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Many guidelines have been published to help diagnose food allergies, which have included feeding difficulties as a presenting symptom (particularly for non-IgE-mediated gastrointestinal allergies). This study aimed to investigate the prevalence of feeding difficulties in children with non-IgE-mediated gastrointestinal allergies and the association of such difficulties with symptoms and food elimination. An observational study was performed at Great Ormond Street Hospital for Children NHS Foundation Trust, London, UK. Children aged 4 weeks to 16 years without non-allergic co-morbidities who improved on an elimination diet using a previously published Likert scale symptom score were included. This study recruited 131 children, and 114 (87%) parents completed the questionnaire on feeding difficulties. Feeding difficulties were present in 61 (53.5%) of the 114 children. The most common feeding difficulties were regular meal refusals (26.9%), extended mealtimes (26.7%), and problems with gagging on textured foods (26.5%). Most children (40/61) had ≥2 reported feeding difficulties, and eight had ≥4. Children with feeding difficulties had higher rates of constipation and vomiting: 60.7% (37/61) vs. 35.8% (19/53), p = 0.008 and 63.9% (39/61) vs. 41.5% (22/53), p = 0.017, respectively. Logistic regression analysis demonstrated an association between having feeding difficulties, the age of the child, and the initial symptom score. Gender and the number of foods excluded in the elimination diet were not significantly associated with feeding difficulties. This study found that feeding difficulties are common in children with non-IgE-mediated gastrointestinal allergies, but there is a paucity of food allergy specific tools for establishing feeding difficulties, which requires further research in the long-term and consensus in the short term amongst healthcare professions as to which tool is the best for food allergic children.

The liver is a rare site for anastomosing hemangiomas with only a few cases reported that characterize the lesions on magnetic resonance imaging (MRI). These lesions may be underreported due to overlapping features with classic hemangiomas. Anastomosing hemangiomas have a well-defined histological profile and are often diagnosed by biopsy in the setting of atypical imaging features. We report a case of biopsy-proven hepatic anastomosing hemangioma found on a screening MRI for hepatocellular carcinoma in a 52-year-old female with cirrhosis. This lesion initially demonstrated interval growth but has shown no local recurrence in the 2-year surveillance period following microwave ablation.

Abstract Background Bilateral ureteropelvic junction obstruction is a common cause of secondary hypertension in the pediatric population, often due to congenital malformation. On the other hand, it is less frequently encountered in the adult population and is usually due to an acquired condition, most commonly by a bilaterally obstructing nephrolithiasis causing hydronephrosis and subsequent hypertension. The aim of this study was to investigate and highlight the underlying mechanisms by which acute bilateral ureteropelvic junction obstruction causes hypertensive crisis and why early detection and prompt treatment are necessary to mitigate the effects of elevated blood pressure on target organs. Case presentation A 41-year-old African American man with hypertensive cardiomyopathy presented with anuria. He was found to have elevated blood pressure with evidence of target organ damage on laboratory examination, demonstrated by sudden elevation of his serum creatinine level. He was initially treated with oral and intravenous antihypertensives, with minimal improvement. The work-up was unremarkable apart from the imaging finding of acute bilateral ureteropelvic junction obstruction from obstructing nephrolithiasis causing hydronephrosis. Bilateral ureteral stents were placed for decompression, with resolution of the hypertensive crisis and improvement of renal function. Conclusion This case highlights the importance of prompt diagnosis and treatment of underlying acute bilateral ureteropelvic junction obstruction to mitigate the deleterious effects of sudden blood pressure elevation on target organs.

Background: Cow’s milk allergy (CMA) is one of the most common and complex food allergies affecting children worldwide and, with a few exceptions, presents in the first few months of life. Baked-milk-containing diets are well tolerated in the majority of milk-allergic children and allow dietary restrictions to be relaxed. In addition, the early introduction of tolerated forms of allergenic foods to an infant’s diet in small amounts may enhance the outgrowth of their milk allergy through oral tolerance induction. The methods of milk introduction vary widely across the globe. Methods: We convened an expert group to develop a comprehensive milk ladder based on the calculated milk protein content of Indian foods. To validate the milk ladder, the foods chosen for the ladder were analyzed and the ladder was re-evaluated based on the cooked milk protein content. Results: Combining expert consensus and validation of milk protein content, we created the world’s first milk ladder containing Indian foods. This is the first ladder that provides information on the timing and temperature of cooking, with validated milk protein content. Conclusions: This is the first milk ladder based on the unique features of Indian food habits built by the consensus of Indian experts along with international collaboration with laboratory quantification of milk protein in each step. We believe the “The Indian Milk Ladder” will be a very helpful tool for pediatricians helping manage CMA in children as well as their parents and caregivers, not only in India, but in countries world-wide where these foods are commonly consumed.

