Type I Interferon Orchestrates Demand-Adapted Monopoiesis during Influenza A Virus Infection via STAT1-Mediated Upregulation of Macrophage Colony-Stimulating Factor Receptor Expression.

Whether and how a local virus infection affects the hematopoietic system in the bone marrow is largely unknown, unlike with systemic infection. In this study, we showed that influenza A virus (IAV) infection leads to demand-adapted monopoiesis in the bone marrow. The beta interferon (IFN-ß) promoter stimulator 1 (IPS-1)-type I IFN-IFN-α receptor 1 (IFNAR1) axis-mediated signaling was found to induce the emergency expansion of the granulocyte-monocyte progenitor (GMP) population and upregulate the expression of the macrophage colony-stimulating factor receptor (M-CSFR) on bipotent GMPs and monocyte progenitors via the signal transducer and activator of transcription 1 (STAT1), leading to a scaled-back proportion of granulocyte progenitors. To further address the influence of demand-adapted monopoiesis on IAV-induced secondary bacterial infection, IAV-infected wild-type (WT) and Stat1-/- mice were challenged with Streptococcus pneumoniae. Compared with WT mice, Stat1-/- mice did not demonstrate demand-adapted monopoiesis, had more infiltrating granulocytes, and were able to effectively eliminate the bacterial infection. IMPORTANCE Our findings show that influenza A virus infection induces type I interferon (IFN)-mediated emergency hematopoiesis to expand the GMP population in the bone marrow. The type I IFN-STAT1 axis was identified as being involved in mediating the viral-infection-driven demand-adapted monopoiesis by upregulating M-CSFR expression in the GMP population. As secondary bacterial infections often manifest during a viral infection and can lead to severe or even fatal clinical complications, we further assessed the impact of the observed monopoiesis on bacterial clearance. Our results suggest that the resulting decrease in the proportion of granulocytes may play a role in diminishing the IAV-infected host's ability to effectively clear secondary bacterial infection. Our findings not only provide a more complete picture of the modulatory functions of type I IFN but also highlight the need for a more comprehensive understanding of potential changes in hematopoiesis during local infections to better inform clinical interventions.

A machine learning model for identifying systemic lupus erythematosus through laboratory information system and electronic medical record.

OBJECTIVES: Systemic lupus erythematosus (SLE) is a heterogeneous autoimmune disease. Its diagnosis poses significant challenges especially at early stages and in atypical cases. The aim of this study was to develop a machine learning model based on common laboratory tests that can aid SLE diagnosis. METHODS: A standard protocol was developed to collect data of SLE and control immune diseases. A 10-fold cross-validation was performed in the modeling dataset (n=862), and an external dataset (n=198) was used for model validation. Machine learning algorithms were applied to construct a diagnostic model. Performance was evaluated based on area under the curve (AUC) values, F1-score, negative predictive value, positive predictive value, accuracy, sensitivity, and specificity. RESULTS: The optimal model was based on a random forest algorithm with 10 clinical features. Thrombin time, prothrombin activity, and uric acid contributed most to the diagnostic model. The SLE diagnostic model showed sufficient predictive accuracy, with AUC values of 0.8286 in the validation dataset. CONCLUSIONS: Our diagnostic model based on 10 common laboratory tests identified the patients with SLE with high accuracy. An online version of the model can potentially be applied in clinical settings for the differential diagnosis of SLE.

The impact of insomnia on anxiety and depression: a longitudinal study of non-clinical young Chinese adult males.

Insomnia, anxiety, and depression commonly co-occured and were closely related. Most of the prior studies were cross-sectional, with a poor ability to infer causality. Longitudinal study was needed to classify the relationships. The present study conducted a longitudinal study of non-clinical young Chinese males to investigate whether insomnia predicted the likelihood of future anxiety and depression, and vice versa. Convenient sampling method was applied, and 288 participants was recruited from Shanghai in October 2017 with Athens Insomnia Scale (AIS), Generalized Anxiety Disorder-7 (GAD-7) and Patient Health Questionnaire-9 (PHQ-9). 120 of them were re-tested in June 2018. The drop-out rate was 58.33%. Correlation analyses and cross-lagged analysis showed that AIS global score was significantly positively related with scores of depression and anxiety at baseline and follow-up. Insomnia was a predictive factor of anxiety, but it can't predict depression. In sum, insomnia may be an important cause of anxiety, while no predictive relationship was found between insomnia and depression.

