Ultra-low dose chest CT with silver filter and deep learning reconstruction significantly reduces radiation dose and retains quantitative information in the investigation and monitoring of lymphangioleiomyomatosis (LAM).

Purpose: Frequent CT scans to quantify lung involvement in cystic lung disease increases radiation exposure. Beam shaping energy filters can optimize imaging properties at lower radiation dosages. The aim of this study is to investigate whether use of SilverBeam filter and deep learning reconstruction algorithm allows for reduced radiation dose chest CT scanning in patients with lymphangioleiomyomatosis (LAM).

Computer grading of lung disease severity in patients with lymphangioleiomyomatosis referred for transplantation.

Objectives: Lymphangioleiomyomatosis (LAM) patients with severe lung disease may be considered for lung transplantation. Clinical, physiologic, and quality of life data are usually employed for referral. The aim of this study was to determine whether computed tomographic measurement of lung volume occupied by cysts (cyst score) complemented clinical and physiologic data in supporting referral for transplantation.

Ultra-Small Lung Cysts Impair Diffusion Without Obstructing Air Flow in Lymphangioleiomyomatosis.

Background: Lymphangioleiomyomatosis (LAM) is a rare lung disease found primarily in women of childbearing age, characterized by the formation of air-filled cysts, which may be associated with reductions in lung function. An experimental, regional ultra-high resolution CT scan identified an additional volume of cysts relative to standard chest CT imaging, which consisted primarily of ultra-small cysts.

Research Question: What is the impact of these ultra-small cysts on the pulmonary function of patients with LAM?

Study Design And Methods: A group of 103 patients with LAM received pulmonary function tests and a CT examination in the same visit.

Choice of Laboratory Tissue Homogenizers Matters When Recovering Nucleic Acid From Medically Important Ticks.

Ticks can vector and transmit many pathogens and pose a serious human health threat throughout the world. After collection, many diagnostic laboratories must mechanically disrupt tick specimens for diagnostic testing and research purposes, but few studies have evaluated how well-commercial tissue homogenizers perform this task. We evaluated four commercially available tissue homogenizers: The Bead Ruptor 24 Elite, the Bullet Blender Storm, the gentleMACS Dissociator, and the Precellys 24.

Clinical CT underestimation of the percentage volume occupied by cysts in patients with lymphangioleiomyomatosis.

Purpose: To evaluate the accuracy of cyst score measurements by standard high-resolution helical volume chest CT (HRCT) in patients with lymphangioleiomyomatosis (LAM), using a short z-length ultra-high resolution re-scan (UH re-scan) as the reference. In cystic lung diseases, cyst score is derived from CT scans and defined as the percentage of the total lung parenchymal volume occupied by cysts, a biomarker which measures the severity of the disease.

Methods: In a prospective study of 73 LAM patients, each patient received the standard HRCT chest scan and a short z-length UH re-scan.

Phenotypic distinctions between mosaic forms of tuberous sclerosis complex.

Purpose: To determine if mosaic tuberous sclerosis complex (TSC) can be stratified into subtypes that correspond with prognosis and extent of disease.

Methods: Next-generation sequencing of skin tumor and other samples was used to identify patients with mosaic pathogenic variants in TSC1 or TSC2. Extent of disease, onset age, and family history of TSC were determined through retrospective analysis of patient records.

Expanding the phenotype of COPA syndrome: a kindred with typical and atypical features.

Background: Copa syndrome is a rare autosomal dominant disorder with abnormal intracellular vesicle trafficking. The objective of this work is to expand the knowledge about this disorder by delineating phenotypic features of an unreported COPA family.

Methods And Results: A heterozygous missense variant (c.

Chest CT Scan at Radiation Dose of a Posteroanterior and Lateral Chest Radiograph Series: A Proof of Principle in Lymphangioleiomyomatosis.

Background: Given the rising utilization of medical imaging and the risks of radiation, there is increased interest in reducing radiation exposure. The objective of this study was to evaluate, as a proof of principle, CT scans performed at radiation doses equivalent to that of a posteroanterior and lateral chest radiograph series in the cystic lung disease lymphangioleiomyomatosis (LAM).

