Adiposity and Coagulation: Predicting Postinjury Coagulation With Advanced Imaging Analysis.

INTRODUCTION: Anatomic distribution of adipose tissue has demonstrated variable associations with hypercoagulability. Utilizing a retrospective analysis of a previously enrolled prospective cohort, we assessed computed tomography (CT) scan-based anthropometric and volumetric measures of adiposity as predictors of postinjury hypercoagulability. METHODS: Segmentation analysis of arrival CT scans in significantly injured patients at a single level-I trauma center enrolled from December 2017 to August 2021 were analyzed for anthropometric indices of waist circumference (WC) and sagittal abdominal diameter (SAD), and volumetric parameters of visceral adipose tissue, superficial/deep subcutaneous adipose tissue, psoas/paravertebral muscle volume, and abdominal wall muscle volume. Associations with thromboelastography (TEG) were explored. RESULTS: Data from 91 patients showed strong correlations between body mass index and standard anthropometric measures of WC and SAD (P < 0.001); calculated volumes of subcutaneous adipose tissue and visceral adipose tissue (P < 0.001); and ratios of subcutaneous adipose:psoas muscle (SP ratio) and visceral adipose:psoas muscle ratio (both with P < 0.001, respectively). Correlation between TEG maximal amplitude (MA) and body mass index and SAD were not significant, with only weak correlation between TEG-MA and WC (r = 0.238, P = 0.041). Moderate but significant correlations existed between SP ratio and TEG-MA (r = 0.340, P = 0.005), but not visceral adipose:psoas muscle ratio (r = 0.159, P = 0.198). The relationship between TEG-MA and SP ratio remained significant when adjusted for injury severity score and lactate level (b = 0.302, P = 0.001). CONCLUSIONS: SP ratio is more strongly correlated with TEG-MA than standard obesity measures, and independently predicts increasing clot strength/stability after injury. Coagulation-relevant measures of sarcopenic obesity can be measured on CT scan, and may be used to optimize thromboprophylaxis strategies for obese injured patients.

Enhancing Targeted Therapy in Breast Cancer by Ultrasound-Responsive Nanocarriers.

Currently, the response to cancer treatments is highly variable, and severe side effects and toxicity are experienced by patients receiving high doses of chemotherapy, such as those diagnosed with triple-negative breast cancer. The main goal of researchers and clinicians is to develop new effective treatments that will be able to specifically target and kill tumor cells by employing the minimum doses of drugs exerting a therapeutic effect. Despite the development of new formulations that overall can increase the drugs' pharmacokinetics, and that are specifically designed to bind overexpressed molecules on cancer cells and achieve active targeting of the tumor, the desired clinical outcome has not been reached yet. In this review, we will discuss the current classification and standard of care for breast cancer, the application of nanomedicine, and ultrasound-responsive biocompatible carriers (micro/nanobubbles, liposomes, micelles, polymeric nanoparticles, and nanodroplets/nanoemulsions) employed in preclinical studies to target and enhance the delivery of drugs and genes to breast cancer.

Virus-Based Immuno-Oncology Models.

Immunotherapy has been extensively explored in recent years with encouraging results in selected types of cancer. Such success aroused interest in the expansion of such indications, requiring a deep understanding of the complex role of the immune system in carcinogenesis. The definition of hot vs. cold tumors and the role of the tumor microenvironment enlightened the once obscure understanding of low response rates of solid tumors to immune check point inhibitors. Although the major scope found in the literature focuses on the T cell modulation, the innate immune system is also a promising oncolytic tool. The unveiling of the tumor immunosuppressive pathways, lead to the development of combined targeted therapies in an attempt to increase immune infiltration capability. Oncolytic viruses have been explored in different scenarios, in combination with various chemotherapeutic drugs and, more recently, with immune check point inhibitors. Moreover, oncolytic viruses may be engineered to express tumor specific pro-inflammatory cytokines, antibodies, and antigens to enhance immunologic response or block immunosuppressive mechanisms. Development of preclinical models capable to replicate the human immunologic response is one of the major challenges faced by these studies. A thorough understanding of immunotherapy and oncolytic viruses' mechanics is paramount to develop reliable preclinical models with higher chances of successful clinical therapy application. Thus, in this article, we review current concepts in cancer immunotherapy including the inherent and synthetic mechanisms of immunologic enhancement utilizing oncolytic viruses, immune targeting, and available preclinical animal models, their advantages, and limitations.

Applications of Ultrasound-Mediated Drug Delivery and Gene Therapy.

Gene therapy has continuously evolved throughout the years since its first proposal to develop more specific and effective transfection, capable of treating a myriad of health conditions. Viral vectors are some of the most common and most efficient vehicles for gene transfer. However, the safe and effective delivery of gene therapy remains a major obstacle. Ultrasound contrast agents in the form of microbubbles have provided a unique solution to fulfill the need to shield the vectors from the host immune system and the need for site specific targeted therapy. Since the discovery of the biophysical and biological effects of microbubble sonification, multiple developments have been made to enhance its applicability in targeted drug delivery. The concurrent development of viral vectors and recent research on dual vector strategies have shown promising results. This review will explore the mechanisms and recent advancements in the knowledge of ultrasound-mediated microbubbles in targeting gene and drug therapy.

