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Predictive biomarkers of response to immune checkpoint-based therapies (ICI) remain a critically unmet need in the management of advanced renal cell carcinoma (RCC). The complex interplay of the tumour microenvironment (TME) and the circulating immune response has proven to be challenging to decipher. MicroRNAs have gained increasing attention for their role in post-transcriptional gene expression regulation, particularly because they can have immunomodulatory properties. We evaluated the presence of immune-specific extracellular vesicle (EV) microRNAs in the plasma of patients with metastatic RCC (mRCC) prior to initiation of ICI. We found significantly lower levels of microRNA155-3p (miR155) in responders to ICI, when compared to non-responders. This microRNA has unique immunomodulatory properties, thus providing potential biological rationale for our findings. Our results support further work in exploring microRNAs as potential biomarkers of response to immunotherapy., (© 2024. The Author(s).)

Primary mediastinal germ cell tumors (PMGCTs) are a rare type of cancer affecting young adults. They have different molecular and clinical features compared to testicular germ cell tumors. Non-seminoma PMGCTs have the shortest 5-year overall survival and the poorest prognosis among all of the germ cell tumor presentations, while seminomas share the same survival and prognosis as their testicular counterparts. There is an unmet need for better treatment options for patients with non-seminoma PMGCTs in both first-line and salvage therapy, as the available options are associated with underwhelming outcomes. Identifying biological and genetic factors to predict treatment responses would be helpful in improving the survival of these patients.

Background and Objective: Germ cell tumors (GCTs) are uncommon malignancies generally originating from gonads. However, about 5% of GCTs arise outside the gonad (extragonadal), of which 80% develop from the mediastinum. While the prognosis of seminomas is not affected by the gonadal or extragonadal primary location, the prognosis of nonseminoma primary mediastinal GCTs (NS-PMGCTs) is poor, compared to its gonadal counterpart with an estimated 5-year overall survival of about 50%. The current treatments are sub-optimal to increase the cure rate of these rare GCTs. Therefore, molecular insights into these tumors would be valuable to develop novel therapies. The main objective of this review is to describe and dissect the genomic features associated with primary mediastinal GCTs (PMGCTs), highlighting the more frequent genomic alterations and their correlation with clinical outcomes., Methods: We conducted a narrative review of the English literature available in PubMed and Google Scholar between 1982 and 2021, including meta-analyses, systematic reviews, case series and case reports regarding the genomic and clinical features of PMGCTs. We analyzed the available data to describe the molecular characteristics of PMGCTs compared to testicular GCTs (TGCTs), highlighting the most relevant biological and prognostic factors., Key Content and Findings: The high percentage of platinum resistance, the unique association with hematologic malignancies (HMs) and other malignancies, the higher prevalence of P53 mutations, and a distinct genomic landscape characterize this rare disease., Conclusions: Although some studies have unveiled recurrent molecular alterations in PMGCTs, few are particularly suitable for targeted therapy. Due to the rarity of PMGCTs, data sharing and the creation of an international consortium would be helpful to have a better understanding of the molecular drivers of these tumors., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://med.amegroups.com/article/view/10.21037/med-22-4/coif). The series “New Treatments and Novel Insights of Thymic Epithelial Tumors and Mediastinal Germ Cell Tumors” was commissioned by the editorial office without any funding or sponsorship. The authors have no other conflicts of interest to declare., (2022 Mediastinum. All rights reserved.)

Background: Primary mediastinal nonseminoma germ cell tumors (PMNSGCT) are a subgroup of nonseminoma germ cell tumors (GCT) with poor prognosis. In this study, PMNSGCT-specific genomic landscape was analyzed and correlated with clinical outcomes., Methods: DNA was extracted and sequenced from 28 archival tumor tissue of patients with mediastinal GCT (3 seminoma and 25 nonseminoma). Overall survival (OS) and association with gene alterations were estimated using the Kaplan-Meier and univariate Cox regression methods., Results: Three patients (11%) had a karyotype XXY, 17/28 (61%) tumor samples presented chromosome 12p amplification. Somatic mutations were detected in 19/28 (68%) samples. The most frequently mutated genes were: TP53 (13/28; 46%), KIT (5/28; 18%), and KRAS (5/28; 18%). Deleterious TP53 alterations were associated with significantly reduced overall survival (HR: 7.16; P = .012)., Conclusions: TP53 alterations are common in PMNSGCT and are associated with reduced overall survival, potentially underlying the poor sensitivity to chemotherapy observed in these patients., (© The Author(s) 2022. Published by Oxford University Press.)

