Prescription Opioids and Brain Structure in Community-Dwelling Older Adults.

OBJECTIVE: To evaluate the associations between prescription opioid exposures in community-dwelling older adults and gray and white matter structure by magnetic resonance imaging. METHODS: Secondary analysis was conducted of a prospective, longitudinal population-based cohort study employing cross-sectional imaging of older adult (≥65 years) enrollees between November 1, 2004, and December 31, 2017. Gray matter outcomes included cortical thickness in 41 structures and subcortical volumes in 6 structures. White matter outcomes included fractional anisotropy in 40 tracts and global white matter hyperintensity volumes. The primary exposure was prescription opioid availability expressed as the per-year rate of opioid days preceding magnetic resonance imaging, with a secondary exposure of per-year total morphine milligram equivalents (MME). Multivariable models assessed associations between opioid exposures and brain structures. RESULTS: The study included 2185 participants; median (interquartile range) age was 80 (75 to 85) years, 47% were women, and 1246 (57%) received opioids. No significant associations were found between opioids and gray matter. Increased opioid days and MME were associated with decreased white matter fractional anisotropy in 15 (38%) and 16 (40%) regions, respectively, including the corpus callosum, posterior thalamic radiation, and anterior limb of the internal capsule, among others. Opioid days and MME were also associated with greater white matter hyperintensity volume (1.02 [95% CI, 1.002 to 1.036; P=.029] and 1.01 [1.001 to 1.024; P=.032] increase in the geometric mean, respectively). CONCLUSION: The duration and dose of prescription opioids were associated with decreased white matter integrity but not with gray matter structure. Future studies with longitudinal imaging and clinical correlation are warranted to further evaluate these relationships.

Arabidopsis Apoplast TET8 Positively Correlates to Leaf Senescence and tet3tet8 Double Mutants are Delayed in Leaf Senescence.

Extracellular vesicles (EVs) are membrane-bound exosomes secreted into the apoplast. Two distinct populations of EVs have been described in Arabidopsis: PEN1-associated and TET8-associated. We previously noted early leaf senescence in the pen1 single and pen1pen3 double mutant. Both PEN1 and PEN3 are abundant in EV proteomes suggesting EVs might regulate leaf senescence in soil-grown plants. We observed that TET8 is more abundant in the apoplast of early senescing pen1 and pen1pen3 mutant rosettes and in older WT rosettes. The increase in apoplast TET8 in the pen1 mutant did not correspond to increased TET8 mRNA levels. In addition, apoplast TET8 was more abundant in the early leaf senescence myb59 mutant, meaning the increase in apoplast TET8 protein during leaf senescence is not dependent on pen1 or pen3 . Genetic analysis showed a significant delay in leaf senescence in tet3tet8 double mutants after six weeks of growth suggesting that these two tetraspanin paralogs operate additively and are positive regulators of leaf senescence. This is opposite of the effect of pen1 and pen1pen3 mutants that show early senescence and suggest PEN1 to be a negative regulator of leaf senescence. Our work provides initial support that PEN1-associated EVs and TET8-associated EVs may have opposite effects on soil-grown plants undergoing age-related leaf senescence.

Improvement in Accuracy and Concordance of American Society of Anesthesiologist's Physical Status (ASA-PS) Scoring Assignment over a 11 Year Time Period Using Patient BMI as a Comorbidity Finding.

