Exploring the role of Müller cells-derived exosomes in diabetic retinopathy.

Exosomes are nanosized vesicles that have been reported as cargo-delivering vehicles between cells. Müller cells play a crucial role in the pathogenesis of diabetic retinopathy (DR). Activated Müller cells in the diabetic retina mediate disruption of barrier integrity and neovascularization. Endothelial cells constitute the inner blood-retinal barrier (BRB). Herein, we aim to evaluate the effect of Müller cell-derived exosomes on endothelial cell viability and barrier function under normal and hyperglycemic conditions. Müller cell-derived exosomes were isolated and characterized using Western blotting, nanoparticle tracking, and electron microscopy. The uptake of Müller cells-derived exosomes by the human retinal endothelial cells (HRECs) was monitored by labeling exosomes with PKH67. Endothelial cell vitality after treatment by exosomes under normo- and hypoglycemic conditions was checked by MTT assay and Western blot for apoptotic proteins. The barrier function of HRECs was evaluated by analysis of ZO-1 and transcellular electrical resistance (TER) using ECIS. Additionally, intracellular Ca+2 in HRECs was assessed by spectrofluorimetry. Analysis of the isolated exosomes showed a non-significant change in the number of exosomes isolated from both normal and hyperglycemic condition media, however, the average size of exosomes isolated from the hyperglycemic group showed a significant rise when compared to that of the normoglycemic group. Müller cells derived exosomes from hyperglycemic condition media markedly reduced HRECs cell count, increased caspase-3 and Annexin V, decreased ZO-1 levels and TER, and increased intracellular Ca+ when compared to other groups. However, treatment of HRECs under hyperglycemia with normo-glycemic Müller cells-derived exosomes significantly decreased cell death, preserved cellular integrity and barrier function, and reduced intracellular Ca+2. Collectively, Müller cell-derived exosomes play a remarkable role in the pathological changes associated with hyperglycemia-induced inner barrier dysfunction in DR. Further in vivo research will help in understanding the role of exosomes as therapeutic targets and/or delivery systems for DR.

Pan-inhibition of the three H2S synthesizing enzymes restrains tumor progression and immunosuppression in breast cancer.

BACKGROUND: Hydrogen sulfide (H2S) is a significant endogenous mediator that has been implicated in the progression of various forms of cancer including breast cancer (BC). Cystathionine-ß-synthase (CBS), cystathionine-γ-lyase (CSE), and 3-mercaptopyruvate sulfurtransferase (3MST) are the three principal mammalian enzymes responsible for H2S production. Overexpression of CBS, CSE and 3MST was found to be associated with poor prognosis of BC patients. Moreover, H2S was linked to an immune-suppressive tumor microenvironment in BC. Recently it was observed that BC cells, in response to single or dual inhibition of H2S synthesizing enzymes, develop an escape mechanism by overexpressing alternative sources of H2S generation. Thus, the aim of this work is to escape the H2S compensatory mechanism by pan repressing the three enzymes using microRNAs (miRNAs) and to investigate their impact on the oncogenic and immunogenic profile of BC cells. METHODS: BC female patients (n = 25) were recruited. In-silico analysis was used to identify miRNAs targeting CBS, CSE, and 3MST. MDA-MB-231 cells were cultured and transfected using oligonucleotides. Total RNA was extracted using Biazol, reverse transcribed and quantified using qRT-PCR. H2S levels were measured using AzMc assay. BC hallmarks were assessed using trans-well migration, wound healing, MTT, and colony forming assays. RESULTS: miR-193a and miR-548c were validated by eight different bioinformatics software to simultaneously target CBS, CSE and 3MST. MiR-193a and miR-548c were significantly downregulated in BC tissues compared to their non-cancerous counterparts. Ectopic expression of miR-193a and miR-548c in MDA-MB-231 TNBC cells resulted in a marked repression of CBS, CSE, and 3MST transcript and protein levels, a significant decrease in H2S levels, reduction in cellular viability, inhibition of migration and colony forming ability, repression of immune-suppressor proteins GAL3 GAL9, and CD155 and upregulation of the immunostimulatory MICA and MICB proteins. CONCLUSION: This study sheds the light onto miR-193a and miR-548c as potential pan-repressors of the H2S synthesizing enzymes. and identifies them as novel tumor suppressor and immunomodulatory miRNAs in TNBC.

