A Lipopolysaccharide-Enriched Cow's Milk Allergy Microbiome Promotes a TLR4-Dependent Proinflammatory Intestinal Immune Response.

We have previously reported that the gut microbiota of healthy infants harbors allergy-protective bacteria taxa that are depleted in infants with cow's milk allergy (CMA). Few reports have investigated the role of the gut microbiota in promoting allergic responses. In this study we selected a CMA-associated microbiota with increased abundance of Gram-negative bacteria for analysis of its proinflammatory potential. LPS is the major component of the outer membrane of Gram-negative bacteria. Colonization of mice with a global or conditional mutation of the LPS receptor TLR4 with this CMA microbiota induced expression of serum amyloid A1 (Saa1) and other Th17-, B cell-, and Th2-associated genes in the ileal epithelium in a TLR4-dependent manner. In agreement with the gene expression data, mice colonized with the CMA microbiota have expanded populations of Th17 and regulatory T cells and elevated concentrations of fecal IgA. Importantly, we used both antibiotic-treated specific pathogen-free and germ-free rederived mice with a conditional mutation of TLR4 in the CD11c+ compartment to demonstrate that the induction of proinflammatory genes, fecal IgA, and Th17 cells is dependent on TLR4 signaling. Furthermore, metagenomic sequencing revealed that the CMA microbiota has an increased abundance of LPS biosynthesis genes. Taken together, our results show that a microbiota displaying a higher abundance of LPS genes is associated with TLR4-dependent proinflammatory gene expression and a mixed type 2/type 3 response in mice, which may be characteristic of a subset of infants with CMA.

How dietary advanced glycation end products could facilitate the occurrence of food allergy.

BACKGROUND: Food allergy (FA) is one of the most common chronic conditions in children with an increasing prevalence facilitated by the exposure to environmental factors in predisposed individuals. It has been hypothesized that the increased consumption of ultra-processed foods, containing high levels of dietary advanced glycation end products (AGEs), could facilitate the occurrence of FA. OBJECTIVE: We sought to provide preclinical and clinical evidence on the potential role of AGEs in facilitating the occurrence of FA. METHODS: Human enterocytes, human small intestine organ culture, and PBMCs from children at risk for allergy were used to investigate the direct effect of AGEs on gut barrier, inflammation, TH2 cytokine response, and mitochondrial function. Intake of the 3 most common glycation products in Western diet foods, Nε-(carboxymethyl) lysine, Nε-(1-carboxyethyl) lysin, and Nδ-(5-hydro-5- methyl-4-imidazolone-2-yl)-ornithine (MG-H1), and the accumulation of AGEs in the skin were comparatively investigated in children with FA and in age-matched healthy controls. RESULTS: Human enterocytes exposed to AGEs showed alteration in gut barrier, AGE receptor expression, reactive oxygen species production, and autophagy, with increased transepithelial passage of food antigens. Small intestine organ cultures exposed to AGEs showed an increase of CD25+ cells and proliferating crypt enterocytes. PBMCs exposed to AGEs showed alteration in proliferation rate, AGE receptor activation, release of inflammatory and TH2 cytokines, and mitochondrial metabolism. Significant higher dietary AGE intake and skin accumulation were observed children with FA (n = 42) compared with age-matched healthy controls (n = 66). CONCLUSIONS: These data, supporting a potential role for dietary AGEs in facilitating the occurrence of FA, suggest the importance of limiting exposure to AGEs children as a potential preventive strategy against this common condition.

Skin, gut, and lung barrier: Physiological interface and target of intervention for preventing and treating allergic diseases.

The epithelial barriers of the skin, gut, and respiratory tract are critical interfaces between the environment and the host, and they orchestrate both homeostatic and pathogenic immune responses. The mechanisms underlying epithelial barrier dysfunction in allergic and inflammatory conditions, such as atopic dermatitis, food allergy, eosinophilic oesophagitis, allergic rhinitis, chronic rhinosinusitis, and asthma, are complex and influenced by the exposome, microbiome, individual genetics, and epigenetics. Here, we review the role of the epithelial barriers of the skin, digestive tract, and airways in maintaining homeostasis, how they influence the occurrence and progression of allergic and inflammatory conditions, how current treatments target the epithelium to improve symptoms of these disorders, and what the unmet needs are in the identification and treatment of epithelial disorders.

