Low-Temperature Activation and Coupling of Methane on MgO Nanostructures Embedded in Cu2O/Cu(111).

The efficient conversion of methane into valuable hydrocarbons, such as ethane and ethylene, at relatively low temperatures without deactivation issues is crucial for advancing sustainable energy solutions. Herein, AP-XPS and STM studies show that MgO nanostructures (0.2-0.5 nm wide, 0.4-0.6 Šhigh) embedded in a Cu2O/Cu(111) substrate activate methane at room temperature, mainly dissociating it into CHx (x = 2 or 3) and H adatoms, with minimal conversion to C adatoms. These MgO nanostructures in contact with Cu2O/Cu(111) enable C-C coupling into ethane and ethylene at 500 K, a significantly lower temperature than that required for bulk MgO catalysts (>700 K), with negligible carbon deposition and no deactivation. DFT calculations corroborate these experimental findings. The CH4,gas → *CH3 + *H reaction is a downhill process on MgO/Cu2O/Cu(111) surfaces. The activation of methane is facilitated by electron transfer from copper to MgO and the existence of Mg and O atoms with a low coordination number in the oxide nanostructures. The formation of O-CH3 and O-H bonds overcomes the energy necessary for the cleavage of a C-H bond in methane. DFT studies reveal that smaller Mg2O2 model clusters provide stronger binding and lower activation barriers for C-H dissociation in CH4, while larger Mg3O3 clusters promote C-C coupling due to weaker *CH3 binding. All of these results emphasize the importance of size when optimizing the catalytic performance of MgO nanostructures in the selective conversion of methane.

Early Readmission and Revision After Total Joint Arthroplasty: An Analysis of Cause and Cost.

Background: Bundled payments for total joint arthroplasty (TJA) were instituted by the Centers for Medicare and Medicaid Services (CMS) to reimburse providers a lump sum for operative and 90-day postoperative costs. Gaining a better understanding of which TJA patients are at risk for early return to the operating room (OR) is critical in preoperative optimization of those with modifiable risks, which could improve bundled-payment performance. Purpose: We sought to identify the most common reason for readmissions, as well as patient characteristics and costs, associated with early return to the OR among TJA patients. Methods: This was a retrospective cohort study of Medicare patients who had undergone primary total hip or knee arthroplasty (THA or TKA) between 2013 and 2018 at a tertiary care hospital. We used the CMS research identifiable files database to identify the most common reasons for readmissions and revisions within 90 days of surgery. Total billing claims were used to determine the cost of early readmissions and revisions. Multivariate regression analysis was used to determine the characteristics associated with early readmission or revision. Results: Out of 20 166 primary TJA patients identified, we found 1349 readmissions (5.6%) and 163 (0.8%) revisions within 90 days of surgery. Dislocation was the most common indication for readmission, and periprosthetic joint infection was the most common indication for revision. Early return to the OR was associated with a mean $105,988 (standard deviation [SD] = $76,865) in CMS claims for the inpatient stay. Factors associated with a higher risk of early reoperation were female sex, THA, longer length of stay, and discharge to long-term care facility. Conclusions: This retrospective cohort study found that early return to the OR after TJA increased overall 90-day costs by 260%, suggesting that early reoperation might have a significant impact on bundled payments. Further study is warranted.

Single inhaler combination inhaled corticosteroid-formoterol as both maintenance and reliever (SMART) compared with a step up of treatment with fixed-dose inhaled corticosteroid-long-acting ß2-agonist maintenance with a short-acting ß2-agonist as reliever in adolescents and adults with poorly controlled asthma in Colombia: a cost-utility analysis.

