87 first-diagnosed, drug-naïve patients with depression and 50 healthy controls (HCs) were included in the cross-sectional study. The levels and turnovers of neurotransmitters (glutamine (GLN), glutamic acid (GLU), γ-2Aminobutiric acid (GABA), kainate (KA), vanillylmandelic acid (VMA), 3-methoxy 4-hydroxyphenyl ethylene glycol (MHPG), noradrenaline (NE), homovanillic acid (HVA), dihydroxy-phenyl acetic acid (DOPAC), dopamine (DA), tryptophane (TRP), kynurenine (KYN), serotonin (5-HT), 5-hydroxyindoleacetic acid (5-HIAA)) were determined and the confounding factors were adjusted. Then a correlation and a predictive analysis towards neurotransmitters for MDD were performed. RESULTS: After adjusting confounding factors, GLU (OR = 1.159), (GLU+ GABA)/GLN (OR = 1.217), DOPAC (OR = 1.106), DOPAC/DA (OR = 1.089) and (DOPAC+ HVA)/DA (OR = 1.026) enacted as risk factors of MDD, while KYN (OR = 0.992) was a protective factor. GABAergic and TRPergic pathways were associated with severity of depressive and anxiety symptoms in patients with depression. The predictive model for MDD (AUC = 0.775, 95%CI 0.683-0.860) consisted of KYN (OR = 0.990) and (GLU + GABA)/GLN (OR = 4.101). CONCLUSIONS: First-diagnosed, drug-naïve depression patients showed abnormal neurotransmitter composition. GLU, (GLU + GABA)/GLN, DOPAC, DOPAC/DA and (DOPAC + HVA)/DA were risk factors of MDD, while KYN was a protective factor. GABAergic and TRPergic pathways were correlated with MDD clinical characteristics. KYN and (GLU + GABA)/GLN may have a predictive value for MDD.

Omega-3 polyunsaturated fatty acids supplementation improves memory in first-diagnosed, drug-naïve patients with depression: Secondary analysis of data from a randomized controlled trial.

INTRODUCTION: Cognitive impairments are found in most patients with major depressive disorder (MDD). It is believed that low Omega-3 polyunsaturated fatty acids (n-3 PUFAs) level raise the risk of anxiety, depressive symptoms and cognition dysfunction. Since our previous research has found n-3 PUFAs supplementation improves anxiety in MDD, this study was to further explore the effectiveness on cognitive impairment among depressed patients. METHODS: A total of 72 venlafaxine treated outpatients with first-diagnosed, drug-naïve depression were enrolled. Daily n-3 PUFAs supplementation (2.4 g/d of fish oil, including 1440 mg eicosapentaenoic acid and 960 mg of docosahexaenoic acid) or placebo was used for 12 weeks. Cognitive function, measure by repeatable battery for the assessment of neuropsychological status ([RBANS]) scores, was compared over time. RESULTS: Immediate memory, delayed memory and RBANS total scores were significant higher in both groups at week 4 and week 12 compared with baseline. Both groups exhibited improvement on attention scores at week 12. No significant differences were observed comparing n-3 PUFAs with placebo groups in the improvement of total RBANS scores and other subscales except in the change of immediate memory at both week 4 and week 12 (p < 0.05). LIMITATIONS: Sample size was relatively low. Moreover, multiple ethnic populations and the income of patients should be considered. Lastly, we used raw scores instead of the standardized scores of RBANS. CONCLUSION: N-3 PUFAs supplementation yielded a small but statistically significant improvement on immediate memory in first-diagnosed, drug-naïve depressed patients. While, antidepressant treatment resulted in significant improvement of cognitive function.

Quantitative assessment of inflammation and evaluation of spatial heterogeneity for non-alcoholic fatty liver disease in mice based on iron-adjustive T1.