Growth pattern of paediatric patients affected by cow milk protein allergy fed with rice hydrolyzed formula.

OBJECTIVES: Formulas made from hydrolyzed rice proteins (HRPF) are well-tolerated plant-based alternatives to cow's milk protein (CMP)-based formulas for the dietary management of paediatric patients with CMP allergy (CMPA). Growth in patients with CMPA fed with HRPF has been evaluated in several studies with conflicting results. The aim was to evaluate the growth pattern of children with CMPA over a 12-month follow-up period. METHODS: Prospective cohort study evaluating growth patterns in challenge proven CMPA paediatric patients receiving HRPF for 12 months. Outcomes were anthropometry (body weight, body length, head circumference), adherence to the study formula and occurrence of adverse events (AEs). RESULTS: Sixty-six children were included and completed the 12-month study. At baseline, all CMPA patients were weaned. For the entire CMPA pediatric patients' cohort, from baseline to the end of the study period, the growth pattern resulted within the normal range of World Health Organization (WHO) growth references. The formula was well tolerated. Adherence was optimal and no AEs related to HRPF use were reported. CONCLUSIONS: HRPF is well tolerated and can help support healthy growth and development in infants and young children with CMPA. These type of formula can be given with complementary foods in the dietary management of CMPA.

The step-down approach in children with cow's milk allergy: Results of a randomized controlled trial.

BACKGROUND: The Step-Down Approach for Cow's Milk Allergy (SDACMA) trial evaluated the tolerability and the rate of immune tolerance acquisition in CMA children starting dietary treatment with amino acid-based formula (AAF) and then switching to EHCF containing the probiotic Lacticaseibacillus rhamnosus GG (EHCF + LGG). METHODS: Randomized controlled trial involving IgE-mediated CMA children receiving AAF from at least 4 weeks. EHCF + LGG tolerance was evaluated by the results of double-blind placebo-controlled food challenge (DBPCFC). Subjects tolerating EHCF + LGG were randomly allocated to remain on AAF, or to switch to EHCF + LGG. Immune tolerance acquisition to cow's milk proteins was evaluated with DBPCFC after 12 months of treatment. Allergy screening tests and body growth were also monitored. RESULTS: Sixty IgE-mediated CMA children were enrolled. The proportion of children treated with AAF who resulted tolerant to the first exposure of EHCF + LGG was 0.98 (exact 95% CI 0.91-0.99). The rate of the immune tolerance acquisition to cow milk proteins after 12 months treatment was higher in the EHCF + LGG (0.48, 95% exact CI 0.29-0.67, n/N = 14/29) than in the AAF group (0.03, 95% exact CI 0.001-0.17, n/N = 1/30). There was an absolute benefit increase (ABI) of tolerance rate equal to 0.45 (95% CI 0.23-0.63, Newcombe method 10) for EHCF + LGG versus AAF, corresponding to a NNT of 2 (2-4, Bender's method). A normal body growth pattern was observed in the two study groups. CONCLUSION: In IgE-mediated CMA children the step-down from AAF to EHCF + LGG is well tolerated and could facilitate the immune tolerance acquisition.

Imaging of Small-Bowel Neuroendocrine Neoplasms: AJR Expert Panel Narrative Review.

Neuroendocrine neoplasms (NENs) of the small bowel are typically slow-growing lesions that remain asymptomatic until reaching an advanced stage. Imaging modalities for lesion detection, staging, and follow-up in patients with known or suspected NEN include CT enterography, MR enterography, and PET/CT using a somatostatin receptor analog. FDG PET/CT may have a role in the evaluation of poorly differentiated NENs. Liver MRI, ideally with a hepatocyte-specific contrast agent, should be used in the evaluation of hepatic metastases. Imaging informs decisions regarding both surgical approaches and systematic therapy (specifically, peptide receptor radionuclide therapy). This AJR Expert Panel Narrative Review describes the multimodality imaging features of small-bowel NENs; explores the optimal imaging modalities for their diagnosis, staging, and follow-up; and discusses how imaging may be used to guide therapy.

Therapeutic effects elicited by the probiotic Lacticaseibacillus rhamnosus GG in children with atopic dermatitis. The results of the ProPAD trial.

