Implications of the Centers for Medicare and Medicaid Services decision to expand indications for carotid artery stenting.

OBJECTIVE: On October 11, 2023, the Centers for Medicare and Medicaid Services (CMS) expanded the indications for carotid artery stenting (CAS) to include patients with ≥50% symptomatic or ≥70% asymptomatic carotid stenosis. The aim of this article was to investigate the implications of this decision. METHODS: The reasons behind the increased coverage for CAS are analyzed and discussed, as well as the various Societies supporting or opposing the expansion of indications for CAS. RESULTS: The benefits associated with expanding CAS indications include providing an additional therapeutic option to patients and enabling individualization of treatment according to patient-specific characteristics. The drawbacks of expanding CAS indications include a possible bias in decision-making and an increase in inappropriate CAS procedures. CONCLUSIONS: The purpose of the CMS recommendation to expand indications for CAS is to improve the available therapeutic options for patients. Hopefully this decision will not be misinterpreted and will be used to improve patient options and patient outcomes.

Clinical outcomes of transcarotid artery revascularization vs carotid endarterectomy from a large single-center experience.

BACKGROUND: Transcarotid artery revascularization (TCAR) has been practiced as an alternative for both carotid endarterectomy (CEA) and transfemoral carotid artery stenting, specifically in high-risk patients. More recently, the Centers for Medicare and Medicaid Services expanded coverage for TCAR in standard surgical risk patients if done within the Society for Vascular Surgery Vascular Quality Initiative TCAR surveillance project. A few registry studies (primarily from the Society for Vascular Surgery Vascular Quality Initiative) compared the early and up to 1-year outcomes of TCAR vs CEA or transfemoral carotid artery stenting. There is no large single-center study that reported late clinical outcomes. The present study compares intermediate clinical outcomes of TCAR vs CEA. METHODS: This study retrospectively analyzed collected data from TCAR surveillance project patients enrolled in our institution and compare it with CEA patients done by the same providers at the same time period. The primary outcome was combined perioperative stroke/death and late stroke/death. Secondary outcomes included combined stroke, death, and myocardial infarction, cranial nerve injury (CNI), and bleeding. Propensity matching was done to analyze outcome. Kaplan-Meier analysis was used to estimate freedom from stroke, stroke/death, and ≥50% and ≥80% restenosis. RESULTS: We analyzed 646 procedures (637 patients) (404 CEA, 242 TCAR). There was no significant difference in the indications for carotid intervention. However, TCAR patients had more high-risk criteria, including hypertension, coronary artery disease, congestive heart failure, and renal failure. There was no significant differences between CEA vs TCAR in 30-day perioperative stroke (1% vs 2%), stroke/death rate (1% vs 3%; P = .0849), or major hematomas (2% vs 2%). The rate of CNI was significantly different (5% for CEA vs 1% for TCAR; P = .0138). At late follow-up (2 years), the rate of stroke was 1% vs 4% (P = .0273), stroke/death 8% vs 15% (P = .008), ≥80 % restenosis 0.5% vs 3% (P = .0139) for CEA patients vs TCAR patients, respectively. After matching 242 CEAs and 242 TCARs, the perioperative stroke rate was 1% for CEA vs 2% for TCAR (P = .5037), the stroke/death rate was 2% vs 3% (P = .2423), and the CNI rate was 3% vs 1% (P = .127). At late follow-up, rates of stroke were 1% for CEA vs 4% for TCAR (P = .0615) and stroke/death were 8% vs 15% (P = .0345). The rate of ≥80% restenosis was 0.9% for CEA vs 3% for TCAR (P = .099). The rates of freedom from stroke at 6, 12, 18, and 24 months for CEA vs TCAR were 99%, 99%, 99%, and 99% vs 97%, 95%, 93% and 93%, respectively (P = .0806); stroke/death were 94%, 90%, 87%, and 86% vs 93%, 87%, 76%, and 75%, respectively (P = .0529); and ≥80% restenosis were 100%, 99%, 98%, and 98% vs 97%, 95%, 93%, and 93%, respectively (P = .1132). CONCLUSIONS: In a propensity-matched analysis, both CEA and TCAR have similar perioperative clinical outcomes. However, CEA was superior to TCAR for the rates of late stroke/death and had a somewhat lower rate of ≥80% restenosis at 2 years, but this difference was not statistically significant.

