iSleepFirst: burnout, fatigue, and wearable-tracked sleep deprivation among residents staffing the medical intensive care unit.

PURPOSE: This study aimed to evaluate the relationship between sleep, burnout, and psychomotor vigilance in residents working in the medical intensive care unit (ICU). METHODS: A prospective cohort study of residents was implemented during a consecutive 4-week. Residents were recruited to wear a sleep tracker for 2 weeks before and 2 weeks during their medical ICU rotation. Data collected included wearable-tracked sleep minutes, Oldenburg burnout inventory (OBI) score, Epworth sleepiness scale (ESS), psychomotor vigilance testing, and American Academy of Sleep Medicine sleep diary. The primary outcome was sleep duration tracked by the wearable. The secondary outcomes were burnout, psychomotor vigilance (PVT), and perceived sleepiness. RESULTS: A total of 40 residents completed the study. The age range was 26-34 years with 19 males. Total sleep minutes measured by the wearable decreased from 402 min (95% CI: 377-427) before ICU to 389 (95% CI: 360-418) during ICU (p < 0.05). Residents overestimated sleep, logging 464 min (95% CI: 452-476) before and 442 (95% CI: 430-454) during ICU. ESS scores increased from 5.93 (95% CI: 4.89, 7.07) to 8.33 (95% CI: 7.09,9.58) during ICU (p < 0.001). OBI scores increased from 34.5 (95% CI: 32.9-36.2) to 42.8 (95% CI: 40.7-45.0) (p < 0.001). PVT scores worsened with increased reaction time while on ICU rotation (348.5 ms pre-ICU, 370.9 ms post-ICU, p < 0.001). CONCLUSIONS: Resident ICU rotations are associated with decreased objective sleep and self-reported sleep. Residents overestimate sleep duration. Burnout and sleepiness increase and associated PVT scores worsen while working in the ICU. Institutions should ensure resident sleep and wellness checks during ICU rotation.

Hospital-Wide Intervention in Billing and Coding to Capture Complexity of Care at an Academic Referral Center.

GOAL: Downcoding at nonprofit healthcare institutions can account for significant revenue losses that, in turn, can affect the amount and quality of care they provide. Using the inpatient medical note to assess the complexity of care, we wanted to quantify the visit coding distribution at the largest tertiary care center in West Virginia and to improve the documentation and coding if found to be below national benchmarks. METHODS: We measured the number of encounters and associated documentation of level 1, 2, and 3 visits among hospitalists. We compared our data to national benchmark data. We then implemented a multifaceted, multidisciplinary intervention to improve documentation and coding. PRINCIPAL FINDINGS: We found a significant average increase of level 3 admission history and physical visits of 76% ( p < .0001) and 112% ( p < .001) for subsequent encounters compared with baseline preintervention visit types. With team-based coding interventions in place, documentation accurately now reflects the complexity of care delivered. Based on Medicare reimbursement rates, this new accuracy has led to an increase in revenue of $233, 988.79 per 10,000 encounters. APPLICATIONS TO PRACTICE: Provider knowledge of medical billing and coding guidelines is essential. In particular, large academic institutions typically operate on small margins, so even simple adjustments and quality improvement efforts in billing and coding can help immensely by accurately representing the amount and quality of medical services. An institution can markedly improve revenues by coding notes to reflect the true complexity of care that is delivered.

Trends in Location of Death in Patients With Aortic Aneurysm and Dissection.

Aortic dissections and aneurysms (ADA) are associated with significant morbidity and mortality, and location of death for these patients is important in determining impact on end of life care. We analyzed the Centers for Disease Control and Prevention Wide-ranging Online Data for Epidemiologic Research database. Black and Hispanic backgrounds had decreased odds of dying at home from ADA. Married or educated individuals tended to die at home at a higher rate than unmarried individuals. Overall, we have shown place of death in individuals with ADA is different among individuals of different demographics.

A data-driven modeling approach to identify disease-specific multi-organ networks driving physiological dysregulation.