Methods: From November 2016 to May 2018, 105 consecutive subjects with LAM received chest CT scans at standard and ultra-low radiation doses.

Pseudoneutropenia in lymphangioleiomyomatosis (LAM) patients receiving sirolimus: evaluation in a 100 patient cohort.

http://ow.ly/jPFz30iysgV.

Rates of change in FEV and as potential indicators for mTOR inhibitor therapy in premenopausal lymphangioleiomyomatosis patients.

The value of rates of change in forced expiratory volume in 1 s (FEV) and diffusing capacity of the lung for carbon monoxide () to predict disease progression, and initiation of mTOR (mechanistic target of rapamycin) inhibitor therapy has not been evaluated.In 84 premenopausal lymphangioleiomyomatosis patients, individual rates of change in FEV and and their 95% confidence intervals were used to derive subsequent lowest values of FEV and that would prompt initiation of sirolimus therapy. These treatment criteria were compared with a criterion based on FEV or ≤70% predicted.

Mounier-Kuhn Syndrome Mimicking Lymphangioleiomyomatosis.

We present the case of a man with Mounier-Kuhn syndrome (MKS), or tracheobronchomegaly, who was referred to the National Institutes of Health Clinical Research Center because of a potential diagnosis of lymphangioleiomyomatosis (LAM), a rare condition in men. The patient was evaluated using ongoing protocols and provided written informed consent. The case demonstrates the presence of chronic inflammation surrounding the dilated airways and histologic changes of the lung parenchyma with emphysematouslike disruption in areas adjacent to the dilated airways.

Long-Term Effect of Sirolimus on Serum Vascular Endothelial Growth Factor D Levels in Patients With Lymphangioleiomyomatosis.

Background: Sirolimus reduces serum levels of vascular endothelial growth factor D (VEGF-D); the size of chylous effusions, lymphangioleiomyomas, and angiomyolipomas; and stabilizes lung function in patients with lymphangioleiomyomatosis (LAM).

Methods: To determine whether reductions in VEGF-D levels are sustained over time, as well as parallel changes in lung function and lymphatic disease, we evaluated 25 patients with LAM and measured VEGF-D levels, lung function, and extent of lymphatic disease before and during sirolimus therapy.

Results: Treatment with sirolimus stabilized FEV and diffusion capacity for carbon monoxide (Dlco) over a period of 4.

Sirolimus and Autophagy Inhibition in Lymphangioleiomyomatosis: Results of a Phase I Clinical Trial.

Background: Animal and cellular studies support the importance of autophagy inhibition in lymphangioleiomyomatosis (LAM). In a cohort of subjects with LAM, we tested the hypothesis that treatment with sirolimus and hydroxychloroquine (an autophagy inhibitor) at two different dose levels is safe and well tolerated. Secondary end points included changes in lung function.

HIV Testing Among Internet-Using MSM in the United States: Systematic Review.

Regular HIV testing enables early identification and treatment of HIV among at-risk men who have sex with men (MSM). Characterizing HIV testing needs for Internet-using MSM informs development of Internet-facilitated testing interventions. In this systematic review we analyze HIV testing patterns among Internet-using MSM in the United States who report, through participation in an online study or survey, their HIV status as negative or unknown and identify demographic or behavioral risk factors associated with testing.

Incidence of Pneumothorax in Patients With Lymphangioleiomyomatosis Undergoing Pulmonary Function and Exercise Testing.

Because pneumothorax is frequent in lymphangioleiomyomatosis, patients have expressed concerns regarding the risk of pneumothorax associated with pulmonary function or exercise testing. Indeed, pneumothorax has been reported in patients with lung disease after both of these tests. The aim of this study was to determine the incidence of pneumothorax in patients with lymphangioleiomyomatosis during admissions to the National Institutes of Health Clinical Research Center between 1995 and 2015.

Effects of glucose and insulin on secretion of amyloid-β by human adipose tissue cells.

Objective: Obesity and type 2 diabetes mellitus are risk factors for developing Alzheimer disease. Overlapping patterns of metabolic dysfunction may be common molecular links between these complex diseases. Amyloid-β (Aβ) precursor protein and associated β- and γ-secretases are expressed in adipose tissue.

Effect of fasting on the size of lymphangioleiomyomas in patients with lymphangioleiomyomatosis.

