Mid-Term Follow Up of the Nexel Total Elbow Arthroplasty.

INTRODUCTION: Aseptic loosening is one of the most common complications of total elbow arthroplasty (TEA). Modern implants, such as the Nexel, have been designed in an attempt to decrease loosening. The present study aims to report implant survivorship, radiographic assessment of loosening and lucency, and patient-reported outcome measures (PROMs) in patients treated with the Nexel TEA at mid-term follow-up. METHODS: Consecutive series of adult patients underwent TEA using the Nexel by a single surgeon via standardized technique. Patients with minimum 3 year follow-up with radiographic and PROM data were included. Survivorship was defined by the absence of revision. Loosening was assessed via Wrightington method by three independent fellowship-trained shoulder and elbow surgeons. Lucency was analyzed across individual radiographic zones on orthogonal radiographs. PROMs included the Quick Dash (QDASH), Patient Rated Elbow Evaluation (PREE), and EuroQoL (EQ5D). RESULTS: 38 consecutive patients (22 female, 16 male) with mean age of 67 underwent TEA via triceps-sparing isolated medial window approach. Mean follow-up was 5.5 years (range 3-9). Primary diagnoses were: 19 osteoarthritis (OA), 9 rheumatoid arthritis (RA), 9 post-traumatic arthritis (PA), 1 conversion of elbow arthrodesis. Overall survivorship was 97.4%, with one patient undergoing revision for infection. Loosening was found in 5.3% of elbows, averaged across three observers. Lucency was most pronounced at the level of the humeral condyles. PROMs demonstrated significant and clinically meaningful improvements in 76%, 92%, and 73% of patients for QDASH, PREE, and EQ5D, respectively. No significant correlations were found between patient age, gender, loosening, lucency, and PROMs. CONCLUSION: At mid-term follow-up, the Nexel TEA demonstrated excellent overall survivorship and low rate of implant loosening. The single failure requiring revision for infection was conversion of a prior elbow arthrodesis. PROMs overall exhibited marked and consistent improvement from preop to final postop follow-up. Although promising, these results should be interpreted with some caution as long term data regarding this prosthesis are still lacking.

Sample average treatment effect on the treated (SATT) analysis using counterfactual explanation identifies BMT and SARS-CoV-2 vaccination as protective risk factors associated with COVID-19 severity and survival in patients with multiple myeloma.

Patients with multiple myeloma (MM), an age-dependent neoplasm of antibody-producing plasma cells, have compromised immune systems and might be at increased risk for severe COVID-19 outcomes. This study characterizes risk factors associated with clinical indicators of COVID-19 severity and all-cause mortality in myeloma patients utilizing NCATS' National COVID Cohort Collaborative (N3C) database. The N3C consortium is a large, centralized data resource representing the largest multi-center cohort of COVID-19 cases and controls nationwide (>16 million total patients, and >6 million confirmed COVID-19+ cases to date). Our cohort included myeloma patients (both inpatients and outpatients) within the N3C consortium who have been diagnosed with COVID-19 based on positive PCR or antigen tests or ICD-10-CM diagnosis code. The outcomes of interest include all-cause mortality (including discharge to hospice) during the index encounter and clinical indicators of severity (i.e., hospitalization/emergency department/ED visit, use of mechanical ventilation, or extracorporeal membrane oxygenation (ECMO)). Finally, causal inference analysis was performed using the Coarsened Exact Matching (CEM) and Propensity Score Matching (PSM) methods. As of 05/16/2022, the N3C consortium included 1,061,748 cancer patients, out of which 26,064 were MM patients (8,588 were COVID-19 positive). The mean age at COVID-19 diagnosis was 65.89 years, 46.8% were females, and 20.2% were of black race. 4.47% of patients died within 30 days of COVID-19 hospitalization. Overall, the survival probability was 90.7% across the course of the study. Multivariate logistic regression analysis showed histories of pulmonary and renal disease, dexamethasone, proteasome inhibitor/PI, immunomodulatory/IMiD therapies, and severe Charlson Comorbidity Index/CCI were significantly associated with higher risks of severe COVID-19 outcomes. Protective associations were observed with blood-or-marrow transplant/BMT and COVID-19 vaccination. Further, multivariate Cox proportional hazard analysis showed that high and moderate CCI levels, International Staging System (ISS) moderate or severe stage, and PI therapy were associated with worse survival, while BMT and COVID-19 vaccination were associated with lower risk of death. Finally, matched sample average treatment effect on the treated (SATT) confirmed the causal effect of BMT and vaccination status as top protective factors associated with COVID-19 risk among US patients suffering from multiple myeloma. To the best of our knowledge, this is the largest nationwide study on myeloma patients with COVID-19.