Antibacterial and in vitro anticancer activities of the antimicrobial peptide NRC-07 encapsulated in chitosan nanoparticles.

Antimicrobial peptides (AMPs) are promising alternatives to conventional antibiotics and chemotherapy in the treatment of multidrug-resistant pathogens and drug-resistant cancers. Clinical application of AMPs is limited due to low stability and inefficient transport. Encapsulation in nanocarriers may improve their therapeutic potential. Chitosan nanoparticles (CS-NPs) are efficient carriers for proteins and peptides, improving the treatment of microbial infections and targeted drug delivery. We examined toxicity against cancer cell lines and antibacterial activities of the pleurocidin-like AMP NRC-07 upon encapsulation in CS-NPs by ionotropic gelation. The biological activities of various formulations of free and encapsulated NRC-07 and free nanoparticles were evaluated against Pseudomonas aeruginosa and breast cancer cells, using assays for cell viability and lactate dehydrogenase cytolysis with non-cancer cell lines as controls. NRC-07-containing nanoparticles decreased the bacterial and cancer cell viability in a concentration-dependent manner. Activities of encapsulated peptide were >2-fold higher than those of free NRC-07 peptide. Unloaded CS-NPs and free peptide were not cytotoxic against control cells. Encapsulation of NRC-07 into CS-NPs enhanced the antibacterial and selective cytotoxicity of the peptide, possibly enhancing anticancer activities. Encapsulation presents a promising tool for the development of efficient drug delivery systems.

Synthesis, and Biological Evaluation of Benzamide compounds as Insecticides Agents against Spodoptera frugiperda (Lepidoptera: Noctuidae).

Due to its severe damage, Spodoptera frugiperda is receiving attention as one of the biggest dangers to world food security. Although there are numerous insecticides that are widely and successfully used to control S. frugiperda, they do not have an immediate effect. In our work focusing for synthesized twelve novel benzamide derivatives and examined their insecticidal effectiveness against S. frugiperda larvae in their second & fourth larvae instars, with the aim of further improving the insecticidal activity based on combination principles. Several spectroscopic methods, including elemental analysis, NMR & infrared spectroscopy, were employed for confirming the structure of the newly designed products. It has been discovered that most compounds show good of promising efficacy. With an LC50 of 24.8 mg/L for larvae in the second instar & 56.2 mg/L for larvae in the fourth instar, compound 23 was the most active. Among all compounds 11, 22 and 20 exhibited excellent results. Furthermore, a number of biological and histopathological properties of the demonstration compounds of the produced goods under laboratory conditions were also examined. This work further demonstrates the anti-proliferation of S. frugiperda and offers fresh ideas for the manufacture of benzamide derivatives.

Green synthesis and bioefficacy screening of new insect growth regulators as eco-friendly insecticides against the cotton mealybug Phenacoccus solenopsis.

Overcoming or reducing the majority of difficulties caused by the use of common pesticides requires the use of developed, secure, unique and selective organic compounds. Due to their clear mechanism of action on pests and lower poisonousness towards vertebrates than conventional insecticides, juvenile hormone analogues as an example of insect growth regulators appear promising. Thus, a unique set of pure insect growth regulators has been synthesized. The structure of these synthesized compounds, which were related to the most well-known insect growth regulator insecticides, was confirmed by elemental and contemporary spectroscopic investigations (IR, UV, 1 H-NMR, 13 C NMR, and Dept 135 spectrum). Under laboratory conditions, the effectiveness of a chemically newly synthesized products was tested against the cotton mealybug, Phenacoccus solenopsis, and compared with Fenoxycarb as a reference insecticide. Compound 7 was discovered to be more effective than the other synthetic compounds, with LC50 values of 0.907 mg/L for adult female P. solenopsis and 0.377 mg/L for third instar nymphs. Furthermore, this results concluded that the adult female's stage of P. solenopsis was less sensitive to the checked treatments as matched to the third instar nymphs.

