ABSTRACT
BACKGROUND: Direct oral anticoagulants (DOACs) have been the drug of choice for preventing ischemic stroke in patients with atrial fibrillation since 2014. In previous studies, the stroke risk while taking warfarin was 2 per 100 patient-years and 1.5% per year while taking DOACs. We hypothesized that even if ischemic stroke occurred during anticoagulation therapy with DOACs, the prognosis was likely to be better than that with warfarin. METHODS AND RESULTS: Data from 2002 to 2019, sourced from a nationwide claims database, were used to identify atrial fibrillation patients using International Classification of Diseases codes. Patients who experienced an ischemic stroke during anticoagulation were categorized by the drugs used (warfarin, dabigatran, apixaban, rivaroxaban, and edoxaban). The primary outcome was mortality within 3 months and 1 year after the ischemic stroke. Among the 9578 patients with ischemic stroke during anticoagulation, 3343 received warfarin, and 6235 received DOACs (965 dabigatran, 2320 apixaban, 1702 rivaroxaban, 1248 edoxaban). The DOACs group demonstrated lower risks of 3-month (adjusted hazard ratio [HR], 0.550, [95% CI, 0.473-0.639]; P<0.0001) and 1-year mortality (adjusted HR, 0.596 [95% CI, 0.536-0.663]; P<0.0001) than the warfarin group. Apixaban and edoxaban within the DOAC group exhibited particularly reduced 1-year mortality risk compared with other DOACs (P<0.0001). CONCLUSIONS: Our study confirmed that DOACs have a better prognosis than warfarin after ischemic stroke. The apixaban and edoxaban groups had a lower risk of death after ischemic stroke than the other DOAC groups.
Subject(s)
Anticoagulants , Atrial Fibrillation , Factor Xa Inhibitors , Ischemic Stroke , Warfarin , Humans , Warfarin/therapeutic use , Warfarin/adverse effects , Ischemic Stroke/prevention & control , Ischemic Stroke/mortality , Ischemic Stroke/diagnosis , Male , Female , Aged , Anticoagulants/adverse effects , Anticoagulants/therapeutic use , Anticoagulants/administration & dosage , Atrial Fibrillation/drug therapy , Atrial Fibrillation/complications , Atrial Fibrillation/mortality , Prognosis , Administration, Oral , Factor Xa Inhibitors/therapeutic use , Factor Xa Inhibitors/adverse effects , Factor Xa Inhibitors/administration & dosage , Middle Aged , Aged, 80 and over , Pyridones/adverse effects , Pyridones/therapeutic use , Pyridones/administration & dosage , Retrospective Studies , Pyrazoles/therapeutic use , Pyrazoles/adverse effects , Dabigatran/therapeutic use , Dabigatran/adverse effects , Dabigatran/administration & dosage , Rivaroxaban/therapeutic use , Rivaroxaban/adverse effects , Rivaroxaban/administration & dosage , Risk Factors , Risk Assessment , Taiwan/epidemiology , Pyridines , ThiazolesABSTRACT
Background: Falls after orthopaedic surgery can cause serious injuries, which lengthen hospital stays and increase medical expenses. This has prompted hospitals to implement various fall-prevention protocols. The aims of this study were to determine the incidence of in-hospital falls after spine surgery, to analyze the overall risk factors, to discern factors that have a major influence on falls, and to evaluate the effectiveness of the fall-prevention protocol that we implemented. Methods: This was a retrospective, single-center study including patients who underwent spine surgery from January 2011 to November 2021 at the National Health Insurance Service Ilsan Hospital (NHISIH) in Goyang, Republic of Korea. Reported falls among these patients were examined. Patient demographics; surgery type, date, and diagnosis; and fall date and time were evaluated. Results: Overall, 5,317 spine surgeries were performed, and 128 in-hospital falls were reported (overall incidence: 2.31%). From the multivariable analyses, older age and American Society of Anesthesiologists (ASA) score were identified as independent risk factors for in-hospital patient falls (multivariable adjusted hazard ratio [aHR] for age 70 to 79 years, 1.021 [95% confidence interval (CI), 1.01 to 1.031]; for age ≥80 years, 1.035 [1.01 to 1.06]; and for ASA score of 3, 1.02 [1.01 to 1.031]). Similar results were seen in the subgroup who underwent primary surgery. Within 2 weeks following surgery, the highest frequency of falls occurred at 3 to 7 days postoperatively. The lowest fall rate was observed in the evening (6 to 10 p.m.). Morbidities, including rib, spine, and extremity