Recent advances and controversial issues in the optimal management of asymptomatic carotid stenosis.

OBJECTIVE: The optimal management of patients with asymptomatic carotid stenosis (AsxCS) is enduringly controversial. We updated our 2021 Expert Review and Position Statement, focusing on recent advances in the diagnosis and management of patients with AsxCS. METHODS: A systematic review of the literature was performed up to August 1, 2023, using PubMed/PubMed Central, EMBASE and Scopus. The following keywords were used in various combinations: "asymptomatic carotid stenosis," "carotid endarterectomy" (CEA), "carotid artery stenting" (CAS), and "transcarotid artery revascularization" (TCAR). Areas covered included (i) improvements in best medical treatment (BMT) for patients with AsxCS and declining stroke risk, (ii) technological advances in surgical/endovascular skills/techniques and outcomes, (iii) risk factors, clinical/imaging characteristics and risk prediction models for the identification of high-risk AsxCS patient subgroups, and (iv) the association between cognitive dysfunction and AsxCS. RESULTS: BMT is essential for all patients with AsxCS, regardless of whether they will eventually be offered CEA, CAS, or TCAR. Specific patient subgroups at high risk for stroke despite BMT should be considered for a carotid revascularization procedure. These patients include those with severe (≥80%) AsxCS, transcranial Doppler-detected microemboli, plaque echolucency on Duplex ultrasound examination, silent infarcts on brain computed tomography or magnetic resonance angiography scans, decreased cerebrovascular reserve, increased size of juxtaluminal hypoechoic area, AsxCS progression, carotid plaque ulceration, and intraplaque hemorrhage. Treatment of patients with AsxCS should be individualized, taking into consideration individual patient preferences and needs, clinical and imaging characteristics, and cultural, ethnic, and social factors. Solid evidence supporting or refuting an association between AsxCS and cognitive dysfunction is lacking. CONCLUSIONS: The optimal management of patients with AsxCS should include BMT for all individuals and a prophylactic carotid revascularization procedure (CEA, CAS, or TCAR) for some asymptomatic patient subgroups, additionally taking into consideration individual patient needs and preference, clinical and imaging characteristics, social and cultural factors, and the available stroke risk prediction models. Future studies should investigate the association between AsxCS with cognitive function and the role of carotid revascularization procedures in the progression or reversal of cognitive dysfunction.

Small-Angle Scattering Indicates Equilibrium Instead of Metastable Capillary Condensation in SBA-15 Mesoporous Silica.

Questions about the origin of the adsorption/desorption hysteresis in mesoporous materials are as old as sorption experiments themselves. The historical conception that underlines most existing methods to extract pore size distributions from sorption data assumes that adsorption is a metastable process and that desorption takes place at thermodynamic equilibrium. In this work, we measure nitrogen and argon sorption on a series of 14 SBA-15 ordered mesoporous silicas and use small-angle X-ray scattering to independently determine their pore sizes. We find that capillary condensation systematically occurs close to thermodynamic equilibrium according to a Derjaguin-Broekhoff-de Boer calculation. Our analysis suggests that many earlier works have significantly underestimated the actual pore size in SBA-15 materials. It also highlights the critical role of the reference isotherm used to calibrate the fluid-solid interaction in the models.

Baseline azithromycin resistance in the gut microbiota of preterm born infants.

BACKGROUND: Macrolides, including azithromycin, are increasingly used in preterm-born infants to treat Ureaplasma infections. The baseline carriage of macrolide resistance genes in the preterm stool microbiota is unknown. OBJECTIVES: Identify carriage of azithromycin resistant bacteria and the incidence of macrolide resistant genes. METHODS: Azithromycin resistant bacteria were isolated from serial stool samples obtained from preterm infants (≤32 weeks' gestation) by culturing aerobically/anaerobically, in the presence/absence of azithromycin. Using quantitative PCR, we targeted 6 common macrolide resistance genes (erm(A), erm(B), erm(C), erm(F), mef(A/E), msr(A)) in DNA extracted from selected bacteria resistant to azithromycin. RESULTS: From 89 stool samples from 37 preterm-born infants, 93.3% showed bacterial growth in aerobic or anaerobic conditions. From the 280 azithromycin resistant isolates that were identified, Staphylococcus (75%) and Enterococcus (15%) species dominated. Macrolide resistance genes were identified in 91% of resistant isolates: commonest were erm(C) (46% of isolates) and msr(A) (40%). Multiple macrolide resistance genes were identified in 18% of isolates. CONCLUSION: Macrolide resistance is common in the gut microbiota of preterm-born infants early in life, most likely acquired from exposure to the maternal microbiota. It will be important to assess modulation of macrolide resistance, if macrolide treatment becomes routine in the management of preterm infants. IMPACT STATEMENT: Azithromycin resistance is present in the stool microbiota in the first month of life in preterm infants 91% of azithromycin resistant bacteria carried at least one of 6 common macrolide resistant genes Increasing use of macrolides in the preterm population makes this an important area of study.

