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Background: Echocardiographic deformation-based ratios and novel multi-parametric scores have been suggested to discriminate transthyretin cardiac amyloidosis (ATTR-CM) from other causes of increased left ventricular wall thickness among patients referred for ATTR-CM evaluation. Their relative predictive accuracy has not been well studied. We sought to (1) identify echocardiographic parameters predictive of ATTR-CM and (2) compare the diagnostic accuracy of these parameters in patients with suspected ATTR-CM referred for technetium-99m-pyrophosphate scintigraphy. Methods: Echocardiograms from 598 patients referred to 3 major amyloidosis centers for technetium-99m-pyrophosphate to detect ATTR-CM were analyzed, including longitudinal strain (LS) analysis. Deformation ratios (septal apex to base ratio, relative apical sparing, ejection fraction to global LS), a multi-center European increased wall thickness score, and Mayo Clinic derived ATTR score (transthyretin cardiac amyloidosis score) were calculated. A logistic regression model was used to identify the parameters that best associated with a diagnosis of ATTR-CM. Comparison of the diagnostic capacity of the parameters was performed by receiver operating characteristic curves and the area under the curve (AUC). Results: Over half of the subjects (54.2%) were diagnosed with ATTR-CM (78% were men, median age of 76 years). Age, inferolateral wall thickness, and basal LS were the strongest predictors of ATTR-CM, AUC of 0.87 (95% CI: 0.83, 0.90), superior to the increased wall thickness score AUC of 0.78 (95% CI: 0.73, 0.83; P =0.004). An inferolateral wall thickness of ≥14 mm (AUC: 0.73) was as accurate as the published cut-offs for transthyretin cardiac amyloidosis score and septal apex to base (AUC: 0.72 and 0.69, P =0.8 and P =0.1, respectively), and was superior to ejection fraction to global LS and relative apical sparing (AUC: 0.64 and 0.53, P P =0.2); outperforming the other indices ( P Conclusion: Inferolateral wall thickness and average basal LS performed as well as or better than more complex echo ratios and multiparametric scores to predict ATTR-CM.

The relation of high-sensitivity cardiac troponin I (hs-cTnI) concentration and presence of obstructive coronary artery disease (CAD) in patients without myocardial infarction (MI) is unclear. Study participants selected from patients free of MI who underwent coronary angiography with or without intervention were enrolled, and hs-cTnI measured. A gradient boosting model was implemented to build a model for detection of CAD. Cox proportional hazard regression was used to assess the association of hs-cTnI and adverse cardiovascular (CV) outcome. Among 978 study participants, 607 patients (62%) had CAD. Higher concentrations of hs-cTnI were associated with chronic kidney disease, heart failure, CAD, male gender, current tobacco use, anemia, age, and low-density lipoprotein cholesterol. History of CAD, male gender, type 2 diabetes mellitus, hs-cTnI, anemia, age, and high-density lipoprotein cholesterol were the most influential factors for detection of CAD. The gradient boosting model had an area under the curve of 0.82, accuracy of 75%, sensitivity of 88%, specificity of 52%, positive predictive value of 76%, and negative predictive value of 72% for detection of CAD. Increase in 1 log unit of hs-cTnI was significantly associated with increased risk of incident MI (hazard ratio [HR] 1.34, 95% confidence interval [CI] 1.22 to 1.47, p0.001), CV mortality (HR 1. 24, 95% CI 1.11 to 1.39, p0.001), and composite of incident MI or CV mortality (HR 1.29, 95% CI 1.20 to 1.40, p0.001). In conclusion, among patients without acute MI and CAD, higher concentrations of hs-cTnI were associated with the presence of CAD and linked to increased risk of future CV events. ClinicalTrials.gov Identifier: NCT00842868.

Psychiatric-Mental Health nurses can build cultural competence when caring for clients who are Sexual and Gender Minorities (LGBTQIA+) in the following ways: by learning how health care pathologized core aspects of Sexual and Gender Minorities' (SGM) identities; by understanding historical and current SGM minority stressors and consequent health disparities and inequities; and by framing health disparities and inequities as forms of cultural violence. To begin building trust among SGMs and health care providers, trust damaged by cultural violence and stigma, nurses can implement the Nonviolent Communication Process in clinical settings.

