Intracystic injection of large surface area microparticle paclitaxel for chemoablation of intraductal papillary mucinous neoplasms: Insights from an expanded access protocol.

AIMS: A novel large surface area microparticle paclitaxel (LSAM-PTX) has unique properties of long retention in cystic spaces while maintaining high drug concentration. We prospectively evaluated the safety and response of EUS-guided fine needle injection (EUS-FNI) of LSAM-PTX to chemoablate branch duct (BD)-IPMNs. METHODS: Subjects diagnosed with BD-IPMNs exhibiting at least one worrisome criteria and considered non-surgical were enrolled in a multicenter clinical trial (NCT03188991) and subsequently included in an Expanded Access Protocol (EAP) where they received EUS-FNI of LSAM-PTX (15 mg/mL). RESULTS: Six BD-IPMNs measuring (mean ± SD) 3.18 ± 0.76 cm in diameter among 5 subjects (mean age: 66 years) were treated by EUS-FNI of LSAM-PTX. A mean of 4 doses of LSAM-PTX (mean dose/cyst: 73 ± 31 mg) were administered, and subjects were followed for up to 32 months. The mean volume reduction/cyst ranged from 42 to 89% (9.58 ± 5.1 ml to 2.2 ± 1.1 ml (p = 0.016)). The mean surface area reduction ranged from 31 to 83% (21.9 ± 8.7 cm2 to 5.7 ± 2.5 cm2 (p = 0.009)). Higher dosing-frequency of EUS-FNI of LSAM-PTX significantly correlated with a reduction in cyst volume (R2 = 0.87, p = 0.03) and surface area (R2 = 0.83, p = 0.04). Comparing pre- and post-ablation samples, molecular analysis of the cyst fluid revealed a loss of IPMN-associated mutations in 5 cases (83.3%), while reemergence was observed in 1 case and persistence in 1 case. Intracystic changes (fibrosis/calcification) were observed in 83.3% (n = 5). One subject developed mild acute pancreatitis (1 of 22 EUS-FNIs of LSAM-PTX). CONCLUSION: In this EAP, EUS-FNI of LSAM-PTX into BD-IPMNs was safe and resulted in volume and surface area reduction, morphological changes, and loss of pathogenic mutations.

Advancements in Microwave Ablation Techniques for Managing Pancreatic Lesions.

Thermal ablation, including microwave ablation, has become increasingly important in the management of many solid tumors, including primary and metastatic tumors of the liver, kidney, and lung. However, its adoption to treat pancreatic lesions has been slowed due to concerns about potential adverse events. The success of radiofrequency ablation (RFA) in inoperable pancreatic cancers paved the way for its use in pancreatic neuroendocrine tumors and pancreatic cystic neoplasms (PCLs). In the last decade, other thermal ablation techniques, like microwave ablation, have emerged as alternatives to RFA. Microwaves, with frequencies ranging from 900 to 2450 MHz, generate heat by rapidly oscillating water molecules. Microwave ablation's advantage lies in its ability to achieve higher intra-lesion temperatures and uniform heating compared with RFA. Microwave ablation's application in pancreatic cancer and pancreatic neuroendocrine tumors has demonstrated promise with similar technical success to RFA. Yet, concern for peri-procedure complications, as well as a dearth of studies comparing RFA and microwave ablation, emphasize the need for further research. No studies have evaluated microwave ablation in PCLs. We herein review thermal ablation's potential to treat pancreatic lesions.

Update on endoscopic ultrasound-guided liver biopsy.

