Assessing the impact of atrial fibrillation self-care interventions: A systematic review.

This systematic review evaluates the efficacy of self-care interventions for atrial fibrillation (AF), focusing on strategies for maintenance, monitoring, and management applied individually or in combination. Adhering to the 2020 PRISMA guidelines, the search strategy spanned literature from 2005 to 2023, utilizing keywords and subject headings for "atrial fibrillation" and "self-care" combined with the Boolean operator AND. The databases searched included Medline, Embase, and CINAHL. The initial search, conducted on February 17, 2021, and updated on May 16, 2023, identified 5160 articles, from which 2864 unique titles and abstracts were screened. After abstract screening, 163 articles were reviewed in full text, resulting in 27 articles being selected for data extraction; these studies comprised both observational and randomized controlled trial designs. A key finding in our analysis reveals that self-care interventions, whether singular, dual, or integrated across all three components, resulted in significant improvements across patient-reported, clinical, and healthcare utilization outcomes compared to usual care. Educational interventions, often supported by in-person sessions or telephone follow-ups, emerged as a crucial element of effective AF self-care. Additionally, the integration of mobile and web-based technologies alongside personalized education showed promise in enhancing outcomes, although their full potential remains underexplored. This review highlights the importance of incorporating comprehensive, theory-informed self-care interventions into routine clinical practice and underscores the need for ongoing innovation and the implementation of evidence-based strategies. The integration of education and technology in AF self-care aligns with the recommendations of leading health organizations, advocating for patient-centered, technology-enhanced approaches to meet the evolving needs of the AF population.

The post-emergence period for denning Polar Bears: phenology and influence on cub survival.

Among polar bears (Ursus maritimus), only parturient females den for extended periods, emerging from maternal dens in spring after having substantially depleted their energy reserves during a fast that can exceed 8 months. Although den emergence coincides with a period of increasing prey availability, polar bears typically do not depart immediately to hunt, but instead remain at the den for up to a month. This delay suggests that there are likely adaptive advantages to remaining at the den between emergence and departure, but the influence of the timing and duration of this post-emergence period on cub survival has not been evaluated previously. We used temperature and location data from 70 denning bears collared within the Southern Beaufort Sea and Chukchi Sea subpopulations to estimate the phenology of the post-emergence period. We evaluated the influence of various spatial and temporal features on duration of the post-emergence period and evaluated the potential influence of post-emergence duration on litter survival early in the spring following denning. For dens that likely contained viable cubs at emergence (n = 56), mean den emergence occurred on 16 March (SE = 1.4 days) and mean departure on 24 March (SE = 1.6 days), with dates typically occurring later in the Chukchi Sea relative to Southern Beaufort Sea and on land relative to sea ice. Mean duration of the post-emergence period was 7.9 days (SE = 1.4) for bears that were observed with cubs later in the spring, which was over 4 times longer than duration of those observed without cubs (1.9 days). Litter survival in the spring following denning (n = 31 dens) increased from 0.5 to 0.9 when duration of the post-emergence period increased by ~4 days and other variables were held at mean values. Our limited sample size and inability to verify cub presence at emergence suggests that future research is merited to improve our understanding of this relationship. Nonetheless, our results highlight the importance of the post-emergence period in contributing to reproductive success and can assist managers in developing conservation and mitigation strategies in denning areas, which will be increasingly important as human activities expand in the Arctic.

Association between right ventricular global longitudinal strain and mortality in intermediate-risk pulmonary embolism.

