The fear for adverse bleeding and cardiovascular events in hemophilia patients using (non-)selective non-steroidal anti-inflammatory drugs: A systematic review reporting on safety.

(Non-)selective non-steroidal anti-inflammatory drugs (NSAIDs) are commonly used for musculoskeletal related pain. These cheap and easily accessible drugs may be of great value for hemophilia patients in developing countries and countries with a high rate of opioid poisoning, but also in developed countries due to potential joint protective effects. However, fear for adverse bleeding and cardiovascular events during the use of these drugs restrains prescription within this population. To give a complete overview of all publications reporting on safety, a systematic search till March 2021 was performed. All studies were reviewed and critically appraised and this resulted in 19 studies eligible for inclusion. Most studies with (non-)selective NSAIDs showed no evident risk for relevant adverse bleeding or cardiovascular events. However, some studies had a high risk of bias and studies reporting on cardiovascular events were limited. Future studies with longitudinal follow-up in well-defined large patient populations, including older patients, focusing on both adverse bleeding and cardiovascular events are required to confirm the alleged safe use.

Pediatric medulloblastoma express immune checkpoint B7-H3

PurposeMedulloblastomas (MB) are highly malignant brain tumors that predominantly occur in young infants. Immunotherapy to boost the immune system is emerging as a novel promising approach, but is often hampered by inhibitory immune checkpoints. In the present study, we have studied immune checkpoint B7-H3 expression in a tissue cohort of human pediatric MB.MethodsExpression of B7-H3 was detected by immunohistochemistry and classified via B7-H3 staining intensity and percentage of B7-H3 positive tumor cells. Subsequently, B7-H3 protein expression was distinguished in MB molecular subtypes and correlated to immune cell infiltrates, patient characteristics, and survival.ResultsB7-H3 protein expression was found in 23 out of 24 (96%) human pediatric MB cases and in 17 out of 24 (71%) MB cases > 25% of tumor cells had any level of B7-H3 expression. B7-H3 protein expression was more frequent on Group-4 MB as compared with other molecular subtypes (p = 0.02). Tumors with high B7-H3 expression showed less influx of γδT cells (p = 0.002) and CD3+ T cells (p = 0.041).ConclusionImmune checkpoint B7-H3 is differentially expressed by the large majority of pediatric MB. This further warrants the development of novel B7-H3-directed (immuno)therapeutic methods for children with incurable, metastatic, or chemo-resistant MB.

Pediatric medulloblastoma express immune checkpoint B7-H3.

PURPOSE: Medulloblastomas (MB) are highly malignant brain tumors that predominantly occur in young infants. Immunotherapy to boost the immune system is emerging as a novel promising approach, but is often hampered by inhibitory immune checkpoints. In the present study, we have studied immune checkpoint B7-H3 expression in a tissue cohort of human pediatric MB. METHODS: Expression of B7-H3 was detected by immunohistochemistry and classified via B7-H3 staining intensity and percentage of B7-H3 positive tumor cells. Subsequently, B7-H3 protein expression was distinguished in MB molecular subtypes and correlated to immune cell infiltrates, patient characteristics, and survival. RESULTS: B7-H3 protein expression was found in 23 out of 24 (96%) human pediatric MB cases and in 17 out of 24 (71%) MB cases > 25% of tumor cells had any level of B7-H3 expression. B7-H3 protein expression was more frequent on Group-4 MB as compared with other molecular subtypes (p = 0.02). Tumors with high B7-H3 expression showed less influx of γδT cells (p = 0.002) and CD3+ T cells (p = 0.041). CONCLUSION: Immune checkpoint B7-H3 is differentially expressed by the large majority of pediatric MB. This further warrants the development of novel B7-H3-directed (immuno)therapeutic methods for children with incurable, metastatic, or chemo-resistant MB.