BACKGROUND: Atopic dermatitis (AD) is a chronic inflammatory skin disease affecting up to 20% of the pediatric population associated with alteration of skin and gut microbiome. Probiotics have been proposed for AD treatment. The ProPAD study aimed to investigate the therapeutic effects of the probiotic Lacticaseibacillus rhamnosus GG (LGG) in children with AD. METHODS: In total, 100 AD patients aged 6-36 months were enrolled in a randomized, double-blind, controlled trial to receive placebo (Group A) or LGG (1 x 1010 CFU/daily) (Group B) for 12 weeks. The primary outcome was the evaluation of the efficacy of LGG supplementation on AD severity comparing the Scoring Atopic Dermatitis (SCORAD) index at baseline (T0) and at 12-week (T12). A reduction of ≥8.7 points on the SCORAD index was considered as minimum clinically important difference (MCID). The secondary outcomes were the SCORAD index evaluation at 4-week (T16) after the end of LGG treatment, number of days without rescue medications, changes in Infant Dermatitis Quality Of Life questionnaire (IDQOL), gut microbiome structure and function, and skin microbiome structure. RESULTS: The rate of subjects achieving MCID at T12 and at T16 was higher in Group B (p < .05), and remained higher at T16 (p < .05)The number of days without rescue medications was higher in Group B. IDQOL improved at T12 in the Group B (p < .05). A beneficial modulation of gut and skin microbiome was observed only in Group B patients. CONCLUSIONS: The probiotic LGG could be useful as adjunctive therapy in pediatric AD. The beneficial effects on disease severity and quality of life paralleled with a beneficial modulation of gut and skin microbiome.

The Impact of Formula Choice for the Management of Pediatric Cow's Milk Allergy on the Occurrence of Other Allergic Manifestations: The Atopic March Cohort Study.

OBJECTIVES: To compare the impact of different formulas on the occurrence of other atopic manifestations and the time of immune tolerance acquisition. STUDY DESIGN: In a 36-month prospective cohort study, the occurrence of other atopic manifestations (eczema, urticaria, asthma, and rhinoconjunctivitis) and the time of immune tolerance acquisition were comparatively evaluated in immunoglobulin E-mediated children with cow's milk allergy (CMA) treated with extensively hydrolyzed casein formula containing the probiotic L. rhamnosus GG (EHCF + LGG), rice hydrolyzed formula, soy formula, extensively hydrolyzed whey formula (EHWF), or amino acid-based formula. RESULTS: In total, 365 subjects were enrolled into the study, 73 per formula cohort. The incidence of atopic manifestations was 0.22 (Bonferroni-corrected 95% CI 0.09-0.34) in the EHCF + LGG cohort; 0.52 (0.37-0.67) in the rice hydrolyzed formula cohort; 0.58 (0.43-0.72) in the soy formula cohort; 0.51 (0.36-0.66) in the EHWF cohort; and 0.77 (0.64-0.89) in the amino acid-based formula cohort. The incidence of atopic manifestations in the rice hydrolyzed formula, soy formula, EHWF, and amino acid-based formula cohorts vs the EHCF + LGG cohort was always greater than the prespecified absolute difference of 0.25 at an alpha-level of 0.0125, with corresponding risk ratios of 2.37 (1.46-3.86, P < .001) for rice hydrolyzed formula vs EHCF + LGG; 2.62 (1.63-4.22, P < .001) for soy formula vs EHCF + LGG; 2.31 (1.42-3.77, P < .001) for EHWF vs EHCF + LGG; and 3.50 (2.23-5.49, P < .001) for amino acid-based formula vs EHCF + LGG. The 36-month immune tolerance acquisition rate was greater in the EHCF + LGG cohort. CONCLUSIONS: The use of EHCF + LGG for CMA treatment is associated with lower incidence of atopic manifestations and greater rate of immune tolerance acquisition.

Small Bowel Neoplasms: A Pictorial Review.