Design, Characterization and SAR Studies of Novel Bioactive Benzylideneacetophenone Derivatives as Insecticidal Agents against Spodoptera frugiperda (Lepidoptera: Noctuidae).

Unintentional environmental effects brought on by insecticides encourage the creation of safer substitutes. A very polyphagous migrating lepidopteran pest species in Africa called S. Frugiperda causes terrible damage. In the current paper, treatment of 4-acetylphenyl 4-methylbenzenesulfonate with different aromatic aldehydes in the presence of NaOH afforded benzylideneacetophenones. The structure of the newly prepared compounds were proved by different spectroscopic techniques such as IR, 1 H-NMR, 13 C NMR, and elemental analysis. We looked at the association between contact with S. frugiperda and stricture reaction to examine their harmful effect. Additionally, S. frugiperda was used for testing the newly created compounds for their ability to kill insects. The majority of substances have been proven to be effective and promising. It has been found that 4-[3-(4-Methylphenyl)prop-2-enoyl]phenyl-4-methyl benzenesulfonate (4) was the most active with an LC50 =3.46 mg/L of 2nd instar larvae and LC50 =9.45 mg/L of 4th instar larvae. Moreover, some of biological and histopathological aspects of the synthesized products were investigated under laboratory conditions.

Synthesis and Insecticidal Evaluation of 3,5-Dicyanopyridines Against Cotton Aphids via Microwave-Assisted Multicomponent Reactions.

Certain 2-amino-6-alkoxy-4-arylpyridine-3,5-dicyanide 1a-e were prepared via a straightforward process using microwave technology rather than conventional methods. This involved reaction of arylidenemalononitrile thru propanedinitrile in the occurrence of sodium alkoxide under MW. While, their positional isomer 4-amino-6-alkoxy-2-arylpyridine-3,5-dicyanide 3a-j have been separated from the reaction of aryl aldehydes with 2-aminoprop-1-ene-1,1,3-tricarbonitrile 2 in the presence of sodium alkoxide using microwave technic. Furthermore, the insecticidal properties of all synthesized compounds were observed with respect to Cotton aphid nymphs and adults. Neonicotinoid pesticides are indicated as the most effective pesticides toward aphids and many other pests. Many insecticides are discovered as novelties. As a result, several pyridine compounds were chemical method synthesized to serve as equivalents of neonicotinoids, a broad class of insecticides. With LC50 value of 0.03 mg/L, components 3g exhibit the highest insecticidal bioactivity. This work discusses how to find new chemicals that could be used as insecticidal agents in the future.

Exploration of Some Heterocyclic Compounds Containing Trifluoromethylpyridine Scaffold as Insecticides Toward Aphis gossypii Insects.

Five types of heterocyclic compounds containing trifloromethylpyridine scaffold namely; 3-cyano-2-(N-phenyl)carbamoylmethylthio-6-(thiophen-2-yl)-4-trifluoromethyl-pyridine (6a), thieno[2,3-b]pyridines 3-5 and 7a-c, pyrido[3',2':4,5]thieno[3,2-d] pyrimidines 8-13 and 15a-c, pyrido[3',2':4,5]thieno[3,2-d][1,2,3]triazines 16a,b, and 9-(thiophen-2-yl)-7-(trifluoromethyl) pyrido [3',2':4,5]thieno[2,3-e][1,2,4]triazolo[1,5-c]pyrimidine (14) were synthesized in excellent yields and very pure state. The structures of these compounds were confirmed by elemental and spectral analyses. Most of the synthesized compounds were evaluated as insecticidal agents toward Aphis gossypii insects and promising results obtained. Among all tested compounds, only 6, 7a, 7c and 15c being the most potent compounds against nymphs and adults of Aphis gossypii and their activities are nearly to that of acetamiprid as a reference. The effect of 6a compounds 7a, 7c and 15c on the Aphis digestive system from histological point of view was also included.