Effects of Slit Edge Notches on Mechanical Properties of 3D-Printed PA12 Nylon Kirigami Specimens.

Kirigami structures, a Japanese paper-cutting art form, has been widely adopted in engineering design, including robotics, biomedicine, energy harvesting, and sensing. This study investigated the effects of slit edge notches on the mechanical properties, particularly the tensile stiffness, of 3D-printed PA12 nylon kirigami specimens. Thirty-five samples were designed with various notch sizes and shapes and printed using a commercial 3D printer with multi-jet fusion (MJF) technique. Finite element analysis (FEA) was employed to determine the mechanical properties of the samples computationally. The results showed that the stiffness of the kirigami samples is positively correlated with the number of edges in the notch shape and quadratically negatively correlated with the notch area of the samples. The mathematical relationship between the stretching tensile stiffness of the samples and their notch area was established and explained from an energy perspective. The relationship established in this study can help fine-tune the stiffness of kirigami-inspired structures without altering the primary parameters of kirigami samples. With the rapid fabrication method (e.g., 3D printing technique), the kirigami samples with suitable mechanical properties can be potentially applied to planar springs for hinge structures or energy-absorbing/harvesting structures. These findings will provide valuable insights into the development and optimization of kirigami-inspired structures for various applications in the future.

Data quality considerations for evaluating COVID-19 treatments using real world data: learnings from the National COVID Cohort Collaborative (N3C).

BACKGROUND: Multi-institution electronic health records (EHR) are a rich source of real world data (RWD) for generating real world evidence (RWE) regarding the utilization, benefits and harms of medical interventions. They provide access to clinical data from large pooled patient populations in addition to laboratory measurements unavailable in insurance claims-based data. However, secondary use of these data for research requires specialized knowledge and careful evaluation of data quality and completeness. We discuss data quality assessments undertaken during the conduct of prep-to-research, focusing on the investigation of treatment safety and effectiveness. METHODS: Using the National COVID Cohort Collaborative (N3C) enclave, we defined a patient population using criteria typical in non-interventional inpatient drug effectiveness studies. We present the challenges encountered when constructing this dataset, beginning with an examination of data quality across data partners. We then discuss the methods and best practices used to operationalize several important study elements: exposure to treatment, baseline health comorbidities, and key outcomes of interest. RESULTS: We share our experiences and lessons learned when working with heterogeneous EHR data from over 65 healthcare institutions and 4 common data models. We discuss six key areas of data variability and quality. (1) The specific EHR data elements captured from a site can vary depending on source data model and practice. (2) Data missingness remains a significant issue. (3) Drug exposures can be recorded at different levels and may not contain route of administration or dosage information. (4) Reconstruction of continuous drug exposure intervals may not always be possible. (5) EHR discontinuity is a major concern for capturing history of prior treatment and comorbidities. Lastly, (6) access to EHR data alone limits the potential outcomes which can be used in studies. CONCLUSIONS: The creation of large scale centralized multi-site EHR databases such as N3C enables a wide range of research aimed at better understanding treatments and health impacts of many conditions including COVID-19. As with all observational research, it is important that research teams engage with appropriate domain experts to understand the data in order to define research questions that are both clinically important and feasible to address using these real world data.

Successful Use of Continuous Erector Spinae Plane Blocks in a Patient With Variant Angina After Large Ventral Hernia Repair.

