Marathon running and cell-cycle arrest biomarkers of acute kidney injury.

OBJECTIVES: Endurance exercise is known to cause a rise in serum creatinine. It is not known to what extent this rise reflects renal stress and a potential acute kidney injury (AKI). Increases in Insulin Like Growth Factor Binding Protein 7 (IGFBP7) and Tissue Inhibitor of Metalloprotinases-2 (TIMP-2), urinary biomarkers of cell cycle arrest and renal stress, are associated with the development of AKI in clinical populations. DESIGN: Repeated measures study. METHODS: Runners were recruited at the 2019 Brighton Marathon (UK) and provided urine and blood samples at baseline, immediately post-race and 24 h post-race. Serum creatinine, urinary creatinine and urinary IGFBP7 and TIMP-2 were analysed from the samples. RESULTS: Seventy nine participants (23 females, 56 males), aged 43 ±â€¯10 yrs. (mean ±â€¯SD), finish time 243 ±â€¯40mins were included for analysis. Serum creatinine increased over the race by 40 ±â€¯26% (p < 0.001), TIMP-2 increased by 555 ±â€¯697% (p < 0.001) and IGFBP7 increased by 1094 ±â€¯1491% (p < 0.001) over the race. A subset of twenty-two participants supplied samples 24 h post-race, reporting values similar to baseline for all variables. CONCLUSIONS: This study is the first to report large rises in IGFBP7 and TIMP-2 following marathon running. This suggests that rises in creatinine are not fully explained by changes in production and clearance and marathon running induces a state of kidney stress and potential injury.

Irritant Contact Dermatitis.

Contact dermatitis accounts for 95% of occupational skin disorders. Irritant contact dermatitis (ICD) is often caused by cumulative exposure to weak irritants, accounting for 80% of all cases of contact dermatitis. ICD can co-exist with atopic dermatitis (AD) and allergic contact dermatitis (ACD). Patients with AD and ACD may have a lower inflammatory threshold for developing ICD. Therefore, it needs to be distinguished from lesions of AD and ACD. ICD Patients report stinging and burning in excess of pruritus. Pruritus is classically reported by patients with AD and ACD. ICD lesions are typically well-demarcated unlike AD and ACD. ICD is diagnosed by exclusion. Patients undergo testing to rule out type I and type IV hypersensitivity. Negative results suggest a diagnosis of ICD. Management consists of irritant identification and avoidance with regular emollient use. Although ICD is more common in certain occupations, genetics and environment play significant roles in its development.

Identification of asthma phenotypes in a tertiary care medical center.

BACKGROUND: Asthma affects 5% to 10% of the population and its severity is assessed using 4 parameters: lung function, symptom frequency, rescue inhaler use, and number of asthma exacerbations. Asthma is increasingly recognized as a clinical syndrome rather than a single disease. However, the current classification system fails to reflect the heterogeneous characteristics of the disease. METHODS: A retrospective chart review of 139 patients with mild, moderate, and severe persistent asthma was performed. Variables including baseline and maximal forced expiratory volume over first second (percent predicted), and age of asthma onset were used to classify patients. RESULTS: This yielded 5 clusters similar to Severe Asthma Research Program (SARP). Subjects in cluster 1 (n = 32) and cluster 2 (n = 47) had early-onset atopic asthma and reduced lung function but differed in medication requirement and health care utilization. Cluster 3 (n = 32) consisted of older obese women with late-onset asthma, less atopy, and mildly reduced forced expiratory volume over first second. Members of cluster 4 (n = 20) and cluster 5 (n = 8) had atopic asthma with severe obstruction but differed in bronchodilator response, age of onset, and oral corticosteroid use. Compared with SARP, our subjects were older, had a higher percentage of African Americans and obesity, and less severe asthma (P < 0.05). The observed clusters differed from SARP clusters in the following: (1) more frequent asthma exacerbations and medication use among cluster 1 and cluster 2; (2) lower medication use in cluster 3 and cluster 4; (3) although total health care utilization was similar, there were fewer emergency department visits in cluster 3 (P < 0.05). CONCLUSIONS: The SARP algorithm may be used to classify diverse asthmatic populations into a clinically reproducible phenotypic cluster.