Small bowel tumors are rare and account for approximately 3% of all gastrointestinal tumors in the United States. The incidence of small bowel neoplasms is rising-in particular, there is a rising incidence of small bowel carcinoid tumors. This may in part be due to small bowel lesion identification in an increasing number of cross-sectional imaging studies performed for other indications as well as increased use of advanced imaging techniques to assess specifically for small bowel disease. Diagnosis is a challenge owing to nonspecific clinical manifestation, rare occurrence, and low index of clinical suspicion. Yet, various small bowel neoplasms have characteristic imaging features at CT and MRI when optimal distention of the small bowel is achieved, correlating well with features seen in gross specimens. Understanding the imaging features of small bowel neoplasms is important to improve the radiologist's ability to diagnose and characterize small bowel neoplasms. Most small bowel tumors are clinically silent for long periods, and nearly half of the benign tumors are found incidentally during surgery or at cross-sectional imaging performed for other reasons. The authors review the imaging features of common benign and malignant small bowel neoplasms to aid the radiologist in diagnosis of small bowel tumors. ©RSNA, 2020.

Gut Microbiome Modulation for Preventing and Treating Pediatric Food Allergies.

The increasing prevalence and severity of pediatric food allergies (FA) demands innovative preventive and therapeutic strategies. Emerging evidence suggests a pivotal role for the gut microbiome in modulating susceptibility to FA. Studies have demonstrated that alteration of gut microbiome could precede FA, and that particular microbial community structures early in life could influence also the disease course. The identification of gut microbiome features in pediatric FA patients is driving new prevention and treatment approaches. This review is focused on the potential role of the gut microbiome as a target for FA prevention and treatment.

Dietary Treatment with Extensively Hydrolyzed Casein Formula Containing the Probiotic Lactobacillus rhamnosus GG Prevents the Occurrence of Functional Gastrointestinal Disorders in Children with Cow's Milk Allergy.

OBJECTIVE: To investigate whether the addition of the probiotic Lactobacillus rhamnosus GG (LGG) to the extensively hydrolyzed casein formula (EHCF) for cow's milk allergy (CMA) treatment could reduce the occurrence of functional gastrointestinal disorders (FGIDs). STUDY DESIGN: This cohort study included children with a positive history for CMA in the first year of life who were treated with EHCF alone or in combination with LGG and had evidence of immune tolerance acquisition to cow's milk for at least 12 months. FGID was diagnosed according to the Rome III diagnostic criteria by investigators unaware of previous treatment. A cohort of consecutive healthy children was also evaluated as a control population. RESULTS: A total of 330 subjects were included, 110 per cohort (EHCF, EHCF+LGG, and healthy controls). The rate of subjects with ≥1 FGID was significantly lower in the EHCF+LGG cohort compared with the EHCF cohort (40% vs 16.4%; P < .05). In the EHCF+LGG cohort, a lower incidence was observed for all components of the main study outcome. The prevalence of FGIDs in the healthy cohort was lower than that in the EHCF cohort and similar to that in the EHCF+LGG cohort. The incidence rate ratio of FGIDs for the EHCF+LGG cohort vs the EHCF cohort (0.40; 95% CI, 0.25-0.65; P < .001) was unmodified after correction for age at CMA diagnosis, breastfeeding, weaning time, and presence of a first-degree relative with an FGID. CONCLUSIONS: These results confirm the increased risk for developing FGIDs in children with CMA and suggest that EHCF+LGG could reduce this risk.

Bladder volume correction factors measured with 3D ultrasound and BladderScan.

INTRODUCTION: The aim of this study was to investigate conventional 3D ultrasound and portable BladderScan volume measurements and implement correction factors to ensure accurate volume metrics. MATERIALS AND METHODS: Healthy participants without urinary urgency were recruited for a prospective hydration study in which three consecutive voids were analyzed for two separate visits. Just before and after voiding, 3D ultrasound and BladderScan volumes were measured. Estimated voided volumes were calculated as the volume immediately prior to void minus any post void residual and were compared to actual voided volumes measured using a graduated container. Percent errors were calculated, and an algebraic method was implemented to create correction factors for 3D ultrasound and BladderScan. RESULTS: Sixteen individuals completed the study, and six voids were recorded for each participant. A total of 96 volume measurements ranging from 0 mL to 1050 mL with an average of 394 +/- 26 mL were analyzed. Both 3D ultrasound and BladderScan significantly underestimated voided volumes with averages of 296 +/- 22 and 362 +/- 27, respectively. Average percent error for the 3D ultrasound group was 30.1% (pre-correction) and 20.7% (post-correction) (p < 0.01) and 22.4% (pre-correction) and 21.8% (post-correction) for the BladderScan group (p = 0.20). The voided volume correction factors for 3D ultrasound and BladderScan were 1.30 and 1.06, respectively. CONCLUSION: BladderScan and 3D ultrasound typically underestimate voided volumes. Correction factors enabled more accurate measurements of voided volumes for both 3D ultrasound and BladderScan. Accurate volume measurements will be valuable for the development of non-invasive urodynamics techniques.