BACKGROUND: Immune checkpoint inhibitors (ICI) are widely used cancer treatments. There are limited data the risk for developing venous thromboembolism (VTE) among patients on an ICI. METHODS: This was a retrospective study of 2854 patients who received ICIs at a single academic center. VTE events, defined as a composite of deep vein thrombosis (DVT) or pulmonary embolism (PE), were identified by individual chart review and were blindly adjudicated using standard imaging criteria. A self-controlled risk-interval design was applied with an “at-risk period” defined as the two-year period after, and the “control period”, defined as the two-year prior to treatment. The hazard ratio (HR) was calculated using a fixed-effect proportional hazards model. RESULTS: Of the 2854 patients, 1640 (57.5%) were men; mean age was 64±13 years. The risk for VTE was 7.4% at 6 months and 13.8% at 1 year after starting an ICI. The rate of VTE was >4-fold higher after starting an ICI (HR 4.98, 95% CI 3.65 – 8.59, p

BACKGROUND Management of abdominal aortic aneurysms (AAAs) requires serial imaging surveillance to evaluate the aneurysm dimension. Natural language processing (NLP) has been previously developed to retrospectively identify patients with AAA from electronic health records (EHRs). However, there are no reported studies that use NLP to identify patients with AAA in near real-time from radiology reports. OBJECTIVE This study aims to develop and validate a rule-based NLP algorithm for near real-time automatic extraction of AAA diagnosis from radiology reports for case identification. METHODS The AAA-NLP algorithm was developed and deployed to an EHR big data infrastructure for near real-time processing of radiology reports from May 1, 2019, to September 2020. NLP extracted named entities for AAA case identification and classified subjects as cases and controls. The reference standard to assess algorithm performance was a manual review of processed radiology reports by trained physicians following standardized criteria. Reviewers were blinded to the diagnosis of each subject. The AAA-NLP algorithm was refined in 3 successive iterations. For each iteration, the AAA-NLP algorithm was modified based on performance compared to the reference standard. RESULTS A total of 360 reports were reviewed, of which 120 radiology reports were randomly selected for each iteration. At each iteration, the AAA-NLP algorithm performance improved. The algorithm identified AAA cases in near real-time with high positive predictive value (0.98), sensitivity (0.95), specificity (0.98), F1 score (0.97), and accuracy (0.97). CONCLUSIONS Implementation of NLP for accurate identification of AAA cases from radiology reports with high performance in near real time is feasible. This NLP technique will support automated input for patient care and clinical decision support tools for the management of patients with AAA.

Background Coronary vasospasm is a recognized side effect of 5-fluorouracil (5-FU). There are limited and conflicting data on the incidence, risk factors, and prognostic effect of 5-FU–associated vasospasm. Objectives This study sought to assess the incidence, risk factors, and prognostic implications of 5-FU coronary vasospasm among patients receiving 5-FU regimens at a single tertiary care center. Methods The study conducted a retrospective analysis of all patients who received 5-FU at a single academic center from January 2009 to July 2019. Vasospasm was defined as the occurrence of a typical chest pain syndrome in the presence of 5-FU. The presence of associated electrocardiogram changes or elevated biomarkers was used to further confirm the diagnosis. Patients with vasospasm were compared with patients treated with 5-FU without vasospasm in a 1:2 ratio. Data regarding demographics, medical history, and follow-up were collected by manual chart review. Results From approximately 4,019 individual patients who received 5-FU from 2009 to 2019 at a single center, 87 (2.16%) developed vasospasm. Patients who developed vasospasm were younger (age 58 ± 13 years vs. 64 ± 13 years; p = 0.001) and were less likely to have any cardiovascular risk factors (70.1% vs. 84.5%; p = 0.007). Patients with vasospasm and patients without vasospasm were otherwise similar in terms of types of cancer, stage of cancer, sex, and race. There was no significant difference in progression-free survival, overall mortality or cancer specific mortality between patients who developed vasospasm versus those who did not. Conclusions In a large, single-center report of 5-FU–associated vasospasm, patients who developed vasospasm were younger, had lower rates of traditional cardiovascular risk factors, and had no significant difference in progression-free or overall survival compared with those who did not develop vasospasm.