Background: Anesthesia providers categorize patients utilizing the American Society of Anesthesiologists Physical Status (ASA-PS) classification originally created by the ASA in 1941. There is published variability and discordance among providers when assigning patient ASA scores in part due to the subjectivity of scoring utilizing patient medical conditions, but variability is also found using objective findings like BMI. To date, there are few studies evaluating the accuracy of anesthesia providers' ASA assignment based on objective body mass index (BMI) alone. The aim of this retrospective chart review is to determine improvement in accuracy of anesthesia providers to correctly assign patient ASA scores, based on BMI criteria added to the ASA-PS in October of 2014, utilizing a multifaceted strategy including creation of an active finance committee in the fall of 2015, multiple e-mail communications about the updated definitions and recommendations for ASA-PS scoring in the fall of 2015 and spring of 2016, a department grand rounds presentation in February 2016, placement of laminated copies of the ASA definitions and recommendations in the anesthesia chartrooms, and the development of a tool embedded into our EMR providing a recommendation of ASA-PS based on patient comorbidity findings. Methods: After attaining IRB approval, all eligible patients over the age of 18 who had surgical procedures under general anesthesia at Mayo Clinic in Rochester, MN, between January 1, 2010, and December 31, 2020, were retrospectively analyzed. A segmented logistic regression model was used to estimate the trends (per-year change in odds) of ASA under classification according to severity of obesity during 3 epochs: preimplementation (2010-2014), implementation (2015), and postimplementation (2016-2020). Results: A total of 16,467 patients of the 200,423 (8.2%) patients with obesity (class 1, 2, and 3) were underscored based on BMI alone. Accuracy of ASA-PS classification, as it pertains to BMI alone, was found to show meaningful improvement year-to-year following the updated ASA-PS guidelines with examples released in October of 2014 (P < 0.001). Most of the improvement occurred in 2015-2017 with relatively little between-year variability in the rate of underscoring from 2017-2020. Conclusion: Despite updated ASA-PS published guidelines, providers may still be unaware of the updated guidelines and inclusion of examples used within the ASA-PS classification system. Accuracy of scoring did improve annually following the release of the updated guidelines with examples as well as department-wide educational activities on the topic. Additional education and awareness should be offered to those responsible for preanesthesia evaluation and assignment of ASA-PS in patients to improve accuracy as it pertains to BMI.

Individualized prediction of critical illness in older adults: Validation of an elders risk assessment model.

BACKGROUND: The electronic health record (EHR) presents new opportunities for the timely identification of patients at high risk of critical illness and the implementation of preventive strategies. This study aims to externally validate an EHR-based Elders Risk Assessment (ERA) score to identify older patients at high risk of future critical illness during a primary care visit. METHODS: This historical cohort study included patients aged ≥65 years who had primary care visits at Mayo Clinic Rochester, MN, between July 2019 and December 2021. The ERA score at the time of the primary care visit was used to predict critical illness, defined as death or ICU admission within 1 year of the visit. RESULTS: A total of 12,885 patients were included in the analysis. The median age at the time of the primary care visit was 75 years, with 44.6% being male. 93.7% of participants were White, and 64.2% were married. The median (25th, 75th percentile) ERA score was 4 (0, 9). 11.3% of study participants were admitted to the ICU or died within 1 year of the visit. The ERA score predicted critical illness within 1 year of a primary care visit with an area under the receiver operating characteristic curve of 0.84 (95% CI 0.83-0.85), which indicates good discrimination. An ERA score of 9 was identified as optimal for implementing and testing potential preventive strategies, with the odds ratio of having the primary outcome in patients with ERA score ≥9 being 11.33 (95%CI 9.98-12.87). CONCLUSIONS: This simple EHR-based risk assessment model can predict critical illness within 1 year of primary care visits in older patients. The findings of this study can serve as a basis for testing and implementation of preventive strategies to promote the well-being of older adults at risk of critical illness and its consequences.

DERIVATION OF A MORTALITY PREDICTION MODEL IN CRITICAL CARE PATIENTS WITH CIRRHOSIS AND SEPSIS.

