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Abstract Background Immune thrombocytopenia (ITP) is a common cause of severe thrombocytopenia in dogs. The pathogenesis of nonassociative, primary ITP (pITP) appears complex, with ill‐defined thrombopoietic response. Objectives Develop an immunoassay to measure plasma canine thrombopoietin (TPO) concentration and characterize TPO concentrations in dogs with pITP. Animals Forty‐one healthy dogs, 8 dogs in an induced ITP model (3 control, 5 ITP), and 58 pITP dogs. Methods Recombinant canine TPO (rcTPO) was purchased and its identity confirmed by mass spectrometry. Monoclonal antibodies were raised to rcTPO and used to configure a sandwich ELISA using streptavidin‐biotin detection. Assay performance, coefficients of variability, and healthy dog plasma TPO reference interval (RI) were determined, followed by assay of ITP samples. Results Assay dynamic range was 15 pg/mL (lower limit of detection) to 1000 pg/mL TPO, with limit of quantitation of 62 pg/mL. Plasma TPO RI was 0 to 158 pg/mL, with plasma TPO 6000 pg/mL. In contrast, only 2/58 pITP dogs had TPO values above RI. Conclusions and Clinical Importance Plasma TPO concentration is paradoxically low at diagnosis for most dogs with pITP. This finding suggests that ineffective thrombopoiesis contributes to thrombocytopenia in pITP dogs and supports evaluating TPO receptor agonist treatment as used for pITP in humans. The TPO assay provides a new tool to study thrombopoiesis in pITP and other thrombocytopenic syndromes in dogs.

Abstract Background Reported incidence of blood transfusion reactions (TR) varies greatly. Objective To prospectively evaluate the incidence of acute TRs in dogs receiving allogenic blood products, using consensus definitions, and to assess factors associated with TRs. Animals Dogs (n = 858) administered allogenic blood products (n = 1542) between March and November 2022. Methods Prospective, multicenter surveillance study occurring in referral hospitals in the United States, United Kingdom, and Australia recording TRs in dogs administered blood products as defined by the consensus guidelines published by The Association of Veterinary Hematology and Transfusion Medicine in 2021. Results The incidence of acute TR was 8.9% (95% CI 7.0‐11.1) for packed red blood cells (pRBCs) and 4.5% (95% CI 2.9‐6.6) for plasma products. The most frequently reported TRs were febrile nonhemolytic TRs (FNHTR; 4%, 95% CI 2.8‐5.5) when administering pRBCs and allergic TRs (3.2%, 95% CI 1.80‐5.10) when administering plasma products. A higher dose of pRBC (adjusted odds ratio [aOR] 1.04 [95% CI 1.00‐1.08]) was associated with a higher odds of TR. Administration of pRBCs stored for longer than 28 days was associated with higher odds of FNHTR (aOR 4.10 [95% CI 1.58‐10.65]) and acute hemolytic TR (AHTR; OR 15.2 [95% CI 3.35‐68.70]) when compared with pRBCs stored for 14 days or fewer. Leukoreduction of pRBC was not associated with lower odds of developing a TR (OR 1.47 [95% CI 0.89‐2.42]). Conclusions and Clinical Importance Clinicians should be mindful of the age and dose of pRBC prescribed to dogs.

Abstract Immune thrombocytopenia (ITP) is the most common acquired primary hemostatic disorder in dogs. Immune thrombocytopenia less commonly affects cats but is an important cause of mortality and treatment‐associated morbidity in both species. Immune thrombocytopenia remains a diagnosis of exclusion for which diagnostic guidelines are lacking. Primary, or non‐associative, ITP refers to autoimmune platelet destruction. Secondary, or associative, ITP arises in response to an underlying disease trigger. However, evidence for which comorbidities serve as ITP triggers has not been systematically evaluated. To identify key diagnostic steps for ITP and important comorbidities associated with secondary ITP, we developed 12 Population Evaluation/Exposure Comparison Outcome (PECO) format questions. These questions were addressed by evidence evaluators utilizing a literature pool of 287 articles identified by the panelists using a structured search strategy. Evidence evaluators, using panel‐designed templates and data extraction tools, summarized evidence and created guideline recommendations that then were integrated by diagnosis and comorbidity domain chairs. The revised PECO responses underwent a Delphi survey process to reach consensus on final guidelines. A combination of panel expertise and PECO responses were employed to develop algorithms for diagnosis of ITP in dogs and cats, which also underwent 4 iterations of Delphi review. Comorbidity evidence evaluators employed an integrated measure of evidence (IME) tool to determine evidence quality for each comorbidity; IME values combined with evidence summaries for each comorbidity were integrated to develop ITP screening recommendations, which also were subjected to Delphi review. Commentary was solicited from multiple relevant professional organizations before finalizing the consensus. The final consensus statement provides clinical guidelines for the diagnosis of, and underlying disease screening for, ITP in dogs and cats. The systematic consensus process identified numerous knowledge gaps that should guide future studies. This statement is a companion manuscript to the ACVIM Consensus Statement on the Treatment of Immune Thrombocytopenia.