BACKGROUND: Right ventricular (RV) systolic dysfunction has been identified as a prognostic marker for adverse clinical events in patients presenting with acute pulmonary embolism (PE). However, challenges exist in identifying RV dysfunction using conventional echocardiography techniques. Strain echocardiography is an evolving imaging modality which measures myocardial deformation and can be used as an objective index of RV systolic function. This study evaluated RV Global Longitudinal Strain (RVGLS) in patients with intermediate risk PE as a parameter of RV dysfunction, and compared to traditional echocardiographic and CT parameters evaluating short-term mortality. METHODS: Retrospective single center cohort study of 251 patients with intermediate-risk PE between 2010 and 2018. The primary outcome was all-cause mortality at 30 days. Statistical analysis evaluated each parameter comparing survivors versus non-survivors at 30 days. Receiver operating characteristic (ROC) curves and Kaplan-Meier curves were used for comparison of the two cohorts. RESULTS: Altogether 251 patients were evaluated. Overall mortality rate was 12.4%. Utilizing an ROC curve, an absolute cutoff value of 17.7 for RVGLS demonstrated a sensitivity of 93% and specificity of 70% for observed 30-day mortality. Individuals with an RVGLS ≤17.7 had a 25 times higher mortality rate than those with RVGLS above 17.7 (HR 25.24, 95% CI = 6.0-106.4, p < .001). Area under the curve was (.855), RVGLS outperformed traditional echocardiographic parameters, CT findings, and cardiac biomarkers on univariable and multivariable analysis. CONCLUSIONS: Reduced RVGLS values on initial echocardiographic assessment of patients with intermediate-risk PE identified patients at higher risk for mortality at 30 days.

Unnatural amino acid substitutions to improve in vivo stability and tumor uptake of 68Ga-labeled GRPR-targeted TacBOMB2 derivatives for cancer imaging with positron emission tomography.

BACKGROUND: Overexpressed in various solid tumors, gastrin-releasing peptide receptor (GRPR) is a promising cancer imaging marker and therapeutic target. Although antagonists are preferable for the development of GRPR-targeted radiopharmaceuticals due to potentially fewer side effects, internalization of agonists may lead to longer tumor retention and better treatment efficacy. In this study, we systematically investigated unnatural amino acid substitutions to improve in vivo stability and tumor uptake of a previously reported GRPR-targeted agonist tracer, [68Ga]Ga-TacBOMB2 (68Ga-DOTA-Pip-D-Phe6-Gln7-Trp8-Ala9-Val10-Gly11-His12-Leu13-Thz14-NH2). RESULTS: Unnatural amino acid substitutions were conducted for Gln7, Trp8, Ala9, Val10, Gly11 and His12, either alone or in combination. Out of 25 unnatural amino acid substitutions, tert-Leu10 (Tle10) and NMe-His12 substitutions were identified to be preferable modifications especially in combination. Compared with the previously reported [68Ga]Ga-TacBOMB2, the Tle10 and NMe-His12 derived [68Ga]Ga-LW01110 showed retained agonist characteristics and improved GRPR binding affinity (Ki = 7.62 vs 1.39 nM), in vivo stability (12.7 vs 89.0% intact tracer in mouse plasma at 15 min post-injection) and tumor uptake (5.95 vs 16.6 %ID/g at 1 h post-injection). CONCLUSIONS: Unnatural amino acid substitution is an effective strategy to improve in vivo stability and tumor uptake of peptide-based radiopharmaceuticals. With excellent tumor uptake and tumor-to-background contrast, [68Ga]Ga-LW01110 is promising for detecting GRPR-expressing cancer lesions with PET. Since agonists can lead to internalization upon binding to receptors and foreseeable long tumor retention, our optimized GRPR-targeted sequence, [Tle10,NMe-His12,Thz14]Bombesin(7-14), is a promising template for use for the design of GRPR-targeted radiotherapeutic agents.

The Experiences of Endurance Athletes With Atrial Fibrillation: Tensions and Takeaways.

