The matricellular protein CCN3 regulates NOTCH1 signalling in chronic myeloid leukaemia

Deregulated NOTCH1 has been reported in lymphoid leukaemia, although its role in chronic myeloid leukaemia (CML) is not well established. We previously reported BCR‐ABL down‐regulation of a novel haematopoietic regulator, CCN3, in CML; CCN3 is a non‐canonical NOTCH1 ligand. This study characterizes the NOTCH1–CCN3 signalling axis in CML. In K562 cells, BCR‐ABL silencing reduced full‐length NOTCH1 (NOTCH1‐FL) and inhibited the cleavage of NOTCH1 intracellular domain (NOTCH1‐ICD), resulting in decreased expression of the NOTCH1 targets c‐MYC and HES1. K562 cells stably overexpressing CCN3 (K562/CCN3) or treated with recombinant CCN3 (rCCN3) showed a significant reduction in NOTCH1 signalling (> 50% reduction in NOTCH1‐ICD, p < 0.05). Gamma secretase inhibitor (GSI), which blocks NOTCH1 signalling, reduced K562/CCN3 colony formation but increased that of K562/control cells. GSI combined with either rCCN3 or imatinib reduced K562 colony formation with enhanced reduction of NOTCH1 signalling observed with combination treatments. We demonstrate an oncogenic role for NOTCH1 in CML and suggest that BCR‐ABL disruption of NOTCH1–CCN3 signalling contributes to the pathogenesis of CML. © 2013 The Authors. Journal of Pathology published by John Wiley & Sons Ltd on behalf of Pathological Society of Great Britain and Ireland.     

沉默DLL3基因增强白血病K562/ADM细胞对阿霉素的敏感性

目的 探讨沉默Delta-like ligand 3（DLL3）基因对白血病K562/ADM细胞对阿霉素（ADM）耐药性的影响及其分子机制。 方法 将干扰人DLL3基因表达的shRNA质粒和无义对照质粒转染K562/ADM细胞,采用RT-PCR法检测DLL3的mRNA表达水平,采用CCK-8法检测ADM对K562和K562/ADM细胞的毒性作用,采用流式细胞术检测细胞凋亡和细胞内ADM浓度,采用Western blotting方法检测DLL3、谷胱甘肽S转移酶-π（GST-π）和P-糖蛋白（P-gp）的蛋白表达水平。 结果 K562/ADM细胞DLL3的mRNA和蛋白表达水平均显著高于其亲代K562细胞（P<0.05）;ADM对K562和K562/ADM细胞的IC₅₀ 分别为1.08 mg/L和34.93 mg/L;沉默DLL3基因后,K562/ADM细胞的耐药倍数下降至13.12,反转倍数为2.47;尽管抑制DLL3基因表达未对K562/ADM细胞凋亡产生影响,但可下调P-gp和GST-π的蛋白表达水平（P<0.05）,增加K562/ADM细胞内ADM的蓄积量（P<0.05）,从而增强ADM诱导的K562/ADM细胞凋亡（P<0.05）。 结论 沉默DLL3基因可反转K562/ADM细胞对ADM的耐药性,这可能与下调P-gp和GST-π蛋白水平、从而减少K562/ADM细胞内阿霉素蓄积量有关。     

Effect of a seashell protein Haishengsu on the immunological function of mice with Ehrlich ascites tumor

