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Postoperative stroke is a severe and potentially disabling complication following surgical intervention for acute type A aortic dissection (ATAAD). This retrospective study aims to compare the early and late outcomes between patients who had hemorrhagic and ischemic stroke after undergoing ATAAD repair surgery. Between January 2007 and June 2020, a total of 685 consecutive patients underwent ATAAD repair at our institution. Patients who had a preoperative stroke or were unconscious at presentation were excluded from this study. Of the 656 included for analysis, 102 (15.5%) patients had a postoperative stroke confirmed by computed tomography angiography. The strokes were classified into the ischemia group (n = 83, 12.7%) and hemorrhage group (n = 19, 2.9%). Clinical features, surgical information, postoperative complications, modified Rankin Scale (mRS) scores after discharge, and 5-year cumulative survival rates were compared. Demographics, comorbidities, and presentations of ATAAD were similar between the two groups, except a higher rate of preoperative antithrombotic medication was found in the hemorrhage group. The hemorrhage group was associated with a higher complexity of aortic arch replacement, longer cardiopulmonary bypass, and aortic clamping times than the ischemia group. A higher in-hospital mortality rate (42.1% versus 20.5%; p = 0.048) and a higher median mRS score at the 3-month follow-up after discharge (6[3–6] versus 4[2–6]; p = 0.027) were found in the hemorrhage group. The hemorrhage group showed a lower 5-year cumulative survival rate (23.4% versus 57.8%; p = 0.003) compared with the ischemia group. Postoperative hemorrhagic stroke was associated with poorer neurological outcomes and lower survival rates than those with ischemic stroke. Patients who have complex arch replacement, long cardiopulmonary bypass and aortic clamping times are at risk for postoperative hemorrhagic stroke and should have intensive neurological surveillance for early diagnosis and treatment after ATAAD repair surgery.

It’s a challenge for detecting the therapeutic targets of a polypharmacological drug from variations in the responsed networks in the differentiated populations with complex diseases, as stable coronary heart disease. Here, in an adaptive, 31-center, randomized, double-blind trial involving 920 patients with moderate symptomatic stable angina treated by 14-day Danhong injection(DHI), a kind of polypharmacological drug with high quality control, or placebo (0.9% saline), with 76-day following-up, we firstly confirmed that DHI could increase the proportion of patients with clinically significant changes on angina-frequency assessed by Seattle Angina Questionnaire (ΔSAQ-AF ≥ 20) (12.78% at Day 30, 95% confidence interval [CI] 5.86–19.71%, P = 0.0003, 13.82% at Day 60, 95% CI 6.82–20.82%, P = 0.0001 and 8.95% at Day 90, 95% CI 2.06–15.85%, P = 0.01). We also found that there were no significant differences in new-onset major vascular events (P = 0.8502) and serious adverse events (P = 0.9105) between DHI and placebo. After performing the RNA sequencing in 62 selected patients, we developed a systemic modular approach to identify differentially expressed modules (DEMs) of DHI with the Zsummary value less than 0 compared with the control group, calculated by weighted gene co-expression network analysis (WGCNA), and sketched out the basic framework on a modular map with 25 functional modules targeted by DHI. Furthermore, the effective therapeutic module (ETM), defined as the highest correlation value with the phenotype alteration (ΔSAQ-AF, the change in SAQ-AF at Day 30 from baseline) calculated by WGCNA, was identified in the population with the best effect (ΔSAQ-AF ≥ 40), which is related to anticoagulation and regulation of cholesterol metabolism. We assessed the modular flexibility of this ETM using the global topological D value based on Euclidean distance, which is correlated with phenotype alteration (r2: 0.8204, P = 0.019) by linear regression. Our study identified the anti-angina therapeutic module in the effective population treated by the multi-target drug. Modular methods facilitate the discovery of network pharmacological mechanisms and the advancement of precision medicine. (ClinicalTrials.gov identifier: NCT01681316).

Objectives: Recently, Stereotactic Body Radiotherapy (SBRT) has been suggested for managing hepatocellular carcinoma (HCC) curatively. Thus, we conducted this clinical study to evaluate retrospectively the effect of individualized audio-visual (AV) coaching, respiratory modulated SBRT. Materials and Methods: Between 2014 and 2018, 29 patients with inoperable Barcelona Clinic Liver Cancer (BCLC) stage 0-B HCC received AV coaching, respiratory-modulated SBRT. We constructed a task-oriented multidisciplinary team to establish a standard operation process of respiratory modulation procedures and developed our AV coaching devices. In the training period, a goodness-of-fit test was applied individually. SBRT was delivered with a total dose of 40–54 Gy in 5–6 fractions individually. Freedom from local progression (FFLP) and overall survival (OS) were estimated using SPSS (version 17, SPSS Inc., Chicago, IL, USA) life tables. Results: The patient characteristics were as follows: 32.7 ± 16 mm in maximum tumor diameter (range 11–94); BCLC stage 0: 3.4%, BCLC A: 48.3%, BCLC B: 48.3%; Child-Pugh classification A: 86.2%, Child-Pugh classification B: 13.8%, and a median of 2 prior liver-directed treatments (range 0–7). One-, 2-, and 3-year rates of FFLP of SBRT were 96.6%, 96.6%, and 96.6%, respectively. One-, 2-, and 3-year rates of OS were 81.5%, 72.4%, and 67.2%, respectively. No adverse event (AE) occurred in 41.4% of patients, 48.3% developed grade (G) 1–2 AE, 10.3% had G3 AE and none had G4-5 AE. Conclusion: Respiration-modulated SBRT is a promising noninvasive treatment option for patients with inoperable and localized HCC. Our data show that SBRT provides comparable tumor control to historical curative options like surgery and radiofrequency ablation of localized tumors. Thus, we are conducting a further prospective clinical trial with the intent to demarcate the clinical effectiveness of SBRT in a larger population of patients with HCC.

Percutaneous computed tomography (CT)-guided transthoracic needle biopsy (TTNB) is a valuable procedure for obtaining tissue or cells for diagnosis, which is especially indispensable in thoracic oncology. Pneumothorax and hemoptysis are the most common complications of percutaneous needle biopsy of the lung. According to reports published over the past decades, pneumothorax incidence in patients who underwent TTNB greatly varies. The morbidity of pneumothorax after CT-guided TTNB depends on several factors, including size and depth of lesions, emphysema, the number of pleural surfaces and fissure crossed, etc. Attention to biopsy planning and technique and post-biopsy precautions help to prevent or minimize potential complications. Many measures can be taken to help prevent the progression of a pneumothorax, which in turn might reduce the number of pneumothoraces requiring chest tube placement. A multitude of therapeutic options is available for the treatment of pneumothorax, varying from observation and oxygen treatment, simple manual aspiration, to chest tube placement. When a pneumothorax develops during the biopsy procedure, it can be manually aspirated after the needle is retracted back into the pleural space or by inserting a separate needle into the pleural space. Biopsy side down positioning of the patient after biopsy significantly reduces the incidence of pneumothorax and the requirement of chest tube placement. Aspiration in biopsy side down position is also recommended for treating pneumothorax when simple manual aspiration is unsuccessful or delayed pneumothorax occurred. Chest tube placement is an important treatment strategy for patients with a large or symptomatic pneumothorax. Clinicians are encouraged to understand the development, prevention, and treatment of pneumothorax. Efforts should be made to reduce the incidence of pneumothorax in biopsy planning and post-biopsy precautions. When pneumothorax occurs, appropriate treatment should be adopted to reduce the risk of worsening pneumothorax.

Background Mechanical power (MP) refers to the energy delivered by a ventilator to the respiratory system per unit of time. MP referenced to predicted body weight (PBW) or respiratory system compliance have better predictive value for mortality than MP alone in acute respiratory distress syndrome (ARDS). Our objective was to assess the potential impact of consecutive changes of MP on hospital mortality among ARDS patients receiving extracorporeal membrane oxygenation (ECMO). Methods We performed a retrospective analysis of patients with severe ARDS receiving ECMO in a tertiary care referral center in Taiwan between May 2006 and October 2015. Serial changes of MP during ECMO were recorded. Results A total of 152 patients with severe ARDS rescued with ECMO were analyzed. Overall hospital mortality was 53.3%. There were no significant differences between survivors and nonsurvivors in terms of baseline values of MP or other ventilator settings. Cox regression models demonstrated that mean MP alone, MP referenced to PBW, and MP referenced to compliance during the first 3 days of ECMO were all independently associated with hospital mortality. Higher MP referenced to compliance (HR 2.289 [95% CI 1.214–4.314], p = 0.010) was associated with a higher risk of death than MP itself (HR 1.060 [95% CI 1.018–1.104], p = 0.005) or MP referenced to PBW (HR 1.004 [95% CI 1.002–1.007], p 14.4 J/min) during the first 3 days of ECMO was significantly higher than that of patients with low MP (≦ 14.4 J/min) (70.7% vs. 46.8%, p = 0.004), and the 90-day hospital mortality of patients with high MP referenced to compliance (> 0.53 J/min/ml/cm H2O) during the first 3 days of ECMO was significantly higher than that of patients with low MP referenced to compliance (≦ 0.53 J/min/ml/cm H2O) (63.6% vs. 29.7%, p Conclusions MP during the first 3 days of ECMO was the only ventilatory variable independently associated with 90-day hospital mortality, and MP referenced to compliance during ECMO was more predictive for mortality than was MP alone.