Background: A sensitive and non-invasive method is necessary to diagnose non-alcoholic fatty liver disease (NAFLD). We explored the iron-adjustive T1 (aT1) ability to quantify the degree of liver inflammation and evaluate the spatial heterogeneity. Methods: Male C57BL/6J mice were randomly categorized as the NAFLD model (n=40), NAFLD-related liver cirrhosis model (n=20), and normal mice (n=10). T1 and T2* maps were acquired using a 3.0T scanner of magnetic resonance imaging (MRI) and aT1 maps through post-processing corrected iron's effect on T1 using T2*. Pathological changes in the left and right liver lobes were assessed using the Non-alcoholic Steatohepatitis-Clinical Research Network scoring system, though hepatic ballooning lesion were rare in models. Spearman's and partial correlation analyses were used to evaluate correlations, and the receiver operating characteristic curve was used to analyze the diagnostic performance. Results: aT1 was highly correlated with NAFLD activity score (NAS) (r=0.747, P<0.001) but not with the fibrosis stage when adjusted by NAS (r=-0.135, P=0.147). The area under the curve (AUC) of the aT1 value distinguishing groups with 0< NAS <4 and NAS ≥4 was 0.802. On analyzing the histogram features of aT1, the entropy, interquartile range, range, and variance were significantly different between the groups with 0< NAS <4 and NAS ≥4 (P<0.05). The entropy was the risk factor of NAS ≥4. Conclusions: aT1 could help evaluate the inflammatory activity in NAFLD mice unaffected by mild fibrosis, and the higher the degree of inflammation, the higher the heterogeneity of the aT1 map.

Correlation between sarcopenia and esophageal cancer: a narrative review.

BACKGROUND: In recent years, the research on the relationship between sarcopenia before and after the treatment of esophageal cancer, as well as its impact on prognosis of esophageal cancer, has increased rapidly, which has aroused people's attention to the disease of patients with esophageal cancer complicated with sarcopenia. This review examines the prevalence of sarcopenia in patients with esophageal cancer, as well as the relationship between sarcopenia (before and after surgery or chemotherapy) and prognosis in patients with esophageal cancer. Moreover, we summarized the potential pathogenesis of sarcopenia and pharmacologic and non-pharmacologic therapies. METHODS: A narrative review was performed in PubMed and Web of Science using the keywords ("esophageal cancer" or "esophageal neoplasm" or "neoplasm, esophageal" or "esophagus neoplasm" or "esophagus neoplasms" or "neoplasm, esophagus" or "neoplasms, esophagus" or "neoplasms, esophageal" or "cancer of esophagus" or "cancer of the esophagus" or "esophagus cancer" or "cancer, esophagus" or "cancers, esophagus" or "esophagus cancers" or "esophageal cancer" or "cancer, esophageal" or "cancers, esophageal" or "esophageal cancers") and ("sarcopenia" or "muscular atrophy" or "aging" or "senescence" or "biological aging" or "aging, biological" or "atrophies, muscular" or "atrophy, muscular" or "muscular atrophies" or "atrophy, muscle" or "atrophies, muscle" or "muscle atrophies"). Studies reporting relationship between sarcopenia and esophageal cancer were analyzed. RESULTS: The results of the review suggest that the average prevalence of sarcopenia in esophageal cancer was 46.3% ± 19.6% ranging from 14.4 to 81% and sarcopenia can be an important predictor of poor prognosis in patients with esophageal cancer. Patients with esophageal cancer can suffer from sarcopenia due to their nutritional deficiencies, reduced physical activity, chemotherapy, and the effects of certain inflammatory factors and pathways. When classic diagnostic values for sarcopenia such as skeletal muscle index (SMI) are not available clinically, it is also feasible to predict esophageal cancer prognosis using simpler metrics, such as calf circumference (CC), five-count sit-up test (5-CST), and six-minute walk distance (6MWD). CONCLUSIONS: Identifying the potential mechanism of sarcopenia in patients with esophageal cancer and implementing appropriate interventions may hold the key to improving the prognosis of these patients.

Perspectives and gaps in the management of food allergy and anaphylaxis in the Asia-Pacific Region.