Endoscopic ultrasound guided liver biopsy (EUS-LB) has emerged as a minimally-invasive alternative to the traditional (percutaneous or transjugular) liver biopsy techniques for the diagnosis of liver parenchymal diseases. Po-tentially, EUS-LB combines the advantages of percutaneous and transjugular liver biopsy in addressing focused sampling in addition to measuring portal pressure. Additionally, EUS-LB facilitates access to both the lobes of the liver which is not considered with the traditional percutaneous liver biopsy. Multiple studies have compared EUS-LB with conventional liver biopsy and reported comparable diagnostic yield, increased acquisition of complete portal tracts, and longer specimen length as compared to the traditional approaches. EUS-LB is associated with lesser post-procedural pain and shorter recovery time, while providing lower risk of complications when compared to traditional liver biopsy. Innovations in needle types, needle sizes and suction techniques have aimed at further optimizing the EUS-LB technique. This review article updates current literature with focus on the variations in the technique and equipment used for EUS-LB, and compares EUS-LB with traditional methods of liver biopsy.

Intraductal Papillary Mucinous Neoplasms in Hereditary Cancer Syndromes.

Hereditary pancreatic cancer, which includes patients with familial pancreatic cancer (FPC) and hereditary pancreatic cancer syndromes, accounts for about 10% of all pancreatic cancer diagnoses. The early detection of pre-cancerous pancreatic cysts has increasingly become a focus of interest in recent years as a potential avenue to lower pancreatic cancer incidence and mortality. Intraductal papillary mucinous cystic neoplasms (IPMNs) are recognized precursor lesions of pancreatic cancer. IPMNs have high prevalence in patients with hereditary pancreatic cancer and their relatives. While various somatic mutations have been identified in IPMNs, certain germline mutations associated with hereditary cancer syndromes have also been identified in IPMNs, suggesting a role in their formation. While the significance for the higher prevalence of IPMNs or similar germline mutations in these high-risk patients remain unclear, IPMNs do represent pre-malignant lesions that need close surveillance. This review summarizes the available literature on the incidence and prevalence of IPMNs in inherited genetic predisposition syndromes and FPC and speculates if IPMN and pancreatic cancer surveillance in these high-risk individuals needs to change.

Application of Artificial Intelligence in the Management of Pancreatic Cystic Lesions.

The rate of incidentally detected pancreatic cystic lesions (PCLs) has increased over the past decade and was recently reported at 8%. These lesions pose a unique challenge, as each subtype of PCL carries a different risk of malignant transformation, ranging from 0% (pancreatic pseudocyst) to 34-68% (main duct intraductal papillary mucinous neoplasm). It is imperative to correctly risk-stratify the malignant potential of these lesions in order to provide the correct care course for the patient, ranging from monitoring to surgical intervention. Even with the multiplicity of guidelines (i.e., the American Gastroenterology Association guidelines and Fukuoka/International Consensus guidelines) and multitude of diagnostic information, risk stratification of PCLs falls short. Studies have reported that 25-64% of patients undergoing PCL resection have pancreatic cysts with no malignant potential, and up to 78% of mucin-producing cysts resected harbor no malignant potential on pathological evaluation. Clinicians are now incorporating artificial intelligence technology to aid in the management of these difficult lesions. This review article focuses on advancements in artificial intelligence within digital pathomics, radiomics, and genomics as they apply to the diagnosis and risk stratification of PCLs.

Recent advances in the diagnostic evaluation of pancreatic cystic lesions.

Pancreatic cystic lesions (PCLs) are becoming more prevalent due to more frequent abdominal imaging and the increasing age of the general population. It has become crucial to identify these PCLs and subsequently risk stratify them to guide management. Given the high morbidity associated with pancreatic surgery, only those PCLs at high risk for malignancy should undergo such treatment. However, current diagnostic testing is suboptimal at accurately diagnosing and risk stratifying PCLs. Therefore, research has focused on developing new techniques for differentiating mucinous from non-mucinous PCLs and identifying high risk lesions for malignancy. Cross sectional imaging radiomics can potentially improve the predictive accuracy of primary risk stratification of PCLs at the time of detection to guide invasive testing. While cyst fluid glucose has reemerged as a potential biomarker, cyst fluid molecular markers have improved accuracy for identifying specific types of PCLs. Endoscopic ultrasound guided approaches such as confocal laser endomicroscopy and through the needle microforceps biopsy have shown a good correlation with histopathological findings and are evolving techniques for identifying and risk stratifying PCLs. While most of these recent diagnostics are only practiced at selective tertiary care centers, they hold a promise that management of PCLs will only get better in the future.

