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Genetic Risk Surveillance for Invasive Aspergillosis in Hematology Patients: A Prospective Observational Study.

ABSTRACT: INTRODUCTION:The association between genetic background and the risk of invasive aspergillosis (IA) has not been addressed in Thailand. We conducted genetic risk surveillance for IA among Thai hematologic patients. METHODS:We conducted a prospective observational cohort study including moderate- to high-risk hematology patients at Ramathibodi Hospital. IA occurrence, relevant clinical data, and genetic analyses were assessed. Odds ratios (ORs) of IA were assessed for the presence of the selected single nucleotide polymorphism genotype using logistic regression. RESULTS:A total of 357 patients were enrolled. The most common hematologic disease was non-Hodgkin lymphoma (45.1%). IA was diagnosed in 36 patients (10.10%). The C allele of IL10rs1800896 was associated with an increased risk of IA (adjusted OR 5.297; 95% confidence interval [CI] 2.032-13.809, p?=?0.001). In multivariate Cox regression analysis, prolonged neutropenia and the C allele of IL10rs1800896 were associated with IA (hazard ratio [HR] 12.585; 95% CI 3.866-40.967, p < 0.001 and HR 2.449; 95% CI 1.097-5.468, p = 0.042, respectively). CONCLUSIONS:Carrying the C allele of IL10rs1800896 was associated with an increased risk of IA among moderate- to high-risk Thai patients with hematologic diseases. This finding can potentially lead to a novel risk stratification scheme to further prevent IA in resource-limited settings.

SUBMITTER: Tanpaibule T

PROVIDER: S-EPMC7680473 | biostudies-literature | 2020 Dec

REPOSITORIES: biostudies-literature

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Genetic Risk Surveillance for Invasive Aspergillosis in Hematology Patients: A Prospective Observational Study.

Tanpaibule Tananun T Jinawath Natini N Taweewongsounton Aruchalean A Niparuck Pimjai P Rotjanapan Porpon P

Infectious diseases and therapy 20200828 4

<h4>Introduction</h4>The association between genetic background and the risk of invasive aspergillosis (IA) has not been addressed in Thailand. We conducted genetic risk surveillance for IA among Thai hematologic patients.<h4>Methods</h4>We conducted a prospective observational cohort study including moderate- to high-risk hematology patients at Ramathibodi Hospital. IA occurrence, relevant clinical data, and genetic analyses were assessed. Odds ratios (ORs) of IA were assessed for the presence ...[more]

PMID: 32860206

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Project description:BackgroundPulmonary computed tomography (CT) scans are commonly used as part of the clinical criteria in diagnostic workup of invasive fungal diseases like invasive aspergillosis, and may identify radiographic abnormalities, such as halo signs or air-crescent signs. We assessed the diagnostic utility of CT assessment in patients with hematologic malignancies or those who had undergone allogeneic hematopoietic stem cell transplantation in whom invasive aspergillosis was suspected.MethodsThis post-hoc analysis assessed data from a prospective, multicenter, international trial of voriconazole (with and without anidulafungin) in patients with suspected invasive aspergillosis (IA; proven, probable, or possible, using 2008 European Organisation for Research and Treatment of Cancer/Invasive Fungal Infections Cooperative Group and the National Institute of Allergy and Infectious Diseases Mycoses Study Group criteria) [NCT00531479]. Eligible patients received at least one baseline lung CT scan.ResultsOf 395 patients included in this post-hoc analysis, 240 patients (60.8%) had 'confirmed' proven (9/240, 3.8%) or probable (231/240, 96.3%) invasive aspergillosis (cIA) and 155 patients (39.2%) had 'non-confirmed' invasive aspergillosis (all nIA; all possible IA (de Pauw et al., Clin Infect Dis 46:1813-21, 2008)). Mean age was 52.3 and 50.5 years, 56.3 and 60.0% of patients were male, and most patients were white (71.7 and 71.0%) in the cIA and nIA populations, respectively. Median baseline galactomannan was 1.4 (cIA) and 0.2 (nIA), mean Karnofsky score was 65.3 (cIA) and 66.8 (nIA), and mean baseline platelet count was 48.0 (cIA) and 314.1 (nIA). Pulmonary nodules (46.8% of all patients), bilateral lung lesions (37.5%), unilateral lung lesions (28.4%), and consolidation (24.8%) were the most common radiographic abnormalities. Ground-glass attenuation (cIA: 24.2%; nIA: 11.6%; P < 0.01) and pulmonary nodules (cIA: 52.5%; nIA: 38.1%; P < 0.01) were associated with cIA. Other chest CT scan abnormalities (including halo signs and air-crescent signs) at baseline in patients with hematologic malignancy or hematopoietic stem cell transplantation, and suspected IA, were not associated with cIA.ConclusionsThese findings highlight the limitations in the sensitivity of chest CT scans for the diagnosis of IA, and reinforce the importance of incorporating other available clinical data to guide management decisions on individual patients, including whether empirical treatment is reasonable, pending full evaluation.Trial registrationNCT00531479 (First posted on ClinicalTrials.gov on September 18, 2007).

