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.

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.

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).

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.

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.

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.

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.

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.

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.

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.

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.

Food allergy knowledge, attitudes, and beliefs of parents with food-allergic children in the United States.

Parents of food-allergic children are responsible for risk assessment and management of their child's condition. Such practices are likely informed by parental knowledge, attitudes, and beliefs of food allergy. Our objective was to characterize food allergy knowledge and perceptions among parents with food-allergic children. Parents were recruited nationally between January 2008 and 2009 to complete the validated, web-based Chicago Food Allergy Research Survey for Parents of Children with Food Allergy. Findings were analyzed to provide composite/itemized knowledge scores, describe attitudes and beliefs, and examine the effects of participant characteristics on response. A sample of 2945 parents was obtained. Participants had an average knowledge score of 75% correct (range 19-100%). Strengths were observed in each content domain; e.g., 95% of participants accurately identified the signs of a milk-induced reaction. Weaknesses were limited to items assessing food allergy triggers/environmental risks and perceptions of susceptibility/prevalence; e.g., 52% of parents incorrectly believed young children are at higher risk for fatal anaphylaxis than adolescents. Parental attitudes/beliefs were diverse, although 85% agreed children should carry an EpiPen at school and 91% felt schools should have staff trained in food allergy. One in four parents reported food allergy caused a strain on their marriage/relationship, and 40% reported experiencing hostility from other parents when trying to accommodate their child's food allergy. In conclusion, parents in our study exhibited solid baseline knowledge although several important misconceptions were identified. While a broad spectrum of parental perceptions was observed, a large proportion of parents reported that their child's food allergy had an adverse impact on personal relationships and also agreed on certain policies to address food allergy in schools.

Age-related differences in the involvement of the prefrontal cortex in attentional control.

We investigated the relative involvement of cortical regions supporting attentional control in older and younger adults during performance on a modified version of the Stroop task. Participants were exposed to two different types of incongruent trials. One of these, an incongruent-ineligible condition, produces conflict at the non-response level, while the second, an incongruent-eligible condition, produces conflict at both non-response and response levels of information processing. Greater attentional control is needed to perform the incongruent-eligible condition compared to other conditions. We examined the cortical recruitment associated with this task in an event-related functional magnetic resonance imaging paradigm in 25 older and 25 younger adults. Our results indicated that while younger adults demonstrated an increase in the activation of cortical regions responsible for maintaining attentional control in response to increased levels of conflict, such sensitivity and flexibility of the cortical regions to increased attentional control demands was absent in older adults. These results suggest a limitation in older adults' capabilities for flexibly recruiting the attentional network in response to increasing attentional demands.

Development of the Chicago Food Allergy Research Surveys: assessing knowledge, attitudes, and beliefs of parents, physicians, and the general public.

BACKGROUND: Parents of children with food allergy, primary care physicians, and members of the general public play a critical role in the health and well-being of food-allergic children, though little is known about their knowledge and perceptions of food allergy. The purpose of this paper is to detail the development of the Chicago Food Allergy Research Surveys to assess food allergy knowledge, attitudes, and beliefs among these three populations. METHODS: From 2006-2008, parents of food-allergic children, pediatricians, family physicians, and adult members of the general public were recruited to assist in survey development. Preliminary analysis included literature review, creation of initial content domains, expert panel review, and focus groups. Survey validation included creation of initial survey items, expert panel ratings, cognitive interviews, reliability testing, item reduction, and final validation. National administration of the surveys is ongoing. RESULTS: Nine experts were assembled to oversee survey development. Six focus groups were held: 2/survey population, 4-9 participants/group; transcripts were reviewed via constant comparative methods to identify emerging themes and inform item creation. At least 220 participants per population were recruited to assess the relevance, reliability, and utility of each survey item as follows: cognitive interviews, 10 participants; reliability testing > or = 10; item reduction > or = 50; and final validation, 150 respondents. CONCLUSION: The Chicago Food Allergy Research surveys offer validated tools to assess food allergy knowledge and perceptions among three distinct populations: a 42 item parent tool, a 50 item physician tool, and a 35 item general public tool. No such tools were previously available.

Dissociation between the prevalence of atopy and allergic disease in rural China among children and adults.