Efficacy of Constraint-Induced Movement Therapy Versus Bimanual Intensive Training on Motor and Psychosocial Outcomes in Children With Unilateral Cerebral Palsy: A Randomized Trial.

IMPORTANCE: Emerging research has demonstrated that constraint-induced movement therapy (CIMT) and bimanual intensive training (BIT) show promising effectiveness for children with unilateral cerebral palsy (UCP). Considering that neurorehabilitative programs have always been designed with long training periods, psychosocial outcomes have received scarce attention and thus have not been investigated sufficiently. OBJECTIVE: To compare the efficacy of CIMT and BIT with 36-hr interventional dosages for both motor and psychosocial outcomes. DESIGN: Randomized trial. SETTING: Community. PARTICIPANTS: Forty-eight children with UCP, ages 6 to 12 yr. INTERVENTION: Both CIMT and BIT delivered via individual intervention for 2.25 hr/day, twice a week, for 8 wk. OUTCOMES AND MEASURES: The Melbourne Assessment 2, Pediatric Motor Activity Log-Revised, Bruininks-Oseretsky Test of Motor Proficiency, ABILHAND-Kids measure, and Parenting Stress Index-Short Form were administrated at pretreatment, midterm, posttreatment, and 6 mo after intervention. An engagement questionnaire for investigating the child's engagement in the intervention was used to collect the perspectives of the children and the parents weekly. RESULTS: Children with UCP who received either CIMT or BIT achieved similar motor improvements. The only difference was that CIMT yielded larger improvements in frequency and quality of use of the more affected hand at the 6-mo follow-up. Similar child engagement and parental stress levels were found in the two groups. CONCLUSIONS AND RELEVANCE: This study comprehensively compared the efficacy of motor and psychosocial outcomes for 36-hr dosages of CIMT and BIT. The promising findings support the clinical efficacy and feasibility of the proposed protocols. What This Article Adds: The core therapeutic principle of CIMT (i.e., remind the child to use the more affected hand) may be more easily duplicated by parents. Parents may have overestimated their child's engagement and given relatively higher scores; therefore, occupational therapists should also consider the opinions of the children themselves.

Management of Restenosis after Stenting in Left Main Coronary Artery Disease.

Background: The optimal alternative treatment strategy to coronary artery bypass graft surgery (CABG) for in-stent restenosis (ISR) in left main (LM) coronary artery disease remains uncertain. Methods: We retrospectively screened all intervention reports from an intervention database and extracted those mentioning an LM stent. We then manually confirmed reports involving LM ISR and divided them into two groups, those in which the patient received a new drug-eluting stent (new-DES) strategy, and those in which the patient received a drug-coated balloon (DCB) only. A composite endpoint of major adverse cardiovascular events (MACEs) and each individual endpoint were compared. We also performed a brief analysis of similar designed studies. Results: Between the new-DES (n = 40) and DCB-only (n = 22) groups, during median respective follow-up times of 581.5 and 642.5 days, no significant statistical differences were detected in MACEs (50.0% vs. 50.0%, p = 0.974), cardiovascular death (27.5% vs. 13.6%, p = 0.214), nonfatal myocardial infarction (30.0% vs. 31.8%, p = 0.835), or target lesion revascularization (35.0% vs. 45.5%, p = 0.542). We analyzed four similar studies and found comparable MACE findings (odds ratio: 0.85, 95% CI: 0.44-1.67). Conclusions: Our findings support both DCB angioplasty and repeat DES implantation for LMISR lesions in patients who were clinically judged to be unsuitable for CABG; the treatments achieved comparable clinical results in terms of MACEs in the medium term.

Association of leukocyte mitochondrial DNA copy number with longitudinal C-reactive protein levels and survival in older adults: a cohort study.

