Growth in Infants with Cow's Milk Protein Allergy Fed an Amino Acid-Based Formula

Purpose: The present study assessed the role of an amino acid-based formula (AAF) in the growth of infants with cow's milk protein allergy (CMPA). Methods: Non-breastfed, term infants aged 0-6 months with symptoms suggestive of CMPA were recruited from 10 pediatric centers in China. After enrollment, infants were started on AAF for two weeks, followed by an open food challenge (OFC) with cow's milk-based formula (CMF). Infants with confirmed CMPA remained on AAF until 9 months of age, in conjunction with a cow's milk protein-free complementary diet. Body weight, length, and head circumference were measured at enrollment and 9 months of age. Measurements were converted to weight-for-age, length-for-age, and head circumference-for-age Z scores (WAZ, LAZ, HCAZ), based on the World Health Organization growth reference. Results: Of 254 infants (median age 16.1 weeks, 50.9% male), 218 (85.8%) were diagnosed with non-IgE-mediated CMPA, 33 (13.0%) tolerated CMF, and 3 (1.2%) did not complete the OFC. The mean WAZ decreased from 0.119 to -0.029 between birth and enrollment (p=0.067), with significant catch-up growth to 0.178 at 9 months of age (p=0.012) while being fed the AAF. There were no significant changes in LAZ (0.400 vs. 0.552; p=0.214) or HCAZ (-0.356 vs. -0.284; p=0.705) from the time of enrollment to age 9 months, suggesting normal linear and head growth velocity. Conclusion: The amino acid-based study formula, in conjunction with a cow's milk protein-free complementary diet, supported normal growth till 9 months of age in a cohort of Chinese infants with challenge-confirmed non-IgE-mediated CMPA.Peer reviewe

Impaired antibody-mediated protection and defective IgA B cell memory in experimental infection of adults with respiratory syncytial virus

Rationale: Despite relative antigenic stability, respiratory syncytial virus (RSV) re-infects throughout life. After >40 years of research, no effective human vaccine exists and correlates of protection remain poorly defined. Most current vaccine candidates seek to induce high levels of RSV-specific serum neutralizing antibodies, which are associated with reduced RSV-related hospitalization rates in observational studies but may not actually prevent infection. Objectives: Characterize correlates of protection from infection and the generation of RSV-specific humoral memory to promote effective vaccine development. Methods: We inoculated 61 healthy adults with live RSV and studied protection from infection by serum and mucosal antibody. We analyzed RSV-specific peripheral blood plasmablast and memory B cell frequencies and antibody longevity. Measurements and Main Results: Despite moderately high levels of pre-existing serum antibody, 34 (56%) became infected, of whom 23 (68%) developed symptomatic colds. Prior RSV-specific nasal IgA correlated significantly more strongly with protection from PCR-confirmed infection than serum neutralizing antibody. Increases in virus-specific antibody titers were variable and transient in infected subjects, but correlated with plasmablasts that peaked around day 10. During convalescence, only IgG (and no IgA) RSV-specific memory B cells were detectable in peripheral blood. This contrasted with natural influenza infection, where virus-specific IgA memory B cells were readily recovered. Conclusions: This observed specific defect in IgA memory may partly explain RSV's ability to cause recurrent symptomatic infections. If so, vaccines able to induce durable RSV-specific IgA responses may be more protective than those generating systemic antibody alone

Impaired antibody-mediated protection and defective IgA B cell memory in experimental infection of adults with respiratory syncytial virus

Rationale: Despite relative antigenic stability, respiratory syncytial virus (RSV) re-infects throughout life. After >40 years of research, no effective human vaccine exists and correlates of protection remain poorly defined. Most current vaccine candidates seek to induce high levels of RSV-specific serum neutralizing antibodies, which are associated with reduced RSV-related hospitalization rates in observational studies but may not actually prevent infection. Objectives: Characterize correlates of protection from infection and the generation of RSV-specific humoral memory to promote effective vaccine development. Methods: We inoculated 61 healthy adults with live RSV and studied protection from infection by serum and mucosal antibody. We analyzed RSV-specific peripheral blood plasmablast and memory B cell frequencies and antibody longevity. Measurements and Main Results: Despite moderately high levels of pre-existing serum antibody, 34 (56%) became infected, of whom 23 (68%) developed symptomatic colds. Prior RSV-specific nasal IgA correlated significantly more strongly with protection from PCR-confirmed infection than serum neutralizing antibody. Increases in virus-specific antibody titers were variable and transient in infected subjects, but correlated with plasmablasts that peaked around day 10. During convalescence, only IgG (and no IgA) RSV-specific memory B cells were detectable in peripheral blood. This contrasted with natural influenza infection, where virus-specific IgA memory B cells were readily recovered. Conclusions: This observed specific defect in IgA memory may partly explain RSV's ability to cause recurrent symptomatic infections. If so, vaccines able to induce durable RSV-specific IgA responses may be more protective than those generating systemic antibody alone

Patterns of systemic and local inflammation in patients with asthma hospitalised with influenza.