Coronary artery spasm constitutes the primary underlying pathology of variant angina. Because provocation of coronary artery spasm may occur with both excess sympathetic and excess parasympathetic stimulation, patients with this disorder have extremely limited options for perioperative pain control. This is especially true for procedures involving extensive abdominal incision/manipulation. Whereas neuraxial analgesia might otherwise be appropriate in these cases, several studies have demonstrated that coronary artery spasm can occur as a result of epidural placement, and therefore, that this may not be an optimal choice for patients with variant angina. This report discusses the case of a patient with a preexisting diagnosis of variant angina who underwent an exploratory laparotomy with large ventral hernia repair and for whom continuous erector spinae plane blocks were successfully used as analgesic adjuncts without triggering coronary artery spasm.

Sample average treatment effect on the treated analysis using counterfactual explanation identifies BMT and SARS-CoV-2 vaccination as protective risk factors associated with COVID-19 severity and survival in patients with multiple myeloma

Patients with multiple myeloma (MM), an age-dependent neoplasm of antibody-producing plasma cells, have compromised immune systems and might be at increased risk for severe COVID-19 outcomes. This study characterizes risk factors associated with clinical indicators of COVID-19 severity and all-cause mortality in myeloma patients utilizing NCATS National COVID Cohort Collaborative (N3C) database. The N3C consortium is a large, centralized data resource representing the largest multi-center cohort of COVID-19 cases and controls nationwide (>16 million total patients, and >6 million confirmed COVID-19+ cases to date). Our cohort included myeloma patients (both inpatients and outpatients) within the N3C consortium who have been diagnosed with COVID-19 based on positive PCR or antigen tests or ICD-10-CM diagnosis code. The outcomes of interest include all-cause mortality (including discharge to hospice) during the index encounter and clinical indicators of severity (i.e., hospitalization/emergency department/ED visit, use of mechanical ventilation, or extracorporeal membrane oxygenation (ECMO)). Finally, causal inference analysis was performed using the propensity score matching (PSM) method. As of 05/16/2022, the N3C consortium included 1,061,748 cancer patients, out of which 26,064 were MM patients (8,588 were COVID-19 positive). The mean age at COVID-19 diagnosis was 65.89 years, 46.8% were females, and 20.2% were of black race. 4.47% of patients died within 30 days of COVID-19 hospitalization. Overall, the survival probability was 90.7% across the course of the study. Multivariate logistic regression analysis showed histories of pulmonary and renal disease, dexamethasone, proteasome inhibitor/PI, immunomodulatory/IMiD therapies, and severe Charlson Comorbidity Index/CCI were significantly associated with higher risks of severe COVID-19 outcomes. Protective associations were observed with blood-or-marrow transplant/BMT and COVID-19 vaccination. Further, multivariate cox proportional hazard analysis showed that high and moderate CCI levels, International Staging System (ISS) moderate or severe stage, and PI therapy were associated with worse survival, while BMT and COVID-19 vaccination were associated with lower risk of death. Finally, matched sample average treatment effect on the treated (SATT) confirmed the causal effect of BMT and vaccination status as top protective factors associated with COVID-19 risk among US patients suffering from multiple myeloma. To the best of our knowledge, this is the largest nationwide study on myeloma patients with COVID-19.

In-line sample concentration in capillary electrophoresis by cyclodextrin to admicelle microextraction.

Cyclodextrins (CDs) as a pseudophase in pseudophase-to-pseudophase microextraction (P2ME) in capillary zone electrophoresis (CZE) are proposed. In this P2ME mode called CD to admicelle ME, a long plug of dilute analyte solution prepared in cetyltrimethylammonium bromide (CTAB) at the critical micellar concentration was injected into the capillary. This formed CTAB admicelles at the interface between the solution and the negatively charged capillary surface, where the analytes were trapped. The injection of CD solution released the admicelles and the analytes from the capillary surface due to the formation of stable CD/CTAB inclusion complexes. The analytes are concentrated at the CD front during injection and voltage separation. Various neutral CDs were found to be effective for CD to admicelle ME. To implement this in-line sample concentration technique in CZE, CD concentration, sample injection time, and sample:CD solution injection ratio were optimized. The optimized conditions for five model anionic analytes, namely, 4-bromophenol, sulindac, sulfamethizole, 4-vinylbenzoic acid, and succinylsulfathiazole, were 20 mM α-CD in 20 mM sodium tetraborate (pH 9.2) solution, sample injection time of 370 s, and CD:sample injection ratio of 1:2. The sensitivity enhancement factors (SEFs) were between 112 and 168. The SEFs of sulindac and sulfamethizole in particular were similar to previously published off-line microextraction techniques, which are typically time-consuming. The calculated values of LOQ, intra-/inter-day (n = 6/n = 10, 3 days) repeatability, and linearity (R2) of CD to admicelle ME were 0.0125-0.05 µg/mL, 1.5-4.6%, 1.8-4.8%, and ≥0.999, respectively. Finally, the potential of CD to admicelle ME to the analysis of artificial urine samples was demonstrated.

