The future of cow's milk allergy - milk ladders in IgE-mediated food allergy.

Cow's milk allergy (CMA) is one of the most common and complex presentations of allergy in early childhood. CMA can present as IgE and non-IgE mediated forms of food allergy. Non-IgE mediated CMA includes food protein-induced enterocolitis syndrome (FPIES), eosinophilic gastrointestinal disorders (EGIDs), and food protein-induced proctocolitis (FPIAP). There are recent guidelines addressing CMA diagnosis, management, and treatment. Each of these guidelines have their own strengths and limitations. To best manage CMA, individualized avoidance advice should be given. Cow's milk (CM) can be replaced in the diet by using hypoallergenic formulas or plant-based milk, depending on factors such as the child's age and their current food intake. Oral and epicutaneous immunotherapy is used to increase tolerance in children with CMA but is not without risk, and the long-term outcome of sustained unresponsiveness is still unclear. The allergenicity of CM proteins are affected differently by different forms of heating, leading to the use of baked milk or milk ladders in the management of CMA, most likely the most promising option for future management and treatment of CMA. Future management of children with CMA will also include discussion around the immunomodulatory potential of the child's dietary intake.

Dietary management of IgE and non-IgE-mediated food allergies in pediatric patients.

Food allergies (FA) consist of both IgE and non-IgE-mediated entities, with varying phenotypes and overlapping and different considerations for each specific disease presentation. In general, all FAs place children at increased risk for inadequate nutritional intake and negative impacts on their nutritional status, as well as negative impacts on the quality of life for the entire family. To minimize these untoward effects, a multidisciplinary approach should be taken, including consultation and management with a dietitian trained in the varying presentations of FA. Families should be instructed on label reading as a first line of nutritional management. During a nutrition consultation, the age of the child, growth, and nutritional status should be considered. Food refusal should be assessed and addressed. Families should be educated on avoidance and appropriate substitutions. In the case of cow's milk allergy, a suitable specialized formula should be suggested if the infant is not breastfed or if breast milk supply is not sufficient. Other mammalian milk should be avoided and careful consideration should be given before plant-based milk is used in young children. Specific food allergies may differ in terms of advice provided on the level of avoidance required, whether precautionary advisory labels should be avoided, and if a maternal avoidance of the allergen during breastfeeding should be advised. The role of immunonutrition on overall health should be discussed.

Early Detection of Severe Acute Respiratory Syndrome Coronavirus 2 Variants Using Traveler-based Genomic Surveillance at 4 US Airports, September 2021-January 2022.

We enrolled arriving international air travelers in a severe acute respiratory syndrome coronavirus 2 genomic surveillance program. We used molecular testing of pooled nasal swabs and sequenced positive samples for sublineage. Traveler-based surveillance provided early-warning variant detection, reporting the first US Omicron BA.2 and BA.3 in North America.

Anaphylaxis in Children.

ABSTRACT: Anaphylaxis is a potentially life-threatening event in children, commonly encountered in the prehospital and emergency department settings. Recently published clinical guidelines emphasize early recognition of anaphylaxis and administration of epinephrine as the mainstay of management. Literature regarding adjuvant therapies, biphasic reactions, observation times, and disposition of patients with anaphylaxis remains controversial. In this article, we will review the background and pathophysiology of anaphylaxis, as well as the diagnostic approach, management, and future directions of anaphylaxis in children.

Seeking Opportunity in Crisis: Redesigning Care for High-risk Diabetics During the Pandemic.

Management of uncontrolled diabetic (DM) patients has always been a challenge across healthcare settings, but recently we noticed a surge in the number of uncontrolled DM patient in our clinic patients' population during the COVID19 pandemic. This in part a combination of disruptions to care, delayed or inaccessible care, and poor diet and physical activity. To address this issue, we formed a multidisciplinary Diabetes Initiative Team consisting of attending physicians, residents, clinical pharmacist, nurse manager, care manager, and coordinator, along with supportive staffs in our Internal Medicine Residency clinic. Our aim was to reengage diabetic patients in the outpatient setting and to overcome barriers limiting diabetic care.

