The role of PD-L1 in biological behavior of intracranial meningiomas

Meningiomas are considered a substantially benign disease that can be treated surgically in the vast majority of patients. However, there are forms of meningioma characterized by greater aggressiveness and/or tendency to recurrence. To date, grading is the only known factor that provides some information about the biological behavior of meningiomas. As a matter of fact, patients with high grade meningiomas (WHO grade 2 and 3) have a significant higher risk to develop local recurrence after treatment and, consequently, they tend to have a shorter survival compared to patients with WHO grade 1 meningiomas .However, even grade 1 meningiomas can recur even if with less frequency. Given that to date there are no approved pharmacological treatments for meningiomas and that the use of treatments such as hormone-therapy and chemotherapy have not shown any substantial benefit, it seems appropriate to hypothesize new innovative therapeutic strategies and verify their biological plausibility. To our knowledge, this is the first report of increased PD-L1 expression in meningioma recurrences compared to their primary presentation, regardless of their grade. The high prevalence of PD-L1 expression in the meningioma population and its correlation with grade and clinical behavior may be an important tool to tailor therapeutical strategies and follow up, in particular in high grade and recurrent cases. Moreover, the results obtained contribute to build a rational basis for designing therapeutic trials that use immunotherapy in the treatment of meningiomas

Clipping Strategies and Intraoperative Tools to Detect Aneurysm Obliteration and Cerebral Vessel Patency

Cerebral aneurysms are common cerebrovascular diseases most frequently manifest with vascular rupture and subsequent subarachnoid hemorrhage. Microsurgical clipping is considered the best long-term treatment, despite of the increase of endovascular interventional treatments in the latest years. Vascular control is a pivotal concept for aneurysms surgery, which provides the application of temporary clip in case of rupture, whereas the application of permanent clip requires the perfect knowledge of aneurysm anatomy. Several techniques to obtain the obliteration of the aneurysm while preserving the parent vessels and its branches have been described. Micro-Doppler ultrasonography (MUSG), indocyanine green video angiography (ICG-VA), and electrophysiological neuromonitoring (IONM) are all useful intraoperative tools, which can improve the safety of surgical procedures and achieve the goal of aneurysm obliteration with parent vessel and perforating preservation

Primary Cardiac High-grade Myxofibrosarcoma Presenting with Multiple Brain Metastases: A Case Report

Herein we describe the case of a young patient who presented with a recent history of epilepsy due to multiple brain lesions; he did not complain about any cardiopulmonary impairments. The patient died as a consequence of hemorrhagic progression of brain metastatic disease. Regardless of a thorough investigation, the heart tumor remained occult. Primary cardiac tumors are very rare entities. Most of these are benign, but approximately 25% are malignant, and the majority of these are sarcomas. Myxofibrosarcoma and osteosarcoma are exceptionally rare. To date, we find only small series of cardiac myxofibrosarcoma, and to our knowledge, this one exceptionally presented with multiple brain metastatic lesions without cardiopulmonary symptoms

Hyperglycemia and angiotensin II cooperate to enhance collagen I deposition by cardiac fibroblasts through a ROS-STAT3-dependent mechanism

AbstractCardiac fibroblasts significantly contribute to diabetes-induced structural and functional changes in the myocardium. The objective of the present study was to determine the effects of high glucose (alone or supplemented with angiotensin II) in the activation of the JAK2/STAT3 pathway and its involvement in collagen I production by cardiac fibroblasts. We observed that the diabetic environment 1) enhanced tyrosine phosphorylation of JAK2 and STAT3; 2) induced nuclear localization of tyrosine phosphorylated STAT3 through a reactive oxygen species-mediated mechanism, with angiotensin II stimulation further enhancing STAT3 nuclear accumulation; and 3) stimulated collagen I production. The effects were inhibited by depletion of reactive oxygen species or silencing of STAT3 in high glucose alone or supplemented with exogenous angiotensin II. Combined, our data demonstrate that increased collagen I deposition in the setting of high glucose occurred through a reactive oxygen species- and STAT3-dependent mechanism. Our results reveal a novel role for STAT3 as a key signaling molecule of collagen I production in cardiac fibroblasts exposed to a diabetic environment

Lymphoplasmacyte-rich meningioma with hematologic signs and PD-L1 over-expression

Lymphoplasmacyte-rich meningioma (LPRM) is one of the rarest variants of grade I meningiomas. It can be clinically associated with prominent peripheral blood abnormalities, anemia, and/or various gammopathy, which usually disappear after surgical removal of the tumor. We document a case of right frontal LPRM in a 72-year-old male who presented general cognitive decadence. The patient suffered from mild anemia. The LPRM is a rare variant of meningioma, with only a few cases globally reported in the literature. It has been categorized as a grade I tumor in the 2021 World Health Organization (WHO) classification central nervous system. Due to the rarity, this meningioma variant origin and biological behavior are still not clear. Immunohistochemistry profile showed prominent PD-L1 expression, leading to additional interrogation on LPRM immunomorphological characteristics, the significance of the inflammatory tumoral microenvironment and its correlation with the immune-checkpoints