This study sought to assess associations between longitudinal change in atrial natriuretic peptide (ANP) and reverse cardiac remodeling following initiation of sacubitril/valsartan in patients with heart failure with reduced ejection fraction (HFrEF).Neprilysin inhibition results in an increase of several vasoactive peptides that may mediate the beneficial effects of sacubitril/valsartan, including ANP.In a prospective study of initiation and titration of sacubitril/valsartan in patients with HFrEF, blood was collected at scheduled time points into tubes containing protease inhibitors. This pre-specified exploratory analysis included patients in whom ANP was measured at baseline and serially through 12 months of treatment.Among 144 participants (mean age: 64.5 years; left ventricular ejection fraction: 30.8%), following initiation of sacubitril/valsartan, there was an early and significant increase in ANP, with the majority of rise from 99 pg/ml at baseline to 156 pg/ml at day 14 (p 0.001). There was a further trend toward a second increase from day 30 to day 45 (p = 0.07). At maximal rise, ANP had doubled. In longitudinal analyses, early rise in ANP was followed by a subsequent increase in urinary cycle guanosine monophosphate. Larger early increase in ANP was associated with larger later improvements in left ventricular ejection fraction and left atrial volume index (p 0.001 for both).Concentrations of ANP doubled after initiation of sacubitril/valsartan in patients with HFrEF. Larger early increases in ANP were associated with a greater magnitude of subsequent reverse cardiac remodeling. (Effects of Sacubitril/Valsartan Therapy on Biomarkers, Myocardial Remodeling and Outcomes [PROVE-HF]; NCT02887183).

Background Management of abdominal aortic aneurysms (AAAs) requires serial imaging surveillance to evaluate the aneurysm dimension. Natural language processing (NLP) has been previously developed to retrospectively identify patients with AAA from electronic health records (EHRs). However, there are no reported studies that use NLP to identify patients with AAA in near real-time from radiology reports. Objective This study aims to develop and validate a rule-based NLP algorithm for near real-time automatic extraction of AAA diagnosis from radiology reports for case identification. Methods The AAA-NLP algorithm was developed and deployed to an EHR big data infrastructure for near real-time processing of radiology reports from May 1, 2019, to September 2020. NLP extracted named entities for AAA case identification and classified subjects as cases and controls. The reference standard to assess algorithm performance was a manual review of processed radiology reports by trained physicians following standardized criteria. Reviewers were blinded to the diagnosis of each subject. The AAA-NLP algorithm was refined in 3 successive iterations. For each iteration, the AAA-NLP algorithm was modified based on performance compared to the reference standard. Results A total of 360 reports were reviewed, of which 120 radiology reports were randomly selected for each iteration. At each iteration, the AAA-NLP algorithm performance improved. The algorithm identified AAA cases in near real-time with high positive predictive value (0.98), sensitivity (0.95), specificity (0.98), F1 score (0.97), and accuracy (0.97). Conclusions Implementation of NLP for accurate identification of AAA cases from radiology reports with high performance in near real time is feasible. This NLP technique will support automated input for patient care and clinical decision support tools for the management of patients with AAA.

