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Obesity is well-appreciated to result in poor cardiovascular and metabolic outcomes. Dietary and medical weight loss strategies are frequently unsuccessful and unsustainable. Bariatric surgery is quite effective, but is reserved for the most obese patients because of the associated intraoperative/post-operative risks. In preclinical and early clinical case series, a novel therapy, transcatheter bariatric embolotherapy (TBE) of the left gastric artery, has been reported to promote weight loss by reducing ghrelin, an appetite-stimulating hormone secreted from the gastric fundus.The purpose of this study was to examine TBE in a single-blind, sham procedure randomized trial.Obese subjects (body mass index 35 to 55 kg/mEligible subjects (n = 44; age 45.5 ± 9.4 years; 8 men/36 women; body mass index 39.6 ± 3.8 kg/mIn this randomized pilot trial, we have established the proof-of-principle that transcatheter bariatric embolotherapy of the left gastric artery is well-tolerated and promotes clinically significant weight loss over a sham procedure.(The Lowering Weight in Severe Obesity by Embolization of the Gastric Artery Trial [LOSEIT]; NCT03185949).

Transcatheter therapies to treat tricuspid regurgitation are being developed, but few have attempted the gold standard of surgical repair: ring annuloplasty. We describe the first-ever fully percutaneous implantation of a circumferential, semirigid annuloplasty ring to treat massive secondary tricuspid regurgitation. (Level of Difficulty: Advanced.), Central Illustration

Introduction: Obesity is an important risk factor associated with poor cardiovascular outcomes. Lifestyle modification, pharmaceutical, and intragastric balloons weight loss therapy are often unsuccessful, unsustainable, or accompanied by risks. Transcatheter bariatric embolotherapy (TBE) is a promising therapy in which the left gastric artery is embolized to reduce the expression of “hunger” hormones from the gastric fundus. Despite several early clinical trials, long-term safety or efficacy has yet to be studied. We originally studied TBE in a double-blind, sham procedure, first in human RCT of 40 obese patients (pts) (NCT03185949). Complete details regarding the initial RCT were previously published, briefly the study demonstrated up to 9.3% TBWL at 1-year post-TBE. Following completion of the initial study at 1 year follow-up, we asked subjects to return for long-term evaluation. Methods: Subjects who previously completed the RCT with no major protocol deviations were asked to return for SOC follow-up visits at 2-, 2.5-, and 3-years post-embolization for further evaluation on weight loss, blood pressure, pre-diabetic clinical status, satiety, and Quality of Life (QoL). Given the evolving situation of the COVID-19 pandemic, the study site was unable to complete all planned study visits. Results: Between 2-3 years post-TBE subjects (n=11) demonstrated a mean 9% TBWL and 25% EBWL. This cohort of patients demonstrated a long-term weight loss maintenance, with previously reported weight loss of 8% TBWL at 1-year post-embolization. Overall QoL at 2 years post-TBE increased by approximately 22%. The volume to achieve satiety was reduced by 33% in long-term follow-up. Oral Disposition Index increased from 1.89 mM -1 at 6 months post-TBE to 4.41 mM -1 2 years post-TBE. 1-hr Oral Glucose Tolerance Test (OGTT) C-Peptide levels decreased from 3.22 nmol/L at 6 months to 2.53 nmol/L at 2 years post-TBE. 2-hr OGTT C-Peptide levels also showed a decrease from 2.95 nmol/L at 6 months to 1.78 nmol/L at 2 years post-TBE, possibly indicating an improvement in pre-diabetic status. Conclusions: Bariatric embolization is safe and when used along with lifestyle therapy, results in clinically significant and sustained weight loss up to 2-3 years post-TBE.

Introduction: Acute respiratory distress syndrome (ARDS) is one of the main causes of mortality in patients with COVID-19. Despite numerous studies, therapies for ARDS in COVID-19 remain significantly limited. Currently, there have been reports of the efficient use of mesenchymal stem cell (MSC) for the treatment of ARDS. Several studies have reported that MSC produces anti-inflammatory cytokines, promotes the maturation of dendritic cells, and modulates NK cells. The safety of MSC therapy has been demonstrated in early-stage clinical studies with a relatively small number of patients. We investigated the influence of freeze-dried human placental mesenchymal stem cells (HPMSC) in a preclinical rodent model of ARDS. Methods: Sixty rats were randomly divided into three groups of 20: the first group was the control, the second group received dexamethasone, and the third group received HPMSC. Results: Survival was highest in the HPMSC group (75%, 95%CI: 50, 88) when compared to the control group. In a cox regression model, mortality of HPMSC group (HR: 11.30 [95% CI: 4.05, 31.50]) when compared to control was statistically significant (p < 0.001). Mortality in the dexamethasone (HR: 64.25 [95% CI: 32.71, 126.19]) was not statistically significant (p = 0.199). Plasma serum TNF-α levels were statistically significant in the HMPSC group when compared to the control (p < 0.001) and dexamethasone group (p < 0.001). Single factor ANOVA comparing TNF-α levels between all groups was also significant (p < 0.0001). Trends (Table 1) indicated that plasma serum cytokine levels for TNF-α, IL-1β, and Il-6 were less in the HPMSC group than the control and dexamethasone groups. Conclusions: These experiments demonstrated that HPMSC significantly decreased mortality, endogenous intoxication, and a reduction in the release of pro-inflammatory cytokines. The freeze-dried placental stem cell is a promising biomaterial that can be used nebulized for the treatment of coronavirus disease.

