Citations

Abstract Engrams are neuronal alterations that encode associations between environmental contexts and subjectively rewarding or aversive experiences within sparsely activated neuronal assemblies that regulate behavioral responses. How positive- or negative-hedonic states are represented in brain neurocircuits is a fundamental question relevant for understanding the processing of emotionally meaningful stimuli that drive appropriate or maladaptive behavior, respectively. It is well-known that animals avoid noxious stimuli and experiences. Little is known, however, how the conditioning of environmental or contextual stimuli to behavior that leads to amelioration of dysphoric states establishes powerful associations leading to compulsive maladaptive behavior. Here we have studied engrams that encode the conditioned effects of alcohol-related stimuli associated with the reversal of the dysphoric withdrawal state in alcohol dependent rats and document the recruitment of engrams in the paraventricular nucleus of the thalamus (PVT), the central nucleus of the amygdala (CeA), and the Dorsal Striatum (DS). The findings suggest that the encoding of associations between reversal of negative hedonic states and environmental contexts in these engrams may serve as a neural mechanism for compulsive alcohol seeking and vulnerability to relapse associated with dysregulation of reward to a pathological allostatic level.

Background: The application of artificial intelligence (AI) in cardiac imaging has rapidly evolved, offering enhanced accuracy and efficiency in the diagnosis and management of cardiovascular diseases. This bibliometric study aimed to evaluate research trends, impact, and scholarly output in this expanding field. Methods: A systematic search was conducted on 14 August 2024 using the Web of Science Core Collection database. VOSviewer, CiteSpace, and Biblioshiny were utilized for data analysis. Results: The findings revealed a significant increase in publications on AI in cardiovascular imaging, particularly from 2018 to 2023, with the United States leading in research output. England and the United States have emerged as central hubs in the global research network, highlighting their role in generating high-quality and impactful publications. The University of London was identified as the top contributing institution, while Frontiers in Cardiovascular Medicine was the most prolific journal. Keyword analysis highlighted machine learning, echocardiography, and diagnosis as the most frequently occurring terms. A time trend analysis showed a shift in research focus toward AI applications in cardiac computed tomography (CT) and magnetic resonance imaging (MRI), with recent keywords like ejection fraction, risk, and heart failure reflecting emerging areas of interest. Conclusion: Healthcare providers should consider integrating AI tools into cardiovascular imaging practice, as AI has demonstrated the potential to enhance diagnostic accuracy and improve patient outcomes. This study highlights the rising importance of AI in personalized and predictive cardiovascular care, urging healthcare providers to stay informed about these advancements to enhance clinical decision-making and patient management.

ImportanceAcute promyelocytic leukemia (APL) is an acute illness that presents with cytopenia, infections, and disseminated intravascular coagulation. Achieving remission has been shown to make a major difference in patient outcomes; however, early death rates in the first month have been as high as 30% due to acute presentation, comorbidities, the rarity of APL, and clinician inexperience.ObjectiveTo develop treatment strategies that would decrease estimated 1-month mortality from 30% to below 15%.Design, Setting, and ParticipantsIn this nonrandomized clinical trial, a treatment algorithm that focused on supportive care was used to prevent early death in patients with APL treated at academic and community health centers between August 2017 and July 2021. Because of the rarity of the disease, expert support was available 24/7 from 7 designated APL experts at 6 participating academic lead centers, and included an additional 293 community centers. When a patient presented with APL, an expert was contacted and a consensus treatment plan was developed using the algorithm and expert suggestions. There were no exclusion criteria and all patients with a confirmed diagnosis of APL regardless of age or comorbid conditions were enrolled. Expert support was provided throughout induction. Initial data analysis was conducted May 2023.Main Outcomes and MeasuresOne-month mortality; additional objectives were to compare outcomes in academic and community centers and assess 1-year and overall survival.ResultsA total of 201 patients were enrolled from 43 centers; 62 at lead centers and 139 from 37 community centers. The median age was 53 years (range, 18-91 years), with 72 patients (35.8%) who were aged 60 years or older; 105 patients (52.2%) were male. Fifty-two patients (26.4%) were diagnosed with high-risk APL. The 1-month mortality rate was 6 deaths of 201 patients (3.0%; 95% CI, 1.1%-6.4%) after adjusting for 1 interim analysis. In a secondary analysis using the Kaplan-Meier method, the 1-month overall survival (OS) rate was 97.0% (95% CI, 93.5%-98.6%) and the 1-year OS rate was 94.5% (95% CI, 90.3%-96.9%).Conclusions and RelevanceIn this nonrandomized clinical trial, use of an algorithm combined with expert support resulted in a dramatic decrease in early death in academic and community centers. Population-wide survival improved in this highly curable disease, which suggests that implementing an accessible support system with APL experts for comanagement is the most logical next step.Trial RegistrationClinicalTrials.gov Identifier: NCT03253848