A Spectrum of Entities That May Mimic Abdominopelvic Abscesses Requiring Image-guided Drainage.

A variety of entities may mimic drainable abscesses. This can lead to misdiagnosis of these entities, unnecessary percutaneous placement of a pigtail drainage catheter, other complications, and delay in appropriate treatment of the patient. Types of entities that may mimic drainable abscesses include neoplasms (lymphoma, gallbladder cancer, gastrointestinal stromal tumor, ovarian cancer, mesenteric fibromatosis, ruptured mature cystic teratoma, recurrent malignancy in a surgical bed), ischemia/infarction (liquefactive infarction of the spleen, infarcted splenule), diverticula (calyceal, Meckel, and giant colonic diverticula), and congenital variants (obstructed duplicated collecting system). Postoperative changes, including expected anatomy after urinary diversion or Roux-en-Y gastric bypass and small bowel resection, may also pose a diagnostic challenge. Nonpyogenic infections (Mycobacterium tuberculosis, Mycobacterium avium complex, echinococcal cysts) and inflammatory conditions such as xanthogranulomatous pyelonephritis and gossypiboma could also be misinterpreted as drainable fluid collections. Appropriate recognition of these entities is essential for optimal patient care. This article exposes radiologists to a variety of entities for which percutaneous drainage may be requested, but is not indicated, and highlights important imaging findings associated with these entities to facilitate greater diagnostic accuracy and treatment in their practice. ©RSNA, 2018.

Consensus Statement of Society of Abdominal Radiology Disease-Focused Panel on Barium Esophagography in Gastroesophageal Reflux Disease.

OBJECTIVE: The Society of Abdominal Radiology established a panel to prepare a consensus statement on the role of barium esophagography in gastroesophageal reflux disease (GERD), as well as recommended techniques for performing the fluoroscopic examination and the gamut of findings associated with this condition. CONCLUSION: Because it is an inexpensive, noninvasive, and widely available study that requires no sedation, barium esophagography may be performed as the initial test for GERD or in conjunction with other tests such as endoscopy.

Follow the Stream: Imaging of Urinary Diversions.

Urinary diversion is a surgical technique to redirect the stream of urine, most often after cystectomy. Cystectomy may be performed both for benign and for malignant conditions. Bladder cancer is the most common indication for cystectomy, and most patients who undergo radical cystectomy and urinary diversion have muscle-invasive or high-risk non-muscle-invasive bladder cancer. There are two major surgical approaches for urinary diversions performed after radical cystectomy: continent and incontinent diversions. For incontinent urinary diversions, a cutaneous ostomy is used for continuous urine drainage (eg, ileal conduit). With a continent diversion procedure, the patient may void through the native urethra or self-catheterize through a surgically created stoma. The goals of imaging after urinary diversion are to assess postoperative anatomy, detect postoperative complications, evaluate for residual or recurrent tumor and metastatic disease, and monitor for upper tract distention and/or deterioration. Multiple imaging modalities and techniques may be used to evaluate urinary diversions, including computed tomographic and magnetic resonance urography, intravenous pyelography, ultrasonography, pouchography, loopography, and nephrostomy studies. Knowledge of the expected postoperative appearance after urinary diversions and potential postoperative complications is crucial because many complications may be clinically silent. Radiologists must be able to recognize the expected postoperative appearance as well as complications to facilitate appropriate diagnosis and treatment of patients after cystectomy and urinary diversion. (©)RSNA, 2016.

Dysphagia secondary to anterior cervical fusion: radiologic evaluation and findings in 74 patients.