Functionalized pyrazole: Synthesis, Insecticide Evaluation & Molecular Docking Studies of Some New Pyrazole Derivatives against the Cotton leafworm, Spodoptera littoralis.

5-(Cyanomethyl)-3-((5,5-dimethyl-3-oxocyclohex-1-en-1-yl)amino)-1H-pyrazole-4-carbonitrile (3) is used as a key for the synthesis of arylidenes 5a-fvia its reaction with some aldehydes 4a-f. 5-[(5,5-Dimethyl-3-oxocyclohex-1-en-1-yl)amino]-3-(2-imino-2H-chromen-3-yl)-1H-pyrazole-4-carbonitrile (7) was synthesized via the reaction of compound (3) with 2-hydroxybenzaldehyde in EtOH/piperidine. The target compounds were tested against cotton leafworm larvae in their second and fourth instar. The available data demonstrated that the LC50 values for commercial phenylpyrazole were 3.37 mg/L and 4.55 mg/L for the most affected synthesized compound, 5b. The chemical structure of compound 5b has two cyano moieties, a pyrazole ring and a chlorophenyl, which may be increasing it efficiency. Evaluation of the latent effects of the examined synthesized compounds on various biological parameters, including adult longevity, pupal weight, proportion of normal, deformed pupae, adult emergency, fecundity, and egg hatchability, was done in an additional effort to slightly improve insecticidal compounds. Twelve synthesized compounds were subjected to a molecular docking analysis against glutamate-activated chloride channels. Twelve artificial compounds with the PDB ID of 4COF were subjected to a molecular docking study against the gamma-aminobutyric acid receptor (GABA).

A tolerant hydrologic technique for real-time selection of optimum QPFs from NWPMs for flood warning applications.

The most important information required to successfully issue a flood warning is the quantitative precipitation forecasts (QPFs). This is important to run subsequent rainfall-runoff simulations. A rainfall-runoff simulation derives its accuracy mainly from the accuracy of the input QPFs. The dynamically based global numerical weather prediction models (NWPMs) are strong candidate sources of QPFs. A main problem is the real-time selection of which NWPM should be used to provide the QPFs for flood warning simulations. This paper develops an automated technique to solve this problem. The technique performs real-time comparisons with measured rainfall fields using a novel 'tolerant' hydrologic approach. The 'tolerant' approach performs the comparison on the basin scale and allows for timing shifts in the forecasts. This is because QPFs can be good but only a few hours early or late. Two events are used for illustration, and the proposed real-time application in flood warning is presented. The developed technique, employing the tolerant approach, could eliminate the effects of the timing shifts and, accordingly, succeeded to select the QPFs to be used. A Python package was developed for automation. The developed technique is expected to also be useful for offline assessments of historical performances of NWPMs.

Highlights of Cardiovascular Disease Prevention Studies Presented at the 2022 American Heart Association Scientific Sessions.