fractures, were recorded for 14 patients, but none of these patients underwent operative treatment related to the fall. The NHISIH implemented a comprehensive nursing care service in May 2015 and a fall protocol in May 2017, but the annual incidence rate did not improve. The fall rate was higher after thoracolumbar surgeries (2.47%) than after cervical surgeries (1.20%). Moreover, a higher fall rate was observed in thoracolumbar cases with a greater number of fusion levels and revision spine surgeries. Conclusions: Patients with advanced age, more comorbidities, a greater number of fusion levels, and revision surgeries and who are female are more vulnerable to in-hospital falls after spine surgery. Novel strategies that target these risk factors are warranted. Level of Evidence: Prognostic Level III. See Instructions for Authors for a complete description of levels of evidence.
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Background: Determining the cost structure of medical care from diagnosis to the death of patients with cancer is crucial for establishing budgets to support patients with cancer. The breakdown of the cost estimation in distinct phases of survival is essential for optimizing the allocation of limited funds. Therefore, this study aims to examine the patterns of direct medical costs of cancer care associated with seven major cancer types and estimate cost thresholds to distinguish each phase based on the incurred cost. Methods: In this nationwide, population-based study, we used claims data from the National Health Insurance Service, Korea. Patients newly diagnosed with cancer since 2006 and who died in 2016-2017 were enrolled, and their use of medical services during cancer survival from at least 6 months up to 12 years was observed. The monthly cost exhibited a non-linear function with two unknown thresholds resembling a U-shape; therefore, we fitted three linear segment models. Individual costs were assessed by dividing the survival time into the initial, continuing, and terminal phases by estimated thresholds, and the average medical cost for each phase was calculated. Results: Based on survival durations of 12 years or less, the initial phase occurred within 1.1-4.8 months after diagnosis, while the terminal phase was observed in 1.4-4.7 months before death. The length of these two phases increased with the increased survival time of the patients. Medical costs in these phases ranged from $4067-7431 and $3127-6114 (US dollars), respectively, regardless of the variations in survival time. However, the average costs in the continuing phase were higher for patients with a short survival time. Conclusions: This study highlights the cost dynamics in cancer care through a breakdown of the phases of survival. It suggests that through a more refined definition of the initial and terminal phases, the average cost in these stages increases, indicating the significant implications of the findings for resource allocation and tailored financial support strategies for patients with cancer with varying prognoses.
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BACKGROUND: Many studies have evaluated stroke using claims data; most of these studies have defined ischemic stroke using an operational definition following the rule-based method. Rule-based methods tend to overestimate the number of patients with ischemic stroke. OBJECTIVES: We aimed to identify an appropriate algorithm for identifying stroke by applying machine learning (ML) techniques to analyze the claims data. METHODS: We obtained the data from the Korean National Health Insurance Service database, which is linked to the Ilsan Hospital database (n = 30,897). The performance of prediction models (extreme gradient boosting [XGBoost] or gated recurrent unit [GRU]) was evaluated using the area under the receiver operating characteristic curve (AUROC), the area under precision-recall curve (AUPRC), and calibration curve. RESULTS: In total, 30,897 patients were enrolled in this study, 3145 of whom (10.18%) had ischemic stroke. XGBoost, a tree-based ML technique, had the AUROC was 94.46% and AUPRC was 92.80%. GRU showed the highest accuracy (99.81%), precision (99.92%) and recall (99.69%). CONCLUSIONS: We proposed recurrent neural network-based deep learning techniques to improve stroke phenotyping. This can be expected to produce rapid and more accurate results than the rule-based methods.