OBJECTIVE: The aim of the present study was to determine the cost-utility of single inhaler combination inhaled corticosteroid and a long-acting ß2-agonist (ICS/LABAs) as both maintenance and reliever (SMART) compared with a step-up maintenance treatment with a fixed medium to high dose of ICS combined with LABA and a short-acting ß2-agonist (SABA) as reliever (ICS-LABA maintenance plus SABA) among patients aged 12 years or more with poorly controlled asthma in Colombia. METHODS: A Markov-type model was developed to estimate the costs and health outcomes of a simulated cohort of patients aged 12 years or more with uncontrolled asthma treated for 12 months. The main effectiveness data were obtained from a recent meta-analysis. The main outcome was the variable ''quality-adjusted life-years'' (QALYs). RESULTS: The base-case analysis showed that the budesonide/formoterol (BUD/FORM) SMART strategy was associated with lower overall treatment costs (US $3,062.37 vs. $4,462.02 average cost per patient over 12 months) and the greatest gain in QALYs (0.8511 vs. 0.8258 QALYs on average per patient over 12 months) compared with ICS-LABA maintenance plus SABA at step 4, thus leading to dominance. CONCLUSIONS: In patients aged 12 years or more with uncontrolled asthma at GINA step 3 or 4, the BUD/FORM SMART strategy at either step 3 or 4 is cost-effective compared with the ICS-LABA maintenance plus SABA at step 4 strategy, because it shows a greater gain in QALYs at lower total treatment costs.

From Methane to Methanol: Pd-iC-CeO2 Catalysts Engineered for High Selectivity via Mechanochemical Synthesis.

In the pursuit of selective conversion of methane directly to methanol in the liquid-phase, a common challenge is the concurrent formation of undesirable liquid oxygenates or combustion byproducts. However, we demonstrate that monometallic Pd-CeO2 catalysts, modified by carbon, created by a simple mechanochemical synthesis method exhibit 100% selectivity toward methanol at 75 °C, using hydrogen peroxide as oxidizing agent. The solvent free synthesis yields a distinctive Pd-iC-CeO2 interface, where interfacial carbon (iC) modulates metal-oxide interactions and facilitates tandem methane activation and peroxide decomposition, thus resulting in an exclusive methanol selectivity of 100% with a yield of 117 µmol/gcat at 75 °C. Notably, solvent interactions of H2O2 (aq) were found to be critical for methanol selectivity through a density functional theory (DFT)-simulated Eley-Rideal-like mechanism. This mechanism uniquely enables the direct conversion of methane into methanol via a solid-liquid-gas process.

Structural Elucidation and Absolute Stereochemistry for Pharma Compounds Using MicroED.

Microcrystal electron diffraction (microED) is an emerging technique for rapid crystallographic analysis of small molecule micro- and nanocrystals. In this report, we evaluate the applicability of microED to pharmaceutical compounds through the analysis of 30 samples obtained from the process and medicinal chemistry groups at Amgen Inc. Using only 40 h of microscope time, 15 of 30 crystal structures were elucidated. From these crystal structures, all chiral compounds had the correct absolute stereochemistry assigned by dynamical refinement of continuous rotation electron diffraction data, confirming dynamical refinement as a promising tool for the absolute stereochemistry determination of pharmaceutically relevant compounds.

PSMF1 variants cause a phenotypic spectrum from early-onset Parkinson's disease to perinatal lethality by disrupting mitochondrial pathways.

Dissecting biological pathways highlighted by Mendelian gene discovery has provided critical insights into the pathogenesis of Parkinson's disease (PD) and neurodegeneration. This approach ultimately catalyzes the identification of potential biomarkers and therapeutic targets. Here, we identify PSMF1 as a new gene implicated in PD and childhood neurodegeneration. We find that biallelic PSMF1 missense and loss-of-function variants co-segregate with phenotypes from early-onset PD and parkinsonism to perinatal lethality with neurological manifestations across 15 unrelated pedigrees with 22 affected subjects, showing clear genotype-phenotype correlation. PSMF1 encodes the proteasome regulator PSMF1/PI31, a highly conserved, ubiquitously expressed partner of the 20S proteasome and neurodegeneration-associated F-box-O 7 and valosin-containing proteins. We demonstrate that PSMF1 variants impair mitochondrial membrane potential, dynamics and mitophagy in patient-derived fibroblasts. Additionally, we develop models of psmf1 knockdown Drosophila and Psmf1 conditional knockout mouse exhibiting age-dependent motor impairment, with diffuse gliosis in mice. These findings unequivocally link defective PSMF1 to early-onset PD and neurodegeneration and suggest mitochondrial dysfunction as a mechanistic contributor.

