38 research outputs found

    Erdheim Chester Disease treated successfully with cladribine

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    AbstractA 61-year-old previously healthy male with a history of progressive fatigue, lower extremity edema, and dyspnea for 4 months was hospitalized with pericardial and pleural effusions (Figure 1A, B). Lung, pleural, and pericardial biopsies were consistent with Erdheim-Chester disease. He was treated with systemic steroids, and ultimately tried on PEG-interferon. He deteriorated clinically and the disease progressed to include CNS manifestations. Ultimately he was treated with Cladribine, at a dose 0.014 mg/kg on day 1, followed by 0.09 mg/kg/day = 6.4 mg IV for 6 additional days. He received 2 further cycles of 0.14 mg kg/day for 7 days (1 month apart). After 3 cycles he improved significantly both clinically and radiographically. Six months post-treatment objective testing showed improvement in cardiac, neurologic, and pulmonary disease.Erdheim Chester Disease (ECD) is a rare non Langerhans cell histiocytosis. Only several hundred cases have been reported in the literature. Treatment for ECD is reserved for those with symptomatic disease, asymptomatic CNS involvement, or evidence of organ dysfunction. There is no standard treatment regimen: Current options include corticosteroids, Interferon alpha (IFN), systemic chemotherapy, and radiation therapy. The occurrence of the V600EBRAF mutation in about 50% of patients can make these patients amenable to targeted therapy with BRAF kinase inhibitors (e.g. Vemurafenib). More recently the presence of N/KRAS, and PIK3CA mutations have provided further rational for targeted therapies. The cytokine profile in patients with ECD suggests monocyte activation cladribine, a purine analogue toxic to monocytes, has also been studied as a treatment for ECD, especially in patients who test negative for the BRAF mutation

    Case Report: A Case of Wood-Smoke–Related Pulmonary Disease

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    CONTEXT: Biomass serves as a major fuel source for > 50% of the world’s population. The global burden of disease attributed to indoor air pollution from biomass combustion accounts for approximately 3% of worldwide disability-adjusted life-years lost. This is due to pneumonia in children and chronic obstructive pulmonary disease and lung cancer in women. CASE PRESENTATION: A 53-year-old man from Mexico was referred to the pulmonary clinic for evaluation of chronic productive cough and pulmonary nodules. In his youth, he worked at a charcoal plant in Mexico, where he burned wood and was exposed to massive amounts of smoke. His evaluation revealed thickened bronchovascular bundles with nodules on thoracic computed tomography, dark black plaques in large airways on bronchoscopy, and carbon-laden macrophages and fibrotic scars on lung biopsy. DISCUSSION: The patient was diagnosed with “hut lung,” a term that refers to the noninfectious, nonmalignant respiratory manifestations of chronic, high-level exposures to biomass smoke. This is the first reported case of hut lung associated with charcoal production. This case highlights that histopathologic abnormalities of the lung parenchyma may be present in patients with only mild symptoms and that clinical progression is likely a function of both the duration and intensity of exposure. RELEVANCE TO CLINICAL PRACTICE: As residents of lesser developed countries continue to be exposed to high levels of biomass smoke at work or at home and continue to immigrate to developed countries, it is important that health care providers in developed countries be aware of biomass-smoke–related pulmonary disease

    Sclerosing angiomatoid nodular transformation of the spleen: CT, MR, PET, and 99mTc-sulfur colloid SPECT CT findings with gross and histopathological correlation

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    Sclerosing angiomatoid nodular transformation (SANT) is a benign, proliferative vascular lesion affecting the spleen. Few reports detailing the cross sectional and PET appearance of this lesion are available, and the lesion’s behavior with 99mTc-sulfur colloid scintigraphy is previously unreported. Sclerosing nodular transformation of the spleen shows increased tracer accumulation on positron emission tomography, and a central scar-like appearance with an enhancing capsule and radiating septae on CT and MR studies that reflects the gross and histopathological features of the lesion may be visible. An understanding of this pathological finding may allow prospective recognition of the sclerosing nodular transformation of the spleen on cross sectional imaging studies

    Infigratinib in children with achondroplasia:the PROPEL and PROPEL 2 studies

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    BACKGROUND: Achondroplasia is the most common short-limbed skeletal dysplasia resulting from gain-of-function pathogenic variants in fibroblast growth factor receptor 3 (FGFR3) gene, a negative regulator of endochondral bone formation. Most treatment options are symptomatic, targeting medical complications. Infigratinib is an orally bioavailable, FGFR1–3 selective tyrosine kinase inhibitor being investigated as a direct therapeutic strategy to counteract FGFR3 overactivity in achondroplasia. OBJECTIVES: The main objective of PROPEL is to collect baseline data of children with achondroplasia being considered for future enrollment in interventional studies sponsored by QED Therapeutics. The objectives of PROPEL 2 are to obtain preliminary evidence of safety and efficacy of oral infigratinib in children with achondroplasia, to identify the infigratinib dose to be explored in future studies, and to characterize the pharmacokinetic (PK) profile of infigratinib and major metabolites. DESIGN: PROPEL (NCT04035811) is a prospective, noninterventional clinical study designed to characterize the natural history and collect baseline data of children with achondroplasia over 6−24 months. PROPEL 2 (NCT04265651), a prospective, phase II, open-label study of infigratinib in children with achondroplasia, consists of a dose-escalation, dose-finding, and dose-expansion phase to confirm the selected dose, and a PK substudy. METHODS AND ANALYSIS: Children aged 3−11 years with achondroplasia who completed ⩾6 months in PROPEL are eligible for PROPEL 2. Primary endpoints include treatment-emergent adverse events and change from baseline in annualized height velocity. Four cohorts at ascending dose levels are planned for dose escalation. The selected dose will be confirmed in the dose-expansion phase. ETHICS: PROPEL and PROPEL 2 are being conducted in accordance with the International Conference on Harmonization Good Clinical Practice guidelines, principles of the Declaration of Helsinki, and relevant human clinical research and data privacy regulations. Protocols have been approved by local health authorities, ethics committees, and institutions as applicable. Parents/legally authorized representatives are required to provide signed informed consent; signed informed assent by the child is also required, where applicable. DISCUSSION: PROPEL and PROPEL 2 will provide preliminary evidence of the safety and efficacy of infigratinib as precision treatment of children with achondroplasia and will inform the design of future studies of FGFR-targeted agents in achondroplasia. REGISTRATION: ClinicalTrials.gov: NCT04035811; NCT04265651
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