Abstract Management of immune thrombocytopenia (ITP) in dogs and cats is evolving, but there are no evidence‐based guidelines to assist clinicians with treatment decisions. Likewise, the overall goals for treatment of ITP have not been established. Immunosuppressive doses of glucocorticoids are the first line treatment, but optimal treatment regimens beyond glucocorticoids remain uncertain. Additional options include secondary immunosuppressive drugs such as azathioprine, modified cyclosporine, and mycophenolate mofetil, usually selected based on clinician preference. Vincristine, human IV immunoglobulin (hIVIg), and transfusion of platelet or red blood cell–containing products are often used in more severe cases. Splenectomy and thrombopoietin receptor agonists are usually reserved for refractory cases, but when and in which patient these modalities should be employed is under debate. To develop evidence‐based guidelines for individualized treatment of ITP patients, we asked 20 Population Intervention Comparison Outcome (PICO) format questions. These were addressed by 17 evidence evaluators using a literature pool of 288 articles identified by a structured search strategy. Evidence evaluators, using panel‐designed templates and data extraction tools, summarized evidence and created guideline recommendations. These were integrated by treatment domain chairs and then refined by iterative Delphi survey review to reach consensus on the final guidelines. In addition, 19 non‐PICO questions covering scenarios in which evidence was lacking or of low quality were answered by expert opinion using iterative Delphi surveys with panelist integration and refinement. Commentary was solicited from multiple relevant professional organizations before finalizing the consensus. The rigorous consensus process identified few comparative treatment studies, highlighting many areas of ITP treatment requiring additional studies. This statement is a companion manuscript to the ACVIM Consensus Statement on the Diagnosis of Immune Thrombocytopenia in Dogs and Cats.

Abstract Objective The purpose of this study was to determine the association of a multi‐pronged treatment program in emergency department (ED) patients with an acute presentation of opioid use disorder (OUD) on the rate of subsequent opioid overdose (OD). This approach included ED‐initiated take‐home naloxone, prescription buprenorphine, and an ED‐based peer support and recovery program. Methods This was a retrospective observational analysis of adult patients presenting to the ED at a large urban hospital system from November 1, 2017 to March 17, 2023. Patients with an ED discharge diagnosis of OD or OUD were included. Outcomes determined were subsequent 90‐day OD and 180‐day OD death. Post hoc analyses were performed to identify intervention utilization throughout the study period including the COVID‐19 pandemic as well as ED characteristics associated with subsequent OD and OD death. Statistical comparisons were made using logistic regression and chi‐squared test. Results A total of 2634 patients presented to the ED with an opioid OD or diagnosis of OUD. Subsequent 90‐day OD decreased significantly over time (11.5%–2.3%, odds ratio [OR] 0.85, confidence interval [CI] 0.82–0.89). No single intervention was independently associated with 90‐day OD or 180‐day OD death. Resource utilization was stable during the COVID‐19 pandemic and increased afterward. A higher buprenorphine fill‐rate among all patients and the Back race subgroup was associated with a decrease in 90‐day OD. Conclusions Subsequent OD and OD death decreased over time after implementation of a multi‐pronged treatment program to ED patients with OUD. No single intervention was associated with a decrease of subsequent OD or OD death.

ABSTRACT Background Interindividual variability in oncology patients' symptom experiences poses significant challenges in prioritizing symptoms for targeted intervention(s). In this study, computational approaches were used to unbiasedly characterize the heterogeneity of the symptom experience of oncology patients to elucidate symptom patterns and drivers of symptom burden. Methods Severity ratings for 32 symptoms on the Memorial Symptom Assessment Scale from 3088 oncology patients were analyzed. Gaussian Graphical Model symptom networks were constructed for the entire cohort and patient subgroups identified through unsupervised clustering of symptom co‐severity patterns. Network characteristics were analyzed and compared using permutation‐based statistical tests. Differences in demographic and clinical characteristics between subgroups were assessed using multinomial logistic regression. Results Network analysis of the entire cohort revealed three symptom clusters: constitutional, gastrointestinal‐epithelial, and psychological. Lack of energy was identified as central to the network which suggests that it plays a pivotal role in patients' overall symptom experience. Unsupervised clustering of patients based on shared symptom co‐severity patterns identified six patient subgroups with distinct symptom patterns and demographic and clinical characteristics. The centrality of individual symptoms across the subgroup networks differed which suggests that different symptoms need to be prioritized for treatment within each subgroup. Age, treatment status, and performance status were the strongest determinants of subgroup membership. Conclusions Computational approaches that combine unbiased stratification of patients and in‐depth modeling of symptom relationships can capture the heterogeneity in patients' symptom experiences. When validated, the core symptoms for each of the subgroups and the associated clinical determinants may inform precision‐based symptom management.