This study was designed to investigate the effect of a seashell protein Haishengsu (HSS) on the immuno logical function in mice with Ehrlich ascites tumor. Ehrlich ascites tumor-bearing mice were divided into three HSS groups (25, 50 and 100?mg/kg, i.v., respectively), cyclophosphamide (10?mg i.p.) and control group. The immunological function was assessed by measuring the phagocytizing capacity of the peritoneal macrophages and neutrophils, as well as the number of spleen hemolytic plaque-forming cells. The percentage of blood T-lymphocytes was also evaluated. The number and the percentage of phagocytizing macrophages and neutrophils in the 50 and 100?mg/kg HSS groups were higher than in the control and the cyclophosphamide groups (P?<?0.01). The hemolytic plaque-forming cells in the three HSS groups (10.8?±?1.2, 16.9?±?3.9 and 25.3?±?2.9, respectively), was greater than in the control (7.3?±?1.4), or the cyclophosphamide group (0.33?±?0.4) (all P?<?0.01). In all HSS groups, the percentage of blood T3, T4 and T8 was higher than in the cyclophosphamide and the control group (all P?<?0.01). We conclude that HSS has significant immune-modulating effect in mice with Ehrlich ascites tumor.     

小檗胺诱导K562细胞凋亡及其与bcr/ablgene及P210表达的关系

目的:探讨小檗胺(BER)诱导K562细胞凋亡及其可能的机制。方法:以流式细胞仪(FCM)分析、电镜观察细胞微结构变化及基因组DNA电泳等方法检测细胞凋亡。以RT-PCR及Westernblot方法检测K562细胞BCR/ABLmRNA和蛋白质水平表达。结果:FCM检测见到典型的凋亡峰,8.0mg/LBER作用24-72h,随药物作用时间延长,细胞凋亡率由(29.20±3.82)%上升至(61.77±4.35)%(P＜0.01);以2.0-8.0mg/LBER作用24h,随药物浓度增加,K562细胞的凋亡率也增加。电镜下可见明确的细胞凋亡的形态学改变。DNA电泳呈现典型的梯形条带。16.0mg/LBER处理24h,K562细胞bcr/ablmRNA相对表达量及BCR/ABL融合蛋白质P210水平均明显低于对照组,分别为0.73±0.02vs1.19±0.02(P＜0.01)和0.63±0.01vs1.04±0.02(P＜0.01),呈时间-浓度依赖效应。经BER作用后,K562细胞bcr/ablmRNA表达强度与P210水平呈正相关(r=0.928,P＜0.05),且细胞凋亡率与bcr/ablmRNA表达呈负相关(r=-0.997,P＜0.01)。结论:在体外BER对K562细胞有明显的促凋亡作用,抑制bcr/ablmRNA表达及其蛋白质水平可能是其作用的重要机制之一。     

海生素对K562细胞生长及凋亡基因表达的影响

目的 探讨海生素对白血病K562细胞生长及凋亡基因表达的影响. 方法实验分为对照组、10mg/L海生素组和20rag/L海生素组.采用流式细胞术(FcM)、四唑蓝(MTT)和免疫细胞化学法测定海生素对K562细胞周期、细胞生长及细胞凋亡基因bcl-2和bax表达的影响. 结果海生素浓度为10mg/L和20mg/L时,可阻止K562细胞周期于G1/S期;海生素浓度为20mg/L时对K562细胞有抑制作用,在此浓度下随时间的延长细胞存活率有下降趋势;海生素浓度为20mg/L和40mg,L时,可下调凋亡抑制基因bcl-2的表达,上调凋亡促进基因hax的表达.结论 海生素可明显抑制K562细胞的增殖,使其阻滞于细胞周期的G1/S期;海生素还通过减少bcl-2的表达及增加bax的表达从而促进K562细胞的凋亡.     

A near‐haploid clone harboring a BCR/ABL1 gene fusion in an adult patient with newly diagnosed B‐lymphoblastic leukemia