Abstract A crime is a deliberate act that can cause physical or psychological harm, as well as property damage or loss, and can lead to punishment by a state or other authority according to the severity of the crime. The number and forms of criminal activities are increasing at an alarming rate, forcing agencies to develop efficient methods to take preventive measures. In the current scenario of rapidly increasing crime, traditional crime-solving techniques are unable to deliver results, being slow paced and less efficient. Thus, if we can come up with ways to predict crime, in detail, before it occurs, or come up with a “machine” that can assist police officers, it would lift the burden of police and help in preventing crimes. To achieve this, we suggest including machine learning (ML) and computer vision algorithms and techniques. In this paper, we describe the results of certain cases where such approaches were used, and which motivated us to pursue further research in this field. The main reason for the change in crime detection and prevention lies in the before and after statistical observations of the authorities using such techniques. The sole purpose of this study is to determine how a combination of ML and computer vision can be used by law agencies or authorities to detect, prevent, and solve crimes at a much more accurate and faster rate. In summary, ML and computer vision techniques can bring about an evolution in law agencies.

Introduction: Necrotising fasciitis (NF) is a relatively rare but aggressive infection with high mortality and morbidity if not treated early. Presentation can be vague which can contribute to the treatment delays and poorer patients’ outcomes. The aim of this paper was to reflect on incidence, causation, management and mortality of head and neck (HN) NF cases in the UK by conducting a literature review and present a case series. Method: The literature search was undertaken using PubMed, CINAHL, EMBASE and Medline for HN NF in accordance to PRISMA. Our case series were collected from patients treated between 2010 and 2020 in two hospitals; in East London and Merseyside regions. The data parameters include patients’ demographics, co-morbidities, radiographic investigations, management, microbiology, length of stay and mortality. Results: A total of fifty-one cases were included. Only 59.5% of cases reported of underlying health condition. The main origin of infection was odontogenic (29.4%) and traumatic (27.5%). Before their acute presentation of NF, 41.2% had sought medical treatment either from primary care or emergency services. All patients received IV antibiotics of varying types and 90.2% had surgical debridement. Overall, the mortality rate was 17.6%; cases of traumatic origin had a higher mortality (35.7%). Conclusion: There is a need for awareness for early detection of clinical diagnosis of H&N NF in primary care and emergency services. Prompt referral to the specialist services is crucial to allow early management and improve patients’ outcomes particularly in patients with a history of H&N trauma.

Adult forms of inflammatory bowel disease (IBD) are of a polygenic nature, but paediatric and very early onset (VEO) IBD also occur as monogenic forms. Here, using whole exome sequencing, the authors explore both the monogenic and polygenic contribution to VEO-IBD and characterize a rare somatic mosaic VEO-IBD patient.

Background: Oral food challenges remain the most reliable method for allergy confirmation. Although consensus guidelines have been published to unify Immunoglobulin E (IgE)-mediated challenges, this does not exist for non-IgE mediated gastrointestinal allergies outside of Food Protein Induced Enterocolitis Syndrome. We therefore set out to establish the use of home introduction protocols (HIP) for confirmation of food allergy for milk, soya, egg and wheat using a ladder approach in children with non-IgE mediated allergy.Materials and Methods: Patients with suspected non-IgE mediated gastrointestinal allergies (0–16 years) were recruited following symptom improvement on an elimination diet. All children had skin prick or specific IgE tests to rule out IgE-mediated allergies prior to suggestion the HIP. Number of trials and outcome was documented. HIPs were developed using a published ladder approach for cow's milk as baseline and final dose was calculated based on guidelines for food protein induced enterocolitis syndrome and portions for age from the National Diet and Nutrition Survey. First foods were baked/highly processed and every 4th day patients moved to a more unprocessed/unheated food.Results: From 131 recruited patients, 117 (89.3%) followed the HIP for food allergens. No adverse events were documented. In more than 50% of cases one attempt at the HIP was sufficient to establish allergy status, but many required 2–5 attempts before the outcome was clear. About half of the children were fully tolerant to foods they initially eliminated: 36, 26 and 30% were partially tolerant to milk, soya, and egg and only 15% achieved partial tolerance to wheat. Wheat was the allergen introduced earliest, followed by soya, cow's milk and egg.Conclusions: This study indicates that home HIPs are safe in non-IgE mediated gastrointestinal food allergy and that the ladder approach may be useful in re-introducing allergens in children at home with non-IgE mediated gastrointestinal allergies. From this study we can also conclude that tolerance to processed/baked allergens was observed in many children. Further studies should be performed on the HIP and ideally reintroduction should occur pre-defined time intervals.