An update on EUS-guided ablative techniques for pancreatic cystic lesions.

Pancreatic cystic lesions (PCLs) are increasingly being recognized due to improvements and widespread use of cross-sectional imaging. With an estimated prevalence of 15% in general population, incidentally discovered PCLs represent a dilemma in management. While pancreatectomies offer a chance of cure, the morbidity is considerable in patients with high surgical risks. More recently, EUS-guided approaches for cyst ablation are being offered in clinical trials for the management of PCLs. EUS-chemoablation studies have progressed from first investigating safety and efficacy of EUS-guided alcohol lavage to single-agent paclitaxel ablation. Recent studies have shown that alcohol lavage may not be required, and long-term resolution can be achieved by chemoablation alone. EUS-guided lauromacrogol ablation and EUS-guided radiofrequency ablation (RFA) are new techniques that have shown promising results in a few small studies. Overall, the current literature suggests that EUS-guided paclitaxel ablation has better cyst resolution rates compared to other existing minimally invasive techniques including ethanol injection, lauromacrogol ablation, or RFA. This article will review EUS-guided PCL ablation approaches and future directions the field is headed into.

Chest X-Ray to Predict Difficult Right Transradial Cardiac Catheterization Due to Vascular Tortuosity: A Retrospective Study.

Tortuous brachiocephalic artery may lead to procedural difficulties among patients undergoing right transradial cardiac catheterization. By prospectively identifying patients with this anatomic barrier, operators may choose an alternate catheterization site to avoid complications from switching midway. To assess brachiocephalic artery tortuosity, 23 patients who underwent challenging diagnostic coronary angiography by right transradial access were compared to a control group of 29 patients who lacked brachiocephalic artery tortuosity. Preprocedural, plain chest x-rays were analyzed for measurable anatomic parameters and assessed for statistical significance between groups. The vertebrocarinal distance-the distance in centimeters between the spinous process of the first thoracic vertebra (T1) and the most caudal point of tracheal bifurcation, measured at and parallel to the midline-was the most reliable and statistically significant radiographic predictor of brachiocephalic artery tortuosity. Using this novel concept reduces procedure duration and radiation exposure by decreasing transradial cardiac catheterization failure rates.

The dilemma of aspirin resistance in obese patients.

Aspirin resistance (AR) commonly refers to the concept of reduced aspirin efficacy in preventing cardiovascular disease and platelet inhibition. Obesity increases the risk of heart disease three- to four-fold and has been associated with AR. Aspirin is used as a tool for both primary and secondary prevention, but recent studies suggest that its lack of efficacy for primary prevention is partly attributable to obesity. Several mechanisms have been described that contribute to AR in obese patients using pharmacokinetics and pharmacodynamics. AR may be attenuated through weight loss, alternative dosing regimens, and different drug formulations. With the global rise of obesity, it is imperative to find preventive therapies that adequately address atherosclerotic cardiovascular disease (ASCVD) risk in this population.

From WOEST to AUGUSTUS: a review of safety and efficacy of triple versus dual antithrombotic regimens in patients with atrial fibrillation requiring percutaneous coronary intervention for acute coronary syndrome.

For patients with atrial fibrillation with concomitant acute coronary syndrome (ACS) requiring percutaneous coronary intervention (PCI), the increased risk of bleeding associated with the use triple therapy is well established. However, there is question whether it is a necessary risk for patients to prevent stroke and stent thrombosis. The purpose of this article is to highlight the findings of prior studies evaluating the comparative safety and efficacy of dual and triple antithrombotic regimens in the subgroup of atrial fibrillation patients requiring PCI for ACS. Trials that evaluated dual versus triple antithrombotic therapy demonstrated post-PCI treatment with a P2Y12 inhibitor alone was safer than aspirin plus a P2Y12 inhibitor in patients also taking an anticoagulant for atrial fibrillation. Data regarding ischemic outcomes have not suggested harm with the omission of aspirin, but these studies have not been powered to assess efficacy outcomes, especially in ACS patients. These studies also demonstrate a significant reduction in bleeding events when aspirin is excluded from the post-PCI regimen in the ACS subgroup of atrial fibrillation patients. Further studies, with added focus on the ACS subgroup, are needed to potentially confirm that dual therapy may be as efficacious as triple therapy in ACS patients with atrial fibrillation.

