Swertisin, a novel SGLT2 inhibitor, with improved glucose homeostasis for effective diabetes therapy.

Failing pancreas and subsequent loss of pancreatic ß cells worsen diabetic conditions which are further alleviated by the mounting up of glucose levels. Inhibition of sodium glucose cotransporter 2 (SGLT2) in the kidney responsible for glucose reabsorption strikingly reduces blood glucose levels. Bioactive swertisin showed a promising glucose-lowering effect. Hence, we aimed to mechanistically dissect the glucose lowering property of swertisin. A systematic in silico, in vitro, and in vivo approach was directed for target analysis of swertisin. Molecular docking was performed with Swertisn-hSGLT2 complex. Glucose uptake assay and protein expression for SGLT2 and regulatory proteins were performed under swertisin effect. Various physiological and metabolic parameters were evaluated in STZ induced BALB/c mice using swertisin treatment. SGLT2 expression was evaluated in the kidney tissue of mice. Swertisn-hSGLT2 molecularly docked complex showed similar binding energy compared to the Canagliflozin-hSGLT2 complex. Swertisin inhibited glucose uptake and decreased expression of SGLT2 in HEK293 cells. Swertisin does not affect GLUT mediated glucose transport. Swertisin treated diabetic mice demonstrated remarkable improvement in overall glucose homeostasis. Reduced expression of SGLT2 was found in kidney tissue along with reduced PKC expression which is one of the key regulators of SGLT2. Our study explored SGLT2 as a selective target of swertisin for its swift glucose-lowering action which not only inhibits SGLT2 but also reduces its expression in diabetic condition. Thus, the potential property of swertisin as a glucose-lowering agent is remarkable which points towards the likelihood of a wider avenue of diabetes therapy.

Commercial claims costs related to health care resource use associated with a diagnosis of peanut allergy.

BACKGROUND: Peanut allergy (PA) affects approximately 1.6 million US children. The current standard of care is strict avoidance and prompt reaction treatment. Peanut allergy health care costs and health care resource utilization (HCRU) are poorly understood. OBJECTIVE: To estimate PA health care costs and HCRU using a nationally representative commercial payer database. METHODS: The IBM MarketScan Commercial Claims and Encounters Database was examined for PA diagnosis/reaction codes between January 2010 and October 2016 in patients 64 years of age or younger, with age cohort-matched controls. Outcomes were measured 12 months before and after the first claim date. Health care costs and HCRU were compared using Student's t tests and χ2 tests. RESULTS: Patients with a PA-related diagnostic code (n = 41,675) incurred almost double all-cause health care costs vs controls ($6436 vs $3493, P < .001), mainly from inpatient and outpatient medical costs ($5002 vs $2832, P < .001). More than one third of the PA group patients (36%) had a code indicative of an anaphylactic reaction during follow-up. Mean PA or reaction-related code costs per visit totaled $7921 for hospitalizations and $1115 for emergency department (ED) visits. Costs were 30% lower in patients with asthma codes without PA codes vs those with both codes ($5678 vs $8112, P < .001); all-cause ED costs were more than double in patients with atopic dermatitis codes with PA codes vs those without PA codes ($654 vs $308, P < .001). CONCLUSION: National commercial payer claims data indicate a significant health care burden associated with a PA-related code, including over $6400/patient in annual all-cause costs and increased health care utilization.

Increased Nonalternans Repolarization Variability Precedes Ventricular Tachycardia Onset in Patients with Implantable Defibrillators.