The detection of recurrent genetic abnormalities in B‐lymphoblastic leukemia (B‐ALL) is critical for risk stratification and therapy‐related decisions. Near‐haploidy (24‐30 chromosomes), a subgroup of hypodiploidy (<46 chromosomes), and BCR/ABL1 gene fusions are both recurrent genetic abnormalities in B‐ALL and are considered adverse prognostic findings, although outcomes in BCR/ABL1‐positive patients have improved with tyrosine kinase inhibitor therapy. While near‐haploid clones are primarily observed in children and rarely harbor structural abnormalities, BCR/ABL1‐positive B‐ALL is primarily observed in adults. Importantly, recurrent genetic abnormalities are considered mutually exclusive and rarely exist within the same neoplastic clone. We report only the second case to our knowledge of a near‐haploid clone that harbors a BCR/ABL1 fusion in an adult with newly diagnosed B‐ALL. Conventional chromosome studies revealed a near‐haploid clone (27 chromosomes) along with a der(22)t(9;22)(q34.1;q11.2) in 17 of 20 metaphases analyzed. Our B‐ALL fluorescence in situ hybridization (FISH) panel confirmed the BCR/ABL1 fusion and monosomies consistent with chromosome studies in approximately 95% of interphase nuclei. Moreover, no evidence of a “doubled” near‐haploid clone was observed by chromosome or FISH studies. This highly unusual case illustrates that while rare, recurrent genetic abnormalities in B‐ALL can exist within the same neoplastic clone.     

Rhino/enteroviruses in hospitalized children: A comparison to influenza viruses

BackgroundThe relative impact of human rhino/enteroviruses (HRV/EV) compared to influenza viruses on hospitalized children is unknown.ObjectivesThis retrospective study compared the epidemiology and clinical characteristics of hospitalized patients with HRV/EV to patients hospitalized with influenza virus.Study designRespiratory specimens from hospitalized children submitted between January 1, 2009 and December 31, 2009 to Children's Hospital Colorado Virology Laboratory in Aurora, CO were tested by a commercial multiplex PCR for 16 respiratory viruses and subtypes. Patients with specimens positive for HRV/EV or influenza virus without bacterial or viral co-infection were selected for retrospective chart review.ResultsOf the 2299 patients with specimens tested during the study period, 427 (18.6%) were singly positive for HRV/EV and 202 (8.8%) for influenza virus (p < 0.01). Children with HRV/EV were more likely to present with increased work of breathing (67.9% vs. 52.5%, p < 0.01) with crackles (36.3% vs. 23.3%, p < 0.01) and wheezing (41.7% vs. 22.8%, p < 0.01) noted on exam. Children hospitalized with HRV/EV had a shorter median length of stay (2 days vs. 3 days, p < 0.01), duration of fever (1 days vs. 3 days, p < 0.01), and duration of hypoxemia (2 days vs. 3 days, p < 0.01) than children with influenza virus. Similar percentages of children with HRV/EV and influenza virus were admitted to the PICU and required positive pressure ventilation. There were no deaths in children hospitalized with HRV/EV, whereas 6 children with influenza virus expired.ConclusionsHRV/EVs are common pathogens in hospitalized children associated with serious lower respiratory tract disease and significant morbidity, similar to influenza viruses.     

Microbiological features,clinical characteristics and outcomes of infective endocarditis in adults with and without hemodialysis: A 10-year retrospective study in Northern Taiwan

Background/purposesInfective endocarditis (IE) is an important cause of morbidity and mortality in hemodialysis (HD) patients. Data on the differences in the microbiological features as well as clinical characteristics and outcomes of HD and non-HD patients with IE are limited.MethodsMedical records of patients (aged over 20 years) with IE were retrospectively reviewed from January 2008 to June 2017 in a tertiary care center in Northern Taiwan. Those with definite or possible IE were included in the study. The clinical characteristics, microbiological results, echocardiographic findings and outcomes of patients were analyzed.ResultsOf the 183 patients with definite or possible IE, 47 had undergone HD and 136 had not. Advanced age (67.3 vs. 61.5 years, p = 0.027), more female gender (51.1% vs. 33.8%, p = 0.036), comorbidities (a high Charlson comorbidity index, 8.17 vs. 4.21, p < 0.001), diabetes mellitus (68.1% vs. 35.3%, p < 0.001), and hypertension (85.1% vs. 53.7%, p < 0.001) were commonly observed in HD patients than in non-HD patients. The yield rate of the blood cultures was higher in HD group than in non-HD group (89.4% vs. 72.8%, p = 0.02). The proportion of methicillin-resistant Staphylococcus aureus was significantly higher in HD group than in non-HD group (31.9% vs. 5.9%, p < 0.001). HD patients versus non-HD patients had higher cardiac complication rates (38.3% vs. 14%, p < 0.001).ConclusionAdvanced age, sex (female), comorbidities, diabetes mellitus, and hypertension were more common in HD patients than in non-HD patients with IE. HD patients had higher proportion of methicillin-resistant S. aureus and cardiac complication rates than non-HD patients with IE. Culture-negative IE was more common in non-HD patients.     