ABSTRACT: Objective : The aim of the study is to develop a predictive model for in-hospital mortality in critically ill patients with cirrhosis and sepsis, using clinical and laboratory data. Design : This is a retrospective cohort study. Setting: Medical and mixed intensive care units (ICUs) of a tertiary medical center. Patients : Cirrhotic adults were admitted with sepsis to the ICUs from January of 2007 to May of 2017. Interventions : None. Measurements and Main Results : Of 2,595 ICU admissions of patients with cirrhosis, 277 with first ICU admission for sepsis were included in the analysis, and 37% died in the hospital. Patients who stayed in the ICU for at least 6 h (n = 275) were considered for the multivariate model. Ten-fold cross-validation was used to estimate best parameter values and model performance, and the final model was chosen as the model maximizing area under the receiver-operating characteristic curve. Variables in order of impact were Acute Physiology and Chronic Health Evaluation (APACHE) III score, initial serum lactate, conjugated bilirubin, serum creatinine, model for end-stage liver disease score, age, body mass index, and serum hemoglobin. The final best model from cross-validation presented an area under the receiver operator characteristic curve (AUC) of 0.75, using a cut-point of 50% estimated probability, sensitivity and specificity were 0.46 and 0.90, respectively, with positive predictive value of 0.72 and negative predictive value of 0.74. These results were similar to the APACHE III only model (AUC = 0.74, sensitivity = 0.43, specificity = 0.89, positive predictive value = 0.69, negative predictive value = 0.73). Conclusion : The combination of initial serum lactate level, conjugated bilirubin, initial serum creatinine, model for end-stage liver disease score, age, body mass index, and serum hemoglobin did not yield meaningful improvement in the AUC and did not provide advantage over the APACHE III score for the prediction of in-hospital mortality in critically ill patients with cirrhosis and sepsis.

Preoperative Anemia and Postoperative Outcomes in Cardiac Surgery: A Mediation Analysis Evaluating Intraoperative Transfusion Exposures.

BACKGROUND: Preoperative anemia is associated with adverse outcomes in cardiac surgery, yet it remains unclear what proportion of this association is mediated through red blood cell (RBC) transfusions. METHODS: This is a historical observational cohort study of adults undergoing coronary artery bypass grafting or valve surgery on cardiopulmonary bypass at an academic medical center between May 1, 2008, and May 1, 2018. A mediation analysis framework was used to evaluate the associations between preoperative anemia and postoperative outcomes, including a primary outcome of acute kidney injury (AKI). Intraoperative RBC transfusions were evaluated as mediators of preoperative anemia and outcome relationships. The estimated total effect, average direct effect of preoperative anemia, and percent of the total effect mediated through transfusions are presented with 95% confidence intervals and P -values. RESULTS: A total of 4117 patients were included, including 1234 (30%) with preoperative anemia. Overall, 437 of 4117 (11%) patients went on to develop AKI, with a greater proportion of patients having preoperative anemia (219 of 1234 [18%] vs 218 of 2883 [8%]). In multivariable analyses, the presence of preoperative anemia was associated with increased postoperative AKI (6.4% [4.2%-8.7%] absolute difference in percent with AKI, P < .001), with incremental decreases in preoperative hemoglobin concentrations displaying greater AKI risk (eg, 11.9% [6.9%-17.5%] absolute increase in probability of AKI for preoperative hemoglobin of 9 g/dL compared to a reference of 14 g/dL, P < .001). The association between preoperative anemia and postoperative AKI was primarily due to direct effects of preoperative anemia (5.9% [3.6%-8.3%] absolute difference, P < .001) rather than mediated through intraoperative RBC transfusions (7.5% [-4.3% to 21.1%] of the total effect mediated by transfusions, P = .220). Preoperative anemia was also associated with longer hospital durations (1.07 [1.05-1.10] ratio of geometric mean length of stay, P < .001). Of this total effect, 38% (22%, 62%; P < .001) was estimated to be mediated through subsequent intraoperative RBC transfusion. Preoperative anemia was not associated with reoperation or vascular complications. CONCLUSIONS: Preoperative anemia was associated with higher odds of AKI and longer hospitalizations in cardiac surgery. The attributable effects of anemia and transfusion on postoperative complications are likely to differ across outcomes. Future studies are necessary to further evaluate mechanisms of anemia-associated postoperative organ injury and treatment strategies.