BACKGROUND: Systemic chronic inflammation occurs with age. The association of the leukocyte mitochondrial DNA copy number, a measure of mitochondrial function in aging, with the temporal profile of serum high-sensitivity C-reactive protein and mortality risk remains uncertain. The objectives of this study were to examine the association of the leukocyte mitochondrial DNA copy number with longitudinal high-sensitivity C-reactive protein levels and the association of the longitudinal high-sensitivity C-reactive protein levels with mortality risk. METHODS: This prospective cohort study included 3928 adults aged ≥ 55 years without systemic inflammation in the baseline examination of the Healthy Aging Longitudinal Study in Taiwan, which started in 2009. Each participant received leukocyte mitochondrial DNA copy number measurement using a fluorescence-based quantitative polymerase chain reaction at baseline, serum high-sensitivity C-reactive protein measurements at baseline and the follow-up examination five years later, and the ascertainment of all-cause death (until November 30, 2021). The relationships among the leukocyte mitochondrial DNA copy number, longitudinal serum high-sensitivity C-reactive protein levels, and time to all-cause mortality were examined using the joint longitudinal and survival modeling analysis. RESULTS: Of the 3928 participants (mean age: 69 years; 2060 [52%] were women), 837 (21%) died during follow-up. In the adjusted analysis, one standard deviation lower natural log-transformed baseline leukocyte mitochondrial DNA copy number was associated with an increase of 0.05 (95% confidence interval [CI], 0.02 to 0.08) standard deviation in serum high-sensitivity C-reactive protein in subsequent years. An increase of 1 standard deviation in instantaneous high-sensitivity C-reactive protein levels was associated with a hazard ratio (HR) for all-cause mortality of 1.22 (95% CI, 1.14 to 1.30). Similar results were obtained after further adjusting for baseline high-sensitivity C-reactive protein levels (HR [95% CI], 1.27 [1.16 to 1.38]) and after excluding those with serum high-sensitivity C-reactive protein above 10 mg/L (HR [95% CI], 1.21[1.11 to 1.31]) or 3 mg/L (HR [95% CI], 1.19 [1.06 to 1.31]) during follow-up. CONCLUSIONS: A lower leukocyte mitochondrial DNA copy number was associated with persistently higher high-sensitivity C-reactive protein levels. Moreover, these higher time-varying high-sensitivity C-reactive protein levels were instantaneously associated with a higher risk of death.

Crk1/2 and CrkL play critical roles in maintaining podocyte morphology and function.

Podocytes are actin-rich epithelial cells whose effacement and detachment are the main cause of glomerular disease. Crk family proteins: Crk1/2 and CrkL are reported to be important intracellular signaling proteins that are involved in many biological processes. However, the roles of them in maintaining podocyte morphology and function remain poorly understood. In this study, specific knocking down of Crk1/2 and CrkL in podocytes caused abnormal cell morphology, actin cytoskeleton rearrangement and dysfunction in cell adhesion, spreading, migration, and viability. The p130Cas, focal adhesion kinase, phosphatidylinositol 3-kinase/Akt, p38 and JNK signaling pathways involved in these alterations. Furthermore, knocking down CrkL alone conferred a more modest phenotype than did the Crk1/2 knockdown and the double knockdown. Kidney biopsy specimens from patients with focal segmental glomerulosclerosis and minimal change nephropathy showed downregulation of Crk1/2 and CrkL in glomeruli. In zebrafish embryos, Crk1/2 and CrkL knockdown compromised the morphology and caused abnormal glomerular development. Thus, our results suggest that Crk1/2 and CrkL expression are important in podocytes; loss of either will cause podocyte dysfunction, leading to foot process effacement and podocyte detachment.

Clinical manifestation and genetic findings in three boys with low molecular Weight Proteinuria - three case reports for exploring Dent Disease and Fanconi syndrome.

BACKGROUND: Dent disease is an X-linked form of progressive renal disease. This rare disorder was characterized by hypercalciuria, low molecular weight (LMW) proteinuria and proximal tubular dysfunction, caused by pathogenic variants in CLCN5 (Dent disease 1) or OCRL (Dent disease 2) genes. Fanconi syndrome is a consequence of decreased water and solute resorption in the proximal tubule of the kidney. Fanconi syndrome caused by proximal tubular dysfunction such as Dent disease might occur in early stage of the disease. CASE PRESENTATION: Three cases reported in this study were 3-, 10- and 14-year-old boys, and proteinuria was the first impression in all the cases. All the boys presented with LMW proteinuria and elevated urine albumin-to-creatinine ratio (ACR). Case 1 revealed a pathogenic variant in exon 11 of CLCN5 gene [NM_001127899; c.1444delG] and a nonsense mutation at nucleotide 1509 [p.L503*], and he was diagnosed as Dent disease 1. Case 2 carried a deletion of exon 3 and 4 of OCRL1 gene [NM_000276.4; c.120-238delG…A] and a nonsense mutation at nucleotide 171 in exon 5 [p.E57*], and this boy was diagnosed as Dent disease 2. Genetic analysis of Case 3 showed a missense mutation located in exon 2 of HNF4A gene [EF591040.1; c.253C > T; p.R85W] which is responsible for Fanconi syndrome. All of three pathogenic variants were not registered in GenBank. CONCLUSIONS: Urine protein electrophoresis should be performed for patients with proteinuria. When patients have LMW proteinuria and/or hypercalciuria, definite diagnosis and identification of Dent disease and Fanconi syndrome requires further genetic analyses.