Abstract Background Primary immune thrombocytopenia (pITP) in dogs presents a diagnostic challenge, and clinical markers of severity are lacking. Objectives Identify clinicopathologic features that differentiate pITP from secondary ITP (sITP) and markers related to bleeding severity, transfusion, and survival of dogs with pITP. Animals Ninety‐eight thrombocytopenic dogs (58 pITP and 40 sITP). Methods Client‐owned dogs with platelet counts

Background High blood pressure (BP) increases recurrent stroke risk. Methods and Results We assessed hypertension prevalence, treatment, control, medication adherence, and predictors of uncontrolled BP 90 days after ischemic or hemorrhagic stroke among 561 Mexican American and non‐Hispanic White (NHW) survivors of stroke from the BASIC (Brain Attack Surveillance in Corpus Christi) cohort from 2011 to 2014. Uncontrolled BP was defined as average BP ≥140/90 mm Hg at 90 days poststroke. Hypertension was uncontrolled BP or antihypertensive medication prescribed or hypertension history. Treatment was antihypertensive use. Adherence was missing zero antihypertensive doses per week. We investigated predictors of uncontrolled BP using logistic regression adjusting for patient factors. Median (interquartile range) age was 68 (59–78) years, 64% were Mexican American, and 90% of strokes were ischemic. Overall, 94.3% of survivors of stroke had hypertension (95.6% Mexican American versus 92.0% non‐Hispanic White; P=0.09). Of these, 87.9% were treated (87.3% Mexican American versus 89.1% non‐Hispanic White; P=0.54). Among the total population, 38.3% (95% CI, 34.4%–42.4%) had uncontrolled BP. Among those with uncontrolled BP prescribed an antihypertensive, 84.5% reported treatment adherence (95% CI, 78.8%–89.3%). Uncontrolled BP 90 days poststroke was less likely in patients with stroke who had a primary care physician (adjusted odds ratio [aOR], 0.45 [95% CI, 0.24–0.83]; P=0.01), greater stroke severity (aOR per‐1‐point‐higher National Institutes of Health Stroke Scale score, 0.96 [95% CI, 0.93–0.99]; P=0.02), or more depressive symptoms (aOR per‐1‐point‐higher Personal Health Questionnaire Depression Scale‐8 score, 0.95 [95% CI, 0.92–0.99] among those with a history of hypertension at baseline; P=0.009). Conclusions Greater than one third of survivors of stroke have uncontrolled BP at 90 days poststroke in this population‐based study. Interventions are needed to improve BP control after stroke.

Abstract During the 2015–2016 El Niño, the Amazon basin released almost one gigaton of carbon (GtC) into the atmosphere due to extreme temperatures and drought. The link between the drought impact and recovery of the total carbon pools and its biogeochemical drivers is still unknown. With satellite‐constrained net carbon exchange and its component fluxes including gross primary production and fire emissions, we show that the total carbon loss caused by the 2015–2016 El Niño had not recovered by the end of 2018. Forest ecosystems over the Northeastern (NE) Amazon suffered a cumulative total carbon loss of ∼0.6 GtC through December 2018, driven primarily by a suppression of photosynthesis whereas southeastern savannah carbon loss was driven in part by fire. We attribute the slow recovery to the unexpected large carbon loss caused by the severe atmospheric aridity coupled with a water storage deficit during drought. We show the attenuation of carbon uptake is three times higher than expected from the pre‐drought sensitivity to atmospheric aridity and ground water supply. Our study fills an important knowledge gap in our understanding of the unexpectedly enhanced response of carbon fluxes to atmospheric aridity and water storage deficit and its impact on regional post‐drought recovery as a function of the vegetation types and climate perturbations. Our results suggest that the disproportionate impact of water supply and demand could compromise resiliency of the Amazonian carbon balance to future increases in extreme events.

Key Clinical Message While orbital encephaloceles secondary to orbital roof fractures, in the setting of gunshot wound injuries, are rare, it is important to discuss diagnosis, treatment, and outcomes. This comprehensive manuscript aims to accomplish these objectives.

Abstract Background United States drug overdose deaths are being driven by the increasing prevalence of fentanyl, but whether patients are knowingly using fentanyl is unclear. We examined the analytical confirmation of fentanyl in emergency department (ED) patients with documented heroin overdose. Hypothesis We hypothesized that the proportion of fentanyl and fentanyl analogs would be higher than that of confirmed heroin. Methods This is a subgroup analysis from a prospective multicenter consecutive cohort of ED patients age 18+ with opioid overdose presenting to 10 US sites within the Toxicology Investigators Consortium from 2020 to 2021. Toxicology analysis was performed using liquid chromatography quadrupole time‐of‐flight mass spectrometry. De‐identified toxicology results were paired with the clinical database. The primary outcome was the proportion of patients with fentanyl analytes detected in their serum. Results Of 1006 patients screened, 406 were eligible, and of 168 patients who reported that they had taken heroin or had a documented heroin overdose, 88% (n = 147) were in fact found to have fentanyl and/or a fentanyl analog present on serum analysis (p

