Trends and Disparities in Cardiovascular Deaths in Systemic Lupus Erythematosus: A Population-Based Retrospective Study in the United States From 1999 to 2020.

PURPOSE: This study aimed to analyze two decades of consecutive mortality data to investigate cardiovascular deaths in Systemic Lupus Erythematosus (SLE) across the United States (US), identifying patterns and disparities in mortality rates. METHODS: A retrospective analysis was conducted using mortality data from the CDC WONDER database spanning 1999-2020. ICD-10 codes for diseases of circulatory system (I00-I99) and for SLE (M32) were used to identify cardiovascular-related deaths in SLE among adults aged 25 years and older at the time of death. Age-adjusted mortality rates (AAMRs) per 1,000,000 persons were calculated, and trends were assessed using Average Annual Percentage Change (AAPC) and Annual Percent Change (APC) using Joinpoint. Data were stratified by year, sex, race/ethnicity, and geographical regions. RESULTS: Between 1999 and 2020, cardiovascular-related deaths in SLE accounted for 6,548 deaths among adults aged 25 and older in the US. The overall AAMR for cardiovascular-related deaths in SLE decreased from 1.81 in 1999 to 1.53 in 2020, with an AAPC of -1.00 (95% CI: -1.91 to -0.24, p=0.025). A significant decline occurred from 1999 to 2014 with an APC of -3.20 (95% CI: -5.56 to -2.18; p=0.02), followed by a notable increase of 4.73 (95% CI: 0.41 to 18.29, p=0.23) from 2014 to 2020. Women exhibited higher AAMRs compared to men (women: 2.12, men: 0.53). The AAMR decreased for both men and women, with a steeper decline for men from 1999 to 2014 (APC: -4.85 95% CI: -15.58 to -2.62; p<0.02) compared to women in the same period (APC: -2.81 95% CI: -5.78 to -1.73; p<0.03). The Black cohort had a higher AAMR (3.54 95% CI: 3.37 to 3.70), compared to the White cohort (1.12 95% CI: 1.09 to 1.16). The highest mortality was in the Western region (AAMR: 1.60 95% CI: 1.52 to 1.68). Geographically, AAMRs ranged from 0.62 in Massachusetts to 3.11 in Oklahoma. Metropolitan areas had higher AAMRs than Non-metropolitan areas [(1.41 95% CI: 1.37 to 1.45) vs (1.29 95% CI: 1.21 to 1.37)], with a significant mortality reduction in Metropolitan area from 1999-2020 (AAPC: -1.04 95% CI: -1.95 to -0.28, p=0.0064) compared to Non-metropolitan areas in the same time frame (AAPC: -0.86, 95% CI: -2.43 to 0.33 p=0.152). CONCLUSIONS: This analysis highlights notable differences in mortality rates related to cardiovascular deaths in SLE. The target population was adult patients aged 25 and older in the United States. These results are based on demographic and geographic factors. Initially, there was a considerable decrease, but recently the mortality rates have started to rise. This highlights the importance of patient focused interventions to address disparities and improve health outcomes.

Neutrophils Expressing Programmed Death-Ligand 1 Play an Indispensable Role in Effective Bacterial Elimination and Resolving Inflammation in Methicillin-Resistant Staphylococcus aureus Infection.

Programmed death ligand 1 (PD-L1) is a co-inhibitory molecule expressed on the surface of various cell types and known for its suppressive effect on T cells through its interaction with PD-1. Neutrophils also express PD-L1, and its expression is elevated in specific situations; however, the immunobiological role of PD-L1+ neutrophils has not been fully characterized. Here, we report that PD-L1-expressing neutrophils increased in methicillin-resistant Staphylococcus aureus (MRSA) infection are highly functional in bacterial elimination and supporting inflammatory resolution. The frequency of PD-L1+ neutrophils was dramatically increased in MRSA-infected mice, and this population exhibited enhanced activity in bacterial elimination compared to PD-L1- neutrophils. The administration of PD-L1 monoclonal antibody did not impair PD-L1+ neutrophil function, suggesting that PD-L1 expression itself does not influence neutrophil activity. However, PD-1/PD-L1 blockade significantly delayed liver inflammation resolution in MRSA-infected mice, as indicated by their increased plasma alanine transaminase (ALT) levels and frequencies of inflammatory leukocytes in the liver, implying that neutrophil PD-L1 suppresses the inflammatory response of these cells during the acute phase of MRSA infection. Our results reveal that elevated PD-L1 expression can be a marker for the enhanced anti-bacterial function of neutrophils. Moreover, PD-L1+ neutrophils are an indispensable population attenuating inflammatory leukocyte activities, assisting in a smooth transition into the resolution phase in MRSA infection.