Sacubitril/valsartan (Sac/Val) improves outcomes in patients with heart failure with reduced ejection fraction (HFrEF).In this study, the authors sought to explore age differences in effects of Sac/Val on biomarkers, Kansas City Cardiomyopathy Questionnaire (KCCQ)-23 scores and cardiac remodeling.After initiation and titration of Sac/Val, concentrations of N-terminal pro-B-type natriuretic peptide (NT-proBNP), high-sensitivity troponin T (hs-cTnT), and soluble suppressor of tumorigenicity 2 (sST2) were measured and KCCQ-23 scores obtained from baseline to 12 months. Left ventricular ejection fraction (LVEF), and indexed left ventricular end-systolic (LVESVi) and indexed left ventricular end-diastolic (LVEDVi) and left atrial volume index (LAVi) volumes were measured with the use of echocardiography. Safety end points were assessed. Age-stratified analysis was performed for groups aged 65, 65-74, and ≥75 years.Among 794 participants with HFrEF (mean age 65.1 years, 28.5% women), compared with patients aged 65 years (n = 369), 65-74 years (n = 237), and those aged ≥75 years (n = 188), had similar reductions in hs-cTnT and sST2, but less NT-proBNP reduction (-45.6% vs -40.2% vs -30.5%, respectively; P = 0.02). Gains in KCCQ-23 were smaller (+11.8 vs +11.4 vs +6.0 points; P = 0.03) in patients aged ≥75 years, although similar proportions of each age group achieved ≥10-point and ≥20-point increases in KCCQ-23 by month 12. Improvements in LVEF, LVEDVi, LVESVi, and LAVi were similar among age groups. Incidence of safety end points was also similar.Sac/Val resulted in significant improvements in prognostic biomarkers and measures of cardiac remodeling and health status from baseline to month 12 across age categories. Older study participants showed somewhat blunted reduction in NT-proBNP and less improvement in KCCQ-23 overall summary scores. (Effects of Sacubitril/Valsartan Therapy on Biomarkers, Myocardial Remodeling, and Outcomes [PROVE-HF]; NCT02887183).

It has long been observed that heart failure (HF) is associated with measures of systemic inflammation. In recent years, there have been significant advancements in our understanding of how inflammation contributes to the pathogenesis and progression of HF. However, although numerous studies have validated the association between measures of inflammation and HF severity and prognosis, clinical trials of anti-inflammatory therapies have proven mostly unsuccessful. On this backdrop emerges the yet unmet goal of targeting precise phenotypes within the syndrome of HF; if such precise definitions can be realized, and with better understanding of the roles played by specific inflammatory mediators, the expectation is that targeted anti-inflammatory therapies may improve prognosis in patients whose HF is driven by inflammatory pathobiology. Here, the authors describe mechanistic links between inflammation and HF, discuss traditional and novel inflammatory biomarkers, and summarize the latest evidence from clinical trials of anti-inflammatory therapies.

Issue: The physical examination has been in decline for many years and poorer skills contribute to medical errors and adverse events. Diagnostic error is also increasing with the complexity of medicine. Comparing the physical examination in Ireland and the United States with a focus on education, assessment, culture, and health systems may provide insight into the decline of the physical exam in the United States, uncover possible strategies to improve clinical skills, and limit diagnostic error. Evidence: The physical exam is a core component of both undergraduate and postgraduate medical education in Ireland. This is reflected by the time and effort invested by medical schools and medical societies in Ireland in teaching and assessing skills. This high standard of skills results in the physical exam being a key component of the diagnostic process and a gatekeeper to expensive investigations essential in a resource-limited health system such as Ireland. Use of the physical exam in the United States is hindered by the high-tech transformation of healthcare and a more litigious society. Known strategies to highlight the role of the physical exam in clinical practice include creating an evidence base to show that better physical exam skills improve outcomes, identifying accurate physical exam maneuvers, stressing the therapeutic alliance the physical exam brings to the patient encounter, and the incorporation of technology into the bedside exam. Implications: Contrasting the education and clinical use of the physical examination in the United States with Ireland allowed us to identify a number of strategies which could be used to promote the physical exam among learners in both countries. Highlighting simple and pragmatic physical exam maneuvers combined with evidence-based physical exam diagnostic data may renew confidence in the physical exam as a core diagnostic tool. Use of the hypothesis-driven approach may streamline a clinician's physical exam during a patient encounter, focusing on the key examination components and avoiding unnecessary and low yield maneuvers. The absence of assessment of physical exam skills using real patients in United States licensing exams communicates to learners that these skills are not important. However, steps to introduce a culture of assessment to drive learning are being introduced. One area Ireland could learn from the United States is incorporating more technology into the bedside exam. Enhanced physical examination skills in both countries could reduce reliance on expensive investigations and improve diagnostic accuracy.

