The molecular mechanism for worsening left ventricular (LV) function after mitral valve (MV) repair for chronic mitral regurgitation remains unknown. We wished to assess the LV transcriptome and ...identify determinants associated with worsening LV function post-MV repair. A total of 13 patients who underwent MV repair for chronic primary mitral regurgitation were divided into two groups, preserved LV function (N = 8) and worsening LV function (N = 5), for the study. Specimens of LV from the patients taken during surgery were used for the gene microarray study. Cardiomyocyte cell line HL-1 cells were transfected with gene-containing plasmids and further evaluated for mRNA and protein expression, apoptosis, and contractile protein degradation. Of 67,258 expressed sequence tags, microarrays identified 718 genes to be differentially expressed between preserved-LVF and worsening-LVF, including genes related to the protein ubiquitination pathway, bone morphogenetic protein (BMP) receptors, and regulation of eIF4 and p70S6K signaling. In addition, worsening-LVF was associated with altered expressions of genes pathologically relevant to heart failure, such asdownregulated apelin receptors and upregulated peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PPARGC1A). HL-1 cardiomyocyte cells transfected with ubiquitination-related genes demonstrated activation of the protein ubiquitination pathwaywith an increase in the ubiquitin activating enzyme E1 (UAE-E1). It also led to increased apoptosis, downregulated and ubiquitinated X-linked inhibitor of apoptosis protein (XIAP), and reduced cell viability. Overexpression of ubiquitination-related genes also resulted in degradation and increased ubiquitination of α-smooth muscle actin (SMA). In conclusion, worsening-LVF presented differential gene expression profiles from preserved-LVF after MV repair. Upregulation of protein ubiquitination-related genes associated with worsening-LVF after MV repair may exert adverse effects on LV through increased apoptosis and contractile protein degradation.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
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.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Neoadjuvant concurrent chemoradiation (CCRT) is standard treatment for clinical stage II/III rectal cancers. However, whether patients with pathological complete response (pT0N0, pCR) should receive ...adjuvant chemotherapy and whether delayed surgery will influence the pCR rate remains controversial. A nationwide population study was conducted using the Taiwan Cancer Registry Database from January 2007 to December 2013. Kaplan‐Meier survival analysis was performed. Cox proportional hazards models were used to estimate multivariate adjusted hazard ratios (HR) and 95% confidence intervals (95% CI). Of the 1,914 patients who received neoadjuvant CCRT, 259 (13.6%) achieved pCR and had better survival (adjusted HR: 0.37, 95% CI: 0.24‐0.58; p < 0.001). The cumulative rate of pCR rose up to 83.4% in the 9th week and slowly reached a plateau after the 11th week. Among the patients with pCR, those who received adjuvant chemotherapy had no survival benefits compared to those without adjuvant chemotherapy (adjusted HR: 0.72, 95 CI: 0.27–1.93; p = 0.52). By subgroup analysis, those younger than 70‐year old and received adjuvant chemotherapy had better survival benefit than those without adjuvant chemotherapy (adjusted HR: 0.19, 95% CI: 0.04–0.97; p = 0.046). Delayed surgery by 9–12 weeks after the end of neoadjuvant CCRT can maximize the pCR rate, which is correlated with better survival. Adjuvant chemotherapy may be considered in patients with pCR and aged <70‐year old, but further prospectively randomized controlled trials are warranted to validate these findings.
What's new?
