National Trends of Structural Heart Disease Interventions from 2016 to 2020 in the United States and the Associated Impact of COVID-19 Pandemic.

BACKGROUND: The Coronavirus Disease-2019 (COVID-19) pandemic placed an enormous strain on the healthcare system. Data on the impact of COVID-19 on the utilization and outcomes of structural heart disease (SHD) interventions in the United States are scarce. METHODS AND RESULTS: The National Inpatient Sample from 2016 to 2020 was queried to identify adult admissions for transcatheter aortic valve replacement (TAVR), left atrial appendage occlusion (LAAO), and transcatheter end-to-end repair (TEER). The primary outcome was temporal trends of procedure utilization rate per 100,000 admissions over quarters from 2016 to 2020. The secondary outcomes were adjusted rates of in-hospital mortality, major complications, and length of stay (LOS). Among 434,630 weighted admissions (TAVR: 305,550; LAAO: 89,300; TEER: 40,160), 95,010 admissions (22%) were during the COVID-19 era. There was a decline during the second quarter of 2020 followed by an increase to the pre pandemic levels (TAVR: 220 to 253, LAAO: 57 to 109, and TEER:31 to 36 per 100,000 admissions, Ptrend<0.001). There were no differences in the mortality or major complication rates. Median LOS has decreased in TAVR (4 days to 1 day) and in TEER (3 days to 1 day) but remained stable in LAAO (1 day). CONCLUSION: This nationwide analysis showed that SHD interventions decreased during the early waves of COVID-19 pandemic. There was a significant reduction in hospital LOS without differences in in-hospital mortality or complication rates during the pandemic. These data suggest that hospitals adapted to the unprecedent challenges during the pandemic to provide advanced cardiac care to patients.

Supply Chain Disruptions During COVID-19 Pandemic Uncover Differences in Keratinocyte Culture Media.

Various culture media are used to propagate keratinocytes (KCs) in vitro. The COVID-19 pandemic resulted in supply chain shortages necessitating substitutions to standard laboratory protocols, which resulted in many laboratories having to use culture media different from those they typically use. We screened available media on the KC line N/TERT2G and found that biological responses varied considerably across three culture media: KC serum-free media, KC growth medium 2, and defined media. We observed qualitative and quantitative differences in proliferation; KCs cultured in defined media had significantly lower proliferative capacity. KC differentiation was assessed by western blot for CLDN1, occludin, cytokeratin-10, and loricrin. Elevated expression of differentiation markers was observed in cells cultured in either KC growth medium 2 or defined media compared with those in cells cultured in KC serum-free media. KC barrier function was measured by transepithelial electrical resistance. KCs cultured in KC growth medium 2 and defined media developed significantly higher transepithelial electrical resistance than those cultured in KC serum-free media, and when treated with IL-4 and IL-13 or IL-17A, we observed variable responses. H&E staining on day 5 -post-differentiation showed greater epithelial thickness in KCs cultured in defined media and KC growth medium 2 than in those cultured in KC serum-free media. These findings show that the choice of culture media impacts the biological response of KCs in a manner that persists through differentiation in the same media.

Iota-carrageenan extracted from red algae is a potent inhibitor of SARS-CoV-2 infection in reconstituted human airway epithelia.

Iota-carrageenan (IC) nasal spray, a medical device approved for treating respiratory viral infections, has previously been shown to inhibit the ability of a variety of respiratory viruses, including severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), to enter and replicate in the cell by interfering with the virus binding to the cell surface. The aim of this study was to further investigate the efficacy and safety of IC in SARS-CoV-2 infection in advanced in vitro models of the human respiratory epithelium, the primary target and entry port for SARS-CoV-2. We extended the in vitro safety assessment of nebulized IC in a 3-dimensional model of reconstituted human bronchial epithelium, and we demonstrated the efficacy of IC in protecting reconstituted nasal epithelium against viral infection and replication of a patient-derived SARS-CoV-2 strain. The results obtained from these two advanced models of human respiratory tract epithelia confirm previous findings from in vitro SARS-CoV-2 infection assays and demonstrate that topically applied IC can effectively prevent SARS-CoV-2 infection and replication. Moreover, the absence of toxicity and functional and structural impairment of the mucociliary epithelium demonstrates that the nebulized IC is well tolerated.