Multiple physiological systems interact throughout the development of a complex disease. Knowledge of the dynamics and connectivity of interactions across physiological systems could facilitate the prevention or mitigation of organ damage underlying complex diseases, many of which are currently refractory to available therapeutics (e.g., hypertension). We studied the regulatory interactions operating within and across organs throughout disease development by integrating in vivo analysis of gene expression dynamics with a reverse engineering approach to infer data-driven dynamic network models of multi-organ gene regulatory influences. We obtained experimental data on the expression of 22 genes across five organs, over a time span that encompassed the development of autonomic nervous system dysfunction and hypertension. We pursued a unique approach for identification of continuous-time models that jointly described the dynamics and structure of multi-organ networks by estimating a sparse subset of ∼12,000 possible gene regulatory interactions. Our analyses revealed that an autonomic dysfunction-specific multi-organ sequence of gene expression activation patterns was associated with a distinct gene regulatory network. We analyzed the model structures for adaptation motifs, and identified disease-specific network motifs involving genes that exhibited aberrant temporal dynamics. Bioinformatic analyses identified disease-specific single nucleotide variants within or near transcription factor binding sites upstream of key genes implicated in maintaining physiological homeostasis. Our approach illustrates a novel framework for investigating the pathogenesis through model-based analysis of multi-organ system dynamics and network properties. Our results yielded novel candidate molecular targets driving the development of cardiovascular disease, metabolic syndrome, and immune dysfunction.

Systemic leukotriene B4 receptor antagonism lowers arterial blood pressure and improves autonomic function in the spontaneously hypertensive rat.

KEY POINTS: Evidence indicates an association between hypertension and chronic systemic inflammation in both human hypertension and experimental animal models. Previous studies in the spontaneously hypertensive rat (SHR) support a role for leukotriene B4 (LTB4 ), a potent chemoattractant involved in the inflammatory response, but its mode of action is poorly understood. In the SHR, we observed an increase in T cells and macrophages in the brainstem; in addition, gene expression profiling data showed that LTB4 production, degradation and downstream signalling in the brainstem of the SHR are dynamically regulated during hypertension. When LTB4 receptor 1 (BLT1) receptors were blocked with CP-105,696, arterial pressure was reduced in the SHR compared to the normotensive control and this reduction was associated with a significant decrease in systolic blood pressure (BP) indicators. These data provide new evidence for the role of LTB4 as an important neuro-immune pathway in the development of hypertension and therefore may serve as a novel therapeutic target for the treatment of neurogenic hypertension. ABSTRACT: Accumulating evidence indicates an association between hypertension and chronic systemic inflammation in both human hypertension and experimental animal models. Previous studies in the spontaneously hypertensive rat (SHR) support a role for leukotriene B4 (LTB4 ), a potent chemoattractant involved in the inflammatory response. However, the mechanism for LTB4 -mediated inflammation in hypertension is poorly understood. Here we report in the SHR, increased brainstem infiltration of T cells and macrophages plus gene expression profiling data showing that LTB4 production, degradation and downstream signalling in the brainstem of the SHR are dynamically regulated during hypertension. Chronic blockade of the LTB4 receptor 1 (BLT1) receptor with CP-105,696, reduced arterial pressure in the SHR compared to the normotensive control and this reduction was associated with a significant decrease in low and high frequency spectra of systolic blood pressure, and an increase in spontaneous baroreceptor reflex gain (sBRG). These data provide new evidence for the role of LTB4 as an important neuro-immune pathway in the development of hypertension and therefore may serve as a novel therapeutic target for the treatment of neurogenic hypertension.

MicroRNA network changes in the brain stem underlie the development of hypertension.

