scholarly journals A Case Report with Severe Thrombocytopenia Induced by Axitinib

2020 ◽  
Vol 2020 ◽  
pp. 1-4
Author(s):  
Ulkuhan I. Koksal ◽  
Janeiro Valle Goffin ◽  
Brian Lewis ◽  
Oliver A. Sartor ◽  
Elizaveta Belyaeva ◽  
...  
Keyword(s):  
Multidisciplinary Approach ◽  
Kinase Inhibitor ◽  
Checkpoint Inhibitors ◽  
Severe Thrombocytopenia ◽  
Vascular Endothelial ◽  
Successful Management ◽  
Antiangiogenic Therapies ◽  
Diagnostic Work ◽  
Endothelial Growth Factor ◽  
Work Up

Axitinib is an oral, second-generation tyrosine kinase inhibitor that is selective for vascular endothelial growth factor receptors (VEGFR). This agent is approved as monotherapy or in combination with immune checkpoint inhibitors for the treatment of metastatic renal cell carcinoma. Axitinib is associated with a safety profile very similar to other anti-VEGFR inhibitors but usually with fewer hematologic adverse events, due to the selectivity for VEGF. In this report, we presented a rare case of grade 4 axitinib-induced thrombocytopenia, not observed with other antiangiogenic therapies. We discuss the differential diagnostic work-up, the necessary multidisciplinary approach, and the successful management of the case.

scholarly journals Abnormal Crosstalk between Endothelial Cells and Podocytes Mediates Tyrosine Kinase Inhibitor (TKI)-Induced Nephrotoxicity

Cells ◽  
2021 ◽  
Vol 10 (4) ◽  
pp. 869
Author(s):  
Xiaoying Gu ◽  
Su Zhang ◽  
Ti Zhang
Keyword(s):  
Tyrosine Kinase ◽  
Kinase Inhibitors ◽  
Kinase Inhibitor ◽  
Underlying Mechanism ◽  
Signal Pathways ◽  
Vascular Endothelial ◽  
Podocyte Injury ◽  
Antiangiogenic Therapies ◽  
Foot Process ◽  
Endothelial Growth Factor

Vascular endothelial growth factor A (VEGFA) and its receptor VEGFR2 are the main targets of antiangiogenic therapies, and proteinuria is one of the common adverse events associated with the inhibition of the VEGFA/VEGFR2 pathway. The proteinuric kidney damage induced by VEGFR2 tyrosine kinase inhibitors (TKIs) is characterized by podocyte foot process effacement. TKI therapy promotes the formation of abnormal endothelial‒podocyte crosstalk, which plays a key role in TKI-induced podocyte injury and proteinuric nephropathy. This review article summarizes the underlying mechanism by which the abnormal endothelial‒podocyte crosstalk mediates podocyte injury and discusses the possible molecules and signal pathways involved in abnormal endothelial‒podocyte crosstalk. What is more, we highlight the molecules involved in podocyte injury and determine the essential roles of Rac1 and Cdc42; this provides evidence for exploring the abnormal endothelial‒podocyte crosstalk in TKI-induced nephrotoxicity.

scholarly journals COVID-19 lung injury as a primer for immune checkpoint inhibitors (ICIs)-related pneumonia in a patient affected by squamous head and neck carcinoma treated with PD-L1 blockade: a case report

2021 ◽  
Vol 9 (2) ◽  
pp. e001870
Author(s):  
Angelo Dipasquale ◽  
Pasquale Persico ◽  
Elena Lorenzi ◽  
Daoud Rahal ◽  
Armando Santoro ◽  
...  
Keyword(s):  
Lung Injury ◽  
Head And Neck ◽  
Checkpoint Inhibitors ◽  
Experimental Therapy ◽  
Common Mechanism ◽  
Nasopharyngeal Swab ◽  
Immune Mediated ◽  
Diagnostic Work ◽  
Work Up ◽  
Diagnostic Work Up

By the beginning of the global pandemic, SARS-CoV-2 infection has dramatically impacted on oncology daily practice. In the current oncological landscape, where immunotherapy has revolutionized the treatment of several malignancies, distinguishing between COVID-19 and immune-mediated pneumonitis can be hard because of shared clinical, radiological and pathological features. Indeed, their common mechanism of aberrant inflammation could lead to a mutual and amplifying interaction.We describe the case of a 65–year-old patient affected by metastatic squamous head and neck cancer and candidate to an experimental therapy including an anti-PD-L1 agent. COVID-19 ground-glass opacities under resolution were an incidental finding during screening procedures and worsened after starting immunotherapy. The diagnostic work-up was consistent with ICIs-related pneumonia and it is conceivable that lung injury by SARS-CoV-2 has acted as an inflammatory primer for the development of the immune-related adverse event.Patients recovered from COVID-19 starting ICIs could be at greater risk of recall immune-mediated pneumonitis. Nasopharyngeal swab and chest CT scan are recommended before starting immunotherapy. The awareness of the phenomenon could allow an easier interpretation of radiological changes under treatment and a faster diagnostic work-up to resume ICIs. In the presence of clinical benefit, for asymptomatic ICIs-related pneumonia a watchful-waiting approach and immunotherapy prosecution are suggested.