Background Coronary vasospasm is a known side effect of 5-FU (fluorouracil) therapy. Beyond switching to non-5FU-based chemotherapy, there are no established treatments for 5-FU associated coronary vasospam. Our objective was to assess the safety and efficacy of re-challenge with 5-FU after pre-treatment with calcium channel blockers (CCBs) and long-acting nitrates among patients 5-FU associated coronary vasospasm. Methods We conducted a retrospective study of patients with 5-FU coronary vasospasm at a single academic center. By protocol, those referred to cardio-oncology received pre-treatment with either combination [nitrates and CCBs] or single-agent therapy [nitrates or CCBs]) prior to re-challenge with 5-FU. Our primary outcome was overall survival. Other important outcomes included progression-free survival and safety. Results Among 6,606 patients who received 5-FU from January 2001 to Dec 2020, 115 (1.74%) developed coronary vasospasm. Of these 115 patients, 81 patients continued 5-FU therapy, while 34 stopped. Of the 81 who continued, 78 were referred to cardio-oncology and prescribed CCBs and/or nitrates prior to subsequent 5-FU, while the remaining 3 continued 5-FU without cardiac pre-treatment. Of the 78, 56.4% (44/78) received both nitrates and CCBs, 19.2% (15/78) received CCBs alone, and 24.4% (19/78) received nitrates alone. When compared to patients who stopped 5-FU, those who continued 5-FU after pre-treatment (single or combination therapy) had a decreased risk of death (HR 0.42, P = 0.005 [95% CI 0.23–0.77]) and a trend towards decreased cancer progression (HR 0.60, P = 0.08 [95% CI 0.34–1.06]). No patient in the pre-treatment group had a myocardial infarct after re-challenge; however, chest pain (without myocardial infarction) recurred in 19.2% (15/78) among those who received cardiac pre-treatment vs. 66.7% (2/3) among those who did not (P = 0.048). There was no difference in efficacy or the recurrence of vasospasm among patients who received pre-treatment with a single agent (nitrates or CCBs) or combination therapy (14.7% (5/34) vs. 25.0% (11/44), P = 0.26). Conclusion Re-challenge after pre-treatment with CCBs and nitrates guided by a cardio-oncology service was safe and allowed continued 5-FU therapy.

This study assessed changes in B-type natriuretic peptide (BNP) among patients with heart failure with reduced ejection fraction (HFrEF) treated with sacubitril/valsartan (Sac/Val) according to standard prescribing information.Through inhibition of neprilysin, Sac/Val may increase BNP concentrations.In an individual patient analysis from the EVALUATE-HF (Study of Effects of Sacubitril/Valsartan vs. Enalapril on Aortic Stiffness in Patients With Mild to Moderate HF With Reduced Ejection Fraction) (n = 221) and the PROVE-HF (Effects of Sacubitril/Valsartan Therapy on Biomarkers, Myocardial Remodeling and Outcomes) (n = 146) studies, we examined changes in BNP, N-terminal pro-BNP (NT-proBNP), and urinary cyclic guanosine monophosphate (ucGMP) from baseline to week 4 and week 12.Median (IQRs) concentration of BNP at baseline, week 4, and week 12 were 145 [IQR: 55-329], 136 [IQR: 50-338], and 135 [IQR: 51-299] ng/L, respectively. There was no significant change from baseline to week 4 (0% [-30% to +41%]; P = 0.36) or week 12 (+1% [-36% to +50%]; P = 0.97). By week 12, one-half of the study participants had a BNP decline. There was no association between Sac/Val dose and BNP changes. Change in BNP was directly associated with change in NT-proBNP (rho: = 0.81; P 0.001), which decreased by -30% (-50% to -8%) and -32% (-54% to -1%) to weeks 4 and 12 (P 0.001 for both). In contrast, change in BNP was only weakly associated with change in ucGMP (rho: = 0.19; P 0.001). Increases in ucGMP were observed regardless of whether BNP was decreased (+11% [-34% to +115%]), unchanged (+34% [-15% to +205%]), or increased (+57% [-12% to +14%]).In this pooled analysis of patients with HFrEF with standard indications for Sac/Val treatment, there was no significant overall increase in BNP concentrations, and patients demonstrated increase in ucGMP regardless of the trajectory of BNP change. (Study of Effects of Sacubitril/Valsartan vs. Enalapril on Aortic Stiffness in Patients With Mild to Moderate HF With Reduced Ejection Fraction [EVALUATE-HF]; NCT02874794) (Effects of Sacubitril/Valsartan Therapy on Biomarkers, Myocardial Remodeling and Outcomes [PROVE-HF]; NCT02887183).