Abstract Purpose In a learning health system (LHS), data gathered from clinical practice informs care and scientific investigation. To demonstrate how a novel data and analytics platform can enable an LHS at a regional cancer center by characterizing the care provided to breast cancer patients. Methods Socioeconomic information, tumor characteristics, treatments and outcomes were extracted from the platform and combined to characterize the patient population and their clinical course. Oncologists were asked to identify examples where clinical practice guidelines (CPGs) or policy changes had varying impacts on practice. These constructs were evaluated by extracting the corresponding data. Results Breast cancer patients (5768) seen at the Juravinski Cancer Centre between January 2014 and June 2022 were included. The average age was 62.5 years. The commonest histology was invasive ductal carcinoma (74.6%); 77% were estrogen receptor‐positive and 15.5% were HER2 Neu positive. Breast‐conserving surgery (BCS) occurred in 56%. For the 4294 patients who received systemic therapy, the initial indications were adjuvant (3096), neoadjuvant (828) and palliative (370). Metastases occurred in 531 patients and 495 patients died. Lowest‐income patients had a higher mortality rate. For the adoption of CPGs, the uptake for adjuvant bisphosphonate was very low, 8% as predicted, compared to 64% for pertuzumab, a HER2 targeted agent and 40.2% for CD4/6 inhibitors in metastases. During COVID‐19, the provincial cancer agency issued a policy to shorten the duration of radiation after BCS. There was a significant reduction in the average number of fractions to the breast by five fractions. Conclusion Our platform characterized care and the clinical course of breast cancer patients. Practice changes in response to regulatory developments and policy changes were measured. Establishing a data platform is important for an LHS. The next step is for the data to feedback and change practice, that is, close the loop.

Background Adverse cardiovascular events during pregnancy (eg, preeclampsia) occur at higher rates among individuals with overweight or obesity (body mass index ≥25 kg/m2) and have been associated with postpartum depression. The present study examined whether changes in cardiovascular health (CVH) during the perinatal period, as defined by the American Heart Association's Life's Essential 8 framework, predicted postpartum psychological functioning among individuals with prepregnancy body mass index ≥25 kg/m2. Methods and Results Pregnant individuals (N = 226; mean ± SD age = 28.43 ± 5.4 years; mean body mass index = 34.17 ± 7.15 kg/m2) were recruited at 12 to 20 weeks of gestation (mean, 15.64 ± 2.45 weeks) for a longitudinal study of health and well‐being. Participants completed ratings of depression and perceived stress and reported on CVH behaviors (dietary intake, physical activity, nicotine exposure, and sleep) at baseline and at 6 months postpartum. Body mass index and CVH behaviors were used to calculate a composite CVH score at both time points. Linear regression analyses were performed to examine whether change in CVH related to postpartum symptom scores. Because sleep was measured in only a subset of participants (n = 114), analyses were conducted with and without sleep. Improved CVH was associated with lower postpartum depression (β = −0.18, P0.4). Conclusions Improvements in CVH from early pregnancy to 6 months postpartum were associated with lower postpartum depressive symptoms and perceived stress but not when including sleep in the CVH metric, potentially due to the large reduction in sample size. These data suggest that intervening during pregnancy to promote CVH may improve postpartum psychological functioning among high‐risk individuals.

Abstract Objectives To assess the safety, tolerability, and key pharmacodynamic effects of subcutaneous batoclimab, a fully human anti‐neonatal Fc receptor monoclonal antibody, in patients with generalized myasthenia gravis and anti‐acetylcholine receptor antibodies. Methods A Phase 2a, proof‐of‐concept, randomized, double‐blind, placebo‐controlled trial is described. Eligible patients were randomized (1:1:1) to receive once‐weekly subcutaneous injections of batoclimab 340 mg, batoclimab 680 mg, or matching placebo for 6 weeks. Subsequently, all patients could enter an open‐label extension study where they received batoclimab 340 mg once every 2 weeks for 6 weeks. Primary endpoints were safety, tolerability, and change from baseline in total immunoglobulin G, immunoglobulin G subclasses, and anti‐acetylcholine receptor antibodies at 6 weeks post‐baseline. Secondary endpoints included changes from baseline to 6 weeks post‐baseline for Myasthenia Gravis Activities of Daily Living, Quantitative Myasthenia Gravis, Myasthenia Gravis Composite, and revised 15‐item Myasthenia Gravis Quality of Life scores. Results Seventeen patients were randomized to batoclimab 680 mg (n = 6), batoclimab 340 mg (n = 5), or placebo (n = 6). Batoclimab was associated with significantly greater reductions in total immunoglobulin G and anti‐acetylcholine receptor antibodies from baseline to 6 weeks post‐baseline than placebo. Reductions in immunoglobulin G subclasses were generally consistent with total immunoglobulin G. While clinical measures showed directionally favorable improvements over time, the study was not powered to draw conclusions about therapeutic efficacy. No safety issues were identified. Interpretation The safety profile, pharmacodynamics, and preliminary clinical benefits observed in this study support further investigation of subcutaneous batoclimab injections as a potential patient‐administered therapy for seropositive generalized myasthenia gravis.