Introduction: Perivascular epithelioid celltumor (PEComa) is a rare mesenchymal neoplasia and can be found in various body sites. On the other hand, hepatic PEComa is very rare, with only a few studies having reported hepatic malignant PEComa. There is no gold standard regarding the use of diagnostic imaging studies. The diagnosis of hepatic PEComa is made by a positive immunohistochemical staining for HMB45 and Melan A. Herein, we discussed the therapeutic and follow-up process of a symptomatic hepatic PEComa case., Presentation of Case: A 22-year-old woman presented with a palpable mass in abdomen. A computerized tomographic examination showed a giant hepatic mass of left lobe origin, which was excised surgically. The pathology result was reported as a PEComa., Discussion: The diagnostic approach, treatment modalities, and follow-up procedures are not standard. The main treatment modality for PEComa is surgical excision with adequate surgical margin., Conclusion: A longer follow-up is required for patients with hepatic PEComa because the nature of the disease is not entirely clear., (Copyright © 2018 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Objectives: We aimed to investigate the effect of lipoic acid in the prevention of myocardial infarction in diabetic rats., Methods: Rats were divided into five groups as control, ISO, LA+ISO, STZ+ISO and STZ+LA+ISO. To induce diabetes, single dose of streptozotocin was injected to STZ+ISO and STZ+LA+ISO groups. Lipoic acid (10 mg/kg/day) was injected for 14 days to LA+ISO and STZ+LA+ISO groups. To induce myocardial infarction, isoproterenol was injected to ISO, LA+ISO, STZ+ISO and STZ+LA+ISO groups on the days 13 and 14 of lipoic acid treatment. Cardiac necrosis and leucocyte infiltration were investigated histopathologically. Serum malondialdehyde levels, paraoxonase and lactonase activities were measured spectrophotometrically., Results: Isoproterenol caused a significant increase in cardiac necrosis, leucocyte infiltration and serum lipid peroxidation whereas a significant decrease in serum paraoxonase and lactonase activities. In myocardial infarcted non-diabetic rats, while lipoic acid caused a significant decrease in cardiac necrosis, leucocyte infiltration and serum lipid peroxidation and a significant increase in serum paraoxonase and lactonase activities, it did not change these histopathologic or biochemical parameters in myocardial infarcted diabetic rats., Conclusion: Lipoic acid, at the dose of 10 mg/kg, is effective to prevent myocardial infarction in non-diabetic rats but it is insufficient in diabetic rats (Tab. 1, Fig. 2, Ref. 35).

Background: Elderly patients constitute the majority of patients undergoing treatment in the intensive care unit (ICU). Patients over the age of 65 account for 42%-52% of admission to ICU. Previous studies have shown that malnutrition is an important factor influencing the prognosis in intensive care., Objectives: In this study, the effect of body mass index (BMI) and albumin values at first admission to the ICU on the course and prognosis of geriatric patients were investigated., Patients and Methods: Patients over the age of 65 who were admitted to the anesthesia ICU were included in the study. Demographic and clinical data were recorded retrospectively. Major outcome variables were length of ICU and hospital stay, mortality rate, BMI, and albumin values. APACHE II and SOFA scores at admission were evaluated., Results: Overall, 113 patients were included in the study. Mean BMI (kg/m(2)) value was found to be lower in the died group than in the discharged and transferred groups (P < 0.001). Albumin levels were lower in the died group than in the discharged and transferred groups (P < 0.001). An inverse relation was found between Apache and BMI and albumin values, whereas a significant direct relation was found between Apache and mechanical ventilation day (P < 0.05). A significant negative correlation was found between SOFA and BMI and albumin, values, respectively, and a positive correlation was found between SOFA and mechanical ventilation duration (P < 0.005)., Conclusions: In this study, a low albumin level (≤ 3 mg/dL) was an indicator of nutritional status. Patients' albumin levels, BMI, nutritional status, APACHE II score, and SOFA score were associated with mortality. Age in itself did not predict mortality in the elderly.

Intracranial chondroma is a rare benign neoplasm that occurs most often at the skull base. In extremely rare instances, it arises from the dura mater of the convexity or from the falx cerebri. The tumor cells are thought to originate from meningeal fibroblasts, perivascular mesenchymal tissue, or ectopic chondrocytes. Because the clinical presentation of such cases is nonspecific and because neuroimaging findings are not pathognomonic, intracranial chondromas mimic other intracranial tumors. Herein, we report a chondroma originating from the dura mater in the frontal region. The patient had been followed-up radiologically for 3 years after a preliminary diagnosis of meningioma until the correct diagnosis of chondroma was established with postoperative histological examination.

Introduction: Local anesthesia with prilocaine has become a routine part of ambulatory circumcision procedures. Methemoglobinemia is a rare but potentially lethal complication of local anesthetics., Case Presentation: We report the case of a 40-day-old Turkish boy who presented with cyanosis after receiving local anesthesia with prilocaine. His methemoglobin level revealed severe methemoglobinemia (methemoglobin = 44%). His cyanosis resolved after intravenous administration of methylene blue., Conclusion: Although the association between prilocaine use and methemoglobinemia has generally restricted the use of prilocaine in babies, it is still widely used in ambulatory procedures, especially during circumcision in the neonatal period. Prilocaine should not be used in babies who are less than 3 months old because of the risk of methemoglobinemia; other local anesthetics may be used for this age group. Furthermore, general anesthesia by mask ventilation may be favored for babies less than 3 months of age instead of local anesthetics.