The Perceval sutureless valve has gained in popularity for treating degenerative aortic valve stenosis but not for congenital type 0 bicuspid aortic valve owing to anatomic challenges. We modified implant techniques following the four principles of ECHO—an acronym for elasticity, circularity, height, and orientation—to prevent paravalvular leakage and malposition.

BACKGROUND The 23-valent pneumococcal polysaccharide vaccine (PPSV23) is indicated for adults who have a high risk of pneumonia; however, its effectiveness in patients with prostate cancer who are at a risk of pneumonia because of age and cancer treatments, including androgen-deprivation therapy, is unknown. METHODS Between 2000 and 2010, 38,735 patients with prostate cancer were diagnosed in Taiwan. After exclusions and exact matching for age, previous pneumonia, and influenza vaccination, 2188 vaccinated patients and 2188 unvaccinated patients were recruited. The incidence density of all-cause bacterial pneumonia hospitalizations was analyzed. RESULTS Over 7 years of follow-up, patients who received the PPSV23 had a significantly lower incidence density, with 142.8 per 1000 person-years versus 162.0 per 1000 person-years for unvaccinated patients. More patients in the vaccinated cohort were never hospitalized for pneumonia compared with those in the unvaccinated cohort (64.2% vs 62.2%, respectively). After adjusting for the Charlson comorbidity index, cancer treatment modalities, and socioeconomic levels, the risk of pneumonia-related hospitalization in the PPSV23 vaccination cohort was 0.48 times lower than that in the unvaccinated cohort (adjusted incidence rate ratio, 0.48; P = .046). For patients who received the influenza vaccination, subgroup analysis demonstrated that PPSV23 vaccination significantly decreased the risk (adjusted incidence rate ratio, 0.45; P < .001). Compared with unvaccinated controls, PPSV23-vaccinated patients had a lower cumulative incidence for the first occurrence of pneumonia-related hospitalization (34.49% vs 36.36%; P = .178) and higher overall survival (47.5% and 42.3%, respectively; P < .001). CONCLUSIONS Vaccination of elderly patients who have prostate cancer with the relatively common and inexpensive PPSV23 can decrease the risk of pneumonia and prolong survival.

Background Circular RNAs (circRNAs) play a crucial role in gene expression regulation. CircHIPK3 is a circRNA derived from Exon 2 of HIPK3 gene and its role in prostate cancer (PCa) is still unclear. Methods CCK8 assays, flow cytometry and colony formation assays were performed to assess the effects of circHIPK3 in PCa cells. Bioinformatics analysis, RNA pull-down assay, RNA immunoprecipitation assay (RIP), and luciferase activity assay were performed to dissect the mechanism underlying circHIPK3-mediated G2/M transition in PCa cells. Results CircHIPK3 expression was upregulated in PCa cells and prostate cancer tissues. Overexpression of circHIPK3 or circHIPK3 silencing altered PCa viability, proliferation and apoptosis in vitro. CircHIPK3 could sponge miR-338-3p and inhibit its activity, resulting in increased expression of Cdc25B and Cdc2 in vitro. Conclusion CircHIPK3 promotes G2/M transition and induces PCa cell proliferation by sponging miR-338-3p and increasing the expression of Cdc25B and Cdc2. CircHIPK3 may play an oncogenic role in PCa.

ObjectiveTo investigate the clinical features of multicentric reticulohistiocytosis (MRH). MethodsThe clinical manifestations, laboratory examination results and histologic characteristics of eleven patients with MRH were collected and compared with those of 33 patients with rheumatoid arthritis. ResultsIn total, 72.7% of the MRH patients were women. The median age was 46 years (range: 33-84 years). Diagnosed by specific pathologic features, all MRH patients exhibited cutaneous involvement. The dorsa of the hands, arms, face and auricle were the most commonly affected areas. Nodules were also located on the legs, scalp, trunk, neck, and even the hypoglossis and buccal mucosa. Ten MRH patients (90.9%) had symmetric polyarthritis. Compared with rheumatoid arthritis (RA) patients, MRH patients were more likely to have distal interphalangeal joint (DIP) involvement (63.6% vs 24.2%, P=0.017) and less likely to have elbow (36.4% vs 72.7%, P=0.003), ankle (45.5% vs 93.9%, P

Myelodysplastic syndromes (MDS) are hematopoietic stem and progenitor cell (HSPC) malignancies characterized by ineffective hematopoiesis and an increased risk of leukemia transformation. Epigenetic regulators are recurrently mutated in MDS, directly implicating epigenetic dysregulation in MDS pathogenesis. Here, we identified a tumor suppressor role of the acetyltransferase p300 in clinically relevant MDS models driven by mutations in the epigenetic regulators TET2, ASXL1, and SRSF2. The loss of p300 enhanced the proliferation and self-renewal capacity of Tet2-deficient HSPCs, resulting in an increased HSPC pool and leukemogenicity in primary and transplantation mouse models. Mechanistically, the loss of p300 in Tet2-deficient HSPCs altered enhancer accessibility and the expression of genes associated with differentiation, proliferation, and leukemia development. Particularly, p300 loss led to an increased expression of Myb, and the depletion of Myb attenuated the proliferation of HSPCs and improved the survival of leukemia-bearing mice. Additionally, we show that chemical inhibition of p300 acetyltransferase activity phenocopied Ep300 deletion in Tet2-deficient HSPCs, whereas activation of p300 activity with a small molecule impaired the self-renewal and leukemogenicity of Tet2-deficient cells. This suggests a potential therapeutic application of p300 activators in the treatment of MDS with TET2 inactivating mutations.

Acute respiratory distress syndrome (ARDS) is a heterogeneous syndrome caused by direct (local damage to lung parenchyma) or indirect lung injury (insults from extrapulmonary sites with acute systemic inflammatory response), the clinical and biological complexity can have a profound effect on clinical outcomes. We performed a retrospective analysis of 152 severe ARDS patients receiving extracorporeal membrane oxygenation (ECMO). Our objective was to assess the differences in clinical characteristics and outcomes of direct and indirect ARDS patients receiving ECMO. Overall hospital mortality was 53.3%. A total of 118 patients were assigned to the direct ARDS group, and 34 patients were assigned to the indirect ARDS group. The 28-, 60-, and 90-day hospital mortality rates were significantly higher among indirect ARDS patients (all p &lt, 0.05). Cox regression models demonstrated that among direct ARDS patients, diabetes mellitus, immunocompromised status, ARDS duration before ECMO, and SOFA score during the first 3 days of ECMO were independently associated with mortality. In indirect ARDS patients, SOFA score and dynamic compliance during the first 3 days of ECMO were independently associated with mortality. Our findings revealed that among patients receiving ECMO, direct and indirect subphenotypes of ARDS have distinct clinical outcomes and different predictors for mortality.

Extracorporeal membrane oxygenation (ECMO) is considered a salvage therapy in cases of severe acute respiratory distress syndrome (ARDS) with profound hypoxemia. However, the need for high-volume fluid resuscitation and blood transfusions after ECMO initiation introduces a risk of fluid overload. Positive fluid balance is associated with mortality in critically ill patients, and conservative fluid management for ARDS patients has been shown to shorten both the duration of mechanical ventilation and time spent in intensive care, albeit without a significant effect on survival. Nonetheless, few studies have addressed the influence of fluid balance on clinical outcomes in severe ARDS patients undergoing ECMO. In the current retrospective study, we examined the impact of cumulative fluid balance (CFB) on hospital mortality in 152 cases of severe ARDS treated using ECMO. Overall hospital mortality was 53.3%, and we observed a stepwise positive correlation between CFB and the risk of death. Cox regression models revealed that CFB during the first 3 days of ECMO was independently associated with higher hospital mortality (adjusted hazard ratio 1.110 [95% CI 1.027–1.201], p = 0.009). Our findings indicate the benefits of a conservative treatment approach to avoid fluid overload during the early phase of ECMO when dealing with severe ARDS patients.

