Abstract Side experiments are performed on radiomics models to improve their reproducibility. We measure the impact of myocardial masks, radiomic side experiments and data augmentation for information transfer (DAFIT) approach to differentiate patients with and without pulmonary hypertension (PH) using cardiac MRI (CMRI) derived radiomics. Feature extraction was performed from the left ventricle (LV) and right ventricle (RV) myocardial masks using CMRI in 82 patients (42 PH and 40 controls). Various side study experiments were evaluated: Original data without and with intraclass correlation (ICC) feature-filtering and DAFIT approach (without and with ICC feature-filtering). Multiple machine learning and feature selection strategies were evaluated. Primary analysis included all PH patients with subgroup analysis including PH patients with preserved LVEF (≥ 50%). For both primary and subgroup analysis, DAFIT approach without feature-filtering was the highest performer (AUC 0.957–0.958). ICC approaches showed poor performance compared to DAFIT approach. The performance of combined LV and RV masks was superior to individual masks alone. There was variation in top performing models across all approaches (AUC 0.862–0.958). DAFIT approach with features from combined LV and RV masks provide superior performance with poor performance of feature filtering approaches. Model performance varies based upon the feature selection and model combination.
The management of pulmonary sarcoidosis is a complex interplay of disease characteristics, the impact of medications, and patient preferences. Foremost, it is important to weigh the risk of anti-granulomatous treatment with the benefits of lung preservation and improvement in quality of life. Because of its high spontaneous resolution rate, pulmonary sarcoidosis should only be treated in cases of significant symptoms due to granulomatous inflammation, lung function decline, or substantial inflammation on imaging that can lead to irreversible fibrosis. The longstanding basis of treatment has historically been corticosteroid therapy for the control of granulomatous inflammation. However, several corticosteroid-sparing options have increasing evidence for use in refractory disease, inability to taper steroids to an acceptable dose, or in those with toxicity to corticosteroids. Treatment of sarcoidosis should be individualized for each patient due to the heterogeneity of the clinical course, comorbid conditions, response to therapy, and tolerance of medication side effects.
Vitamin D deficiency has been implicated as a factor in a number of infectious and inflammatory lung diseases. In the lung, alveolar macrophages play a key role in inflammation and defense of infection, but there are little data exploring the immunomodulatory effects of vitamin D on innate lung immunity in humans. The objective of this study was to determine the effects of vitamin D supplementation on gene expression of alveolar macrophages. We performed a parallel, double-blind, placebo-controlled, randomized trial to determine the effects of vitamin D on alveolar macrophage gene expression. Vitamin D3 (1000 international units/day) or placebo was administered to adults for three months. Bronchoscopy was performed pre- and post-intervention to obtain alveolar macrophages. Messenger RNA was isolated from the macrophages and subjected to whole genome exon array analysis. The primary outcome was differential gene expression of the alveolar macrophage in response to vitamin D supplementation. Specific genes underwent validation by polymerase chain reaction methods. Fifty-eight subjects were randomized to vitamin D (n = 28) or placebo (n = 30). There was a marginal overall difference between treatment group and placebo group in the change of 25-hydroxyvitaminD levels (4.43 ng/ml vs. 0.2 ng/ml, p = 0.10). Whole genome exon array analysis revealed differential gene expression associated with change in serum vitamin D levels in the treated group. CCL8/MCP-2 was the top-regulated cytokine gene and was further validated. Although only a non-significant increased trend was seen in serum vitamin D levels, subjects treated with vitamin D supplementation had immune-related differential gene expression in alveolar macrophages. ClinicalTrials.org: NCT01967628 .