Trait mindfulness and intrinsic exercise motivation uniquely contribute to exercise self-efficacy.

Objective: Traditional views of exercise motivation emphasize the long-term health benefits of exercise. We investigated whether mindfulness, present-moment awareness, is associated with greater exercise motivation and exercise self-efficacy in college students. Exercise self-efficacy reflects how confident individuals are that they can persist in exercising despite obstacles. Participants: Undergraduate students (N = 188) were recruited from the psychology participant pool in Fall 2017. Methods: Participants completed an online survey assessing trait mindfulness, exercise motivation, exercise self-efficacy, and demographic information. Results: Hierarchical regression analyses revealed positive associations between intrinsic and extrinsic exercise motivation and exercise self-efficacy, mindfulness and intrinsic exercise motivation, and mindfulness and exercise self-efficacy. The latter relationship was partially mediated by intrinsic exercise motivation. Extrinsic exercise motivation was not associated with mindfulness. Conclusions: Both mindfulness and intrinsic exercise motivation independently predict exercise self-efficacy, suggesting that mindfulness may uniquely contribute to positive health behaviors in college students.

Accidental ingestions to known allergens by food allergic children and adolescents.

BACKGROUND: Accidental ingestions (AI) of food allergens in children compared with adolescents with food allergies are poorly characterized. It is suggested that AIs are higher in adolescents than children and that their reactions may be more severe, presumptively due, at least in part, to increased risk-taking behavior. We compared reported AIs in children versus adolescents. METHODS: An online cross-sectional survey was distributed to parents of children with food allergies via Twitter, food allergy advocacy groups in the UK, South Africa, and Australia, and locally at Children's Hospital Colorado. RESULTS: Of 558 respondents, 105 were parents of adolescents, and 453 had children <12 years. 73% (341) reported an AI since diagnosis, with 85% of adolescents having had an AI versus 70% of children (p = 0.0058). The annualized rate of AI was significantly lower in the adolescent population at 0.21 versus 0.53 in children (p = <0.0001). Although adolescents reported fewer severe reactions (2% vs. 16%, p = 0.0283), more adolescents required epinephrine administered by a medical professional for their most severe AI, (48% vs. 24%, p = 0.0378). Comparison of the two age groups is limited by the fact that many AIs in the adolescent group occurred prior to age 12. There was no significant difference between the groups as to where the food was consumed or the type of food. There was a significant difference in accidental ingestions in patients in all age groups with more than one reported food allergy; 78% of those with more than one food allergy reported a prior history of at least one accidental ingestion, compared with 59% in those with a single food allergy (p < 0.0001). Regional differences were also noted with respondents in the United States reporting 0.3 accidental ingestions a year, 0.4 in the UK, and 0.5 in other countries (p = 0.0455). The number of reactions was, on average, 27% lower (95% CI: 40, 11%) in the United States compared with the UK (p = 0.0019). CONCLUSION: The number of severe reactions, and epinephrine need, differs in children compared with adolescents, although many of the reported reactions in both groups occurred before the age of 12. There were also regional differences with the United States reporting a lower number of AIs and less AIs per year than the other participating regions, as well as increased rates of AI in participants with more than one food allergy. Further characterization of the differences in AIs between children and adolescents, as well as between regions, is needed to assist with more patient-centered anticipatory guidance.

A Multidisciplinary Quality Improvement Initiative to Facilitate Penicillin Allergy Delabeling Among Hospitalized Pediatric Patients.