BACKGROUND: Growing evidence indicates that chronic high-intensity endurance exercise predisposes male, middle-aged athletes to increased risk of atrial fibrillation (AF). The aetiology of AF in endurance athletes is multifactorial and remains incompletely understood. Despite their unique training demands, AF care in athletes remains largely based on evidence derived from the general population. Understanding the experiences of athletes with AF provides a necessary foundation for addressing challenges in managing their condition and identifying gaps in care. AIM: The purpose of this interpretive descriptive qualitative study was to describe the experiences and perspectives of endurance athletes living with AF. METHOD: Masters athletes diagnosed with AF and aged between 35 and 60 years were recruited internationally through cardiology practices and social media. Ten middle-aged, male endurance athletes with AF and >1,500 lifetime training hours participated in individual, semi-structured interviews. Data were analysed using inductive thematic analysis. RESULTS: Three key themes were constructed: (1) tensions with training, (2) tensions with treatment plans, and (3) tensions with clinicians. Participants experienced a wide range of symptoms from AF that significantly affected their ability to train, and reacted negatively to medical treatment strategies that affected their exercise capacity and training performance. Athletes experienced tensions with providers who failed to acknowledge their athletic needs. CONCLUSIONS: Our results highlight the unique difficulties that male athletes with AF face in navigating between training and their disease, treatment, and clinicians. Shared decision-making between the athlete and provider is likely necessary for effective management of athletic AF.

Robotic colorectal surgery in the emergent diverticulitis setting: is it safe? A review of large national database.

BACKGROUND: As robotic colorectal surgery continues to advance in conjunction with improved recovery protocols, we began implementing robotic surgery (RS) as an option for emergent diverticulitis surgery. Our hospital system utilizes the Da Vinci Xi system, and staff are required to undergo training, making emergent colorectal surgery a feasible option. However, it is essential to determine the safety with reproducibility of our experiences. METHODS: A de-identified retrospective review was performed of Intuitive's national database which obtained data from 262 facilities from January 2018 through December 2021. This identified over 22,000 emergent colorectal surgeries. Of those, over 2500 were performed for diverticulitis in which 126 were RS, 446 laparoscopic surgery (LS), and 1952 open surgery (OS). Clinical outcome metrics including conversion rates, anastomotic leaks, intensive care unit (ICU) admissions, length of stay, mortality, and readmissions were obtained. The cohort was defined by patients who were seen in the emergency department (ED) with diverticulitis and proceeded to have a sigmoid colectomy within 24 h of ED arrival. RESULTS: RS was associated with increased operating time (RS 262, LS 207, OS 182 min), but data has shown many benefits of emergent RS compared to OS. We identified significant decreases in ICU admission rates (OS 19.0%, RS 9.5%, p = 0.01) and anastomotic leak rates (OS 4.4%, RS 0.8%, p = 0.04), with borderline improvement in overall length of stay (OS 9.9, RS 8.9 days, p = 0.05). When compared with LS, RS showed many comparable results. However, RS witnessed a statistically significant improvement in anastomotic leak rates (LS 4.5%, RS 0.8%, p = 0.04). Importantly, there was a striking difference in conversion rates to OS. LS converted over 28.7% of cases to OS, whereas RS only converted 7.9%, p = 0.000005. CONCLUSION: Given these findings, RS is another MIS tool that could be a safe and feasible option for the acute management of emergent diverticulitis.

Cardiovascular assessment in cirrhosis: is global longitudinal strain altered in cirrhosis? A meta-analysis and review.

BACKGROUND AND AIMS: Evaluation of cardiac function and determining the potential risk of cardiac complications with liver transplantation has been both a topic of contention and discussion. Global longitudinal strain (GLS) imaging has been used to identify subclinical myocardial dysfunction in other pathologies; however, its use in the cirrhosis population is unclear. A meta-analysis was performed to assess GLS values in patients with cirrhosis compared to healthy controls. METHODS: A literature search was conducted for studies that evaluated GLS in patients with cirrhosis compared to healthy controls published until September 18, 2020. Primary outcomes looked at differences in GLS values between these populations. RESULTS: Thirteen total studies were included in the meta-analysis. Overall, 802 patients with cirrhosis and 540 healthy controls were included in the analysis. The GLS values were numerically more negative in the healthy control group versus patients with cirrhosis (raw mean difference -2.5%, 95% CI -3 to -1.9, P = < .001), I2  = 81%. CONCLUSION: GLS can be used as an early marker of subclinical myocardial dysfunction. We noted a difference in GLS values in patients with cirrhosis compared to healthy control subjects in this meta-analysis. Other traditional systolic and diastolic echocardiographic parameters were not found to be significantly different between patients with cirrhosis versus healthy controls. This may indicate utilization of GLS when screening for cardiac dysfunction prior to liver transplantation.