Clinical features of gingivostomatitis due to primary infection of herpes simplex virus in children.

BACKGROUND: Primary herpetic gingivostomatitis (PHGS) in children, though usually self-limited, might mimic bacterial and enteroviral pharyngitis clinically. We conducted a study to define the clinical features of PHGS in children. METHODS: Between January 2012 and December 2016, 282 inpatients aged less than 19 years with cell culture-confirmed herpes simplex virus (HSV) infection in a medical center were identified from the virologic laboratory logbook. Clinical data were retrospectively collected. RESULTS: Among the 282 inpatients, 185 cases were considered as PHGS and were included for analysis. Fever was present in 99.5%. The mean duration of fever was 5.11 days (±2.24) with the longest being 17 days. Common oral manifestations included oral ulcers (84.3%), which equally resided in the anterior and posterior part of the oral cavity (65.4% vs. 63.2%), gum swelling and/or bleeding (67.6%), and exudate coated tonsils (16.8%). Leukocytosis (WBC count > 15,000/uL3) was noted in 52 patients (28.1%) and a serum C-reactive protein level > 40 mg/L in 55 patients (29.7%). Fixty-five patients (35%) were diagnosed with PHGS on admission and were significantly more likely to have ulcers over the anterior oral cavity (76.1% vs. 26.7%) and gum swelling/bleeding (76.2% vs. 7.5%, p-value all < 0.001) on admission and were significantly less likely to receive antibiotic treatment (16.9 vs. 36.7%, p-value < 0.01) than others. Forty-six patients (25%) undiagnosed as PHGS on discharge were significantly more likely to have exudate coated on the tonsils, to receive antibiotic treatment and significantly less likely to have gum swelling/bleeding and oral ulcers (all p-values < 0.01). CONCLUSIONS: Meticulously identifying specific oral manifestations of gum swelling/bleeding and ulcers over the anterior oral cavity in children can help making the diagnosis of PHGS earlier and subsequently reduce unnecessary prescription of antibiotics.

Baseline Glycated Albumin Predicts the Renal Dysfunction in a Five-Year Prospective Population-Based Study.

BACKGROUND: Glycated albumin (GA) was reported to be associated with renal dysfunction in non-diabetic CKD population. This study assessed the correlation of GA and renal dysfunction and explored risk factors affecting renal progression in a general population-based study through a five-year follow-up. METHODS: Individuals who underwent a physical examination between September 2010 and September 2015 were enrolled. Multivariate linear regression was performed to assess the relationship between GA and eGFR change rate. The relationship between GA and renal progression was analyzed by multivariate logistic regression among 1,501 participants. Other risk factors were also explored and their predictive value was evaluated by ROC analysis, external validation was carried out in another 603 participants from the general population. RESULTS: The frequencies of subjects with renal progression increased obviously with the increment of baseline and mean GA according to quartile stratification (p for trend < 0.001). Baseline GA, age, and uric acid (p < 0.05) were identified as risk factors for renal dysfunction with a 30% or more decrease of eGFR. For every 1% increase of GA, the risk of deterioration of renal function increased to 1.585 in the population (95% CI, 1.299 - 1.935, p < 0.001). The predictive value of the model-building equation was confirmed by ROC analysis (AUC = 0.82, 95% CI: 0.773 - 0.832, p < 0.001) and in the validation group, predictive sensitivity and specificity were 85.7% and 73.5%. CONCLUSIONS: Baseline GA is independently associated with renal dysfunction. Uric acid and age are also considered risk factors. GA combining with age, serum creatinine and uric acid can serve as predictive indicators for the progression of renal dysfunction.

Associations between estimated glomerular filtration rate and cardiac biomarkers.