BACKGROUND: Penicillin allergy is reported in up to 10% of the general population; however, >90% of patients reporting an allergy are tolerant. Patients labeled as penicillin allergic have longer hospital stays, increased exposure to suboptimal antibiotics, and an increased risk of methicillin-resistant Staphylococcus aureus and Clostridioides difficile. The primary aim with our quality improvement initiative was to increase penicillin allergy delabeling to at least 10% among all hospitalized pediatric patients reporting a penicillin allergy with efforts directed toward patients determined to be low risk for true allergic reaction. METHODS: Our quality improvement project included several interventions: the development of a multidisciplinary clinical care pathway to identify eligible patients, workflow optimization to support delabeling, an educational intervention, and participation in our institution's quality improvement incentive program. Our interventions were targeted to facilitate appropriate delabeling by the primary hospital medicine team. Statistical process control charts were used to assess the impact of this intervention pre- and postpathway implementation. RESULTS: After implementation of the clinical pathway, the percentage of patients admitted to hospital medicine delabeled of their penicillin allergy by discharge increased to 11.7%. More than one-half of those delabeled (51.2%) received a penicillin-based antimicrobial at time of discharge. There have been no adverse events or allergic reactions requiring emergency medication administration since pathway implementation. CONCLUSIONS: Our quality improvement initiative successfully increased the rate of penicillin allergy delabeling among low-risk hospitalized pediatric patients, allowing for increased use of optimal antibiotics.

Increased power from conditional bacterial genome-wide association identifies macrolide resistance mutations in Neisseria gonorrhoeae.

The emergence of resistance to azithromycin complicates treatment of Neisseria gonorrhoeae, the etiologic agent of gonorrhea. Substantial azithromycin resistance remains unexplained after accounting for known resistance mutations. Bacterial genome-wide association studies (GWAS) can identify novel resistance genes but must control for genetic confounders while maintaining power. Here, we show that compared to single-locus GWAS, conducting GWAS conditioned on known resistance mutations reduces the number of false positives and identifies a G70D mutation in the RplD 50S ribosomal protein L4 as significantly associated with increased azithromycin resistance (p-value = 1.08 × 10-11). We experimentally confirm our GWAS results and demonstrate that RplD G70D and other macrolide binding site mutations are prevalent (present in 5.42% of 4850 isolates) and widespread (identified in 21/65 countries across two decades). Overall, our findings demonstrate the utility of conditional associations for improving the performance of microbial GWAS and advance our understanding of the genetic basis of macrolide resistance.

Adaptation to the cervical environment is associated with increased antibiotic susceptibility in Neisseria gonorrhoeae.

Neisseria gonorrhoeae is an urgent public health threat due to rapidly increasing incidence and antibiotic resistance. In contrast with the trend of increasing resistance, clinical isolates that have reverted to susceptibility regularly appear, prompting questions about which pressures compete with antibiotics to shape gonococcal evolution. Here, we used genome-wide association to identify loss-of-function (LOF) mutations in the efflux pump mtrCDE operon as a mechanism of increased antibiotic susceptibility and demonstrate that these mutations are overrepresented in cervical relative to urethral isolates. This enrichment holds true for LOF mutations in another efflux pump, farAB, and in urogenitally-adapted versus typical N. meningitidis, providing evidence for a model in which expression of these pumps in the female urogenital tract incurs a fitness cost for pathogenic Neisseria. Overall, our findings highlight the impact of integrating microbial population genomics with host metadata and demonstrate how host environmental pressures can lead to increased antibiotic susceptibility.

Targeted surveillance strategies for efficient detection of novel antibiotic resistance variants.

Genotype-based diagnostics for antibiotic resistance represent a promising alternative to empiric therapy, reducing inappropriate antibiotic use. However, because such assays infer resistance based on known genetic markers, their utility will wane with the emergence of novel resistance. Maintenance of these diagnostics will therefore require surveillance to ensure early detection of novel resistance variants, but efficient strategies to do so remain undefined. We evaluate the efficiency of targeted sampling approaches informed by patient and pathogen characteristics in detecting antibiotic resistance and diagnostic escape variants in Neisseria gonorrhoeae, a pathogen associated with a high burden of disease and antibiotic resistance and the development of genotype-based diagnostics. We show that patient characteristic-informed sampling is not a reliable strategy for efficient variant detection. In contrast, sampling informed by pathogen characteristics, such as genomic diversity and genomic background, is significantly more efficient than random sampling in identifying genetic variants associated with resistance and diagnostic escape.

An adolescent girl with signs and symptoms of anaphylaxis and negative immunologic workup: a case report.