Intravenous cangrelor as a peri-procedural bridge with applied uses in ischemic events.

Cangrelor is a relatively new antiplatelet drug that has been approved for use as an adjunct therapy to percutaneous coronary intervention (PCI) to decrease peri-procedural myocardial infarction (MI), coronary revascularization, and stent thrombosis. Cangrelor is an adenosine triphosphate analogue with a pharmacokinetic mechanism based on a reversible, dose-dependent inhibition adenosine diphosphate (ADP)-induced platelet aggregation. This drug has lately been in the spotlight as a possible bridge therapy for anti-platelet medication prior to cardiac and non-cardiac surgeries. Platelet function is usually restored within sixty minutes of cessation of therapy, thereby decreasing the risk of bleeding while providing adequate pre-procedural coverage to reduce ischemic events. This manuscript reviews the literature on cangrelor and summarizes its role as a peri-procedural bridge.

Targeting ticagrelor: a novel therapy for emergency reversal.

Newer P2Y12 inhibitors are prescribed in place of clopidogrel for patients with acute coronary syndrome (ACS) and are associated with significant bleeding risks. Currently, limited options exist for the management of life-threatening bleeding or acute reversal for patients on P2Y12 inhibitor therapy, specifically ticagrelor. Various interventions, including platelet transfusion and desmopressin, have been studied for ticagrelor reversal demonstrating limited success. PB2452 is a novel monoclonal antibody which binds to both ticagrelor and its active metabolite resulting in a rapid return of platelet aggregation. PB2452 has been studied in animal models and, most recently, in a Phase I trial in healthy volunteers. In animal models, PB2452 displayed rapid reversal of ticagrelor and its metabolites and return to near normal levels of platelet aggregation within 60 min. In healthy human volunteers, cohorts that received higher dose bolus and infusions of PB2452 over 12-16 h resulted in maximal and sustained reversal of ticagrelor inhibition of platelet aggregation. While it is currently not US Food and Drug Administration approved, future Phase 2 and 3 studies are currently underway that may lead to new directions for patients on ticagrelor therapy who require urgent reversal.

Current status of oral anticoagulant reversal strategies: a review.

Utilization of direct oral anticoagulants (DOAC) have steadily increased since their approval and are now recommended over warfarin for both stroke prevention in nonvalvular atrial fibrillation and treatment of venous thromboembolism (VTE). With increased DOAC use, the number of major bleeding events requiring medical intervention will continue to rise. Until 2015, warfarin maintained an advantage as the only oral anticoagulant with a specific reversal agent. Since then, idarucizumab has been approved for dabigatran reversal and recently, andexanet alfa was granted approval for the reversal of apixaban or rivaroxaban in patients with life-threatening or uncontrolled bleeding events. Due to the manufacturing practices required to yield these reversal therapies, they are available at high cost to hospital systems and as a result, have been met with resistance. Data exists describing both prothrombin complex concentrates (PCC) and andexanet alfa for DOAC reversal, however, without head-to-head comparison. Until future studies are available, current literature must be critically evaluated to aid in the clinical decision-making process of how to treat patients with life-threatening DOAC-related bleeding.

After COACT trial-new perspectives for the management of non-ST elevation myocardial infarction: early versus late cardiac catheterization post cardiac arrest.