Subject(s)
Ischemic Stroke , Stroke , Humans , Stroke/diagnosis , Stroke/epidemiology , Algorithms , Area Under Curve , Machine LearningABSTRACT
Pathogenic loss-of-function SCN1A variants cause a spectrum of seizure disorders. We previously identified variants in individuals with SCN1A -related epilepsy that fall in or near a poison exon (PE) in SCN1A intron 20 (20N). We hypothesized these variants lead to increased PE inclusion, which introduces a premature stop codon, and, therefore, reduced abundance of the full-length SCN1A transcript and Na v 1.1 protein. We used a splicing reporter assay to interrogate PE inclusion in HEK293T cells. In addition, we used patient-specific induced pluripotent stem cells (iPSCs) differentiated into neurons to quantify 20N inclusion by long and short-read sequencing and Na v 1.1 abundance by western blot. We performed RNA-antisense purification with mass spectrometry to identify RNA-binding proteins (RBPs) that could account for the aberrant PE splicing. We demonstrate that variants in/near 20N lead to increased 20N inclusion by long-read sequencing or splicing reporter assay and decreased Na v 1.1 abundance. We also identified 28 RBPs that differentially interact with variant constructs compared to wild-type, including SRSF1 and HNRNPL. We propose a model whereby 20N variants disrupt RBP binding to splicing enhancers (SRSF1) and suppressors (HNRNPL), to favor PE inclusion. Overall, we demonstrate that SCN1A 20N variants cause haploinsufficiency and SCN1A -related epilepsies. This work provides insights into the complex control of RBP-mediated PE alternative splicing, with broader implications for PE discovery and identification of pathogenic PE variants in other genetic conditions.
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How exercise elicits systemic metabolic benefits in both muscles and non-contractile tissues is unclear. Autophagy is a stress-induced lysosomal degradation pathway that mediates protein and organelle turnover and metabolic adaptation. Exercise activates autophagy in not only contracting muscles but also non-contractile tissues including the liver. However, the role and mechanism of exercise-activated autophagy in non-contractile tissues remain mysterious. Here, we show that hepatic autophagy activation is essential for exercise-induced metabolic benefits. Plasma or serum from exercised mice is sufficient to activate autophagy in cells. By proteomic studies, we identify fibronectin (FN1), which was previously considered as an extracellular matrix protein, as an exercise-induced, muscle-secreted, autophagy-inducing circulating factor. Muscle-secreted FN1 mediates exercise-induced hepatic autophagy and systemic insulin sensitization via the hepatic receptor α5ß1 integrin and the downstream IKKα/ß-JNK1-BECN1 pathway. Thus, we demonstrate that hepatic autophagy activation drives exercise-induced metabolic benefits against diabetes via muscle-secreted soluble FN1 and hepatic α5ß1 integrin signaling.