Anti-Tax antibody levels in asymptomatic carriers,oligosymptomatic carriers,patients with rheumatologic disease or with HAM/TSP do not correlate with HTLV-1 proviral load

BackgroundHTLV-1 infects millions of people around the world and induces myelopathy (HAM/TSP), adult T-cell leukemia (ATL) or other inflammatory or rheumatologic diseases. The host–virus interaction causes asymptomatic carriers to develop HAM/TSP. Biomarkers are needed to predict patients who are at risk for HAM/TSP. Tax is highly immunogenic and is a major target protein recognized by cytotoxic T lymphocytes. Anti-Tax antibodies are involved in HAM/TSP pathogenesis.ObjectivesTo assess anti-Tax IgG reactivity with a flow cytometry assay (FCA) using an infection/transfection system with Vaccinia virus and pLW44/Tax-expressing Tax and to correlate the anti-Tax response and the HTLV-1 proviral load.Study design: We enrolled 81 individuals: 9 HTLV-1 seronegative (NP) and 72 HTLV-1 positive (23 HTLV-1 asymptomatic carriers (AC), 12 oligosymptomatic patients (OL), 7 with rheumatologic diseases (DR) and 30 with HAM/TSP (HT)). Anti-Tax reactivity was assessed by FCA, and HTLV-1 proviral load was measured with real time PCR.ResultsThe HT and DR groups showed greater anti-Tax IgG reactivity (p < 0.001 and p < 0.05 comparing HT to the OL and AC group, respectively; p < 0.05 comparing DR to the OL group), and the reactivity in the DR + HT group was significantly different when compared to the AC group (p < 0.05) and to the OL group (p < 0.001). The proviral load was higher in the HT group compared to the OL (p < 0.001) and in the HT + DR group compared to OL (p < 0.001). There was no correlation between anti-Tax IgG reactivity and proviral load in any of the HTLV-1-infected groups.ConclusionThese findings suggest that although anti-Tax IgG reactivity and the HTLV-1 proviral load are important markers of the development of HTLV-1-associated diseases, their levels are not correlated.     

Postoperative bleeding adversely affects total knee arthroplasty outcomes in hemophilia