Association between sinusitis and incident rheumatic diseases: a population-based study.

OBJECTIVES: To determine whether antecedent sinusitis is associated with incident rheumatic disease. METHODS: This population-based case-control study included all individuals meeting classification criteria for rheumatic diseases between 1995 and 2014. We matched three controls to each case on age, sex and length of prior electronic health record history. The primary exposure was presence of sinusitis, ascertained by diagnosis codes (positive predictive value 96%). We fit logistic regression models to estimate ORs for incident rheumatic diseases and disease groups, adjusted for confounders. RESULTS: We identified 1729 incident rheumatic disease cases and 5187 matched controls (mean age 63, 67% women, median 14 years electronic health record history). After adjustment, preceding sinusitis was associated with increased risk of several rheumatic diseases, including antiphospholipid syndrome (OR 7.0, 95% CI 1.8 to 27), Sjögren's disease (OR 2.4, 95% CI 1.1 to 5.3), vasculitis (OR 1.4, 95% CI 1.1 to 1.9) and polymyalgia rheumatica (OR 1.4, 95% CI 1.0 to 2.0). Acute sinusitis was also associated with increased risk of seronegative rheumatoid arthritis (OR 1.8, 95% CI 1.1 to 3.1). Sinusitis was most associated with any rheumatic disease in the 5-10 years before disease onset (OR 1.7, 95% CI 1.3 to 2.3). Individuals with seven or more codes for sinusitis had the highest risk for rheumatic disease (OR 1.7, 95% CI 1.3 to 2.4). In addition, the association between sinusitis and incident rheumatic diseases showed the highest point estimates for never smokers (OR 1.7, 95% CI 1.3 to 2.2). CONCLUSIONS: Preceding sinusitis is associated with increased incidence of rheumatic diseases, suggesting a possible role for sinus inflammation in their pathogenesis.

Transfusion targets and adverse events in pediatric perioperative acute Anemia.

STUDY OBJECTIVE: To evaluate the association between pretransfusion and posttransfusion hemoglobin concentrations and the outcomes of children undergoing noncardiac surgery. DESIGN: Retrospective review of patient records. We focused on initial postoperative hemoglobin concentrations, which may provide a more useful representation of transfusion adequacy than pretransfusion hemoglobin triggers (the latter often cannot be obtained during acute surgical hemorrhage). SETTING: Single-center, observational cohort study. PATIENTS: We evaluated all pediatric patients undergoing noncardiac surgery who received intraoperative red blood cell transfusions from January 1, 2008, through December 31, 2018. INTERVENTIONS: None. MEASUREMENTS: Associations between pre- and posttransfusion hemoglobin concentrations (g/dL), hospital-free days, intensive care unit admission, postoperative mechanical ventilation, and infectious complications were evaluated with multivariable regression modeling. MAIN RESULTS: In total, 113,713 unique noncardiac surgical procedures in pediatric patients were evaluated, and 741 procedures met inclusion criteria (median [range] age, 7 [1-14] years). Four hundred ninety-eight patients (68%) with a known preoperative hemoglobin level had anemia; of these, 14% had a preexisting diagnosis of anemia in their health record. Median (IQR) pretransfusion hemoglobin concentration was 8.1 (7.4-9.2) g/dL and median (IQR) initial postoperative hemoglobin concentration was 10.4 (9.3-11.6) g/dL. Each decrease of 1 g/dL in the initial postoperative hemoglobin concentration was associated with increased odds of transfusion within the first 24 postoperative hours (odds ratio [95% CI], 1.62 [1.37-1.93]; P < .001). No significant relationships were observed between postoperative hemoglobin concentrations and hospital-free days (P = .56), intensive care unit admission (P = .71), postoperative mechanical ventilation (P = .63), or infectious complications (P = .74). CONCLUSIONS: In transfused patients, there was no association between postoperative hemoglobin values and clinical outcomes, except the need for subsequent transfusion. Most transfused patients presented to the operating room with anemia, which suggests a potential opportunity for perioperative optimization of health before surgery.