Subject(s)
Fibronectins , Proteomics , Mice , Animals , Fibronectins/metabolism , Liver/metabolism , Autophagy , IntegrinsABSTRACT
Introduction: Non-vitamin K antagonist oral anticoagulants (NOACs) has been the drug of choice for preventing ischemic stroke in patients with atrial fibrillation (AF) since 2014. Many studies based on claim data revealed that NOACs had comparable effect to warfarin in preventing ischemic stroke with fewer hemorrhagic side effects. We analyzed the difference in clinical outcomes according to the drugs in patients with AF based on the clinical data warehouse (CDW). Methods: We extracted data of patients with AF from our hospital's CDW and obtained clinical information including test results. All claim data of the patients were extracted from National Health Insurance Service, and dataset was constructed by combining it with CDW data. Separately, another dataset was constructed with patients who could obtain sufficient clinical information from the CDW. The patients were divided NOAC and warfarin groups. The occurrence of ischemic stroke, intracranial hemorrhage, gastrointestinal bleeding, and death were confirmed as clinical outcome. The factors influencing the risk of clinical outcomes were analyzed. Results: The patients who were diagnosed AF between 2009 and 2020 were included in the dataset construction. In the combined dataset, 858 patients were treated with warfarin, 2,343 patients were treated with NOACs. After the diagnosis of AF, the incidence of ischemic stroke during follow-up was 199 (23.2%) in the warfarin group, 209 (8.9%) in the NOAC group. Intracranial hemorrhage occurred in 70 patients (8.2%) among the warfarin group, 61 (2.6%) of the NOAC group. Gastrointestinal bleeding occurred in 69 patients (8.0%) in the warfarin group, 78 patients (3.3%) in the NOAC group. NOAC's hazard ratio (HR) of ischemic stroke was 0.479 (95% CI 0.39-0.589, p < 0.0001), HR of intracranial hemorrhage was 0.453 (95% CI 0.31-0.664, p < 0.0001), and HR of gastrointestinal bleeding was 0.579 (95% CI 0.406-0.824, p = 0.0024). In the dataset constructed using only CDW, the NOAC group also had a lower risk of ischemic stroke and intracranial hemorrhage than warfarin group. Conclusions: In this CDW based study, NOACs are more effective and safer than warfarin in patients with AF even with long-term follow-up. NOACs should be used to prevent ischemic stroke in patients with AF.
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We investigated the interference of apical constriction position and diameter on the accuracy of electronic apex locators using 3D-printed tooth models. Single-rooted tooth models with the same length, canal taper and major foramen, but variation in apical constriction position or size, were designed and 3D-printed. A mounting model was custom-made for precise measurement of both marks (0.5 and APEX/0.0) of two electronic apex locators. The electronic measurements of both devices were correlated significantly to the major foramen rather than apical constriction. The mean measurements of the group with 0.45 mm in apical constriction width were significantly shorter than those of the other groups for both marks of the two devices (p < 0.05). The variations in apical constriction position and width negatively affected the precision of the 0.5 mark of the tested devices. The 0.0 or APEX mark was consistently located the major foramen.
Subject(s)
Dental Pulp Cavity , Tooth Apex , Tooth Apex/diagnostic imaging , Tooth Apex/anatomy & histology , Dental Pulp Cavity/diagnostic imaging , Dental Pulp Cavity/anatomy & histology , Root Canal Preparation , Constriction , Odontometry , Electronics , Printing, Three-DimensionalABSTRACT
Many psychiatric disorders accompany deficits in cognitive functions and synaptic plasticity, and abnormal lipid modifications of neuronal proteins are associated with their pathophysiology. Lipid modifications, including palmitoylation and myristoylation, play crucial roles in the subcellular localization and trafficking of proteins. Cyclin Y (CCNY), enriched in the postsynaptic compartment, acts as an inhibitory modulator of functional and structural long-term potentiation (LTP) in the hippocampal neurons. However, cellular and molecular mechanisms underlying CCNY-mediated inhibitory functions in the synapse remain largely unknown. Here, we report that myristoylation located CCNY to the trans-Golgi network (TGN), and subsequent palmitoylation directed the myristoylated CCNY from the TGN to the synaptic cell surface. This myristoylation-dependent palmitoylation of CCNY was required for the inhibitory role of CCNY in excitatory synaptic transmission, activity-induced dynamics of AMPA receptors and PSD-95, LTP, and spatial learning. Furthermore, spatial learning significantly reduced palmitoyl- and myristoyl-CCNY levels, indicating that spatial learning lowers the synaptic abundance of CCNY. Our findings provide mechanistic insight into how CCNY is clustered adjacent to postsynaptic sites where it could play its inhibitory roles in synaptic plasticity and spatial learning.