Development of a dispersive solid phase microextraction method based on the application of MgAl, NiAl, and CoAl-layered double hydroxides for the efficient removal of α- and ß-naphthol isomers from water samples by capillary electrophoresis.

The present work describes a quick, simple, and efficient method based on the use of layered double hydroxides (LDH) coupled to dispersive solid phase micro-extraction (DSPME) to remove α-naphthol (α-NAP) and ß-naphthol (ß-NAP) isomers from water samples. Three different LDHs (MgAl-LDH, NiAl-LDH, and CoAl-LDH) were used to study how the interlayer anion and molar ratio affected the removal performance. The critical factors in the DSPME procedure (pH, LDH amount, contact time) were optimized by the univariate method under the optimal conditions: pH, 4-8; LDH amount, 5 mg; and contact time, 2.5 min. The method can be successfully applied in real sample waters, removing NAP isomers even in ultra-trace concentrations. The large volume sample stacking (LVSS-CE) technique provides limits of detections (LODs) of 5.52 µg/L and 6.36 µg/L for α-naphthol and ß-naphthol, respectively. The methodology's precision was evaluated on intra- and inter-day repeatability, with %RSD less than 10% in all cases. The MgAl/Cl--LDH selectivity was tested in the presence of phenol and bisphenol A, with a removal rate of >92.80%. The elution tests suggest that the LDH MgAl/Cl--LDH could be suitable for pre-concentration of α-naphthol and ß-naphthol in future works.

Simultaneous Bilateral Total Hip Arthroplasty with Either the Direct Anterior or Posterior Approaches: A Propensity Score Match Study.

INTRODUCTION: Bilateral hip osteoarthritis is evident in approximately 20% of patients who present to the clinic for evaluation of hip pain, and for those undergoing total hip arthroplasty (THA), 22% will end up needing a contralateral THA. The risk and benefits of simultaneous bilateral THA (SBTHA) versus staged bilateral THA procedures have been well studied, demonstrating equivalent safety profiles comparable to unilateral and SBTHA. However, the influence of the surgical approach on SBTHA on postoperative outcomes remains unclear. We sought to compare perioperative outcomes and complication rates between the direct anterior approach (DAA) and posterior approach (PA) in patients undergoing SBTHA. METHODS: We performed a 1:1 propensity score match based on age, sex, and body mass index (BMI). A total of 252 patients were available after matching, 126 patients in the DAA group and 126 in the PA group. Perioperative outcomes as well as surgical complications at the latest follow-up were retrospectively collected for each group. The mean follow-up was 36.7 months (range, 12.5 to 74.4). RESULTS: A SBTHA with DAA had significantly shorter surgical time (P < 0.001), anesthesia time (P < 0.001), and length of stay (P < 0.001), compared to the PA. A greater percentage of patients in the DAA group (91%) were discharged home compared to the PA group (57%) (P < 0.001). There were no differences in in-hospital complications (P = 0.617), 90-day complications (P = 0.605), or reoperation rates (P = 0.309) between surgical approaches. CONCLUSION: A SBTHA, either through the DAA or PA, can be safely performed with low complication rates. The DAA in the setting of SBTHA provides shorter surgical times, a shorter length of stay, and a greater percentage of patients discharged home.

Influenza Vaccination Uptake and Associated Factors among Individuals with Diabetes Mellitus in Spain: A Cross-Sectional Study Using Data from the European Health Interview Survey 2020.

BACKGROUND: Vaccination against influenza has proven to reduce influenza-caused hospital entries, treatment times in intensive care units and hospitalisation costs for treating people with Diabetes Mellitus (DM). Despite the existing influenza vaccination recommendations for all persons with DM, in Spain, vaccination hesitancy remains substantial, and vaccination rates lag behind target. We aimed to assess predictors for influenza vaccination uptake and reasons for non-adherence among individuals with DM. METHODS: Data from the 2020 European Health Interview Survey were analysed using uni- and multivariable logistic regression models, stratified by age group and including possible confounders and vaccination as an outcome. Associations with the sociodemographic profile, healthcare access and substance use were explored. RESULTS: Our analysis included 2194 individuals with DM over the age of 15, showing an influenza vaccination rate of 53%. The findings revealed significant predictors of vaccination uptake, including age over 60 years and robust social support. Conversely, younger age, higher education levels, infrequent healthcare interactions and economic barriers emerged as significant obstacles to vaccination. CONCLUSIONS: To enhance vaccination rates, targeted public health interventions should emphasise the importance of vaccination for younger, more educated individuals with DM, those facing economic barriers and those with lower levels of social support, which could bridge the existing gap in vaccination coverage.

