Citations

Abstract The American Thoracic Society Core Curriculum updates clinicians annually in adult and pediatric pulmonary disease, medical critical care, and sleep medicine in a 3- to 4-year recurring cycle of topics. The topics of the 2020 Pulmonary Core Curriculum include pulmonary vascular disease (submassive pulmonary embolism, chronic thromboembolic pulmonary hypertension, and pulmonary hypertension) and pulmonary infections (community-acquired pneumonia, pulmonary nontuberculous mycobacteria, opportunistic infections in immunocompromised hosts, and coronavirus disease [COVID-19]).

Chronic myeloid leukemia (CML) is defined by the presence of Philadelphia chromosome (Ph) which results from a reciprocal translocation between chromosomes 9 and 22 [t(9;22] that gives rise to a BCR-ABL1 fusion gene. CML occurs in 3 different phases (chronic, accelerated, and blast phase) and is usually diagnosed in the chronic phase. Tyrosine kinase inhibitor therapy is a highly effective first-line treatment option for all patients with newly diagnosed chronic phase CML. This manuscript discusses the recommendations outlined in the NCCN Guidelines for the diagnosis and management of patients with chronic phase CML.

Abstract BACKGROUND Cerebral cavernous angioma (CA) is a capillary microangiopathy predisposing more than a million Americans to premature risk of brain hemorrhage. CA with recent symptomatic hemorrhage (SH), most likely to re-bleed with serious clinical sequelae, is the primary focus of therapeutic development. Signaling aberrations in CA include proliferative dysangiogenesis, blood-brain barrier hyperpermeability, inflammatory/immune processes, and anticoagulant vascular domain. Plasma levels of molecules reflecting these mechanisms and measures of vascular permeability and iron deposition on magnetic resonance imaging are biomarkers that have been correlated with CA hemorrhage. OBJECTIVE To optimize these biomarkers to accurately diagnose cavernous angioma with symptomatic hemorrhage (CASH), prognosticate the risk of future SH, and monitor cases after a bleed and in response to therapy. METHODS Additional candidate biomarkers, emerging from ongoing mechanistic and differential transcriptome studies, would further enhance the sensitivity and specificity of diagnosis and prediction of CASH. Integrative combinations of levels of plasma proteins and characteristic micro-ribonucleic acids may further strengthen biomarker associations. We will deploy advanced statistical and machine learning approaches for the integration of novel candidate biomarkers, rejecting noncorrelated candidates, and determining the best clustering and weighing of combined biomarker contributions. EXPECTED OUTCOMES With the expertise of leading CA researchers, this project anticipates the development of future blood tests for the diagnosis and prediction of CASH to clinically advance towards precision medicine. DISCUSSION The project tests a novel integrational approach of biomarker development in a mechanistically defined cerebrovascular disease with a relevant context of use, with an approach applicable to other neurological diseases with similar pathobiologic features.

AbstractNeuronal intranuclear inclusion disease (NIID) is a clinically heterogeneous neurodegenerative condition characterized by pathological intranuclear eosinophilic inclusions. A CGG repeat expansion in NOTCH2NLC was recently identified to be associated with NIID in patients of Japanese descent. We screened pathologically confirmed European NIID, cases of neurodegenerative disease with intranuclear inclusions and applied in silico‐based screening using whole‐genome sequencing data from 20 536 participants in the 100 000 Genomes Project. We identified a single European case harbouring the pathogenic repeat expansion with a distinct haplotype structure. Thus, we propose new diagnostic criteria as European NIID represents a distinct disease entity from East Asian cases.

Abstract Phosphoglucomutase 1 (PGM1) deficiency is a rare genetic disorder that affects glycogen metabolism, glycolysis, and protein glycosylation. Previously known as GSD XIV, it was recently reclassified as a congenital disorder of glycosylation, PGM1‐CDG. PGM1‐CDG usually manifests as a multisystem disease. Most patients present as infants with cleft palate, liver function abnormalities and hypoglycemia, but some patients present in adulthood with isolated muscle involvement. Some patients develop life‐threatening cardiomyopathy. Unlike most other CDG, PGM1‐CDG has an effective treatment option, d ‐galactose, which has been shown to improve many of the patients' symptoms. Therefore, early diagnosis and initiation of treatment for PGM1‐CDG patients are crucial decisions. In this article, our group of international experts suggests diagnostic, follow‐up, and management guidelines for PGM1‐CDG. These guidelines are based on the best available evidence‐based data and experts' opinions aiming to provide a practical resource for health care providers to facilitate successful diagnosis and optimal management of PGM1‐CDG patients.

Abstract Introduction We aimed to test the feasibility and acceptability of SleepWell24, a multicomponent, smartphone-delivered intervention to increase positive airway pressure (PAP) adherence among newly diagnosed OSA patients. Methods SleepWell24 targets PAP adherence along with other health behaviors through education, trouble-shooting, goal-setting, and near real-time biofeedback of PAP machine use, and sleep and physical activity levels (via Fitbit integration), and other chronic disease self-management components. Patients with a first-time diagnosis of OSA (AHI≥5) and prescribed PAP therapy were enrolled from the Centers for Sleep Medicine at Mayo Clinic in Rochester, MN and Phoenix, AZ. Patients were randomized to SleepWell24 or usual care (UC) and assessed for PAP use over 60 consecutive nights. UC patients received a Fitbit monitor to control for non-specific intervention effects related to the introduction of a new personal technology. Feasibility was assessed with recruitment and retention rates and acceptability was assessed post-intervention with the validated, 8-item Treatment Evaluation Questionnaire (TEQ; range:0-4). ANCOVA models, adjusting for age, sex, and AHI severity, compared intervention arms on acceptability ratings. Results OSA patients were consented and randomized (N=111). Before the intervention began 4 participants withdrew, 12 were lost to follow-up, and 5 could not start the trial due to durable medical equipment (DME) vendor barriers. Ninety OSA patients (n=41 SleepWell24, n=49 UC; age M±SD=57.2±12.2; 44.4% female, 61.1% AHI≥15) started the intervention, with 2 participants withdrawing, 1 becoming deceased (unrelated to treatment) and 7 with missing PAP data due to DME vendor barriers. There was no significant between-groups differences on post-treatment acceptability (SleepWell24 M±SD=2.7±1.1 vs. UC M±SD=3.1±0.9, F[1,73]=2.3, p=0.11), and 77% of SleepWell24 participants found the app to be moderately to totally acceptable. Conclusion Overall, SleepWell24 was found to be feasible for delivery in two large clinical sleep medicine centers, and patients found the app to be acceptable. A number of challenges in trial delivery were encountered that have implications for scaled-up efficacy testing: (a) partnerships with DME vendors for near real-time PAP data integration; (b) alignment with clinical practice (i.e., referral, medical record integration); and (c) patient engagement. Support National Institute of Nursing Research / National Institutes of Health: R21NR016046