Background: Food allergy (FA), which is a condition that has no effective cure and can result in severe life-threatening allergic reactions, remains a global public health concern; however, little is known about how FAs are currently managed in the Asia-Pacific region. Objective: The main objective of this survey was to evaluate the epidemiology of FA, as well as the availability of resources and practices for management of FA and anaphylaxis by health care providers across Asia. Methods: From June 2022 to September 2022, a questionnaire-based survey comprising 66 questions was electronically sent to member societies of the Asia Pacific Association of Allergy Asthma and Clinical Immunology by using Survey Monkey. Results: A total of 20 responses were received from 15 member countries and territories. Compared with the pediatric data, there was a lack of prevalence data for FA in adults. Except for Australia and Japan, most regions had between 0.1 and 0.5 allergists per 100,000 population and some had fewer than 0.1 allergists per 100,000 population. The perceived rate of FA in regions with a short supply of allergists was high. Although specific IgE tests and oral food challenges were available in all regions, the median wait time for oral food challenges at government facilities was 37 days (interquartile range = 10.5-60 days). Seven regions still relied on prescriptions of ampules and syringes of injectable adrenaline, and adrenaline autoinjectors were not accessible in 4 regions. Oral immunotherapy as FA treatment was available in half of the surveyed countries and territories. Conclusions: Our study offers a cross-sectional evaluation of the management practices for FA in each Asia Pacific Association of Allergy Asthma and Clinical Immunology member country or territory. Urgent actions are required to enhance allergy services, improve the accessibility and affordability of adrenaline autoinjectors, and conduct robust epidemiologic studies.

OFFSPRING: A SPRING Follow-Up Study Assessing the Efficacy of Maternal Probiotics and Allergic Disease in the Child.

INTRODUCTION: There are a variety of factors that contribute to the development of allergic diseases in children, including environmental exposures during the maternal prenatal period. It has been proposed that probiotic supplementation during pregnancy could be used as a possible preventative measure to target childhood allergic disease. METHODS: Participants from a previously conducted prospective double-blind randomised control trial of probiotics versus placebo study (Study of PRrobiotics IN Gestation) were sent electronic questionnaires to complete about their child, who are now between 3 and 7 years of age. Demographic data and rates of allergic diseases were compared between the two groups. RESULTS: One hundred and seven women responded to the questionnaires. Between the two groups, there was no difference in the frequency of allergic diseases, with similar rates of eczema, asthma, and hospital presentations seen. CONCLUSION: In this follow-up study, infants of mothers who were exposed to probiotics during their pregnancy do not appear to have any paediatric health advantages in terms of allergic diseases.

Interaction Between Baseline Participant Factors and Treatment Effects Following Peanut Oral Immunotherapy.

BACKGROUND: The Probiotic Peanut Oral Immunotherapy-003 multicenter randomized trial found that both probiotic peanut oral immunotherapy (PPOIT) and peanut OIT alone (OIT) were effective compared with placebo in inducing clinical remission after 18 months of treatment, and improving health-related quality of life (HRQL) at 12 months after treatment. Understanding treatment effect modifiers can optimize outcomes through precision care. OBJECTIVES: This post hoc study examined baseline clinical and demographic participant factors that modified treatment effects. METHODS: The study sample included 201 children (aged 1-10 years) with challenge-confirmed peanut allergy. Exposure variables were baseline clinical and demographic factors. Outcomes were remission (double-blind, placebo-controlled food challenge, cumulative 4,950-mg peanut protein at 8 weeks after treatment) and HRQL (change in Food Allergy Quality of Life Questionnaire-Parent Form score). Interactions between baseline factors and treatment effects on remission and HRQL were explored with regression models. RESULTS: A higher degree of peanut sensitivity (large peanut skin prick test, high peanut specific IgE, and low reaction-eliciting dose at study entry challenge) and other concurrent allergic conditions (multiple food allergies, asthma, or wheeze) were associated with the decreased likelihood of attaining remission after both PPOIT and OIT treatment. History of anaphylaxis was associated with the reduced likelihood of remission after PPOIT compared with OIT. For the HRQL outcome, there was evidence that sex, history of anaphylaxis, and age modified treatment effects. CONCLUSIONS: Baseline participant factors modify PPOIT and OIT effects on remission and HRQL. Considering modifiers of treatment effect during participant selection may optimize treatment success and clinical trial design toward specific outcomes, such as the achievement of remission.

Cost-effectiveness analysis of probiotic peanut oral immunotherapy (PPOIT) versus placebo in Australian children with peanut allergy alongside a randomised trial.