Out-of-hospital cardiac arrest (OHCA) is the leading cause of death in the United States, as 90% of them are fatal per the 2018 American Heart Association statistics. As many as fifty-percent of cardiac arrest events display an initial rhythm of pulseless ventricular tachycardia (pVT) and ventricular fibrillation (VF), and of those, coronary artery disease (CAD) is found in 60-80% of patients. Following return of spontaneous circulation, patients who present with ST-elevation myocardial infarction (STEMI) should undergo an early invasive strategy and primary intervention, which is well-established guideline-based management. The support of such a strategy in patients suspected to have underlying cardiac cause but without ST-elevation has been waxing and waning in the literature. The Coronary Angiography after Cardiac Arrest (COACT) trial was designed to compare survival between an immediate or delayed coronary angiography strategy in non-STEMI (NSTEMI) OHCA patients, following successful resuscitation. We present a systematic review of the history of management strategies in OHCA and propose guidelines to manage such patients in light of the COACT trial.

Is there an optimal "door to cath time" in the treatment of acute pulmonary embolism with catheter-directed thrombolysis?

Ultrasound assisted catheter-directed thrombolysis (UACT) is a relatively novel approach to treating acute pulmonary embolism (PE). It is an alternative to systemic thrombolysis with good success rates and low reported in-hospital mortality, and low rates of procedure-related major and minor bleeding. Since UACT received FDA approval for the treatment of PE in 2014, there is paucity of data regarding the optimal timing of initiation of the procedure after the initial diagnosis is made. We reviewed the available literature regarding UACT for acute PE and found six studies that included time to procedure. Based on our review, patients may benefit from early (<24-48 h after presentation) rather than delayed (>48 h) initiation. Early initiation of therapy has shown to improve pulmonary arterial pressures, right ventricular (RV) to left ventricular (LV) ratios, with low rates of bleeding and low post procedural and in hospital mortality. However, further studies are required to confirm these findings and establish the appropriate timeline for initiation of UACT.

Right ventricular metastasis from unclassified Renal Cell Carcinoma.

BACKGROUND: Cardiac metastasis of unclassified renal cell carcinoma (RCC) subtype is very rare, and even more so is an isolated right ventricular (RV) metastasis without vena cava extension or right atrial involvement. To the best of our knowledge, this is the first report of a cardiac metastasis of an unclassified RCC (an aggressive RCC) without vena cava extension. CASE PRESENTATION: A 61-year-old African American male with past medical history of hypertension and schizophrenia presented to the emergency room following 2 episodes of syncope and 3-month history of progressive neck mass. CT scan of neck, abdomen and pelvis showed bulky left cervical, supraclavicular and axillary lymph node, mass in anterior aspect of heart, and multiple solid left renal masses and probable right renal mass. Echocardiogram revealed a large RV mass with deformation of the RV free wall suggesting malignant growth. Core biopsy of the right superficial gluteal mass revealed a metastatic poorly differentiated carcinoma of likely renal origin, with a possibility of an unclassified RCC. Due to the extent and burden of metastasis, patient and family members agreed to conservative management and evaluation for hospice care. CONCLUSION: Cardiac metastasis of unclassified RCC is rare, and even more so is an isolated RV metastasis without vena cava extension or right atrial involvement, and the present case, to the best of knowledge is the first of such rare presentation.

From Tick Bite to Heart Failure: Ehrlichial Myocarditis.

Cardiac involvement in myocarditis induced by Human Monocytic Ehrlichiosis infection is an incredibly uncommon complication with sparsely available literature. Also, this case highlights the importance of early recognition as a first step in management.

Une atteinte cardiaque secondaire à une myocardite induite par une ehrlichiose monocytaire humaine constitue une complication extrêmement rare et très peu documentée. Le cas présenté fait ressortir l'importance d'une reconnaissance rapide du problème comme première étape de la prise en charge.

A review of racial disparities in transcatheter aortic valve replacement (TAVR): accessibility, referrals and implantation.

Racial disparities in transcatheter aortic valve replacement (TAVR) implantation results from several factors, including socioeconomic disparities, inherent biases in healthcare provision, fewer referrals to specialists and language barriers in some minority populations. In this review article, we discuss the current data on the racial disparities in TAVR, explore the prevalence of aortic stenosis in different demographics in the United States and we proffer practical solutions to these problems.