Measurement of the major ignored burden of multiple myeloma, pernicious anaemia and of other haematological conditions on partners and family members: A cross-sectional study.

BACKGROUND: Having a haematological condition can adversely affect the quality of life (QoL) of family members/partners of patients. It is important to measure this often ignored burden in order to implement appropriate supportive interventions. OBJECTIVE: To measure current impact of haematological conditions on the QoL of family members/partners of patients, using the Family Reported Outcome Measure-16 (FROM-16). METHODS: A cross-sectional study, recruited online through patient support groups, involved UK family members/partners of people with haematological conditions completing the FROM-16. RESULTS: 183 family members/partners (mean age = 60.5 years, SD = 13.2; females = 62.8%) of patients (mean age = 64.1, SD = 12.8; females = 46.4%) with 12 haematological conditions completed the FROM-16. The FROM-16 mean total score was 14.0 (SD = 7.2), meaning 'a moderate effect on QoL'. The mean FROM-16 scores of family members of people with multiple myeloma (mean = 15.8, SD = 6.3, n = 99) and other haematological malignancies (mean = 13.9, SD = 7.8, n = 29) were higher than of people with pernicious anaemia (mean = 10.7, SD = 7.5, n = 47) and other non-malignant conditions (mean = 11, SD = 7.4, n = 56, p < .01). Over one third (36.1%, n = 183) of family members experienced a 'very large effect' (FROM-16 score>16) on their quality of life. CONCLUSIONS: Haematological conditions, in particular those of malignant type, impact the QoL of family members/partners of patients. Healthcare professionals can now, using FROM-16, identify those most affected and should consider how to provide appropriate holistic support within routine practice.

Dexamethasone versus methylprednisolone for multiple organ dysfunction in COVID-19 critically ill patients: a multicenter propensity score matching study.

BACKGROUND: Dexamethasone usually recommended for patients with severe coronavirus disease 2019 (COVID-19) to reduce short-term mortality. However, it is uncertain if another corticosteroid, such as methylprednisolone, may be utilized to obtain better clinical outcome. This study assessed dexamethasone's clinical and safety outcomes compared to methylprednisolone. METHODS: A multicenter, retrospective cohort study was conducted between March 01, 2020, and July 31, 2021. It included adult COVID-19 patients who were initiated on either dexamethasone or methylprednisolone therapy within 24 h of intensive care unit (ICU) admission. The primary outcome was the progression of multiple organ dysfunction score (MODS) on day three of ICU admission. Propensity score (PS) matching was used (1:3 ratio) based on the patient's age and MODS within 24 h of ICU admission. RESULTS: After Propensity Score (PS) matching, 264 patients were included; 198 received dexamethasone, while 66 patients received methylprednisolone within 24 h of ICU admission. In regression analysis, patients who received methylprednisolone had a higher MODS on day three of ICU admission than those who received dexamethasone (beta coefficient: 0.17 (95% CI 0.02, 0.32), P = 0.03). Moreover, hospital-acquired infection was higher in the methylprednisolone group (OR 2.17, 95% CI 1.01, 4.66; p = 0.04). On the other hand, the 30-day and the in-hospital mortality were not statistically significant different between the two groups. CONCLUSION: Dexamethasone showed a lower MODS on day three of ICU admission compared to methylprednisolone, with no statistically significant difference in mortality.

Superconducting NbC nanoparticles synthesized by laser ablation in a liquid.

