Citations

AbstractINPP4A has been shown to be involved in the regulation of cell proliferation and apoptosis of multiple cell types including fibroblasts. Previous reports from our group have demonstrated the role of inositol polyphosphate 4‐phosphatase Type I A (INPP4A) in these functions. Though existing evidences suggest a critical role for INPP4A in the maintenance of lung homeostasis, its role in chronic lung diseases is relatively under explored. In the current study, we made an attempt to understand the regulation of INPP4A in idiopathic pulmonary fibrosis (IPF). Through integration of relevant INPP4A gene expression data from public repositories with our results from in vitro experiments and mouse models, we show that INPP4A is altered in IPF. Interestingly, the direction of the change is dependent both on the disease stage and the region of the lung used. INPP4A was found to be upregulated when analyzed in lung sample representative of the whole lung, but was downregulated in the fibrotic regions of the lung. Similarly, INPP4A was found to be high, compared to controls, only in the early stage of the disease. Though the observed increase in INPP4A was found to be negatively correlated to physiological indices, FVC, and DLCO, of lung function, treatment with anti‐INPP4A antibody worsened the condition in bleomycin treated mice. These contrasting results taken together are suggestive of a nuanced regulation of INPP4A in IPF which is dependent on the disease stage, cellular state and extent of fibrosis in the lung region being analyzed.

Abstract Background Postoperative nausea and vomiting (PONV) is frequent after bariatric surgery. We hypothesized that when compared with a volatile-based technique incorporating propofol infusions, the need for rescue antiemetics would be reduced by the use of two strategies: 1) the addition of dexmedetomidine infusions, and 2) the avoidance of opioid and volatile anesthetics, and that this reduction would be observed in the PACU following PACU discharge. Methods In this retrospective observational study we included patients undergoing bariatric surgery from 2018–2022 who received one of three anesthetic strategies: 1) volatile anesthetic and propofol infusion (VOL + PROP), 2) VOL + PROP with the addition of dexmedetomidine (DEX), or 3) opioid-sparing total intravenous anesthesia (PROP + DEX). Inverse probability of treatment weighting analysis determined the association between the need for rescue-antiemetics in the PACU following PACU discharge. Results 332 patients received VOL + PROP, 354 VOL + PROP + DEX, and 166 PROP + DEX. PROP + DEX received fewer rescue antiemetics in PACU compared to VOL + PROP (11% vs 24%, P = 0.002), and VOL + PROP + DEX fewer compared to VOL + PROP (16% vs 24%, P = 0.023). This differential effect was limited to PACU stay; antiemetic use increased across all groups following PACU discharge until midnight (ranging from 38–46% across groups, P = 0.71) and through the first postoperative day (ranging from 47–57%, P = 0.20). Conclusions The benefit associated with two PONV prevention strategies, the addition of dexmedetomidine infusion or avoidance of opioid and volatile anesthetics, did not persist after PACU discharge. These findings highlight the challenge of PONV on postoperative wards, and the need for a novel multimodal team approach to mitigate this complication.

Background Self-scheduling of medical visits is becoming more common but the complexity of applying multiple requirements for self-scheduling has hampered implementation. Mayo Clinic implemented self-scheduling in 2019 and has been increasing its portfolio of self-schedulable visits since then. Our aim was to show measures quantifying the complexity associated with medical visit scheduling and to describe how opportunities and challenges of scheduling complexity apply in self-scheduling. Methods We examined scheduled visits from January 1, 2022, through August 24, 2023. For seven visit categories, we counted all unique visit types that were scheduled, for both staff-scheduled and self-scheduled. We examined counts of self-scheduled visit types to identify those with highest uptake during the study period. Results There were 9555 unique visit types associated with 20.8 M (million) completed visits. Self-scheduled visit types accounted for 4.0% (838,592/20,769,699) of the completed total visits. Of seven visit categories, self-scheduled established patient visits, testing visits, and procedure visits accounted for 93.5% (784,375/838,592) of all self-scheduled visits. Established patient visits in primary care (10 visit types) accounted for 273,007 (32.6%) of all self-scheduled visits. Testing visits (blood and urine testing, 2 visit types) accounted for 183,870 (21.9%) of all self-scheduled visits. Procedure visits for screening mammograms, bone mineral density, and immunizations (8 visit types) accounted for 147,358 (17.6%) of all self-scheduled visits. Conclusion Large numbers of unique visit types comprise a major challenge for self-scheduling. Some visit types are more suitable for self-scheduling. Guideline-based procedure visits such as screening mammograms, bone mineral density exams, and immunizations are examples of visits that have high volumes and can be standardized for self-scheduling. Established patient visits and laboratory testing visits also can be standardized for self-scheduling. Despite the successes, there remain thousands of specific visit types that may need some staff-scheduler intervention to properly schedule.