BACKGROUND: Chronic kidney disease (CKD) is associated with an increased cardiovascular disease (CVD) mortality risk. Elevation of cardiac biomarkers in patients with renal dysfunction is ambiguous in the diagnosis of CVD. The purpose of this study was to investigate the associations between estimated glomerular filtration rate (eGFR) and cardiac biomarkers, and the influence of renal dysfunction on the cardiac biomarkers. METHODS: We examined the cross-sectional associations of eGFR with cardiac troponin I (cTnI), creatine kinase (CK), CK-MB, lactic dehydrogenase (LDH), hydroxybutyrate dehydrogenase (HBDH), and brain natriuretic peptide (BNP) in 812 adults and 215 child. Spearman correlation and logistic regression analysis were performed to evaluate the associations. RESULTS: For adults, lower eGFR CKD-EPI had significantly higher cTnI, CK-MB, LDH, HBDH, and BNP. There were negative correlations between eGFRCKD-EPI and cTnI, CK-MB, LDH, HBDH, and BNP. After adjustment for potential confounders, as compared with eGFRCKD-EPI  ≥ 90 mL/min/1.73 m2 , eGFRCKD-EPI  < 60 mL/min/1.73 m2 remained associated with a 2.83 (1.08-7.41) [ratio (95% CI)] times higher cTnI and a 6.50 (2.32-18.22) [ratio (95% CI)] times higher HBDH. For child, lower eGFRSchwartz had significant higher CK and CK-MB. There were negative correlations between eGFRSchwartz and CK, and eGFRSchwartz and CK-MB. After adjustment for potential confounders, as compared with eGFRSchwartz  ≥ 90 mL/min/1.73 m2 , eGFRSchwartz  < 90 mL/min/1.73 m2 revealed no significant higher CVD biomarkers. CONCLUSION: Reduced eGFR is associated with elevated cTnI and HBDH among adults without clinically evident CVD, but not child.

A performance guide for major risk factors control in patients with atherosclerotic cardiovascular disease in Taiwan.

Atherosclerotic cardiovascular disease (ASCVD), including coronary artery disease, cerebrovascular disease, and peripheral artery disease, carries a high morbidity and mortality. Risk factor control is especially important for patients with ASCVD to reduce recurrent cardiovascular events. Clinical guidelines have been developed by the Taiwan Society of Cardiology, Taiwan Society of Lipids and Atherosclerosis, and Diabetes Association of Republic of China (Taiwan) to assist health care professionals in Taiwan about the control of hypertension, hypercholesterolemia and diabetes mellitus. This article is to highlight the recommendations about blood pressure, cholesterol, and sugar control for ASCVD. Some medications that are beneficial for ASCVD were also reviewed. We hope the clinical outcomes of ASCVD can be improved in Taiwan through the implementation of these recommendations.

Spatial Attention Disregard in Children With Hemiplegic Cerebral Palsy.

IMPORTANCE: Children with hemiplegic cerebral palsy (CP) demonstrate spatial attention disregard, but the rehabilitation approach to CP is traditionally motor oriented. OBJECTIVE: To explore spatial attention disregard in children with hemiplegic CP and its relationship to their motor performance in daily activities. DESIGN: Cross-sectional study. SETTING: Community. PARTICIPANTS: Twenty-five children with hemiplegic CP and 25 age-matched typically developing children. OUTCOMES AND MEASURES: For spatial attention performance, the Random Visual Stimuli Detection Task; for developmental disregard, the Observatory Test of Capacity, Performance, and Developmental Disregard; and for motor performance, the Melbourne Assessment 2. RESULTS: Children with hemiplegic CP evidenced spatial attention disregard on their more affected sides, and this phenomenon was correlated with developmental disregard. CONCLUSIONS AND RELEVANCE: Children with hemiplegic CP demonstrate developmental disregard in both the motor and the visual-spatial attention domains. Including evaluation of and intervention for visual-spatial attention for children with hemiplegic CP in the traditionally motor-oriented rehabilitation approach is recommended. WHAT THIS ARTICLE ADDS: This research provides evidence that children with hemiplegic CP demonstrate disregard in the domain of visual-spatial attention. The findings suggest that evaluation of and intervention for visual-spatial attention should be included in CP rehabilitation in addition to the traditionally motor-oriented approach.

Impact of Platelet Volume on the Clinical Outcomes of Patients with Acute Coronary Syndrome.