Pseudophase-to-solvent microextraction for in-line sample concentration of anionic analytes in capillary zone electrophoresis.

We present pseudophase-to-solvent microextraction (PSME) as a simple pressure-driven in-line sample concentration technique in capillary zone electrophoresis (CZE) for small organic anions. The developed technique is like solid-phase extraction; however, the chromatographic phase is a pseudophase, i.e., in-situ cetyltrimethylammonium bromide (CTAB) interfacial micelles. A large volume of sample (e.g., > 12 capillary volumes) prepared in [CTAB] ∼critical micelle concentration was injected into the capillary. The elution and enrichment of analytes trapped in the CTAB coating was facilitated by the high concentration of methanol in the background solution, which was introduced from the outlet end. Co-electroosmotic flow CZE was conducted after the concentrated analytes reached the tip of the inlet. Parameters such as sample loading time and elution time were optimised. Under optimised conditions, the SEFs of 187-573 achieved for the model anions (4-nitrophenol, 4-vinylbenzoic acid, mecoprop, indoprofen, sulfamethizole and sulindac) were comparable to previously reported off-line microextraction techniques. The calculated LOD (S/N = 3), LOQ (S/N = 10), intra-/inter- (n = 6/n = 9, 3 days) day repeatability and linearity (R2s) values in PSME-CZE were 4.2-20.1 ng/mL, 13.8-67.1 ng/mL, 5%, 10% and > 0.990, respectively. The PSME-CZE of fortified urine samples showed % recovery values of 93-108% with %RSDs (n = 3) of 4-10% for the model analytes.

Anti-IL-8 antibody activates myeloid cells and potentiates the anti-tumor activity of anti-PD-1 antibody in the humanized pancreatic cancer murine model.

Pancreatic ductal adenocarcinoma(PDAC) does not respond to single-agent immune checkpoint inhibitor therapy, including anti-PD-1 antibody(aPD-1) therapy. Higher plasma levels of IL-8 are associated with poorer outcomes in patients who receive aPD-1 therapies, providing a rationale for combination immunotherapy with an anti-IL-8 antibody(aIL-8) and aPD-1. We thus investigated whether human aIL-8 therapy can potentiate the antitumor activity of aPD-1 and further investigated how the combination affects the immune response by regulating myeloid cells in the tumor microenvironment in a humanized murine model of PDAC with a reconstituted immune system consisting of human T cells and a combination of CD14+ and CD16+ myeloid cells. The results show that the combination of aIL-8 and aPD-1 treatment significantly enhanced antitumor activity following the infusion of myeloid cells. Our results further showed that the target of IL-8 is mainly present in CD16+ myeloid cells and is likely to be granulocytes. FACS analysis showed that aIL-8 treatment increased granulocytic myeloid cells in tumors. Consistently, single-nuclear RNA-sequencing analysis of tumor tissue showed that the innate immune response and cytokine response pathways in the myeloid cell cluster were activated by aIL-8 treatment. This is the first preclinical study using a humanized mouse model for new combination immunotherapeutic development and supports the further clinical testing of aIL-8 in combination with aPD-1 for PDAC treatment. This study also suggests that peripherally derived myeloid cells can potentiate the antitumor response of T cells, likely through the innate immune response, and aIL-8 re-educates tumor-infiltrating myeloid cells by activating the innate immune response.

Risk and Outcome of Breakthrough COVID-19 Infections in Vaccinated Patients With Cancer: Real-World Evidence From the National COVID Cohort Collaborative.