Niobium carbide (NbC) is a high-field type II superconductor with a critical temperature (TC) of 11.1 K, slightly exceeding that of pure Nb (TC = 9 K). The reduction of NbC to the nanoparticle scale leads to significant changes in its critical field and/or the superconducting temperature. This study presents findings on superconducting NbC nanoparticles with TC ≃ 10 K produced through laser ablation in acetone, where different conditions of laser fluence and centrifugation were studied. Analysis by X-ray diffraction confirmed the cubic NbC phase, while electron microscopy images displayed approximately 8 nm spherical particles, showing no noticeable size variation with laser fluence. Additionally, magnetization curves exhibited both magnetic and superconducting loops for all investigated samples. A decrease in laser fluence resulted in the suppression of diamagnetic behavior below TC. Furthermore, all samples exhibited a weak electron spin resonance (ESR) Curie-like signal at g ≃ 2.0, probably linked to localized defects on the particle's surface. The simultaneous existence of superconductivity and magnetism in nanoparticles has recently garnered significant research attention. This intricate scenario and unique properties arise from the significant enhancement of the surface-to-volume ratio in these superconducting NbC nanoparticles, emphasizing the need for further investigation to unveil novel material properties and shed new light on our comprehension of the superconducting phenomenon in this particular morphology.

Mapping of Family Reported Outcome Measure (FROM-16) scores to EQ-5D: algorithm to calculate utility values.

OBJECTIVE: Although decision scientists and health economists encourage inclusion of family member/informal carer utility in health economic evaluation, there is a lack of suitable utility measures comparable to patient utility measures such those based on the EQ-5D. This study aims to predict EQ-5D-3L utility values from Family Reported Outcome Measure (FROM-16) scores, to allow the use of FROM-16 data in health economic evaluation when EQ-5D data is not available. METHODS: Data from 4228 family members/partners of patients recruited to an online cross-sectional study through 58 UK-based patient support groups, three research support platforms and Welsh social services departments were randomly divided five times into two groups, to derive and test a mapping model. Split-half cross-validation was employed, resulting in a total of ten multinomial logistic regression models. The Monte Carlo simulation procedure was used to generate predicted EQ-5D-3L responses, and utility scores were calculated and compared against observed values. Mean error and mean absolute error were calculated for all ten validation models. The final model algorithm was derived using the entire sample. RESULTS: The model was highly predictive, and its repeated fitting using multinomial logistic regression demonstrated a stable model. The mean differences between predicted and observed health utility estimates ranged from 0.005 to 0.029 across the ten modelling exercises, with an average overall difference of 0.015 (a 2.2% overestimate, not of clinical importance). CONCLUSIONS: The algorithm developed will enable researchers and decision scientists to calculate EQ-5D health utility estimates from FROM-16 scores, thus allowing the inclusion of the family impact of disease in health economic evaluation of medical interventions when EQ-5D data is not available.

In silico assessment of biocompatibility and toxicity: molecular docking and dynamics simulation of PMMA-based dental materials for interim prosthetic restorations.

AIM: This study aimed to comprehensively assess the biocompatibility and toxicity profiles of poly(methyl methacrylate) (PMMA) and its monomeric unit, methyl methacrylate (MMA), crucial components in dental materials for interim prosthetic restorations. METHODOLOGY: Molecular docking was employed to predict the binding affinities, energetics, and steric features of MMA and PMMA with selected receptors involved in bone metabolism and tissue development, including RANKL, Fibronectin, BMP9, NOTCH2, and other related receptors. The HADDOCK standalone version was utilized for docking calculations, employing a Lamarckian genetic algorithm to explore the conformational space of ligand-receptor interactions. Furthermore, molecular dynamics (MD) simulations over 100 nanoseconds were conducted using the GROMACS package to evaluate dynamic actions and structural stability. The LigandScout was utilized for pharmacophore modeling, which employs a shape-based screening approach to identify potential ligand binding sites on protein targets. RESULTS: The molecular docking studies elucidated promising interactions between PMMA and MMA with key biomolecular targets relevant to dental applications. MD simulation results provided strong evidence supporting the structural stability of PMMA complexes over time. Pharmacophore modeling highlighted the significance of carbonyl and hydroxyl groups as pharmacophoric features, indicating compounds with favorable biocompatibility profiles. CONCLUSION: This study underscores the potential of PMMA in dental applications, emphasizing its structural stability, molecular interactions, and safety considerations. These findings lay a foundation for future advancements in dental biomaterials, guiding the design and optimization of materials for enhanced biocompatibility. Future directions include experimental validation of computational findings and the development of PMMA-based dental materials with improved biocompatibility and clinical performance.