Multifocal IgG4-related aortitis and periaortitis simulating aortic dissection.

Immunoglobulin G4-related aortitis (IgG4-RA) is histologically characterized by the infiltration of IgG4 positive plasma cells and fibrosis in systemic organs and the elevation of serum IgG4 levels. The cardiovascular system is commonly involved with various possible presentations such as aortitis, arteritis, periaortitis, periarteritis, and inflammatory aneurysm. We present a case of a 48-year-old male without known previous medical history, admitted for further workup of long-standing chest pain and shortness of breath with suspected aortic dissection on initial assessment. Investigation with computed tomography angiography (CTA) and magnetic resonance angiography (MRA) indicated severe thoracic and abdominal aortoarteritis associated with an ascending thoracic aortic aneurysm, which was confirmed to be IgG4-RA on histopathologic analysis. Thoracic and abdominal IgG4-RA clinical and radiological presentation may simulate other causes of acute aortic syndrome such as aortic dissection, atherosclerotic aneurysm and inflammatory conditions. Accurate recognition of IgG4-RA diagnostic imaging features are essential for early diagnosis and treatment surveillance.

Left ventricular pseudoaneurysm: An unexpected finding.

A left ventricle pseudoaneurysm (LV PSA) is defined as a free wall rupture of the left ventricle contained by the adjacent pericardial tissue. This rare complication is most commonly encountered following myocardial infarction, trauma, or infection. Surgery is typically warranted to avoid progression to spontaneous rupture, which may potentially lead to cardiac tamponade and death. Cardiac magnetic resonance imaging is the modality of choice to characterize left ventricle morphology and function. Accurate distinction between a pseudoaneurysm and a true aneurysm is crucial, since management and prognosis are significantly different between these 2 entities. We present a case of a 63-year-old male heart transplant recipient, admitted for suspicion of acute cellular rejection, with an unexpected finding of a LV PSA.

Complex Case of Aggressive Intra-abdominal Desmoid-type Fibromatosis Status Post Cholecystectomy.

Desmoid-type fibromatosis (DF), also known as desmoid tumor, is an extremely rare, benign, mesenchymal fibrous tumor with no potential for metastasis. It can arise from any part of the body, most commonly extra-abdominally. Intra-abdominal DF can present sporadically, in sites of previous trauma, surgical scars and irradiation, or in association with familial adenomatous polyposis and Gardner syndrome. Intra-abdominal DF is uncommon and especially rare after a common surgery like cholecystectomy. We report a rare case of a 67-year-old male who presented with a locally aggressive intra-abdominal DF in the gallbladder fossa, status post cholecystectomy. This progressively enlarging infiltrative enhancing solid mass in the gallbladder fossa on serial computed tomography and magnetic resonance imaging demonstrated gastric outlet obstruction, biliary obstruction, portal vein narrowing and encasement of hepatic artery. Diagnosis of DF in this postoperative setting was delayed and challenging due to uncharacteristic clinical presentation. Radiologists should be aware of this unusual diagnosis and spectrum of imaging findings to help in timely surgical management and planning.

Multimodality Thoracoabdominal Imaging Findings in a Rare Case of Thoracic Endometriosis Syndrome.

Thoracic endometriosis syndrome (TES) is an extremely rare disorder, and it is defined as the presence of functional endometrial tissue in pleura, airways, and lung parenchyma. We describe a rare case of a 29-year-old nulliparous female who presented with abdominal pain, dyspareunia, and shortness of breath. She complained of worsening of symptoms around the menstrual cycle. Initial workup showed markedly elevated CA-125 levels. A chest radiograph and CT of the chest, abdomen, and pelvis demonstrated large tension hydrothorax, ascites, and bilateral ovarian cysts. A chest tube was placed to decompress the tension hydrothorax, which drained copious amounts of blood. In view of the unexplained etiology of large hemothorax and elevated CA-125 levels, an MRI of the abdomen and pelvis was performed. This revealed advanced pelvic endometriosis, a right pleural nodule, and ipsilateral hydropneumothorax. Based on these findings, a diagnosis of TES was presumed. The patient was then referred to video-assisted thoracoscopy (VATS) and continuous estrogen suppression for optimal treatment. On early follow-up, she presented with recurrent hydropneumothorax, which was successfully managed with CT-guided chest tube placement and remained stable on further follow-ups. TES diagnosis is often challenging and delayed, demanding a high index of suspicion in patients with risk factors and characteristic clinical presentation. Radiologists should be aware of key imaging findings to help in early diagnosis for timely clinical and surgical management.