Peroxisome proliferator-activated receptor alpha is essential factor in enhanced macrophage immune function induced by angiotensin converting enzyme.

An upregulation of angiotensin-converting enzyme (ACE) expression strengthens the immune activity of myeloid lineage cells as a natural functional regulation mechanism in our immunity. ACE10/10 mice, possessing increased ACE expression in macrophages, exhibit enhanced anti-tumor immunity and anti-bactericidal effects compared to those of wild type (WT) mice, while the detailed molecular mechanism has not been elucidated yet. In this report, we demonstrate that peroxisome proliferator-activated receptor alpha (PPARα) is a key molecule in the functional upregulation of macrophages induced by ACE. The expression of PPARα, a transcription factor regulating fatty acid metabolism-associated gene expressions, was upregulated in ACE-overexpressing macrophages. To pinpoint the role of PPARα in the enhanced immune function of ACE-overexpressing macrophages, we established a line with myeloid lineage-selective PPARα depletion employing the Lysozyme 2 (LysM)-Cre system based on ACE 10/10 mice (named A10-PPARα-Cre). Interestingly, A10-PPARα-Cre mice exhibited larger B16-F10-originated tumors than original ACE 10/10 mice. PPARα depletion impaired cytokine production and antigen-presenting activity in ACE-overexpressing macrophages, resulting in reduced tumor antigen-specific CD8+ T cell activity. Additionally, the anti-bactericidal effect was also impaired in A10-PPARα-Cre mice, resulting in similar bacterial colonization to WT mice in Methicillin-Resistant Staphylococcus aureus (MRSA) infection. PPARα depletion downregulated phagocytic activity and bacteria killing in ACE-overexpressing macrophages. Moreover, THP-1-ACE-derived macrophages, as a human model, expressing upregulated PPARα exhibited enhanced cytotoxicity against B16-F10 cells and MRSA killing. These activities were further enhanced by the PPARα agonist, WY 14643, while abolished by the antagonist, GW6471, in THP-1-ACE cells. Thus, PPARα is an indispensable molecule in ACE-dependent functional upregulation of macrophages in both mice and humans.

Combined Rotational excimer lASER coronary atherectomy (RASER) in non-crossable, non-dilatable coronary artery disease: observations from a single center.

BACKGROUND: Balloon non-crossable stenoses represent a challenging subset of coronary artery disease (CAD). They are clinically associated with patients who are older, frailer, and with multi-morbidities, and angiographically with increased tortuosity and coronary artery calcification. Combined rotational (RA) excimer laser coronary atherectomy (ELCA), or RASER, may facilitate stent delivery and deployment in non-crossable, non-dilatable severely calcified lesions. In this study, we assessed preliminary safety and efficacy of the RASER hybrid technique. METHODS: RASER feasible percutaneous coronary intervention (PCI) procedures performed at a large tertiary hospital in the northeast of England were retrospectively analyzed from September 1, 2008, to February 28, 2022. Major endpoints were in-hospital death from any cause, as well as procedural and angiographic success, defined by stent delivery with less than 50% residual stenosis and without clinical or angiographic complications, respectively. RESULTS: From 74 unique cases, there were 28 RASER, 24 ELCA/RA, 16 balloon angioplasty ± stenting, and 6 medically treated patients. In-hospital mortality rate was 5.2%, including 1 ELCA- and 3 RASER-treated patients. Successful stent delivery was achieved in significantly more RASER-treated patients compared to ELCA/RA- or balloon-treated patients: 96.4% (27/28), 25% (6/24), and 31.3% (5/16) respectively (P less than .001). CONCLUSIONS: In our retrospective, single-center study, patients with CAD who were deemed appropriate for RASER PCI had a high peri-procedural mortality rate. In this context, adjunctive RASER therapy provides acceptable safety and efficacy as a bailout strategy, with at least 3 out of 5 patients achieving satisfactory procedural and angiographic results. Randomized controlled trials are needed to comprehensively compare the clinical outcomes of high-risk RASER PCI vs conservative medical therapy.