Abstract Background Thrombophilia testing is frequently ordered in the inpatient setting despite its limited impact on clinical decision-making and unreliable results in the setting of acute thrombosis or ongoing anticoagulation. We sought to determine the effect of an educational intervention in reducing inappropriate thrombophilia testing for hospitalized patients. Methods During the 2014 academic year, we implemented an educational intervention with a phase implementation design for Internal Medicine interns at Stanford University Hospital. The educational session covering epidemiology, appropriate thrombophilia evaluation and clinical rationale behind these recommendations. Their ordering behavior was compared with a contemporaneous control (non-medicine and private services) and a historical control (interns from prior academic year). From the analyzed data, we determined the proportion of inappropriate thrombophilia testing of each group. Logistic generalized estimating equations were used to estimate odds ratios for inappropriate thrombophilia testing associated with the intervention. Results Of 2151 orders included, 934 were deemed inappropriate (43.4%). The two intervention groups placed 147 orders. A pooled analysis of ordering practices by intervention groups revealed a trend toward reduction of inappropriate ordering (p = 0.053). By the end of the study, the intervention groups had significantly lower rates of inappropriate testing compared to historical or contemporaneous controls. Conclusion A brief educational intervention was associated with a trend toward reduction in inappropriate thrombophilia testing. These findings suggest that focused education on thrombophilia testing can positively impact inpatient ordering practices.

Abstract Background Altered gut microbiota is implicated in cow’s milk allergy (CMA) and differs markedly from healthy, breastfed infants. Infants who suffer from severe CMA often rely on cow’s milk protein avoidance and, when breastfeeding is not possible, on specialised infant formulas such as amino-acid based formulas (AAF). Herein, we report the effects of an AAF including specific synbiotics on oral and gastrointestinal microbiota of infants with non-IgE mediated CMA with reference to healthy, breastfed infants. Methods In this prospective, randomized, double-blind controlled study, infants with suspected non-IgE mediated CMA received test or control formula. Test formula was AAF with synbiotics (prebiotic fructo-oligosaccharides and probiotic Bifidobacterium breve M-16V). Control formula was AAF without synbiotics. Healthy, breastfed infants were used as a separate reference group (HBR). Bacterial compositions of faecal and salivary samples were analysed by 16S rRNA-gene sequencing. Faecal analysis was complemented with the analysis of pH, short-chain fatty acids (SCFAs) and lactic acids. Results The trial included 35 test subjects, 36 controls, and 51 HBR. The 16S rRNA-gene sequencing revealed moderate effects of test formula on oral microbiota. In contrast, the gut microbiota was substantially affected across time comparing test with control. In both groups bacterial diversity increased over time but was characterised by a more gradual increment in test compared to control. Compositionally this reflected an enhancement of Bifidobacterium spp. and Veillonella sp. in the test group. In contrast, the control-fed infants showed increased abundance of adult-like species, mainly within the Lachnospiraceae family, as well as within the Ruminococcus and Alistipes genus. The effects on Bifidobacterium spp. and Lachnospiraceae spp. were previously confirmed through enumeration by fluorescent in situ hybridization and were shown for test to approximate the proportions observed in the HBR. Additionally, microbial activity was affected as evidenced by an increase of l-lactate, a decrease of valerate, and reduced concentrations of branched-chain SCFAs in test versus control. Conclusions The AAF including specific synbiotics effectively modulates the gut microbiota and its metabolic activity in non-IgE mediated CMA infants bringing it close to a healthy breastfed profile. Trial registration Registered on 1 May 2013 with Netherlands Trial Register Number NTR3979.

