Rare variants and survival of patients with idiopathic pulmonary fibrosis.

Background: The clinical course of idiopathic pulmonary fibrosis (IPF) is highly variable and unpredictable, with multiple genetic variants influencing IPF outcomes. Notably, rare pathogenic variants in telomere-related genes are associated with poorer clinical outcomes in these patients. Here we assessed whether rare qualifying variants (QVs) in monogenic adult-onset pulmonary fibrosis (PF) genes are associated with IPF survival.

Imaging, Pulmonary Function, and Histopathologic Findings of Persistent Fibrosis in a Longitudinal Cohort Three Years after Severe COVID-19 Infection.

Fibrotic-like abnormalities are present in 60% of a single-center, longitudinal, multi-ethnic cohort 3-years after severe COVID-19. They are independently associated with male sex, low BMI, shorter telomere length, increased severity of illness, and mechanical ventilation; Black race and asthma are protective. Participants with fibrotic-like abnormalities are more likely to have reduced diffusion capacity and 6-minute walk distance.

Genomic and Serological Rheumatoid Arthritis Biomarkers, Promoter Variant, and Interstitial Lung Abnormalities.

Rationale: Rheumatoid arthritis (RA) has been implicated in interstitial lung disease (ILD) as majority of studies have been comprised of patients with known RA. However, it remains unclear whether an underlying risk for RA in combination with genetic risk for pulmonary fibrosis is associated with radiological markers of early lung injury and fibrosis in broader population samples.

Objective: Determine whether genetic and serological biomarkers of RA risk in combination with the (rs35705950) risk allele (T) are associated with interstitial lung abnormalities (ILA) on computed tomography (CT) scans.

Sleep disruption in patients with active and treated endogenous Cushing's syndrome.

Context: The hypothalamic-pituitary-adrenal axis is a critical regulator of circadian rhythm in humans. Impaired sleep adversely affects metabolic, emotional, and cognitive health.

Objective: To characterize sleep disturbances in patients with active and treated Cushing's syndrome (CS), and identify factors associated with impaired sleep in treated patients.

Comparative Efficacy and Safety of Lorlatinib Versus Alectinib and Lorlatinib Versus Brigatinib for ALK-Positive Advanced/Metastatic NSCLC: Matching-Adjusted Indirect Comparisons.

Introduction: The comparative efficacy and safety of lorlatinib, a third-generation anaplastic lymphoma kinase (ALK) tyrosine kinase inhibitor (TKI), versus second-generation ALK TKIs as a first-line treatment for ALK+ advanced/metastatic nonsmall cell lung cancer (NSCLC) remains uncertain as there are no head-to-head clinical trials.

Methods: Matching-adjusted indirect comparisons (MAICs) were conducted using phase III trial data demonstrating superior efficacy over crizotinib, a first-generation ALK TKI. MAICs were conducted to compare lorlatinib (CROWN) versus alectinib (ALEX and ALESIA) and brigatinib (ALTA-1L) with matching based on prespecified effect modifiers.

Antiaging, Brightening, and Antioxidant Efficacy of Fermented Bilberry Extract (): A Randomized, Double-Blind, Placebo-Controlled Trial.

Strategies for successful aging, including the use of food supplements, are part of the approach to support skin youthfulness. To demonstrate the efficacy of fermented bilberry extract (FBE) against skin aging and uneven complexion, a clinical trial was carried out on 66 subjects with visible "crow's feet" wrinkles, mild-to-moderate skin slackness, and uneven skin tone. The wrinkle depth, skin smoothness (Ra) and roughness (Rz), skin firmness (R0) and elasticity (R2), skin coloration (ITA°), and skin antioxidant capacity were measured before and after 28 (D28), 56 (D56), and 84 (D84) days of product use (either FBE or a placebo).

Alternatives to Conventional Topical Dosage Forms for Targeted Skin Penetration of Diclofenac Sodium.

Skin penetration of an active pharmaceutical ingredient is key to developing topical drugs. This penetration can be adjusted for greater efficacy and/or safety through the selection of dosage form. Two emerging dosage forms, cream-gel and gel-in-oil emulsion, were tested for their ability to deliver diclofenac into the skin, with the target of maximising skin retention while limiting systemic exposure.