BACKROUND: T-wave alternans (TWA) is associated with ventricular tachycardia (VT). Nonalternans repolarization variability (NARV) precedes VT in certain experimental models, but its link to clinical arrhythmia is unproven. This study was conducted to determine if NARV increases prior to VT in patients with implantable cardioverter defibrillators (ICDs). METHODS: TWA and NARV were calculated from shock-channel electrograms preceding onset of VT or non-VT events in patients with an ICD. In each patient, presence of both a VT and a non-VT event with the same QRS morphology before the event was required. Mixed linear model was used for data analysis, using heart rate (HR) and the number of analyzed beats as covariates. RESULTS: Five hundred and sixty-eight events from 64 patients (males/females 51/13, 67 ± 13 years) were analyzed. HR preceding non-VT events was higher than before VT events (RR interval 595 ± 159 vs 706 ± 111 ms; P < 0.0001). Both TWA and NARV increased with increasing HR (P < 0.001). TWA decreased with increasing number of analyzed beats. When controlled for number of analyzed beats and HR, both TWA and NARV were higher before VT than before non-VT events (P < 0.002 and P < 0.0005, respectively). CONCLUSIONS: NARV is elevated prior to spontaneous VT onset. Both NARV and TWA increase with HR. The decrease of TWA with increasing number of analyzed beats may indicate contamination with NARV or noise when only a small number of beats is available for analysis. NARV might be useful for VT prediction in the future.

Communication aid requirements of intensive care unit patients with transient speech loss.

Alert and transiently nonvocal intensive care unit (ICU) patients are dependent on augmentative and alternative communication (AAC). Unfortunately, the literature demonstrates that existent AAC devices have not been widely adopted, and unaided methods are often the primary modalities used despite being insufficient, and frustrating. We present the results of a qualitative semi-structured interview study with 8 ex-ICU patients, 4 ICU patient relatives, and 6 ICU staff, exploring their AAC needs and requirements. Participants identified important AAC hardware, software, and content requirements. Salient factors impacting on AAC adoption in the ICU setting were also highlighted and included the need for staff training and bedside patient assessment. Based on the study results, we propose a series of recommendations regarding the design and implementation of future AAC tools specifically targeted at this group.

Mortality, Hospital Costs, Payments, and Readmissions Associated With Clostridium difficile Infection Among Medicare Beneficiaries.

BACKGROUND: The management of Clostridium difficile infection (CDI) among hospitalized patients is costly, and ongoing payment reform is compelling hospitals to reduce its burden. To assess the impact of CDI on mortality, hospital costs, healthcare use, and Medicare payments for beneficiaries who were discharged with CDI listed as a secondary International Classification of Diseases, Ninth Revision, Clinical Modification claim diagnosis. METHODS: Data were analyzed from the 2009 to 2010 5% random sample Medicare Standard Analytic Files of beneficiary claims. Patients with index hospitalizations with CDI as a secondary diagnosis and no previous hospitalization within 30 days were identified. Outcomes included inpatient and 30-day mortality, inpatient costs, index hospital payments, all-provider payments, net hospital losses, payment to cost ratio, length of stay (LOS), and 30-day readmission; outcomes were each risk adjusted using propensity score matching and regression modeling techniques. RESULTS: A total of 3262 patients with CDI were identified after matching to patients without a CDI diagnosis. After risk adjustment, secondary CDI was associated with statistically significantly (all P < 0.05) greater inpatient mortality (3.1% vs. 1.7%), 30-day mortality (4.1% vs. 2.2%), longer LOS (7.0 days vs. 3.8 days), higher rates of 30-day hospital readmissions (14.8% vs. 10.4%), and greater hospital costs ($16,184 vs. $13,954) compared with the non-CDI cohort. The risk-adjusted payment-to-cost ratio was shown to be lower for patients with CDI than those without (0.76 vs. 0.85). CONCLUSIONS: Secondary CDI is associated with greater adjusted mortality, costs, LOS, and hospital readmissions, while receiving similar hospital reimbursement compared with patients without CDI in a Medicare population.

QT prolongation and T-wave alternans during catheter ablation of atrial fibrillation: a case report.

We report a case of a 63-year-old woman who developed profound QT prolongation, T-wave alternans, and spontaneous ventricular fibrillation during catheter ablation of atrial fibrillation. A thorough search into the possible mechanisms identified the use of sevoflurane, an inhalational gas anesthetic as the culprit. The patient was converted to propofol anesthesia and her QT interval normalized promptly.

Mechanisms of inappropriate defibrillator therapy in a modern cohort of remotely monitored patients.

