Background Patients with prolonged hospitalizations in the surgical intensive care unit often have ongoing medical needs that require further care at long-term, acute-care hospitals upon discharge. ...Setting expectations for patients and families after protracted operative intensive care unit hospitalization is challenging, and there are limited data to guide these conversations. The purpose of this study was to determine patient survival and readmission rates after discharge from the surgical intensive care unit directly to a long-term, acute-care hospital. Methods All patients who were admitted to the surgical intensive care unit at an academic, tertiary care medical center from 2009–2014 and discharged directly to long-term, acute-care hospitals were retrospectively reviewed. Patients represented all surgical subspecialties excluding cardiac and vascular surgery patients. Primary outcomes included 30-day readmission, and 1- and 3-year mortality rates following discharge. Results In total, 296 patients were discharged directly from the surgical intensive care unit to a long-term, acute-care hospital during the study period. There were 190 men (64%) and mean age was 61 ± 16 years. Mean duration of stay in the surgical intensive care unit was 27 ± 17 days. The most frequent complication was prolonged mechanical ventilation (277, 94%) followed by pneumonia (139, 47%), sepsis (78, 26%), and acute renal failure (32, 11%); 93% of patients required tracheostomy and enteral feeding access prior to discharge, and 19 patients (6%) were newly dependent on hemodialysis. The readmission rate was 20%. There were 86 deaths within 1 year from discharge (29%) with an overall 3-year mortality of 32%. In a multiple logistic regression analysis, a history of end-stage renal disease had a greater odds of readmission (odds ratio 6.07, P = .028). Patients with history of cancer had greater odds of 1- and 3-year mortality (odds ratio = 2.99, P = .028 and odds ratio 2.56, P = .053, respectively), and patients with a neurologic diagnosis had greater odds of 3-year mortality (odds ratio 4.69, P = .031). Readmission significantly increased the odds of 1- and 3-year mortality (odds ratio 3.12, P = .020 and odds ratio 2.90, P = .027, respectively). Patients who had both private insurance and Medicare had greater odds of 1- and 3-year mortality (odds ratio 10.39, P = .005 and odds ratio 10.65, P = .004, respectively). Conclusion Patients who are discharged to long-term, acute-care hospitals have prolonged hospitalizations with high complication rates. These patients have high readmission and 1-year mortality rates. Patients and families should be counseled regarding these outcomes related to post–intensive care unit recovery after discharge to a long-term, acute-care hospital to allow for realistic expectations of survival after prolonged intensive care unit hospitalization.
Ongoing research suggests preliminary, though not entirely consistent, evidence of neural abnormalities in signalling prediction errors in schizophrenia. Supporting theories suggest mechanistic links ...between the disruption of these processes and the generation of psychotic symptoms. However, it is unknown at what stage in the pathogenesis of psychosis these impairments in prediction-error signalling develop. One major confound in prior studies is the use of medicated patients with strongly varying disease durations. Our study aims to investigate the involvement of the meso-cortico-striatal circuitry during reward prediction-error signalling in earliest stages of psychosis. We studied patients with first-episode psychosis (FEP) and help-seeking individuals at-risk for psychosis due to sub-threshold prodromal psychotic symptoms. Patients with either FEP (n = 14), or at-risk for developing psychosis (n = 30), and healthy volunteers (n = 39) performed a reinforcement learning task during fMRI scanning. ANOVA revealed significant (p < 0.05 family-wise error corrected) prediction-error signalling differences between groups in the dopaminergic midbrain and right middle frontal gyrus (dorsolateral prefrontal cortex, DLPFC). FEP patients showed disrupted reward prediction-error signalling compared to controls in both regions. At-risk patients showed intermediate activation in the midbrain that significantly differed from controls and from FEP patients, but DLPFC activation that did not differ from controls. Our study confirms that FEP patients have abnormal meso-cortical signalling of reward-prediction errors, whereas reward-prediction-error dysfunction in the at-risk patients appears to show a more nuanced pattern of activation with a degree of midbrain impairment but preserved cortical function.
Objectives
To apply the Frailty Phenotype (FP) and Frailty Index (FI) before major elective orthopedic surgery to categorize frailty status and assess associations with postoperative outcomes.
Design
...Prospective cohort study.
Setting
Two tertiary hospitals in Boston, Massachusetts.
Participants
Individuals aged 70 and older undergoing scheduled orthopedic surgery enrolled in the Successful Aging after Elective Surgery (SAGES) Study (N = 415).
Measurements
Preoperative evaluation included assessment of frailty using the FP and FI. The weighted kappa statistic was used to determine concordance between the two frailty measures and multivariable modeling to determine associations between each measure and postoperative complications, postoperative length of stay (LOS) of longer than 5 days, discharge to postacute institutional care (PAC), and 300 day readmission.
Results
Frailty was highly prevalent (FP, 35%; FI, 41%). There was moderate concordance between the FP and FI (κ = 0.42, 95% confidence interval (CI) 0.36–0.49). When using the FP, being prefrail predicted greater risk of complications (relative risk (RR) = 1.6, 95% CI = 1.1–2.1) and discharge to PAC (RR = 1.8, 95% CI = 1.2–2.9) than being robust, and being frail predicted more complications (RR = 1.7, 95% CI = 1.1–2.1), LOS longer than 5 days (RR = 3.1, 95% CI = 1.1–8.8), and discharge to PAC (RR = 2.3 95% CI = 1.4–3.7). When using FI, being prefrail predicted LOS longer than 5 days (RR = 2.1, 95% CI = 1.0–4.8) and discharge to PAC (RR = 1.5, 95% CI = 1.4–2.1), as did being frail (RR = 1.9, 95% CI = 1.4–2.5; RR = 3.1, 95% CI = 1.4–6.8, respectively). The other outcomes were not significantly associated with frailty status.
