Use of Fosaprepitant for Management of Suspected Antimicrobial-Associated Nausea: A Case Report.

Intractable nausea can occur in numerous settings. We report on a 49-year-old woman with a past medical history of cystic fibrosis (CF) with chronic hypoxia, chronic nausea, complex infection history and frequent hospitalizations who was admitted to an academic medical center with a CF exacerbation. Her chronic nausea worsened with the use of antimicrobials, and she was unable to tolerate dopamine or serotonin antagonist antiemetics. Nausea persisted despite the use of benzodiazepines and antihistamines. She was given a one-time dose of fosaprepitant 150 mg intravenously (IV) with marked improvement of her nausea. During subsequent exacerbations, she again developed severe nausea which continued to respond well to a one-time dose of fosaprepitant 150 mg IV. Fosaprepitant is a substance P/neurokinin-1 (NK1) receptor antagonist that is FDA-approved for the prevention of chemotherapy-induced nausea and vomiting and has been used to prevent post-operative nausea and vomiting. Its use in other contexts has not been well established. This case suggests a role for fosaprepitant in the management of nausea outside the context of chemotherapy or general anesthesia.

A Quantitative Evaluation of Functional Recovery after Traumatic Lower Extremity Salvage.

INTRODUCTION: Soft tissue reconstruction is a routine component of lower extremity trauma care and focus is increasingly being directed towards understanding functional outcomes. This study aims to quantify functional recovery and identify variables associated with functional outcomes of patients who undergo traumatic limb salvage. METHODS: A retrospective review was performed of patients with lower extremity traumatic injuries requiring vascularized soft tissue reconstruction at a Level 1 trauma center between July 2007-December 2015. Postoperatively, patients were administered the 36-Item Short Form Health Survey Version 2 (SF-36v2) and the Lower Extremity Functional Scale (LEFS) questionnaires by telephone. Demographics, perioperative variables, and postoperative outcomes were analyzed by univariate and bivariate analysis. RESULTS: Forty-two patients with 42 flaps and a mean of 12.7 months follow up were included in the study. Limb salvage was successful in 38 patients (90.5%). Patients ≥ 40 years old had significantly worse SF-36v2 scores in physical functioning (P ≤0.01) and mental health (P ≤0.05) than their younger counterparts. Patients who had pre-existing hypertension demonstrated significantly lower physical functioning (P ≤0.01). Role limitation due to emotional health was significantly lower in patients who were female (P ≤0.01) or required revision surgery (P ≤0.01). The mean LEFS score was 37.7 ± 18.5. CONCLUSIONS: Patients exhibited poor functional outcomes following major limb trauma with attempted limb salvage based on two validated patient reported outcomes measures (PROMs). Patient characteristics should be considered in evaluating candidates for reconstruction to optimize outcomes and to effectively counsel patients on their functional prognosis.

Management of thumb carpometacarpal joint dislocations: A systematic review.

Although rare, thumb Carpometacarpal (CMC) joint dislocations can have significant complications which impact hand function. Optimal management is crucial in restoring pinch and grasp strength, but no agreement exists regarding treatment due to a paucity of literature on this subject. Systematic review was conducted involving non-operative and operative management of the CMC joint. 15 articles with a total of 60 thumbs were evaluated from published literature. 12/60 thumbs with isolated CMC joint dislocations were treated with closed reduction, with 4 cases needing additional ligament repair due to joint instability post-reduction. 51/60 of the isolated CMC joint dislocations had ligament reconstruction, with flexor carpi radialis tendon autograft (29/51) as the most popular option. 60/60 patients regained full function and stability of the CMC joint with significant pain relief. Although good surgical outcomes have been achieved, long term clinical outcome reporting is needed to develop a standardized approach to treatment.

A Systematic Review of Prognostic Factors for Sensory Recovery After Digital Nerve Reconstruction.