Abstract Background Here we report follow-up data from a double-blind, randomized, controlled multicenter trial, which investigated fecal microbiota changes with a new amino acid-based formula (AAF) including synbiotics in infants with non-immunoglobulin E (IgE)-mediated cow’s milk allergy (CMA). Methods Subjects were randomized to receive test product (AAF including fructo-oligosaccharides and Bifidobacterium breve M-16V) or control product (AAF) for 8 weeks, after which infants could continue study product until 26 weeks. Fecal percentages of bifidobacteria and Eubacterium rectale/Clostridium coccoides group (ER/CC) were assessed at 0, 8, 12, and 26 weeks. Additional endpoints included stool markers of gut immune status, clinical symptoms, and safety assessments including adverse events and medication use. Results The trial included 35 test subjects, 36 controls, and 51 in the healthy reference group. Study product was continued by 86% and 92% of test and control subjects between week 8–12, and by 71% and 80%, respectively until week 26. At week 26 median percentages of bifidobacteria were significantly higher in test than control [47.0% vs. 11.8% (p

Patients with loss-of-function mutations in IL10 or IL10 receptor (IL10R) genes develop severe, medical-refractory, infantile-onset inflammatory bowel disease (IBD). We have previously reported significant alterations in innate and adaptive immune responses in these patients. Next generation sequencing platforms enable a comprehensive assessment of T cell receptor (TCR) and B cell receptor (BCR) repertoire patterns. We aimed to characterize TCR and BCR features in peripheral blood of patients with deleterious IL10 signaling defects. DNA was isolated from blood of seven patients with IL10R mutations and one with an IL10 mutation, along with eight controls, and subjected to next generation sequencing of TRB and IgH loci. A significant increase in clonality was observed in both TCR and BCR repertoires in circulating lymphocytes of IL10/IL10R-deficient patients, but to a much greater extent in T cells. Furthermore, short CDR3β length and altered hydrophobicity were demonstrated in T cells of patients, but not in B cells, secondary to lower rates of insertions of nucleotides, but not deletions, at the V-, D-, or J-junctions. We were unable to observe specific T or B clones that were limited only to the patients or among controls. Moreover, the expanded T cells clones were unique to each patient. In conclusion, next generation sequencing of the TCR and BCR is a powerful tool for characterizing the adaptive immune cell phenotype and function in immune-mediated disorders. The oligoclonality observed among IL10/IL10R-deficient patients may suggest specialization of unique clones that likely have a role in mediating tissue damage. Nevertheless, the lack of shared clones between patients provides another piece of evidence that the adaptive immune response in IBD is not triggered against common antigens. Additional studies are required to define the specific antigens that interact with the expanded IL10/IL10R-deficient clones.

Heart failure (HF) is one of the leading causes of hospital readmissions and health care expenditures. With a vast degree of advancements in the clinical approach and diagnosis, its management protocol is limited in terms of enhancing quality of life and prognosis. Type 2 diabetes mellitus (T2DM) is considered as one of the commonly associated comorbid conditions in the HF population. The understanding of the molecular and metabolic models of HF has led to the utilization of therapeutic goals of T2DM in improving HFrelated complications. In the recent era, SGLT-2 inhibitors have shown success in decreasing cardiovascular mortality in the T2DM population. This article will help the reviewer to comprehend the pathophysiology of HF and the potential role of SGLT-2 inhibitors in the management algorithm of HF and its associated risk factors in T2DM.

Abstract Background Brachytherapy (BT) is a vital component of the curative treatment of locally advanced cervical cancer. The American Brachytherapy Society has published guidelines for high dose rate (HDR) BT with recommended dose limits. However, recent reports suggest lower doses may be needed to avoid toxicity. The purpose of this study is to investigate incidence and predictive factors influencing gastrointestinal (GI) and genitourinary (GU) toxicity following HDR intracavitary brachytherapy for locally advanced cervical cancer. Methods We retrospectively evaluated a cohort of patients with locally advanced cervical cancer who received CT-based HDR BT. Cumulative doses were calculated using the linear-quadratic model. Statistical analyses were used to investigate clinical and dosimetric predictors of GI and GU toxicity following HDR brachytherapy according to CTCAE v4.0 grading criteria. Results Fifty-six women with FIGO IB1 – IVA cervical cancer were included. The overall rate of any GU adverse event (Grade 1+) was 23.3% (n = 13) and severe adverse events (Grade 3+) was 7.1% (n = 4). Of those, the bladder equivalent dose in 2- Gray (Gy) fractions (EQD2) D2cc was ≥80 for three of the four patients. The overall rate of any GI adverse event was 26.8% (n = 15) and the rate of severe adverse events was 14.3% (n = 8). Of those, six of the eight patients had a rectal EQD2 D2cc ≥ 65 Gy and seven patients had a sigmoid D2cc ≥ 65 Gy. Amongst clinically meaningful factors for development of adverse events (i.e. diabetes, smoking status, ovoid size, and treatment duration), there were no statistically significant prognostic factors identified. Conclusions Severe adverse events are observed even with adherence to current ABS guidelines. In the era of recent multi-institutional study results, our data also supports more stringent dosimetric goals. We suggest cumulative D2cc dose limits of: less than 80 Gy for the bladder and less than 65 Gy for the rectum and sigmoid.