Subject(s)
Long-Term Potentiation , Receptors, AMPA , Cyclins/metabolism , Hippocampus/physiology , Humans , Lipids , Lipoylation/physiology , Long-Term Potentiation/physiology , Neuronal Plasticity/physiology , Receptors, AMPA/metabolism , Spatial Learning , Synapses/metabolismABSTRACT
This study aimed to analyze the risk factors for mortality of septic knee arthritis in Korea through a large nationwide data research. The National Health Insurance Service-Health Screening database was used to analyze 89,120 hospitalizations for septic knee arthritis between 2005 and 2018. In-hospital, thirty-day, and ninety-day mortality, and their association with patient's demographic factors, various comorbidities (i.e., cerebrovascular disease, congestive heart failure, and myocardial infarction) and Charlson Comorbidity Index (CCI) were assessed. Secondary outcomes of complications (osteomyelitis, knee arthroplasty, recurrence) were analyzed. The number of hospitalization with septic knee arthritis increased from 1847 cases in 2005 to 8749 cases in 2018. There was no significant difference in mortality after diagnosis of septic knee arthritis between years. The risk of mortality in patients who hospitalized with septic knee arthritis increased in comorbidities like Congestive heart failure, dementia, myocardial infarction, chronic kidney disease. Hazard ratio (HR) decreased in patients who have comorbidities such as rheumatoid arthritis, liver disease, rheumatologic disease. HR for mortality in septic knee arthritis increased in patients with CCI more than 1. The risk factors for mortality in all periods were male sex, old age, high CCI, comorbidities such as congestive heart failure, dementia, myocardial infarction, chronic kidney disease. Efforts to reduce mortality should be concentrate more on patients with these risk factors.
Subject(s)
Arthritis, Infectious , Dementia , Heart Failure , Myocardial Infarction , Renal Insufficiency, Chronic , Arthritis, Infectious/epidemiology , Comorbidity , Female , Heart Failure/epidemiology , Humans , Male , Retrospective Studies , Risk FactorsABSTRACT
The usage of dexmedetomidine during cancer surgery in current clinical practice is debatable, largely owing to the differing reports of its efficacy based on cancer type. This study aimed to investigate the effects of dexmedetomidine on biochemical recurrence (BCR) and radiographic progression in patients with prostate cancer, who have undergone robot-assisted laparoscopic radical prostatectomy (RALP). Using follow-up data from two prospective randomized controlled studies, BCR and radiographic progression were compared between individuals who received dexmedetomidine (n = 58) and those who received saline (n = 56). Patients with complete follow-up records between July 2013 and June 2019 were enrolled in this study. There were no significant between-group differences in the number of patients who developed BCR and those who showed positive radiographic progression. Based on the Cox regression analysis, age (p = 0.015), Gleason score ≥ 8 (p < 0.001), and pathological tumor stage 3a and 3b (both p < 0.001) were shown to be significant predictors of post-RALP BCR. However, there was no impact on the dexmedetomidine or control groups. Low-dose administration of dexmedetomidine at a rate of 0.3-0.4 µg/kg/h did not significantly affect BCR incidence following RALP. In addition, no beneficial effect was noted on radiographic progression.
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Autophagy dysregulation is implicated in metabolic diseases, including type 2 diabetes. However, the mechanism by which the autophagy machinery regulates metabolism is largely unknown. Autophagy is generally considered a degradation process via lysosomes. Here, we unveil a metabolically important non-cell-autonomous, non-degradative mechanism regulated by the essential autophagy protein Becn1 in adipose tissue. Upon high-fat diet challenge, autophagy-hyperactive Becn1F121A mice show systemically improved insulin sensitivity and enhanced activation of AMP-activated protein kinase (AMPK), a central regulator of energy homeostasis, via a non-cell-autonomous mechanism mediated by adiponectin, an adipose-derived metabolic hormone. Adipose-specific Becn1F121A expression is sufficient to activate AMPK in non-adipose tissues and improve systemic insulin sensitivity by increasing adiponectin secretion. Further, Becn1 enhances adiponectin secretion by interacting with components of the exocyst complex via the coiled-coil domain. Together, our study demonstrates that Becn1 improves insulin sensitivity by facilitating adiponectin secretion through binding the exocyst in adipose tissue.