INTRODUCTION: Defibrillator (ICD) technology and monitoring are evolving rapidly. We investigated the mechanisms of inappropriate ICD therapies in a modern cohort of patients followed at our institution via remote monitoring. METHODS: From September 2009 to March 2011, a total of 2,050 ICD patients (19,600 patient-months) were remotely followed. All events (shocks and antitachycardia pacing) were adjudicated by arrhythmia specialists. RESULTS: A total of 249 patients received ICD therapy (34% inappropriate therapy). Inappropriate ICD shocks affected 33 (1.6%) patients. There were a total of 249 inappropriate episodes in 85 patients. Supraventricular tachycardia (SVT) with 1:1 atrioventricular association was the predominant mechanism accounting for 133 episodes in 50 patients, followed by atrial fibrillation (97 episodes in 27 patients). T-wave oversensing (16 episodes in five patients), electromagnetic interference (two episodes in two patients), and ectopic beats (one episode in one patient) accounted for a small proportion of events. There were 35 arrhythmic episodes in five patients that could not be classified, all in patients with single-chamber devices. There were no differences in these results by device manufacturer. CONCLUSIONS: Despite many technological advances, inappropriate ICD shocks still occur but at very low rates and SVT with 1:1 atrioventricular association represents their most common mechanism.

Dual atrioventricular nodal nonreentrant tachycardia with alternating 1:1 and 1:2 AV conduction: mechanistic hypotheses and total suppression using right atrial pacing.

Dual atrioventricular (AV) nodal nonreentrant tachycardia is an uncommon arrhythmia with several pattern types. The primary therapy is ablation of the slow AV nodal pathway. A rare pattern type demonstrates alternating 1:2 and 1:1 AV ratios with longer PR intervals during 1:1 conduction. We report the second intracardiac study of this variant and the first case of using right atrial pacing as the ultimate therapy for any pattern type.

Potential Cardiovascular Events Avoided with Bempedoic Acid Plus Ezetimibe Fixed-Dose Combination Compared with Ezetimibe Alone in Patients with Atherosclerotic Cardiovascular Disease Taking Maximally Tolerated Statins.

BACKGROUND: Patients with atherosclerotic cardiovascular disease who require additional low-density lipoprotein cholesterol (LDL-C) lowering despite maximally tolerated statins have a significant unmet medical need and are at increased risk of future cardiovascular events and a reduced quality of life. OBJECTIVE: We aimed to estimate the percentage of cardiovascular events avoided following treatment with a fixed-dose combination of bempedoic acid plus ezetimibe (BA+EZE FDC) versus ezetimibe (EZE) in patients with atherosclerotic cardiovascular disease receiving maximally tolerated statins across a range of baseline LDL-C levels. METHODS: A Markov cohort simulation model estimated major adverse cardiovascular events avoided over a lifetime horizon among patients with atherosclerotic cardiovascular disease and baseline LDL-C levels from 80 to >200 mg/dL. BA+EZE FDC was compared with EZE based on mean percent LDL-C reductions versus placebo reported in a phase III trial. Health outcomes for the average patient were extrapolated to a US population of 100,000 persons using evidence on contemporary LDL-C levels from the National Health and Nutrition Examination Survey. RESULTS: Among patients with atherosclerotic cardiovascular disease not at the LDL-C goal with maximally tolerated statins, the addition of BA+EZE FDC compared with the addition of EZE was predicted to provide incremental absolute reductions in major adverse cardiovascular events dependent on baseline LDL-C levels at the population level. For those with baseline LDL-C of 101-110 mg/dL (n = 15,237), there were 4.9% (744) fewer events predicted, while for patients with baseline LDL-C of > 200 mg/dL (n = 1689), 10.9% (184) fewer events were predicted through the addition of BA+EZE FDC versus EZE. CONCLUSIONS: Further LDL-C reductions through the addition of BA+EZE FDC to maximally tolerated statins are predicted to reduce major adverse cardiovascular events compared with the addition of EZE. Benefits are potentially greater among those with higher starting LDL-C.

Long-term effects on renal function of dose-reduced calcineurin inhibitor and sirolimus in cardiac transplant patients.