A pilot oral history of plant synthetic biology.

The whole field of synthetic biology (SynBio) is only about 20 years old, and plant SynBio is younger still. Nevertheless, within that short time, SynBio in general has drawn more scientific, philosophical, government, and private-sector interest than anything in biology since the recombinant DNA revolution. Plant SynBio, in particular, is now drawing more and more interest in relation to plants' potential to help solve planetary problems such as carbon capture and storage and replacing fossil fuels and feedstocks. As plant SynBio is so young and so fast-developing, we felt it was too soon to try to analyze its history. Instead, we set out to capture the essence of plant SynBio's origins and early development through interviews with 8 of the field's founders, representing 5 countries and 3 continents. We then distilled these founders' personal recollections and reflections into this review, centering the narrative on timelines for pivotal events, articles, funding programs, and quoting from interviews. We have archived the interview recordings and documented timeline entries. This work provides a resource for future historical scholarship.

Clinical presentation and outcomes in patients with antiphospholipid syndrome-associated adrenal hemorrhage. A multicenter cohort study and systematic literature review.

BACKGROUND: Adrenal hemorrhage (AH) can occur in patients with antiphospholipid Syndrome (APS). We aimed to characterize the clinical manifestations, treatments, and outcomes of patients presenting with APS-associated AH (APS-AH) through a retrospective cohort and a systematic literature review (SLR). METHODS: We performed a mixed-source approach combining a multicenter cohort with an SLR of patients with incident APS-AH. We included patients from Mayo Clinic and published cases with persistent positivity for antiphospholipid antibodies and presenting with AH, demonstrated by imaging or biopsy. We extracted demographics, clinical characteristics, laboratory findings, treatment strategies, and outcomes (primary adrenal insufficiency and mortality). We used Kaplan-Meier and Cox models for survival analysis. RESULTS: We included 256 patients in total, 61 (24%) from Mayo Clinic and 195 (76%) from the SLR. The mean age was 46.8 (SD 15.2) years, and 45% were female. 69% of patients had bilateral adrenal involvement and 64% presented adrenal insufficiency. The most common symptoms at presentation were abdominal pain in 79%, and nausea and vomiting 46%. Hyponatremia (77%) was the most common electrolyte abnormality. Factors associated with primary adrenal insufficiency were bilateral adrenal involvement at initial imaging (OR 3.73, CI; 95%, 1.47-9.46) and anticardiolipin IgG positivity (OR 3.80, CI; 95%, 1.30-11.09). The survival rate at five years was 82%. History of stroke was associated with 3.6-fold increase in mortality (HR 3.62, 95% CI; 1.33-9.85). CONCLUSION: AH is a severe manifestation of APS with increased mortality. Most patients developed permanent primary adrenal insufficiency, particularly those positive for anticardiolipin IgG and bilateral adrenal involvement.

Utilisation of cardiovascular preventive services in a rheumatoid arthritis population-based cohort.