BACKGROUND: Successful digital nerve repair is crucial in preventing painful neuroma formation and restoring sensory function after traumatic hand injury. The purpose of this study is to identify prognostic factors affecting sensory recovery following digital nerve reconstruction. METHODS: A systematic review was conducted according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines including studies reporting patients 18 years and older, greater than 10 reconstructed digital nerves, and greater than or equal to 3 months follow-up. Studies with proximal nerve injuries in the same distribution or inadequate sensory data were excluded. Included studies were evaluated by methodological index for nonrandomized studies score. Possible predictors were examined using the t test and 1-way analysis of variance with α ≤ 0.05. RESULTS: Twenty-five studies met the inclusion criteria, consisting of 818 surgically reconstructed digital nerves (mean age, 38 years; 78% male) with a mean ± SD defect length of 1.5 ± 0.5 cm. Mean follow-up time was 22 months. Fifty-six percent of patients presented with concomitant injuries to tendons (31%) and the digital artery (13%). Mean ± SD time to surgical repair was 36 ± 73.8 days. Reconstructive techniques included 35% end-to-end primary neurorrhaphy, 31% nerve grafts, and 11% synthetic conduits. Postoperatively, 81% of the patients demonstrated sensory recovery of S3+/S4, with 45% complaining of hyperesthesia. Nerve reconstructions performed within 15 days of injury had significantly better static 2-point discrimination than delayed procedures (P = 0.02). Static 2-point discrimination measurements were also significantly better for shorter defect lengths (<1.3 cm, P = 0.05). No significant functional differences were found across age, follow-up time, injured digit or side, nor reconstructive technique. CONCLUSIONS: Digital nerve reconstruction has good to excellent sensory recovery in up to 81% of patients with improved results in nerve gaps less than 1.3 cm. Performing the reconstruction within 15 days of injury is also correlated with improved sensory recovery.

Vectra 3D Imaging for Quantitative Volumetric Analysis of the Upper Limb: A Feasibility Study for Tracking Outcomes of Lymphedema Treatment.

BACKGROUND: Secondary lymphedema of the upper limb is a common sequela following lymphadenectomy during oncologic surgery. The gold standard for evaluating treatment outcomes in upper limb lymphedema is limb volume measurement. However, current techniques lack sensitivity to localized changes. In this study, the Vectra 3D imaging system was used to accurately and precisely obtain volume measurements of the upper limb in patients with lymphedema. METHODS: A feasibility study was performed in 11 patients with lymphedema and 22 upper extremities; 24 arms were evaluated in total. Three-dimensional images were taken of the upper extremities, and Vectra 3D software was used to calculate the volume of the hand, forearm, and upper arm. These measurements were compared to traditional circumference (tape) and water displacement measurements. RESULTS: The 24 arm volumes ranged from 1517 to 4050 cc. The Vectra 3D provided precise and accurate volume measurements (average SD ± 1.0 percent of total volume). Measurements of the forearm and upper arm correlated with circumference measurements (R = 0.991) and were in good agreement, with the mean difference between measurement techniques being 2.8 ± 2.0 percent. Three-dimensional measurements of hand, forearm, and upper arm correlated with water measurements (R = 0.990) and had a mean difference between measurement techniques of 2.6 ± 2.1 percent. CONCLUSIONS: The Vectra 3D system provides precise and accurate data comparable to those of the most commonly used technique to estimate limb volume (tape measurement) and gold-standard water volume measurement. Three-dimensional imaging also offers several advantages, including time efficiency and obtaining localized measurements with high spatial resolution. CLINICAL QUESTION/LEVEL OF EVIDENCE: Diagnostic, II.

A randomized, double-blind, placebo-controlled study of omalizumab combined with oral immunotherapy for the treatment of cow's milk allergy.

BACKGROUND: Although studies of oral immunotherapy (OIT) for food allergy have shown promise, treatment is frequently complicated by adverse reactions and, even when successful, has limited long-term efficacy because benefits usually diminish when treatment is discontinued. OBJECTIVE: We sought to examine whether the addition of omalizumab to milk OIT reduces treatment-related reactions, improves outcomes, or both. METHODS: This was a double-blind, placebo-controlled trial with subjects randomized to omalizumab or placebo. Open-label milk OIT was initiated after 4 months of omalizumab/placebo with escalation to maintenance over 22 to 40 weeks, followed by daily maintenance dosing through month 28. At month 28, omalizumab was discontinued, and subjects passing an oral food challenge (OFC) continued OIT for 8 weeks, after which OIT was discontinued with rechallenge at month 32 to assess sustained unresponsiveness (SU). RESULTS: Fifty-seven subjects (7-32 years) were randomized, with no significant baseline differences in age, milk-specific IgE levels, skin test results, or OFC results. At month 28, 24 (88.9%) omalizumab-treated subjects and 20 (71.4%) placebo-treated subjects passed the 10-g "desensitization" OFC (P = .18). At month 32, SU was demonstrated in 48.1% in the omalizumab group and 35.7% in the placebo group (P = .42). Adverse reactions were markedly reduced during OIT escalation in omalizumab-treated subjects for percentages of doses per subject provoking symptoms (2.1% vs 16.1%, P = .0005), dose-related reactions requiring treatment (0.0% vs 3.8%, P = .0008), and doses required to achieve maintenance (198 vs 225, P = .008). CONCLUSIONS: In this first randomized, double-blind, placebo-controlled trial of omalizumab in combination with food OIT, we found significant improvements in measurements of safety but not in outcomes of efficacy (desensitization and SU).