UNLABELLED: Calcineurin inhibitor (CNI)-associated renal insufficiency is common after cardiac transplantation (CTX); however, the addition of sirolimus allows for CNI dose reduction and this strategy may limit CNI renal toxicity. This study examines the long-term effects of such a strategy. METHODS: Patients from a single center who had CTX from 1990 to 2007 and who were converted to sirolimus and a dose-reduced CNI were compared to group-matched controls maintained on CNI and an antiproliferative agent. RESULTS: One hundred and fifty-five patients (79 sirolimus and 76 controls) were included and had similar baseline characteristics. Sirolimus was started a mean of 1429 d post-CTX and maintained for a mean of 823 d. Reason for conversion to sirolimus was renal insufficiency (34%), vasculopathy (29%), recurrent rejection (19%), and other (18%). The eGFR was not different between groups at baseline (44.7 mL/min/1.73 m(2) vs. 46.0, p = 0.64) or at any point during follow-up: 90 d, 180 d, 1 yr, 2 yr, and 3 yr. conclusion: Patients converted to a regimen of sirolimus and a dosed-reduced CNI have stable renal function over the following three yr, but do not have an improvement in renal outcomes compared to patients maintained on full dose CNI.

Biventricular defibrillator patients have higher complication rates after revision of recalled leads.

BACKGROUND: Since the 2009 revised advisory statement regarding Sprint Fidelis® Defibrillator Lead failure rates (Medtronic Inc., Minneapolis, MN, USA), there has been a significant increase in revision of these leads. We sought to establish the frequency of major procedural complications and determine what patient characteristics were associated with these outcomes. METHODS: We retrospectively reviewed the charts of 621 patients with Fidelis® leads being followed in the University of Pittsburgh Medical Center through January 1, 2010. The population was then examined for rates of lead malfunction, revision, and complication. RESULTS: The average time from implantation of Fidelis® lead to endpoint was 32 ± 16 months. Overall lead survival rates were 89% at 41 months and were lower in biventricular implantable cardioverter defibrillator (BiVICD) as compared to standard implantable cardioverter defibrillator patients (log rank P = 0.053). Prophylactic revisions increased dramatically during 2009 (9.4% vs 1.4%, P < 0.001). Among the 131 patients who underwent revision during the entire time of follow-up, 11 patients had postoperative complications (8.5%). The only significant variable found between patients who did and did not have complications was the presence of a BiVICD (81.8 vs 48.7%, P = 0.036). Of the 40 total patients who underwent lead extraction, all three complications occurred in patients with BiVICDs. CONCLUSION: The number of prophylactic Fidelis® lead revisions has increased dramatically since 2008, and procedure-related complications have been higher than anticipated. Major procedural complication rates are greater among patients with BiVICDs. Overall, lead extraction does not appear to increase procedural risk as compared to abandonment.

The impact of COPD on quality of life, productivity loss, and resource use among the elderly United States workforce.

Abstract To address the gap in knowledge about the impact of chronic obstructive pulmonary disease (COPD) on older working adults, this study examined quality of life, worker productivity, and healthcare resource utilization among employed adults aged 65 and older with and without COPD. Among 2009 National Health and Wellness Survey (a cross-sectional, internet-based survey representative of the US adult population) respondents, employed adults aged 65 years and older, with COPD (n = 297) and without COPD (n = 3061), were included in analyses. Impact of self-reported COPD diagnosis on mean quality of life (using health utilities and mental, MCS, and physical, PCS, component summary scores from SF-12v2), work productivity and activity impairment (using the WPAI questionnaire), and resource use were examined. Adjusting for demographic and health characteristics such as co-morbidities (weighted to project to the US population) in regression models (linear, negative binomial, or logistic, as appropriate given the outcome measure), older workers with COPD reported significantly lower MCS (52.1 vs. 53.4, p < .05), PCS (40.3 vs. 47.2, p < .05), and health utilities (0.72 vs. 0.79, p < .05) than those without COPD, and significantly greater percentages of impairment while at work (presenteeism) (12.6% vs. 8.7%, p < .0001), overall work impairment (absenteeism and presenteeism combined) (19.3% vs. 10.0%, p < .05), and impairment in daily activities (23.9% vs. 13.7%, p < .05). There were no significant differences in absenteeism or healthcare use. Quality of life and work productivity suffered among employed adults aged 65 years and older with COPD, emphasizing the need for disease management in this population.