OBJECTIVES: The objective is to examine utilisation of cardiovascular preventive services in patients with rheumatoid arthritis (RA), compared with a non-RA population, and to examine cardiovascular disease (CVD) screening rates among RA patients without diabetes mellitus (DM), hypertension or hyperlipidaemia to non-RA patients with one of these diagnoses. METHODS: All ≥18-year-old patients with an RA diagnosis living in one of eight Minnesota counties on 1 January 2015 were included and matched (1:1) by sex, age and county to non-RA comparators. Rates of screening for CVD risk factors, including DM (ie, glucose), hypertension (ie, blood pressure) and hyperlipidaemia (ie, lipids), were compared between groups using Cox models. RESULTS: The study included 1614 patients with RA and 1599 non-RA comparators. DM screening was more common among patients with RA (HR: 1.10, 95% CI: 1.01 to 1.19), as was hypertension screening (HR: 1.37, 95% CI: 1.24 to 1.52). Hyperlipidaemia screening in RA was similar to comparators (HR: 0.99, 95% CI: 0.89 to 1.10). Conversely, patients with RA and no CVD risk factors had a lower probability of undergoing diabetes (HR: 0.67, 95% CI: 0.57 to 0.78) and hyperlipidaemia screening (HR: 0.65, 95% CI: 0.54 to 0.79) than non-RA patients with only one CVD risk factor diagnosis. Hypertension screening was similar between both groups. CONCLUSIONS: RA patients undergo CVD preventive screening at rates at least comparable to the general population. However, patients with RA as their sole CVD risk factor were less likely to undergo screenings, despite an equivalent-to-higher risk as the traditional CVD risk factors. These findings demonstrate opportunities for improvement of RA patient care.

Adapting enzymes to improve their functionality in plants: why and how.

Synthetic biology creates new metabolic processes and improves existing ones using engineered or natural enzymes. These enzymes are often sourced from cells that differ from those in the target plant organ with respect to, e.g. redox potential, effector levels, or proteostasis machinery. Non-native enzymes may thus need to be adapted to work well in their new plant context ('plantized') even if their specificity and kinetics in vitro are adequate. Hence there are two distinct ways in which an enzyme destined for use in plants can require improvement: In catalytic properties such as substrate and product specificity, kcat, and KM; and in general compatibility with the milieu of cells that express the enzyme. Continuous directed evolution systems can deliver both types of improvement and are so far the most broadly effective way to deliver the second type. Accordingly, in this review we provide a short account of continuous evolution methods, emphasizing the yeast OrthoRep system because of its suitability for plant applications. We then cover the down-to-earth and increasingly urgent issues of which enzymes and enzyme properties can - or cannot - be improved in theory, and which in practice are the best to target for crop improvement, i.e. those that are realistically improvable and important enough to warrant deploying continuous directed evolution. We take horticultural crops as examples because of the opportunities they present and to sharpen the focus.

Intrathecal Opioid Use in Kidney Transplantation: An Observational Cohort Study.

BACKGROUND: Kidney transplant is the most common transplant operation performed in the United States. Although various approaches to pain management have been described, the optimal analgesic strategy remains undefined. Specifically, the role of intrathecal opioids in this patient population has not been comprehensively evaluated. METHODS: Using a retrospective cohort design, data from kidney transplant operations at a single tertiary care medical center between August 1, 2017, and July 31, 2022, were extracted. Inverse probability of treatment weighting (IPTW) was used to assess differences in clinical outcomes based on the presence or absence of intrathecal opioid administration before surgical incision. The primary outcome was total opioid exposure expressed in milligram morphine equivalents (MME) in the first 72 hours postoperatively, with secondary outcomes including total MME (intraoperative plus postoperative MME, postoperative pain scores, and the presence of postoperative nausea/vomiting [PONV], pruritus, or adverse events). RESULTS: A total of 1014 kidney transplants in 1012 unique patients were included, with 411 (41%) receiving intrathecal opioids preoperatively. Hydromorphone was the intrathecal opioid used in all cases with median dose of 100 µg (interquartile range [IQR], 100, 100; range 50-200). Subjects receiving intrathecal opioids had significantly lower postoperative opioid requirements at 72 hours (30 [0-68] vs 64 [22, 120] MME), with ratio of geometric means in the IPTW analysis (ratio of geometric means 0.34, 95% confidence interval [CI], 0.26-0.43; P < .001). Similar findings were observed for total opioids (45 [30-75] vs 75 [60-90] MME; ratio of geometric means 0.58, 95% CI, 0.54-0.63; P < .001). Maximum reported pain scores in the intrathecal group were lower at 24 hours (4 [2-7] vs 7 [5, 8]; OR, 0.28; 95% CI, 0.21-0.37 for experiencing a higher pain score with intrathecal opioids, P < .001) and 72 hours (6 [4-7] vs 7 [5-8]; OR, 0.41; 95% CI, 0.31-0.54; P < .001). Patients receiving intrathecal opioids were more likely to experience PONV (225 of 411 [55%] vs 232 of 603 [38%]; OR, 2.16; 95% CI, 1.63-2.86; P < .001). CONCLUSIONS: Intrathecal opioid administration was associated with improved pain outcomes in patients undergoing kidney transplantation, including lower opioid requirements and pain scores through 72 hours. However, this was accompanied by an increased risk of PONV.