Obesity is a pandemic. The prevalence of obesity (BMI >30) and morbid obesity (BMI >40) among American adults is approximately 30% and 5%, respectively.1 The condition is strongly associated with medical comorbidities (e.g., heart disease, Type 2 diabetes mellitus, stroke, obstructive sleep apnoea, certain types of cancer, and osteoarthritis) and mortality, and has begun to overtake infectious diseases as the most significant contributor to illness worldwide. Furthermore, it is a leading preventable cause of death worldwide, with increasing prevalence in adults and children, and considered one of the most serious public health problems of the 21st century.2 Currently, there are three clinically viable treatment options for obesity: surgery, pharmacologic intervention, and intragastric balloon administration. However, these methods have varying success rates and are not free of complications. There remains a critical need for a minimally invasive intervention that can target this growing population.

COVID-19 has proven to be particularly challenging given the complex pathogenesis of SARS-CoV-2. Early data have demonstrated how the host response to this novel coronavirus leads to the proliferation of pro-inflammatory cytokines, massive endothelial damage, and generalized vascular manifestations. While SARS-CoV-2 primarily targets the upper and lower respiratory tract, other organ systems are also affected. SARS-CoV-2 relies on 2 host cell receptors for successful attachment: angiotensin-converting enzyme 2 and transmembrane protease serine 2. Clinicopathologic reports have demonstrated associations between severe COVID-19 and viral coagulopathy, resulting in pulmonary embolism; venous, arterial, and microvascular thrombosis; lung endothelial injury; and associated thrombotic complications leading to acute respiratory distress syndrome. Viral coagulopathy is not novel given similar observations with SARS classic, including the consumption of platelets, generation of thrombin, and increased fibrin degradation product exhibiting overt disseminated intravascular coagulation–like syndrome. The specific mechanism(s) behind the thrombotic complications in COVID-19 patients has yet to be fully understood. Parenteral anticoagulants, such as heparin and low-molecular-weights heparins, are widely used in the management of COVID-19 patients. Beyond the primary (anticoagulant) effects of these agents, they may exhibit antiviral, anti-inflammatory, and cytoprotective effects. Direct oral anticoagulants and antiplatelet agents are also useful in the management of these patients. Tissue plasminogen activator and other fibrinolytic modalities may also be helpful in the overall management. Catheter-directed thrombolysis can be used in patients developing pulmonary embolism. Further investigations are required to understand the molecular and cellular mechanisms involved in the pathogenesis of COVID-19-associated thrombotic complications.

BackgroundInfectious disease forecasting aims to predict characteristics of both seasonal epidemics and future pandemics. Accurate and timely infectious disease forecasts could aid public health responses by informing key preparation and mitigation efforts.Main bodyFor forecasts to be fully integrated into public health decision-making, federal, state, and local officials must understand how forecasts were made, how to interpret forecasts, and how well the forecasts have performed in the past. Since the 2013–14 influenza season, the Influenza Division at the Centers for Disease Control and Prevention (CDC) has hosted collaborative challenges to forecast the timing, intensity, and short-term trajectory of influenza-like illness in the United States. Additional efforts to advance forecasting science have included influenza initiatives focused on state-level and hospitalization forecasts, as well as other infectious diseases. Using CDC influenza forecasting challenges as an example, this paper provides an overview of infectious disease forecasting; applications of forecasting to public health; and current work to develop best practices for forecast methodology, applications, and communication.ConclusionsThese efforts, along with other infectious disease forecasting initiatives, can foster the continued advancement of forecasting science.