Conclusion
FP and FI predict postoperative outcomes after major elective orthopedic surgery and should be considered for preoperative risk stratification.
Fibroblast activation protein-α (FAP) identifies stromal cells of mesenchymal origin in human cancers and chronic inflammatory lesions. In mouse models of cancer, they have been shown to be immune ...suppressive, but studies of their occurrence and function in normal tissues have been limited. With a transgenic mouse line permitting the bioluminescent imaging of FAP(+) cells, we find that they reside in most tissues of the adult mouse. FAP(+) cells from three sites, skeletal muscle, adipose tissue, and pancreas, have highly similar transcriptomes, suggesting a shared lineage. FAP(+) cells of skeletal muscle are the major local source of follistatin, and in bone marrow they express Cxcl12 and KitL. Experimental ablation of these cells causes loss of muscle mass and a reduction of B-lymphopoiesis and erythropoiesis, revealing their essential functions in maintaining normal muscle mass and hematopoiesis, respectively. Remarkably, these cells are altered at these sites in transplantable and spontaneous mouse models of cancer-induced cachexia and anemia. Thus, the FAP(+) stromal cell may have roles in two adverse consequences of cancer: their acquisition by tumors may cause failure of immunosurveillance, and their alteration in normal tissues contributes to the paraneoplastic syndromes of cachexia and anemia.
Lytic polysaccharide monooxygenases (LPMOs) catalyze the degradation of recalcitrant carbohydrate polysaccharide substrates. These enzymes are characterized by a mononuclear Cu(I) active site with a ...three-coordinate T-shaped “His-brace” configuration including the N-terminal histidine and its amine group as ligands. This study explicitly investigates the electronic structure of the d10 Cu(I) active site in a LPMO using Kβ X-ray emission spectroscopy (XES). The lack of inversion symmetry in the His-brace site enables the 3d/p mixing required for intensity in the Kβ valence-to-core (VtC) XES spectrum of Cu(I)-LPMO. These Kβ XES data are correlated to density functional theory (DFT) calculations to define the bonding, and in particular, the frontier molecular orbital (FMO) of the Cu(I) site. These experimentally validated DFT calculations are used to evaluate the reaction coordinate for homolytic cleavage of the H2O2 O–O bond and understand the contribution of this FMO to the low barrier of this reaction and how the geometric and electronic structure of the Cu(I)-LPMO site is activated for rapid reactivity with H2O2.
ACC Advocacy Fry, Edward T.A.; Jones, Samuel O.; Morse, Nick
Journal of the American College of Cardiology,
11/2022, Letnik:
80, Številka:
19
Journal Article
In multicopper oxidases (MCOs), the type 1 (T1) Cu accepts electrons from the substrate and transfers these to the trinuclear Cu cluster (TNC) where O2 is reduced to H2O. The T1 potential in MCOs ...varies from 340 to 780 mV, a range not explained by the existing literature. This study focused on the ∼350 mV difference in potential of the T1 center in Fet3p and Trametes versicolor laccase (TvL) that have the same 2His1Cys ligand set. A range of spectroscopies performed on the oxidized and reduced T1 sites in these MCOs shows that they have equivalent geometric and electronic structures. However, the two His ligands of the T1 Cu in Fet3p are H-bonded to carboxylate residues, while in TvL they are H-bonded to noncharged groups. Electron spin echo envelope modulation spectroscopy shows that there are significant differences in the second-sphere H-bonding interactions in the two T1 centers. Redox titrations on type 2-depleted derivatives of Fet3p and its D409A and E185A variants reveal that the two carboxylates (D409 and E185) lower the T1 potential by 110 and 255–285 mV, respectively. Density functional theory calculations uncouple the effects of the charge of the carboxylates and their difference in H-bonding interactions with the His ligands on the T1 potential, indicating 90–150 mV for anionic charge and ∼100 mV for a strong H-bond. Finally, this study provides an explanation for the generally low potentials of metallooxidases relative to the wide range of potentials of the organic oxidases in terms of different oxidized states of their TNCs involved in catalytic turnover.
Delirium, a costly, life-threatening, and potentially preventable condition, is a common complication for older adults following major surgery. Although the basic epidemiology of delirium after ...surgery has been defined, the contribution of delirium to long term outcomes remains uncertain, and novel biomarkers from plasma and neuroimaging have yet to be examined. This program project was designed to contribute to our understanding of the complex multifactorial syndrome of delirium.
Long term prospective cohort study.
Three academic medical centers (2 hospitals and 1 coordinating center).
Patients without recognized dementia (targeted cohort= 550 patients) age 70 and older scheduled to undergo elective major surgery are assessed at baseline before surgery, daily during their hospital stay, and for 18 to 36 months after discharge.
The Successful Aging after Elective Surgery (SAGES) study is an innovative, interdisciplinary study that includes biomarkers, neuroimaging, cognitive reserve markers, and serial neuropsychological testing to examine the contribution of delirium to long term cognitive and functional decline. The primary goal is to examine the contribution of delirium to long term cognitive and functional decline. In addition, novel risk markers for delirium are being examined, including plasma biomarkers (eg, cytokines, proteomics), advanced neuroimaging markers (eg, volumetric, white matter hyperintensity, noncontrast blood flow, and diffusion tensor measures), and cognitive reserve markers (eg, education, occupation, lifetime activities).
Results from this study will contribute to a fuller understanding of the etiology and prognosis of delirium. Ultimately, we hope this project will provide the groundwork for future development of prevention and treatment strategies for delirium, designed to minimize the long term negative impact of delirium in older adults.
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