Synthesis and Preclinical Evaluation of Three Novel 68Ga-Labeled Bispecific PSMA/FAP-Targeting Tracers for Prostate Cancer Imaging.

Tumor heterogeneity limits the efficacy and reliability of monospecific radiopharmaceuticals in prostate cancer diagnosis and therapy. To overcome this limitation and improve lesion detection sensitivity, we developed and evaluated three bispecific radiotracers that can target both prostate-specific membrane antigen (PSMA) and fibroblast activation protein (FAP), which are the two key proteins overexpressed in prostate cancer. Three FAP-targeting ligands with various linker lengths were synthesized through multistep organic synthesis, and then connected to the PSMA-targeting motif. IC50(PSMA) and IC50(FAP) values of Ga-complexed bispecific ligands, Ga-AV01017, Ga-AV01030, and Ga-AV01038 were 25.2-71.6 and 1.25-2.74 nM, respectively. The uptake values in PSMA-expressing LNCaP tumor xenografts were 4.38 ± 0.55, 5.17 ± 0.51, and 4.25 ± 0.86 %ID/g for [68Ga]Ga-AV01017, [68Ga]Ga-AV01030, and [68Ga]Ga-AV01038, respectively, which were lower than the monospecific PSMA-targeting tracer [68Ga]Ga-HTK03041 (23.1 ± 6.11 %ID/g). The uptake values in FAP-expressing HEK293T:hFAP tumor xenografts were 2.99 ± 0.37, 3.69 ± 0.81, 3.64 ± 0.83 %ID/g for [68Ga]Ga-AV01017, [68Ga]Ga-AV01030, and [68Ga]Ga-AV01038, respectively, which were also lower than the monospecific FAP-targeting tracer, [68Ga]Ga-FAPI-04 (12.5 ± 2.00 %ID/g). We observed that the bispecific tracers had prolonged blood retention, in which tracers with a longer linker tend to have a higher blood uptake and lower tumor uptake. Further investigations are needed to optimize the linker selection to generate promising bispecific PSMA/FAP-targeting tracers for prostate cancer imaging.

Patients' Experiences With the Fit of Virtual Atrial Fibrillation Care During the Pandemic: Qualitative Descriptive Study.

BACKGROUND: In-person health care has been the standard model of care delivery for patients with atrial fibrillation (AF). Despite the growing use of remote technology, virtual health care has received limited formal study in populations with AF. Understanding the virtual care experiences of patients in specialized AF clinics is essential to inform future planning of AF clinic care. OBJECTIVE: This qualitative descriptive study aimed to understand patients' virtual AF clinic care experiences during the COVID-19 pandemic. METHODS: Participants were recruited from a pool of patients who were receiving care from an AF clinic and who were enrolled in a larger survey study. A total of 8 virtual focus groups (n=30) were conducted in 2 waves between March 2021 and May 2021. Facilitators used a semistructured discussion guide to ask participants questions about their experiences of virtual care and the perceived quality of virtual care and technology support. Three team members initially open coded group data to create a preliminary coding framework. As the analysis progressed, with subsequent focus groups, the code clusters were refined. RESULTS: The participants were primarily male (21/30, 70%), aged ≥65 years (20/30, 67%), and college graduates (22/30, 73%). Patients found virtual care to be highly beneficial. Central to their experiences of virtual care was its fit or lack of fit with their health needs, which was integrally connected to communication effectiveness and their preferred virtual care future. Practical benefits included flexibility, convenience, and time and cost savings of virtual care. Virtual care fit occurred for small, quick, and mundane issues (eg, medication refills) but was suboptimal for new and more complex issues that patients thought warranted an in-person visit. Fit often reflected the effectiveness of communication between patient and provider and that of in-clinic follow-up. There was near-complete agreement among participants on the acceptability of virtual communication with their providers in addressing their needs, but this depended on adequate reciprocal communication. Without the benefit of in-person physical assessments, patients were uncertain and lacked confidence in communicating the needed, correct, and comprehensive information. Finally, participants described concerns related to ongoing virtual care with recommendations for their preferred future using a hybrid model of care and integrating patient-reported data (ie, blood pressure measurements) in virtual care delivery. CONCLUSIONS: Virtual care from a specialty AF clinic provides practical benefits for patients, but they must be weighed against the need for virtual care's fit with patients' needs and problems. The stability and complexity of patients' health needs, their management, and their perceptions of communication effectiveness with providers and clinics must be considered in decisions about appointment modality. Patients' recommendations for future virtual care through use of hybrid models together with systems for data sharing have the potential to optimize fit.