Background: Current strategies for COVID-19 therapy involve the systemic administration of drugs While pharmaceutical treatments continue to be evaluated, device-based therapies have yet to be explored We propose several transcatheter-based approaches for the treatment of COVID-19 Methods: Four transcatheter-based solutions were explored in their potential uses for COVID-19 therapy: local drug delivery, energy-based and photodynamic therapy, and neuromodulation Results: First is local, catheter-directed delivery of therapeutics directly to the lungs A localized delivery of therapeutics could increase the bioavailability of drug(s) at the site of action, in comparison to systemic delivery alone A second approach is light-based therapy Considering the antiviral, anti-inflammatory, antimicrobial, and vasculoprotective characteristics of visible light energy (380 to 750 nm), a localized, light-based catheter therapeutic approach could prove to be effective Given the distinct features of COVID-19 disease progression and its attack on hemoglobin and porphyrins, we suggest the infusion of porphyrin-based photosensitizers (PS) COVID-19 has an affinity for PS and would attach to these molecules, which would reduce hypoxic symptoms and allow for their deactivation through the photoactivation or sonoactivation of PS molecules A third approach considers that several studies have demonstrated that viruses hold electrical charges Neutralizing the charge of the virus within an electrical field is feasible to reduce the viral load using pacing wires and catheters placed near lungs A final approach is the neuromodulation of the host inflammatory response In a small preclinical study, the release of proinflammatory cytokines was reduced following transcutaneous low intensity focused ultrasound treatment of the spleen Conclusion: Several catheter-based therapies for COVID-19 were discussed It should be noted that in all approaches, the combination of a catheter-based therapy with systemic pharmaceutical therapy is recommended Robust clinical trials with clinically meaningful and relevant endpoints will be needed to assess the feasibility and safety of these approaches Categories Other: COVID-19

• COVID-19 is largely localized in lungs. • SARS-CoV-2 binds to the heme groups in hemoglobin that leads to severe hypoxia. • Porphyrin-based photosensitizers (PS) act as a ‘decoy’ in which the SARS-CoV-2 virions would attach to PS molecules. • Photoactivation capable of destroying the bonded SARS-CoV-2 virions.

Depression is associated with poor prognosis for cardiovascular disease (CVD) including mortality. Among multiple mechanisms linking depression and CVD, changes in platelet reactivity are known to be one of the major confounders of such adverse association. However, there are very limited data in children. Thus, we evaluated some conventional hemostatic indices including whole blood platelet aggregation in patients with documented pediatric depression and compared these data with those obtained from healthy children. The pediatric patients fulfilled criteria for major depression with a minimum score of 19 on the 21-item Beck Depression Inventory Scale. Plasma fibrinogen, D-dimer, platelet count, mean platelet volume, and platelet aggregation induced by ADP and collagen were measured in 67 pediatric patients with depression and matched by age and sex with 78 healthy controls. As expected, the depressed children had significantly higher BECK scales (P = 0.001) compared with the normal subjects. Platelet aggregation induced by ADP and collagen (P = 0.0001 for both) was significantly higher in depressed children. BECK scale scores correlated significantly with platelet aggregation induced by ADP (r = 0.3, P = 0.001) and collagen (r = 0.4, P = 0.01). In contrast, platelet counts, fibrinogen, D-dimer, mean platelet volume, and antithrombin-III levels were almost identical between both groups. Children with depression exhibit mostly intact hemostatic parameters, with the exception of significantly higher platelet activity when compared with healthy controls. These data match well with prior evidence from depressed adults supporting the hypothesis that platelets participate in the pathogenesis of depression. However, beyond pure assessment of platelet activity, other elements including serotonin content and cell receptor changes in pediatric depression should be elucidated before randomized trial(s) can be justified.

Aggressive dual antiplatelet therapy is associated not only with more bleeding, impaired wound healing, and potentially more solid cancer rates but it also causes higher infection risks including sepsis, and systemic inflammatory response syndrome (SIRS). This may be especially true considering the alarming off-label use of prasugrel. A 65-year-old white male patient with a history of myocardial infarction treated with percutaneous coronary intervention and implantation of 2 bare metal stents, was treated with off-label clopidogrel for 4 years, including a double daily dose (150 mg) for the initial 13 months. Still on clopidogrel, the patient was hospitalized with suspected pneumonia. A diagnostic cardiac catheterization revealed a 60%-70% blockage of the mid left anterior descending, but there was no need for coronary intervention. At discharge, clopidogrel 75 mg/d was switched over to off-label prasugrel 10 mg/d on top of aspirin (81 mg/d). On day 3 after prasugrel was given, a football-sized bruise appeared on the patient's lower right abdomen, but computed tomography results were unremarkable. On day 6 after administration of prasugrel, the patient became dizzy, disoriented, confused, experienced difficulty breathing, severe headache, weakness, intensive petechial rash covering the entire body, and breathing difficulty requiring ventilation. Within 24 hours, the patient was unable to correctly identify his age; his eyes were pale in color to almost colorless and when hearing a sound he would turn his entire head toward the sound and he appeared to be blind. His lungs, liver, and kidneys began to show signs of failure over the next 5-9 days. Sixteen days after the administration of the first prasugrel dose, the patient died of sepsis complicated with SIRS. Aggressive off-label use of clopidogrel (double dose for 13 months, and >4 years overall duration), followed by off-label switchover to the highest daily dose (10 mg) prasugrel may trigger sepsis and fatal SIRS. The mechanism responsible for such harmful association is probably indirect, and involves the weakening of platelet-neutrophil-endothelial crosstalk necessary to combat infections, and/or keep inflammation from spreading.

