Impact of Upper Limb Motor Recovery on Functional Independence after Traumatic Low Cervical Spinal Cord Injury

Cervical Spinal Cord Injury (SCI) causes devastating loss of upper limb function and independence. Restoration of upper limb function can have a profound impact on independence and quality-of-life. In low-cervical SCI (level C5-C8), upper limb function can be restored via reinnervation strategies such as nerve transfer surgery. However, the translation of recovered upper limb motor function into functional independence in activities of daily living (ADLs) remains unknown in low cervical SCI (i.e., tetraplegia). The objective of this study was to evaluate the association of patterns in upper limb motor recovery with functional independence in ADLs. This will then inform prioritization of reinnervation strategies focused to maximize function in patients with tetraplegia. This retrospective study performed a secondary analysis of low cervical SCI patients (C5-C8) enrolled in the SCI Model Systems (SCIMS) database. Baseline neurological examinations and their association with functional independence in major ADLs, i.e., eating, bladder management, and transfers (bed/wheelchair/chair) were evaluated. Motor functional recovery was defined as achieving motor strength, in modified research council (MRC) grade, of 3/5 at one-year from 2/5 at baseline. The association of motor function recovery with functional independence at one year follow-up was compared in patients with recovered elbow flexion (C5), wrist extension (C6), elbow extension (C7), and finger flexion (C8). A multivariable logistic regression analysis, adjusting for known factors influencing recovery following SCI, was performed to evaluate the impact of motor function at one year on a composite outcome of functional independence in major ADLs. Composite outcome was defined as functional independence measure score of 6 or higher (complete independence) in at least 2 domains among eating, bladder management, and transfers. Between 1992 and 2016, 1,090 patients with low cervical SCI and complete neurological/ functional measures were included. At baseline, 67% of patients had complete SCI and 33% had incomplete SCI. The majority of patients were dependent in eating, bladder management, and transfers. At one-year follow-up, the largest proportion of patients who recovered motor function in finger flexion (C8) and elbow extension (C7) gained independence in eating, bladder management, and transfers. In multivariable analysis, patients who had recovered finger flexion (C8) or elbow extension (C7) had higher odds of gaining independence in a composite of major ADLs (odds ratio [OR]=3.13 and OR=2.87, respectively, p<0.001). Age 60 years (OR=0.44, p=0.01), and complete SCI (OR=0.43, p=0.002) were associated with reduced odds of gaining independence in ADLs. After cervical SCI, finger flexion (C8) and elbow extension (C7) recovery translate into greater independence in eating, bladder management and transfers. These results can be used to design individualized reinnervation plans to reanimate upper limb function and maximize independence in patients with low cervical SCI

Association of upper-limb neurological recovery with functional outcomes in high cervical spinal cord injury

High cervical spinal cord injury (SCI) results in complete loss of upper-limb function, resulting in debilitating tetraplegia and permanent disability. Spontaneous motor recovery occurs to varying degrees in some patients, particularly in the 1st year postinjury. However, the impact of this upper-limb motor recovery on long-term functional outcomes remains unknown. The objective of this study was to characterize the impact of upper-limb motor recovery on the degree of long-term functional outcomes in order to inform priorities for research interventions that restore upper-limb function in patients with high cervical SCI. A prospective cohort of high cervical SCI (C1-4) patients with American Spinal Injury Association Impairment Scale (AIS) grade A-D injury and enrolled in the Spinal Cord Injury Model Systems Database was included. Baseline neurological examinations and functional independence measures (FIMs) in feeding, bladder management, and transfers (bed/wheelchair/chair) were evaluated. Independence was defined as score ≥ 4 in each of the FIM domains at 1-year follow-up. At 1-year follow-up, functional independence was compared among patients who gained recovery (motor grade ≥ 3) in elbow flexors (C5), wrist extensors (C6), elbow extensors (C7), and finger flexors (C8). Multivariable logistic regression evaluated the impact of motor recovery on functional independence in feeding, bladder management, and transfers. Between 1992 and 2016, 405 high cervical SCI patients were included. At baseline, 97% of patients had impaired upper-limb function with total dependence in eating, bladder management, and transfers. At 1 year of follow-up, the largest proportion of patients who gained independence in eating, bladder management, and transfers had recovery in finger flexion (C8) and wrist extension (C6). Elbow flexion (C5) recovery had the lowest translation to functional independence. Patients who achieved elbow extension (C7) were able to transfer independently. On multivariable analysis, patients who gained elbow extension (C7) and finger flexion (C8) were 11 times more likely to gain functional independence (OR 11, 95% CI 2.8-47, p < 0.001) and patients who gained wrist extension (C6) were 7 times more likely to gain functional independence (OR 7.1, 95% CI 1.2-56, p = 0.04). Older age (≥ 60 years) and motor complete SCI (AIS grade A-B) reduced the likelihood of gaining independence. After high cervical SCI, patients who gained elbow extension (C7) and finger flexion (C8) had significantly greater independence in feeding, bladder management, and transfers than those with recovery in elbow flexion (C5) and wrist extension (C6). Recovery of elbow extension (C7) also increased the capability for independent transfers. This information can be used to set patient expectations and prioritize interventions that restore these upper-limb functions in patients with high cervical SCI