Properties of a novel composite elastomeric polymer vinyl polyether siloxane in comparison to its parent materials: a systemic review and meta-analysis.

BACKGROUND: The effectiveness of newly developed elastomeric polymer hybrid siloxane (PVES), which combines the properties of polyethylene (PE) and polyvinyl siloxane (PVS) elastomers, has been a subject of interest in recent studies. This study aimed to assess the physical properties of hybrid PVES materials by analyzing existing data from recent studies on this topic. METHODS: A systematic literature search was conducted to retrieve peer-reviewed articles published up to February 5, 2023. The population, intervention, comparison, and pertinent outcomes were specified under the PICO framework. The primary data analysis was performed in Microsoft Excel, while statistical analysis used Meta-Essentials. RESULTS: Of the 1152 articles assessed, 14 met the inclusion criteria. The meta-analysis of the selected studies indicated that polyether (PE) and polyvinyl siloxane (PVS) were highly correlated (two-tailed p-values of 0.000 and 0.001, respectively) with the improved tensile strength of vinyl polyether siloxane (PVES) with a significantly positive effect size. Similarly, the hydrophilic characteristics of PVES were significantly improved compared to those of PE and PVS. PE was a significant contributor to the hydrophilic characteristics of PVES, with a two-tailed p-value of 0.000. The effect size was highly positive for hydrophilicity but showed high heterogeneity. It was also observed that the dimensional accuracy of PVES was comparable to those of PE and PVS, with no statistically significant differences among the three materials. CONCLUSIONS: PVES showed promising features, with improved tensile strength and hydrophilic characteristics compared to those of PE and PVS.

The flexural strength of 3D-printed provisional restorations fabricated with different resins: a systematic review and meta-analysis.

BACKGROUND: Three-dimensional (3D) printing technology has revolutionized dentistry, particularly in fabricating provisional restorations. This systematic review and meta-analysis aimed to thoroughly evaluate the flexural strength of provisional restorations produced using 3D printing while considering the impact of different resin materials. METHODS: A systematic search was conducted across major databases (ScienceDirect, PubMed, Web of Sciences, Google Scholar, and Scopus) to identify relevant studies published to date. The inclusion criteria included studies evaluating the flexural strength of 3D-printed provisional restorations using different resins. Data extraction and quality assessment were performed using the CONSORT scale, and a meta-analysis was conducted using RevMan 5.4 to pool results. RESULTS: Of the 1914 initially identified research articles, only 13, published between January 2016 and November 2023, were included after screening. Notably, Digital Light Processing (DLP) has emerged as the predominant 3D printing technique, while stereolithography (SLA), Fused Deposition Modeling (FDM), and mono-liquid crystal displays (LCD) have also been recognized. Various printed resins have been utilized in different techniques, including acrylic, composite resins, and methacrylate oligomer-based materials. Regarding flexural strength, polymerization played a pivotal role for resins used in 3D or conventional/milled resins, revealing significant variations in the study. For instance, SLA-3D and DLP Acrylate photopolymers displayed distinct strengths, along with DLP bisacrylic, milled PMMA, and conventional PMMA. The subsequent meta-analysis indicated a significant difference in flexure strength, with a pooled Mean Difference (MD) of - 1.25 (95% CI - 16.98 - 14.47; P < 0.00001) and a high I2 value of 99%, highlighting substantial heterogeneity among the studies. CONCLUSIONS: This study provides a comprehensive overview of the flexural strength of 3D-printed provisional restorations fabricated using different resins. However, further research is recommended to explore additional factors influencing flexural strength and refine the recommendations for enhancing the performance of 3D-printed provisional restorations in clinical applications.

Evaluation of the effect of chemical disinfection and ultraviolet disinfection on the dimensional stability of polyether impression material: an in-vitro study.