Neoadjuvant concurrent chemoradiation (CCRT) followed by surgery is the standard treatment for stage II and III rectal cancer. However, the benefit of adjuvant chemotherapy for patients with pathological complete response (pCR) and the timing of surgery after the end of neoadjuvant CCRT have been debated. Using a nationwide population dataset in Taiwan, this study confirms that pCR predicts better overall survival. The findings also suggest that delaying surgery by 9 to 12 weeks after the end of neoadjuvant CCRT can boost pCR rate and that adjuvant chemotherapy may potentially be considered in patients with pCR and aged <70‐year old.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
The incidence and prevalence of inflammatory bowel disease (IBD) are low but increasing in Taiwan. We aimed to investigate the epidemiology and clinical outcomes of IBD in central Taiwan. We ...retrospectively analyzed patients with IBD diagnosed at our hospital between January 2000 and September 2018. The diagnostic criteria were based on endoscopic and pathologic findings. Clinical characteristics, treatment regimens, and treatment outcomes were analyzed. A total of 190 patients with IBD were enrolled (80 with Crohn’s disease (CD) and 110 with ulcerative colitis (UC)). The mean age at diagnosis was 38.4 years (CD: 36 years, UC: 40 years). Male patients accounted for the majority of patients (71.1%). The male-to-female ratio was 3 : 1 for CD and 2.1 : 1 for UC. Current and ever smokers accounted for 30.5% of all patients. Only 4.2% of patients had a family history of IBD. Extraintestinal manifestations (EIMs) were reported in 7.9%, and colorectal cancers (CRCs) were reported in 2.1% of all patients. In patients with CD, the ileal type was the most common disease phenotype (57.5%), and the stricturing type was the most common disease behavior (60.0%). In patients with UC, left-sided colitis was the predominant disease extent (42.7%). The seroprevalence of hepatitis B virus (HBV) was 13.3%. The incidence of perinuclear anti-neutrophil cytoplasmic antibody (p-ANCA) in patients with UC was 22%. 5-Aminosalicylic acids were the preferred treatment for UC, whereas corticosteroids, immunomodulators, and biologic agents were preferred for CD. In patients with CD, the bowel resection rate was 38.8%, and the incidence of hip avascular necrosis was 3.8%. In Taiwan, patients with IBD showed a male predominance, lack of familial clustering, a higher prevalence of HBV infection, and a lower prevalence of p-ANCA, EIMs, and CRC. Moreover, a higher incidence of the ileal type with poor outcomes of CD and left-sided predominance in UC were found.
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FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, UL, UM, UPUK
Tidal current‐induced cyclonic eddies cause cold‐water upwelling and periodic sea surface temperature (SST) drops around the coral reef area in Nanwan Bay, which is located at the southern tip of ...Taiwan. This study used Himawari‐8 satellite data and tide gauge and coastal ocean dynamics application radar (CODAR) data to analyze the characteristics of the SST drops and cyclonic eddy propagation and used an oceanic general circulation model (OGCM) to simulate the tidal current flowing process. According to the CODAR data analysis, the mixed primary semidiurnal tide had an average current velocity of 0.3–0.4 m s−1 throughout the bay, and the average life cycle of a cyclonic eddy is 6.6 hr, with a propagation speed of 0.35 m s−1. The SST drop during the spring tide period was greater than that during the neap tide period, and the SST dropped in both summer and winter. The average daily SST drop in the summer reached 2 °C with a maximum observed value of 4.7 °C, and the SST drop rate was 0.3–0.5 °C hr−1. The annual mean chlorophyll‐a concentration was 0.25 mg m−3. This study explored the special properties of the Nanwan Bay coral reef area from the perspective of ocean physics to allow ecologists to facilitate the implementation of long‐term conservation and monitoring programs.
Plain Language Summary
In recent years, the increased global sea temperatures have caused severe coral bleaching; however, Nanwan Bay has suffered a comparatively smaller impact. To understand why, we analyzed satellite and radar data. We found that Nanwan Bay experienced an almost daily sea surface temperature (SST) drop during the summer and that this periodic variation was caused by a cyclonic eddy upwelling cold water to the surface. In the summer, the SST drop was 2 °C on average and dropped at a rate of 0.3–0.5 °C hr−1. The observational record indicated that the water cooled as much as 4.7 °C in 1 day. These eddies were caused by the unique topography in this area of the bay; they survived an average of 6.6 hr and moved at a rate of 0.35 m s−1. The formed eddies disappeared in the bay or flowed southward out of the bay. With this study, we hope to help marine ecologists understand the Nanwan Bay environment from a geophysical perspective so that they have sufficient background knowledge when investigating coral biology and coral reef ecology in the future.