Enhancing prediction of short linear protein motifs with Wregex 3.0.

Short linear motifs (SLiMs) play an important role in protein-protein interactions. However, SLiM patterns are intrinsically permissive and result into many matches that occur just by chance, specially when targeting large datasets. To prioritize these matches as candidates for functional testing, we developed Wregex (Weighted regular expression), which uses a position-specific scoring matrix (PSSM) to order a list of regular expression matches according to a PSSM-derived score. Here we present Wregex 3.0, an improved version with new functionalities such as the support for a second auxiliary motif to help refining prediction of a primary SLiM, and post-translational modifications (PTMs) enrichment taking into account that many regulatory SLiM-mediated interactions are modulated by one or more PTMs. This version also incorporates a number of new features such as a convenient use of subproteomes, showing UniProt annotations such as disordered regions, searching for all known motifs and generating decoy databases for enrichment analysis. We provide case studies to illustrate how these new Wregex functionalities enhance prediction of short linear protein motifs. The Wregex 3.0 server is freely accessible at https://ehubio.ehu.eus/wregex3/.

A critical analysis of the effect of OM-85 for the prevention of recurrent respiratory tract infections or wheezing/asthma from systematic reviews with meta-analysis.

Acute respiratory tract infections (RTIs) are one of the most common causes of pediatric consultations/hospitalizations and a major trigger for asthma exacerbations. Some consensus statements have recommended the use of immunostimulants to boost natural defenses against severe or repeated infections. One of the most common immunostimulants is OM-85; while several randomized clinical trials (RCTs) have evaluated its efficacy in preventing acute RTIs and wheezing/asthma exacerbations, results have been conflicting. Similarly, various systematic reviews with meta-analyses (SRMs) on OM-85 have used different strategies, populations, and outcomes; moreover, SRM conclusions are limited when the original studies are highly heterogeneous or have a low quality, hindering the generalizability of the findings. Here we summarize the evidence on the effect of OM-85 to prevent acute RTIs, wheezing/asthma episodes, or loss of asthma control in children, by including and critically evaluating all SRMs published to date. We searched for SRMs on OM-85 in three publication databases and found nine SRMs (seven for RTI, and two for wheezing/asthma). Among those, one had a high confidence evaluation of quality (AMSTAR-2 tool) and found a reduction in the total number of acute RTIs among the OM-85 group. Overall, no strong recommendations can be derived from the existing literature, mainly due to the high heterogeneity among included RCTs and SRMs. Further, large, high-quality RCTs are needed to confirm the true efficacy of OM-85 for the prevention of acute RTIs, asthma development, and asthma exacerbations.

Theoretical Prediction and Experimental Verification of IrOx Supported on Titanium Nitride for Acidic Oxygen Evolution Reaction.

Reducing iridium (Ir) catalyst loading for acidic oxygen evolution reaction (OER) is a critical strategy for large-scale hydrogen production via proton exchange membrane (PEM) water electrolysis. However, simultaneously achieving high activity, long-term stability, and reduced material cost remains challenging. To address this challenge, we develop a framework by combining density functional theory (DFT) prediction using model surfaces and proof-of-concept experimental verification using thin films and nanoparticles. DFT results predict that oxidized Ir monolayers over titanium nitride (IrOx/TiN) should display higher OER activity than IrOx while reducing Ir loading. This prediction is verified by depositing Ir monolayers over TiN thin films via physical vapor deposition. The promising thin film results are then extended to commercially viable powder IrOx/TiN catalysts, which demonstrate a lower overpotential and higher mass activity than commercial IrO2 and long-term stability of 250 h to maintain a current density of 10 mA cm-2. The superior OER performance of IrOx/TiN is further confirmed using a proton exchange membrane water electrolyzer (PEMWE), which shows a lower cell voltage than commercial IrO2 to achieve a current density of 1 A cm-2. Both DFT and in situ X-ray absorption spectroscopy reveal that the high OER performance of IrOx/TiN strongly depends on the IrOx-TiN interaction via direct Ir-Ti bonding. This study highlights the importance of close interaction between theoretical prediction based on mechanistic understanding and experimental verification based on thin film model catalysts to facilitate the development of more practical powder IrOx/TiN catalysts with high activity and stability for acidic OER.