Abstract Compression sonography has been proposed as a method for non‐invasive measurement of venous pressures during spaceflight, but initial reports of venous pressure measured by compression ultrasound conflict with prior reports of invasively measured central venous pressure (CVP). The aim of this study is to determine the agreement of compression sonography of the internal jugular vein (IJVP) with invasive measures of CVP over a range of pressures relevant to microgravity exposure. Ten healthy volunteers (18–55 years, five female) completed two 3‐day sessions of supine bed rest to simulate microgravity. IJVP and CVP were measured in the seated position, and in the supine position throughout 3 days of bed rest. The range of CVP recorded was in line with previous reports of CVP during changes in posture on Earth and in microgravity. The correlation between IJVP and CVP was poor when measured during spontaneous breathing (r = 0.29; R2 = 0.09; P = 0.0002; standard error of the estimate (SEE) = 3.0 mmHg) or end‐expiration CVP (CVPEE; r = 0.19; R2 = 0.04; P = 0.121; SEE = 3.0 mmHg). There was a modest correlation between the change in CVP and the change in IJVP for both spontaneous ΔCVP (r = 0.49; R2 = 0.24; P

Background The new heart allocation policy places veno‐arterial extracorporeal membrane oxygenation (VA‐ECMO)‐supported heart transplant (HT) candidates at the highest priority status. Despite increasing evidence supporting left ventricular (LV) unloading during VA‐ECMO, the effect of LV unloading on transplant outcomes following bridging to HT with VA‐ECMO remains unknown. Methods and Results From October 18, 2018 to March 21, 2023, 624 patients on VA‐ECMO at the time of HT were identified in the United Network for Organ Sharing database and were divided into 2 groups: VA‐ECMO alone (N=384) versus VA‐ECMO with LV unloading (N=240). Subanalysis was performed in the LV unloading group: Impella (N=106) versus intra‐aortic balloon pump (N=134). Recipient age was younger in the VA‐ECMO alone group (48 versus 53 years, P=0.018), as was donor age (VA‐ECMO alone, 29 years versus LV unloading, 32 years, P=0.041). One‐year survival was comparable between groups (VA‐ECMO alone, 88.0±1.8% versus LV unloading, 90.4±2.1%; P=0.92). Multivariable Cox hazard model showed LV unloading was not associated with posttransplant mortality after HT (hazard ratio, 0.92; P=0.70). Different LV unloading methods had similar 1‐year survival (intra‐aortic balloon pump, 89.2±3.0% versus Impella, 92.4±2.8%; P=0.65). Posttransplant survival was comparable between different Impella versions (Impella 2.5, versus Impella CP, versus Impella 5.0, versus Impella 5.5). Conclusions Under the current allocation policy, LV unloading did not impact waitlist outcome and posttransplant survival in patients bridged to HT with VA‐ECMO, nor did mode of LV unloading. This highlights the importance of a tailored approach in HT candidates on VA‐ECMO, where routine LV unloading may not be universally necessary.

Abstract Observed links between parasites, such as ticks, and climate change have aroused concern for human health, wildlife population dynamics, and broader ecosystem effects. The one‐host life history of the winter tick (Dermacentor albipictus) links each annual cohort to environmental conditions during three specific time periods when they are predictably vulnerable: spring detachment from hosts, summer larval stage, and fall questing for hosts. We used mixed‐effects generalized linear models to investigate the drivers of tick loads carried by moose (Alces alces) relative to these time periods and across 750 moose, 10 years, and 16 study areas in the western United States. We tested for the effects of biotic factors (moose density, shared winter range, vegetation, migratory behavior) and weather conditions (temperature, snow, humidity) during each seasonal period when ticks are vulnerable and off‐host. We found that warm climatic regions, warm seasonal periods across multiple partitions of the annual tick life cycle, and warm years relative to long‐term averages each contributed to increased tick loads. We also found important effects of snow and other biotic factors such as host density and vegetation. Tick loads in the western United States were, on average, lower than those where tick‐related die‐offs in moose populations have occurred recently, but loads carried by some individuals may be sufficient to cause mortality. Lastly, we found interannual variation in tick loads to be most correlated with spring snowpack, suggesting this environmental component may have the highest potential to induce change in tick load dynamics in the immediate future of this region.

Abstract The four‐tiered NOVA food classification defines foods based on their degree of processing and ranges from native unprocessed foods to so‐called “ultra‐processed” foods. Recent publications have suggested that foods classified as ultra‐processed are unhealthy and contribute to the obesity epidemic. It is important to distinguish between formulation and processing of a food. In most cases it is the formulation more than the processing that results in foods that are not recommended as part of a healthy diet. Such “ultra‐formulated” foods are unhealthy because they are high in added sugar and other caloric sweeteners, refined flours saturated fats and salt to increase palatability. The understanding that processing and formulation are distinct will assist health professionals in identifying the types of foods that are unhealthy and contribute to overconsumption and obesity. It furthermore will help to destigmatize food technology and promote discussions amongst health professionals, food scientists, corporate scientists, government officials and the general public. Novel food processing techniques are urgently needed in times of population growth, climate change and war‐induced food shortages.