Urinary liver-type fatty acid binding protein (L-FABP) is a novel biomarker with promising performance in detecting kidney injury. Previous studies reported that L-FABP showed moderate discrimination in patients that underwent cardiac surgery, and other studies revealed that longer duration of cardiopulmonary bypass (CPB) was associated with a higher risk of postoperative acute kidney injury (AKI). This study aims to examine assessing CPB duration first, then examining L-FABP can improve the discriminatory ability of L-FABP in postoperative AKI. A total of 144 patients who received cardiovascular surgery were enrolled. Urinary L-FABP levels were examined at 4 to 6 and 16 to 18 h postoperatively. In the whole study population, the AUROC of urinary L-FABP in predicting postoperative AKI within 7 days was 0.720 at 16 to 18 h postoperatively. By assessing patients according to CPB duration, the urinary L-FABP at 16 to 18 h showed more favorable discriminating ability with AUROC of 0.742. Urinary L-FABP exhibited good performance in discriminating the onset of AKI within 7 days after cardiovascular surgery. Assessing postoperative risk of AKI through CPB duration first and then using urinary L-FABP examination can provide more accurate and satisfactory performance in predicting postoperative AKI.

The high mortality rate of patients with severe acute respiratory distress syndrome (ARDS) warrants aggressive clinical intervention. Extracorporeal membrane oxygenation (ECMO) is a salvage therapy for life-threatening hypoxemia. Randomized controlled trials of ECMO for severe ARDS comprise a number of ethical and methodological issues. Therefore, indications and optimal timing for implementation of ECMO, and predictive risk factors for outcomes have not been adequately investigated. We performed propensity score matching to match ECMO-supported and non-ECMO-supported patients at 48 h after ARDS onset for comparisons based on clinical outcomes and hospital mortality. A total of 280 severe ARDS patients were included, and propensity score matching of 87 matched pairs revealed that the 90-d hospital mortality rate was 56.3% in the ECMO group and 74.7% in the non-ECMO group (p = 0.028). Subgroup analysis revealed that greater severity of ARDS, higher airway pressure, or a higher Sequential Organ Failure Assessment score tended to benefit from ECMO treatment in terms of survival. Multivariate logistic regression revealed that hospital mortality was significantly lower among patients who received ECMO than among those who did not. Our findings suggested that early initiation of ECMO (within 48 h) may increase the likelihood of survival for patients with severe ARDS.

Objectives: Chronic heart failure (CHF) is a chronic and progressive disease with high incidence. The aim of this study was to evaluate the effectiveness and safety of Xinmailong injection...

Objective The aim of this study was to explore the relationship between preoperative right ventricular (RV) function and high vasoactive-inotropic score (VIS) after cardiac surgery. Design Prospective observational study. Setting A single medical center setting. Participants One hundred three patients undergoing elective cardiac surgery. Interventions None. Measurements and Main Results Consecutive patients referred for cardiac surgery were enrolled prospectively. Comprehensive transesophageal echocardiography was performed before sternal incision. Specific RV indices, encompassing RV fractional area change, tricuspid annular plane systolic excursion, and RV global longitudinal strain (RVGLS), were measured offline. High VIS was defined as a maximum VIS of ≥20 in 24 hours postoperatively. Postoperative adverse events were recorded. One hundred three patients (mean age 61.2 ± 11.0, 72 men) were included in this study, where 17 patients (16.5%) achieved high VIS with a mean maximum VIS of 39 in 24 hours postoperatively. Patients with high VIS encountered increased occurrence of extracorporeal membrane oxygenation placement, acute kidney injury, and mortality. Risk factors for high VIS included operation type, cardiopulmonary bypass duration, left atrium size, and pre-incisional RV indices. After adjustment for age, left ventricular ejection fraction, and the covariates, only RVGLS (odds ratio 1.19, p = 0.011) showed an independent association with high VIS. The optimal cutoff of RVGLS was −16.7% (sensitivity of 88.2%, specificity of 75.6%). Conclusion Preoperative RV dysfunction is an independent risk factor for postoperative high VIS. Pre-incisional RVGLS is a reliable tool to predict high VIS after cardiac surgery. Patients with high VIS had increased adverse events postoperatively.

Background: Coronary artery bypass grafting is one of the most common interventional revascularisation procedures used to treat coronary artery disease worldwide. With a wide variability in postoperative cardiac symptoms, identification of symptom trajectories during the 3-month postoperative recovery period may improve clinicians’ abilities to support symptom recovery. Aims: To identify distinct trajectories of cardiac symptoms seen over time in a cohort of patients during the 3-month post-coronary artery bypass grafting period, and determine clinical characteristics associated with different symptom trajectories postoperatively. Methods: A prospective trial used the cardiac symptom survey to determine patient symptoms at baseline prior to surgery, and at 1 week, 6 weeks and 3 months following coronary artery bypass grafting. A latent class growth model and multivariate logistic regression analyses were used. Results: Data were obtained from patients ( N=198) undergoing coronary artery bypass grafting in six medical centres of Taiwan, through patient medical records and interviews. Based on their frequency, trajectories were explored for the six most common postoperative symptoms including angina, dyspnoea, fatigue, depression, sleep problems and anxiety. We identified two to three distinct classes of trajectories for each symptom. Age, longer intensive care unit stay, fewer vessels bypassed, off-pump coronary artery bypass grafting, smoking history and lack of regular exercise were associated with worse symptom outcome trends over time. Conclusions: Using this unique trajectories-based research method, we are able to achieve a better understanding of symptom recovery patterns over time among coronary artery bypass grafting patients. Recognising risk factors and potential recovery patterns prior to surgery may allow healthcare providers to deliver targeted discharge planning and individualised care after coronary artery bypass grafting.

Patients with primary mitral regurgitation (MR) may remain asymptomatic for many years. For unknown reasons, some shift from a compensated to a decompensated state and progress to fatal heart failure. To elucidate the genetic determinants of this process, we recruited 28 patients who underwent mitral valve surgery and stratified them into control, compensated MR, and decompensated MR groups. Tissue biopsies were obtained from the patients’ left ventricular (LV) lateral wall for a transcriptome-wide profiling of 64,769 probes to identify differentially expressed genes (DEGs). Using cutoff values at the 1% FDR significance level and sex- and age-adjusted regression models, we identified 12 significant DEGs (CTGF, MAP1B, SERPINE1, MYH9, MICAL2, MYO1D, CRY1, AQP7P3, HTRA1, PRSS23, IGFBP2, and FN1). The most significant gene was CTGF (adjusted R2 = 0.74, p = 1.80 × 10−8). We found that the majority of genes expressed in the more advanced decompensated MR group were pro-fibrotic genes associated with cardiac fibrosis. In particular, six pro-fibrotic genes (CTGF, SERPINE1, MYH9, HTRA1, PRSS23, and FN1) were overexpressed and enriched in pathways involved in ECM (extracellular matrix) protein remodeling. Therapeutic interventions that antagonize these six genes may slow the progression toward decompensated MR.

Nucleophosmin (NPM1) is the most commonly mutated gene in acute myeloid leukemia (AML) resulting in aberrant cytoplasmic translocation of the encoded nucleolar protein (NPM1c+). NPM1c+ maintains a unique leukemic gene expression program, characterized by activation of HOXA/B clusters and MEIS1 oncogene to facilitate leukemogenesis. However, the mechanisms by which NPM1c+ controls such gene expression patterns to promote leukemogenesis remain largely unknown. Here, we show that the activation of HOXBLINC, a HOXB locus-associated long non-coding RNA (lncRNA), is a critical downstream mediator of NPM1c+-associated leukemic transcription program and leukemogenesis. HOXBLINC loss attenuates NPM1c+-driven leukemogenesis by rectifying the signature of NPM1c+ leukemic transcription programs. Furthermore, overexpression of HoxBlinc (HoxBlincTg) in mice enhances HSC self-renewal and expands myelopoiesis, leading to the development of AML-like disease, reminiscent of the phenotypes seen in the Npm1 mutant knock-in (Npm1c/+) mice. HoxBlincTg and Npm1c/+ HSPCs share significantly overlapped transcriptome and chromatin structure. Mechanistically, HoxBlinc binds to the promoter regions of NPM1c+ signature genes to control their activation in HoxBlincTg HSPCs, via MLL1 recruitment and promoter H3K4me3 modification. Our study reveals that HOXBLINC lncRNA activation plays an essential oncogenic role in NPM1c+ leukemia. HOXBLINC and its partner MLL1 are potential therapeutic targets for NPM1c+ AML., Nucleophosmin (NPM1) gene mutation induces a specific gene expression program leading to acute myeloid leukaemia. Here, the authors show that mutant NPM1 activates a HOXB locus-associated long non-coding RNA which is essential for its associated oncogenic transcriptional program and leukaemia development.