The Surface Chemistry of Methanol on Pd(111) and H-Pd(111) Surfaces: C-O Bond Cleavage and the Effects of Metal Hydride Formation.

Palladium catalysts are frequently employed in processes where methanol is an energy vector or carrier, being useful for the synthesis of methanol from mixtures of carbon dioxide and hydrogen (CO2/H2) or its steam reforming on demand. Results of synchrotron-based ambient pressure X-ray photoelectron spectroscopy for the adsorption of methanol on a Pd(111) model catalyst show a rich surface chemistry and complex phenomena that strongly depend on pressure and temperature. At low pressures (<10-6 Torr) and temperatures (<300 K), CO is the dominant decomposition product. As the pressure increases, cleavage of C-H, O-H, and C-O bonds is observed, and at elevated temperatures (400-600 K) the formation of CO and CHx/C fragments compete on the surface. Thus, existing reaction networks for methanol decomposition must be modified. Furthermore, surface and subsurface hydrogen (coming from PdHx) play a significant role in the stability and removal of CHx and C species.

3D Nanocrystallography and the Imperfect Molecular Lattice.

Crystallographic analysis relies on the scattering of quanta from arrays of atoms that populate a repeating lattice. While large crystals built of lattices that appear ideal are sought after by crystallographers, imperfections are the norm for molecular crystals. Additionally, advanced X-ray and electron diffraction techniques, used for crystallography, have opened the possibility of interrogating micro- and nanoscale crystals, with edges only millions or even thousands of molecules long. These crystals exist in a size regime that approximates the lower bounds for traditional models of crystal nonuniformity and imperfection. Accordingly, data generated by diffraction from both X-rays and electrons show increased complexity and are more challenging to conventionally model. New approaches in serial crystallography and spatially resolved electron diffraction mapping are changing this paradigm by better accounting for variability within and between crystals. The intersection of these methods presents an opportunity for a more comprehensive understanding of the structure and properties of nanocrystalline materials.

Role of Atomicity and Interface on InOx-TiO2 Composites: Thermo-Photo Valorization of CO2.

The synthesis, physicochemical, and functional properties of composite solids resulting from the surface spread of oxidized indium species onto nanoplatelets of anatase were investigated. Both the size and the interaction between the indium- and titanium-containing components control the functional properties. In the reduction of CO2 to CO, the best samples have an indium content between ca. 2 and 5 mol % and showed an excess rate over the photo and thermo-alone processes above 33% and an energy efficiency of 1.3%. Subnanometric (monomeric and dimeric) indium species present relatively weak thermal catalytic response but strong thermo-photo promotion of the activity. A gradual change in functional properties was observed with the growth of the indium content of the solids, leading to a progressive increase of thermal activity but lower thermo-photo promotion. The study provides a well-defined structure-activity relationship rationalizing the dual thermo-photo properties of the catalysts and establishes a guide for the development of highly active and stable composite solids for the elimination and valorization of CO2.

The Use of Aspirin for Venous Thromboembolism Prophylaxis in Patients Who Have Morbid Obesity Undergoing Primary and Revision Total Joint Arthroplasty.