Synthesis, Physicochemical Characterization, In Vitro 2D/3D Human Cell Culture, and In Vitro Aerosol Dispersion Performance of Advanced Spray Dried and Co-Spray Dried Angiotensin (1-7) Peptide and PNA5 with Trehalose as Microparticles/Nanoparticles for Targeted Respiratory Delivery as Dry Powder Inhalers.

The peptide hormone Angiotensin (1-7), Ang (1-7) or (Asp-Arg-Val-Tyr-Ile-His-Pro), is an essential component of the renin-angiotensin system (RAS) peripherally and is an agonist of the Mas receptor centrally. Activation of this receptor in the CNS stimulates various biological activities that make the Ang (1-7)/MAS axis a novel therapeutic approach for the treatment of many diseases. The related O-linked glycopeptide, Asp-Arg-Val-Tyr-Ile-His-Ser-(O-ß-D-Glc)-amide (PNA5), is a biousian revision of the native peptide hormone Ang (1-7) and shows enhanced stability in vivo and greater levels of brain penetration. We have synthesized the native Ang (1-7) peptide and the glycopeptide, PNA5, and have formulated them for targeted respiratory delivery as inhalable dry powders. Solid phase peptide synthesis (SPPS) successfully produced Ang (1-7) and PNA5. Measurements of solubility and lipophilicity of raw Ang (1-7) and raw PNA5 using experimental and computational approaches confirmed that both the peptide and glycopeptide have high-water solubility and are amphipathic. Advanced organic solution spray drying was used to engineer the particles and produce spray-dried powders (SD) of both the peptide and the glycopeptide, as well as co-spray-dried powders (co-SD) with the non-reducing sugar and pharmaceutical excipient, trehalose. The native peptide, glycopeptide, SD, and co-SD powders were comprehensively characterized, and exhibited distinct glass transitions (Tg) consistent with the amorphous glassy state formation with Tgs that are compatible with use in vivo. The homogeneous particles displayed small sizes in the nanometer size range and low residual water content in the solid-state. Excellent aerosol dispersion performance with a human DPI device was demonstrated. In vitro human cell viability assays showed that Ang (1-7) and PNA5 are biocompatible and safe for different human respiratory and brain cells.

Modulating the Barrier Function of Human Alveolar Epithelial (hAELVi) Cell Monolayers as a Model of Inflammation.

The incidence of inflammatory lung diseases such as acute respiratory distress syndrome (ARDS) remains an important problem, particularly in the present time with the Covid-19 pandemic. However, an adequate in vitro test system to monitor the barrier function of the alveolar epithelium during inflammation and for assessing anti-inflammatory drugs is urgently needed. Therefore, we treated human Alveolar Epithelial Lentivirus-immortalised cells (hAELVi cells) with the pro-inflammatory cytokines TNF-α (25 ng/ml) and IFN-γ (30 ng/ml), in the presence or absence of hydrocortisone (HC). While TNF-α and IFN-γ are known to reduce epithelial barrier properties, HC could be expected to protect the barrier function and result in an anti-inflammatory effect. We investigated the impact of anti-inflammatory/inflammatory treatment on transepithelial electrical resistance (TEER) and the apparent permeability coefficient (Papp) of the low permeability marker sodium fluorescein (NaFlu). After incubating hAELVi cells for 48 hours with a combination of TNF-α and IFN-γ, there was a significant decrease in TEER and a significant increase in the Papp. The presence of HC maintained the TEER values and barrier properties, so that no significant Papp change was observed. By using hAELVi cells to study anti-inflammatory drugs in vitro, the need for animal experiments could be reduced and pulmonary drug development accelerated.