Hypertension is a major chronic disease whose molecular mechanisms remain poorly understood. We compared neuroanatomical patterns of microRNAs in the brain stem of the spontaneous hypertensive rat (SHR) to the Wistar Kyoto rat (WKY, control). We quantified 419 well-annotated microRNAs in the nucleus of the solitary tract (NTS) and rostral ventrolateral medulla (RVLM), from SHR and WKY rats, during three main stages of hypertension development. Changes in microRNA expression were stage- and region-dependent, with a majority of SHR vs. WKY differential expression occurring at the hypertension onset stage in NTS versus at the prehypertension stage in RVLM. Our analysis identified 24 microRNAs showing time-dependent differential expression in SHR compared with WKY in at least one brain region. We predicted potential gene regulatory targets corresponding to catecholaminergic processes, neuroinflammation, and neuromodulation using the miRWALK and RNA22 databases, and we tested those bioinformatics predictions using high-throughput quantitative PCR to evaluate correlations of differential expression between the microRNAs and their predicted gene targets. We found a novel regulatory network motif consisting of microRNAs likely downregulating a negative regulator of prohypertensive processes such as angiotensin II signaling and leukotriene-based inflammation. Our results provide new evidence on the dynamics of microRNA expression in the development of hypertension and predictions of microRNA-mediated regulatory networks playing a region-dependent role in potentially altering brain-stem cardiovascular control circuit function leading to the development of hypertension.

Healthcare Providers' Experiences of Caring for Patients With COVID-19 Requiring Extracorporeal Membrane Oxygenation Support.

BACKGROUND: Coronavirus 19 (COVID-19) affected healthcare workers (HCW) in ways more than increasing the volume of patients needing care. Increased numbers of patients at younger ages required support with extracorporeal membrane oxygenation (ECMO). Providing this care requires an interdisciplinary team. AIM: This study explored the experiences of HCW caring for patients with COVID-19 on ECMO. METHODS: Face-to-face semi-structured interviews were conducted via videoconferencing, and transcript comparison was used for the analysis. FINDINGS: Open coding of the data generated 7 categories including (1) fearing the unknown, (2) confronting challenges in patient and/or family interactions, (3) encountering barriers to providing care, (4) facing moral distress, (5) working through exhaustion, (6) persevering by strengthening teamwork, (7) and acknowledging frustration with non-believers. DISCUSSION: HCW balanced pessimism and optimism while caring for patient with COVID-19 on ECMO. They used negative experiences caring for these patients to strength teamwork and bonding among peers. CONCLUSION: The practice implications for caring for patients with COVID-19 on ECMO include viligance by clinician and organization to protect the wellbeing of healthcare providers, particularly in ICU and ECMO units were moral distress and burnout can be high.

Trends and cardiovascular outcomes of Takotsubo syndrome with cardiogenic shock vs. mixed cardiogenic and septic shock: a nationwide propensity matched analysis.

INTRODUCTION: Takotsubo syndrome (TTS), also known as stress-induced cardiomyopathy, can be complicated by shock. The outcomes of patients with TTS complicated with cardiogenic shock (CS) versus mixed cardiogenic and septic shock (MS) is not known. METHODS: We queried Nationwide Inpatient Sample (NIS) from 2009-2020 to compare TTS patients with CS and MS using International Classification of Disease, Ninth & Tenth Edition, Clinical Modification (ICD- 9 & 10-CM) coding. In-hospital outcomes were compared using one: one propensity score matched (PSM) analysis. The primary outcome was in-hospital mortality. RESULTS: Of 23,126 patients with TTS 17,132 (74%) had CS, and 6,269 (26%) had MS. The mean age was 67 years in CS and 66 years in MS, and majority of patients were female (n = 17,775, 77%). On adjusted multivariate analysis, MS patients had higher odds of in-hospital mortality (aOR 1.44, 95% CI 1.36-1.52), AKI (aOR 1.53, 95% CI 1.48-1.58), pressor requirement (aOR 1.37, 95% CI 1.25-1.50). However, had lower odds of MCS use (aOR 0.44, 95% CI 0.40-0.48) and cardiac arrest (aOR: 0.81, 95% CI 0.73-0.90) (p-value <0.0001). Mean LOS and inflation-adjusted hospital charges were higher in MS. CONCLUSION: MS in the setting of TTS have higher rates of in-hospital mortality, AKI, and pressor requirements.

Isolated pulmonary amyloidoma: A rare cause of solitary pulmonary nodule.