Predictors for mucormycosis in COVID era: A case-control study from Gujarat.

Context: Mucormycosis has been increasingly described in the coronavirus disease (COVID-19) era, however, there is a lack of robust epidemiological studies to understand the predictors for the development of mucormycosis from India. Aims: To document the risk factors of mucormycosis with or without COVID-19 and estimate the strength of association of various risk factors. Settings and Design: A case-control study was conducted in the Ahmedabad districts of Gujarat from June to August 2021. Methods and Material: One hundred participants (25 cases with mucor, 75 without mucor) were enrolled in the study. The cases and controls were then matched based on age and gender. Ethical approval was sought from the Institutional Ethics Committee of the Indian Institute of Public Health Gandhinagar, Gujrat, India. Statistical Analysis Used: Data were collected using the Epi Collect 5 application, and the descriptive, inferential analysis was done using the SPSS version 21 statistical software. Results: About 68% of the cases were from a rural area and had past comorbidity conditions. About 80% of the cases reported a previous history of COVID-19, whereas 67% of the controls reported the same. The factors which remained significant after applying the hierarchical model were rural residents (OR = 3.2 [95% CI: 1.05-10.3]) and history of oxygen therapy (OR = 5.42 [95% CI: 1.24-23.8]). Conclusions: This study concludes that mucormycosis is independent of the COVID-19 status. Rural residents and oxygen therapy were found to be the most significant risk factors for mucormycosis. The findings of this study are also not conclusive to establish an association; thus, further exploration and in-depth research with larger samples are recommended.

A US Time and Motion Pilot Study of Nebulized COPD Therapy in an Inpatient and a Long-Term Care Setting.

INTRODUCTION: There is a lack of quantitative data on healthcare professionals' (HCPs) time dedicated to nebulized chronic obstructive pulmonary disease (COPD) therapy in inpatient and long-term care (LTC) settings. Using time and motion methodology, we quantified HCP time and opportunity costs (time and materials) associated with nebulized COPD therapy in inpatient and LTC settings and estimated efficiencies of changing to once-daily therapy. METHODS: A case report form was built to reflect local nebulization workflow. Primary outcomes were mean active HCP time per predefined task and mean total active HCP time associated with short-acting beta agonist (SABA) and SABA/short-acting muscarinic antagonist (SAMA) combination nebulization processes. RESULTS: Twenty observations occurred within each setting. Inpatient observations included three SABA and 17 SABA/SAMA (from 18 different patients), and LTC observations included five SABA and 15 SABA/SAMA (from eight different patients). Mean total process time was 16.12 min in the inpatient setting (95% CI 14.48-17.76) and 21.0 min in the LTC setting (95% CI 18.8-23.2), with the actual nebulization comprising over 50% of process time for both. In LTC, CIs suggest a difference by cognitive impairment status: mean 24.1 min (95% CI 21.3-26.9) if cognitively impaired versus 19.0 min (95% CI 16.1-21.8) if not. In the inpatient setting, the estimated process time/admission was 7.8 h; a once-daily nebulized drug would require only 2.3 h. In LTC, the estimated process time was 32.1 h/month; a once-daily nebulized drug would require only 13.7 h/month. Estimated nebulization cost was $243/admission for current versus $72 for once-daily dosing in inpatient, and $1177/month versus $504 in LTC. CONCLUSIONS: The nebulization process for COPD patients in both inpatient and LTC settings consumes considerable HCP time. A switch from SABA or SABA/SAMA to a drug with a once-daily nebulization frequency could generate substantial time savings depending on the setting and site characteristics.

Sinus node sparing novel hybrid approach for treatment of inappropriate sinus tachycardia/postural sinus tachycardia: multicenter experience.