OBJECTIVE: To compared the cost-effectiveness of coadministration of a probiotic adjuvant with peanut oral immunotherapy (PPOIT) with placebo (no treatment) in children with peanut allergy. DESIGN: Prospectively planned cost-effectiveness analysis alongside a randomised control trial. SETTING: The Royal Children's Hospital, Melbourne, Australia. PARTICIPANTS: 56 children with peanut allergy aged 1-10 years at recruitment. INTERVENTION: A daily dose of probiotic Lactobacillus rhamnosus CGMCC 1.3724 (NCC4007) and peanut oral immunotherapy administered for 1.5 years. MAIN OUTCOMES MEASURES: Costs were considered from a healthcare system perspective and included costs of treatment delivery and adverse events. Effectiveness outcomes included rate of sustained unresponsiveness (SU) and quality-adjusted life years (QALYs). The cost-effectiveness of PPOIT versus placebo was analysed using patient-level data. Time horizon was 10 years from commencement of PPOIT treatment, comprising 1.5 years of treatment (actual data), 4 years of post-treatment follow-up (actual data), and 4.5 years of extrapolation thereafter (modelling). RESULTS: Healthcare cost per patient over 10 years was higher for PPOIT compared with placebo ($A9355 vs $A1031, p<0.001). Over half of the per patient healthcare cost (53%) in the PPOIT group was attributable to treatment delivery, while the remaining cost was attributable to adverse events. Both measures of effectiveness were superior in the PPOIT group: the average SU rate over 10 years was 54% for PPOIT versus 6% for placebo (p<0.001); QALYs over 10 years were 9.05 for PPOIT versus 8.63 for placebo (p<0.001). Overall, cost per year of SU achieved was $A1694 (range $A1678, $A1709) for PPOIT compared with placebo, and cost per additional QALY gained was $A19 386 (range $A19 024, $A19 774). CONCLUSIONS: Cost per QALY gained using PPOIT compared with no treatment is approximately $A20 000 (£10 000) and is well below the conventional value judgement threshold of $A50 000 (£25 000) per QALY gained, thus deemed good value for money ($A1= £0.5 approximately). TRIAL REGISTRATION NUMBER: Australian New Zealand Clinical Trials Registry ACTRN12608000594325; Post-results.

Effects of prenatal alcohol exposure on infant lung function, wheeze, and respiratory infections in Australian children.

BACKGROUND: Prenatal alcohol exposure (PAE) is a known risk factor for a range of adverse outcomes, such as facial dysmorphism, adverse birth outcomes, and neurodevelopmental changes. Preclinical research shows that PAE also inhibits lung development, lowers surfactant protein expression, has detrimental effects on alveolar macrophages, and decreases both T and B cell numbers. However, clinical evidence of respiratory impacts from PAE is limited. This study explored whether lung function, wheeze, and incidence of respiratory infections differ in children with PAE compared with unexposed children. METHODS: Data from the Barwon Infant Study (n = 1074) were examined. PAE data were extracted from maternal questionnaires at trimesters 1 and 2 (combined), and trimester 3, and included as "total standard drinks" during each trimester and total pregnancy intake, a binary yes/no for PAE, and binge drinking (>5 standard drinks in one session). Respiratory outcomes were parent-reported wheeze, lung function (measured by multiple breath washout), and parent report and medical record indicators of health service attendances for respiratory conditions. Linear and logistic regressions were performed to quantify relationships between PAE and respiratory outcomes, controlling for socioeconomic status, birthweight, sex, gestational age, and maternal smoking. RESULTS: Binge drinking was associated with increased health service attendance for respiratory condition(s) in the first 12 months of life (OR = 5.0, 95% CI (1.7, 20.7), p = 0.008). We did not find a relationship between binary PAE and binge drinking with lung function at 4 weeks of age or wheeze at 12 months. The number of standard drinks consumed in trimester two was associated with a lower lung clearance index (ß = -0.011 turnovers, 95% CI (-0.0200, -0.0013), p = 0.03), and a small increase in functional residual capacity (ß = 0.34 mL, 95% CI (0.02, 0.66), p = 0.04). CONCLUSIONS: We found an association between binge drinking and health service utilization for respiratory conditions in infancy, but no evidence that low-level PAE was associated with adverse respiratory outcomes.