Bleeding with vascular endothelial growth factor tyrosine kinase inhibitor: A network meta-analysis

2021 ◽  
Vol 157 ◽  
pp. 103186
Author(s):  
Avash Das ◽  
Somnath Mahapatra ◽  
Dhrubajyoti Bandyopadhyay ◽  
Santanu Samanta ◽  
Sandipan Chakraborty ◽  
...  
Keyword(s):  
Vascular Endothelial Growth Factor ◽  
Growth Factor ◽  
Tyrosine Kinase ◽  
Tyrosine Kinase Inhibitor ◽  
Kinase Inhibitor ◽  
Meta Analysis ◽  
Vascular Endothelial ◽  
Endothelial Growth Factor

DNA damage repair (DDR) pathway alteration in advanced renal cell carcinoma (RCC) is association with good progression-free survival with tyrosine kinase inhibitor (TKI) therapy.

2021 ◽  
Vol 39 (6_suppl) ◽  
pp. 346-346
Author(s):  
Wei Zhai ◽  
Junyun Wang ◽  
Ning He ◽  
Jiale Zhou ◽  
Jianfei Wang ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Tyrosine Kinase ◽  
Tyrosine Kinase Inhibitor ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Kinase Inhibitor ◽  
Progression Free Survival ◽  
Vascular Endothelial ◽  
Damage Repair ◽  
Endothelial Growth Factor

346 Background: Alterations in DNA damage repair (DDR) genes are associated with human tumorigenesis and may be as potential biomarkers for vascular endothelial growth factor (VEGF) tyrosine kinase inhibitor (TKI) therapy in renal cell carcinoma. However, biologic significance and relevance to TKI targeted therapy in metastatic RCC are unknown. Methods: Genomic data and treatment outcomes were retrospectively collected for patients with metastatic RCC. Tumor and germline DNA were subject to targeted next generation sequencing across 642 genes of interest, including 60 DDR genes. Patients were dichotomized according to underlying DDR gene alteration into (1) DDR gene alterations present (Mut DDR); (2) wildtype (WT) DDR gene alterations present (WT DDR). Association between DDR status and therapeutic benefit was investigated separately for and vascular endothelial growth factor (VEGF) tyrosine kinase inhibitor (TKI) therapy. Results: Mut DDR were detected in 17/40 patients (42.5%). The most frequently DDR altered genes were TP53. For patients with TKI treatment, Mut DDR status was associated with superior progression free survival (log-rank p = 0.048), but not with superior overall survival (log-rank p = 0.39); after adjusting for International Metastatic Renal Cell Carcinoma Database Consortium risks and extent of prior therapy, the HR for Mut DDR was 2.68 (95% CI: 0.96–7.46; p = 0.059). Conclusions: DDR alterations are recurrent genomic events in patients with advanced RCC and were mostly clonal in this cohort. Dysfunction events in these genes may affect outcome with TKI therapy in adanced RCC, and these hypothesis-generating results deserve further study.

scholarly journals Rhino- Orbito- Cerebral- Mucormycosis with Osteomyelitis in a Patient with Diabetes mellitus: A Case Report and Literature Review

2012 ◽  
Vol 2 (2) ◽  
pp. 124-128 ◽  
Author(s):  
Rumana Habib ◽  
Rashedul Islam ◽  
Aminur Rahman ◽  
NB Bhowmik ◽  
Amirul Haque
Keyword(s):  
Case Report ◽  
Fungal Infection ◽  
Acquired Immunodeficiency Syndrome ◽  
Hematologic Malignancies ◽  
Successful Management ◽  
Acquired Immunodeficiency ◽  
Diagnostic Work ◽  
Immunodeficiency Syndrome ◽  
Work Up ◽  
Diagnostic Work Up

Mucormycosis is a form of fulminant invasive fungal infection of the sinonasal tract that often extends to the orbit, brain, palate, and skin. It is caused by members of the order Mucorales, and it is considered to be the most fatal fungal infection known to man. It is most commonly associated with diabetic ketoacidosis, hematologic malignancies, acquired immunodeficiency syndrome acquired immunodeficiency syndrome, see AIDS. , and immunosuppressive therapy. This rare opportunistic infection exists in many forms, the most common of which is rhinocerebral mucormycosis. Treatment includes aggressive surgical debridement of the necrotic tissue combined with systemic antifungal therapy. In this case report, we describe the successful management of rhinoorbitocerebral mucormycosis, a subtype of the rhinocerebral variety, complicated by osteomyelitis of cranium. We review the diagnostic work-up and discuss the literature with respect to the presentation, pathophysiology, management, and outcome of the disease.DOI: http://dx.doi.org/10.3329/birdem.v2i2.12331(Birdem Med J 2012; 2(2):124-127)

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