PURPOSE: To provide real-world evidence on risks and outcomes of breakthrough COVID-19 infections in vaccinated patients with cancer using the largest national cohort of COVID-19 cases and controls. METHODS: We used the National COVID Cohort Collaborative (N3C) to identify breakthrough infections between December 1, 2020, and May 31, 2021. We included patients partially or fully vaccinated with mRNA COVID-19 vaccines with no prior SARS-CoV-2 infection record. Risks for breakthrough infection and severe outcomes were analyzed using logistic regression. RESULTS: A total of 6,860 breakthrough cases were identified within the N3C-vaccinated population, among whom 1,460 (21.3%) were patients with cancer. Solid tumors and hematologic malignancies had significantly higher risks for breakthrough infection (odds ratios [ORs] = 1.12, 95% CI, 1.01 to 1.23 and 4.64, 95% CI, 3.98 to 5.38) and severe outcomes (ORs = 1.33, 95% CI, 1.09 to 1.62 and 1.45, 95% CI, 1.08 to 1.95) compared with noncancer patients, adjusting for age, sex, race/ethnicity, smoking status, vaccine type, and vaccination date. Compared with solid tumors, hematologic malignancies were at increased risk for breakthrough infections (adjusted OR ranged from 2.07 for lymphoma to 7.25 for lymphoid leukemia). Breakthrough risk was reduced after the second vaccine dose for all cancers (OR = 0.04; 95% CI, 0.04 to 0.05), and for Moderna's mRNA-1273 compared with Pfizer's BNT162b2 vaccine (OR = 0.66; 95% CI, 0.62 to 0.70), particularly in patients with multiple myeloma (OR = 0.35; 95% CI, 0.15 to 0.72). Medications with major immunosuppressive effects and bone marrow transplantation were strongly associated with breakthrough risk among the vaccinated population. CONCLUSION: Real-world evidence shows that patients with cancer, especially hematologic malignancies, are at higher risk for developing breakthrough infections and severe outcomes. Patients with vaccination were at markedly decreased risk for breakthrough infections. Further work is needed to assess boosters and new SARS-CoV-2 variants.

Chiral separation using cyclodextrins as mobile phase additives in open-tubular liquid chromatography with a pseudophase coating.

The chiral separation of various analytes (dichlorprop, mecoprop, ibuprofen, and ketoprofen) was demonstrated with different cyclodextrins as mobile phase additives in open-tubular liquid chromatography using a stationary pseudophase semipermanent coating. The stable coating was prepared by a successive multiple ionic layer approach using poly(diallyldimethylammonium chloride), polystyrene sulfonate, and didodecyldimethyl ammonium bromide. Increasing concentrations (0-0.2 mM) of various native and derivatized cyclodextrins in 25 mM sodium tetraborate (pH 9.2) were investigated. Chiral separation was achieved for the four test analytes using 0.05-0.1 mM ß-cyclodextrin (resolution between 1.11 and 1.34), γ-cyclodextrin (resolution between 0.78 and 1.27), carboxymethyl-ß-cyclodextrin (resolution between 1.64 and 2.59), and 2-hydroxypropyl-ß-cyclodextrin (resolution between 0.71 and 1.76) with the highest resolutions obtained with 0.1 mM carboxymethyl-ß-cyclodextrin. %RSD values were <10%. This is the first demonstration of chiral open-tubular liquid chromatography using achiral chromatographic coatings and cyclodextrins as mobile phase additives.

Pseudophase microextraction for in-line sample concentration in micellar electrokinetic chromatography.