Guidelines for the diagnosis and management of food allergy in the United States: summary of the NIAID-Sponsored Expert Panel report

Section 1. Introduction1.1. Overview1.2. Relationship of the US Guidelines to other guidelines1.3. How the Guidelines were developed1.3.1. The Coordinating Committee1.3.2. The Expert Panel1.3.3. The independent, systematic literature review and report1.3.4. Assessing the quality of the body of evidence1.3.5. Preparation of the draft Guidelines and Expert Panel deliberations1.3.6. Public comment period and draft Guidelines revision1.4. Defining the strength of each clinical guideline1.5. SummarySection 2. Definitions, prevalence, and epidemiology of food allergy2.1. Definitions2.1.1. Definitions of food allergy, food, and food allergens2.1.2. Definitions of related terms2.1.3. Definitions of specific food-induced allergic conditions2.2. Prevalence and epidemiology of food allergy2.2.1. Systematic reviews of the prevalence of food allergy2.2.2. Prevalence of allergy to specific foods, food-induced anaphylaxis, and food allergy with comorbid conditionsSection 3. Natural history of food allergy and associated disorders3.1. Natural history of food allergy in children3.2. Natural history of levels of allergen-specific IgE to foods in children3.3. Natural history of food allergy in adults3.4. Natural history of conditions that coexist with food allergy3.4.1. Asthma3.4.2. Atopic dermatitis3.4.3. Eosinophilic esophagitis3.4.4. Exercise-induced anaphylaxis3.5. Risk factors for the development of food allergy3.6. Risk factors for severity of allergic reactions to foods3.7. Incidence, prevalence, and consequences of unintentional exposure to food allergensSection 4. Diagnosis of food allergy4.1. When should food allergy be suspected?4.2. Diagnosis of IgE-mediated food allergy4.2.1. Medical history and physical examination4.2.2. Methods to identify the causative food4.2.2.1. Skin prick test4.2.2.2. Intradermal tests4.2.2.3. Total serum IgE4.2.2.4. Allergen-specific serum IgE4.2.2.5. Atopy patch test4.2.2.6. Use of skin prick tests, sIgE tests, and atopy patch tests in combination4.2.2.7. Food elimination diets4.2.2.8. Oral food challenges4.2.2.9. Nonstandardized and unproven procedures4.3. Diagnosis of non-IgE-mediated immunologic adverse reactions to food4.3.1. Eosinophilic gastrointestinal diseases4.3.2. Food protein-induced enterocolitis syndrome4.3.3. Food protein-induced allergic proctocolitis4.3.4. Food protein-induced enteropathy syndrome4.3.5. Allergic contact dermatitis4.3.6. Systemic contact dermatitis4.4. Diagnosis of IgE-mediated contact urticariaSection 5. Management of nonacute allergic reactions and prevention of food allergy5.1. Management of individuals with food allergy5.1.1. Dietary avoidance of specific allergens in IgE-mediated food allergy5.1.2. Dietary avoidance of specific allergens in non-IgE-mediated food allergy5.1.3. Effects of dietary avoidance on associated and comorbid conditions, such as atopic dermatitis, asthma, and eosinophilic esophagitis5.1.4. Food avoidance and nutritional status5.1.5. Food labeling in food allergy management5.1.6. When to re-evaluate patients with food allergy5.1.7. Pharmacologic intervention for the prevention of food-induced allergic reactions5.1.7.1. IgE-mediated reactions5.1.7.2. Non-IgE-mediated reactions5.1.8. Pharmacologic intervention for the treatment of food-induced allergic reactions5.1.9. Immunotherapy for food allergy management5.1.9.1. Allergen-specific immunotherapy5.1.9.2. Immunotherapy with cross-reactive allergens5.1.10. Quality-of-life issues associated with food allergy5.1.11. Vaccinations in patients with egg allergy5.1.11.1. Measles, mumps, rubella, and varicella vaccine5.1.11.2. Influenza vaccine5.1.11.3. Yellow fever vaccine5.1.11.4. Rabies vaccines5.2. Management of individuals at risk for food allergy5.2.1. Nonfood allergen avoidance in at-risk patients5.2.2. Dietary avoidance of foods with cross-reactivities in at-risk patients5.2.3. Testing of allergenic foods in patients at high risk prior to introduction5.2.4. Testing in infants and children with persistent atopic dermatitis5.3. Prevention of food allergy5.3.1. Maternal diet during pregnancy and lactation5.3.2. Breast-feeding5.3.3. Special diets in infants and young children5.3.3.1. Soy infant formula versus cow's milk formula5.3.3.2. Hydrolyzed infant formulas versus cow's milk formula or breast-feeding5.3.4. Timing of introduction of allergenic foods to infantsSection 6. Diagnosis and management of food-induced anaphylaxis and other acute allergic reactions to foods6.1. Definition of anaphylaxis6.2. Diagnosis of acute, life-threatening, food-induced allergic reactions6.3. Treatment of acute, life-threatening, food-induced allergic reactions6.3.1. First-line and adjuvant treatment for food-induced anaphylaxis6.3.2. Treatment of refractory anaphylaxis6.3.3. Possible risks of acute therapy for anaphylaxis6.3.4. Treatment to prevent biphasic or protracted food-induced allergic reactions6.3.5. Management of milder, acute food-induced allergic reactions in health care settings6.4. Management of food-induced anaphylaxisAppendix A. Primary author affiliations and acknowledgmentsAppendix B. List of abbreviationsReference<br/