Objectives Neuropsychiatric events (NEs) reported with montelukast during post-marketing surveillance by the US Food & Drug Administration resulted in a 2008 safety alert and a black box warning in 2020. Our objective was to evaluate montelukast exposure and NEs risk using sequence symmetry analysis.Methods National Veterans Health Administration (VHA) administrative data were used to identify 11 840 patients prescribed incident montelukast during fiscal year 2014. Incident prescribing of neuropsychiatric medication was used as a proxy marker for incident NEs and included antidepressants, benzodiazepines, hypnotics, antipsychotics, mood stabilizers, and buspirone. Symmetry ratios were calculated as the ratio of patients with an incident neuropsychiatric event in the year following montelukast initiation to the year preceding initiation. Exposure counterfactual analyses were used to examine the relationship between potential therapeutic alternatives to montelukast and risk for NEs.Results Incident NEs were observed in 2305 patients following montelukast initiation and 2734 patients preceding montelukast initiation (SR 0.84, 95% CI 0.80–0.89). Sensitivity analyses examining each of the 6 sub-types of psychiatric medications also failed to show increased risk of NEs following montelukast initiation. Therapeutic alternatives to montelukast, such as inhaled corticosteroids, were also not associated increased NE risk.Conclusions Initiation of montelukast was not associated with increased risk of a variety of NEs in this sequence symmetry analysis involving adult patients in the VHA. Our findings do not support the hypothesis that NEs are associated with montelukast initiation.
In patients treated with repository corticotrophin injection (RCI) for pulmonary sarcoidosis, effective management of adverse events may improve adherence. However, management of adverse events may be challenging due to limitations in real-world clinical experience with RCI and available published guidelines. We surveyed 12 physicians with a modified Delphi process using three questionnaires. Questionnaire 1 consisted of open-ended questions. Panellists' answers were developed into a series of statements for Questionnaires 2 and 3. In these, physicians rated their agreement with the statements using a Likert scale. Key consensus recommendations included a starting dose of 40 units twice a week for patients with less severe disease, continued at a maintenance dose for patients who responded, particularly those with chronic refractory sarcoidosis. Panellists reached consensus that concomitant steroids should be quickly tapered in patients receiving RCI, but that concomitant use of immunosuppressive medications should be continued. Panellists developed consensus recommendations for adverse event management, and reached consensus that RCI should be down-titrated or discontinued if other interventions for the adverse effects fail or if the adverse effect is severe. In the absence of clinical evidence, our Delphi consensus opinions may provide practical guidance to physicians on the management of RCI to treat pulmonary sarcoidosis.
'%3e%3cpath fill='%23012169' d='M0 0v30h60V0z'/%3e%3cpath stroke='%23fff' stroke-width='6' d='m0 0 60 30m0-30L0 30'/%3e%3cpath stroke='%23C8102E' stroke-width='4' d='m0 0 60 30m0-30L0 30' clip-path='url(%23b)'/%3e%3cpath stroke='%23fff' stroke-width='10' d='M30 0v30M0 15h60'/%3e%3cpath stroke='%23C8102E' stroke-width='6' d='M30 0v30M0 15h60'/%3e%3c/g%3e%3c/svg%3e)
'%3e%3ccircle r='9'/%3e%3cg id='d'%3e%3cg id='c'%3e%3cg id='b'%3e%3cpath d='m-19 0 1.169 1.169L0 0l-17.831-1.169z'/%3e%3cpath id='a' d='m-.884.116.05.05L0 0z' transform='scale(19.2381)'/%3e%3cuse xlink:href='%23a' transform='scale(1 -1)'/%3e%3c/g%3e%3cuse xlink:href='%23b' transform='rotate(45)'/%3e%3c/g%3e%3cuse xlink:href='%23c' transform='rotate(90)'/%3e%3c/g%3e%3cuse xlink:href='%23d' transform='rotate(180)'/%3e%3cg transform='translate(-2.02)'%3e%3cg id='f' transform='translate(37.962)'%3e%3cpath id='e' d='M5 0 1.618 1.176l-.073 3.58-2.163-2.854-3.427 1.037L-2 0z'/%3e%3cuse xlink:href='%23e' transform='scale(1 -1)'/%3e%3c/g%3e%3cuse xlink:href='%23f' transform='rotate(120)'/%3e%3cuse xlink:href='%23f' transform='rotate(-120)'/%3e%3c/g%3e%3c/g%3e%3c/svg%3e)