Subject(s)
AMP-Activated Protein Kinases/metabolism , Adiponectin/metabolism , Beclin-1/metabolism , Insulin/metabolism , Lysosomes/metabolism , Animals , Autophagy , Humans , Mice , TransfectionABSTRACT
Drug abuse is a foremost public health problem. Cocaine is a widely abused drug worldwide that produces various reward-related behaviors. The mechanisms that underlie cocaine-induced disorders are unresolved, and effective treatments are lacking. Here, we found that an autophagy-related protein Becn2 is a previously unidentified regulator of cocaine reward behaviors. Becn2 deletion protects mice from cocaine-stimulated locomotion and reward behaviors, as well as cocaine-induced dopamine accumulation and signaling, by increasing presynaptic dopamine receptor 2 (D2R) autoreceptors in dopamine neurons. Becn2 regulates D2R endolysosomal trafficking, degradation, and cocaine-induced behaviors via interacting with a D2R-bound adaptor GASP1. Inactivating Becn2 by upstream autophagy inhibitors stabilizes striatal presynaptic D2R, reduces dopamine release and signaling, and prevents cocaine reward in normal mice. Thus, the autophagy protein Becn2 is essential for cocaine psychomotor stimulation and reward through regulating dopamine neurotransmission, and targeting Becn2 by autophagy inhibitors is a potential strategy to prevent cocaine-induced behaviors.
Subject(s)
Cocaine , Animals , Autophagy-Related Proteins , Cocaine/pharmacology , Dopamine/metabolism , Dopamine Uptake Inhibitors/pharmacology , Intracellular Signaling Peptides and Proteins , Mice , RewardABSTRACT
We investigated the optimal combinations of systolic blood pressure (SBP) and diastolic blood pressure (DBP) levels for lowest mortality in participants not taking hypertensive medication at the study baseline using nationwide representative databases. Survival rates and hazard ratios (HRs) were calculated using Kaplan-Meier curves and multivariable Cox regression analyses. The discriminatory ability for clinical outcomes was assessed by Harrell's C-index analysis. A survival spline curve was presented, and Classification and Regression Tree (CART) analysis was performed. SBP ≥ 140 group and DBP ≥ 90 group had the highest risk of mortality. Within SBP < 120, the HR (95% CIs) for all-cause mortality (ACM) was the lowest for DBP 70-79. Within SBP 120-139, the HR (95% CIs) for ACM was significantly lower for DBP 70-79. Within SBP ≥ 140, the HR (95% CIs) for ACM was significantly lower for DBP 80-89. Conversely, within SBP ≥ 140, DBP < 70 showed the highest risk for ACM. Similar relationships were observed when survival spline curves and CART analysis were used. The combination of SBP and DBP discriminated better than SBP or DBP alone for mortality. The effect of DBP on mortality varies according to the SBP range. It is more effective to evaluate the effect of SBP and DBP jointly for clinical outcomes.
Subject(s)
Cardiovascular Diseases , Hypertension , Blood Pressure , Cohort Studies , Humans , Hypertension/diagnosis , Hypertension/drug therapy , Hypertension/epidemiology , Republic of Korea/epidemiology , Risk FactorsABSTRACT
PURPOSE: Critical care medicine continues to evolve. However, critical care cases require increasing amount of medical resources. Intensive care unit (ICU) mortality significantly impacts the overall efficiency of healthcare resources within a system of limited medical resources. This study investigated the factors related to ICU mortality using long-term nationwide cohort data in South Korea. MATERIALS AND METHODS: This retrospective cohort study used data of 14905721 patients who submitted reimbursement claims to the Korean Health Insurance Service between January 1, 2011 and December 31, 2015. A total of 1498102 patients who were admitted to all ICU types, except neonatal and long-term acute care hospitals, were enrolled. RESULTS: Of the total 1498102 participants, 861397 (57.5%) were male and 636705 (42.5%) were female. The mean age at admission was 63.4±18.2 years; most of the subjects were aged over 60 years. During the 5-year period, in-hospital mortality rate was 12.9%. In Cox analysis, both in-hospital and 28-day mortality rates were significantly higher in male patients and those of lower socioeconomic status. As age increased and the number of nursing staff decreased, the mortality risk increased significantly by two or three times. The mortality risk was lower in patients admitted to an ICU of a tertiary university hospital and an ICU where intensivists worked. CONCLUSION: The number of nursing staff and the presence of an intensivist in ICU were associated with the ICU mortality rate. Also, increasing the number of nursing staff and the presence of intensivist might reduce the mortality rate among ICU patients.