Surgical treatment of obesity is characterized by both early and late complications, and thus, there is a need to develop safe and non-invasive techniques. Ghrelin is an orexigenic hormone produced by the fundus of the stomach, which may represent a novel target for obesity management. Unfortunately, numerous attempts to alter ghrelin levels have failed to present significant clinical results. We describe a novel procedure that involves modifying arterial blood flow to the gastric fundus for limiting plasma ghrelin levels. A gastroscope was advanced into the gastric fundus of 13 healthy Yorkshire swine, and the fundus was clipped under direct visualization to restrict left gastric artery blood flow. Body weights and ghrelin levels were recorded before and once a week for 4 weeks after the procedure. Compared to controls, gastroscopic clipping of the fundus decreased plasma ghrelin levels and prevented further weight gain in the 4 weeks of follow-up. Immunohistochemistry and histomorphometry revealed reduced numbers of ghrelin-positive cells in the fundus of experimental animals. We also observed thrombosis in submucosal arteries and submucosal fibrosis. Histological studies demonstrated minimal gastric mucosal injury. Gastroscopic clipping of the fundus in an experimental porcine model resulted in sustained weight loss and a reduction in plasma ghrelin levels at 1 month post-procedure, with no adverse events. Further experimental studies in human patients are needed to examine the clinical utility of this procedure and to optimize a technique, which can facilitate adequate weight loss while minimizing the risk of mucosal injury.

Radiocontrast-induced nephropathy is a well known consequence of cardiologic interventions. Acute radiocontrast nephropathy is the third most common cause of acute renal failure in patients admitted to a hospital ([1][1]). Up to 7% of patients with this condition need temporary dialysis or progress

Valsartan is known to inhibit platelet activity in both in vitro and ex vivo clinical setting, whereas aliskiren in vitro modulates antithrombin-III in plasma. The authors tested how aliskiren and valsartan combination versus aliskiren monotherapy will affect hemostatic biomarkers in mild-to-moderate hypertensive diabetics in the frame of the Aliskiren and Valsartan Impact in Diabetics (AVID) trial. A total of 52 patients with type 2 diabetes and mild-to-moderate hypertension were equally randomized to aliskiren (150-300 mg/d) and valsartan (160 mg/d) versus aliskiren (150-300 mg/d) alone for 4 weeks. A total of 25 biomarkers were serially measured, of which 16 are related to platelet function, 6 to coagulation, and 3 to fibrinolysis. Aliskiren monotherapy has no significant impact on any of the assessed biomarkers. In contrast, valsartan on top of aliskiren provided significant inhibition of ADP-induced platelet aggregation (P=0.032), decreased shear-induced activation measured with PFA-100 analyzer (P=0.041), and diminished expression of GP IIb/IIIa activity (P=0.027) measured by PAC-1 antibody, GP Ib (CD42b, P=0.033), vitronectin receptor (CD51/61, P=0.046), P-selectin (CD62p, P=0.026), lysosome-associated membrane protein (CD107a, P=0.042), and CD40-ligand (CD154, P=0.048). In AVID trial, valsartan in combination with aliskiren mildly but significantly inhibited platelets, confirming previous observations. In contrast, aliskiren monotherapy does not enhance antithrombin activity, suggesting that previous data probably represent a laboratory artifact. Importantly, these randomized data were generated on top of low-dose daily aspirin, supporting extra benefit for combination use of angiotensin receptor blockers and renin inhibitors in high-risk diabetic population.

The recent report by Miyamoto et al. [(1)][1]presents the results of an experimental study evaluating the coronary vessel dilatory effect of transcutaneous low-frequency ultrasound. The investigators used a quite sophisticated animal model and demonstrated by various means that transcutaneous