ABSTRACT:We report three siblings, offspring of normal consanguineous parents, with a progressive neurological illness that began in midlife and was characterized primarily by chorea and leading to death in the fourth decade. The proband had erythrocyte acanthocytosis with normal serum β-lipoprotein. Biopsy of left gastrocnemius muscle showed neurogenic muscular atrophy. There was a decrease in the numbers of large myelinated axons of the sural nerve. Postmortem examination of two cases showed marked atrophy, neuronal loss and gliosis of the caudate nucleus and putamen. Autosomal recessive inheritance is likely in this family.

Background Imbalance in l-arginine and nitric oxide (NO) metabolism has been implicated in the pathophysiology of asthma and obstructive sleep apnea (OSA), and both diseases impact the other’s morbidity. We sought to determine whether l-arginine/NO metabolism differs between adults with asthma with or without comorbid OSA, and its association with asthma morbidity. Methods This is a cross-sectional study of 322 adults with asthma recruited in Denver, CO and New York City, NY. Data were collected on OSA status, spirometry, and metrics of asthma control and morbidity. l-Arginine metabolites were quantified in patient serum. Bivariate analyses and multiple regression were performed to determine differences between l-arginine metabolism, OSA and association with asthma morbidity. Results Among the 322 participants, 92 (28.5%) had OSA. The cohort was 81.6% female, 23.4% identified as Black and 30.6% as Latino. Patients with asthma and OSA had significantly higher serum concentrations of NO synthase inhibitor asymmetric dimethylarginine (ADMA) (p-value = 0.019), lower L-arginine to ornithine ratios (p-value = 0.003), and increased ornithine (p-value = 0.001) and proline levels (p-value < 0.001) compared to those without OSA. In adjusted models, OSA was associated with worse asthma control, adjusted mean difference in asthma control questionnaire of 0.36 (95% confidence interval [CI]: 0.06 to 0.65), and asthma quality of life questionnaire, adjusted mean difference: − 0.53 (95% CI: − 0.85 to − 0.21), after adjusting for relevant covariates including body mass index and L-arginine metabolites. Conclusions Adults with asthma and OSA had increased ADMA, an inhibitor of nitric oxide synthase, and greater metabolism of l-arginine via the arginase pathway compared to those with asthma alone, indicating a possible shared pathophysiological mechanism of these diseases.

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Background Imbalance in L-arginine and nitric oxide (NO) metabolism has been implicated in the pathophysiology of asthma and obstructive sleep apnea (OSA), and both diseases impact the other’s morbidity. We sought to determine whether L-arginine/NO metabolism differs between adults with asthma with or without comorbid OSA, and its association with asthma morbidity. Methods This is a cross-sectional study of 322 adults with asthma recruited in Denver, CO and New York City, NY. Data were collected on OSA status, spirometry, and metrics of asthma control and morbidity. L-arginine metabolites were quantified in patient serum. Bivariate analyses and multiple regression were performed to determine differences between L-arginine metabolism, OSA and association with asthma morbidity. Results Among the 322 participants, 92 (28.5%) had OSA. The cohort was 81.6% female, 23.4% identified as Black and 30.6% as Latino. Patients with asthma and OSA had significantly higher serum concentrations of NO synthase inhibitor asymmetric dimethylarginine (ADMA) (p-value = 0.019), lower L-arginine to ornithine ratios (p-value = 0.003), and increased ornithine (p-value = 0.001) and proline levels (p-value < 0.001) compared to those without OSA. In adjusted models, OSA was associated with worse asthma control, mean difference in asthma control questionnaire of 0.36 (95% confidence interval [CI]: 0.06 to 0.65), and asthma quality of life questionnaire, mean difference: -0.53 (95% CI: -0.85 to -0.21), after adjusting for relevant covariates including body mass index and L-arginine metabolites. Conclusions Adults with asthma and OSA had increased ADMA, an inhibitor of nitric oxide synthase, and greater metabolism of L-arginine via the arginase pathway compared to those with asthma alone, indicating a possible shared pathophysiological mechanism of these diseases.

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Legal status in the United States is an important social determinant of health. Undocumented immigrants face several obstacles in obtaining equivalent healthcare to United States citizens or resident aliens. Despite these obstacles, undocumented individuals are eligible to be listed for and receive organ transplant for advanced disease. We hypothesize that this population represents healthy workers, and has significantly different social and clinical needs pre-transplantation than the population of listed US Citizens or resident aliens. We sought to describe this population of undocumented patients, listed for lung transplantation, for the first time, to identify potential disparities in care and develop strategies to address the needs of this unique patient population.METHODS: Using the de-identified United Network for Organ Sharing (UNOS) Thoracic dataset we identified 64,585 individuals who had been listed for lung transplant between 1985 and 2020. We identified 232 undocumented individuals; nonresident aliens who did not travel to the US for the purpose of transplant evaluation or have their care paid for by a foreign healthcare system. We evaluated demographic, disease characteristic, and payer differences between documented and undocumented individuals using bivariate tests of difference. We report Cohen's d statistics, when possible, to characterize the degree of difference between the two populations. RESULTS:The mean age of undocumented individuals listed for transplant was 41.1 years, which was significantly lower than that of documented individuals (p < 0.00001). The proportion of individuals with the listing diagnoses of idiopathic pulmonary fibrosis (IPF), pulmonary arterial hypertension (PAH), and bronchiectasis was significantly higher in the undocumented cohort of patients (p-values of 0.002, < 0.001, and <0.001 respectively). However, the proportion of undocumented individuals with a listing diagnosis of chronic obstructive pulmonary disease (COPD) was significantly lower (p < 0.001). Patients within the undocumented cohort also had a higher initial Lung Allocation Score (LAS) than documented individuals with an average score of 43.1 indicating more severe disease (p = 0.046). Undocumented individuals were less likely to have a history of tobacco use (p < 0.001). The majority of undocumented individuals were self-pay and there were no significant differences in Medicaid users between both cohorts. CONCLUSIONS: Undocumented patients listed for lung transplant represent a younger population of non-smokers who likely have very different medical and social needs than US citizens or resident aliens. Further evaluation of the specific needs of this population is warranted, particularly in areas with high populations of undocumented individuals.CLINICAL IMPLICATIONS: These patients are not more likely than US citizens or resident aliens to rely on public insurance programs (e.g. Medicare and Medicaid) indicating that the current practice of listing these individuals does not place an excessive burden on...