Large vessel involvement in antineutrophil cytoplasmic antibody-associated vasculitis.

OBJECTIVES: Anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is currently categorized under the small vessel vasculitides. There is limited knowledge about large vessel involvement in AAV (L-AAV), mainly described in case reports and small series. L-AAV can involve temporal arteries (TA-AAV), aorta (A-AAV), and periaortic soft tissue (PA-AAV). We sought to characterize the features of patients with L-AAV. METHODS: Patients older than 18 years at diagnosis of TA-AAV, A-AAV and PA-AAV seen at the Mayo Clinic, Rochester between January 1, 2000, and December 31, 2021, were identified through a proprietary medical text search algorithm. Patients were included if diagnosed with L-AAV, fulfilled 2022 ACR/EULAR classification criteria for GPA, MPA, or EGPA, had positive ANCA test results, and had more than one outpatient or inpatient visit. RESULTS: The study cohort consists of 36 patients with L-AAV. Of those, 23 had p-ANCA and/or MPO-ANCA; 13 had c-ANCA and/or PR3-ANCA. Mean (SD) age at AAV diagnosis was 63.4 (12.79); 20 (56%) were male. Seventeen patients had TA-AAV, 10 had A-AAV and 9 had PA-AAV. Most patients (n = 25, 69%) were diagnosed with large vessel vasculitis and AAV within a one-year timespan. Twenty-five (69%) patients had histopathologic confirmation of AAV diagnosis in a location other than temporal artery, aorta, or periaortic soft tissue. Glucocorticoids (36/36), rituximab (19/36), and methotrexate (18/36) were the most frequent treatments. CONCLUSIONS: This is the largest single-center cohort of patients with L-AAV to date. AAV can involve large arteries, albeit infrequent. AAV-targeted therapy should be considered in patients with L-AAV.

Mental Health Questions on State Medical License Applications and Evaluation of Updates.

This cross-sectional study evaluates the consistency of US medical license renewal applications with the Federation of State Medical Boards recommendations for questions regarding physician mental health.

Clinical features, risk factors, and outcomes of diffuse alveolar hemorrhage in antiphospholipid syndrome: A mixed-method approach combining a multicenter cohort with a systematic literature review.

BACKGROUND: Antiphospholipid syndrome (APS) is a systemic autoimmune disease clinically associated with thrombotic and obstetric events. Additional manifestations have been associated with APS, like diffuse alveolar hemorrhage (DAH). We aimed to summarize all the evidence available to describe the presenting clinical features, their prognostic factors, and short- and long-term outcomes. METHODS: We performed a mixed-method approach combining a multicenter cohort with a systematic literature review (SLR) of patients with incident APS-associated DAH. We described their clinical features, treatments, prognostic factors, and outcomes (relapse, mortality, and requirement of mechanical ventilation [MV]). Kaplan-Meier methods were used to estimate relapse and mortality rates, and Cox and logistic regression models were used to assess the factors associated as appropriate. RESULTS: We included 219 patients with incident APS-associated DAH (61 from Mayo Clinic and 158 from SLR). The median age was 39.5 years, 51% were female, 29% had systemic lupus erythematosus, and 34% presented with catastrophic APS (CAPS). 74% of patients had a history of thrombotic events, and 26% of women had a history of pregnancy morbidity; half of the patients had a history of thrombocytopenia, and a third had valvulopathy. Before DAH, 55% of the patients were anticoagulated. At DAH onset, 65% of patients presented hemoptysis. The relapse rate was 47% at six months and 52% at one year. Triple positivity (HR 4.22, 95% CI 1.14-15.59) was associated with relapse at six months. The estimated mortality at one and five years was 30.3% and 45.8%. Factors associated with mortality were severe thrombocytopenia (< 50 K/µL) (HR 3.10, 95% CI 1.39-6.92), valve vegetations (HR 3.22, 95% CI 1.14-9.07), CAPS (HR 3.80, 95% CI 1.84-7.87), and requirement of MV (HR 2.22, 95% CI 1.03-4.80). Forty-two percent of patients required MV on the incident DAH episode. Patients presenting with severe thrombocytopenia (OR 6.42, 95% CI 1.77-23.30) or CAPS (OR 4.30, 95% CI 1.65-11.16) were more likely to require MV. CONCLUSION: APS-associated DAH is associated with high morbidity and mortality, particularly when presenting with triple positivity, thrombocytopenia, valvular involvement, and CAPS.