Clinical Impact of Telomere Length Testing for Interstitial Lung Disease.

Background: Shortened telomere length (TL) is a genomic risk factor for fibrotic interstitial lung disease (ILD), but its role in clinical management is unknown.

Research Question: What is the clinical impact of TL testing on the management of ILD?

Study Design And Methods: Patients were evaluated in the Columbia University ILD clinic and underwent Clinical Laboratory Improvement Amendments-certified TL testing by flow cytometry and fluorescence in situ hybridization (FlowFISH) as part of clinical treatment. Short TL was defined as below the 10th age-adjusted percentile for either granulocytes or lymphocytes by FlowFISH.

Improved pulmonary function and exercise tolerance despite persistent pulmonary fibrosis over 1 year after severe COVID-19 infection.

We conducted a prospective single-centre cohort study of 104 multi-ethnic severe COVID-19 survivors from the first wave of the pandemic 15 months after hospitalisation. Of those who were assessed at 4 and 15 months, improvement of ground glass opacities correlated with worsened fibrotic reticulations. Despite a high prevalence of fibrotic patterns (64%), pulmonary function, grip strength, 6 min walk distance and frailty normalised.

Pulmonary Fibrosis Stakeholder Summit: A Joint NHLBI, Three Lakes Foundation, and Pulmonary Fibrosis Foundation Workshop Report.

Despite progress in elucidation of disease mechanisms, identification of risk factors, biomarker discovery, and the approval of two medications to slow lung function decline in idiopathic pulmonary fibrosis and one medication to slow lung function decline in progressive pulmonary fibrosis, pulmonary fibrosis remains a disease with a high morbidity and mortality. In recognition of the need to catalyze ongoing advances and collaboration in the field of pulmonary fibrosis, the NHLBI, the Three Lakes Foundation, and the Pulmonary Fibrosis Foundation hosted the Pulmonary Fibrosis Stakeholder Summit on November 8-9, 2022. This workshop was held virtually and was organized into three topic areas: ) novel models and research tools to better study pulmonary fibrosis and uncover new therapies, ) early disease risk factors and methods to improve diagnosis, and ) innovative approaches toward clinical trial design for pulmonary fibrosis.

Dietary supplementation with a wheat polar lipid complex improves skin conditions in women with dry skin and mild-to-moderate skin aging.

Background: Aging, menopause, and seasonal changes alter the lipid composition of the outermost skin layer, the stratum corneum, resulting in dry and itchy skin.

Aims: This clinical trial aimed at evaluating the effects of a wheat polar lipid complex (WPLC) on skin characteristics in women showing dry and wrinkled skin, investigating its effects in a subgroup of postmenopausal women, and assessing if benefits were maintained after supplementation.

Methods: Seventy-two women with dry and wrinkled skin were recruited in this double-blind, randomized, parallel-group study, and allocated to three groups of 24 subjects, each including at least 10 postmenopausal women.

Efficacy of a wheat polar lipid complex in reducing hair loss and improving hair growth in healthy women: A randomized, double-blind, placebo-controlled clinical study.

Objective: Hair loss is a major source of psychological distress for affected people. Safe and natural ingredients are therefore needed to help reduce hair loss and stimulate hair growth. This pilot clinical study aimed at exploring the efficacy of a wheat polar lipid complex (WPLC, Ceramosides™), containing sphingolipids and digalactosyl diglycerides, on hair characteristics improvement in women showing acute hair shedding.

The World's First Acne Dysbiosis-like Model of Human 3D Ex Vivo Sebaceous Gland Colonized with and .

Acne-prone skin is associated with dysbiosis involving () and () causing increased seborrhea in sebaceous glands (SG) and inflammation. Human primary sebocytes were cultivated using 1.10 UFC/mL Type IA (facial acne, ATCC6919) and/or 1.

Telomere length and immunosuppression in non-idiopathic pulmonary fibrosis interstitial lung disease.

Background: Studies suggest a harmful pharmacogenomic interaction exists between short leukocyte telomere length (LTL) and immunosuppressants in idiopathic pulmonary fibrosis (IPF). It remains unknown if a similar interaction exists in non-IPF interstitial lung disease (ILD).