BACKGROUND: Patients with asthma are at risk of hospitalisation with influenza, but the reasons for this predisposition are unknown. STUDY SETTING: A prospective observational study of adults with PCR-confirmed influenza in 11 UK hospitals, measuring nasal, nasopharyngeal and systemic immune mediators and whole-blood gene expression. RESULTS: Of 133 admissions, 40 (30%) had previous asthma; these were more often female (70% versus 38.7%, OR 3.69, 95% CI 1.67 to 8.18, p=0.0012), required less mechanical ventilation (15% versus 37.6%, χ2 6.78, p=0.0338) and had shorter hospital stays (mean 8.3 versus 15.3 d, p=0.0333) than those without. In patients without asthma, severe outcomes were more frequent in those given corticosteroids (OR=2.63, 95% CI=1.02-6.96, p=0.0466) or presenting >4 days after disease onset (OR 5.49, 95% CI 2.28-14.03, p=0.0002). Influenza vaccination in at-risk groups (including asthma) were lower than intended by national policy and the early use of antiviral medications were less than optimal. Mucosal immune responses were equivalent between groups. Those with asthma had higher serum IFN-α but lower serum TNF, IL-5, IL-6, CXCL8, CXCL9, IL-10, IL-17 and CCL2 levels (all p<0.05); both groups had similar serum IL-13, total IgE, periostin and blood eosinophil gene expression levels. Asthma diagnosis was unrelated to viral load, IFN-α, IFN-γ, IL-5 or IL-13 levels. CONCLUSIONS: Asthma is common in those hospitalised with influenza, but may not represent classical Type 2-driven disease. Those admitted with influenza tend to be female with mild serum inflammatory responses, increased serum IFN-α levels and good clinical outcomes.MOSAIC (Mechanisms of Severe Influenza Consortium) was supported by the MRC (UK) and Wellcome Trust (090382/Z/09/Z). The study was also supported by the National Institute of Healthcare Research (NIHR) Biomedical Research Centres (BRCs) in London and Liverpool and by the National Institute for Health Research Health Protection Research Unit (NIHR HPRU) in Respiratory Infections at Imperial College London in partnership with Public Health England (PHE). P.J.O. was supported by EU FP7 PREPARE project 602525

Author Correction: Progression of whole-blood transcriptional signatures from interferon-induced to neutrophil-associated patterns in severe influenza.

In the version of this article initially published, a source of funding was not included in the Acknowledgements section. That section should include the following: P.J.M.O. was supported by EU FP7 PREPARE project 602525. The error has been corrected in the HTML and PDF version of the article

Oxaliplatin, Fluorouracil, and Leucovorin as Adjuvant Treatment for Colon Cancer

Background: The standard adjuvant treatment of colon cancer is fluorouracil plus leucovorin (FL). Oxaliplatin improves the efficacy of this combination in patients with metastatic colorectal cancer. We evaluated the efficacy of treatment with FL plus oxaliplatin in the postoperative adjuvant setting. Methods: We randomly assigned 2246 patients who had undergone curative resection for stage II or III colon cancer to receive FL alone or with oxaliplatin for six months. The primary end point was disease-free survival. Results: A total of 1123 patients were randomly assigned to each group. After a median follow-up of 37.9 months, 237 patients in the group given FL plus oxaliplatin had had a cancer-related event, as compared with 293 patients in the FL group (21.1 percent vs. 26.1 percent; hazard ratio for recurrence, 0.77; P=0.002). The rate of disease-free survival at three years was 78.2 percent (95 percent confidence interval, 75.6 to 80.7) in the group given FL plus oxaliplatin and 72.9 percent (95 percent confidence interval, 70.2 to 75.7) in the FL group (P=0.002 by the stratified log-rank test). In the group given FL plus oxaliplatin, the incidence of febrile neutropenia was 1.8 percent, the incidence of gastrointestinal adverse effects was low, and the incidence of grade 3 sensory neuropathy was 12.4 percent during treatment, decreasing to 1.1 percent at one year of follow-up. Six patients in each group died during treatment (death rate, 0.5 percent). Conclusions: Adding oxaliplatin to a regimen of fluorouracil and leucovorin improves the adjuvant treatment of colon cancer

Assessment of the Cow's Milk-related Symptom Score (CoMiSS) as a diagnostic tool for cow's milk protein allergy : a prospective, multicentre study in China (MOSAIC study)

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