BACKGROUND: The prevalence of allergic diseases is increasing worldwide, but the reasons are not well understood. Previous studies suggest that this trend might be associated with lifestyle and urbanization. OBJECTIVE: We sought to describe patterns of sensitization and allergic disease in an unselected agricultural Chinese population. METHODS: The data were derived from a community-based twin study in Anqing, China. Skin prick tests were performed to foods and aeroallergens. Atopy was defined as sensitization to 1 or more allergens. Allergic disease was ascertained by means of self-report. The analysis was stratified by sex and age (children [11-17 years] and adults [>or=18 years]) and included 1059 same-sex twin pairs. RESULTS: Of 2118 subjects, 57.6% were male (n = 1220). Ages ranged from 11 to 71 years, and 43.3% were children (n = 918). Atopy was observed in 47.2% (n = 999) of participants. The most common sensitizing foods were shellfish (16.7%) and peanut (12.3%). The most common sensitizing aeroallergens were dust mite (30.6%) and cockroach (25.2%). Birth order and zygosity had no effect on sensitization rates. Multivariate logistic regression models revealed that risk factors for sensitization include age for foods and sex for aeroallergens. The rates of food allergy and asthma were estimated to be less than 1%. CONCLUSIONS: Atopic sensitization was common in this rural farming Chinese population, particularly to shellfish, peanut, dust mite, and cockroach. The prevalence of allergic disease, in contrast, was quite low.

Food allergy knowledge, attitudes and beliefs: focus groups of parents, physicians and the general public.

BACKGROUND: Food allergy prevalence is increasing in US children. Presently, the primary means of preventing potentially fatal reactions are avoidance of allergens, prompt recognition of food allergy reactions, and knowledge about food allergy reaction treatments. Focus groups were held as a preliminary step in the development of validated survey instruments to assess food allergy knowledge, attitudes, and beliefs of parents, physicians, and the general public. METHODS: Eight focus groups were conducted between January and July of 2006 in the Chicago area with parents of children with food allergy (3 groups), physicians (3 groups), and the general public (2 groups). A constant comparative method was used to identify the emerging themes which were then grouped into key domains of food allergy knowledge, attitudes, and beliefs. RESULTS: Parents of children with food allergy had solid fundamental knowledge but had concerns about primary care physicians' knowledge of food allergy, diagnostic approaches, and treatment practices. The considerable impact of children's food allergies on familial quality of life was articulated. Physicians had good basic knowledge of food allergy but differed in their approach to diagnosis and advice about starting solids and breastfeeding. The general public had wide variation in knowledge about food allergy with many misconceptions of key concepts related to prevalence, definition, and triggers of food allergy. CONCLUSION: Appreciable food allergy knowledge gaps exist, especially among physicians and the general public. The quality of life for children with food allergy and their families is significantly affected.

Pediatric atopic dermatitis: the importance of food allergens.

Food allergy and atopic dermatitis often occur in the same patients. Food-induced eczema may be perceived as a controversial topic because the immunologic mechanisms have yet to be fully elucidated. Nevertheless, published clinical studies have clearly demonstrated that foods can induce symptoms in a subset of patients with atopic dermatitis. Those at greatest risk are young children in whom eczematous lesions are severe or recalcitrant to therapy. Allergy testing can be helpful but must be applied judiciously. A medical history obtained by a skilled and knowledgeable health care provider is of paramount importance to interpret test results appropriately. Finally, the implementation of proper dietary avoidance can improve symptoms and provide safety from potentially fatal anaphylaxis. However, if inappropriate prescribed, elimination diets can have significant negative nutritional and social consequences.

Food allergy: diagnosis, treatment, prognosis, and prevention.

Primary care providers are advised to refer to an allergist those children in whom they suspect a food allergic reaction. Approximately 6% of U.S. children have food allergy, although many more parents will present with concerns of a food-induced condition. At higher risk are young children with atopic dermatitis. Generally, the stronger the test response (wheal size or sIgE concentration), the more likely there is to be clinical allergy. However, testing must be applied judiciously. Most importantly, the medical history must be considered in order to interpret test results appropriately. Avoidance of the offending food allergen is currently the only way to prevent reactions. Because exposures and reactions can occur unexpectedly, patients and their families must be prepared to treat symptoms quickly with intramuscular epinephrine in the lateral thigh. Hopefully, additional treatment options will become available in the near future to ease the anxiety and fearfulness that parents and patients face on a daily basis. Until then, healthcare providers are urged to demonstrate the correct administration of autoinjectable epinephrine using a placebo device and review the technique with families on an ongoing basis.

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.