PURPOSE OF REVIEW: Summarize selected late-breaking science on cardiovascular (CV) disease prevention presented at the 2022 scientific session of the American Heart Association (AHA). RECENT FINDINGS: The PROMINENT trial compared pemafibrate to a placebo in patients with type 2 diabetes mellitus (DM) and mild-to-moderate hypertriglyceridemia and high-density lipoprotein cholesterol (HDL-C)<40 mg/dL who were already on guideline-directed statin therapy. The RESPECT-EPA trial compared purified eicosapentaenoic acid (EPA) and statin therapy to statin therapy alone for secondary prevention of atherosclerotic CV disease (ASCVD). SPORT compared the efficacy of low-dose statin therapy with a placebo and six commonly used dietary supplements on lipid and inflammatory markers. Data from long-term follow-up of the FOURIER-OLE study was presented to evaluate the efficacy of very low low-density lipoprotein cholesterol (LDL-C) levels with proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors. Patient-level meta-analyses evaluated the association of statin therapy with new-onset DM and worse glycemic control. PROMPT-LIPID evaluated if automated electronic alerts to physicians with guideline-based recommendations improved the management of hyperlipidemia in patients at very high risk. NOTIFY-1 trial evaluated if notifying physicians and patients about coronary artery calcium (CAC) scores in non-ECG gated computed tomography scans led to increased prescription of statin therapy for primary ASCVD prevention. The DCP trial compared hydrochlorothiazide and chlorthalidone for blood pressure control and CV outcomes in hypertension. The CRHCP study compared the effectiveness of a village doctor for hypertension management and CV outcomes in rural areas of China. The QUARTET USA trial compared the effectiveness and safety of 4 antihypertensive medications in ultra-low doses with angiotensin-receptor blocker monotherapy. The late-breaking science presented at the 2022 scientific session of the AHA paves the way for future pragmatic trials and provides meaningful information to guide management strategies in cardiovascular disease prevention.

Health technology assessment (HTA) readiness in Uganda: stakeholder's perceptions on the potential application of HTA to support national universal health coverage efforts.

INTRODUCTION: Health technology assessment (HTA) is an area that remains less implemented in low- and lower middle-income countries. The aim of the study is to understand the perceptions of stakeholders in Uganda toward HTA and its role in decision making, in order to inform its potential implementation in the country. METHODS: The study takes a cross-sectional mixed methods approach, utilizing an adapted version of the International Decision Support Initiative questionnaire with both semi-structured and open-ended questions. We interviewed thirty key informants from different stakeholder institutions in Uganda that support policy and decision making in the health sector. RESULTS: All participants perceived HTA as an important tool for decision making. Allocative efficiency was regarded as the most important use of HTA receiving the highest average score (8.8 out of 10), followed by quality of healthcare (7.8/10), transparency (7.6/10), budget control (7.5/10), and equity (6.5/10). There was concern that some of the uses of HTA may not be achieved in reality if there was political interference during the HTA process. The study participants identified development partners as the most likely potential users of HTA (66.7 percent of participants), followed by Ministry of Health (43.3 percent). CONCLUSION: Interviewed stakeholders in Uganda viewed the role of HTA positively, suggesting that there exists a promising environment for the establishment and operationalization of HTA as a tool for decision making within the health sector. However, sustainable development and application of HTA in Uganda will require adequate capacity both to undertake HTAs and to support their use and uptake.

Design and Synthesis of Pyridine and Thiazole Derivatives as Eco-friendly Insecticidal to Control Olive Pests.

Treatment of p-tosyloxybenzaldehyde (1) with ethyl cyanoacetate afforded ethyl 2-cyano-3-(4-{[(4-methylphenyl)sulfonyl]oxy}phenyl)acrylate (2) which reacted with some active methylene derivatives under microwave irradiation in presence of ammonium acetate yielded pyridine derivatives 3-7. On the other hand, when treatment of compound 1 with thiosemicarbazide gave 4-tosyloxybenzylidenethiosemicarbazone (8), which allowed to react with some active methylene compounds, such as: ethyl bromoacetate, chloroacetonitrile or phenacyl bromide derivatives gave thiazole derivatives 9-13. The structure of all products were confirmed by elemental and spectroscopic analyses such as IR, 1 H-NMR, 13 CNMR and mass spectra. The advanced of this method are short reaction time (3-7 min), excellent yield, pure products, and low-cost processing. In the final category, the toxicological characteristics of all compounds were tested towards Saissetia oleae (Olivier, 1791) (Hemiptera: Coccidae). With respect to the LC50 values. It has been found that compound 3 possesses the highest insecticidal bioefficacy compared with other products, with values of 0.502 and 1.009 ppm, for nymphs and adults female, respectively. This study paves the way towards discovering new materials for potential use as insecticidal active agents.

