Left atrial appendage structural characteristics predict thrombus formation.

INTRODUCTION: Nonvalvular atrial fibrillation (NVAF) is a highly prevalent arrhythmia where loss of synchronized atrial contraction increases the risk of intracardiac thrombus particularly within the left atrial appendage (LAA). Anticoagulation is the mainstay of stroke prevention based on the CHA2 DS2 -VASc score; however, it does not account for LAA structural characteristics. METHODS: The research comprises a retrospective matched case-control study of 196 subjects with NVAF who underwent transesophageal echo (TEE). The control group, without thrombus (n = 117), was selected from two different groups, both pools had: NVAF and CHA2 DS2 -VASc score ≥ 3. One group underwent screening TEE before Watchman closure device placement from January 2015 to December 2019 (n = 74) the second underwent TEE before cardioversion from February to October 2014 (n = 43). The study group, with thrombus (n = 79), included patients with NVAF, TEE study performed between February 2014 and December 2020, and LAA thrombus. The propensity score method was utilized to determine the matched controls while accounting for confounding from prognostic variables resulting in 61 matched pairs included in the analysis data set. LAA ostial area (OA) (calculated from orthogonal measurements 0°, 90° or 45°, 135°), LAA maximal depth, and peak LAA outflow velocity were measured. RESULTS: Patient characteristics and TEE data were collected and compared using the t test or χ2 analysis. We observed a lower LAA peak exit velocity in the thrombus group as compared to the control group. Additionally, we found that patients in the thrombus group had smaller LAA OA at 0° and 90°, at 45° and 135°, using largest diameter, as well as using aggregate OA, and smaller maximum LAA depth compared to patients in the control group. Candidate conditional logistic regression models for the outcome of the presence of thrombus were evaluated. Statistical results from the best-fitting conditional regression model were calculated showing a significant association between aggregate OA and LAA exit velocity with presence of thrombus. CONCLUSION: Utilizing LAA structural characteristics to predict thrombus formation may help refine current cardioembolic stroke (CES) risk estimation.

A Convoluted Picture of Diabetic Myonecrosis.

INTRODUCTION: A patient with well-controlled type 2 diabetes was found to have diabetic myonecrosis, a rare condition associated with poorly controlled type 2 diabetes. Diagnosis was masked by concern for lumbosacral plexopathy from a history of spinal cord infarct. CASE PRESENTATION: A 49-year-old African American woman with type 2 diabetes and paraplegia secondary to spinal cord infarct presented to the emergency department with left leg swelling and weakness from her hip to toes. Hemoglobin A1c was 6.0%, and there was no leukocytosis or elevated inflammatory markers. Computed tomography showed evidence of infectious process or possible diabetic myonecrosis. DISCUSSION: Recent reviews show fewer than 200 reports of diabetic myonecrosis since first described in 1965. It typically is seen in poorly controlled types 1 and 2 diabetes, with average hemoglobin A1c of 9.34% at time of diagnosis. CONCLUSIONS: Diabetic myonecrosis should be considered in diabetic patients with unexplained swelling and pain - particularly in the thigh - even with unremarkable lab values.

Oncolytic vaccinia virus reinvigorates peritoneal immunity and cooperates with immune checkpoint inhibitor to suppress peritoneal carcinomatosis in colon cancer.

BACKGROUND: Peritoneal carcinomatosis (PC) is a common and devastating manifestation of colon cancer and refractory to conventional anticancer therapeutics. During the peritoneal dissemination of colon cancer, peritoneal immunity is nullified by various mechanisms of immune evasion. Here, we employed the armed oncolytic vaccinia virus mJX-594 (JX) to rejuvenate the peritoneal antitumor immune responses in the treatment of PC. METHODS: PC model of MC38 colon cancer was generated and intraperitoneally treated with JX and/or anti-programmed cell death protein 1 (PD-1) antibody. The peritoneal tumor burden, vascular leakage, and malignant ascites formation were then assessed. Tumors and peritoneal lavage cells were analyzed by flow cytometry, multiplex tissue imaging, and a NanoString assay. RESULTS: JX treatment effectively suppressed peritoneal cancer progression and malignant ascites formation. It also restored the peritoneal anticancer immunity by activating peritoneal dendritic cells (DCs) and CD8+ T cells. Moreover, JX selectively infected and killed peritoneal colon cancer cells and promoted the intratumoral infiltration of DCs and CD8+ T cells into peritoneal tumor nodules. JX reinvigorates anticancer immunity by reprogramming immune-related transcriptional signatures within the tumor microenvironment. Notably, JX cooperates with immune checkpoint inhibitors (ICIs), anti-programmed death-1, anti-programmed death-ligand 1, and anti-lymphocyte-activation gene-3 to elicit a stronger anticancer immunity that eliminates peritoneal metastases and malignant ascites of colon cancer compared with JX or ICI alone. CONCLUSIONS: Intraperitoneal immunotherapy with JX restores peritoneal anticancer immunity and potentiates immune checkpoint blockade to suppress PC and malignant ascites in colon cancer.

A Rare Complication of HVAD Outflow Thrombosis and the Importance of HVAD Waveform Analysis.

We present a case of a 64-year-old female who was supported with an HVAD as bridge-to-transplant (BTT) who presented with a gastrointestinal (GI) bleeding and underwent esophagogastroduodenoscopy (EGD) and colonoscopy. Her waveforms changed abruptly following the procedure, and she decompensated. With various imaging modalities and hemodynamic monitoring, we felt that she had thrombus in her outflow graft, which improved following systemic heparinization. She was listed for cardiac transplantation and remained hospitalized. At the time of surgery, her outflow graft was noted to be compressed externally and pathology was consistent with platelet-fibrin thrombus deposition.

Suspensions for intravenous (IV) injection: a review of development, preclinical and clinical aspects.

There has been growing interest in nanoparticles as an approach to formulate poorly soluble drugs. Besides enhanced dissolution rates, and thereby, improved bioavailability, nanoparticles can also provide targeting capabilities when injected intravenously. The latter property has led to increased research and development activities for intravenous suspensions. The first intravenously administered nanoparticulate product, Abraxane (a reformulation of paclitaxel), was approved by the FDA in 2006. Additional clinical trials have been conducted or are ongoing for multiple other indications such as oncology, infective diseases, and restenosis. This article reviews various challenges associated with developing intravenous nanosuspension dosage forms. In addition, various formulation considerations specific to intravenous nanosuspensions as well as reported findings from various clinical studies have been discussed.