Emerging evidence suggests that the coupling relating the structural connectivity (SC) of the brain to its functional connectivity (FC) exhibits remarkable changes during development, normal aging, and diseases. Although altered structural-functional connectivity couplings (SC-FC couplings) have been previously reported in schizophrenia patients, the alterations in SC-FC couplings of different illness stages of schizophrenia (SZ) remain largely unknown. In this study, we collected structural and resting-state functional MRI data from 73 normal controls (NCs), 61 first-episode (FeSZ) and 78 chronic (CSZ) schizophrenia patients. Positive and negative syndrome scale (PANSS) scores were assessed for all patients. Structural and functional brain networks were constructed using gray matter volume (GMV) and resting-state magnetic resonance imaging (rs-fMRI) time series measurements. At the connectivity level, the CSZ patients showed significantly increased SC-FC coupling strength compared with the FeSZ patients. At the node strength level, significant decreased SC-FC coupling strength was observed in the FeSZ patients compared to that of the NCs, and the coupling strength was positively correlated with negative PANSS scores. These results demonstrated divergent alterations of SC-FC couplings in FeSZ and CSZ patients. Our findings provide new insight into the neuropathological mechanisms underlying the developmental course of SZ.

This retrospective study aimed to clarify the short-term and mid-term outcomes of and prognostic factors for patients who underwent surgical repair for uncomplicated acute type A aortic dissection (ATAAD). Between January 2007 and June 2019, 603 consecutive patients underwent ATAAD repair at our institution. According to patients’ preoperative presentations and imaging studies, uncomplicated ATAAD was found in 276 (45.8%) patients by excluding preoperative complicated factors. Patients with uncomplicated ATAAD were classified into the survivor (n = 243) and non-survivor (n = 33) groups. Clinical features, surgical information, and postoperative complications were compared. Three-year survival and freedom from reoperation rates for survivors were analyzed using the Kaplan–Meier actuarial method. The in-hospital surgical mortality rate of uncomplicated ATAAD patients was 11.9%. The non-survivor group had a higher rate of postoperative malperfusion-related complications, and a multivariate analysis revealed that repeat surgery, retrograde cerebral perfusion, and intraoperative extracorporeal membrane oxygenation support were predictors of in-hospital mortality. In the survivor group, 3-year cumulative survival and freedom from aortic reoperation rates were 89.6% (95% confidence interval [CI] 84.8–92.9%) and 83.1% (95% CI 76.8–87.7%), respectively. In conclusion, uncomplicated and complicated ATAAD rates were similar; the short-term and mid-term surgical outcomes in patients with uncomplicated ATAAD were generally acceptable.

Aldehyde dehydrogenase 2 (ALDH2) is an enzyme that detoxifies reactive oxygen species (ROS)-generated aldehyde adducts such as 4-hydroxy-trans-2-nonenal (4-HNE). Previous meta-analyses have shown an increase in the risk of atrial fibrillation (AF) in patients with chronic alcohol consumption. ALDH2*2, a common dysfunctional polymorphism in the ALDH2 gene, has been linked to an increased risk of cancer and heart disease. We tested the effect of ALDH2 deficiency on alcohol-induced AF in a murine model of chronic-binge ethanol feeding, with ALDH2*2 knock-in (KI) mice generated by a CRISPR/CAS9 system. In addition, right atrial appendages were obtained from eight patients with AF undergoing open heart surgery. The results showed that burst atrial pacing induced a greater susceptibility to AF in ALDH2*2 KI mice exposed to chronic ethanol intoxication than in wild-type mice, resulting from a higher degree of 4-HNE accumulation and collagen deposition in their atria. Alda-1 attenuated transforming growth factor beta 1 (TGF-&beta, 1) expression and collagen deposition in the atria and reduced AF inducibility. Patients with AF and the ALDH2*2 allele exhibited greater oxidative stress and substrate remodeling in their atria than non-carriers. In conclusion, ALDH2 deficiency may increase the risk of chronic alcohol and tachypacing-induced AF through the accumulation of 4-HNE and increased ROS production.

BackgroundPreventing relapse of schizophrenic patients is really a challenge. The present study sought to provide more explicit evidence and factors of different grades and weights by a series of step-by-step analysis through χ2 test, logistic regression analysis and decision-tree model. The results of this study may contribute to controlling relapse of schizophrenic patients.MethodsA total of 1,487 schizophrenia patients were included who were 18–65 years of age and discharged from 10 hospitals in China from January 2009 to August 2009 and from September 2011 to February 2012 with improvements or recovery of treatment effect. We used a questionnaire to collect information about relapse and correlative factors during one year after discharge by medical record collection and telephone interview. The χ2 test and logistic regression analysis were used to identify risk factors and high-risk factors firstly, and then a decision-tree model was used to find predictive factors.ResultsThe χ2 test found nine risk factors which were associated with relapse. Logistic regression analysis also showed four high-risk factors further (medication adherence, occupational status, ability of daily living, payment method of medical costs). At last, a decision-tree model revealed four predictors of relapse; it showed that medication adherence was the first grade and the most powerful predictor of relapse (relapse rate for adherence vs. nonadherence: 22.9 vs. 55.7%, χ2 = 116.36, p < 0.001). The second grade factor was occupational status (employment vs. unemployment: 19.7 vs. 42.7%, χ2 = 17.72, p < 0.001); the third grade factors were ability of daily living (normal vs. difficult: 28.4 vs. 54.3%, χ2 = 8.61, p = 0.010) and household income (household income ≥ 3000 RMB vs.

Background Neurofibromatosis type 1 (NF1) is a common genetic disorder characterized by plexiform neurofibromas (pNF), which are thought to be congenital tumors that arise in utero and enlarge throughout life. Genetic studies in murine models delineated an indispensable role for the stem cell factor (SCF)/c-kit pathway in pNF initiation and progression. A subsequent phase 2 clinical trial using imatinib mesylate to inhibit SCF/c-kit demonstrated tumor shrinkage in a subset of preexisting pNF; however, imatinib's role on preventing pNF development has yet to be explored. Procedure We evaluated the effect of imatinib dosed at 10-100 mg/kg/day for 12 weeks to one-month-old Nf1flox/flox ;PostnCre(+) mice, prior to onset of pNF formation. To determine durability of response, we then monitored for pNF growth at later time points, comparing imatinib- with vehicle-treated mice. We assessed gross and histopathological analysis of tumor burden. Results Imatinib administered preventatively led to a significant decrease in pNF number, even at doses as low as 10 mg/kg/day. Tumor development continued to be significantly inhibited after cessation of imatinib dosed at 50 and 100 mg/kg/day. In the cohort of treated mice that underwent prolonged follow-up, the size of residual tumors was significantly reduced as compared with age-matched littermates that received vehicle control. Conclusions Early administration of imatinib inhibits pNF genesis in vivo, and effects are sustained after discontinuation of therapy. These findings may guide clinical use of imatinib in young NF1 patients prior to the substantial development of pNF.

Background Pancreatic adenoma can potentially transform into adenocarcinoma, so it is recommended to be resected surgically or endoscopically. Endoscopic papillectomy is one of the main treatments for papillary adenoma, and bleeding, perforation, and pancreatitis are the most frequent and critical adverse events that restrict its wider use. There is no standard procedure for endoscopic papillectomy yet. The procedure is relevant to postoperative adverse events. Aim To reduce the postoperative adverse event rates and improve patients' postoperative condition, we developed a standard novel procedure for endoscopic papillectomy. Methods The novel endoscopic papillectomy had two main modifications based on the conventional method: The isolation of bile from pancreatic juice with a bile duct stent and wound surface protection with metal clips and fibrin glue. We performed a single-center retrospective comparison study on the novel and conventional methods to examine the feasibility of the novel method for reducing postoperative adverse events. Results A total of 76 patients, of whom 23 underwent the novel procedure and 53 underwent the conventional procedure, were retrospectively evaluated in this study. The postoperative bleeding and pancreatitis rates of the novel method were significantly lower than those of the conventional method (0 vs 20.75%, P = 0.028, and 17.4% vs 41.5%, P = 0.042, respectively). After applying the novel method, the most critical adverse event, perforation, was entirely prevented, compared to a prevalence of 5.66% with the conventional method. Several postoperative symptoms, including fever, rapid pulse, and decrease in hemoglobin level, were significantly less frequent in the novel group (P = 0.042, 0.049, and 0.014, respectively). Overall, the total adverse event rate of the novel method was lower (0 vs 24.5%, P = 0.007) than that of the conventional method. Conclusion Patients who underwent the novel procedure had lower postoperative adverse event rates. This study demonstrates the potential efficacy and safety of the novel endoscopic papillectomy in reducing postoperative adverse events.