Key Points
Himawari‐8 satellite and coastal radar data are used to analyze the characteristics of eddy‐induced sea surface temperature drop in a bay
In summer, ebb current‐induced cyclonic eddies cause 2 °C sea surface temperature drops that reduce thermal stress
The average life cycle of eddies was 6.6 hr with propagation speed of 0.35 m s−1, which was close to the tidal currents around the bay
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
A novel automated method for measuring left ventricular (LV) global longitudinal strain (GLS) along the endocardium has advantages in terms of its rapid application and excellent reproducibility. ...However, it remains unclear whether the available normal range for conventional GLS using the manual method is applicable to the automated GLS method. This study aimed to compare automated GLS head-to-head with manual layer-specific GLS, and to identify whether a specialized normal reference range for automated GLS is needed and explore the main determinants.
In total, 1683 healthy volunteers (men, 43%; age, 18–80 years) were prospectively enrolled from 55 collaborating laboratories. LV GLS was measured using both manual layer-specific and automated methods.
Automated GLS was higher than endocardial, mid-myocardial, and epicardial GLS. Women had a higher automated GLS than men. GLS had no significant age dependency in men, but first increased and then decreased with age in women. Accordingly, sex- and age-specific normal ranges for automated GLS were proposed. Moreover, GLS appeared to have different burdens in relation to dominant determinants between the sexes. GLS in men showed no dominant determinants; however, GLS in women correlated with age, body mass index, and heart rate.
Using the novel automated method, was LV GLS higher than when using the manual GLS method. The normal ranges of automated GLS stratified according to sex and age were provided, with dominant determinants showing sex disparities that require full consideration in clinical practice.
Left Ventricular Global Longitudinal Strain Using a Novel Fully Automated Method: a Head-to-head Comparison with a Manual Layer-specific Strain and Establishment of Normal Reference Ranges. Display omitted
•Automated GLS was higher than the conventional manual GLS.•Sex- and age-specific normal ranges in relation to automated GLS were provided.•The dominant determinants were shown to have sex disparities that need consideration.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
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 <65 years (non-elderly group). Clinical features, surgical information, postoperative complications, and three-year survival rates were compared. The average ages were 74.2 ± 6.4 and 45.2 ± 12.6 years in the elderly and non-elderly groups, respectively. The elderly group had a higher predicted mortality rate and a lower incidence of preoperative septic emboli-related complications. Echocardiographic assessments of infected valves were generally homogenous between the groups. The elderly patients had a higher in-hospital mortality rate than the non-elderly patients (26.3% vs. 5.7%, 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.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Abstract
Background
Sustained, chronic activation of β-adrenergic receptor (β-AR) signaling leads to cardiac arrhythmias, with exchange proteins directly activated by cAMP (Epac1 and Epac2) as key ...mediators. This study aimed to evaluate whether CD44, a transmembrane receptor mediating various cellular responses, participates in Epac-dependent arrhythmias.
Methods
The heart tissue from CD44 knockout (CD44
−/−
) mice, cultured HL-1 myocytes and the tissue of human ventricle were used for western blot, co-immunoprecipitaiton and confocal studies. Line-scanning confocal imaging was used for the study of cellular Ca
2+
sparks on myocytes. Optical mapping and intra-cardiac pacing were applied for arrhythmia studies on mice’s hearts.