Background: Lymphangioleiomyomas occur in 38% of patients with sporadic lymphangioleiomyomatosis (LAM) and may cause pain and increased abdominal girth, mimicking the presence of a malignancy. Lymphatic involvement in LAM is closely associated with elevated serum levels of vascular endothelium growth factor-D (VEGF-D). Because lymphangioleiomyomas undergo diurnal variation in volume, we hypothesized that daytime ingestion of food, by increasing chyle formation and lymphatic flow, is the cause of an increase in lymphangioleiomyoma volume.

Severity and outcome of cystic lung disease in women with tuberous sclerosis complex.

What are the clinical features, severity, and rate of progression of lung disease in women with tuberous sclerosis and lymphangioleiomyomatosis (LAM) and how do they differ from patients with sporadic LAM? Data from 94 tuberous sclerosis/LAM and 460 sporadic LAM women were compared. 40 tuberous sclerosis/LAM and 40 sporadic LAM patients were age- and lung function-matched, and changes in volume occupied by cysts (cyst score) and pulmonary function occurring over 6.5 years were evaluated.

Sustained effects of sirolimus on lung function and cystic lung lesions in lymphangioleiomyomatosis.

Rationale: Sirolimus therapy stabilizes lung function and reduces the size of chylous effusions and lymphangioleiomyomas in patients with lymphangioleiomyomatosis.

Objectives: To determine whether sirolimus has beneficial effects on lung function, cystic areas, and adjacent lung parenchyma; whether these effects are sustained; and whether sirolimus is well tolerated by patients.

Methods: Lung function decline over time, lung volume occupied by cysts (cyst score), and lung tissue texture in the vicinity of the cysts were quantified with a computer-aided diagnosis system in 38 patients.

Retrospective review of combined sirolimus and simvastatin therapy in lymphangioleiomyomatosis.

Background: Combined simvastatin and sirolimus therapy reduces tuberous sclerosis complex 2-null lesions and alveolar destruction in a mouse model of lymphangioleiomyomatosis (LAM), suggesting that therapy with both drugs may benefit patients with LAM.

Methods: To determine whether simvastatin changed the prevalence of adverse events or altered the therapeutic effects of sirolimus, we recorded adverse events and changes in lung function in patients with LAM treated with simvastatin plus sirolimus (n = 14), sirolimus alone (n = 44), or simvastatin alone (n = 20).

Results: Sirolimus-related adverse events in the simvastatin plus sirolimus and sirolimus-only groups were 64% and 66% for stomatitis, 50% and 52% for diarrhea, 50% and 45% for peripheral edema, 36% and 61% for acne, 36% and 30% for hypertension, 29% and 27% for proteinuria, 29% and 27% for leukopenia, and 21% and 27% for hypercholesterolemia.

Role of state mental health leaders in supporting evidence-based practices over time.

State administrative supports of evidence-based practices (EBPs) may critically affect sustainability. As part of a larger follow-up to the multistate National Implementing Evidence-Based Practices Project, 13 leaders from eight States reported on recent statewide policies and resources that influenced the maintenance of 49 EBP programs 6 years after implementation. Nearly three-quarters (71 %) of the programs were currently operational and adhering to State fidelity standards.

Predicting the long-term sustainability of evidence-based practices in mental health care: an 8-year longitudinal analysis.

Few studies have examined predictors of long-term sustainability of evidence-based practices in mental health. This study used assessments of five evidence-based practices implemented in 49 sites in eight states at baseline and years 2, 4, and 8. Program characteristics, implementation characteristics, reinforcement activities, and sustainability factors were used to predict program survival status.

Long-term sustainability of evidence-based practices in community mental health agencies.

This study examined rates of sustainability, defined as program continuation, and factors associated with sustainability 6 years after full implementation of five evidence-based practices in 49 sites in the National Implementing Evidence-Based Practices Project. Based on interviews with agency leaders and state leaders, 47 % of sites sustained the practice for 6 years, 16 % restarted the practice after a period of discontinuation, and 37 % discontinued the practice permanently. Agency leaders from discontinuing sites identified inadequate financial support, lack of prioritization, and workforce issues as barriers to continuation.