OBJECTIVES: Acute hypoxemic respiratory failure in immunocompromised patients remains the leading cause of admission to the ICU, with high case fatality. The response to the initial oxygenation strategy may be predictive of outcome. This study aims to assess the response to the evolutionary profiles of oxygenation strategy and the association with survival. DESIGN: Post hoc analysis of EFRAIM study with a nonparametric longitudinal clustering technique (longitudinal K-mean). SETTING AND PATIENTS: Multinational, observational prospective cohort study performed in critically ill immunocompromised patients admitted for an acute respiratory failure. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: A total of 1547 patients who did not require invasive mechanical ventilation (iMV) at ICU admission were included. Change in ventilatory support was assessed and three clusters of change in oxygenation modality over time were identified. Cluster A: 12.3% iMV requirement and high survival rate, n = 717 patients (46.3%); cluster B: 32.9% need for iMV, 97% ICU mortality, n = 499 patients (32.3%); and cluster C: 37.5% need for iMV, 0.3% ICU mortality, n = 331 patients (21.4%). These clusters demonstrated a high discrimination. After adjustment for confounders, clusters B and C were independently associated with need for iMV (odds ratio [OR], 9.87; 95% CI, 7.26–13.50 and OR, 19.8; 95% CI, 13.7–29.1). CONCLUSIONS: This study identified three distinct highly performing clusters of response to initial oxygenation strategy, which reliably predicted the need for iMV requirement and hospital mortality.

OBJECTIVES: Estimated glomerular filtration rate is more accurate with combined creatinine and cystatin C equations (eGFRcr-cys) than creatinine alone. This study created and evaluated a cefepime dosing nomogram based on eGFRcr-cys for initial dosing in the critically ill. DESIGN: Pharmacokinetic modeling and simulation study. SETTING: Academic medical center. PATIENTS: Critically ill adults treated with cefepime. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Data from 120 patients with baseline cystatin C and follow-up cefepime levels were used to develop a nomogram based on eGFRcr-cys and weight for initial cefepime dosing. The predicted proportion of patients who achieved a free cefepime concentration above the minimum inhibitory concentration of the organism for 100% of the dosing interval in the first 24 hours (100% ƒT > MIC at 24 hr) was compared between administered doses and those predicted by the nomogram doses. Overall drug exposure was estimated with the free area under the concentration time curve from 0 to 24 hours (ƒAUC0–24) and compared between administered and nomogram doses. Achievement of 100% ƒT > MIC at 24 hours was predicted to be significantly better with the nomogram compared with the administered dose (76% vs. 38%; p < 0.001). The median ƒAUC0–24 as predicted by the nomogram (666 mg·hr/L) was slightly higher than the actual ƒAUC0–24 with administered doses (612 mg·hr/L; p = 0.01), but the nomogram led to fewer ƒAUC0–24 values which were either too high (> 900) or too low (< 300) (7% vs. 20%; p = 0.004). CONCLUSIONS: Use of a cystatin C-inclusive dosing nomogram for cefepime could improve target attainment without increasing the risk of potentially toxic levels in the critically ill.