Background Type 2 myocardial infarction (T2MI) is common and associated with high cardiovascular event rates. However, the relationship between T2MI and heart failure (HF) is uncertain. Methods and Results We identified patients with T2MI at a large tertiary hospital between October 2017 and May 2018. Patient characteristics, causes of T2MI, and subsequent HF hospitalizations were determined by physician chart review. We identified 359 patients with T2MI over the study period; 184 patients had a history of HF. Among patients with ejection fraction (EF) assessment (N=180), the majority had preserved EF (N=107; 59.4%), followed by reduced EF (N=54; 30.0%), and mid‐range EF (N=19; 10.6%). Acute HF was the most common cause of T2MI (20.9%). Of those whose T2MI was precipitated by HF (N=75), the mean EF was 53.0±16.8% and 16 (21.3%) were de novo diagnoses of HF. Among patients with T2MI who were discharged alive with available follow‐up (N=289), 5.5% were hospitalized with acute HF within 30 days, 17.3% within 180 days, and 22.1% within 1 year. In subgroup analyses, among patients with T2MI with prevalent or new HF (N=161), the rate of HF hospitalization at 1 year was 34.2%, considerably higher than those with T2MI and no HF diagnosis at discharge (7.0%; N=9/128). Conclusions Index presentations of HF or worsening chronic HF represent the most common causes of T2MI. ≈1 in 5 patients with T2MI will be readmitted for HF within 1 year of their event. Strategies to prevent HF events after a T2MI are needed.

Yield assessment in broadacre crops is often base on time-consuming and labor-intensive approximations. However, the emergence of unmanned aerial systems (UAS) has allowed for rapid and cost-effective data acquisition. We evaluated red beet plant counts using multispectral UAS data via computer vision and regression analysis. Flight data were captured twice during summer 2019. Our preprocessing steps included i) vegetation detection, ii) feature generation, and iii) feature selection. Partial least squares regression was used as a statistical predictor. Results showed that plant count could be predicted with an acceptable coefficient of determination ( $R^{2}=0.76$ for calibration; $R^{2}=0.54$ for cross-validation) and a low root-mean-square-error ( $\text{RMSE} =12.27$ plants/plot for calibration, $\text{RMSE} =17.45$ plants/plot for cross-validation). These results are promising, since the error margin, relative to the average density (175 plants/plot), was below 10%. Future efforts should include different geographical locations, higher resolution imagery, and more advanced approaches such as deep learning algorithms with potential for improved accuracy and precision.

Background: Sacubitril/valsartan (S/V) treatment is associated with reverse cardiac remodeling and reductions in biomarkers reflecting ventricular wall stress and myocardial injury, such as NT-proBNP (N-terminal pro-B-type natriuretic peptide), hs-cTnT (high-sensitivity cardiac troponin T), and soluble suppressor of tumorigenicity 2 (sST2). How longitudinal changes in these biomarkers analyzed collectively are associated with cardiac remodeling in patients with heart failure with reduced ejection fraction treated with S/V is uncertain. Methods: In a prospective study of S/V in patients with heart failure with reduced ejection fraction, this prespecified exploratory analysis included patients with serially collected biomarkers and echocardiographic measures of cardiac remodeling through 12 months of treatment. A multivariate latent growth curve model assessed associations between simultaneous changes in biomarkers and left ventricular ejection fraction and left atrial volume index. Results: Seven hundred fifteen out of 794 total study participants were included (mean age 65 years, 73% male). Mean baseline left ventricular ejection fraction and left atrial volume index were 29% and 40 mL/m 2 , respectively. Adjusted geometric mean baseline concentrations for biomarkers included NT-proBNP of 649 pg/mL, hs-cTnT of 15.9 ng/L, and sST2 of 24.7 ng/mL. Following initiation of S/V, circulating concentrations of NT-proBNP, hs-cTnT, and sST2 significantly decreased within 30 days and remained significantly different than baseline at all subsequent timepoints. From baseline to month 12, decreases in adjusted biomarker concentrations averaged −27.9% (95% CI, −35.1% to −20.7%; P P P Conclusions: Following initiation of S/V, NT-proBNP, hs-cTnT, and sST2 concentrations decreased significantly. Longitudinal changes in NT-proBNP and hs-cTnT together associated with left atrial and left ventricular reverse remodeling. Registration: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT02887183.