Pseudophase microextraction (PPME) as a simple in-line sample concentration technique in micellar electrokinetic chromatography (MEKC) is presented. In contrast to popular electric-field driven stacking techniques in MEKC such as sweeping, PPME is pressure-driven. The technique afforded up to 403-2968x improvements in peak heights for fenoprop, dichlorprop, 1- and 2-naphthol compared to typical injection. Under the same MEKC conditions, the improvements in PPME were up to 23-59x better compared to sweeping. Briefly in PPME, the entire capillary was loaded (up to 20 capillary volumes) with the sample prepared in a dilute solution of cetyltrimethylammonium bromide ([CTAB] > critical surface aggregation concentration). The CTAB formed aggregates at the inner capillary walls and these aggregates acted as a stationary chromatographic pseudophase. After clean-up via flushing the capillary with purified water, the MEKC background solution (BGS) with sodium dodecyl sulfate was then introduced by pressure from the outlet end to elute the retained analytes. The analytes concentrate at front of the BGS and the front was moved to the inlet end of the capillary prior to MEKC. Optimization strategies and current limitations in PPME-MEKC are described. The linear ranges using a 4 capillary volume sample load obtained for fenoprop, dichlorprop, 1- and 2-naphthol were between 1 and 160 ng/mL (r2s ≥ 0.996), LOQs = 1-2.5 ng/mL and repeatability %RSDs (n = 6) were ≤5% (intra-day) and ≤7% (inter-day) (using low analyte concentrations 1-5x LOQ). PPME-MEKC with simple dilution of fortified real samples (no off-line sample concentration) was also able to detect low levels of dichlorprop (10 ng/mL, limit set in Australia) and 1- and 2-naphthol (7.5-15 ng/mL) in a drinking water and natural water sample, respectively (% recovery = 84-108%). The concept of PPME may find use in other modes of capillary electrophoresis and other nano-microscale separations.

Bile Salts in Chiral Micellar Electrokinetic Chromatography: 2000-2020.

Bile salts are naturally occurring chiral surfactants that are able to solubilize hydrophobic compounds. Because of this ability, bile salts were exploited as chiral selectors added to the background solution (BGS) in the chiral micellar electrokinetic chromatography (MEKC) of various small molecules. In this review, we aimed to examine the developments in research on chiral MEKC using bile salts as chiral selectors over the past 20 years. The review begins with a discussion of the aggregation of bile salts in chiral recognition and separation, followed by the use of single bile salts and bile salts with other chiral selectors (i.e., cyclodextrins, proteins and single-stranded DNA aptamers). Advanced techniques such as partial-filling MEKC, stacking and single-drop microextraction were considered. Potential applications to real samples, including enantiomeric impurity analysis, were also discussed.

Outcomes of COVID-19 in Patients With Cancer: Report From the National COVID Cohort Collaborative (N3C).

PURPOSE: Variation in risk of adverse clinical outcomes in patients with cancer and COVID-19 has been reported from relatively small cohorts. The NCATS' National COVID Cohort Collaborative (N3C) is a centralized data resource representing the largest multicenter cohort of COVID-19 cases and controls nationwide. We aimed to construct and characterize the cancer cohort within N3C and identify risk factors for all-cause mortality from COVID-19. METHODS: We used 4,382,085 patients from 50 US medical centers to construct a cohort of patients with cancer. We restricted analyses to adults ≥ 18 years old with a COVID-19-positive or COVID-19-negative diagnosis between January 1, 2020, and March 25, 2021. We followed N3C selection of an index encounter per patient for analyses. All analyses were performed in the N3C Data Enclave Palantir platform. RESULTS: A total of 398,579 adult patients with cancer were identified from the N3C cohort; 63,413 (15.9%) were COVID-19-positive. Most common represented cancers were skin (13.8%), breast (13.7%), prostate (10.6%), hematologic (10.5%), and GI cancers (10%). COVID-19 positivity was significantly associated with increased risk of all-cause mortality (hazard ratio, 1.20; 95% CI, 1.15 to 1.24). Among COVID-19-positive patients, age ≥ 65 years, male gender, Southern or Western US residence, an adjusted Charlson Comorbidity Index score ≥ 4, hematologic malignancy, multitumor sites, and recent cytotoxic therapy were associated with increased risk of all-cause mortality. Patients who received recent immunotherapies or targeted therapies did not have higher risk of overall mortality. CONCLUSION: Using N3C, we assembled the largest nationally representative cohort of patients with cancer and COVID-19 to date. We identified demographic and clinical factors associated with increased all-cause mortality in patients with cancer. Full characterization of the cohort will provide further insights into the effects of COVID-19 on cancer outcomes and the ability to continue specific cancer treatments.

Ionic liquids in electrokinetic chromatography.

