New hematologic populations at risk of invasive aspergillosis: focus on new targeted, biological, and cellular therapies

Girmenia, Corrado

doi:10.12688/f1000research.17836.1

Cited by 4 publications

(8 citation statements)

References 61 publications

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“…[28][29][30] This increase can be explained by improved diagnosis, broader use of old and new immunosuppressive agents, and increase in organ transplantations. 29,31 ►Fig. 2 presents the range of incidences in most frequent underlying conditions predisposing to the development of IA.…”

Section: Epidemiologymentioning

confidence: 99%

Invasive Pulmonary Aspergillosis

Ledoux

Guffroy

Nivoix

et al. 2020

Semin Respir Crit Care Med

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Invasive pulmonary aspergillosis (IPA) remains difficult to diagnose and to treat. Most common risk factors are prolonged neutropenia, hematopoietic stem cell or solid organ transplantation, inherited or acquired immunodeficiency, administration of steroids or other immunosuppressive agents including monoclonal antibodies and new small molecules used for cancer therapy. Critically ill patients are also at high risk of IPA. Clinical signs are unspecific. Early computed tomography (CT)-scan identifies the two main aspects, angioinvasive and airway invasive aspergillosis. Although CT-scan findings are not fully specific they usually allow early initiation of therapy before mycological confirmation of the diagnosis. Role of 18F-fludeoxyglucose positron emission tomography with computed tomography (18F-FDG PET/CT) is discussed. Confirmation is based on microscopy and culture of respiratory samples, histopathology in case of biopsy, and importantly by detection of Aspergillus galactomannan using an immunoassay in serum and bronchoalveolar lavage fluid. Deoxyribonucleic acid detection by polymerase chain reaction is now standardized and increases the diagnosis yield. Two point of care tests detecting an Aspergillus glycoprotein using a lateral flow assay are also available. Mycological results allow classification into proven (irrespective of underlying condition), probable or possible (for cancer and severely immunosuppressed patients) or putative (for critically ill patients) IPA. New antifungal agents have been developed over the last 2 decades: new azoles (voriconazole, posaconazole, isavuconazole), lipid formulations of amphotericin B (liposomal amphotericin B, amphotericin B lipid complex), echinocandins (caspofungin, micafungin, anidulafungin). Results of main trials assessing these agents in monotherapy or in combination are presented as well as the recommendations for their use according to international guidelines. New agents are under development.

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Section: Epidemiologymentioning

confidence: 99%

Invasive Pulmonary Aspergillosis

Ledoux

Guffroy

Nivoix

et al. 2020

Semin Respir Crit Care Med

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“…17 Invasive aspergillosis is a common complication in patients with hematologic malignancies and it increases the mortality rates in this patient population. 18 This is especially true for patients undergoing new targeted biological and cellular therapies. 18 To further complicate matters, antifungals commonly inhibit cytochrome enzymes that modulate certain kinase inhibitors used for the management of the underlying malignant conditions.…”

Section: Discussionmentioning

confidence: 99%

“…18 This is especially true for patients undergoing new targeted biological and cellular therapies. 18 To further complicate matters, antifungals commonly inhibit cytochrome enzymes that modulate certain kinase inhibitors used for the management of the underlying malignant conditions. 18 This makes the management of such patients and the choice of medication and dosage challenging.…”

Section: Discussionmentioning

confidence: 99%

“…18 To further complicate matters, antifungals commonly inhibit cytochrome enzymes that modulate certain kinase inhibitors used for the management of the underlying malignant conditions. 18 This makes the management of such patients and the choice of medication and dosage challenging. 18,19 conclusIon It is imperative that maxillary aspergillosis be diagnosed and managed properly and promptly to improve prognosis.…”

Section: Discussionmentioning

confidence: 99%

“…18 This makes the management of such patients and the choice of medication and dosage challenging. 18,19 conclusIon It is imperative that maxillary aspergillosis be diagnosed and managed properly and promptly to improve prognosis. Advanced imaging is required; however, it plays an adjunct role to histopathology and microbiology.…”

Section: Discussionmentioning

confidence: 99%

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A Case Report of Maxillary Aspergillosis with Unusual Clinical and Imaging Presentations

Jan

Jadu

2020

The Journal of Contemporary Dental Practice

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Aim:The aim of the present study was to present a case of maxillary aspergillosis with unusual clinical presentation and imaging findings. Background: The range of lesions and conditions that affect the maxillary sinus is wide and vast. This necessitates a dynamic multidisciplinary approach for proper diagnosis and effective management. Case description: We present an unusual case of maxillary aspergillosis that mimicked apical periodontitis and was most consistent with lymphoma from the diagnostic imaging perspective. Histopathology, however, established the correct diagnosis; appropriate management commenced promptly. Conclusion: It is imperative that maxillary aspergillosis be diagnosed and managed properly and promptly to improve prognosis. Advanced imaging is required, but it plays an adjunct role to histopathology. Long-term follow-up is also necessary to ensure complete resolution of the infection. Clinical significance: Correlating clinical and imaging findings is a crucial step and any inconsistencies should be resolved promptly so as not to delay adequate management. Histopathology often serves to dispute any inconsistencies and allows the establishment of a proper diagnosis.

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Discovery of N-(4-(3-isopropyl-2-methyl-2H-indazol-5-yl)pyrimidin-2-yl)-4-(4-methylpiperazin-1-yl)quinazolin-7-amine as a Novel, Potent, and Oral Cyclin-Dependent Kinase Inhibitor against Haematological Malignancies

et al. 2021

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Hematologic malignancies (HM) start in blood forming tissue or in the cells of the immune system. Cyclin-dependent kinases (CDKs) regulate cell cycle progression, and some of them control cellular transcription. CDK inhibition can trigger apoptosis and could be particularly useful in hematological malignancies. Herein, we describe our efforts toward the discovery of a novel series of quinazoline derivatives as CDK inhibitors. Intensive structural modifications lead to the identification of compound 37d as the most active inhibitors of CDKs 1, 2, 4, 8 and 9 with balancing potency and selectivity against CDKs. Further biological studies revealed that compound 37d can arrest the cell cycle and induce apoptosis via activating PARP and caspase 3. More importantly, compound 37d showed good antitumor efficacy in multiple HM mice xenograft models with no obvious toxicity. These results indicated that CDK 1, 2, 4, 8, and 9 inhibitors could be potentially used to treat certain hematologic malignancies.

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New hematologic populations at risk of invasive aspergillosis: focus on new targeted, biological, and cellular therapies

Cited by 4 publications

References 61 publications

Invasive Pulmonary Aspergillosis

Invasive Pulmonary Aspergillosis

A Case Report of Maxillary Aspergillosis with Unusual Clinical and Imaging Presentations

Discovery of N-(4-(3-isopropyl-2-methyl-2H-indazol-5-yl)pyrimidin-2-yl)-4-(4-methylpiperazin-1-yl)quinazolin-7-amine as a Novel, Potent, and Oral Cyclin-Dependent Kinase Inhibitor against Haematological Malignancies

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