BACKGROUND: Venous thromboembolism (VTE) poses a major clinical concern due to its life-threatening nature, and obese and morbidly obese patients are thought to be at an increased risk for VTE. The aims of this study were twofold; first, to explore VTE rates in patients who have a body mass index (BMI) > 40 undergoing primary and revision total joint arthroplasty, and second, to investigate aspirin (ASA) efficacy and safety. METHODS: We identified all patients (n = 4,672) who had a BMI > 40 who underwent primary and revision total joint arthroplasty from 2016 to 2022 at a single academic tertiary care center. Patients were stratified by BMI groups: 40 to 44.9 (n = 3,462), 45 to 49.9 (n = 935), and 50+ (n = 275). The primary outcome was any VTE event within 90 days postoperatively. The secondary outcome consisted of wound complications within 90 days postoperatively. RESULTS: The total VTE rate was 0.4% (n = 21) and did not differ statistically between the BMI groups (0.4 versus 0.4 versus 0.7%, P = .669). The VTEs consisted of 6 deep venous thromboses (DVTs), 14 pulmonary embolisms, and one concomitant deep venous thrombosis and pulmonary embolism. The VTE rates were not statistically different between patients who received aspirin 325 mg 0.5% (n = 9), aspirin 81 mg 0.2% (n = 1), aspirin + anticoagulant (AC) 0.5% (n = 6), and AC alone 0.4% (n = 5) (P = .954). In addition, wound complications did not differ significantly between patients who received ASA 325 mg, ASA 81mg, ASA + AC, or AC alone (1.6 versus 1.0 versus 1.8 versus 1.1%, P = .351). CONCLUSIONS: The use of aspirin 325 and 81 mg was found to have similar VTE rates as aspirin + ACs and ACs alone, with no significant increase in wound complications. In patients who have a BMI > 40, the use of aspirin is a safe option for VTE prophylaxis and should be prescribed in the context of the patient who has other risk factors for VTE.

Evaluation of digoxin-boronate ester formation through in-capillary derivatisation-large volume sample stacking-capillary zone electrophoresis.

Determination of digoxin through in-capillary derivatisation based on the formation of o-tolyl- and 2-naphthyl-anionic boronate esters in combination with large volume sample stacking-capillary electrophoresis is proposed. The derivatisation reaction was performed at basic pH values to obtain compounds with a charge and chromophore group during the stacking process. After stacking, the species were separated and detected at 225 nm using p-nitrophenol as an internal standard. Stacking and derivatisation parameters such as pre-concentration time, preconcentration voltage and injection time (relation between the analyte and the derivatisation agent) were evaluated using a Box-Behnken design. Under optimal conditions, the proposed method exhibits a linear range of 1.08-50.00 µM with a limit of detection of 0.36 µM; additionally, adequate repeatability and reproducibility was obtained (%RSD ≤ 5.0%). The methodology was validated by comparing it to an HPLC-UV established methodology and was successfully applied for the determination of digoxin in pharmaceutical tablets and blood serum samples, showing a positive performance for these matrices.

Drug use and COVID-19 testing, vaccination, and infection among underserved, minority communities in Miami, Florida.

The Coronavirus Disease 2019 (COVID-19) pandemic has disproportionately impacted people who use drugs (PWUD). This study explored relationships between drug use, COVID-19 testing, vaccination, and infection. This cross-sectional study was conducted in Miami, Florida between March 2021 and October 2022 as part of the National Institutes of Health (NIH) Rapid Acceleration of Diagnostics-Underserved Populations (RADx-UP) initiative and the Miami Adult Studies on HIV (MASH) cohort. Users of cannabis, cocaine/crack, heroin/fentanyl, methamphetamines, hallucinogens, and/or prescription drug misuse in the previous 12 months were considered PWUD. Sociodemographic data, COVID-19 testing history, and vaccination-related beliefs were self-reported. Vaccinations were confirmed with medical records and positivity was determined with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) testing. Statistical analyses included chi-square tests and logistic regression. Of 1,780 participants, median age was 57 years, 50.7% were male, 50.2% Non-Hispanic Black, and 66.0% reported an annual income less than $15,000. Nearly 28.0% used drugs. PWUD were less likely than non-users to self-report ever testing positive for SARS-CoV-2 (14.7% vs. 21.0%, p = 0.006). However, 2.6% of participants tested positive for SARS-CoV-2, with no significant differences between PWUD and non-users (3.7% vs. 2.2%, p = 0.076). PWUD were more likely than non-users to experience difficulties accessing testing (10.2% vs. 7.1%, p = 0.033), vaccine hesitancy (58.9% vs. 43.4%, p = 0.002) and had lower odds of receiving any dose of a COVID-19 vaccine compared to non-users (aOR, 0.63; 95% CI, 0.49-0.81; p<0.001). PWUD presented with greater difficulties accessing COVID-19 testing, greater vaccine hesitancy, and lower odds of vaccination. Testing and immunization plans that are tailored to the needs of PWUD and consider access, trust-building campaigns, and education may be needed.