There is an interest in the application of ionic liquids as additives into the separation media to improve achiral and chiral separations in electrokinetic chromatography (EKC). This review will critically discuss the developments on the use of ionic liquids in the different modes of EKC during the last five years (2015-mid 2020). A healthy number of 48 research articles searched through Scopus were categorised into two: ionic liquids as sole pseudophase (micelles, microemulsions, ligand exchange pseudophase or molecular pseudophase) and ionic liquids with pseudophase (achiral or chiral). More than half of the papers dealt with chiral separations that were mostly facilitated by another additive or pseudophase. The role of ionic liquids for improvement of separations were analysed, and we provided some recommendations for further investigations. Finally, the use of ionic liquids in different on-line sample concentration or stacking methods (i.e., field enhancement and sweeping) was briefly discussed.

Low Frontal Alpha Power Is Associated With the Propensity for Burst Suppression: An Electroencephalogram Phenotype for a "Vulnerable Brain".

BACKGROUND: A number of recent studies have reported an association between intraoperative burst suppression and postoperative delirium. These studies suggest that anesthesia-induced burst suppression may be an indicator of underlying brain vulnerability. A prominent feature of electroencephalogram (EEG) under propofol and sevoflurane anesthesia is the frontal alpha oscillation. This frontal alpha oscillation is known to decline significantly during aging and is generated by prefrontal brain regions that are particularly prone to age-related neurodegeneration. Given that burst suppression and frontal alpha oscillations are both associated with brain vulnerability, we hypothesized that anesthesia-induced frontal alpha power could also be associated with burst suppression. METHODS: We analyzed EEG data from a previously reported cohort in which 155 patients received propofol (n = 60) or sevoflurane (n = 95) as the primary anesthetic. We computed the EEG spectrum during stable anesthetic maintenance and identified whether or not burst suppression occurred during the anesthetic. We characterized the relationship between burst suppression and alpha power using logistic regression. We proposed 5 different models consisting of different combinations of potential contributing factors associated with burst suppression: (1) a Base Model consisting of alpha power; (2) an Extended Mechanistic Model consisting of alpha power, age, and drug dosing information; (3) a Clinical Confounding Factors Model consisting of alpha power, hypotension, and other confounds; (4) a Simplified Model consisting only of alpha power and propofol bolus administration; and (5) a Full Model consisting of all of these variables to control for as much confounding as possible. RESULTS: All models show a consistent significant association between alpha power and burst suppression while adjusting for different sets of covariates, all with consistent effect size estimates. Using the Simplified Model, we found that for each decibel decrease in alpha power, the odds of experiencing burst suppression increased by 1.33-fold. CONCLUSIONS: In this study, we show how a decrease in anesthesia-induced frontal alpha power is associated with an increased propensity for burst suppression, in a manner that captures individualized information above and beyond a patient's chronological age. Lower frontal alpha band power is strongly associated with higher propensity for burst suppression and, therefore, potentially higher risk of postoperative neurocognitive disorders. We hypothesize that low frontal alpha power and increased propensity for burst suppression together characterize a "vulnerable brain" phenotype under anesthesia that could be mechanistically linked to brain metabolism, cognition, and brain aging.

All-optical reversible control of integrated resonant cavity by a self-assembled azobenzene monolayer.

The next frontier in photonics will rely on the synergistic combination of disparate material systems. One unique organic molecule is azobenzene. This molecule can reversibly change conformations when optically excited in the blue (trans-to-cis) or mid-IR (cis-to-trans). Here, we form an oriented monolayer of azobenzene-containing 4-(4-diethylaminophenylazo)pyridine (Aazo) on SiO2 optical resonators. Due to the uniformity of the Aazo layers, quality factors over 106 are achieved. To control the photo-response, the density of Aazo groups is tuned by integrating methyl spacer molecules. Using a pair of lasers, the molecule is reversibly flipped between molecular conformations, inducing a refractive index change which results in a resonant wavelength shift. The magnitude of the shift scales with the relative surface density of Aazo. To investigate reproducibility and stability of the organic monolayer, three switching cycles are demonstrated, and the performance is consistent even after a device is stored in air for 6 months.