Abstract Background Shortness of breath occurs in 10%–70% of oncology patients. Very little is known about interindividual variability in its severity and distress and associated risk factors. Using latent profile analyses (LPAs), purpose was to identify subgroups of patients with distinct severity and distress profiles for shortness of breath as single symptom dimensions. In addition, a joint LPA was done using patients' severity AND distress ratings. For each of the three LPAs, differences among the shortness of breath classes in demographic, clinical, symptom, stress, and resilience characteristics were evaluated. Methods Patients completed ratings of severity and distress from shortness of breath a total of six times over two cycles of chemotherapy. All of the other measures were completed at enrollment (i.e., prior to the second or third cycle of chemotherapy). Separate LPAs were done using ratings of severity and distress, as well as a joint analysis using severity AND distress ratings. Differences among the latent classes were evaluated using parametric and nonparametric tests. Results For severity, two classes were identified (Slight to Moderate [91.6%] and Moderate to Severe [8.4%]). For distress, two classes were identified (A Little Bit to Somewhat [83.9%] and Somewhat to Quite a Bit [16.1%]). For the joint LPA, two classes were identified (Lower Severity and Distress [79.9%] and Higher Severity and Distress [20.1%]). While distinct risk factors were associated with each of the LPAs, across the three LPAs, the common risk factors associated with membership in the worse class included: a past or current history of smoking, poorer functional status, and higher comorbidity burden. In addition, these patients had a higher symptom burden and higher levels of cancer‐specific stress. Conclusions Clinicians can use the information provided in this study to identify high‐risk patients and develop individualized interventions.

Background Elevated cardiac troponin (cTn) is detected in 10% to 30% of patients with acute ischemic stroke (AIS) and correlates with poor functional outcomes. Serial cTn measurements differentiate a dynamic cTn pattern (rise/fall >20%), specific for acute myocardial injury, from elevated but stable cTn levels (nondynamic), typically attributed to chronic cardiac/noncardiac conditions. We investigated if the direction of the cTn change (rising versus falling) affects mortality and outcome. Methods and Results We retrospectively screened consecutive patients with AIS admitted to 5 stroke centers for elevated cTn at admission and at least 1 additional cTn measurement within 48 hours. The pattern of cTn was defined as rising if >20% increase from baseline, falling if >20% decrease, or nondynamic if ≤20% change in either direction. Logistic regression analyses were performed to assess the association of cTn patterns and 7‐day mortality and unfavorable discharge disposition. Of 3789 patients with AIS screened, 300 were included. Seventy‐two had a rising pattern, 66 falling, and 162 nondynamic. In patients with AIS with rising cTn, acute ischemic myocardial infarction was present in 54%, compared with 33% in those with falling cTn (P

Abstract Background Moderate to severe fatigue occurs in up to 94% of patients with cancer. Recent evidence suggests that morning and evening fatigue are distinct dimensions of physical fatigue. The purposes of this study were to evaluate the transcriptome for common and distinct perturbed inflammatory pathways in patients receiving chemotherapy who reported low versus high levels of morning or low versus high levels of evening cancer‐related fatigue. Methods Patients completed questionnaires during the week prior to their chemotherapy treatment. Severity of morning and evening fatigue was evaluated using the Lee Fatigue Scale. Gene expression and pathway impact analyses (PIA) were performed in two independent samples using RNA‐sequencing (n = 357) and microarray (n = 360). Patterns of interactions between and among these perturbed pathways were evaluated using a knowledge network (KN). Results Across the PIA, nine perturbed pathways (FDR

Background Cardiovascular complications after acute ischemic stroke (AIS) can be related to chronic/comorbid cardiac conditions or acute disruption of the brain–heart autonomic axis (stroke‐heart syndrome). Women are known to be more vulnerable to certain stress‐induced cardiac complications, such as Takotsubo cardiomyopathy. We investigated sex differences in cardiac troponin (cTn) elevation, cardiac events, and outcomes after AIS. Methods and Results We retrospectively analyzed consecutive patients with AIS from 5 stroke centers. Patients with AIS with elevated baseline cTn and at least 2 cTn measurements were included, while patients with acute comorbid conditions that could impact cTn levels were excluded. Poststroke acute myocardial injury was defined as the presence of a dynamic cTn pattern (rise/fall >20% in serial measurements) in the absence of acute atherosclerotic coronary disease (type 1 myocardial infarction) or cardiac death (type 3 myocardial infarction). From a total cohort of 3789 patients with AIS, 300 patients were included in the study: 160 were women (53%). Women were older, had a lower burden of cardiovascular risk factors, and more frequently had cardioembolic stroke and right insula involvement (P values all

Key clinical message Angioinvasive dermatophytosis with necrotizing fasciitis can be a rare complication in immunocompromised patients with early surgical debridement, 12 weeks of oral terbinafine, and reduction in immunosuppression being a viable management strategy.

Key Clinical Message We describe an immunocompromised 73‐year‐old male with a history of neurofibromatosis type 1 (NF1) who presented with a lesion on the thumb concerning for malignancy that was found to be histoplasmosis. This unique case highlights the importance of a thorough history and a broad differential diagnosis in the management of new osteoarticular lesions.