BACKGROUND: Platelets with high hemostatic activity play an important role in the pathophysiology of acute coronary syndrome (ACS), and mean platelet volume (MPV) has been proposed to be an indicator of platelet reactivity. We evaluated the predictive value of MPV and the responsive value of MPV with different antiplatelet agents in association with the clinical outcomes of ACS patients. METHODS: A total of 1094 patients with ACS and 472 patients without ACS were included. Blood samples were taken at hospital admission, at routine follow-up within one year, and beyond one year. The patients were divided into a "high MPV group" (> 9.0 fl, n = 305), "medium MPV group" (7.9-9.0 fl, n = 517), and "low MPV group" (< 7.9 fl, n = 272). The average follow-up time was 2.4 years, and the endpoints were major adverse cardiovascular events (MACEs) including all-cause mortality, time to recurrent ACS, target vessel re-intervention and stroke. RESULTS: MPV was significantly higher in the patients with ACS than in those without ACS (8.6 ± 1.1 vs. 8.4 ± 1.0 fl, p = 0.007). MPV decreased in the following year (8.38 ± 1.02 fl, p < 0.001) and also beyond one year (8.38 ± 0.94 fl, p < 0.001) after ACS events. The changes in MPV were not significantly different between the patients receiving either clopidogrel or ticagrelor. The high MPV group had more cardiovascular risk factors and more MACEs than the low MPV group (p = 0.017). CONCLUSIONS: A higher MPV in patients with ACS was associated with more cardiovascular risk factors and more cardiovascular events during clinical follow-up.

A novel nanostructured supramolecular hydrogel self-assembled from tetraphenylethylene-capped dipeptides.

Herein, we report a tetraphenylethylene-diglycine (TPE-GG) hydrogelator from a systematic study of TPE-capped dipeptides with various amphiphilic properties. From a chemical design, we found that the hydrogelation of TPE-GG molecules can be utilized to generate supramolecular nanostructures with a large TPE-based nanobelt width (∼300 nm) and lateral dimension ratio (>30 fold). In addition, TPE-GG has the lowest molecular weight and minimum number of atoms compared to any TPE-capped peptide hydrogelator reported to date. This minimal self-assembled hydrogelator can fundamentally achieve the gel features compared with other TPE-capped peptides. A combined experimental and computational study indicates the π-π interactions, electrostatic interactions and hydrogen-bonding interactions are the major driving forces behind the formation of self-assembled nanobelts. This study demonstrates the importance of structure-property relationships and provides new insights into the design of supramolecular nanomaterials.

Crayfish plague Aphanomyces astaci detected in redclaw crayfish, Cherax quadricarinatus in Taiwan.

Between December 2013 and January 2014, five outbreaks of an unknown disease with moderate to high cumulative mortality were observed among the freshwater redclaw crayfish (Cherax quadricarinatus) populations at four crayfish farms in Miaoli and Changhua counties (northern Taiwan) and at one crayfish farm in Pingtung County (southern Taiwan). Polymerase chain reaction (PCR) analysis allowed the detection of Aphanomyces astaci DNA in dead crayfish. Histopathological examination revealed an infection of host tissue by fungal hyphae that presented as typical non-septate hyphae within the soft abdominal cuticle from the first to second segment and in the tail fan. In PCR assays completed for the detection of crayfish plague, an expected 568-bp product, specific for the A. astaci ITS gene, was obtained from all sub-adults and adults examined. In a comparison of our strains with the known strains of A. astaci in Europe, nucleotide sequence identities were very similar, with 99.8-100% sequence similarity in that gene region. Positive reactions to in situ hybridization, using a digoxigenin (DIG)-labelled DNA probe, further confirmed A. astaci as the causative agent. This is the first report concerning natural infection of A. astaci in freshwater redclaw crayfish in Asia.

Analysis of the Clinical Characteristics, Management, and Causes of Death in Patients with ST-Segment Elevation Myocardial Infarction Treated With Primary Percutaneous Coronary Intervention from 2005 to 2014.

It is unknown whether there has been any change in the causes of death for acute ST-segment elevation myocardial infarction (STEMI) in the era of aggressive reperfusion. We analyzed the direct causes of in-hospital death in patients with STEMI treated with primary percutaneous coronary intervention (PCI) in a tertiary referral center over the past 10 years.We retrospectively analyzed 878 STEMI patients treated with primary PCI in our hospital between January 2005 and December 2014. There were no significant changes in the age and sex of patients, but the prevalence of hypertension and smoking decreased. STEMI severity increased with more patients in Killip classification > 2. The number of out-ofhospital cardiac arrest events also increased over the 10 years. Symptom onset-to-door time did not change in the 10year study period. The care quality was improved with shorter door-to-balloon time for primary PCI and increased use of dual antiplatelet therapy. The all-cause in-hospital mortality was 9.1%, which did not vary over the 10 years. Multivariable analysis showed that Killip classification > 2 was the most important determinant of death. Cardiogenic shock was the major cause of cardiovascular death. There was an increase in non-cardiovascular causes of death in the most recent 3 years, with infection being a major problem.Despite improvement in care quality for STEMI, the in-hospital mortality did not decrease in this tertiary referral center over these 10 years due to increased disease severity and non-cardiovascular causes of death.