Genome-wide association study identifies peanut allergy-specific loci and evidence of epigenetic mediation in US children.

Food allergy (FA) affects 2%-10% of US children and is a growing clinical and public health problem. Here we conduct the first genome-wide association study of well-defined FA, including specific subtypes (peanut, milk and egg) in 2,759 US participants (1,315 children and 1,444 parents) from the Chicago Food Allergy Study, and identify peanut allergy (PA)-specific loci in the HLA-DR and -DQ gene region at 6p21.32, tagged by rs7192 (P=5.5 × 10(-8)) and rs9275596 (P=6.8 × 10(-10)), in 2,197 participants of European ancestry. We replicate these associations in an independent sample of European ancestry. These associations are further supported by meta-analyses across the discovery and replication samples. Both single-nucleotide polymorphisms (SNPs) are associated with differential DNA methylation levels at multiple CpG sites (P<5 × 10(-8)), and differential DNA methylation of the HLA-DQB1 and HLA-DRB1 genes partially mediate the identified SNP-PA associations. This study suggests that the HLA-DR and -DQ gene region probably poses significant genetic risk for PA.

Baked milk- and egg-containing diet in the management of milk and egg allergy.

Cow's milk (CM) and hen's egg allergies are among the most common food allergies in children. With evidence of increasing food allergy prevalence and more persistent disease, it has become vital to improve the management of CM and egg allergies. The ability to tolerate baked milk or egg, such as in a cake or muffin, has been associated with an increased chance of tolerance development. Studies report that about 70% of CM- and egg-allergic children can tolerate baked milk or egg and that incorporating baked milk or egg into the diet is well tolerated. Being able to add baked milk or egg into the diet can also increase quality of life by expanding the diet, boosting nutrition, and promoting inclusion in social activities. There is some debate over how baked milk and egg should be introduced, at home or in a supervised setting. Anaphylaxis and treatment with epinephrine during baked milk or egg challenges have been reported. Study of potential biomarkers to predict tolerability of baked milk and egg, such as serum specific IgE levels and skin prick test wheal diameters, is ongoing. Many parents can reliably report that their CM- or egg-allergic child is already consuming baked goods without symptoms. However, for those who cannot report such tolerance, the most prudent approach is to perform a supervised oral food challenge to determine the tolerability of baked milk and egg. The purpose of this article was to review the pathophysiology, clinical data, and safety of baked milk and egg and provide a practical guide to managing CM allergy and/or egg allergy. Recipes for baked milk and egg challenges and guidance on how to add baked milk and egg if tolerated to the child's regular diet are provided.

Relating microarray component testing and reported food allergy and food-triggered atopic dermatitis: a real-world analysis.

BACKGROUND: High epitope diversity has been associated with increased IgE-mediated food allergy severity. OBJECTIVE: To characterize associations between results from an automated microarray system and self-reported food allergy and food-triggered atopic dermatitis (AD). METHODS: Families with food allergic children were identified from a Jewish community in Lakewood, New Jersey, with immediate family members without food allergy or food-triggered AD serving as controls for the identified children. Sets of microarray components analyzed were to milk (Bos d 4, Bos d 5, Bos d 8, Bos d lactoferrin), egg (Gal d 1, Gal d 2, Gal d 3, Gal d 5), and peanut (Ara h 1, Ara h 2, Ara h 3, Ara h 6). RESULTS: Seventy-three patients from 23 families were recruited. Culprit foods included milk (n = 20), egg (n = 10), and peanut (n = 6) for food allergy and milk (n = 10) and egg (n = 7) for food-triggered AD. Odds of having had a self-reported related food allergy or food-triggered AD reaction significantly increased with a higher number of detectable microarray components to that food. Ara h 1, Ara h 2, and Ara h 6 were individually associated with reported peanut allergy, and Bos d 4 was individually associated with reported milk allergy. The number of egg components significantly increased the odds of having related food-triggered AD. CONCLUSION: High diversity of food allergen components relates well to self-reported history of food allergy and food-associated AD.