Background Moderate intensity exercise training (MIT) is safe and effective for patients with hypertrophic cardiomyopathy, yet the efficacy of high intensity training (HIT) remains unknown. This study aimed to compare the efficacy of HIT compared with MIT in patients with hypertrophic cardiomyopathy. Methods and Results Patients with hypertrophic cardiomyopathy were randomized to either 5 months of MIT, or 1 month of MIT followed by 4 months of progressive HIT. Peak oxygen uptake (V˙O2; Douglas bags), cardiac output (acetylene rebreathing), and arteriovenous oxygen difference (Fick equation) were measured before and after training. Left ventricular outflow gradient and volumes were measured by echocardiography. Fifteen patients completed training (MIT, n=8, age 52±7 years; HIT, n=7, age 42±8 years). Both HIT and MIT improved peak V˙O2 by 1.3 mL/kg per min (P=0.009). HIT (+1.5 mL/kg per min) had a slightly greater effect than MIT (+1.1 mL/kg per min) but with no statistical difference (group×exercise P=0.628). A greater augmentation of arteriovenous oxygen difference occurred with exercise (Δ1.6 mL/100 mL P=0.005). HIT increased left ventricular end‐diastolic volume (+17 mL, group×exercise P=0.015) compared with MIT. No serious arrhythmias or adverse cardiac events occurred. Conclusions This randomized trial of exercise training in patients with hypertrophic cardiomyopathy demonstrated that both HIT and MIT improved fitness without clear superiority of either. Although the study was underpowered for safety outcomes, no serious adverse events occurred. Exercise training resulted in salutary peripheral and cardiac adaptations. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT03335332.

Abstract Although a higher prevalence of antiphospholipid autoantibodies (aPL) has been observed in some cohorts of sickle cell disease (SCD) patients, the clinical risk factors for the development of aPL and its associated complications remain unclear. In a retrospective study of 63 SCD patients, a lower hemoglobin concentration and higher white blood cell count were independently associated with an elevated aPL. SCD patients with elevated aPL had increased pregnancy complications (≥3 miscarriages, preterm delivery, pre‐eclampsia) and venous thrombotic events. Our findings suggest that SCD may predispose to the generation of aPL and that aPL itself may contribute to the vasculopathy of SCD. Prospective testing for aPL is warranted in patients with SCD.

Abstract Earth system models (ESMs) typically simplify the representation of land surface spectral albedo to two values, which correspond to the photosynthetically active radiation (PAR, 400–700 nm) and the near infrared (NIR, 700–2,500 nm) spectral bands. However, the availability of hyperspectral observations now allows for a more direct retrieval of ecological parameters and reduction of uncertainty in surface reflectance. To investigate sensitivity and quantify biases of incorporating hyperspectral albedo information into ESMs, we examine how shortwave soil albedo affects surface radiative forcing and simulations of the carbon and water cycles. Results reveal that the use of two broadband values to represent soil albedo can introduce systematic radiative‐forcing differences compared to a hyperspectral representation. Specifically, we estimate soil albedo biases of ±0.2 over desert areas, which can result in spectrally integrated radiative forcing divergences of up to 30 W m−2, primarily due to discrepancies in the blue (404–504 nm) and far‐red (702–747 nm) regions. Furthermore, coupled land‐atmosphere simulations indicate a significant difference in net solar flux at the top of the atmosphere (>3.3 W m−2), which can impact global energy fluxes, rainfall, temperature, and photosynthesis. Finally, simulations show that considering the hyperspectrally resolved soil reflectance leads to increased maximum daily temperatures under current and future CO2 concentrations.

Background Clinical practice recommendations for participation in sports and exercise among young competitive athletes with cardiovascular conditions at risk for sudden death are based largely on expert consensus with a paucity of prospective outcomes data. Recent guidelines have taken a more permissive approach, using a shared decision‐making model. However, the impact and outcomes of this strategy remain unknown. Methods The ORCCA (Outcomes Registry for Cardiac Conditions in Athletes) study is a prospective, multicenter, longitudinal, observational cohort study designed to monitor clinical outcomes in athletes with potentially life‐threatening cardiovascular conditions. The study will assess sports eligibility decision‐making, exercise habits, psychosocial well‐being, and long‐term cardiovascular outcomes among young competitive athletes with cardiovascular conditions. Competitive athletes aged 18 to

Abstract Aims This study aims to investigate the acute haemodynamic effects of percutaneous transluminal flow regulation (PTCR®) with an inferior vena cava regulator balloon in heart failure patients. Preload reduction in heart failure has been achieved with high potency diuretics. However, no study has been conducted in humans to assess the effect of inferior vena cava intermittent occlusion for preload reduction. Methods and results Six patients were included in the study: four men (55 ± 6 years old) and two women (63 ± 4 years old). Baseline evaluations included Doppler echocardiogram, coronary angiogram, and right heart catheterization. Caval balloon was kept inflated for 30 min, and right catheterization and control echocardiogram were performed while the balloon was still inflated. The balloon was then deflated and removed. Right haemodynamic variables were evaluated before balloon insertion and with the inflated balloon. The mean right atrial pressure decreased by 42.59% (P = 0.005); systolic right ventricular pressure decreased by 30.19% (P 0.016); and cardiac output increased by 9.92% (P