Guidelines for the diagnosis and management of food allergy in the United States: report of the NIAID-sponsored expert panel

Food allergy is an important public health problem that affects children and adults and may be increasing in prevalence. Despite the risk of severe allergic reactions and even death, there is no current treatment for food allergy: the disease can only be managed by allergen avoidance or treatment of symptoms. The diagnosis and management of food allergy also may vary from one clinical practice setting to another. Finally, because patients frequently confuse nonallergic food reactions, such as food intolerance, with food allergies, there is an unfounded belief among the public that food allergy prevalence is higher than it truly is. In response to these concerns, the National Institute of Allergy and Infectious Diseases, working with 34 professional organizations, federal agencies, and patient advocacy groups, led the development of clinical guidelines for the diagnosis and management of food allergy. These Guidelines are intended for use by a wide variety of health care professionals, including family practice physicians, clinical specialists, and nurse practitioners. The Guidelines include a consensus definition for food allergy, discuss comorbid conditions often associated with food allergy, and focus on both IgE-mediated and non-IgE-mediated reactions to food. Topics addressed include the epidemiology, natural history, diagnosis, and management of food allergy, as well as the management of severe symptoms and anaphylaxis. These Guidelines provide 43 concise clinical recommendations and additional guidance on points of current controversy in patient management. They also identify gaps in the current scientific knowledge to be addressed through future research

Content and Performance of the MiniMUGA Genotyping Array, a New Tool To Improve Rigor and Reproducibility in Mouse Research.

The laboratory mouse is the most widely used animal model for biomedical research, due in part to its well annotated genome, wealth of genetic resources and the ability to precisely manipulate its genome. Despite the importance of genetics for mouse research, genetic quality control (QC) is not standardized, in part due to the lack of cost effective, informative and robust platforms. Genotyping arrays are standard tools for mouse research and remain an attractive alternative even in the era of high-throughput whole genome sequencing. Here we describe the content and performance of a new iteration of the Mouse Universal Genotyping Array, MiniMUGA, an array-based genetic QC platform with over 11,000 probes. In addition to robust discrimination between most classical and wild-derived laboratory strains, MiniMUGA was designed to contain features not available in other platforms: 1) chromosomal sex determination, 2) discrimination between substrains from multiple commercial vendors, 3) diagnostic SNPs for popular laboratory strains, 4) detection of constructs used in genetically engineered mice, and 5) an easy-to-interpret report summarizing these results. In-depth annotation of all probes should facilitate custom analyses by individual researchers. To determine the performance of MiniMUGA we genotyped 6,899 samples from a wide variety of genetic backgrounds. The performance of MiniMUGA compares favorably with three previous iterations of the MUGA family of arrays both in discrimination capabilities and robustness. We have generated publicly available consensus genotypes for 241 inbred strains including classical, wild-derived and recombinant inbred lines. Here we also report the detection of a substantial number of XO and XXY individuals across a variety of sample types, new markers that expand the utility of reduced complexity crosses to genetic backgrounds other than C57BL/6, and the robust detection of 17 genetic constructs. We provide preliminary evidence that the array can be used to identify both partial sex chromosome duplication and mosaicism, and that diagnostic SNPs can be used to determine how long inbred mice have been bred independently from the relevant main stock. We conclude that MiniMUGA is a valuable platform for genetic QC and an important new tool to the increase rigor and reproducibility of mouse research