Neurobiological markers of exercise-related brain plasticity in older adults.

The current study examined how a randomized one-year aerobic exercise program for healthy older adults would affect serum levels of brain-derived neurotrophic factor (BDNF), insulin-like growth factor type 1 (IGF-1), and vascular endothelial growth factor (VEGF) - putative markers of exercise-induced benefits on brain function. The study also examined whether (a) change in the concentration of these growth factors was associated with alterations in functional connectivity following exercise, and (b) the extent to which pre-intervention growth factor levels were associated with training-related changes in functional connectivity. In 65 participants (mean age=66.4), we found that although there were no group-level changes in growth factors as a function of the intervention, increased temporal lobe connectivity between the bilateral parahippocampus and the bilateral middle temporal gyrus was associated with increased BDNF, IGF-1, and VEGF for an aerobic walking group but not for a non-aerobic control group, and greater pre-intervention VEGF was associated with greater training-related increases in this functional connection. Results are consistent with animal models of exercise and the brain, but are the first to show in humans that exercise-induced increases in temporal lobe functional connectivity are associated with changes in growth factors and may be augmented by greater baseline VEGF.

IgE-mediated cow's milk allergy in children.

The age at which the majority of children outgrow cow's milk allergy now appears to be later than previously reported. Recent studies have attempted to elucidate factors that may help prevent cow's milk allergy, assess markers of persistence, and evaluate the usefulness of new diagnostic methods. Strict avoidance of cow's milk has been the mainstay of treatment. However, given the potential nutritional, social, and immunologic ramifications of cow's milk elimination from a child's diet, there has been a focus on reevaluating this therapeutic approach.

Paradigm shift in the management of milk and egg allergy: baked milk and egg diet.

Heat treatment of several foods, including all types of cooking, has been mainly used to minimize the number of viable microbes, reduce pathogenicity, and destroy the undesirable enzymes, maintaining food quality. In addition, food processing improves sensory, nutritional, and physical properties of the foods, due to food protein denaturation. Heat-induced alterations of food proteins can attenuate allergenicity. In this article, the authors review the important role of thermal processing on milk and egg proteins, which comprise the commonest food allergies in infancy and early childhood.

Food allergy: a glimpse into the inner workings of gut immunology.

PURPOSE OF REVIEW: How food protein becomes recognized as an allergen remains a fundamental question. Previous studies indicated that the pathophysiology of food allergy is because of a skewed Th2 response to specific food glycoproteins. The focus has now shifted to understanding how a failure of regulatory mechanisms results in food allergy. This review summarizes the recent findings elucidating the small intestine's role in the pathophysiology of food allergy and the immune mechanisms of oral tolerance. RECENT FINDINGS: Gut homeostasis and immunity occur via a complex interplay of innate and adaptive immune responses. Immune exclusion is performed mainly by secretory IgA, although there are back-up mechanisms in place to induce oral tolerance when secretory IgA is lacking. Oral tolerance cannot occur in murine models lacking T regulatory cells, for which Foxp3+ is a key marker. Migration of Foxp3+ T cells from the mesenteric lymph nodes (MLNs) to the lamina propria occurs via gut-homing signals. Also in the MLNs are CD103+ dendritic cells, which drive the differentiation of Foxp3+ T cells in the presence of TGF-ß and retinoic acid produced from dietary vitamin A. Lastly, microenvironmental signals from the microbiome can serve to enhance these interactions. SUMMARY: We have focused primarily on local immunologic variables that may affect the induction of oral tolerance in the gut and the mechanisms elucidated in animal models. However, many other variables such as genetics, commensal microbiota, and diet are likely to be important factors.

Dietary baked milk accelerates the resolution of cow's milk allergy in children.