BACKGROUND: The ideal treatment of inappropriate sinus tachycardia (IST) and postural orthostatic tachycardia syndrome (POTS) still needs to be defined. Medical treatments yield suboptimal results. Endocardial catheter ablation of the sinus node (SN) may risk phrenic nerve damage and open-heart surgery may be accompanied by unjustified invasive risks. METHODS: We describe our first multicenter experience of 255 consecutive patients (235 females, 25.94 ± 3.84 years) having undergone a novel SN sparing hybrid thoracoscopic ablation for drug-resistant IST (n = 204, 80%) or POTS (n = 51, 20%). As previously described, the SN was identified with 3D mapping. Surgery was performed through three 5-mm ports from the right side. A minimally invasive approach with a bipolar radiofrequency clamp was used to ablate targeted areas while sparing the SN region. The targeted areas included isolation of the superior and the inferior caval veins, and a crista terminalis line was made. All lines were interconnected. RESULTS: Normal sinus rhythm (SR) was restored in all patients at the end of the procedure. All patients discontinued medication during the follow-up. After a blanking period of 6 months, all patients presented stable SR. At a mean of 4.07 ± 1.8 years, normal SN reduction and chronotropic response to exercise were present. In the 51 patients initially diagnosed with POTS, no syncope occurred. During follow-up, pericarditis was the most common complication (121 patients: 47%), with complete resolution in all cases. Pneumothorax was observed in 5 patients (1.9%), only 3 (1.1%) required surgical drainage. Five patients (1.9%) required a dual-chamber pacemaker due to sinus arrest > 5 s. CONCLUSIONS: Preliminary results of this multicenter experience with a novel SN sparing hybrid ablation of IST/POTS, using surgical thoracoscopic video-assisted epicardial ablation combined with simultaneous endocardial 3D mapping may prove to be an efficient and safe therapeutic option in patients with symptomatic drug-resistant IST and POTS. Importantly, in our study, all patients had a complete resolution of the symptoms and restored normal SN activity.

Vacuum-assisted closure therapy with omental transposition for salvage of infected prosthetic femoral-distal bypass involving the femoral anastomosis.

Vascular graft infections are associated with the potential for devastating sequelae, including hemorrhage, septicemia, amputation, and death. Graft excision and debridement of the infected bed with revascularization via an extra-anatomic site or orthotopic vein bypass has been the traditional treatment of choice. Because the morbidity of these operations is substantial, less radical graft preservation techniques are desirable, such as myoplasty, omental flap transposition, and vacuum-assisted closure therapy. We report a patient with infection involving a prosthetic graft that was treated with vacuum-assisted closure and transposition of an omental tongue to enable coverage of the exposed graft.

Examining web equivalence and risk factor sensitivity of the COPD population screener.

OBJECTIVES: The primary aim was to assess the equivalence of an Internet-based chronic obstructive pulmonary disease-population screener (COPD-PS) relative to a validated paper-and-pencil version. A secondary aim was to compare groups based on known COPD risk factors, such as smoking status and gender. METHODS: Using an online panel survey organization, participants were randomized to internet or paper-and-pencil assessment where they completed the COPD-PS and other study forms. A subset of respondents also completed a test-retest reliability assessment. Finally, several thousand additional online respondents completed the COPD-PS for risk factor analyses. RESULTS: A total of 1006 adults completed the randomized study (N = 504 online, N = 502 by mail). There were no differences between the arms in mean COPD-PS scores (mean difference: 0.12; 95% confidence interval: -0.14-+0.37; P = 0.365). In the web arm, 106/504 (21.0%) exceeded the screening cut-off compared to 101/502 (20.1%) in the paper-administration arm (difference in proportions: 0.9%; 95% confidence interval: -4.1%-+5.9%; P = 0.720). Subgroup analyses on a separate cohort of 3001 adults demonstrated hypothesized differences between groups defined by smoking status, presence of COPD, and shortness of breath. CONCLUSION: The methods of administration that were evaluated in this study (internet vs. paper and pencil) resulted in no significant differences in COPD-PS mean scores. Furthermore, the predictive utility of the COPD-PS was not different between methods of administration, even after accounting for age and smoking status.

Left ventricular remodeling and myocardial recovery on mechanical circulatory support.