Water-Soluble Truncated Fatty Acid-Porphyrin Conjugates Provide Photo-Sensitizer Activity for Photodynamic Therapy in Malignant Mesothelioma.

Clinical trials evaluating intrapleural photodynamic therapy (PDT) are ongoing for mesothelioma. Several issues still hinder the development of PDT, such as those related to the inherent properties of photosensitizers. Herein, we report the synthesis, photophysical, and photobiological properties of three porphyrin-based photosensitizers conjugated to truncated fatty acids (C5SHU to C7SHU). Our photosensitizers exhibited excellent water solubility and high PDT efficiency in mesothelioma. As expected, absorption spectroscopy confirmed an increased aggregation as a consequence of extending the fatty acid chain length. In vitro PDT activity was studied using human mesothelioma cell lines (biphasic MSTO-211H cells and epithelioid NCI-H28 cells) alongside a non-malignant mesothelial cell line (MET-5A). The PDT effect of these photosensitizers was initially assessed using the colorimetric WST-8 cell viability assay and the mode of cell death was determined via flow cytometry of Annexin V-FITC/PI-stained cells. Photosensitizers appeared to selectively localize within the non-nuclear compartments of cells before exhibiting high phototoxicity. Both apoptosis and necrosis were induced at 24 and 48 h. As our pentanoic acid-derivatized porphyrin (C5SHU) induced the largest anti-tumor effect in this study, we put this forward as an anti-tumor drug candidate in PDT and photo-imaging diagnosis in mesothelioma.

Characterizing dark state kinetics and single molecule fluorescence of FusionRed and FusionRed-MQ at low irradiances.

The presence of dark states causes fluorescence intermittency of single molecules due to transitions between "on" and "off" states. Genetically encodable markers such as fluorescent proteins (FPs) exhibit dark states that make several super-resolved single-molecule localization microscopy (SMLM) methods possible. However, studies quantifying the timescales and nature of dark state behavior for commonly used FPs under conditions typical of widefield and total internal reflection fluorescence (TIRF) microscopy remain scarce and pre-date many new SMLM techniques. FusionRed is a relatively bright red FP exhibiting fluorescence intermittency and has thus been identified as a potential candidate for SMLM. We herein characterize the rates for dark-state conversion and the subsequent ground-state recovery of FusionRed and its 2.5-fold brighter descendent FusionRed L175M M42Q (FusionRed-MQ) at low irradiances (1-10 W cm-2), which were previously unexplored experimental conditions. We characterized the kinetics of dark state transitions in these two FPs by using single molecule blinking and ensemble photobleaching experiments bridged with a dark state kinetic model. We find that at low irradiances, the recovery process to the ground state is minimally light-driven and FusionRed-MQ has a 1.3-fold longer ground state recovery time indicating a conformationally restricted dark-state chromophore in comparison to FusionRed. Our studies indicate that the brighter FusionRed-MQ variant exhibits higher dark state conversion rates with longer ground state recovery lifetimes, thus it is potentially a better candidate for SMLM applications than its progenitor FusionRed.