BackgroundHemophilic arthropathy can result in severe degenerative arthritis and functional limitations in the knees of relatively young patients. Total knee arthroplasty (TKA) provides pain relief and gain of function in advanced-stage hemophilic arthropathy cases. However, little is known about the long-term effects of early major postoperative bleeding (MPOB) in people with hemophilia (PWH). The aim of this study was to evaluate the effects of early MPOB on the final functional outcome, complications, and implant survival of TKA in a single-center hemophilia cohort.MethodPWH who underwent TKA between 1998 and 2019 in a single center were reviewed. Demographic data, clinical data, and radiographic images were evaluated. Hospital for Special Surgery (HSS), Knee Society Score (KSS), and Knee Society Function Score (KSS-F) scores were used to determine function. Patients with early bleeding complications (wound dehiscence, ecchymosis, hemarthrosis, hematoma formation, prolonged or recurrent bleeding attacks) were defined as the bleeding group. Patients who did not experience these complications were assigned to the control group. The bleeding group was compared with controls. Survival of the primary arthroplasty was analyzed by Kaplan–Meier curves.ResultsForty-five TKAs in 29 patients were included in the study. TKA led to an increase in the mean range of motion from 46.08° to 84.59° (P < 0.01). HSS scores increased from 48.33 preoperatively to 82.67 postoperatively (P < 0.01). There were improvements in both KSS and KSS-F scores from 34.22 and 53.3 preoperatively to 82.00 and 84.63 (P < 0.01), respectively. Ten patients (10 TKAs) (34%) experienced major bleeding during the postoperative period. Six of these patients had moderate hemophilia, and four had severe hemophilia. Three of these patients had hemarthroses (10.2%), one patient had a hematoma (3.4%), one patient had hemorrhagic bullae formation (3.4%), and five had excessive/prolonged bleeding from the wound (17%). The bleeding group (34%) had significantly worse HSS (63.78 vs 92.75, P < 0.001), KSS (61.78 vs 93.25, P < 0.001), and KSS-F (60.71 vs 96.25, P = 0.005) scores compared with controls. Preoperative and postoperative flexion contractures were positively correlated (+0.33, P = 0.003). One of the patients with postoperative hemarthrosis also had an accompanying transient common peroneal nerve palsy, and one patient (3.4%) had a periprosthetic fracture. Three knees (6.6%), two of whom were in the bleeding group, developed periprosthetic infections. Four knees (8.8%) in three patients underwent revision surgery, and two knees (4.4%) ended up in arthrodeses. Kaplan–Meier analysis revealed a mean survival duration of 17.04 years for the bleeding group and 22.15 years for the control group (P = 0.83). Survival rates were 80.0% for the bleeding group and 96.4% for the control group (P = 0.83).ConclusionsIn this study, MPOB after TKA in PWH was common and led to significantly worse function. MPOB after TKA in PWH was associated with a higher rate of complications and lower survival rates, although the differences were not statistically significant. Efforts must be made to avoid MPOB after TKA in PWH.     

Lower levels of low-density lipoprotein cholesterol are associated with a lower prevalence of thin-cap fibroatheroma in statin-treated patients with coronary artery disease

BackgroundReducing low-density lipoprotein cholesterol (LDL-C) levels with statins slows the progression of atherosclerotic plaques and reduces cardiovascular events. The 2019 European Society of Cardiology/European Atherosclerosis Society guidelines recommend absolute LDL-C treatment targets of <100 mg/dL, <70 mg/dL and <55 mg/dL according to coexisting patient risk factors.ObjectiveTo clarify the difference in the plaque characteristics of coronary lesions associated with these LDL-C levels in statin-treated patients.MethodsA total of 685 consecutive statin-treated patients with coronary artery disease (CAD) who underwent optical coherence tomography (OCT) imaging of culprit lesions were enrolled. The characteristics of culprit plaques evaluated by OCT were compared among the high LDL-C group (≥100 mg/dL, n=247), the moderate LDL-C group (70-100 mg/dL, n=289), the low LDL-C group (55-70 mg/dL, n=106) and the very low LDL-C group (<55 mg/dL, n=43).ResultsA significant trend toward a lower prevalence of thin-cap fibroatheroma (TCFA) associated with the LDL-C groups was observed (23.1, 18.3, 9.4 and 11.6%, respectively, in each group; p=0.002). A trend toward a lower prevalence of TCFAs associated with the LDL-C groups was also observed among patients with lower hemoglobin A1c (<6.2%; p=0.003). LDL-C <70 mg/dL (the low/very low group) was independently associated with the lack of TCFAs (odds ratio, 0.50; 95% confidence interval, 0.27-0.87, p=0.014).ConclusionsLower LDL-C levels were associated with a lower prevalence of TCFAs in culprit plaques among statin-treated patients with CAD.     