BackgroundThe transfemoral route is contraindicated in nearly 10% of transcatheter aortic valve replacement (TAVR) candidates because of unsuitable iliofemoral vessels. Transaxillary (TAx) and direct aortic (DAo) routes are the principal nonfemoral TAVR routes; however, few studies have compared their outcomes.MethodsWe performed a systematic review and meta-analysis to compare the rates of mortality, stroke, and other adverse events of TAx and DAo TAVR. The study was prospectively registered with PROSPERO (registration number: CRD42017069788). We searched Medline, PubMed, Embase, and Cochrane databases for studies reporting the outcomes of DAo or TAx TAVR in at least 10 patients. Studies that did not use the Valve Academic Research Consortium definitions were excluded. We included studies that did not directly compare the two approaches and then pooled rates of events from the included studies for comparison.ResultsIn total, 31 studies were included in the quantitative meta-analysis, with 2,883 and 2,172 patients in the DAo and TAx TAVR groups, respectively. Compared with TAx TAVR, DAo TAVR had a lower Society of Thoracic Surgery (STS) score, shorter fluoroscopic time, and less contrast volume use. The 30-day mortality rates were significantly higher in the DAo TAVR group (9.6%, 95% confidence interval (CI) = [8.4–10.9]) than in the TAx TAVR group (5.7%, 95% CI = [4.8–6.8];Pfor heterogeneity Pfor heterogeneity Pfor heterogeneity = 0.005). DAo TAVR was also associated with lower risks of permanent pacemaker implantation (12.3% vs. 20.1%,Pfor heterogeneity = 0.009) and valve malposition (2.0% vs. 10.2%,Pfor heterogeneity = 0.023) than was TAx TAVR.ConclusionsDAo TAVR increased 30-day mortality rate compared with TAx TAVR; by contrast, TAx TAVR increased postoperative stroke, permanent pacemaker implantation, and valve malposition risks compared with DAo TAVR.

BackgroundAcute type A aortic dissection (ATAAD) is a life-threatening disease that requires emergent surgical intervention. This retrospective study aimed to clarify the individual characteristics, short-term and mid-term outcomes, and prognostic factors of patients who underwent surgical repair of ATAAD with preoperative cardiopulmonary resuscitation (CPR).MethodsBetween January 2007 and January 2020, 656 consecutive patients underwent ATAAD repair at our institution; 22 (3.4%) of these patients underwent CPR prior to surgery. Patients who underwent preoperative CPR were classified as the survivor group (n = 9) and non-survivor group (n = 13), according to whether they survived to hospital discharge. Clinical features, surgical information, and postoperative complications were analyzed and compared. Three-year cumulative survival rates and cerebral performance categories (CPC) scores are presented.ResultsIn patients undergoing CPR prior to ATAAD surgery, the in-hospital mortality rate was 59.1%. A total of 72.7% of patients underwent concomitant surgical resuscitation procedures during CPR such as emergent subxiphoid pericardiotomy and/or emergent cardiopulmonary bypass. The survivor group had a higher rate of return of spontaneous heartbeat (ROSB) compared to the non-survivor group (100% versus 53.8%; P = 0.017). The 3-year cumulative survival rates were 35.1% (95% confidence interval [CI], 27.6%-42.6%) and 85.7% (95% CI, 81.9%-88.8%) for overall patients and for survivors, respectively. As for the neurological outcome, 77.8% (7/9) of patients had full cerebral performance (CPC-1) at the 3-month follow-up examination after discharge.ConclusionsPatients with ATAAD undergoing preoperative CPR, especially those without ROSB after CPR, are at high risk for in-hospital mortality. However, the short-term and mid-term outcomes, including the cerebral performance after discharge and 3-year survival rate, are promising for patients who survived to discharge.

Background Hemopericardium is a common and hazardous complication of acute type A aortic dissection (ATAAD). This retrospective study aimed to clarify the short-term and mid-term outcomes in patients who underwent surgical rescues for hemopericardium complicated by ATAAD. Methods Between January 2007 and March 2019, 586 consecutive patients underwent ATAAD repair at our institution. According to preoperative computed tomography, hemopericardium was found in 191 patients (32.6%), 150 were stabilized with medical treatment, and 41 underwent surgical rescues for critical hemodynamics. The 41 patients were classified into groups according to their rescue procedures: emergent subxiphoid pericardiotomy (E-SXP group, n = 26, 63.4%) or emergent cardiopulmonary bypass (E-CPB group, n = 15, 36.6%). Clinical features, surgical information, postoperative complications, and 3-year survival were analyzed and compared. Results Demographics, comorbidities and aortic repair procedures were generally homogenous between the two groups, except for sex. The average systolic blood pressure was 62.4 ± 13.3 mmHg and 67.1 ± 13.1 mmHg in the E-SXP and E-CPB groups, respectively. A total of 29.3% of patients underwent cardiopulmonary resuscitation (CPR) before surgical rescues. The in-hospital mortality was similar (30.8% versus 33.3%, P = 0.865) in the two groups. Multivariate analysis revealed that preoperative CPR was an in-hospital predictor of mortality. For patients who survived to discharge, 3-year cumulative survival rates were 87.8% ± 8.1% and 60.0% ± 19.7% in the E-SXP and E-CPB groups, respectively (P = 0.170). Conclusions Patients who underwent surgical rescues for ATAAD-complicated hemopericardium are at a high risk of in-hospital mortality. The two rescue procedures revealed similar short-term and mid-term outcomes.

This retrospective study aimed to clarify the short- and mid-term outcomes of elderly patients who underwent surgery to treat left-sided native valve infective endocarditis (LSNIE). Between July 2005 and September 2015, 179 patients underwent surgical treatment for active LSNIE at a single institution. Patients were classified into two groups: ≥65 years (elderly group) and P = 0.001). For patients who survived to discharge, the three-year cumulative survival rates were 75.0% ± 8.2% and 81.2% ± 3.4% in the elderly and non-elderly groups, respectively (P = 0.484). In conclusion, elderly patients are at a higher risk of in-hospital mortality after surgery for LSNIE. However, once elderly patients are stabilized by surgical treatment and survive to discharge, the mid-term outcomes are promising.

Radiotherapy (RT) is a crucial treatment modality in managing cancer patients. However, irradiation dose sprinkling to tumor-adjacent normal tissues is unavoidable, generating treatment toxicities, such as radiation-associated cardiovascular dysfunction (RACVD), particularly for those patients with combined therapies or pre-existing adverse features/comorbidities. Radiation oncologists implement several efforts to decrease heart dose for reducing the risk of RACVD. Even applying the deep-inspiration breath-hold (DIBH) technique, the risk of RACVD is though reduced but still substantial. Besides, available clinical methods are limited for early detecting and managing RACVD. The present study reviewed emerging challenges of RACVD in modern radiation oncology, in terms of clinical practice, bench investigation, and multidisciplinary care. Several molecules are potential for serving as biomarkers and therapeutic targets. Of these, miRNAs, endogenous small non-coding RNAs that function in regulating gene expression, are of particular interest because low-dose irradiation, i.e., 200 mGy (one-tenth of conventional RT daily dose) induces early changes of pro-RACVD miRNA expression. Moreover, several miRNAs, e.g., miR-15b and miR21, involve in the development of RACVD, further demonstrating the potential bio-application in RACVD. Remarkably, many RACVDs are late RT sequelae, characterizing highly irreversible and progressively worse. Thus, multidisciplinary care from oncologists and cardiologists is crucial. Combined managements with commodities control (such as hypertension, hypercholesterolemia, and diabetes), smoking cessation, and close monitoring are recommended. Some agents show abilities for preventing and managing RACVD, such as statins and angiotensin-converting enzyme inhibitors (ACEIs); however, their real roles should be confirmed by further prospective trials.