BACKGROUND: Preoperative anemia is common and associated with adverse outcomes in surgical patients. There is limited information to guide the design and implementation of preoperative anemia clinics (PAC), which represents a critical barrier to entry for many practices. METHODS: This is a descriptive observational study highlighting the design and implementation of a multidisciplinary PAC, including key steps in planning, stakeholder engagement, organizational structure, identification of target populations, establishing anemia treatments, information technology and electronic health record integration, provider training, and data infrastructure. Demographic and clinical characteristics, laboratory results, and anemia treatments for individuals evaluated in the PAC from November 4, 2019 through September 15, 2023 are enumerated. Patient-reported outcomes (PROs) assessing changes in anemia symptoms and well-being after surgery are evaluated for 2 subsets of patients (one before PAC implementation [pre-PAC], another after PAC implementation [post-PAC]), without formal statistical comparison given limited sample sizes. RESULTS: The PAC was initiated as a multidisciplinary effort under support from a Mayo Clinic Practice Transformation Award in 2019, including broad representation from anesthesiology, surgery, and medical practices, along with institutional project management support (eg, project manager, information technologists, systems engineers). While initially limited to cardiac surgery patients, the PAC underwent planned incremental expansion to include other surgical services. Over the study period, 1188 PAC consultations across 1159 unique patients met eligibility criteria, with a median age of 66 (57–73) years and 58.1% women. The most common etiology of anemia was iron deficiency (69.1%) followed by anemia related to cancer (17.3%). Anemia-directed therapies were recommended in 1038 (87.4%) encounters, with 730 (70.3%) of those receiving recommended treatment preoperatively. Seven hundred nine (97.1%) treatments included intravenous iron and 146 (20.0%) included erythropoiesis-stimulating agents. Fifteen pre-PAC and 38 post-PAC implementation patients completed PROs. PAC implementation was accompanied by earlier resolution of anemia symptoms and less pronounced declines in postoperative well-being scores. CONCLUSIONS: This report highlights the key steps for successful PAC implementation. Treatment is possible for most patients and may be accompanied by improvements in patient-important outcomes.

Objectives: To report the outcomes of minimally invasive (MIS) nephrectomy following immune checkpoint inhibitor (ICI) therapy. Materials and Methods: This multicenter retrospective cohort study included consecutive patients who underwent nephrectomy following ICI therapy at five high-volume US academic centers between 2015 and 2023. Baseline clinical features and perioperative findings were recorded. After propensity-score matching (PSM), outcomes were compared between MIS and open nephrectomies. The primary outcome was 90-day complications, and secondary outcomes included length of hospital stay (LOS) and 90-day readmission. Results: A total of 158 patients were included, of whom 76 and 82 underwent MIS and open nephrectomies, respectively. The MIS procedures included robotic ( n = 56) and laparoscopic ( n = 20). A total of six (8%) patients converted to open. On multivariable analysis, patients with nonmetastatic vs metastatic renal-cell carcinoma (RCC) (hazard ratio [HR] 3.1, p = 0.01), those with smaller tumor size (HR 1.2 for each cm, p = 0.001), and no clinical evidence of inferior vena cava thrombus (HR 29, p = 0.002) were more likely to undergo the MIS approach compared with open approach. After PSM, including 56 MIS and 36 open nephrectomies, the MIS group compared with the open group had lower estimated blood loss (100 vs 460 mL, p < 0.001) and shorter LOS (2 vs 4 days, p < 0.001). Nevertheless, 90-day complications and readmissions were similar between the two groups. There were no 90-day mortality rates in either group. Conclusion: The MIS approach appears safe and offers more favorable perioperative outcomes compared with open surgery in properly selected patients with advanced RCC who are candidates for nephrectomy following ICI therapy.

MRI and CT play an important role in sports cardiology, including preparticipation evaluation, distinguishing adaptive changes of athlete’s heart from pathologic entities, and evaluation following cardiovascular symptoms or adverse events.

Background/Objectives: Limited spinal range of motion (ROM) is linked to low back disorders, emphasizing the need to maintain mobility in the elderly. This study measured maximum spinal ROM, asymmetrical patterns, and the effects of age and muscle activation on spinal mobility. Methods: Forty healthy participants aged 50 and older were recruited. An optical motion capture system recorded three-dimensional coordinates of reflective markers placed on spinal landmarks. Asymmetry was analyzed in sidebending and axial rotation. Electromyography (EMG) data were collected bilaterally from paraspinal muscles at L3 during flexion, extension, sidebending, and axial rotation. Results: Trunk ROM averaged 111° in flexion, 38° in extension, 46° in sidebending, and 87° in axial rotation. Kinematic asymmetry was observed in sidebending and axial rotation. ROM decreased with age in flexion motion (p ≤ 0.04). EMG activity was significantly correlated with ROM data for all combined motions (p = 0.0002). The strongest EMG signal was recorded during flexion, whereas the weakest signal was observed during extension. EMG activity also correlated with kinematic asymmetry (p ≤ 0.03). Conclusions: Age and muscle activation significantly influence spinal ROM in the elderly. Lumbar kinematic asymmetry can be partially attributed to paraspinal muscle activation, underscoring the importance of analyzing asymmetrical motions in conjunction with EMG activity.