Wetlands in arid landscapes provide critical habitat for millions of migratory waterbirds across the world and throughout their annual cycle. The scope and scale of understanding avian use of these wetlands in conjunction with changes in climate are daunting yet critical to address lest we lose continent-wide migratory pathways. Here, we assess changes in waterbird use of North America’s Pacific Flyway in the Great Basin by examining water availability and climate trends over the past 100 years. We found recent (1980–2015) climate warming has significantly reduced the amount and shifted seasonality of water flowing into wetlands. Further, we found remarkable changes in waterbird species composition over time. We propose that a reduced hydroperiod and lower water quality from reduction in water level and flow limits sites used by waterbirds. These factors reduce chick survivorship as they cannot metabolize saline water, which makes suitable freshwater conditions a limiting resource. Collectively, climate-induced changes in Great Basin wetlands suggest a major shift in freshwater ecosystems, resulting in degradation of a continental migratory route. This work illustrates the importance of examining multi-scale changes in critical regional resources to understand their impact across a hemispheric flyway and provides a model to examine other flyways.

Summary Objectives Skeletal myopathies are highly morbid, and in rare cases even fatal, immune-related adverse events (irAE) associated with immune checkpoint inhibitors (ICI). Skeletal myopathies are also a recognized statin-associated side effect. It is unknown whether concurrent use of statins and ICIs increases the risk of skeletal myopathies. Methods This was a retrospective cohort study of all patients who were treated with an ICI at a single academic institution (Massachusetts General Hospital, Boston, MA, USA). The primary outcome of interest was the development of a skeletal myopathy. The secondary outcome of interest was an elevated creatine kinase level (above the upper limit of normal). Results Among 2757 patients, 861 (31.2%) were treated with a statin at the time of ICI start. Statin users were older, more likely to be male and had a higher prevalence of cardiovascular and non-cardiovascular co-morbidities. During a median follow-up of 194 days (inter quartile range 65–410), a skeletal myopathy occurred in 33 patients (1.2%) and was more common among statin users (2.7 vs. 0.9%, P < 0.001). Creatine kinase (CK) elevation was present in 16.3% (114/699) and was higher among statin users (20.0 vs. 14.3%, P = 0.067). In a multivariable Cox model, statin therapy was associated with a >2-fold higher risk for skeletal myopathy (HR, 2.19; 95% confidence interval, 1.07–4.50; P = 0.033). Conclusion In this large cohort of ICI-treated patients, a higher risk was observed for skeletal myopathies and elevation in CK levels in patients undergoing concurrent statin therapy. Prospective observational studies are warranted to further elucidate the potential association between statin use and ICI-associated myopathies., Graphical Abstract Graphical Abstract

BackgroundMyocarditis is a highly morbid complication of immune checkpoint inhibitor (ICI) use that remains inadequately characterized. The QRS duration and the QTc interval are standardized electrocardiographic measures that are prolonged in other cardiac conditions; however, there are no data on their utility in ICI myocarditis.MethodsFrom an international registry, ECG parameters were compared between 140 myocarditis cases and 179 controls across multiple time points (pre-ICI, on ICI prior to myocarditis, and at the time of myocarditis). The association between ECG values and major adverse cardiac events (MACE) was also tested.ResultsBoth the QRS duration and QTc interval were similar between cases and controls prior to myocarditis. When compared with controls on an ICI (93±19 ms) or to baseline prior to myocarditis (97±19 ms), the QRS duration prolonged with myocarditis (110±22 ms, pConclusionsThe QRS duration is increased in ICI myocarditis and is associated with increased MACE risk. Use of this widely available ECG parameter may aid in ICI myocarditis diagnosis and risk-stratification.