Background: Sutureless aortic valve replacement (SU-AVR) has emerged as a promising alternative for the treatment of patients with aortic valve stenosis. This study aims to assess the safety and efficacy of SU-AVR in an elderly Asian population. Methods: From June 2015 to May 2016, 15 adults with severe aortic stenosis (9 females) with a median age of 79 years underwent Perceval sutureless bioprosthesis (LivaNova, UK) implantation in a single Taiwanese institution; peri-operative recovery, clinical improvement, and valve performance were analyzed. Results: Three (20%) patients underwent concomitant procedures (coronary artery bypass grafting, 1 patient; maze, 2 patients) and 6/12 (50%) patients underwent J-ministernotomy for isolated SU-AVR. Median cardiopulmonary bypass and cross-clamp time were 105 min and 69 min, respectively. All sutureless bioprosthesis were implanted successfully without conversion to a traditional valve, but 2 patients (13.3%) need intraoperative valve repositioning because of paravalvular leakage. Median extubation time and intensive care unit stay were 5 h and 2 days, respectively. One patient experienced in-hospital mortality due to sudden collapse thought secondary to high degree atrioventricular block. Serial echocardiographic evaluations were performed preoperatively and at 1, 3, and 6 months postoperatively. The final echocardiographic exams showed nothing greater than mild aortic insufficiency and the median mean trans-valvular gradient was 13.2 (range, 6.0–26.3) mmHg. Conclusions: By simplified procedure and improved hemodynamics, SU-AVR can be implanted safely in elderly Asian population with excellent valvular performance. Keywords: Aortic valve replacement, Sutureless bioprosthesis, Minimally invasive cardiac surgery

The commonly used vaccine for adults with a high risk of pneumonia is 23-valent pneumococcal polysaccharide vaccine (PPSV23). However, its effectiveness in patients with colorectal cancer has not been investigated. This study aimed to investigate the effectiveness of PPSV23 in reducing the risk of pneumonia among elderly patients with colorectal cancer. A total of 120,605 newly diagnosed patients with colorectal cancer were identified from the Taiwan National Health Insurance Research Database between 1996 and 2010. Of these patients, 18,468 were 75 years or older in 2007 to 2010, and 3515 received PPSV23. People aged 75 years or older have been considered eligible for receiving PPSV23 vaccination in Taiwan since 2007. The specific “vaccination period” of October 2008 to December 2008 was used to minimize the potential immortal time bias. Therefore, 893 patients who received PPSV23 outside this vaccination period or died before 2009 and 2960 unvaccinated patients who died before 2009 were excluded. After the propensity score was matched with a 1:3 ratio, 2622 vaccinated patients and 7866 unvaccinated patients were recruited. A multivariate log-linear Poisson regression model was performed and adjusted for potential confounders, including influenza vaccination, vaccination period, cancer treatment modalities, comorbidities, and sociodemographic variables. After 2 years of follow-up, the incidence rate of the pneumonia hospitalization of the vaccinated patients was significantly lower than that of the unvaccinated patients at 85.53 per 1000 person-years (PYs) of the former and 92.38 per 1000 PYs of the latter. The proportions of patients who had 2, 3, and >3 pneumonia hospitalizations per year were consistently lower in the vaccinated group than in the unvaccinated group (1.9% vs 2.0%, 0.5% vs 0.9%, and 0.7% vs 1.1%, respectively). After adjustment for covariates was made, PPSV23 vaccine was significantly associated with a reduced risk of pneumonia hospitalization, with an adjusted incidence rate ratio of 0.88 (P = .040). The overall pneumonia-free survival rate was also significantly higher in the vaccinated patients than in the unvaccinated patients (P = .001). PPSV23 vaccination was associated with a significantly reduced rate of pneumonia hospitalization in elderly patients with colorectal cancer.

To evaluate the clinical value of 18F-FDG-PET/CT for the diagnosis of fever of unknown origin (FUO) and inflammation of unknown origin (IUO) in Chinese population, as well as the characteristics of PET/CT in different category of etiological disease. A total of 376 consecutive patients with FUO/IUO who underwent FDG-PET/CT at 12 hospitals were retrospectively studied. FDG uptake was quantitatively and visually evaluated, by using SUVmax and a 4-grade scale respectively. A questionnaire survey to the clinicians was used to evaluate the significance of PET/CT in diagnosing of FUO/IUO. Data analysis included the etiological distribution in the study population, image characteristics in different category of diseases, and clinical significance of PET/CT. In 376 studied patients, the infectious diseases accounted for 33.0% of patients, rheumatologic diseases for 32.4%, malignancies for 19.1%, miscellaneous causes for 6.6%, and cause unknown for 8.8%. However, the etiological distribution among hospitals was varied. In addition, the etiological disease composition ratio has changed over time in China. On PET/CT examinations, 358 (95.2%) of the patients had a positive finding. Within them, local high uptake lesion was found in 219 cases, and nonspecific abnormal uptake (NAU) was found in 187 cases. FDG uptake in malignant diseases was significantly higher than in other category diseases both on SUVmax and visual scores (t-value range from 4.098 to 5.612, all P value

Background The mortality rate of patients on extracorporeal membrane oxygenation (ECMO), especially those patients that develop acute kidney injury (AKI) is high. Acute kidney disease (AKD) is a term used to describe the continuum from AKI to chronic kidney disease. However, the role of AKD in predicting the prognosis of patients on ECMO support is unclear. Methods A total of 168 patients who received ECMO support and survived for more than 7 days at a single hospital from 2003 to 2008 were enrolled for this study and followed up for 10 years or till mortality. Kaplan-Meier analysis and Cox proportional hazards model were used to determine the prognostic factors associated with survival. Results The median survival times of patients with stage 0, stage 1, stage 2 and stage 3 AKD were ≥ 10 years, 43.9 months, 1 month, and half a month, respectively. There were statistically significant differences in cumulative survival rate between patients with stage 3 AKD and those with stage 0, 1, and 2 AKD (Cox-Mantel log rank test, p

BACKGROUND Many studies have indicated a sex-specific effect in many aspects of schizophrenia. The presence of depressive symptomatology exists in all phases of schizophrenia. The aim of this study is to investigate the sex differences in the proportion of comorbid depressive symptoms and sex-specific relationships between depressive symptoms and clinical correlates in never-treated Chinese patients with first-episode schizophrenia (NTFE patients), which have not been reported yet. METHODS Via a cross-sectional design, 240 NTFE inpatients (male/female = 111/129) between ages 16 and 45 years and meeting DSM-IV-TR criteria of schizophrenia were recruited. The Positive and Negative Syndrome Scale (PANSS) was used for the psychopathology, and the 17-item Hamilton Depression Rating Scale (HDRS-17) for the comorbid depressive symptoms. This study was conducted from June 2013 to December 2015. RESULTS The proportion of patients with depressive symptoms (total score on HDRS-17 ≥ 8) in men was significantly higher than in women (male: 62.2%, female: 48.1%; χ²₁ = 4.28, P = .039). Male patients had significantly greater depressive symptoms as shown on the HDRS-17 than female patients (t1, 238 = 2.75, P = .006). Further, we found that age, the age at onset, smoking rate, and PANSS total and general psychopathology, negative symptoms, and cognitive factor subscores favored significant sex differences in female patients (all P < .05). Interestingly, we found sex differences in the correlation between the HDRS-17 score and clinical phenotype, showing that in male patients, the PANSS general psychopathology subscore (β = 0.75, t = 7.72, P < .001) and total score (β = 0.44, t = 4.81, P < .001) significantly predicted the HDRS-17 total score, while in female patients, the PANSS general psychopathology subscore (β = 0.74, t = 8.45, P < .001), total score (β = 0.47, t = 5.71, P < .001), and cognitive factor subscore (β = 0.24, t = 2.60, P < .001) significantly predicted the HDRS-17 total score. CONCLUSIONS Our results indicate sex differences in the frequency and severity of comorbid depressive symptoms and in associations between depressive symptoms and clinical correlates in NTFE patients.