Structure and activity of human TMPRSS2 protease implicated in SARS-CoV-2 activation.

Transmembrane protease, serine 2 (TMPRSS2) has been identified as key host cell factor for viral entry and pathogenesis of SARS-CoV-2. Specifically, TMPRSS2 proteolytically processes the SARS-CoV-2 Spike (S) protein, enabling virus-host membrane fusion and infection of the airways. We present here a recombinant production strategy for enzymatically active TMPRSS2 and characterization of its matured proteolytic activity, as well as its 1.95 Å X-ray cocrystal structure with the synthetic protease inhibitor nafamostat. Our study provides a structural basis for the potent but nonspecific inhibition by nafamostat and identifies distinguishing features of the TMPRSS2 substrate binding pocket that explain specificity. TMPRSS2 cleaved SARS-CoV-2 S protein at multiple sites, including the canonical S1/S2 cleavage site. We ranked the potency of clinical protease inhibitors with half-maximal inhibitory concentrations ranging from 1.4 nM to 120 µM and determined inhibitor mechanisms of action, providing the groundwork for drug development efforts to selectively inhibit TMPRSS2.

Modeling spatiotemporal abundance and movement dynamics using an integrated spatial capture-recapture movement model.

Animal movement is a fundamental ecological process affecting the survival and reproduction of individuals, the structure of populations, and the dynamics of communities. Methods to quantify animal movement and spatiotemporal abundances, however, are generally separate and therefore omit linkages between individual-level and population-level processes. We describe an integrated spatial capture-recapture (SCR) movement model to jointly estimate (1) the number and distribution of individuals in a defined spatial region and (2) movement of those individuals through time. We applied our model to a study of polar bears (Ursus maritimus) in a 28,125 km2 survey area of the eastern Chukchi Sea, USA in 2015 that incorporated capture-recapture and telemetry data. In simulation studies, the model provided unbiased estimates of movement, abundance, and detection parameters using a bivariate normal random walk and correlated random walk movement process. Our case study provided detailed evidence of directional movement persistence for both male and female bears, where individuals regularly traversed areas larger than the survey area during the 36-day study period. Scaling from individual- to population-level inferences, we found that densities varied from <0.75 bears/625 km2 grid cell/day in nearshore cells to 1.6-2.5 bears/grid cell/day for cells surrounded by sea ice. Daily abundance estimates ranged from 53 to 69 bears, with no trend across days. The cumulative number of unique bears that used the survey area increased through time due to movements into and out of the area, resulting in an estimated 171 individuals using the survey area during the study (95% credible interval 124-250). Abundance estimates were similar to a previous multiyear integrated population model using capture-recapture and telemetry data (2008-2016; Regehr et al., Scientific Reports 8:16780, 2018). Overall, the SCR-movement model successfully quantified both individual- and population-level space use, including the effects of landscape characteristics on movement, abundance, and detection, while linking the movement and abundance processes to directly estimate density within a prescribed spatial region and temporal period. Integrated SCR-movement models provide a generalizable approach to incorporate greater movement realism into population dynamics and link movement to emergent properties including spatiotemporal densities and abundances.

Intrapopulation differences in polar bear movement and step selection patterns.