Results
In mice, isoproterenol, a β-AR agonist, upregulated CD44 and Epac1 and increased the association between CD44 and Epac1. Isoproterenol upregulated the expression of phospho-CaMKII (p-CaMKII), phospho-ryanodine receptor (p-RyR), and phospho-phospholamban (p-PLN) in mice and cultured myocytes; these effects were attenuated in CD44
−/−
mice compared with wild-type controls. In vitro, isoproterenol, 8-CPT-cAMP (an Epac agonist), and osteopontin (a ligand of CD44) significantly upregulated the expression of p-CaMKII, p-RyR, and p-PLN; this effect was attenuated by CD44 small interfering RNA (siRNA). In myocytes, resting Ca
2+
sparks were induced by isoproterenol and overexpressed CD44, which were prevented by inhibiting CD44. Ex vivo optical mapping and in vivo intra-cardiac pacing studies showed isoproterenol-induced triggered events and arrhythmias in ventricles were prevented in CD44
−/−
mice. The inducibility of ventricular arrhythmias (VAs) was attenuated in CD44
−/−
HF mice compared with wild-type HF controls. In patients, CD44 were upregulated, and the association between CD44 and Epac1 were increased in ventricles with reduced contractility.
Conclusion
CD44 regulates β-AR- and Epac1-mediated Ca
2+
-handling abnormalities and VAs. Inhibition of CD44 is effective in reducing VAs in HF, which is potentially a novel therapeutic target for preventing the arrhythmias and sudden cardiac death in patients with diseased hearts.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
A high risk of stroke occurrence has been reported in several types of irradiated cancer patients. However, clinical data are lacking in irradiated lung cancer patients. The present study intended to ...explore a risk level of ischemic stroke occurrence in irradiated lung cancer patients.
A nationwide population-based database obtained from the Taiwan National Health Insurance was analyzed. Between 2003 and 2006, we recruited 560 resected lung cancer patients into two study groups: surgery-plus-irradiation (n = 112) and surgery-alone (n = 448). Patients treated with chemotherapy were excluded. Propensity score match was used for pairing cases with a ratio of 1∶4. Two-year ischemic-stroke-free survival was defined as the primary endpoint.
Three observations supported a high risk of ischemic stroke occurrence in patients with postoperative irradiation when compared with those patients with surgery alone: first, a high incidence per 1,000 person-year (22.3 versus 11.2, 1.99 folds); second, a low two-year ischemic-stroke-free survival rate (92.2% versus 98.1%, P = 0.019); and third, a high adjusted hazard ratio (HR, 4.19; 95% CI, 1.44-12.22; P = 0.009). More notably, the highest risk of ischemic stroke occurrence was found in irradiated patients who had diabetes mellitus (HR, 34.74; 95% CI, 6.35->100; P<0.0001).
A high incidence of ischemic stroke was observed in irradiated lung cancer patients, especially in those with diabetes mellitus. For these patients, close clinical surveillance and strict diabetes control should be considered. Further studies to define detail biological mechanisms are encouraged.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Gastric carcinogenesis is a commonly diagnosed type of cancer and has a dismal prognosis because of the rate at which it aggressively spreads and because of the lack of effective therapies to stop ...its progression. This study evaluated a type of oral drug delivery system of a potential target-activated nanosizer comprising a fucose-conjugated chitosan and polyethylene glycol-conjugated chitosan complex with gelatin containing encapsulated green tea polyphenol extract epigallocatechin-3-gallate, allowing oral administration of the drug through a site-specific release in gastric cancer cells. The results demonstrated that the nanoparticles effectively reduced drug release within gastric acids and that a controlled epigallocatechin-3-gallate release inhibited gastric cancer cell growth, induced cell apoptosis, and reduced vascular endothelial growth factor protein expression. Furthermore, in vivo assay results indicated that the prepared epigallocatechin-3-gallate-loaded fucose-chitosan/polyethylene glycol-chitosan/gelatin nanoparticles significantly affected gastric tumor activity and reduced gastric and liver tissue inflammatory reaction in an orthotopic gastric tumor mouse model.
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IJS, KILJ, NUK, PNG, UL, UM
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