Abstract This study investigates if laboratory data can be used to assess whether physician-retesting patterns are in line with established guidelines, and if these guidelines identify deteriorating patients in a timely manner. A total of 7594 patients with high cholesterol were studied, along with 2764 patients with diabetes. More than 90% of borderline high cholesterol patients are retested within the 3 year recommended period, however less than 75% of pre-diabetic patients have repeated tests within the suggested 1-year time frame. Patients with borderline high cholesterol typically progress to full high cholesterol in 2–3 years, and pre-diabetic patients progress to full diabetes in 1–2 years. Data from routinely ordered laboratory tests can be used to monitor adherence to clinical guidelines. These data may also be useful in the design of adaptive testing strategies that reduce unnecessary testing, while ensuring that patient deterioration is identified in a timely manner. Established guidelines for testing of total serum cholesterol for hypercholesterolemia are appropriate and are well-adhered to, whereas guidelines for glycated hemoglobin A1c testing for type 2 diabetes mellitus could be improved to bring them in line with current practice and avoid unnecessary testing.

Diabetes is a metabolic disorder that affects more than 400 million people worldwide. Most existing approaches for measuring fasting blood glucose levels (FBGLs) are invasive. This work presents a proof-of-concept study in which saliva is used as a proxy biofluid to estimate FBGL. Saliva collected from 175 volunteers was analysed using portable, handheld sensors to measure its electrochemical properties such as conductivity, redox potential, pH and K^+, Na^+ and Ca^2+ ionic concentrations. These data, along with the person's gender and age, were trained and tested after casewise annotation with their true FBGL values using a set of mathematical algorithms. An accuracy of 87.4 ± 1.7% and a mean relative deviation of 14.1% (R^2 = 0.76) was achieved using a mathematical algorithm. All parameters except the gender were found to play a key role in the FBGL determination process. Finally, the individual electrochemical sensors were integrated into a single platform and interfaced with the authors’ algorithm through a simple graphical user interface. The system was revalidated on 60 new saliva samples and gave an accuracy of 81.67 ± 2.53% (R^2 = 0.71). This study paves the way for rapid, efficient and painless FBGL estimation from saliva.

The early years, between the ages of one and six, are a period of rapid physical, social and cognitive growth and a nutritionally adequate diet is an important factor for optimum development. We investigated the micronutrient adequacy and status of young US children aged 1–6 years (n = 9848) using 24-h dietary recall interviews completed by parents and caregivers participating in the National Health and Nutrition Examination Survey (NHANES) 2001–2016. data. The proportion of the sample not meeting the Dietary Reference Intakes (DRI) increased with increasing age and was most pronounced for calcium. Despite adequate iron intake, 7.4% and 2.5% had signs of iron deficiency and anemia based on serum ferritin and hemoglobin levels, with younger children and WIC participants at most risk and Non-Hispanic Black children the least. Vitamin B6 intake was adequate, but 6.4% had serum pyridoxal-5-phosphate deficiency. For vitamin E, 69% had intakes below the estimated average requirement (EAR), yet serum deficiency was only detected in 0.9%. Vitamin D intake was inadequate for 87%, but true deficiency may be overestimated. Mean DHA intake was 24 mg/d, well below expert recommendations of 70–100 mg/day. Iron and vitamin B6 deficiency and inadequate calcium, fiber, choline, potassium and DHA intakes are a concern for a significant percentage of young children. The discrepancy between nutrient intakes and serum deficiency levels needs to be further investigated.