BACKGROUND: The spatial ecology of individuals often varies within a population or species. Identifying how individuals in different classes interact with their environment can lead to a better understanding of population responses to human activities and environmental change and improve population estimates. Most inferences about polar bear (Ursus maritimus) spatial ecology are based on data from adult females due to morphological constraints on applying satellite radio collars to other classes of bears. Recent studies, however, have provided limited movement data for adult males and sub-adults of both sexes using ear-mounted and glue-on tags. We evaluated class-specific movements and step selection patterns for polar bears in the Chukchi Sea subpopulation during spring. METHODS: We developed hierarchical Bayesian models to evaluate polar bear movement (i.e., step length and directional persistence) and step selection at the scale of 4-day step lengths. We assessed differences in movement and step selection parameters among the three classes of polar bears (i.e., adult males, sub-adults, and adult females without cubs-of-the-year). RESULTS: Adult males had larger step lengths and less directed movements than adult females. Sub-adult movement parameters did not differ from the other classes but point estimates were most similar to adult females. We did not detect differences among polar bear classes in step selection parameters and parameter estimates were consistent with previous studies. CONCLUSIONS: Our findings support the use of estimated step selection patterns from adult females as a proxy for other classes of polar bears during spring. Conversely, movement analyses indicated that using data from adult females as a proxy for the movements of adult males is likely inappropriate. We recommend that researchers consider whether it is valid to extend inference derived from adult female movements to other classes, based on the questions being asked and the spatial and temporal scope of the data. Because our data were specific to spring, these findings highlight the need to evaluate differences in movement and step selection during other periods of the year, for which data from ear-mounted and glue-on tags are currently lacking.

Hot-Band Absorption Can Mimic Entangled Two-Photon Absorption.

It has been proposed that entangled two-photon absorption (E2PA) can be observed with up to 1010 lower photon flux than its classical counterpart, therefore enabling ultralow-power two-photon fluorescence microscopy. However, there is a significant controversy regarding the magnitude of this quantum enhancement in excitation efficiency. We investigated the fluorescence signals from Rhodamine 6G and LDS798 excited with a CW laser or an entangled photon pair source at ∼1060 nm. We observed a signal that originates from hot-band absorption (HBA), which is one-photon absorption from thermally populated vibrational levels of the ground electronic state. This mechanism, which has not been previously discussed in the context of E2PA, produces a signal with a linear power dependence, as would be expected for E2PA. For the typical conditions under which E2PA measurements are performed, contributions from the HBA process could lead to a several orders of magnitude overestimate of the quantum advantage.

The CADILLAC risk score accurately identifies patients at low risk for in-hospital mortality and adverse cardiovascular events following ST elevation myocardial infarction.

BACKGROUND: The CADILLAC risk score was developed to identify patients at low risk for adverse cardiovascular events following ST elevation myocardial infarction (STEMI) treated with primary percutaneous coronary intervention (PPCI). METHODS: We performed a single center retrospective review of STEMI hospitalizations treated with PPCI from 2014 to 2018. Patients were stratified using the CADILLAC risk score into low risk, intermediate risk and high risk groups. Patients presenting with cardiac arrest or cardiogenic shock were excluded from the study. The primary outcome was adverse clinical events during initial hospitalization. Secondary outcomes were adverse clinical events at 30 days and 1 year following index hospitalization. RESULTS: The study included 341 patients. Compared to patients with a low CADILLAC score, adverse clinical events were similar in the intermediate risk group during hospitalization (OR 1.23, CI 0.37-4.05, p 0.733) and at 30 days (OR 2.27, CI 0.93-5.56, p 0.0733) while adverse clinical events were significantly elevated in the high risk group during hospitalization (OR 4.75, CI 1.91-11.84, p 0.0008) and at 30 days (OR 8.73, CI 4.02-18.96, p < 0.0001). At 1 year follow-up, compared to the low risk CADILLAC group (9.4% adverse clinical event rate), cumulative adverse clinical events were significantly higher in the intermediate risk group (22.9% event rate, OR 2.86, CI 1.39-5.89, p 0.0044) and in the elevated risk group (58.6% event rate, OR 13.67, CI 6.81-27.43, p < 0.0001). The mortality rate was 0% for patients defined at low risk by CADILLAC score during hospitalization, as well up to 1 year follow up. On receiver operating curve analysis, discrimination of in-hospital adverse clinical events was fair using CADILLAC (C = 0.66, odds ratio 1.18; 95% CI 1.04-1.33; p = 0.0064) with somewhat better discrimination at 30-day follow-up (C = 0.719) and 1-year follow-up (C = 0.715). CONCLUSION: Patients defined as low risk by the CADILLAC score following a STEMI were associated with lower mortality and adverse clinical event rates during hospitalization and up to 1 year following STEMI when compared to those with an intermediate or high CADILLAC score.