BACKGROUND: The increasing incidence of allergies and allergic reactions among children and adults has become a major public health concern. The etiology of allergic reactions can often be confirmed based on a detailed history and supportive testing. However, there are cases where the underlying factors are more complex and difficult to identify. CASE PRESENTATION: Here we present the case report of a 14-year-old Caucasian  girl with weight loss and a 3-year history of reported angioedema culminating in five intensive care unit admissions over the course of 2.5 months. Her initial clinical presentation included hypotension, dyspnea, and reported facial edema, but allergy and immunological workup were negative. A psychiatric workup identified an eating disorder with food restriction, comorbid major depression, obsessive compulsive disorder, and posttraumatic stress disorder. A close collaboration between Adolescent Medicine, Allergy and Immunology, and Psychiatry helped disentangle medical from psychiatric problems, including fluoxetine medication effects, as well as develop a treatment plan that was acceptable to the family. The angioedema was ultimately diagnosed as factitious disorder. CONCLUSIONS: This patient's treatment highlights the importance of a multidisciplinary team approach, a multifactorial etiology that needed to be addressed by multiple specialists, and the importance of long-term treatment and support.

Impact of coping strategies on perceived stress, depression, and cortisol profiles among gynecologic cancer patients.

We explored associations between problem-focused, emotional processing, and emotional expression coping strategies and markers of stress including perceived stress, depressive symptoms, and diurnal cortisol profiles among women with gynecologic cancer. Problem-focused coping was associated with less perceived stress, fewer depressive symptoms, and more rhythmic diurnal salivary cortisol profiles. Emotional processing was associated with lower perceived stress and fewer depressive symptoms. Emotional expression was associated with fewer depressive symptoms and elevated diurnal mean and evening cortisol levels. Results point to key differences in coping strategies. In this sample, only problem-focused coping was linked with adaptive differences in both psychological and physiological stress measures.

Surveillance to maintain the sensitivity of genotype-based antibiotic resistance diagnostics.

The sensitivity of genotype-based diagnostics that predict antimicrobial susceptibility is limited by the extent to which they detect genes and alleles that lead to resistance. As novel resistance variants are expected to emerge, such sensitivity is expected to decline unless the new variants are detected and incorporated into the diagnostic. Here, we present a mathematical framework to define how many diagnostic failures may be expected under varying surveillance regimes and thus quantify the surveillance needed to maintain the sensitivity of genotype-based diagnostics.

Evaluation of parameters affecting performance and reliability of machine learning-based antibiotic susceptibility testing from whole genome sequencing data.

Prediction of antibiotic resistance phenotypes from whole genome sequencing data by machine learning methods has been proposed as a promising platform for the development of sequence-based diagnostics. However, there has been no systematic evaluation of factors that may influence performance of such models, how they might apply to and vary across clinical populations, and what the implications might be in the clinical setting. Here, we performed a meta-analysis of seven large Neisseria gonorrhoeae datasets, as well as Klebsiella pneumoniae and Acinetobacter baumannii datasets, with whole genome sequence data and antibiotic susceptibility phenotypes using set covering machine classification, random forest classification, and random forest regression models to predict resistance phenotypes from genotype. We demonstrate how model performance varies by drug, dataset, resistance metric, and species, reflecting the complexities of generating clinically relevant conclusions from machine learning-derived models. Our findings underscore the importance of incorporating relevant biological and epidemiological knowledge into model design and assessment and suggest that doing so can inform tailored modeling for individual drugs, pathogens, and clinical populations. We further suggest that continued comprehensive sampling and incorporation of up-to-date whole genome sequence data, resistance phenotypes, and treatment outcome data into model training will be crucial to the clinical utility and sustainability of machine learning-based molecular diagnostics.

The role of dispositional mindfulness in a stress-health pathway among Parkinson's disease patients and caregiving partners.