Abstract Funding Acknowledgements None. Background Hyperoxemia (a high PaO2, i.e. >200-300 mmHg) has been associated with adverse outcomes in general critical care settings as well as in acute cardiovascular care conditions. The association between hyperoxemia and mortality has not been characterized in the heterogeneous population admitted to the cardiac intensive care unit (CICU). We aimed to examine the association between hyperoxemia on CICU admission with in-hospital mortality. Methods We retrospectively analyzed Mayo Clinic CICU patients from January 2007 to April 2018. PaO2 closest on admission was analyzed as a continuous variable (per 100 mmHg) and categorized as: 60-100 mmHg (51.9%), 101-150 mmHg (28.6%), 151-200 mmHg (10.6%), 201-300 mmHg (6.4%), and >300 mmHg (2.5%). Those without PaO2 on admission and those with hypoxemia were excluded. The primary outcome was all-cause in-hospital mortality evaluated using logistic regression, after adjusting for age, Charlson Comorbidity Index, M-CARS, and use of IMV and NIPPV. Results A total of 3,368 patients were included (median 70.3 years, 39.4% women). Admission diagnoses included ACS (37.0%, with 19.8% STEMI), HF (67.8%), shock (33.0%) and cardiac arrest (25.3%). Median admission PaO2 was 99 (IQR 78, 136) mmHg, with no difference in median PaO2 between hospital survivors and inpatient deaths (99 versus 98, p = 0.38). A J-shaped relationship was observed between admission PaO2 and in-hospital mortality (Figure A), with slightly higher mortality below 100 mmHg and incrementally higher mortality above this threshold (esp. at >200 mmHg). The incremental association between higher PaO2 and mortality (adjusted OR 1.17 per 100 mmHg higher, 95% CI 1.01-1.34, P = 0.03) was focused in the highest PaO2 group (i.e., >300 mmHg; Figure B). Conclusion Hyperoxia (esp. PaO2 >300 mmHg) on CICU admission is associated with increased in-hospital mortality, demonstrating a J-shaped association with an inflection point of lowest mortality around 100 mmHg. Further studies are warranted to assess if specific oxygen targets influence outcomes in critically ill cardiac patients.