BACKGROUND: Various methods, chemical and physical, disinfect dental impressions. Common chemicals include 1% Sodium Hypochlorite and 2% glutaraldehyde, while UV radiation is a prevalent physical method. Few studies compare their effects on dimensional stability in polyether impressions. This study aims to assess such stability using different disinfection methods. Therefore, this study was planned to evaluate the dimensional stability of polyether impression material using different disinfection methods. METHODS: This in vitro study compared the effects of chemical disinfectants (1% Sodium Hypochlorite and 2% glutaraldehyde) and UV irradiation on the dimensional stability of polyether impression material. Groups A, B, C, and D, each with ten samples (N = 10), were studied. Group A was untreated (control). Group B was treated with 2% glutaraldehyde for 20 min, Group C with 1% Sodium Hypochlorite for 20 min, and Group D with UV rays for 20 min. A pilot milling machine drill was used to make four parallel holes labeled A, B, C, and D in the anterior and premolar regions from right to left. After sequential drilling, four implant analogs were positioned using a surveyor for accuracy. Ten open-tray polyether impressions were made and treated as described in the groups, followed by pouring the corresponding casts. Distortion values for each disinfection method were measured using a coordinate measuring machine capable of recording on the X- and Y-axes. RESULTS: A comprehensive analysis was conducted using the one-way ANOVA test for distinct groups labeled A, B, C, and D, revealing significant differences in the mean distances for X1, X2, X4, X5, and X6 among the groups, with p-values ranging from 0.001 to 0.000. However, no significant differences were observed in X3. Notably, mean distances for the Y variables exhibited substantial differences among the groups, emphasizing parameter variations, with p-values ranging from 0.000 to 0.033. The results compared the four groups using the one-way ANOVA test, revealing statistically significant distance differences for most X and Y variables, except for X3 and Y4. Similarly, post-hoc Tukey's tests provided specific pairwise comparisons, underlining the distinctions between group C and the others in the mean and deviation distances for various variables on both the X- and Y-axes. CONCLUSIONS: This study found that disinfection with 1% sodium hypochlorite or UV rays for 20 min maintained dimensional stability in polyether impressions.

Dental biomaterials redefined: molecular docking and dynamics-driven dental resin composite optimization.

BACKGROUND: Dental resin-based composites are widely recognized for their aesthetic appeal and adhesive properties, which make them integral to modern restorative dentistry. Despite their advantages, adhesion and biomechanical performance challenges persist, necessitating innovative strategies for improvement. This study addressed the challenges associated with adhesion and biomechanical properties in dental resin-based composites by employing molecular docking and dynamics simulation. METHODS: Molecular docking assesses the binding energies and provides valuable insights into the interactions between monomers, fillers, and coupling agents. This investigation prioritizes SiO2 and TRIS, considering their consistent influence. Molecular dynamics simulations, executed with the Forcite module and COMPASS II force field, extend the analysis to the mechanical properties of dental composite complexes. The simulations encompassed energy minimization, controlled NVT and NPT ensemble simulations, and equilibration stages. Notably, the molecular dynamics simulations spanned a duration of 50 ns. RESULTS: SiO2 and TRIS consistently emerged as influential components, showcasing their versatility in promoting solid interactions. A correlation matrix underscores the significant roles of van der Waals and desolvation energies in determining the overall binding energy. Molecular dynamics simulations provide in-depth insights into the mechanical properties of dental composite complexes. HEMA-SiO2-TRIS excelled in stiffness, BisGMA-SiO2-TRIS prevailed in terms of flexural strength, and EBPADMA-SiO2-TRIS offered a balanced combination of mechanical properties. CONCLUSION: These findings provide valuable insights into optimizing dental composites tailored to diverse clinical requirements. While EBPADMA-SiO2-TRIS demonstrates distinct strengths, this study emphasizes the need for further research. Future investigations should validate the computational findings experimentally and assess the material's response to dynamic environmental factors.

Ketamine-based Sedation Use in Mechanically Ventilated Critically Ill Patients with COVID-19: A Multicenter Cohort Study.