Prognostic significance of preoperative lymphocyte to monocyte ratio in patients with signet ring gastric cancer.

BACKGROUND: The ratio of lymphocytes to monocytes (LMR) has been shown to be an effective predictor of gastric cancer prognosis. However, its predictive accuracy for signet ring gastric cancer is currently not well understood. AIM: To evaluate the prognosis predictive accuracy of preoperative LMR in signet ring gastric cancer. METHODS: A total of 212 signet ring gastric cancer patients admitted at the Xiangya Hospital of Central South University, Department of Gastrointestinal Surgery, from January 2012 to December 2016 were enrolled in the study. The prognosis predictive accuracy of preoperative LMR was explored based on the area under the receiver operating characteristic. Factors that significantly affect the survival of patients were identified using single factor analysis, and those that were independently associated with signet ring gastric cancer were identified through multivariate analysis. RESULTS: The results of the single factor analysis revealed a strong correlation between the survival of signet ring gastric cancer patients and several factors, including tumor invasion (χ2 = 49.726; P < 0.001), lymph node metastasis (χ2 = 30.269; P < 0.001), pTNM stage (χ2 = 49.322; P < 0.001), surgical approach (χ2 = 8.489; P = 0.004), age (t = -2.213; P < 0.028), carcinoembryonic antigen (CEA) (Z = -3.265; P = 0.001), platelet-to-lymphocyte ratio (Z = -2.196; P = 0.028), LMR (Z = -2.226; P = 0.026), ALB (t = 3.284; P = 0.001), prognostic nutritional index (t = -3.789; P < 0.001) and FIB (Z = -3.065; P = 0.002). Furthermore, the multivariate analysis further demonstrated that age (HR: 0.563, 95%CI: 0.363-0.873), tumor invasion depth (HR: 0.226, 95%CI: 0.098-0.520), pTNM stage (HR: 0.444, 95%CI: 0.255-0.771), preoperative CEA level (HR: 0.597, 95%CI: 0.386-8.790), and preoperative LMR level (HR: 1.776, 95%CI: 1.150-2.741) were independent factors influencing the prognosis of signet ring gastric cancer. CONCLUSION: In signet ring gastric cancer patients, a low preoperative LMR level predicts poor prognosis. The death risk ratio of the low LMR group compared to the high LMR group is 1.776.

Potential antidepressant-like effects of N-3 polyunsaturated fatty acids through inhibition of endoplasmic reticulum stress.

RATIONALE: The growing evidence has demonstrated the importance of endoplasmic reticulum stress (ERS) in the pathophysiology of depression. ERS genes were considered to be potential novel therapeutic targets for depression. OBJECTIVES: To clarify the mechanisms of the chronic unpredictable mild stress (CUMS)-induced ERS response and the potential contributing pathways in depression, and further investigate the potential link between N-3 polyunsaturated fatty acids (PUFAs) and stress-induced ERS disturbances. METHODS: This study analyzed the expression of ERS-related genes including GRP78, ATF-4, ATF-6, XBP-1, and CHOP, and sigma-1R with real-time PCR in peripheral blood mononuclear cell (PBMC) RNA samples from participants. All of the rats except for those in the control groups were subjected to 5 consecutive weeks of CUMS to establish the depression model, and the antidepressant effects of N-3 PUFAs were observed by behavior tests. Moreover, the effect of diet and stress on the ERS pathways was also investigated using the western blot. RESULTS: Blood CHOP, ATF-4, and XBP-1 levels were notably elevated in depressed patients relative to healthy individuals. Moreover, increased sigma-1R and decreased ATF-6 implied the protective role of sigma-1R through modulating ERS in patients with depression. Animal studies disclosed the novel findings that supplementary N-3 PUFAs in rats alleviated CUMS-induced disturbance of ERS through the ATF-4/XBP-1/CHOP pathway, implying its potential strategy for depression. CONCLUSION: CUMS-induced depressive-like behaviors are related to the disturbance of ERS. Furthermore, supplementary N-3 PUFAs might be an effective way to alleviate ERS.