In 2020, with the advent of a pandemic touching all aspects of global life, there is a renewed interest in nutrition solutions to support the immune system. Infants are vulnerable to infection and breastfeeding has been demonstrated to provide protection. As such, human milk is a great model for sources of functional nutrition ingredients, which may play direct roles in protection against viral diseases. This review aims to summarize the literature around human milk (lactoferrin, milk fat globule membrane, osteopontin, glycerol monolaurate and human milk oligosaccharides) and infant nutrition (polyunsaturated fatty acids, probiotics and postbiotics) inspired ingredients for support against viral infections and the immune system more broadly. We believe that the application of these ingredients can span across all life stages and thus apply to both pediatric and adult nutrition. We highlight the opportunities for further research in this field to help provide tangible nutrition solutions to support one’s immune system and fight against infections.

Since originally isolated in 1899, the genus Bifidobacterium has been demonstrated to predominate in the gut microbiota of breastfed infants and to benefit the host by accelerating maturation of the immune response, balancing the immune system to suppress inflammation, improving intestinal barrier function, and increasing acetate production. In particular, Bifidobacterium longum subspecies infantis (B. infantis) is well adapted to the infant gut and has co-evolved with the mother-infant dyad and gut microbiome, in part due to its ability to consume complex carbohydrates found in human milk. B. infantis and its human host have a symbiotic relationship that protects the preterm or term neonate and nourishes a healthy gut microbiota prior to weaning. To provide benefits associated with B. infantis to all infants, a number of commercialized strains have been developed over the past decades. As new ingredients become available, safety and suitability must be assessed in preclinical and clinical studies. Consideration of the full clinical evidence for B. infantis use in pediatric nutrition is critical to better understand its potential impacts on infant health and development. Herein we summarize the recent clinical studies utilizing select strains of commercialized B. infantis.

There is extensive knowledge on the relationship of posterior scleral biomechanics and intraocular pressure (IOP) load on glaucomatous optic neuropathy; however, the role for biomechanical influence of the perilimbal scleral tissue on the aqueous humor drainage pathway, including the distal venous outflow system, and IOP regulation is not fully understood. The purpose of this work is to study the outflow characteristics of perfused porcine eyes relative to the biomechanical properties of the perilimbal sclera, the posterior sclera and the cornea. Enucleated porcine eyes from eleven different animals were perfused with surrogate aqueous at two fixed flow rates while monitoring their IOP. After perfusion, mechanical stress-strain and relaxation tests were conducted on specimens of perilimbal sclera, posterior sclera, and cornea from the same perfused eyes. Statistical analysis of the data demonstrated a strong correlation between increased tangent modulus of the perilimbal sclera tissues and increased perfusion IOP (R2 = 0.74, p = 0.0006 at lower flow rate and R2 = 0.71, p = 0.0011 at higher flow rate). In contrast, there were no significant correlations between IOP and the tangent modulus of the other tissues (Posterior sclera: R2 = 0.17 at lower flow rate and R2 = 0.30 at higher flow rate; cornea: R2 = 0.02 at lower flow rate and R2

Cow’s milk protein allergy (CMPA) is the most common food allergy in infants and can affect a family’s quality of life. The purpose of this paper is to evaluate the knowledge and experience of general practitioners (GPs) in terms of CMPA diagnosis and management and to explore the views of parents on the current diagnostic process. Two surveys were conducted in June 2014, which collected data from GPs and parents of infants diagnosed with CMPA in the United Kingdom. The questionnaires included quantitative and qualitative questions, which measured self-reported knowledge, management and perceived treatment progression, and the educational needs of GPs. We also explored parents’ experiences of local healthcare support in relation to CMPA. A total of 403 GPs and 300 parents completed the surveys. The main symptoms of CMPA and diagnosis period differed between GPs and parents. Other key points include different perceptions on symptom presentation and improvement, lack of awareness from GPs about current guidelines, and the significant burden on both families and GPs. This is the first study attempting to establish GP and parental experience in diagnosing CMPA. It is notable that the difference can be improved through training, appropriate diagnostic tools and improved communication between physicians and parents.