Allergic bronchopulmonary aspergillosis.

Allergic bronchopulmonary aspergillosis (ABPA) is caused by an exaggerated T(H)2 response to the ubiquitous mold Aspergillus fumigatus. ABPA develops in a small fraction of patients with cystic fibrosis and asthma, suggesting that intrinsic host defects play a major role in disease susceptibility. This article reviews current understanding of the immunopathology, clinical and laboratory findings, and diagnosis and management of ABPA. It highlights clinical and laboratory clues to differentiate ABPA from cystic fibrosis and asthma, which are challenging given clinical and serologic similarities. A practical diagnostic algorithm and management scheme to aid in the treatment of these patients is outlined.

Current approaches to the diagnosis and treatment of systemic mastocytosis.

OBJECTIVE: To review the clinical manifestations of mastocytosis and examine the recommended diagnostic procedures and therapeutic options available for the treatment of this condition. DATA SOURCES: PubMed searches were performed for articles published regarding presentation and classification of mastocytosis and the diagnostic criteria and treatment options for this condition using the keywords mastocytosis, clinical features, World Health Organization diagnostic criteria, management, pathogenesis, and urticaria pigmentosa. Retrieved articles were surveyed for additional citations. STUDY SELECTION: Articles were reviewed for relevance to the study objectives, and more recent articles were preferentially included. Prospective studies were preferentially included when available. RESULTS: Mastocytosis is a heterogeneous disorder that results from clonal mast cell proliferation. Symptoms are typically limited to the skin in the pediatric population, requiring only symptomatic treatment with spontaneous resolution by puberty. Disease course in adults ranges from minimally symptomatic in most to highly aggressive but tends to be persistent. Symptoms can be protean and nonspecific. The mainstay of treatment consists of avoidance of triggers of mast cell degranulation and symptom-based therapy. CONCLUSIONS: Mastocytosis should be suspected in patients who present with a constellation of symptoms, including flushing, abdominal pain, diarrhea, unexplained syncope, and classic urticaria pigmentosa lesions. Diagnosis should be established by a bone marrow biopsy in all adults. Staging should be performed to assess disease burden and evidence of end-stage organ damage. Patients should be offered symptom-based treatment and cytoreductive therapy only for aggressive systemic mastocytosis or an associated hematologic malignant neoplasm.

Glatiramer acetate: successful desensitization for treatment of multiple sclerosis.

BACKGROUND: Glatiramer acetate is an immunomodulatory drug that is widely prescribed for the treatment of multiple sclerosis. It is frequently associated with local injection site reactions and generalized urticaria. It is also associated with immediate postinjection systemic reactions in approximately 10% of patients. To our knowledge, no desensitization protocols for glatiramer acetate have been published to date. OBJECTIVES: To evaluate the safety and efficacy of glatiramer acetate desensitization in a series of patients with multiple sclerosis. METHODS: Six patients with multiple sclerosis and glatiramer acetate-associated local or systemic reactions underwent a 4-hour outpatient desensitization procedure at Cleveland Clinic between 2003 and 2008. Beginning with 20 ng, we administered subcutaneous glatiramer acetate suspension in increasing dosages every 15 minutes. Patient outcomes were monitored by return clinic visit and telephone follow-up. RESULTS: No episodes of anaphylaxis or serious adverse reactions occurred during or immediately after desensitization. One patient suspended therapy after 14 months due to persistent local injection site reactions. All other patients successfully continued glatiramer acetate therapy. CONCLUSION: Glatiramer acetate offers significant benefit to patients with multiple sclerosis. Our experience suggests that patients who suspend its use owing to local or systemic reactions can be successfully and safely desensitized and can resume medication use. To our knowledge, this is the first report of successful desensitization to glatiramer acetate in patients with multiple sclerosis.