Myeloid cell ACE shapes cellular metabolism and function in PCSK-9 induced atherosclerosis.

The pathogenesis of atherosclerosis is defined by impaired lipid handling by macrophages which increases intracellular lipid accumulation. This dysregulation of macrophages triggers the accumulation of apoptotic cells and chronic inflammation which contributes to disease progression. We previously reported that mice with increased macrophage-specific angiotensin-converting enzyme, termed ACE10/10 mice, resist atherosclerosis in an adeno-associated virus-proprotein convertase subtilisin/kexin type 9 (AAV-PCSK9)-induced model. This is due to increased lipid metabolism by macrophages which contributes to plaque resolution. However, the importance of ACE in peripheral blood monocytes, which are the primary precursors of lesional-infiltrating macrophages, is still unknown in atherosclerosis. Here, we show that the ACE-mediated metabolic phenotype is already triggered in peripheral blood circulating monocytes and that this functional modification is directly transferred to differentiated macrophages in ACE10/10 mice. We found that Ly-6Clo monocytes were increased in atherosclerotic ACE10/10 mice. The monocytes isolated from atherosclerotic ACE10/10 mice showed enhanced lipid metabolism, elevated mitochondrial activity, and increased adenosine triphosphate (ATP) levels which implies that ACE overexpression is already altered in atherosclerosis. Furthermore, we observed increased oxygen consumption (VO2), respiratory exchange ratio (RER), and spontaneous physical activity in ACE10/10 mice compared to WT mice in atherosclerotic conditions, indicating enhanced systemic energy consumption. Thus, ACE overexpression in myeloid lineage cells modifies the metabolic function of peripheral blood circulating monocytes which differentiate to macrophages and protect against atherosclerotic lesion progression due to better lipid metabolism.

Bluegrass Biodesign: Why an Integrated Biomedical Engineering Curriculum is Crucial for Medical Education.

Background Medical education often overlooks the significance of design and innovation literacy, resulting in a knowledge gap in undergraduate medical education (UME) regarding formal training in these areas. Incorporating innovation into UME's core curriculum is crucial as future physicians will encounter evolving technologies, and fostering a transdisciplinary approach can enable collaborative problem-solving and improve patient health outcomes. Methodology We developed a comprehensive medical biodesign curriculum focused on innovation, including problem identification, prototype testing, and product commercialization. Participants were selected based on applications, interviews, and diverse criteria. A survey was conducted before and after the program to assess students' biodesign experiences and knowledge, with data analyzed using descriptive statistics and paired t-tests. Results Of the 41 participants, 24 (58.5%) completed both pre- and post-program surveys. These five-point Likert surveys showed a significant shift from pre-program to responses demonstrating increased "comfort levels in explaining and applying biodesign principles" (p < 0.0001). Specifically, the "comfort level in taking a product to market" increased from 33% to 67% (p = 0.01), while the "comfort level in applying the biodesign process" increased from 29% to 92% (p < 0.0001). Moreover, 58.3% of participants expressed interest in continuing their current projects, and 70.8% of students stated feeling confident in generating ideas and solutions with their team members. Conclusions The medical biodesign curriculum demonstrated success in exposing undergraduate medical and engineering students to the concepts of medical innovation and biodesign. The program has led to a significant improvement in students' knowledge and comfort levels in applying the biodesign process and taking a product to market. The high level of interest and participation in the program highlight the need for incorporating innovative training in UME to foster creativity and prepare future physicians to contribute to the advancements in healthcare.

Value-Based Care and Anesthesiology in the USA.

Value-based care, prioritizing patient outcomes over service volume, is steering a transformative course in anesthesiology in the United States. With the rise of this patient-centric approach, anesthesiologists are adopting dynamic roles to meet the demands of medical institutions, insurers, and patients for high-quality, cost-effective care. The urgency for this transition is accentuated by persistent challenges in reducing postoperative mortality rates and surgical complications, further spotlighted by the coronvirus disease 2019 (COVID-19) pandemic. Anesthesiologists engage in preoperative optimization, personalized care delivery, and evidence-based practices, bolstering their influence in the perioperative environment. Their collaboration with perioperative stakeholders propels the shift toward a value-driven healthcare landscape. This review analyzes the implementation of value-based care in American anesthesiology, assesses the significance of technology in enhancing its delivery, and outlines potential strategies for improving its application.