Background There is no data on the prevalence of vitamin D deficiency in children with non-immunoglobulin-E (IgE) mediated gastrointestinal food allergy. The aims of our study were to understand the prevalence of vitamin D insufficiency and deficiency in children with non-IgE mediated gastrointestinal food allergy and identify predisposing factors.Methods This was a retrospective study which looked at data from Great Ormond Street Hospital from January 2002 to September 2015. Children 0–18 years old with a confirmed diagnosis of non-IgE mediated gastrointestinal food allergy who had a vitamin D level measured during the course of their disease were included. Low vitamin D levels were defined as

Background The impact on health related quality of life (HRQL) has been well studied in children with Immunoglobulin E (IgE)-mediated food allergy. However limited data exists on related quality of life (QOL) of families who have a child suffering from food protein induced non-IgE mediated gastrointestinal allergies. We aimed to establish the QOL of families with children at the beginning of following an elimination diet for non-IgE mediated gastrointestinal food allergies.Methods A prospective, observational study was performed. Parents of children aged 4 weeks–16 years who improved after 4–8 weeks of following an elimination diet for suspected non-IgE mediated allergies were included. The Family Impact Module (FIM) of the Pediatric Quality of Life (PedsQL™) was used and we compared our data to two historical cohorts: one with sickle cell disease and another with intestinal failure.Results One hundred and twenty three children with a median age of 20 months were included (84 boys). The total FIM Score was 57.43 (SD 22.27) and particularly low for daily activities and worry. Factors that impacted significantly included age (p < 0.0001), number of foods excluded (p = 0.008), symptom severity (p = 0.041) and chronic nasal congestion (p = 0.012). Children with non-IgE mediated food allergies had worse scores in all domains (p < 0.0001) compared to sickle cell disease and worse physical (p = 0.04), emotional (p = 0.04) and worry (p = 0.01) domains compared to intestinal failure.Conclusions This study found that parent QOL and family functioning was worse in those families who had a child on an elimination diet for non-IgE mediated allergies compared to those with sickle cell disease and intestinal failure, highlighting the impact this disease has on families. Keywords: Non-IgE mediated allergies, Gastrointestinal allergies, Quality of life, Family impact score

Oncogenic mutations of FLT3 and KIT receptors are associated with poor survival in patients with acute myeloid leukemia (AML) and myeloproliferative neoplasms (MPNs), and currently available drugs are largely ineffective. Although Stat5 has been implicated in regulating several myeloid and lymphoid malignancies, how precisely Stat5 regulates leukemogenesis, including its nuclear translocation to induce gene transcription, is poorly understood. In leukemic cells, we show constitutive activation of focal adhesion kinase (FAK) whose inhibition represses leukemogenesis. Downstream of FAK, activation of Rac1 is regulated by RacGEF Tiam1, whose inhibition prolongs the survival of leukemic mice. Inhibition of the Rac1 effector PAK1 prolongs the survival of leukemic mice in part by inhibiting the nuclear translocation of Stat5. These results reveal a leukemic pathway involving FAK/Tiam1/Rac1/PAK1 and demonstrate an essential role for these signaling molecules in regulating the nuclear translocation of Stat5 in leukemogenesis.

Abstract In the original version of this article [1], published on 23 August 2017, an incorrect version of Additional file 4 has been used. The corrected version of Additional file 4 is given in this correction.

Background Food protein induced gastrointestinal allergies are difficult to characterise due to the delayed nature of this allergy and absence of simple diagnostic tests. Diagnosis is based on an allergy focused history which can be challenging and often yields ambiguous results. We therefore set out to describe a group of children with this delayed type allergy, to provide an overview on typical profile, symptoms and management strategies.Methods This retrospective analysis was performed at Great Ormond Street Children’s Hospital. Medical notes were included from 2002 – 2009 where a documented medical diagnosis of food protein induced gastrointestinal allergies was confirmed by an elimination diet with resolution of symptoms, followed by reintroduction with reoccurrence of symptoms. Age of onset of symptoms, diagnosis, current elimination diets and food elimination at time of diagnosis and co-morbidities were collected and parents were phoned again at the time of data collection to ascertain current allergy status.Results Data from 437 children were analysis. The majority (67.7%) of children had an atopic family history and 41.5% had atopic dermatitis at an early age. The most common diagnosis included, non-IgE mediated gastrointestinal food allergy (n = 189) and allergic enterocolitis (n = 154) with symptoms of: vomiting (57.8%), back-arching and screaming (50%), constipation (44.6%), diarrhoea (81%), abdominal pain (89.9%), abdominal bloating (73.9%) and rectal bleeding (38.5%). The majority of patients were initially managed with a milk, soy, egg and wheat free diet (41.7%). At a median age of 8 years, 24.7% of children still required to eliminate some of the food allergens.Conclusions This large retrospective study on children with food induced gastrointestinal allergies highlights the variety of symptoms and treatment modalities used in these children. However, further prospective studies are required in this area of food allergy.