IQGAP1 Regulates Actin Polymerization and Contributes to Bleomycin-Induced Lung Fibrosis.

We previously found IQ motif containing GTPase activating protein (IQGAP1) to be consistently elevated in lung fibroblasts (LF) isolated from patients with scleroderma (systemic sclerosis, SSc)-associated interstitial lung disease (ILD) and reported that IQGAP1 contributed to SSc by regulating expression and organization of α-smooth muscle actin (SMA) in LF. The aim of this study was to compare the development of ILD in the presence and absence of IQGAP1. Pulmonary fibrosis was induced in IQGAP1 knockout (KO) and wild-type (WT) mice by a single-intratracheal instillation of bleomycin.

Paul Klee's progressive dyspnea: A series of historical and clinical vignettes, part V.

Paul Klee (1879-1940), the 20th-century Swiss-German artist, suffered and died from complications of systemic sclerosis (SSc, scleroderma). This is the fifth in a series of clinical and historical vignettes wherein Klee's cardiopulmonary symptoms are described with an emphasis on how progressive dyspnea impacted Klee's life.

E Carwile LeRoy, MD.

E. Carwile LeRoy, M.D.

Tocilizumab in Patients with Systemic Sclerosis-associated Interstitial Lung Disease: A Systematic Review and Meta-Analysis.

The American Thoracic Society (ATS) convened an international, multidisciplinary panel to develop clinical practice guidelines for the treatment of systemic sclerosis-associated interstitial lung disease (SSc-ILD). To conduct a systematic review and evaluate the literature to determine the impact of treating patients with SSc-ILD with tocilizumab on prespecified critical and important outcomes determined by the ATS guideline panel. A literature search was conducted across MEDLINE, EMBASE, and Cochrane databases through June 2022 for studies using tocilizumab to treat patients with SSc-ILD.

Nintedanib Therapy Alone and Combined with Mycophenolate in Patients with Systemic Sclerosis-associated Interstitial Lung Disease: Systematic Reviews and Meta-analysis.

The American Thoracic Society convened an international multidisciplinary panel to develop clinical practice guidelines for the treatment of systemic sclerosis-associated interstitial lung disease (SSc-ILD). To conduct a systematic review and evaluate the literature to determine whether patients with SSc-ILD should be treated with nintedanib alone or with the combination of nintedanib plus mycophenolate. Literature searches were conducted across MEDLINE, EMBASE, and Cochrane Central Register of Controlled Trials databases through June 2022 for studies using nintedanib or nintedanib plus mycophenolate to treat patients with SSc-ILD.

Rituximab in Patients with Systemic Sclerosis-associated Interstitial Lung Disease: A Systematic Review and Meta-Analysis.

The American Thoracic Society convened an international, multidisciplinary panel to develop clinical practice guidelines for the treatment of systemic sclerosis-associated interstitial lung disease (SSc-ILD). To conduct a systematic review and evaluate the literature to determine whether patients with SSc-ILD should be treated with rituximab. A literature search was conducted across MEDLINE, EMBASE, and Cochrane Central Register of Controlled Trials (CENTRAL) databases through June 2022 for studies using rituximab to treat patients with SSc-ILD.

Cyclophosphamide in Patients with Systemic Sclerosis-associated Interstitial Lung Disease: A Systematic Review and Meta-Analysis.

The American Thoracic Society convened an international, multidisciplinary panel to develop clinical practice guidelines for the treatment of systemic sclerosis-associated interstitial lung disease (SSc-ILD). To conduct a systematic review and evaluate the literature to determine whether patients with SSc-ILD should be treated with cyclophosphamide. A literature search was conducted across the MEDLINE, EMBASE, and Cochrane Central Register of Controlled Trials databases through June 2022 for studies using cyclophosphamide to treat patients with SSc-ILD.

Mycophenolate in Patients with Systemic Sclerosis-associated Interstitial Lung Disease: A Systematic Review and Meta-Analysis.

The American Thoracic Society convened an international, multidisciplinary panel to develop clinical practice guidelines for the treatment of systemic sclerosis-associated interstitial lung disease (SSc-ILD). To conduct a systematic review and evaluate the literature to determine whether patients with SSc-ILD should be treated with mycophenolate. A literature search was conducted across the MEDLINE, EMBASE, and CENTRAL databases through June 2022 for studies using mycophenolate to treat patients with SSc-ILD.

Associations Between Patterns of Esophageal Dysmotility and Extra-Intestinal Features in Patients With Systemic Sclerosis.

Objective: The gastrointestinal tract is commonly involved in patients with systemic sclerosis (SSc) with varied manifestations. As our understanding of SSc gastrointestinal disease pathogenesis and risk stratification is limited, we sought to investigate whether patterns of esophageal dysfunction associate with specific clinical phenotypes in SSc.

Methods: Patients enrolled in the Johns Hopkins Scleroderma Center Research Registry who completed high-resolution esophageal manometry (HREM) studies as part of their clinical care between 2011 and 2020 were identified.

Critical Role of LMCD1 in Promoting Profibrotic Characteristics of Lung Myofibroblasts in Experimental and Scleroderma-Associated Lung Fibrosis.