Advancements in Percutaneous Coronary Intervention Techniques: A Comprehensive Literature Review of Mixed Studies and Practice Guidelines.

Percutaneous coronary intervention (PCI) is a widely used therapy for coronary artery disease (CAD), but it carries risks and complications. Adhering to evidence-based practice guidelines is crucial for optimal outcomes. This review compares the recommendations of the 2021 American College of Cardiology/American Heart Association/Society for Cardiovascular Angiography and Interventions (ACC/AHA/SCAI) and 2018 European Society of Cardiology (ESC) guidelines for coronary artery revascularization and discusses emerging trends and novel devices in PCI. A comprehensive literature review of mixed studies, clinical trials, and guidelines was conducted. Intravascular imaging, including intravascular ultrasound and optical coherence tomography, for stent optimization, is also recommended when feasible. However, differences reflecting variations in evidence quality interpretation and applicability were identified. Furthermore, novel devices and technologies with the potential for improving outcomes were highlighted, but their safety and efficacy compared to standard-of-care techniques require further evaluation through extensive randomized trials. Clinicians should stay updated on advancements and personalize treatment decisions based on individual patient factors. Future research should address evidence gaps and barriers to adopting innovative devices and techniques. This review provides recommendations for clinical practice, emphasizing the need to remain current with the evolving landscape of PCI to optimize patient outcomes. The discoveries provide valuable counsel for the deliberation of clinical interventions and prospective inquiries within the realm of interventional cardiology. Overall, the review underscores the importance of evidence-based practice and ongoing advancements in PCI for CAD management.

Knowledge, attitudes, and practices of the general population of Pakistan regarding typhoid conjugate vaccine: findings of a cross-sectional study.

Typhoid fever, a common enteric disease in Pakistan, caused by Salmonella typhi, is becoming an extended drug-resistant organism and is preventable through the typhoid conjugate vaccine (TCV). Public adherence to preventive measures is influenced by knowledge and attitude toward the vaccine. This study investigates the knowledge, attitudes, and practices of the general population of Pakistan toward TCV. The differences in mean scores and factors associated with typhoid conjugate vaccine knowledge, attitudes, and practices were investigated. A total of 918 responses were received with a mean age of 25.9 ± 9.6, 51% were women, and 59.6% had graduation-level education. The majority of them responded that vaccines prevent illness (85.3%) and decrease mortality and disability (92.6%), and typhoid could be prevented by vaccination (86.7%). In total, 77.7 and 80.8% considered TCV safe and effective, respectively. Of 389 participants with children, 53.47% had vaccinated children, according to the extended program on immunization (EPI). Higher family income has a higher odds ratio (OR) for willingness toward booster dose of TCV [crude odds ratio (COR) = 4.920, p-value <0.01; adjusted odds ratio (aOR) = 2.853, value of p <0.001], and negative attitude regarding the protective effect of TCV has less willingness toward the booster dose with statistical significance (COR = 0.388, value of p = 0.017; aOR = 0.198, value of p = 0.011). The general population of Pakistan had a good level of knowledge about the benefits of TCV, and attitude and practices are in favor of the usage of TCV. However, a few religious misconceptions are prevalent in public requiring the efforts to overcome them to promote the usage of vaccines to prevent the disease and antibiotic resistance.

Early experience of intravascular lithotripsy in unprotected calcified left main coronary artery disease.

BACKGROUND: Treatment of unprotected severely calcified left main coronary artery (LMCA) disease is a complex interventional procedure. Intravascular lithotripsy (IVL) and rotational atherectomy (RA) are safe and effective methods of treating coronary calcification in the non-LMCA setting. This retrospective analysis assessed the feasibility of IVL versus RA in unprotected LMCA disease. METHODS: We analyzed IVL and RA procedures performed at a large tertiary hospital in the Northeast of England from January 1, 2019 to April 31, 2022. Major safety and efficacy endpoints were procedural and angiographic success, defined by stent delivery with <50 % residual stenosis and without clinical or angiographic complications, respectively. Another important clinical endpoint was the composite of major adverse cardiac events (MACE) at 1 year. RESULTS: From 242 patients, 44 had LMCA IVL, 81 had LMCA RA and 117 had non-LMCA IVL. Patients with LMCA disease were older and more likely to have aortic stenosis. IVL was a second-line or bailout technique in 86.4 % LMCA and 92.2 % non-LMCA cases. Procedural and angiographic success rates were ≥ 84 % across all groups (p > 0.05). In 3 LMCA IVL and 3 LMCA RA cases arrhythmias and cardiac tamponade complicated the procedures respectively. At 1 year, MACE occurred in 10/44 (22.7 %) LMCA IVL, 16/81 (19.8 %) LMCA RA and 25/117 (21.4 %) cases (p > 0.05). CONCLUSION: In our single center retrospective analysis, IVL is feasible in unprotected calcified LMCA as a second-line and third-line adjuvant calcium modification technique. Its use in unprotected calcified LMCA disease should be formalized with the undertaking of large randomized controlled trials.