BACKGROUND: Myocardial recovery after ventricular assist devices (VAD) is rare but appears more common in nonischemic cardiomyopathies (NICM). We sought to evaluate left ventricular (LV) end diastolic diameter (LVEDD) for predicting recovery after VAD. METHODS AND RESULTS: NICM patients receiving long-term mechanical support between 1996 and 2008 were reviewed. Subjects were divided into 3 groups: mild, moderate, and severe dilation (Group A: LVEDD <6.0 cm [n = 22]; Group B: 6.0-7.0 cm [n = 32]; Group C: >7.0 cm [n = 48], respectively). Overall, recovery (successful explant without transplantation) occurred in 14 of 102 subjects (14%). Of these, 2 died and 2 required transplantation within 1 year. Recovery was more common in patients without LV dilation (Groups A/B/C = 32%/22%/0%, P < .001), as was sustained recovery (alive and transplant free 1 year after explant; A/B/C = 27%/10%/0%, P = .001). Of the recovery patients in Group A, 6/7 (86%) had sustained recovery versus 3/6 (50%) in Group B. CONCLUSIONS: Recovery occurred in 32% of NICM patients without significant LV dilation at time of VAD, the majority of whom experienced significant sustained recovery. Recovery was not evident in those with severe LV dilation. Routine echocardiography at the time of implant may assist in targeting patients for recovery after VAD.

Subintimal angioplasty is superior to SilverHawk atherectomy for the treatment of occlusive lesions of the lower extremities.

PURPOSE: To evaluate the outcomes of atherectomy versus subintimal angioplasty (SIA) in patients with lower extremity arterial occlusive disease. METHODS: From September 2005 through July 2006, 27 patients (17 women; mean age 65 years, range 37-85) underwent atherectomy of 46 lesions (11 TASC C/D occlusions) with the SilverHawk device. Results were compared to 67 patients (34 men; mean age 69 years, range 46-92) undergoing SIA for 67 lower extremity arterial occlusions from July 1999 through June 2004. RESULTS: Technical success in the atherectomy cohort was 100%. In the 11 patients with occlusions, symptoms improved in 10 and worsened in 1, but 9 (82.0%) of the 11 patients required reintervention, and 8 (72.7%) patients with occlusive lesions re-occluded. Endovascular reintervention was required to maintain primary patency in only 2 (12.5%) of 16 patients treated for stenotic lesions. At 1 year, the assisted primary patency was 37.7% in the atherectomy group. In the 11 patients with occlusive lesions, the patency rates were 36.8% and 12.3% at 6 and 9 months, respectively, versus 100% and 83.3% at the same time intervals in patients with stenotic lesions. SIA was technically successful in 56 (83.6%) of 67 occlusions. The assisted primary patency and limb salvage rates of the entire group (intention-to-treat) at 12 and 24 months were 59.2% and 45.0%, respectively, while the assisted primary patency of the 56 technically successful SIAs at 12 and 24 months were 70.7% and 53.8%, respectively. Limb salvage for the entire group (intention-to-treat) was 90.6% and 87.9% at 12 and 24 months, respectively. CONCLUSION: Atherectomy may yield acceptable primary patency and limb salvage in patients with stenotic lesions. Many of the patients treated for occlusive lesions require reintervention. Based on patency and limb salvage, SIA appears superior to atherectomy for the treatment of lower extremity occlusive disease.

Current global vaccine and drug efforts against COVID-19: Pros and cons of bypassing animal trials.

COVID-19 has become one of the biggest health concern, along with huge economic burden. With no clear remedies to treat the disease, doctors are repurposing drugs like chloroquine and remdesivir to treat COVID-19 patients. In parallel, research institutes in collaboration with biotech companies have identified strategies to use viral proteins as vaccine candidates for COVID-19. Although this looks promising, they still need to pass the test of challenge studies in animal models. As various models for SARS-CoV-2 are under testing phase, biotech companies have bypassed animal studies and moved to Phase I clinical trials. In view of the present outbreak, this looks a justified approach, but the problem is that in the absence of animal studies, we can never predict the outcomes in humans. Since animal models are critical for vaccine development and SARS-CoV-2 has different transmission dynamics, in this review we compare different animal models of SARS-CoV-2 with humans for their pathogenic, immune response and transmission dynamics that make them ideal models for vaccine testing for COVID-19. Another issue of using animal model is the ethics of using animals for research; thus, we also discuss the pros and cons of using animals for vaccine development studies.