Anemia is a component of the pathological triangle in cardiorenal anemia syndrome and is a risk factor for mortality in acute respiratory distress syndrome. This study assessed the predictive value of anemia for outcomes in critically ill patients receiving extracorporeal membrane oxygenation (ECMO) support. This retrospective study analyzed patients who received ECMO support at the cardiovascular surgery intensive care unit in the study institute between July 2003 and March 2012. Patient data, such as demographic information, etiologies of ECMO implementation, clinical parameters, and in-hospital and 6-month mortality rates, were statistically analyzed. The overall in-hospital mortality rate among the enrolled 295 patients was 55.6%. Multivariate logistical regression analysis indicated that age, albumin levels, sequential organ failure assessment (SOFA) score, and hemoglobin (Hb) level on ECMO day 1 exhibited independent prognostic significance for predicting in-hospital mortality rate. The SOFA score exhibited the highest areas under the receiver operating characteristic curve value (0.812 ± 0.025). The Hb level on ECMO day 1 exhibited satisfactory calibration and discriminatory power. The cumulative 6-month survival rates differed significantly between patients with Hb levels less than and more than 8.85 g/dL (30.6 vs. 54.0%, respectively, P

Additional Sex Combs-Like 1 (ASXL1) is mutated at a high frequency in all forms of myeloid malignancies associated with poor prognosis. We generated a Vav1 promoter-driven Flag-Asxl1Y588X transgenic mouse model, Asxl1Y588X Tg, to express a truncated FLAG-ASXL1aa1-587 protein in the hematopoietic system. The Asxl1Y588X Tg mice had an enlarged hematopoietic stem cell (HSC) pool, shortened survival, and predisposition to a spectrum of myeloid malignancies, thereby recapitulating the characteristics of myeloid malignancy patients with ASXL1 mutations. ATAC- and RNA-sequencing analyses revealed that the ASXL1aa1-587 truncating protein expression results in more open chromatin in cKit+ cells compared with wild-type cells, accompanied by dysregulated expression of genes critical for HSC self-renewal and differentiation. Liquid chromatography-tandem mass spectrometry and coimmunoprecipitation experiments showed that ASXL1aa1-587 acquired an interaction with BRD4. An epigenetic drug screening demonstrated a hypersensitivity of Asxl1Y588X Tg bone marrow cells to BET bromodomain inhibitors. This study demonstrates that ASXL1aa1-587 plays a gain-of-function role in promoting myeloid malignancies. Our model provides a powerful platform to test therapeutic approaches of targeting the ASXL1 truncation mutations in myeloid malignancies.

Background/Purpose: Acute kidney injury (AKI) developing during extracorporeal membrane oxygenation (ECMO) is associated with very poor outcome. The Kidney Disease: Improving Global Outcomes (KDIGO) group published a new AKI definition in 2012. This study analyzed the outcomes of patients treated with ECMO and identified the relationship between the prognosis and the KDIGO classification. Methods: This study examined total 312 patients initially, and finally reviewed the medical records of 167 patients on ECMO support at a tertiary care university hospital between March 2002 and November 2011. Demographic, clinical, and laboratory variables were retrospectively collected as survival predicators. Results: The overall mortality rate was 55.7%. In the analysis of the areas under the receiver operating characteristic curves, the KDIGO classification showed relatively higher discriminatory power (0.840 ± 0.032) than the Risk of renal failure, Injury to the kidney, Failure of kidney function, Loss of kidney function, and End-stage renal failure (RIFLE) (0.826 ± 0.033) and Acute Kidney Injury Network (AKIN) (0.836 ± 0.032) criteria in predicting in-hospital mortality. Furthermore, multiple logistic regression analysis showed that KDIGO, hemoglobin, and Glasgow Coma Scale score on the first day of patients on ECMO were independent predictors for in-hospital mortality. Finally, cumulative survival rates at 6-month follow-up after hospital discharge differed significantly for KDIGO stage 3 versus KDIGO stage 0, 1, and 2 (p

Objective The aim of this study was to explore the relationship between perioperative right ventricular (RV) function and postoperative atrial fibrillation (POAF) in the context of cardiac surgery. Design Prospective, observational study. Setting A single medical center setting. Participants The study comprised 92 patients undergoing elective cardiac surgery. Interventions None. Measurements and Main Results Consecutive patients without previous history of atrial fibrillation referred for cardiac surgery were enrolled prospectively. Comprehensive transesophageal echocardiography was recorded at the following 2 specific timeframes: before sternotomy (T1) and after sternal closure (T2). Four RV measurements, including RV global longitudinal strain (RVGLS), were performed offline. POAF was defined as any sustained episode of atrial fibrillation recorded within 14 days postoperatively. Ninety-two patients (mean age 61.2 ± 10.8 yr, 63 men) were included in this study; 25 patients (27%) experienced POAF, with a median occurrence of 3 days after cardiac surgery. Multivariable logistic regression models demonstrated that RVGLST1 (odds ratio 1.13, p = 0.047) and RVGLST2 (odds ratio 1.38, p = 0.001) were associated independently with POAF. However, changes in RV indices were not correlated to POAF. The optimal cutoff points obtained from the receiver operating characteristic curve analysis were as follows: –16.7% of RVGLST1 (positive likelihood ratio 2.21, negative likelihood ratio 0.59) and –16.1% of RVGLST2 (positive likelihood ratio 2.68, negative likelihood ratio 0.38). Conclusions RV dysfunction is associated significantly with the occurrence of POAF in the context of cardiac surgery, and perioperative RVGLS measured using transesophageal echocardiography is a useful index to predict POAF in patients referred for cardiac surgery.

The number of people suffering from diabetes in Taiwan has been increasing in recent years, according to data from the Health Promotion Administration, the prevalence rate of diabetes in Taiwan has reached 5%. In 2019, there were approximately 1.1 million type 1 diabetes patients under the age of 20 in the world, indicating that diabetes is also threatening the health of children and adolescents. Moreover, the vast majority of about 463 million diabetic patients globally between the ages of 20 and 79 suffer from type 2 diabetes. One can see that diabetes is an important public health problem and one of the four major noncommunicable diseases that leaders of all countries should take priority action to address. Type 2 diabetes causes many complications, including cardiovascular disease, impaired vision, amputation, kidney disease, etc. and increases the cost of social medical care. This study takes data from the Data Database of the Health Promotion Administration as the parent population, fuzzy theory and neural network to build predictive models with Matlab tools. The predictive results can be used as a reference for medical personnel in any diagnosis.

Interaction of HOXA9/MEIS1/PBX3 is responsible for hematopoietic system transformation in MLL-rearranged (MLL-r) leukemia. Of these genes, HOXA9 has been shown to be critical for leukemia cell survival, while MEIS1 has been identified as an essential regulator for leukemia stem cell (LSC) maintenance. Although significantly high expression of PBX3 was observed in clinical acute myeloid leukemia (AML) samples, the individual role of PBX3 in leukemia development is still largely unknown. In this study, we explored the specific role of PBX3 and its associated regulatory network in leukemia progression. By analyzing the clinical database, we found that the high expression of PBX3 is significantly correlated with a poor prognosis in AML patients. ChIP-Seq/qPCR analysis in MLL-r mouse models revealed aberrant epigenetic modifications with increased H3K79me2, and decreased H3K9me3 and H3K27me3 levels in LSCs, which may account for the high expression levels of Pbx3. To further examine the role of Pbx3 in AML maintenance and progression, we used the CRISPR/Cas9 system to delete Pbx3 in leukemic cells in the MLL-AF9 induced AML mouse model. We found that Pbx3 deletion significantly prolonged the survival of leukemic mice and decreased the leukemia burden by decreasing the capacity of LSCs and promoting LSC apoptosis. In conclusion, we found that PBX3 is epigenetically aberrant in the LSCs of MLL-r AML and is essential for leukemia development. Significantly, the differential expression of PBX3 in normal and malignant hematopoietic cells suggests PBX3 as a potential prognostic marker and therapeutic target for MLL-r leukemia.