Perioperative Cefazolin for Total Joint Arthroplasty Patients Who Have a Penicillin Allergy: Is It Safe?

BACKGROUND: Cefazolin is the standard of care for perioperative antibiotic prophylaxis in total joint arthroplasty (TJA) in the United States. The potential allergic cross-reactivity between cefazolin and penicillin causes uncertainty regarding optimal antibiotic choice in patients who have a reported penicillin allergy (rPCNA). The purpose of this study was to determine the safety of perioperative cefazolin in PCNA patients undergoing primary TJA. METHODS: We identified all patients (n = 49,842) undergoing primary total hip arthroplasty (n = 25,659) or total knee arthroplasty (n = 24,183) from 2016 to 2022 who received perioperative intravenous antibiotic prophylaxis. Patients who had an rPCNA (n = 5,508) who received cefazolin (n = 4,938, 89.7%) were compared to rPCNA patients who did not (n = 570, 10.3%), and to patients who did not have an rPCNA (n = 43,359). The primary outcome was the rate of allergic reactions within 72 hours postoperatively. Secondary outcomes included the rates of superficial infections, deep infections, and Clostridioides difficile infections within 90 days. RESULTS: The rate of allergic reactions was 0.1% (n = 5) in rPCNA patients who received cefazolin, compared to 0.2% (n = 1) in rPCNA patients who did not (P = .48) and 0.02% (n = 11) in patients who have no rPCNA (P = .02). Allergic reactions were mild in all 5 rPCNA patients who received cefazolin and were characterized by cutaneous symptoms (n = 4) or dyspnea in the absence of respiratory distress (n = 1) that resolved promptly with antibiotic discontinuation and administration of antihistamines and/or corticosteroids. We observed no differences in the rates of superficial infections (0.1 versus 0.2%, P = .58), deep infections (0.3 versus 0.4%, P = .68), or C difficile infections (0.04% versus 0%, P = .99) within 90 days in rPCNA patients who received cefazolin versus alternative perioperative antibiotics. CONCLUSIONS: In this series of more than 5,500 patients who had an rPCNA undergoing primary TJA, perioperative prophylaxis with cefazolin resulted in a 0.1% incidence of allergic reactions that were clinically indolent. Cefazolin can be safely administered to most patients, independent of rPCNA severity. LEVEL OF EVIDENCE: III.

Transcriptomic Analysis of Extracellular Vesicles in the Search for Novel Plasma and Thrombus Biomarkers of Ischemic Stroke Etiologies.

Accurate etiologic diagnosis provides an appropriate secondary prevention and better prognosis in ischemic stroke (IS) patients; still, 45% of IS are cryptogenic, urging us to enhance diagnostic precision. We have studied the transcriptomic content of plasma extracellular vesicles (EVs) (n = 21) to identify potential biomarkers of IS etiologies. The proteins encoded by the selected genes were measured in the sera of IS patients (n = 114) and in hypertensive patients with (n = 78) and without atrial fibrillation (AF) (n = 20). IGFBP-2, the most promising candidate, was studied using immunohistochemistry in the IS thrombi (n = 23) and atrium of AF patients (n = 13). In vitro, the IGFBP-2 blockade was analyzed using thromboelastometry and endothelial cell cultures. We identified 745 differentially expressed genes among EVs of cardioembolic, atherothrombotic, and ESUS groups. From these, IGFBP-2 (cutoff > 247.6 ng/mL) emerged as a potential circulating biomarker of embolic IS [OR = 8.70 (1.84-41.13) p = 0.003], which was increased in patients with AF vs. controls (p < 0.001) and was augmented in cardioembolic vs. atherothrombotic thrombi (p < 0.01). Ex vivo, the blockage of IGFBP-2 reduced clot firmness (p < 0.01) and lysis time (p < 0.001) and in vitro, diminished endothelial permeability (p < 0.05) and transmigration (p = 0.06). IGFBP-2 could be a biomarker of embolic IS and a new therapeutic target involved in clot formation and endothelial dysfunction.