Running the numbers on plant synthetic biology solutions to global problems.

Synthetic biology and metabolic engineering promise to deliver sustainable solutions to global problems such as phasing out fossil fuels and replacing industrial nitrogen fixation. While this promise is real, scale matters, and so do knock-on effects of implementing solutions. Both scale and knock-on effects can be estimated by 'Fermi calculations' (aka 'back-of-envelope calculations') that use uncontroversial input data plus simple arithmetic to reach rough but reliable conclusions. Here, we illustrate how this is done and how informative it can be using two cases: oilcane (sugarcane engineered to accumulate triglycerides instead of sugar) as a source of bio-jet fuel, and nitrogen fixation by bacteria in mucilage secreted by maize aerial roots. We estimate that oilcane could meet no more than about 1% of today's U.S. jet fuel demand if grown on all current U.S. sugarcane land and that, if cane land were expanded to meet two-thirds of this demand, the fertilizer and refinery requirements would create a large carbon footprint. Conversely, we estimate that nitrogen fixation in aerial-root mucilage could replace up to 10% of the fertilizer nitrogen applied to U.S. maize, that 2% of plant carbon income used for growth would suffice to fuel the fixation, and that this extra carbon consumption would likely reduce grain yield only slightly.

Persistent aortic inflammation in patients with giant cell arteritis.

OBJECTIVES: To investigate the clinicopathologic features of patients with giant cell arteritis (GCA) who had thoracic aorta aneurysm or dissection surgery. METHODS: Patients who had thoracic aorta surgery between January 1, 2000, and December 31, 2021, at the Mayo Clinic, Rochester, Minnesota, were identified with current procedural terminology (CPT) codes. The identified patients were screened for a prior diagnosis of GCA with diagnostic codes and electronic text search. The available medical records of all the patients of interest were manually reviewed. Thoracic aorta tissues obtained during surgery were re-evaluated in detail by pathologists. The clinicopathologic features of these patients were analyzed. Overall observed survival was compared with lifetable rates from the United States population. RESULTS: Of the 4621 patients with a CPT code for thoracic aorta surgery, 49 had a previous diagnosis of GCA. Histopathologic evaluation of the aortic tissue revealed active aortitis in most patients with GCA (40/49, 82%) after a median (IQR) of 6.0 (2.6-10.3) years from GCA diagnosis. All patients were considered in clinical remission at the time of aortic surgery. The overall mortality compared to age and sex-matched general population was significantly increased with a standardized mortality ratio of 1.55 (95% CI, 1.05-2.19). CONCLUSION: Histopathologic evaluation of the thoracic aorta obtained during surgery revealed active aortitis in most patients with GCA despite being considered in clinical remission several years after GCA diagnosis. Chronic, smoldering aortic inflammation likely contributes to the development of aortic aneurysm and dissection in GCA.