Studying the association between breast cancer and renal cell carcinoma.

PURPOSE: There are case reports of patients with both primary breast cancer (BC) and renal cell carcinoma (RCC). We explore the association between these two malignancies using SEER population data and our institutional records. METHODS: We studied the association between BC and RCC in the 2000-2016 Surveillance, Epidemiology, and End Results (SEER) database. We then reviewed our hospital records of patients with both BC and RCC and collected information including personal and family history of cancers, genetic testing, and patient outcomes. RESULTS: Of the 813,477 females diagnosed with BC in the SEER database, 1914 later developed RCC. The risk of developing RCC was significantly increased within the first 6 months, 7-12 months, and 1-5 years following BC diagnosis with standardized incidence ratios (SIRs) of 5.08 (95% CI 4.62-5.57), 2.09 (95% CI 1.8-2.42), and 1.15 (95% CI 1.06-1.24), respectively. Of 56,200 females with RCC, 1087 later developed BC. The risk of developing BC following RCC was elevated within the first 6 months (SIR of 1.45 [95% CI 1.20-1.73]). For our hospital patients, 437 had both BC and RCC. 427 (97.71%) were female, and 358 (81.92%) were white, and breast cancer was diagnosed before RCC in 246 (56.3%) patients. There were 15 germline mutations in those with genetic testing. CONCLUSION: Our findings suggest that BC patients are at higher risk of developing RCC and vice versa. BC tended to precede RCC, and patients frequently had personal histories of other malignancies and a family history of cancer, particularly, BC.

Highlights of Cardiovascular Disease Prevention Studies Presented at the 2022 European Society of Cardiology Congress.

PURPOSE OF REVIEW: Focused review of select studies presented at the 2022 European Society of Cardiology Congress. RECENT FINDINGS: Included studies assessed the effects of aspirin and omega-3 fatty acid supplements on heart failure (ASCEND study); the impact of icosapent ethyl on ST-elevation MI incidence (REDUCE-IT); air temperature's effect on cardiovascular mortality (EXHAUSTION project); LVEF outcomes after troponin-guided neurohormonal blockade for the prevention of anthracycline toxicity; efficacy of routine stress testing after high-risk PCI (POST-PCI trial); influenza vaccine among patients with acute coronary syndromes (VIP-ACS trial); empagliflozin in patients with acute myocardial infarction (EMMY); effects of comprehensive imaging-based cardiovascular screening on death and cardiovascular events (DANCANVAS); safety of long-term evolocumab in patients with established atherosclerotic cardiovascular disease (FOURIER-OLE); and use of a cardiovascular polypill as a global strategy to improve secondary prevention (SECURE). Research presented at the 2022 ESC Congress highlighted many novel applications of preventative and treatment strategies in cardiology, including the effects of environmental risk factors on the incidence of cardiovascular disease.

Impact of N6-methyladenosine (m6A) modification on immunity.

N6-methyl-adenosine (m6A) is the most prevalent modification on mRNAs and long noncoding RNAs (lnRNAs) in higher eukaryotes. Modulation of m6A relies on m6A writers, erasers and readers. m6A modification contributes to diverse fundamental biological functions at the molecular, cellular, and physiological levels. The dysregulation of m6A modification has been implicated in various human diseases. Thus, m6A modification has now become a research hotspot for its potential therapeutic applications in the treatment of various cancers and diseases. The immune system is essential to provide defense against infections and cancers. This review summarizes the current knowledge about the roles of m6A in regulating immune cell functions and immune responses. Video abstract.