Methods: A retrospective, multicentre cohort analysis was performed in fibrotic hypersensitivity pneumonitis (fHP), unclassifiable ILD (uILD) and connective tissue disease (CTD)-ILD patients from five centres.

A Polygenic Risk Score for Idiopathic Pulmonary Fibrosis and Interstitial Lung Abnormalities.

In addition to rare genetic variants and the locus, common genetic variants contribute to idiopathic pulmonary fibrosis (IPF) risk. The predictive power of common variants outside the locus for IPF and interstitial lung abnormalities (ILAs) is unknown. We tested the predictive value of IPF polygenic risk scores (PRSs) with and without the region on IPF, ILA, and ILA progression.

Fibrotic-Like Pulmonary Radiographic Patterns Are Not Associated With Adverse Outcomes in COVID-19 Chronic Critical Illness.

Objectives: Pulmonary fibrosis is a feared complication of COVID-19. To characterize the risks and outcomes associated with fibrotic-like radiographic abnormalities in patients with COVID-19-related acute respiratory distress syndrome (ARDS) and chronic critical illness.

Design: Single-center prospective cohort study.

Pulmonary emphysema subtypes defined by unsupervised machine learning on CT scans.

Background: Treatment and preventative advances for chronic obstructive pulmonary disease (COPD) have been slow due, in part, to limited subphenotypes. We tested if unsupervised machine learning on CT images would discover CT emphysema subtypes with distinct characteristics, prognoses and genetic associations.

Methods: New CT emphysema subtypes were identified by unsupervised machine learning on only the texture and location of emphysematous regions on CT scans from 2853 participants in the Subpopulations and Intermediate Outcome Measures in COPD Study (SPIROMICS), a COPD case-control study, followed by data reduction.

Incidence of interstitial lung abnormalities: the MESA Lung Study.

Background: The incidence of newly developed interstitial lung abnormalities (ILA) and fibrotic ILA has not been previously reported.

Methods: Trained thoracic radiologists evaluated 13 944 cardiac computed tomography scans for the presence of ILA in 6197 Multi-Ethnic Study of Atherosclerosis (MESA) longitudinal cohort study participants >45 years of age from 2000 to 2012. Five percent of the scans were re-read by the same or a different observer in a blinded fashion.

Top Ten Tips Palliative Care Clinicians Should Know About Caring for Filipino American and Korean American Patients.

As of 2019, there are 4.2 million Filipino Americans (FAs) and 1.9 million Korean Americans (KAs) in the United States, largely concentrated in New York, California, Texas, Illinois, and Washington.

Telomere length associates with chronological age and mortality across racially diverse pulmonary fibrosis cohorts.

Pulmonary fibrosis (PF) is characterized by profound scarring and poor survival. We investigated the association of leukocyte telomere length (LTL) with chronological age and mortality across racially diverse PF cohorts. LTL measurements among participants with PF stratified by race/ethnicity were assessed in relation to age and all-cause mortality, and compared to controls.

Evaluation of Pulmonary Fibrosis Outcomes by Race and Ethnicity in US Adults.

Importance: Pulmonary fibrosis (PF) is characterized by progressive scarring of lung tissue and poor survival. Racial and ethnic minority populations face the greatest risk of morbidity and mortality from disparities impacting respiratory health, but the pattern of age at clinically relevant outcomes across diverse racial and ethnic populations with PF is unknown.

Objective: To compare the age at PF-related outcomes and the heterogeneity in survival patterns among Hispanic, non-Hispanic Black, and non-Hispanic White participants.

Obstructive Sleep Apnea and Longitudinal Changes in Interstitial Lung Imaging and Lung Function: The MESA Study.

Obstructive sleep apnea (OSA) has been hypothesized to be a risk factor in interstitial lung disease (ILD) and is associated with radiological markers that may represent the earlier stages of ILD. Prior studies have been limited by their cross-sectional design and potential confounding by body habitus. To test the hypothesis that OSA severity is associated with more high-attenuation areas (HAAs) on computed tomography and worse lung function over time among older community-dwelling adults.