Macrophage angiotensin-converting enzyme reduces atherosclerosis by increasing peroxisome proliferator-activated receptor α and fundamentally changing lipid metabolism.

AIMS: The metabolic failure of macrophages to adequately process lipid is central to the aetiology of atherosclerosis. Here, we examine the role of macrophage angiotensin-converting enzyme (ACE) in a mouse model of PCSK9-induced atherosclerosis. METHODS AND RESULTS: Atherosclerosis in mice was induced with AAV-PCSK9 and a high-fat diet. Animals with increased macrophage ACE (ACE 10/10 mice) have a marked reduction in atherosclerosis vs. WT mice. Macrophages from both the aorta and peritoneum of ACE 10/10 express increased PPARα and have a profoundly altered phenotype to process lipids characterized by higher levels of the surface scavenger receptor CD36, increased uptake of lipid, increased capacity to transport long chain fatty acids into mitochondria, higher oxidative metabolism and lipid ß-oxidation as determined using 13C isotope tracing, increased cell ATP, increased capacity for efferocytosis, increased concentrations of the lipid transporters ABCA1 and ABCG1, and increased cholesterol efflux. These effects are mostly independent of angiotensin II. Human THP-1 cells, when modified to express more ACE, increase expression of PPARα, increase cell ATP and acetyl-CoA, and increase cell efferocytosis. CONCLUSION: Increased macrophage ACE expression enhances macrophage lipid metabolism, cholesterol efflux, efferocytosis, and it reduces atherosclerosis. This has implications for the treatment of cardiovascular disease with angiotensin II receptor antagonists vs. ACE inhibitors.

Literature Review: Pathophysiology of Heart Failure with Preserved Ejection Fraction.

Heart failure with preserved ejection fraction is a growing public health concern, a disease with poor health outcomes, and is showing increased prevalence globally. This review paper explores the literature with a focus on the pathophysiology and microbiology of preserved ejection fraction heart failure while drawing connections between preserved and reduced ejection fraction states. The discussion teases out the cellular level changes that affect the overall dysfunction of the cardiac tissue, including the clinical manifestations, microbiological changes (endothelial cells, fibroblasts, cardiomyocytes, and excitation-contraction coupling), and the burden of structural diastolic dysfunction. The goal of this review is to summarize the pathophysiological disease state of heart failure with preserved ejection fraction to enhance understanding, knowledge, current treatment models of this pathology.

Takotsubo cardiomyopathy secondary to alcohol withdrawal.

Physical, mental, and emotional stressors have been well known to adversely affect cardiac function. A rare complication of such stressors is stress cardiomyopathy, otherwise known as takotsubo cardiomyopathy. First identified in Japan in the 1990s, takotsubo cardiomyopathy classically presents with systolic dysfunction and apical ballooning. In this report, we present the case of a patient with a medical history of alcohol abuse who presented to the emergency department after being found unresponsive by her family. Transthoracic echocardiography revealed takotsubo cardiomyopathy, which was likely secondary to alcohol withdrawal. Alcohol withdrawal causes an imbalance between various neurotransmitters such as GABA and glutamate. This imbalance caused autonomic overactivity, which manifested as stress cardiomyopathy.

miR766-3p and miR124-3p Dictate Drug Resistance and Clinical Outcome in HNSCC.