Sex differences in outcomes of transcatheter edge-to-edge repair with MitraClip: A meta-analysis.

BACKGROUND: Transcatheter edge-to-edge repair (TEER) with MitraClip improves outcomes among select patients with moderate-to-severe and severe mitral regurgitation; however, data regarding sex-specific differences in the outcomes among patients undergoing TEER are limited. METHODS: An electronic search of the PubMed, Embase, Central, and Web of Science databases for studies comparing sex differences in outcomes among patients undergoing TEER was performed. Summary estimates were primarily conducted using a random-effects model. RESULTS: Eleven studies with a total of 24,905 patients (45.6% women) were included. Women were older and had a lower prevalence of comorbidities, including diabetes, chronic kidney disease, and coronary artery disease. There was no difference in procedural success (odds ratio [OR]: 0.75, 95% confidence interval [CI]: 0.55-1.05) and short-term mortality (i.e., up to 30 days) between women and men (OR: 1.16, 95% CI: 0.97-1.39). Women had a higher incidence of periprocedural bleeding and stroke (OR: 1.34, 95% CI: 1.15-1.56) and (OR: 1.57, 95% CI: 1.10-2.25), respectively. At a median follow-up of 12 months, there was no difference in mortality (OR: 0.98, 95% CI: 0.89-1.09) and heart failure hospitalizations (OR: 1.07, 95% CI: 0.68-1.67). An analysis of adjusted long-term mortality showed a lower incidence of mortality among women (hazards ratio: 0.77, 95% CI: 0.67-0.88). CONCLUSIONS: Despite a lower prevalence of baseline comorbidities, women undergoing TEER with MitraClip had higher unadjusted rates of periprocedural stroke and bleeding as compared with men. There was no difference in unadjusted procedural success, short-term or long-term mortality. However, women had lower adjusted mortality on long-term follow-up. Future high-quality studies assessing sex differences in outcomes after TEER are needed to confirm these findings.

Association of hospital procedural volume with incidence and outcomes of surgical bailout in patients undergoing transcatheter aortic valve replacement.

OBJECTIVES: This study sought to examine the association of hospital procedural volume with the incidence and outcomes of surgical bailout (SB) in patients who undergo transcatheter aortic valve replacement (TAVR). BACKGROUND: SB is required for serious complications during or after TAVR. It remains unclear whether hospital experiences affect the incidence and outcomes of SB. METHODS: We retrospectively identified patients who underwent endovascular TAVR using the Nationwide Readmissions Database 2012-2017. We examined the association of annual hospital procedural volume (annual number of endovascular TAVR cases in each hospital in each year) with the incidence and in-hospital mortality of SB using multivariable logistic regressions and restricted cubic splines. RESULTS: Among 82,764 eligible patients, the incidence of SB was 0.95% (n = 789) and decreased from 2012 to 2017 (from 2.66% to 0.49%; Ptrend < 0.001), while in-hospital mortality of SB remained high over years (from 26.0% to 23.5%; Ptrend  = 0.773). Very-high-volume hospitals (≥200 cases/year), as compared with low-volume hospitals (≤49 cases/year), showed significantly a lower incidence of SB (0.49% vs. 1.81%; adjusted OR = 0.28, 95% CI = 0.21-0.38), but similar in-hospital mortality of SB (26.2% vs. 25.6%; adjusted OR = 0.88, 95% CI = 0.47-1.66). There was a significant nonlinear, inverse association of hospital volume with the incidence of SB, but not with the in-hospital mortality of SB. CONCLUSIONS: Hospitals with higher TAVR volumes have a lower risk of SB, but the in-hospital mortality after SB does not change with hospital TAVR volume. Our findings highlight the importance that physicians should always be aware of the high mortality risk of SB following TAVR regardless of hospital procedural experiences.