Abstract Funding Acknowledgements Type of funding sources: Foundation. Main funding source(s): Aarhus University Dagmar Marshalls Fond. Background The assessment of left ventricular (LV) function through transthoracic echocardiography (TTE) is essential for guiding diagnosis and treatment in cases of cardiogenic shock (CS). Myocardial global longitudinal strain (GLS) provides an objective and reproducible measure of systolic function, independently predicting outcomes in acute heart failure, regardless of left ventricular ejection fraction (LVEF). However, whether assessment of GLS can predict mortality in patients with CS remains unknown. Purpose In this study, we aimed to evaluate the prognostic significance of GLS in patients with CS. Methods Data from cardiac intensive care unit (CICU) patients admitted between 2007 and 2018 with CS who received vasoactive agents and/or mechanical circulatory support were analysed. GLS (as absolute values) and biplane LVEF were measured via TTE performed within 24 hours of CICU admission. Patients with CS were categorised based on the GLS quartile: mild (GLS >9.7%), moderate (7.0% < GLS <9.6%), severe (5.0% < GLS < 6.9%), and very severe (GLS ≤ 4.9%). CICU and in-hospital mortality were compared across GLS categories, and the relationship between GLS and mortality was assessed using multivariable logistic regression. Results The study included 626 patients with a median age of 68.6 years, a median LVEF of 31% (IQR 24 to 40%), and a median GLS of 7.0% (IQR 5.0 to 9.7%). In-hospital mortality was 29.1%. As GLS deteriorated, there was an increasing need for vasopressors (P<0.001). Patients with progressively lower GLS exhibited significantly higher CICU and in-hospital mortality across the GLS quartiles (Figure A; P<0.001). Patients in the severe (adjusted OR 2.67; p<0.001) and very severe category (adjusted OR 3.54; P<0.001) had significantly increased risk of in-hospital death compared with mild category. In multivariable analysis, every 1% decrease in GLS corresponded to a 14% higher risk of in-hospital mortality (P<0.001). Finally, GLS outperformed LVEF for discrimination of in-hospital mortality (P=0.002), and when both measurements were included in the same multivariable model, only GLS remained significant. When patients were divided according to whether they had GLS and/or LVEF below the median value, patients with low GLS had higher mortality irrespective of the LVEF (Figure B). Conclusion In patients with CS, GLS assessment surpasses LVEF in its prognostic value and improves risk stratification. Routine evaluation of GLS should be considered for patients with CS.Figure AFigure B

The treatment for recurrent/metastatic (R/M) head and neck squamous cell carcinoma (HNSCC) with immune checkpoint inhibitors (anti-PD1) with or without chemotherapy has led to an improvement in survival. Yet, despite this therapeutic advancement, only 15%-19% of patients remain alive at four years, highlighting the poor survival and unmet need for improved therapies for this patient population. Some of the key evolving novel therapeutics beyond anti-PD1 in R/M HNSCC have included therapeutic vaccine therapies, bispecific antibodies/fusion proteins and multitargeted kinase inhibitors, and antibody-drug conjugates (ADCs). Multiple concurrent investigations of novel therapeutics for patients with R/M HNSCC beyond anti-PD(L)1 inhibition are currently underway with some promising early results. Beyond immune checkpoint inhibition, novel immunotherapeutic strategies including therapeutic vaccines ranging from targeting human papillomavirus–specific epitopes to personalized neoantigen vaccines are ongoing with some early efficacy signals and large, randomized trials. Other novel weapons including bispecific antibodies, fusion proteins, and multitargeted kinase inhibitors leverage multiple concurrent targets and modulation of the tumor microenvironment to harness antitumor immunity and inhibition of protumorigenic signaling pathways with emerging promising results. Finally, as with other solid tumors, ADCs remain a promising therapeutic intervention either alone or in combination with immunotherapy for patients with R/M HNSCC. With early enthusiasm across novel therapies in R/M HNSCC, results of larger randomized trials in R/M HNSCC are eagerly awaited.

Behavioral neurology & neuropsychiatry (BNNP) is a field that seeks to understand brain–behavior relationships, including fundamental brain organization principles and the many ways that brain structures and connectivity can be disrupted, leading to abnormalities of behavior, cognition, emotion, perception, and social cognition. In North America, BNNP has existed as an integrated subspecialty through the United Council for Neurologic Subspecialties since 2006. Nonetheless, the number of behavioral neurologists across academic medical centers and community settings is not keeping pace with increasing clinical and research demand. In this commentary, we provide a brief history of BNNP followed by an outline of the current challenges and opportunities for BNNP from the behavioral neurologist’s perspective across clinical, research, and educational spheres. We provide a practical guide for promoting BNNP and addressing the shortage of behavioral neurologists to facilitate the continued growth and development of the subspecialty. We also urge a greater commitment to recruit trainees from diverse backgrounds so as to dismantle persistent obstacles that hinder inclusivity in BNNP—efforts that will further enhance the growth and impact of the subspecialty. With rapidly expanding diagnostic and therapeutic approaches across a range of conditions at the intersection of neurology and psychiatry, BNNP is well positioned to attract new trainees and expand its reach across clinical, research, and educational activities.