Head and neck squamous cell carcinoma (HNSCC) is a highly aggressive disease with poor prognosis, which is mainly due to drug resistance. The biology determining the response to chemo-radiotherapy in HNSCC is poorly understood. Using clinical samples, we found that miR124-3p and miR766-3p are overexpressed in chemo-radiotherapy-resistant (non-responder) HNSCC, as compared to responder tumors. Our study shows that inhibition of miR124-3p and miR766-3p enhances the sensitivity of HNSCC cell lines, CAL27 and FaDu, to 5-fluorouracil and cisplatin (FP) chemotherapy and radiotherapy. In contrast, overexpression of miR766-3p and miR124-3p confers a resistance phenotype in HNSCC cells. The upregulation of miR124-3p and miR766-3p is associated with increased HNSCC cell invasion and migration. In a xenograft mouse model, inhibition of miR124-3p and miR766-3p enhanced the efficacy of chemo-radiotherapy with reduced growth of resistant HNSCC. For the first time, we identified that miR124-3p and miR766-3p attenuate expression of CREBRF and NR3C2, respectively, in HNSCC, which promotes aggressive tumor behavior by inducing the signaling axes CREB3/ATG5 and ß-catenin/c-Myc. Since miR124-3p and miR766-3p affect complementary pathways, combined inhibition of these two miRNAs shows an additive effect on sensitizing cancer cells to chemo-radiotherapy. In conclusion, our study demonstrated a novel miR124-3p- and miR766-3p-based biological mechanism governing treatment-resistant HNSCC, which can be targeted to improve clinical outcomes in HNSCC.

The non-cardiovascular actions of ACE.

Angiotensin converting enzyme (ACE) is well known for its role producing the vasoconstrictor angiotensin II and ACE inhibitors are commonly used for treating hypertension and cardiovascular disease. However, ACE has many different substrates besides angiotensin I and plays a role in many different physiologic processes. Here, we discuss the role of ACE in the immune response. Several studies in mice indicate that increased expression of ACE by macrophages or neutrophils enhances the ability of these cells to respond to immune challenges such as infection, neoplasm, Alzheimer's disease, and atherosclerosis. Increased expression of ACE induces increased oxidative metabolism with an increase in cell content of ATP. In contrast, ACE inhibitors have the opposite effect, and in both humans and mice, administration of ACE inhibitors reduces the ability of neutrophils to kill bacteria. Understanding how ACE affects the immune response may provide a means to increase immunity in a variety of chronic conditions now not treated through immune manipulation.

Semantic Segmentation of Terrestrial Laser Scans of Railway Catenary Arches: A Use Case Perspective.

Having access to accurate and recent digital twins of infrastructure assets benefits the renovation, maintenance, condition monitoring, and construction planning of infrastructural projects. There are many cases where such a digital twin does not yet exist, such as for legacy structures. In order to create such a digital twin, a mobile laser scanner can be used to capture the geometric representation of the structure. With the aid of semantic segmentation, the scene can be decomposed into different object classes. This decomposition can then be used to retrieve cad models from a cad library to create an accurate digital twin. This study explores three deep-learning-based models for semantic segmentation of point clouds in a practical real-world setting: PointNet++, SuperPoint Graph, and Point Transformer. This study focuses on the use case of catenary arches of the Dutch railway system in collaboration with Strukton Rail, a major contractor for rail projects. A challenging, varied, high-resolution, and annotated dataset for evaluating point cloud segmentation models in railway settings is presented. The dataset contains 14 individually labelled classes and is the first of its kind to be made publicly available. A modified PointNet++ model achieved the best mean class Intersection over Union (IoU) of 71% for the semantic segmentation task on this new, diverse, and challenging dataset.

Predictors of In-Hospital Mortality in Patients With End-Stage Renal Disease Undergoing Transcatheter Aortic Valve Replacement: A Nationwide Inpatient Sample Database Analysis.