// Xiaohui Si 1 , Xiaoyun Zhang 1 , Xing Hao 1 , Yunan Li 1 , Zizhen Chen 1 , Yahui Ding 1 , Hui Shi 1 , Jie Bai 1 , Yingdai Gao 1, 2, 3 , Tao Cheng 1, 2, 3, 4 , Feng-Chun Yang 5, 6 , Yuan Zhou 1, 2, 3 1 State Key Laboratory of Experimental Hematology, Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin, China 2 Center for Stem Cell Medicine, Chinese Academy of Medical Sciences, Tianjin, China 3 Department of Stem Cell & Regenerative Medicine, Peking Union Medical College, Tianjin, China 4 Collaborative Innovation Center for Cancer Medicine, Tianjin, China 5 Sylvester Comprehensive Cancer Center, University of Miami Miller School of Medicine, Miami, FL, USA 6 Department of Biochemistry and Molecular Biology, University of Miami Miller School of Medicine, Miami, FL, USA Correspondence to: Yuan Zhou, email: yuanzhou@ihcams.ac.cn Feng-Chun Yang, email: fxy37@med.miami.edu Keywords: leukemia stem cell, microRNA, acute myeloid leukemia, miR-99a Received: July 29, 2016 Accepted: October 14, 2016 Published: October 27, 2016 ABSTRACT Leukemia stem cells (LSCs) can resist available treatments that results in disease progression and/or relapse. To dissect the microRNA (miRNA) expression signature of relapse in acute myeloid leukemia (AML), miRNA array analysis was performed using enriched LSCs from paired bone marrow samples of an AML patient at different disease stages. We identified that miR-99a was significantly upregulated in the LSCs obtained at relapse compared to the LSCs collected at the time of initial diagnosis. We also found that miR-99a was upregulated in LSCs compared to non-LSCs in a larger cohort of AML patients, and higher expression levels of miR-99a were significantly correlated with worse overall survival and event-free survival in these AML patients. Ectopic expression of miR-99a led to increased colony forming ability and expansion in myeloid leukemia cells after exposure to chemotherapeutic drugs in vitro and in vivo , partially due to overcoming of chemotherapeutic agent-mediated cell cycle arrest. Gene profiling and bioinformatic analyses indicated that ectopic expression of miR-99a significantly upregulated genes that are critical for LSC maintenance, cell cycle, and downstream targets of E2F and MYC. This study suggests that miR-99a has a novel role and potential use as a biomarker in myeloid leukemia progression.

Background No study has specifically investigated the duration of continuous renal replacement therapy (CRRT) in patients who experienced acute kidney injury during extracorporeal membrane oxygenation (ECMO) support. However, there are concerns that prolonged CRRT may be futile. Methods We conducted a retrospective population-based cohort study using Taiwan National Health Insurance Research Database data collected between January 1, 2007 and December 31, 2013. Patients who received ECMO and CRRT during the study period were included. We divided patients into three groups based on the duration of CRRT received: ≤ 3 days, 4–6 days, and ≥ 7 days. The outcomes were all-cause mortality, end-stage renal disease, ventilator dependency, and readmission rate. Results There were 247, 134 and 187 patients who survived the hospitalization in the CRRT for ≤3 days, 4–6 days and > 7 days respectively. Survival after discharge did not differ significantly between CRRT for 4–6 days vs. ≤ 3 days (adjusted hazard ratio [aHR] 1.16, 95% confidence interval [CI] 0.85–1.57), between CRRT for > 7 days vs. ≤ 3 days (aHR 1.001, 95% CI 0.73–1.38) and between CRRT for > 7 days vs. 4–6 days (aHR 0.87, 95% CI 0.62–1.22). The patients who received CRRT for ≥7 days had a higher risk of ESRD than did those who received CRRT for ≤3 days (adjusted hazard ratio [aHR] 3.46, 95% confidence interval [CI] 1.47–8.14) and for 4–6 days (aHR 3.10, 95% CI 1.03–9.29). The incidence of ventilator dependence was higher in the patients with CRRT ≥7 days than in those with ≤3 days (aHR 2.45, 95% CI 1.32–4.54). The CRRT ≥7 days group also exhibited a higher readmission rate than did the 4–6 days and ≤ 3 days groups (aHR 1.43, 95% CI 1.04–1.96 and aHR 1.67, 95% CI 1.13–2.47, respectively). Conclusions Our study found similar long-term survival but increased ESRD and ventilator dependency among ECMO patients who underwent CRRT for ≥7 days. These results offer reason to be concerned that this aggressive life support may maintain patient survival but do so at the cost of long-term disabilities and a lower quality of life. Electronic supplementary material The online version of this article (10.1186/s12882-019-1516-6) contains supplementary material, which is available to authorized users.

Background Bilateral PM muscles or combination with rectus abdominis or omentum are commonly used for upper and lower sternal wound infections. Unilateral PM harvesting using endoscopic-assisted method may have a simple, safe, and reliable entire muscle harvesting with comparable result of less donor-site violation. Methods A retrospective review was performed from 2003 till 2015 on 38 patients referred to a single plastic surgeon for treatment of sternal wound infection following median sternotomy for cardiovascular surgery. After the humerus insertion of PM was cut with the assistance of endoscope visualization, all the other PM insertions on the sternum, rib, and clavicle were divided, the unilateral pedicled PM can be advanced approximately 10 cm to cover the cephalad and caudal sternum, and fill the retrosternal mediastinum. Results Four re-explorations in three patients for postoperative hematoma occurred. No early recurrent infection for wound dehiscence experienced. Three patients died of multiple organs failures as 30-day mortality. Two patients underwent late recurrent infections; one patient had twice wire infection removals at 4 and 6 months after transfer, and the other had another PM for rib osteomyelitis in 3 years. Conclusion Unilateral PM transfer is justified to provide a simple, reliable, straightforward procedure for sternal infection management and mediastinal obliteration without violation of second flap in compromised patients.

Background Extracorporeal membrane oxygenation (ECMO) is often used in critical patients with severe myocardial failure. However, the mortality rate of patients on ECMO is often high. Recent studies have suggested that endothelial activation with subsequent vascular barrier breakdown is a critical pathogenic mechanism of organ damage and is related to the outcome of critical illness. This study aimed to determine whether endothelial biomarkers can be served as prognostic factors for the outcome of patients on ECMO. Methods This prospective study enrolled 23 critically ill patients on veno-arterial ECMO in the intensive care units of a tertiary care hospital between March 2014 and February 2015. Serum samples were tested for thrombomodulin, angiopoietin (Ang)-1, Ang-2, and vascular endothelial growth factor (VEGF). Demographic, clinical, and laboratory data were also collected. Results The overall mortality rate was 56.5%. The combination of Ang-2 at the time of ECMO support (day 0) and VEGF at day 2 had the ability to discriminate mortality (area under receiver operating characteristic curve [AUROC], 0.854; 95% confidence interval: 0.645-0.965). Conclusions In this study, we found that the combination of Ang-2 at day 0 and VEGF at day 2 was a modest model for mortality discrimination in this group of patients.

The pathogenesis of rheumatoid arthritis (RA), a systemic autoimmune disease characterized by autoreactive T-cell accumulation and pro-inflammatory cytokine overproduction, is unclear. Systematically addressing T-cell receptor (TCR) repertoires of different CD4+ T-cell subsets could help understand RA pathogenesis. Here, peripheral CD4+ T cells from treatment-naïve RA patients and healthy controls were sorted into seven subsets including naïve, effector, central memory, effector memory (EMT), Th1, Th17, and regulatory T cells. T-cell receptor β chain repertoires were then analyzed by next-generation sequencing. We identified T-cell clonal expansion in EMT and Th17 cells, with highly similar TCR repertoires between them. Ex vivo experiments demonstrated the preferred differentiation from EMT to Th17 cells in RA. Moreover, TCR diversity in subsets including Th17 was negatively correlated with RA disease activity indices such as C-reactive protein and erythrocyte sedimentation rate. Thus, shared and abnormally expanded EMT and Th17 TCR repertoires might be pivotal for RA pathogenesis.

Hepatocellular carcinoma (HCC) accounts for 75–85% of primary liver cancers and is prevalent in the Asia-Pacific region. Till now, trans-arterial chemoembolization (TACE) is still one of common modalities in managing unresectable intermediate-stage HCC. However, post-TACE residual viable HCC is not uncommon, resulting in unsatisfied overall survival after TACE alone. Recently, stereotactic ablative radiotherapy (SABR) has been suggested to manage HCC curatively. However, evidence from phase-III trials is largely lacking. Hence, the present phase III randomized trial is designed to compare clinical outcomes between SABR and re-TACE for unresectable HCC patients who had incomplete response after initial TACE. The present study is an open-label, parallel, randomized controlled trial. A total of 120 patients will be included into two study groups, i.e., SABR and re-TACE, with a 1:1 allocation rate. A 3-year allocating period is planned. Patients with incomplete response after initial TACE will be enrolled and randomized. The primary endpoint is 1-year freedom-form-local-progression rate. Secondary endpoints are disease-progression-free survival, overall survival, local control, response rate, toxicity, and duration of response of the treated tumor. SABR has been reported as an effective modality in managing intermediate-stage HCC patients, but evidence from phase-III randomized trials is largely lacking. As a result, conducting randomized trials to demarcate the role of SABR in these patients is warranted, especially in the Asia-Pacific region, where HBV- and HCV-related HCCs are prevalent. Before enrolling participants, the present study was registered prospectively on ClinicalTrials.gov (trial identifier, NCT02921139 ) on Sep. 29, 2016. This study is ongoing.