Incidence, treatment, and outcomes of acute myocardial infarction following transcatheter or surgical aortic valve replacement.

OBJECTIVES: This study aimed to evaluate the incidence, treatment, and outcomes of acute myocardial infarction (AMI) following transcatheter or surgical aortic valve replacement (TAVR or SAVR). BACKGROUND: Coronary artery disease is common in patients who undergo aortic valve replacement. However, little is known about differences in clinical features of post-TAVR or post-SAVR AMI. METHODS: We retrospectively identified post-TAVR or post-SAVR (including isolated and complex SAVR) patients admitted with AMI using the Nationwide Readmissions Database 2012-2017. Incidence, invasive strategy (coronary angiography or revascularization), and in-hospital outcomes were compared between post-TAVR and post-SAVR AMIs. RESULTS: The incidence of 180-day AMI was higher post-TAVR than post-SAVR (1.59% vs. 0.72%; p < 0.001). Post-TAVR AMI patients (n = 1315), compared with post-SAVR AMI patients (n = 1344), were older, had more comorbidities and more frequent non-ST-elevation AMI (NSTEMI: 86.6% vs. 78.0%; p < 0.001). After propensity-score matching, there was no significant difference in in-hospital mortality between post-TAVR and post-SAVR AMIs (14.7% vs. 16.1%; p = 0.531), but the mortality was high in both groups, particularly in ST-elevation AMI (STEMI: 38.8% vs. 29.2%; p = 0.153). Invasive strategy was used less frequently for post-TAVR AMI than post-SAVR AMI (25.6% vs. 38.3%; p < 0.001). Invasive strategy was associated with lower mortality in both post-TAVR (adjusted odds ratio = 0.40; 95% confidence interval = [0.24-0.66]) and post-SAVR groups (0.60 [0.41-0.88]). CONCLUSIONS: AMI, albeit uncommon, was more frequent post-TAVR than post-SAVR. Patients commonly presented with NSTEMI, but the mortality of STEMI was markedly high. Further studies are needed to understand why a substantial percentage of patients do not receive invasive coronary treatment, particularly after TAVR, despite seemingly better outcomes with invasive strategy.

Two-year outcomes after transcatheter aortic valve-in-valve implantation in degenerated surgical valves.

BACKGROUND: Transcatheter aortic valve-in-valve implantation (ViV-TAVI) has emerged in recent years as a safe alternative to redo surgery in high-risk patients. Although early results are encouraging, data beyond short-term outcomes are lacking. Herein, we aimed to assess the 2-year outcomes after ViV-TAVI. METHODS: Patients undergoing ViV-TAVI for degenerated surgical valves between 2013 and 2019 at the Cleveland Clinic were reviewed. The coprimary endpoints were all-cause mortality and congestive heart failure (CHF) hospitalizations. We used time-to-event analyses to assess the primary outcomes. Further, we measured the changes in transvalvular gradients and the incidence of structural valve deterioration (SVD). RESULTS: One hundred and eighty-eight patients were studied (mean age = 76 years; 65% males). At 2 years of follow-up, all-cause mortality and CHF hospitalizations occurred in 15 (8%) and 28 (14.9%) patients, respectively. On multivariable analysis, the postprocedural length of stay was a significant predictor for both all-cause mortality (hazard ratio [HR] = 1.1; 95% confidence interval [CI]: 1.01, 1.19) and CHF hospitalization (HR = 1.16; 95% CI: 1.07, 1.27). However, the internal diameter of the surgical valve was not associated with significant differences in both primary endpoints. For hemodynamic outcomes, nine patients (4.8%) developed SVD. The mean and peak transvalvular pressure gradients remained stable over the follow-up period. CONCLUSION: ViV-TAVI for degenerated surgical valves was associated with favorable 2-year clinical and hemodynamic outcomes. Further studies are needed to better understand the role of ViV-TAVI as a treatment option in the life management of aortic valve disease.