PURPOSE: Parkinson's disease (PD) patients and their caregivers experience significant distress that impacts physical, emotional and social functioning in the patient, and in turn, has a significant impact on the caregiver. Lower levels of stress have been associated with a better prognosis in PD. The quality of dispositional mindfulness-innate present moment, non-judgmental awareness-has consistently been associated with less perceived stress, greater well-being, and better physical health in both clinical and healthy populations. To date, associations of mindfulness with distress, depression, sleep problems, and other variables that define health-related quality of life have not been examined in the context of PD patient/caregiver dyads. METHODS: We investigated the impact of dispositional mindfulness in a stress-health model among eighteen dyads consisting of PD patients and their caregivers. RESULTS: Multilevel linear modeling (actor-partner interdependence models) revealed significant associations between dispositional mindfulness and stress appraisal, interpersonal support, depressive symptoms, sleep, and health-related quality of life (HRQOL) within both dyadic partners. As expected, results demonstrated significant associations of distress with interpersonal support, depressive symptoms, sleep and HRQOL for both PD patients and caregivers. CONCLUSIONS: Dispositional mindfulness was associated with reduced distress and its downstream clinical consequences. These results support an ameliorative role for dispositional mindfulness among PD patients and caregivers, as a protective factor against psychosocial burdens imposed on couples related to disease and caregiving. Findings suggest future studies should explore mindfulness training as a therapeutic option.

Gut microbiomes of wild great apes fluctuate seasonally in response to diet.

The microbiome is essential for extraction of energy and nutrition from plant-based diets and may have facilitated primate adaptation to new dietary niches in response to rapid environmental shifts. Here we use 16S rRNA sequencing to characterize the microbiota of wild western lowland gorillas and sympatric central chimpanzees and demonstrate compositional divergence between the microbiotas of gorillas, chimpanzees, Old World monkeys, and modern humans. We show that gorilla and chimpanzee microbiomes fluctuate with seasonal rainfall patterns and frugivory. Metagenomic sequencing of gorilla microbiomes demonstrates distinctions in functional metabolic pathways, archaea, and dietary plants among enterotypes, suggesting that dietary seasonality dictates shifts in the microbiome and its capacity for microbial plant fiber digestion versus growth on mucus glycans. These data indicate that great ape microbiomes are malleable in response to dietary shifts, suggesting a role for microbiome plasticity in driving dietary flexibility, which may provide fundamental insights into the mechanisms by which diet has driven the evolution of human gut microbiomes.

Caregiver and expecting caregiver support for early peanut introduction guidelines.

BACKGROUND: Recent guidelines recommend early peanut introduction (EPI) beginning around 4 to 6 months of age in infants with severe eczema and/or egg allergy and around 6 months for all other infants. Caregiver preferences for such practices are unknown. OBJECTIVE: To determine levels of support for early allergenic solid food recommendations among new and expecting caregivers of infants at risk for peanut allergy. METHODS: We explored preferences for EPI and in-office allergy risk assessment (IRA) through a nationally representative survey of expecting (n = 1,000) and new caregivers of infants younger than 1 year (n = 1,000). RESULTS: Among a primarily female (99.7%), married (80.3%), and white (74.4%) sample, 29% had no or vague awareness of the new guidelines, 61% had no or minimal concern for their child developing food allergy, but 54% felt timing of food introduction has moderate to strong importance for developing food allergy. Only 31% expressed willingness for EPI before or around 6 months of age, with 40% reporting willingness to introduce peanut after 11 months of age, similar to tree nuts and seafood. However, 60% reported willingness to introduce egg before 8 months of age. A total of 51% and 56.8% were unwilling to allow IRA methods, such as skin testing and oral challenge, before 11 months of age, respectively. Odds of willingness to delay peanut introduction (odds ratio, 0.79; 95% confidence interval, 0.65-0.96) and undergo challenge (odds ratio, 0.67; 95% confidence interval, 0.54-0.82) after 6 months of age were lower among expecting caregivers. CONCLUSION: Among new and expecting caregivers, there is poor current willingness and questionable support for early allergenic solid food recommendations, including IRA before introduction. Willingness was better among expecting vs current caregivers. These trends underscore a need for broader formal implementation planning to facilitate early allergen introduction and maximize its preventive benefits.