Subject(s)
Critical Illness/mortality , Critical Illness/nursing , Intensive Care Units/statistics & numerical data , Nursing Staff/statistics & numerical data , Physicians/statistics & numerical data , Aged , Aged, 80 and over , Cohort Studies , Female , Hospital Mortality , Humans , Male , Middle Aged , Republic of Korea , Retrospective Studies , Tertiary Care CentersABSTRACT
While positive regulators of hippocampal long-term potentiation (LTP) have extensively been investigated, relatively little is known about the inhibitory regulators of LTP. We previously reported that Cyclin Y (CCNY), a member of cyclin family generally known to function in proliferating cells, is a novel postsynaptic protein that serves as a negative regulator of functional LTP. However, whether CCNY plays a role in structural LTP, which is mechanistically linked to functional LTP, and which mechanisms are involved in the CCNY-mediated suppression of LTP at the molecular level remain elusive. Here, we report that CCNY negatively regulates the plasticity-induced changes in spine morphology through the control of actin dynamics. We observed that CCNY directly binds to filamentous actin and interferes with LTP-induced actin polymerization as well as depolymerization by blocking the activation of cofilin, an actin-depolymerizing factor, thus resulting in less plastic spines and the impairment of structural LTP. These data suggest that CCNY acts as an inhibitory regulator for both structural and functional LTP by modulating actin dynamics through the cofilin-actin pathway. Collectively, our findings provide a mechanistic insight into the inhibitory modulation of hippocampal LTP by CCNY, highlighting a novel function of a cyclin family protein in non-proliferating neuronal cells.
Subject(s)
Neuronal Plasticity , Actin Depolymerizing Factors , Actins , Cyclins , Microfilament Proteins , SynapsesABSTRACT
Hematological abnormalities at admission are common after traumatic brain injuries and are associated with poor outcomes. The objective of this study was to identify the predictive factors of mortality among patients who underwent emergency surgery for the evacuation of epidural hematoma (EDH) or subdural hematoma (SDH).This was a single-center retrospective cohort study of 200 patients who underwent emergency surgical evacuation of EDH or SDH between September 2010 and December 2018. Data on hematological parameters and clinical and intraoperative features were collected. The primary end-point was 1-year mortality after surgery. Univariate and multivariate analysis were performed, and the receiver operating characteristic (ROC) curves were assessed.Of the 200 patients included in this study, 102 (51%) patients died within 1 year of emergency surgery. Lymphocyte count at admission, creatinine levels, activated partial thromboplastin time (aPTT), age, intraoperative epinephrine use, and Glasgow Coma Scale (GCS) score were significantly associated with mortality in the multivariate analysis. The areas under the ROC curve for the GCS score, aPTT, and lymphocyte counts were 0.677 (95% confidence interval [CI] 0.602-0.753), 0.644 (95% CI 0.567-0.721), and 0.576 (95% CI 0.496-0.656), respectively.Patients with elevated lymphocyte counts on admission showed a higher rate of 1-year mortality following emergency craniectomy for EDH or SDH. In addition, prolonged aPTT and a lower GCS score were also related to poor survival.