BACKGROUND: The majority (approximately 75%) of children with cow's milk allergy tolerate extensively heated (baked) milk products. Long-term effects of inclusion of dietary baked milk have not been reported. OBJECTIVE: We report on the outcomes of children who incorporated baked milk products into their diets. METHODS: Children evaluated for tolerance to baked milk (muffin) underwent sequential food challenges to baked cheese (pizza) followed by unheated milk. Immunologic parameters were measured at challenge visits. The comparison group was matched to active subjects (by using age, sex, and baseline milk-specific IgE levels) to evaluate the natural history of development of tolerance. RESULTS: Over a median of 37 months (range, 8-75 months), 88 children underwent challenges at varying intervals (range, 6-54 months). Among 65 subjects initially tolerant to baked milk, 39 (60%) now tolerate unheated milk, 18 (28%) tolerate baked milk/baked cheese, and 8 (12%) chose to avoid milk strictly. Among the baked milk-reactive subgroup (n = 23), 2 (9%) tolerate unheated milk, and 3 (13%) tolerate baked milk/baked cheese, whereas the majority (78%) avoid milk strictly. Subjects who were initially tolerant to baked milk were 28 times more likely to become unheated milk tolerant compared with baked milk-reactive subjects (P < .001). Subjects who incorporated dietary baked milk were 16 times more likely than the comparison group to become unheated milk tolerant (P < .001). Median casein IgG(4) levels in the baked milk-tolerant group increased significantly (P < .001); median milk IgE values did not change significantly. CONCLUSIONS: Tolerance of baked milk is a marker of transient IgE-mediated cow's milk allergy, whereas reactivity to baked milk portends a more persistent phenotype. The addition of baked milk to the diet of children tolerating such foods appears to accelerate the development of unheated milk tolerance compared with strict avoidance.

Living with food allergy: allergen avoidance.

The primary treatment of food allergy is to avoid the culprit foods. This is a complex undertaking that requires education about reading the labels of manufactured products, understanding how to avoid cross-contact with allergens during food preparation, and communicating effectively with persons who are providing allergen-safe meals including relatives and restaurant personnel. Successful avoidance also requires a knowledge of nuances such as appropriate cleaning practices, an understanding of the risks of ingestion compared to skin contact or inhalation, that exposure could occur through unanticipated means such as through sharing utensils or passionate kissing, and that food may be a component of substances that are not ingested such as cosmetics, bath products, vaccines and medications. The authors review the necessary tools of avoidance that physicians and medical practitioners can use to guide their patients through the complexities of food avoidance.

Exercise training increases size of hippocampus and improves memory.

The hippocampus shrinks in late adulthood, leading to impaired memory and increased risk for dementia. Hippocampal and medial temporal lobe volumes are larger in higher-fit adults, and physical activity training increases hippocampal perfusion, but the extent to which aerobic exercise training can modify hippocampal volume in late adulthood remains unknown. Here we show, in a randomized controlled trial with 120 older adults, that aerobic exercise training increases the size of the anterior hippocampus, leading to improvements in spatial memory. Exercise training increased hippocampal volume by 2%, effectively reversing age-related loss in volume by 1 to 2 y. We also demonstrate that increased hippocampal volume is associated with greater serum levels of BDNF, a mediator of neurogenesis in the dentate gyrus. Hippocampal volume declined in the control group, but higher preintervention fitness partially attenuated the decline, suggesting that fitness protects against volume loss. Caudate nucleus and thalamus volumes were unaffected by the intervention. These theoretically important findings indicate that aerobic exercise training is effective at reversing hippocampal volume loss in late adulthood, which is accompanied by improved memory function.

Plasticity of brain networks in a randomized intervention trial of exercise training in older adults.

Research has shown the human brain is organized into separable functional networks during rest and varied states of cognition, and that aging is associated with specific network dysfunctions. The present study used functional magnetic resonance imaging (fMRI) to examine low-frequency (0.008 < f < 0.08 Hz) coherence of cognitively relevant and sensory brain networks in older adults who participated in a 1-year intervention trial, comparing the effects of aerobic and non-aerobic fitness training on brain function and cognition. Results showed that aerobic training improved the aging brain's resting functional efficiency in higher-level cognitive networks. One year of walking increased functional connectivity between aspects of the frontal, posterior, and temporal cortices within the Default Mode Network and a Frontal Executive Network, two brain networks central to brain dysfunction in aging. Length of training was also an important factor. Effects in favor of the walking group were observed only after 12 months of training, compared to non-significant trends after 6 months. A non-aerobic stretching and toning group also showed increased functional connectivity in the DMN after 6 months and in a Frontal Parietal Network after 12 months, possibly reflecting experience-dependent plasticity. Finally, we found that changes in functional connectivity were behaviorally relevant. Increased functional connectivity was associated with greater improvement in executive function. Therefore the study provides the first evidence for exercise-induced functional plasticity in large-scale brain systems in the aging brain, using functional connectivity techniques, and offers new insight into the role of aerobic fitness in attenuating age-related brain dysfunction.