Backgrounds: Ketamine possesses analgesia, anti-inflammation, anticonvulsant, and neuroprotection properties. However, the evidence that supports its use in mechanically ventilated critically ill patients with COVID-19 is insufficient. The study's goal was to assess ketamine's effectiveness and safety in critically ill, mechanically ventilated (MV) patients with COVID-19. Methods: Adult critically ill patients with COVID-19 were included in a multicenter retrospective-prospective cohort study. Patients admitted between March 1, 2020, and July 31, 2021, to five ICUs in Saudi Arabia were included. Eligible patients who required MV within 24 hours of ICU admission were divided into two sub-cohort groups based on their use of ketamine (Control vs. Ketamine). The primary outcome was the length of stay (LOS) in the hospital. P/F ratio differences, lactic acid normalization, MV duration, and mortality were considered secondary outcomes. Propensity score (PS) matching was used (1:2 ratio) based on the selected criteria. Results: In total, 1,130 patients met the eligibility criteria. Among these, 1036 patients (91.7 %) were in the control group, whereas 94 patients (8.3 %) received ketamine. The total number of patients after PS matching, was 264 patients, including 88 patients (33.3 %) who received ketamine. The ketamine group's LOS was significantly lower (beta coefficient (95 % CI): -0.26 (-0.45, -0.07), P = 0.008). Furthermore, the PaO2/FiO2 ratio significantly improved 24 hours after the start of ketamine treatment compared to the pre-treatment period (6 hours) (124.9 (92.1, 184.5) vs. 106 (73.1, 129.3; P = 0.002). Additionally, the ketamine group had a substantially shorter mean time for lactic acid normalization (beta coefficient (95 % CI): -1.55 (-2.42, -0.69), P 0.01). However, there were no significant differences in the duration of MV or mortality. Conclusions: Ketamine-based sedation was associated with lower hospital LOS and faster lactic acid normalization but no mortality benefits in critically ill patients with COVID-19. Thus, larger prospective studies are recommended to assess the safety and effectiveness of ketamine as a sedative in critically ill adult patients.

Metagenomic Sequencing of Monkeypox Virus, Northern Mexico.

Monkeypox virus (MPXV) has gained interest because of a multicountry outbreak of mpox (formerly monkeypox) cases with no epidemiologic link to MPXV-endemic regions. We sequenced the complete genome of MPXV isolated from a patient in northern Mexico. Phylogenetic analysis grouped the virus with isolates from Germany.

COSMIC Cancer Gene Census 3D database: understanding the impacts of mutations on cancer targets.

Mutations in hallmark genes are believed to be the main drivers of cancer progression. These mutations are reported in the Catalogue of Somatic Mutations in Cancer (COSMIC). Structural appreciation of where these mutations appear, in protein-protein interfaces, active sites or deoxyribonucleic acid (DNA) interfaces, and predicting the impacts of these mutations using a variety of computational tools are crucial for successful drug discovery and development. Currently, there are 723 genes presented in the COSMIC Cancer Gene Census. Due to the complexity of the gene products, structures of only 87 genes have been solved experimentally with structural coverage between 90% and 100%. Here, we present a comprehensive, user-friendly, web interface (https://cancer-3d.com/) of 714 modelled cancer-related genes, including homo-oligomers, hetero-oligomers, transmembrane proteins and complexes with DNA, ribonucleic acid, ligands and co-factors. Using SDM and mCSM software, we have predicted the impacts of reported mutations on protein stability, protein-protein interfaces affinity and protein-nucleic acid complexes affinity. Furthermore, we also predicted intrinsically disordered regions using DISOPRED3.

SARS-CoV-2 3D database: understanding the coronavirus proteome and evaluating possible drug targets.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a rapidly growing infectious disease, widely spread with high mortality rates. Since the release of the SARS-CoV-2 genome sequence in March 2020, there has been an international focus on developing target-based drug discovery, which also requires knowledge of the 3D structure of the proteome. Where there are no experimentally solved structures, our group has created 3D models with coverage of 97.5% and characterized them using state-of-the-art computational approaches. Models of protomers and oligomers, together with predictions of substrate and allosteric binding sites, protein-ligand docking, SARS-CoV-2 protein interactions with human proteins, impacts of mutations, and mapped solved experimental structures are freely available for download. These are implemented in SARS CoV-2 3D, a comprehensive and user-friendly database, available at https://sars3d.com/. This provides essential information for drug discovery, both to evaluate targets and design new potential therapeutics.

Vascular Quality Initiative assessment of compliance with Society for Vascular Surgery clinical practice guidelines on the management of extracranial cerebrovascular disease.