Altered adipokine levels are associated with dimethyl fumarate treatment in multiple sclerosis patients.

BACKGROUND: Obesity is linked to increased risk of multiple sclerosis (MS) and worsening disease severity. Recent experimental and clinical data indicates that adipokines are involved in regulating immune response and serve as cross talk between immune and neural system. Dimethyl fumarate (DMF) is an oral MS medication with unknown mechanism of action. It upregulates the nuclear factor E2-related factor 2 (Nrf2) pathway, a pathway for adipocyte differentiation. To determine a possible relationship between treatment with dimethyl fumarate, serum adipokine profiles and treatment response in patients with MS, we conducted an observational cohort study and measured serum adipokine and Vitamin D levels before and after treatment with DMF and examined their association with treatment response. METHODS: We identified patients enrolled in the Comprehensive Longitudinal Investigation of Multiple Sclerosis at Brigham and Women's Hospital (CLIMB) study who were treated with dimethyl fumarate and had available serum samples. Longitudinal pre-treatment and on-treatment samples were available in 23 patients. Cross-sectional on-treatment samples were available in 91 patients, who were classified into DMF responders and non-responders based on radiologic and clinical relapse activity or disability progression. We measured serum leptin, adiponectin, resistin, ghrelin, fatty acid binding protein-4 (FABP-4) and-5 (FABP-5), vitamins D2 and D3. Statistical analysis was performed with paired t-tests, Wilcoxon signed-rank and Mann-Whitney U tests. RESULTS: After treatment with DMF, serum adiponectin levels significantly increased, whereas FABP-4 levels significantly decreased compared to baseline levels, without a statistically significant change in the patients' BMI. Ghrelin levels were insignificantly lower post-treatment. FABP-4 levels were significantly higher in DMF responders compared to non-responders. This effect was sex-specific, with higher FABP4 levels associated with treatment response in males, but not females. CONCLUSION: DMF treatment is associated with significant changes in serum adipokine levels, primarily adiponectin and FABP-4. Sex may affect the association between FABP-4 and treatment response.

Demographic risk assessment for a harvested species threatened by climate change: polar bears in the Chukchi Sea.

Climate change threatens global biodiversity. Many species vulnerable to climate change are important to humans for nutritional, cultural, and economic reasons. Polar bears Ursus maritimus are threatened by sea-ice loss and represent a subsistence resource for Indigenous people. We applied a novel population modeling-management framework that is based on species life history and accounts for habitat loss to evaluate subsistence harvest for the Chukchi Sea (CS) polar bear subpopulation. Harvest strategies followed a state-dependent approach under which new data were used to update the harvest on a predetermined management interval. We found that a harvest strategy with a starting total harvest rate of 2.7% (˜85 bears/yr at current abundance), a 2:1 male-to-female ratio, and a 10-yr management interval would likely maintain subpopulation abundance above maximum net productivity level for the next 35 yr (approximately three polar bear generations), our primary criterion for sustainability. Plausible bounds on starting total harvest rate were 1.7-3.9%, where the range reflects uncertainty due to sampling variation, environmental variation, model selection, and differing levels of risk tolerance. The risk of undesired demographic outcomes (e.g., overharvest) was positively related to harvest rate, management interval, and projected declines in environmental carrying capacity; and negatively related to precision in population data. Results reflect several lines of evidence that the CS subpopulation has been productive in recent years, although it is uncertain how long this will last as sea-ice loss continues. Our methods provide a template for balancing trade-offs among protection, use, research investment, and other factors. Demographic risk assessment and state-dependent management will become increasingly important for harvested species, like polar bears, that exhibit spatiotemporal variation in their response to climate change.