OBJECTIVE: The objective of our study was to assess the frequency, cause, and time course of dysphagia after anterior cervical fusion (ACF). MATERIALS AND METHODS: A review of the surgical database revealed that 1789 patients underwent ACF procedures during the 8-year study period. A radiologic database review indicated that 80 of the 1789 patients underwent radiologic evaluation for the assessment of dysphagia after ACF. Three patients were excluded from the study because they had a history of dysphagia before ACF, and three additional patients were excluded because they had more recently undergone Nissen fundoplication, intubation, and radiation therapy, respectively. Modified barium swallow (MBS) studies and esophagrams of the 74 remaining patients were collected and analyzed to determine the cause of dysphagia and time course of dysphagia onset after surgery. RESULTS: Dysphagia was evaluated radiologically in 74 of the 1789 ACF patients (4.1%) using video MBS studies (n=66) and esophagography (n=26). Patients underwent radiologic evaluation from 1 to 1150 days after surgery (mean, 120 days after surgery); 76% of the patients presented more than 2 weeks after surgery. The location of the ACF in the study group was the upper, mid, and lower cervical spine in 5.4% (n=4), 55.4% (n=41), and 39.2% (n=29) of patients, respectively. Soft-tissue swelling with displacement of the pharynx or esophagus was identified in 91% of patients (n=67). More serious complications of ACF that resulted in dysphagia included surgical hardware displacement or bone graft displacement (n=18), esophageal perforation (n=3), and a retropharyngeal abscess (n=3). Pharyngeal functional abnormalities were detected in 50 patients, with penetration, aspiration, or both seen in 32. CONCLUSION: Dysphagia is an underrecognized but significant complication of ACF. After ACF, 4.1% of patients presented for radiologic evaluation of dysphagia. Although ACF procedures are most frequently performed in the lower cervical spine, dysphagia is a more common clinical problem after ACF in the mid cervical spine. Radiologic examinations should be specifically tailored to evaluate ACF patients.

Dysphagia revisited: common and unusual causes.

Dysphagia is a common clinical problem whose prevalence is increasing with the aging population in the United States. The term dysphagia is commonly used to describe subjective awareness of swallowing difficulty during the passage of a bolus from the mouth to the stomach or the perception of obstruction during swallowing. Dysphagia may be further classified as oropharyngeal or substernal, depending on the location of this sensation. It can be due to benign or malignant structural lesions, esophageal motility abnormalities, oropharyngeal dysfunction (including aspiration), neuromuscular disorders, or postsurgical changes and is also associated with gastroesophageal reflux disease. Pathologic conditions of the oral cavity, pharynx, esophagus, and proximal stomach can manifest with dysphagia. Imaging remains the preferred method for evaluating patients with dysphagia, and dysphagia is an increasingly encountered indication for radiologic evaluation. Fluoroscopic studies, including the modified barium swallow and esophagography in particular, are often used in the assessment of patients with dysphagia, and the techniques used for these studies should be tailored to the patient's needs. Fluoroscopic studies can be used to evaluate the esophagus for structural abnormalities (eg, webs, diverticula, strictures, masses) and to assess function (eg, the swallowing mechanism and esophageal motility). Knowledge of the imaging spectrum of disease entities that may cause dysphagia and thorough radiologic assessment with a tailored approach may help avoid misdiagnosis.

Imaging of bariatric surgery: normal anatomy and postoperative complications.

Obesity is a disease that has reached epidemic proportions in the United States and around the world. During the past 2 decades, bariatric surgery has become an increasingly popular form of treatment for morbid obesity. The most common bariatric procedures performed include laparoscopic Roux-en-Y gastric bypass, laparoscopic adjustable gastric banding, and laparoscopic sleeve gastrectomy. Fluoroscopic upper gastrointestinal examinations and abdominal computed tomography (CT) are the major imaging tests used to evaluate patients after these various forms of bariatric surgery. The purpose of this article is to present the surgical anatomy and normal imaging findings and postoperative complications for these bariatric procedures at fluoroscopic examinations and CT. Complications after Roux-en-Y gastric bypass include anastomotic leaks and strictures, marginal ulcers, jejunal ischemia, small bowel obstruction, internal hernias, intussusception, and recurrent weight gain. Complications after laparoscopic adjustable gastric banding include stomal stenosis, malpositioned bands, pouch dilation, band slippage, perforation, gastric volvulus, intraluminal band erosion, and port- and band-related problems. Finally, complications after sleeve gastrectomy include postoperative leaks and strictures, gastric dilation, and gastroesophageal reflux. The imaging features of these various complications of bariatric surgery are discussed and illustrated.