Pulmonary nodules are a frequent finding on imaging, especially given screening guidelines for lung cancer with low dose computed tomography (CT) scan. Here, we report a case with a single pulmonary nodule in a patient exposed to coal dust and asbestos. The nodule had benign features, but it showed an increase in size on repeated imaging. A CT-guided biopsy followed by mass spectrometry of the sample identified the nodule as the AL subtype of amyloidoma. A bone marrow biopsy was without evidence for malignancy including lymphoma. Nodular pulmonary amyloidosis (NPA) is rare, and a biopsy is required to establish the diagnosis. NPA generally does not affect lung function or impact survival; thus NPA does not require specific therapy. This case is the first documented case associated with coal-dust exposure. High-risk patients need to be followed longitudinally due to association of amyloidosis with lymphoma and other systemic conditions.

Meta-Analysis on the Impact of Coronary Bypass Graft Markers on Angiographic Procedural Outcomes.

Utilization of radio-opaque coronary artery bypass graft markers is known to decrease the amount of contrast dye required to complete the procedure. The practice of marking bypass grafts varies significantly among surgeons. Limited data exist comparing the outcomes of percutaneous coronary intervention with and without coronary artery bypass graft (CABG) markers. We sought to explore the impact of proximal radio-opaque markers placed during CABG in subsequent percutaneous coronary intervention procedural risks. In our understanding of the current literature, this is the first meta-analysis conducted to evaluate the association between procedural angiographic metrics and CABG radio-opaque markers. We performed a query of MEDLINE and Scopus databases through August 2022 to identify relevant studies evaluating procedural metrics among patients with previous CABG with and without radio-opaque markers who underwent angiography. The primary outcomes of interest were fluoroscopy time, amount of contrast, and duration of angiography. We identified a total of 4 studies with 2,046 patients with CABG (CABG with markers n = 688, CABG without markers n = 1,518).2-5 Total fluoroscopy time was significantly reduced among patients with CABG markers compared with those with no markers (odds ratio [OR] -3.63, p <0.0001). The duration of angiography (OR -36.39, p >0.10) was reduced, although the result was not statistically significant. However, the amount of contrast utilization was significantly reduced (OR -33.41, p <0.0001). In patients who underwent CABG with radio-opaque markers, angiographic procedural metrics were improved, including reduced fluoroscopic time and the amount of contrast agent required compared with no markers.

HuR Contributes to TRAIL Resistance by Restricting Death Receptor 4 Expression in Pancreatic Cancer Cells.

UNLABELLED: Pancreatic ductal adenocarcinoma (PDA) is one of the most lethal cancers, in part, due to resistance to both conventional and targeted therapeutics. TRAIL directly induces apoptosis through engagement of cell surface Death Receptors (DR4 and DR5), and has been explored as a molecular target for cancer treatment. Clinical trials with recombinant TRAIL and DR-targeting agents, however, have failed to show overall positive outcomes. Herein, we identify a novel TRAIL resistance mechanism governed by Hu antigen R (HuR, ELAV1), a stress-response protein abundant and functional in PDA cells. Exogenous HuR overexpression in TRAIL-sensitive PDA cell lines increases TRAIL resistance whereas silencing HuR in TRAIL-resistant PDA cells, by siRNA oligo-transfection, decreases TRAIL resistance. PDA cell exposure to soluble TRAIL induces HuR translocation from the nucleus to the cytoplasm. Furthermore, it is demonstrated that HuR interacts with the 3'-untranslated region (UTR) of DR4 mRNA. Pre-treatment of PDA cells with MS-444 (Novartis), an established small molecule inhibitor of HuR, substantially increased DR4 and DR5 cell surface levels and enhanced TRAIL sensitivity, further validating HuR's role in affecting TRAIL apoptotic resistance. NanoString analyses on the transcriptome of TRAIL-exposed PDA cells identified global HuR-mediated increases in antiapoptotic processes. Taken together, these data extend HuR's role as a key regulator of TRAIL-induced apoptosis. IMPLICATIONS: Discovery of an important new HuR-mediated TRAIL resistance mechanism suggests that tumor-targeted HuR inhibition increases sensitivity to TRAIL-based therapeutics and supports their re-evaluation as an effective treatment for PDA patients. Mol Cancer Res; 14(7); 599-611. ©2016 AACR.