Objective: Interstitial lung disease (ILD) is a serious complication and leading cause of mortality in patients with systemic sclerosis (SSc). In this study, we explored the role of LIM and cysteine-rich domains protein 1 (LMCD1) as a novel factor in the pathogenesis of SSc-related ILD (SSc-ILD).

Methods: The expression and effects of LMCD1 were studied in lung tissue samples and fibroblasts from SSc-ILD patients and control subjects as well as in lung tissue samples from animal models.

Paul Klee's gastrointestinal maladies: A series of historical and clinical vignettes, part IV.

Paul Klee (1879-1940), the 20 century Swiss-German artist, suffered and died from complications of systemic sclerosis (SSc, scleroderma). In a series of clinical and historical vignettes the various symptoms and complications of Klee's scleroderma are described. Here, I present evidence of Klee's multiple gastrointestinal (GI) symptoms and the significant impact they had on the quality of his life.

Nodular Regenerative Hyperplasia of the Liver in Rheumatic Disease: Cases and Review of the Literature.

Nodular regenerative hyperplasia (NRH) is a rare disease that is characterized by benign transformation of the hepatic parenchyma into small nodules with little to no fibrosis. Nodular regenerative hyperplasia is a cause of noncirrhotic portal hypertension. Symptoms can range from asymptomatic disease to more serious complications of portal hypertension such as esophageal varices and ascites.

Was Paul Klee's scleroderma an occupational disease? A series of historical and clinical vignettes, part III.

Paul Klee (1879-1940), one of the most influential artists of the 20th century, died at 60 years of age from complications of systemic sclerosis (scleroderma). The precipitating event(s) of Klee's scleroderma, as in most cases, will never be known. Among various potential factors, exposure to heavy metals, crystalline silica, and organic solvents-acting alone or in combination-can now be considered potential factors in the onset of Klee's disease.

Riociguat in patients with early diffuse cutaneous systemic sclerosis (RISE-SSc): randomised, double-blind, placebo-controlled multicentre trial.

Objectives: Riociguat is approved for pulmonary arterial hypertension and has antiproliferative, anti-inflammatory and antifibrotic effects in animal models of tissue fibrosis. We evaluated the efficacy and safety of riociguat in patients with early diffuse cutaneous systemic sclerosis (dcSSc) at high risk of skin fibrosis progression.

Methods: In this randomised, double-blind, placebo-controlled, phase IIb trial, adults with dcSSc of <18 months' duration and a modified Rodnan skin score (mRSS) 10-22 units received riociguat 0.

Systemic sclerosis-associated interstitial lung disease.

Systemic sclerosis is an autoimmune connective tissue disease, which is characterised by immune dysregulation and progressive fibrosis that typically affects the skin, with variable internal organ involvement. It is a rare condition that affects mostly young and middle-aged women, resulting in disproportionate morbidity and mortality. Currently, interstitial lung disease is the most common cause of death among patients with systemic sclerosis, with a prevalence of up to 30% and a 10-year mortality of up to 40%.

Paul Klee's illness-a series of historical and clinical vignettes, part II.

Viewing and analyzing fine art from a medical perspective increases our appreciation of the artist's suffering and teaches an important lesson of the human aspects of medicine. Paul Klee (1879-1940), one of the most influential artists of the 20th century, died at the age of 60 from complications of systemic sclerosis (scleroderma). In this second, in a series of clinical vignettes, I discuss the musculoskeletal manifestations of systemic sclerosis and how they may have influenced the life and art of Paul Klee.

and autoantibodies define scleroderma subtypes and risk in African and European Americans and suggest a role for molecular mimicry.

Systemic sclerosis (SSc) is a clinically heterogeneous autoimmune disease characterized by mutually exclusive autoantibodies directed against distinct nuclear antigens. We examined associations in SSc and its autoantibody subsets in a large, newly recruited African American (AA) cohort and among European Americans (EA). In the AA population, the African ancestry-predominant * and * alleles were associated with overall SSc risk, and the * allele was strongly associated with the severe antifibrillarin (AFA) antibody subset of SSc (odds ratio = 7.

Low-Resistance, High-Yield Electrical Contacts to Atom Scale Si:P Devices Using Palladium Silicide.

Scanning tunneling microscopy (STM) enables the fabrication of two-dimensional -doped structures in Si with atomistic precision, with applications from tunnel field-effect transistors to qubits. The combination of a very small contact area and the restrictive thermal budget necessary to maintain the integrity of the layer make developing a robust electrical contact method a significant challenge to realizing the potential of atomically precise devices. We demonstrate a method for electrical contact using PdSi formed at the temperature of silicon overgrowth (250 °C), minimizing the diffusive impact on the layer.

Antifibrotic efficacy of nintedanib in a cellular model of systemic sclerosis-associated interstitial lung disease.

Objectives: Nintedanib is approved for the treatment of idiopathic pulmonary fibrosis (IPF) and was demonstrated to slow disease progression in patients with IPF by reducing decline in forced vital capacity by 50%. Recently, nintedanib has been reported to exert anti-fibrotic activity on systemic sclerosis (scleroderma, SSc) skin fibroblasts and to diminish skin and lung fibrosis in mouse models. The goal of the present study was to determine the effects of nintedanib on a cellular model of SSc-associated interstitial lung disease (ILD).