BACKGROUND: Patients with end-stage renal disease (ESRD) were excluded from all major trials on the safety of transcatheter aortic valve replacement (TAVR). This study aims to identify the predictors of mortality due to the rising rate of TAVR utilization and subsequent mortality in patients with ESRD. METHODS: The National Inpatient Sample (NIS) (2002-2017) was queried to identify all patients with ESRD undergoing TAVR. The trend of all-cause mortality and its predictors were determined using a binary logistic regression model to obtain adjusted odds ratios (aOR). RESULTS: A total of 6836 patients (6341 survived, 495 died) were included in the analysis. The proportion of demographic and baseline comorbidities for survived vs. non-survived was nearly identical between the two groups. A rising trend in the utilization and mortality of TAVR in ESRD was noted. The adjusted odds of mortality was significantly higher for hypertension (6.92, 95% CI 3.78-12.66, p ≤ 0.0001), liver disease (4.51, 955 CI 3.30-6.17, p ≤ 0.0001), drug abuse (aOR 34.88, 95% CI 12.79-95.13, p ≤ 0.0001), periprocedural pneumonia (aOR 2.80, 95% CI 1.98-3.96, p ≤ 0.0001), cardiogenic shock (aOR, 5.97, 95% CI 4.63-7.70, p ≤ 0.0001), ST-elevation myocardial infarction (aOR 5.13, 95% CI 2.29-11.49, p ≤ 0.0001) and third-degree heart block (aOR 1.47, 955 CI 1.10-1.97, p0.01) in patients with ESRD undergoing TAVR. The mean length of stay and mean number of diagnoses recorded were also significantly higher for non-surviving TAVR patients. CONCLUSION: Baseline hypertension, liver disease, third-degree heart block, periprocedural pneumonia, cardiogenic shock and STEMI can significantly increase the in-hospital mortality rate in ESRD patients undergoing TAVR.

An ACE inhibitor reduces bactericidal activity of human neutrophils in vitro and impairs mouse neutrophil activity in vivo.

Angiotensin-converting enzyme inhibitors (ACEIs) are used by millions of patients to treat hypertension, diabetic kidney disease, and heart failure. However, these patients are often at increased risk of infection. To evaluate the impact of ACEIs on immune responses to infection, we compared the effect of an ACEI versus an angiotensin receptor blocker (ARB) on neutrophil antibacterial activity. ACEI exposure reduced the ability of murine neutrophils to kill methicillin-resistant Staphylococcus aureus (MRSA), Pseudomonas aeruginosa, and Klebsiella pneumoniae in vitro. In vivo, ACEI-treated mice infected with MRSA had increased bacteremia and tissue bacteria counts compared to mice treated with an ARB or with no drug. Similarly, ACEIs, but not ARBs, increased the incidence of MRSA-induced infective endocarditis in mice with aortic valve injury. Neutrophils from ACE knockout (KO) mice or mice treated with an ACEI produced less leukotriene B4 (LTB4) upon stimulation with MRSA or lipopolysaccharide, whereas neutrophils overexpressing ACE produced more LTB4 compared to wild-type neutrophils. As a result of reduced LTB4 production, ACE KO neutrophils showed decreased survival signaling and increased apoptosis. In contrast, neutrophils overexpressing ACE had an enhanced survival phenotype. Last, in a cohort of human volunteers receiving the ACEI ramipril for 1 week, ACEI administration reduced neutrophil superoxide and reactive oxygen species production and neutrophils isolated from volunteers during ramipril treatment had reduced bactericidal activity. Together, these data demonstrate that ACEI treatment, but not ARB treatment, can reduce the bacterial killing ability of neutrophils.

ß-Galactosidase mediated synthesized nanosupport for the immobilization of same enzyme: Its stability and application in the hydrolysis of lactose.

ß-Galactosidase was immobilized on modified nanosilver reduced graphene oxide (Ag@rGO) nanocomposite prepared by in vitro synthesis using same enzyme. The effectiveness factor, η value of the immobilized enzyme was calculated to be 0.968, suggesting enhancement in enzyme activity after immobilization. The morphological structure of the crosslinked biopolymer was analyzed using electron microscopy and other characterization techniques. The kinetics displayed a decrease in Km value from 0.50 to 0.44 mmol L-1 while there was an increase in Vmax values from 0.031 to 0.039 µmol min-1 mL-1. The immobilized enzyme retained 85% activity after its 10th repeated use. Inhibition constant (Ki) value suggests galactose to be a more potent inhibitor of the enzyme. Despite the inhibitory potential of these hydrolysis products, the immobilized enzyme preparation retained 44.2% activity in the presence of both inhibitory sugars. The as-synthesized nanobiocatalyst was found quite effective in hydrolyzing 89% of lactose from whey. Hence, this nanobiocatalyst can be used in removing lactose from dairy waste, whey before releasing it into the water bodies. Also, the cytotoxicity and genotoxicity of Ag@rGO NC was assessed on human blood lymphocytes using flow cytometry and comet assay, respectively.