Subject(s)
Hematoma, Epidural, Cranial/blood , Hematoma, Epidural, Cranial/surgery , Hematoma, Subdural, Intracranial/blood , Hematoma, Subdural, Intracranial/surgery , Adult , Aged , Biomarkers/blood , Craniotomy , Creatinine/blood , Emergency Service, Hospital , Epinephrine/therapeutic use , Female , Glasgow Coma Scale , Hematoma, Epidural, Cranial/mortality , Hematoma, Subdural, Intracranial/mortality , Humans , Intraoperative Period , Lymphocyte Count , Male , Middle Aged , Partial Thromboplastin Time , Prognosis , Retrospective Studies , Vasoconstrictor Agents/therapeutic useABSTRACT
PURPOSE: Oxycodone has affinities for both kappa- and mu-opioid receptors. Therefore, it has been used for postoperative analgesia of surgeries in which visceral pain is expected to be the main cause of pain. However, there are few studies of the 55:1 potency ratio of oxycodone to fentanyl when using it as intravenous patient-controlled analgesia (IV-PCA). Thus, we compared the analgesic and adverse effects of IV-PCA using the 55:1 potency ratio of oxycodone to fentanyl in patients who underwent robot-assisted laparoscopic gastrectomy. PATIENTS AND METHODS: This retrospective study included 100 patients using an automatic PCA pump with oxycodone or fentanyl who underwent robot-assisted laparoscopic gastrectomy between January and November 2017. All patients were provided with an IV-PCA consisting of 20 µg/kg of fentanyl or 1.1 mg/kg of oxycodone mixed with 0.9% normal saline solution to a total volume of 250 mL, which was infused basally at a rate of 0.1 mL/h with a bolus dose of 1 mL and lockout time of 6 min. The primary and secondary endpoints were to evaluate the efficacies of IV-PCA using the 55:1 potency ratio of oxycodone to fentanyl on analgesic and adverse effects. RESULTS: Pain intensity on arrival at the post-anesthesia care unit (PACU; 3.6±1.4 vs 4.4±2.0, P=0.031) and additional analgesic requirement within an hour after surgery (including the PACU period) (12% vs 37%; P=0.005) were significantly lower in the oxycodone group (n=49) than in the fentanyl group (n=51). Regarding adverse effects, the rate of postoperative nausea within 1 h after surgery (2% vs 16%; P=0.031) was also significantly lower in the oxycodone group than that in the fentanyl group. CONCLUSION: Oxycodone-based IV-PCA by dose calculations with a 55:1 potency ratio may achieve better analgesia without any significant adverse effects, when using IV-PCA in patients undergoing robot-assisted laparoscopic gastrectomy.
ABSTRACT
BACKGROUND: Cardiovascular disease (CVD) is an important cause of morbidity and mortality in patients with cancer. However, the real-world CVD burden of adult cancer patients has not been well established. This study aimed to evaluate the prevalence and mortality of pre-existing and new-onset CVD in patients with cancers. METHODS: We analysed the prevalence and mortality of pre-existing and new-onset CVD in 41,034 adult patients with ten common solid cancers in a single payer system using data from the Korean National Health Insurance Service-National Sample Cohort from 2002 to 2013. RESULTS: When all types of cancer were included, 11.3% (n = 4647) of patients had pre-existing CVD when they were diagnosed with cancer. After excluding patients with pre-existing CVD, 15.7% of cancer patients (n = 5703) were newly diagnosed with CVD during the follow-up period (median 68 months). Both pre-existing and new-onset CVD were associated with increased risk of overall mortality and 5-year mortality. Multivariate analysis to predict all-cause mortality indicated both pre-existing and new-onset CVD, male sex, old age, prior history of diabetes or chronic kidney disease, suburban residential area, and low-income status as significant factors. CONCLUSIONS: Eleven percent of cancer patients had pre-existing CVD at the time of cancer diagnosis, and about 16% of cancer patients without pre-existing CVD were newly diagnosed with CVD, mostly within 5 years after the cancer diagnosis. Proper management of pre-existing CVD is necessary and pre-emptive prevention of new-onset CVD may alter treatment options and outcomes.