Project description:AbstractBackgroundInherited thrombocytopenias (ITs) are rare congenital bleeding disorders characterized by different clinical expression and variable prognosis. ITs are poorly known by clinicians and often misdiagnosed with most common forms of thrombocytopenia.Material and methods"CHildren with Inherited Platelet disorders Surveillance" study (CHIPS) is a retrospective - prospective observational cohort study conducted between January 2003 and January 2022 in 17 centers affiliated to the Italian Association of Pediatric Hematology and Oncology (AIEOP). The primary objective of this study was to collect clinical and laboratory data on Italian pediatric patients with inherited thrombocytopenias. Secondary objectives were to calculate prevalence of ITs in Italian pediatric population and to assess frequency and genotype-phenotype correlation of different types of mutations in our study cohort.ResultsA total of 139 children, with ITs (82 male - 57 female) were enrolled. ITs prevalence in Italy ranged from 0.7 per 100,000 children during 2010 to 2 per 100,000 children during 2022. The median time between the onset of thrombocytopenia and the diagnosis of ITs was 1 years (range 0 - 18 years). A family history of thrombocytopenia has been reported in 90 patients (65%). Among 139 children with ITs, in 73 (53%) children almost one defective gene has been identified. In 61 patients a pathogenic mutation has been identified. Among them, 2 patients also carry a variant of uncertain significance (VUS), and 4 others harbour 2 VUS variants. VUS variants were identified in further 8 patients (6%), 4 of which carry more than one variant VUS. Three patients (2%) had a likely pathogenic variant while in 1 patient (1%) a variant was identified that was initially given an uncertain significance but was later classified as benign. In addition, in 17 patients the genetic diagnosis is not available, but their family history and clinical/laboratory features strongly suggest the presence of a specific genetic cause. In 49 children (35%) no genetic defect were identified. In ninetyseven patients (70%), thrombocytopenia was not associated with other clinically apparent disorders. However, 42 children (30%) had one or more additional clinical alterations.ConclusionOur study provides a descriptive collection of ITs in the pediatric Italian population.

Project description:IntroductionCritically ill patients with chronic obstructive respiratory diseases (CORD) who require intensive care unit (ICU) admission are at particular risk for invasive bronchial-pulmonary aspergillosis (IBPA). The purpose of this study is to investigate clinical features for rapid recognition of IBPA in critically ill patients with CORD.MethodsWe included 55 consecutive CORD patients in a respiratory ICU in a prospective, single-center, cohort study. In this study, IBPA combined two entities: ATB and IPA.ResultsThirteen of 55 patients were diagnosed with IBPA. Before ICU admission, three variables were independent predictors of IBPA with statistical significance: more than three kinds of antibiotics used before the ICU admission, accumulated doses of corticosteroids (>350 mg) received before the ICU admission, and APACHE II scores >18 (OR, 1.208; P = 0.022; OR, 8.661; P = 0.038; and OR, 19.488; P = 0.008, respectively). After ICU admission, more IBPA patients had a high fever (>38.5 °C) (46.2% versus 11.9%; P = 0.021), wheeze without exertion (84.6% versus 50.0%; P = 0.027), dry rales (84.6% versus 40.4%; P = 0.005), higher white blood cell counts (21 × 109/L versus 9.4 × 109/L; P = 0.012), lower mean arterial pressures (77.9 mm Hg versus 90.5 mm Hg; P = 0.019), and serum creatinine clearances (36.2 ml/min versus 68.8 ml/min; P < 0.001), and liver-function and coagulation abnormalities. Bronchospasm, sputum ropiness, and plaque formation were more common for IBPA patients during bronchoscopy (66.7% versus 14.3%; P = 0.082; 18% versus 0; P = 0.169; and 73% versus 13%; P = 0.003, respectively). More IBPA patients had nodules and patchiness on chest radiograph on day 1 of admission, which rapidly progressed to consolidation on day 7. IBPA mortality was higher than that of non-IBPA patients (69.2% versus 16.7%; P = 0.001).ConclusionsIBPA may be suspected in critically ill CORD patients with respiratory failure and clinical and bronchoscopic manifestations of severe infection, bronchospasm, and rapid progression of radiologic lesions that are irresponsive to steroids and antibiotics. To avoid misdiagnosis and establish the microbiologic etiology, early bronchoscopy and tight radiologic follow-up should be performed.

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Genetic Risk Surveillance for Invasive Aspergillosis in Hematology Patients: A Prospective Observational Study.

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Genetic Risk Surveillance for Invasive Aspergillosis in Hematology Patients: A Prospective Observational Study.

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