Abstract Objective Endoscopic repair of large anterior skull base (ASB) defects has excellent results when using multilayered repairs with a nasoseptal flap. However, in extensive intranasal tumors, a nasoseptal flap may not always be available. One alternative option is a flexible single‐layer ASB repair. Initial studies indicate low cerebrospinal fluid leak rates with a single‐layer repair. However, the level of frontal lobe support, particularly the propensity for a significant inferior displacement of the frontal lobe, is not known. The goal of this study is to determine the frontal lobe position after single‐layer acellular dermal allograft repair in large ASB defects. Study Design Retrospective cohort study. Setting Tertiary care medical center. Subjects and Methods This cohort study compares the frontal lobe position in adults who underwent endoscopic endonasal ASB tumor resection and single‐layer cadaveric dermal matrix repair (ASB cohort) with control subjects without intracranial abnormalities (control cohort). The ASB cohort includes subjects with an ASB defect of ≥5 cm anterior/posterior and ≥1.5 cm wide and who had imaging at least 2 months after surgery. The frontal lobe position is measured on sagittal CT/MRI using a reference line from the base of the sella to the nasion. A value of zero indicates that the inferior‐most aspect of the frontal lobe is at the level of the nasion−sellar line. A positive value indicates that the frontal lobe is inferior to the nasion−sellar line. The ASB cohort frontal lobe position is compared with the control cohort using the Mann−Whitney U test. A priori we set an absolute difference of 5 mm as a clinically significant difference. Results The ASB cohort includes 47 subjects who are 57% male with an average age of 60 years (range: 31−89 years). The most common ASB pathology is esthesioneuroblastoma (n = 21) and 81% of the ASB cohort had postoperative radiation. The control cohort includes 20 subjects who are 60% male, with a mean age of 45 years (range: 19−74 years). The majority of controls underwent imaging for head trauma (n = 13). The ASB mean frontal lobe position is −0.2 mm superior to the nasion−sellar line (range: −9.2 to 10.4 mm), while the control's mean frontal lobe position is 1.1 mm inferior to the nasion−sellar line. This difference is not statistically significant (P = 0.13) and does not reach our a priori definition of clinical significance. The frontal lobe position of ASB subjects who had radiation is closer to the nasion−sellar line as compared with those who did not undergo radiation. Conclusions Single‐layer acellular dermal graft repair maintains frontal lobe support and position in large ASB defects.

Abstract A 15‐year‐old Miniature Horse mare with persistently increased plasma calcium (total and ionized) and serum parathyroid hormone concentrations was presented for suspected primary hyperparathyroidism. Ultrasonography of the thyroid region identified an enlarged heterogeneous mass axial to the right thyroid lobe suggestive of an enlarged parathyroid gland, which was further confirmed using sestamibi nuclear scintigraphy and 3‐phase computed tomography. Percutaneous ultrasound‐guided ethanol ablation of the mass, a method not previously described in the horse, was performed under general anesthesia resulting in rapid normalization of plasma ionized calcium and serum parathyroid hormone concentrations. Ablation of abnormal parathyroid gland tissue may be a suitable alternative to surgical resection in certain cases of primary hyperparathyroidism in the horse.

Abstract Background Magnetic resonance imaging is the method of choice for diagnosing spinal cord neoplasia, but the accuracy of designating the relationship of a neoplasm to the meninges and agreement among observers is unknown. Objectives To determine agreement among observers and accuracy of diagnosis compared with histology when diagnosing lesion location based on relationship to the meninges. Animals Magnetic resonance images from 53 dogs with intradural extramedullary and intramedullary spinal neoplasms and 17 dogs with degenerative myelopathy. Methods Six observers were supplied with 2 sets of 35 images at different time points and asked to designate lesion location. Agreement in each set was analyzed using kappa (κ) statistics. We tabulated total correct allocations and calculated sensitivity, specificity, and likelihood ratios for location designation from images compared with known histologic location for lesions confined to 1 location only. Results Agreement in the first set of images was moderate (κ = 0.51; 95% confidence interval [CI], 0.43‐0.58) and in the second, substantial (κ = 0.69; 95% CI, 0.66‐0.79). In the accuracy study, 180 (75%) of the 240 diagnostic calls were correct. Sensitivity and specificity were moderate to high for all compartments, except poor sensitivity was found for intradural extramedullary lesions. Positive likelihood ratios were high for intradural extramedullary lesions and degenerative myelopathy. Conclusions and Clinical Importance Overall accuracy in diagnosis was reasonable, and positive diagnostic calls for intradural extramedullary lesions and negative calls for intramedullary lesions are likely to be helpful. Observers exhibited considerable disagreement in designation of lesions relationship to the meninges.

Abstract We describe a case of an otherwise healthy 60‐year‐old female patient who presented 6 days after receipt of the second dose of the BNT162b2 mRNA COVID‐19 (Pfizer/BioNTech) vaccine and was found to have upper extremity deep venous thrombosis.