OBJECTIVES: Compliance with Society for Vascular Surgery (SVS) clinical practice guidelines (CPGs) is associated with improved outcomes for the treatment of abdominal aortic aneurysm, but this has not been assessed for carotid artery disease. The Vascular Quality Initiative (VQI) registry was used to examine compliance with the SVS CPGs for the management of extracranial cerebrovascular disease and its impact on outcomes. METHODS: The 2021 SVS extracranial cerebrovascular disease CPGs were reviewed for evaluation by VQI data. Compliance rates by the center and provider were calculated, and the impact of compliance on outcomes was assessed using logistic regression with inverse probability-weighted risk adjustment for each CPG recommendation, allowing for clustering by the center. Our primary outcome was a composite end point of in-hospital stroke/death. As a secondary analysis, compliance with the 2021 SVS carotid implementation document recommendations and associated outcomes were also assessed. RESULTS: Of the 11 carotid CPG recommendations, 4 (36%) could be evaluated using VQI registry data. Median center-specific CPG compliance ranged from 38% to 95%, and median provider-specific compliance ranged from 36% to 100%. After adjustment, compliance with 2 of the recommendations was associated with lower rates of in-hospital stroke/death: first, the use of best medical therapy (antiplatelet and statin therapy) in low/standard surgical risk patients undergoing carotid endarterectomy for >70% asymptomatic stenosis (event rate in compliant vs noncompliant cases 0.59% vs 1.3%; adjusted odds ratio: 0.44, 95% confidence interval: 0.29-0.66); and second, carotid endarterectomy over transfemoral carotid artery stenting in low/standard surgical risk patients with >50% symptomatic stenosis (1.9% vs 3.4%; adjusted odds ratio: 0.55, 95% confidence interval: 0.43-0.71). Of the 132 implementation document recommendations, only 10 (7.6%) could be assessed using VQI data, with median center- and provider-specific compliance rates ranging from 67% to 100%. The impact of compliance on outcomes could only be assessed for 6 (4.5%) of these recommendations, and compliance with all 6 recommendations was associated with lower stroke/death. CONCLUSIONS: Few SVS recommendations could be assessed in the VQI because of incongruity between the recommendations and the VQI data variables collected. Although guideline compliance was extremely variable among VQI centers and providers, compliance with most of these recommendations was associated with improved outcomes after carotid revascularization. This finding confirms the value of guideline compliance, which should be encouraged for centers and providers. Optimization of VQI data to promote evaluation of guideline compliance and distribution of these findings to VQI centers and providers will help facilitate quality improvement efforts in the care of vascular patients.

The clinical outcomes of COVID-19 critically ill patients co-infected with other respiratory viruses: a multicenter, cohort study.

BACKGROUND: Previous studies have shown that non-critically ill COVID-19 patients co-infected with other respiratory viruses have poor clinical outcomes. However, limited studies focused on this co-infections in critically ill patients. This study aims to evaluate the clinical outcomes of critically ill patients infected with COVID-19 and co-infected by other respiratory viruses. METHODS: A multicenter retrospective cohort study was conducted for all adult patients with COVID-19 who were hospitalized in the ICUs between March, 2020 and July, 2021. Eligible patients were sub-categorized into two groups based on simultaneous co-infection with other respiratory viruses throughout their ICU stay. Influenza A or B, Human Adenovirus (AdV), Human Coronavirus (i.e., 229E, HKU1, NL63, or OC43), Human Metapneumovirus, Human Rhinovirus/Enterovirus, Middle East Respiratory Syndrome Coronavirus (MERS-CoV), Parainfluenza virus, and Respiratory Syncytial Virus (RSV) were among the respiratory viral infections screened. Patients were followed until discharge from the hospital or in-hospital death. RESULTS: A total of 836 patients were included in the final analysis. Eleven patients (1.3%) were infected concomitantly with other respiratory viruses. Rhinovirus/Enterovirus (38.5%) was the most commonly reported co-infection. No difference was observed between the two groups regarding the 30-day mortality (HR 0.39, 95% CI 0.13, 1.20; p = 0.10). The in-hospital mortality was significantly lower among co-infected patients with other respiratory viruses compared with patients who were infected with COVID-19 alone (HR 0.32 95% CI 0.10, 0.97; p = 0.04). Patients concomitantly infected with other respiratory viruses had longer median mechanical ventilation (MV) duration and hospital length of stay (LOS). CONCLUSION: Critically ill patients with COVID-19 who were concomitantly infected with other respiratory viruses had comparable 30-day mortality to those not concomitantly infected. Further proactive testing and care may be required in the case of co-infection with respiratory viruses and COVID-19. The results of our study need to be confirmed by larger studies.