The association of obesity and dengue severity in hospitalized adult patients

BackgroundObesity is associated with unfavorable outcomes for infectious diseases. Most researches exploring the association between nutritional status and dengue severity have focused on pediatric populations, with only few studies assessing adult patients.MethodsAdult patients with laboratory-confirmed dengue admitted to a tertiary hospital in southern Taiwan between 2014 and 2015 were enrolled retrospectively. Demographics, comorbidities, clinical presentation, laboratory findings, and outcomes were obtained from case-record forms. Patients were categorized into obese group and nonobese group. The obese group comprised patients with a body mass index of ≥27.5 kg/m².ResultsA total of 1417 hospitalized patients with dengue were evaluated. The mean age was 57.9 years (range: 18–92 years). The obese and nonobese groups comprised 333 (23.5%) and 1084 (76.5%) patients, respectively. The obese group included more patients with hypertension (85%, p < 0.001), diabetes mellitus (33%, p < 0.001), and congestive heart failure (6.3%, p = 0.049). Multivariate analysis revealed that the obese group had more petechiae (AOR: 1.353, 95% CI: 1.025–1.786, p = 0.033), more dyspnea (AOR: 1.380, 95% CI: 1.015–1.876, p = 0.040), and more severe hepatitis (AOR: 2.061, 95% CI: 1.050–4.048, p = 0.036). The obese group also had higher peak hematocrit values (44.1%, p < 0.001) and lower nadir platelet count (45.3 × 10³/μL, p = 0.049) than the nonobese group.ConclusionIn adult patients with dengue, obese group had more petechiae, dyspnea, severe hepatitis, lower nadir of platelet count, and higher peak hematocrit level. We observed no difference in severe dengue or mortality between obese and nonobese group.     

Effects of a HAPA-based multicomponent intervention to improve self-management precursors of older adults with tuberculosis: A community-based randomised controlled trial

ObjectiveTo evaluate the effectiveness of a multicomponent intervention based on the Health Action Process Approach (HAPA) model to improve the self-management precursors of older adults with tuberculosis (TB).MethodsA cluster-randomised controlled trial was conducted. Older adults with TB in the intervention communities received HAPA-based multicomponent interventions at the beginning of treatment and in the first and sixth months after treatment initiation, and those in the control communities received health education alone. Self-management precursors were measured at baseline and 1 week after each intervention.ResultsAmong 262 randomized patients, 244 (93%) completed the trial. Compared with the control group, self-management precursor scores for the intervention group increased significantly over time (β_group*time = 2.92, p < 0.001) in the following 3 precursors: behaviour belief (β_group*time = 0.35, p < 0.001), behaviour plan (β_group*time = 0.72, p < 0.001), and self-efficacy (β_group*time = 1.85, p < 0.001). Education was significantly associated with behaviour belief (β = 0.18, p < 0.05). Chronic comorbidity was significantly associated with behaviour plan (β=−0.26, p < 0.05).ConclusionCompared with single health education, the HAPA-based multicomponent interventions significantly improved the self-management precursor of older adults with TB.Practice implicationsThis HAPA-based multicomponent intervention strategy may be a promising self-management mode for the routine health care of TB patients.     

HSS膝关节康复方案对单髁置换术后早期关节功能和步态的影响

目的 研究美国特种外科医院（hospital for special surgery, HSS）膝关节康复方案对膝关节单髁置换术（unicompartmental knee arthroplasty, UKA）术后关节功能及步态的近期影响。方法 回顾性分析2018年1月至2021年6月间在湖北省中医院行UKA术的60例患者。将采用HSS膝关节成形术康复指南进行康复治疗的30例患者作为HSS组;将同期采用常规康复方案的30例患者作为常规组。记录术后1周、3个月、6个月、1年两组患者的膝关节活动范围（range of motion, ROM）、美国特种外科医院膝关节HSS评分、人工关节遗忘指数（forgotten joint index, FJS）。分别于术后6个月、1年时采用GaitWatch三维步态分析及运动训练系统进行步态信息数据的采集,并比较两组间差异。结果 两组均完成术后1年以上随访,膝关节功能比较：术后3个月随访,HSS组膝关节ROM、HSS评分高于常规组,差异有统计学意义（P＜0.05）;术后6个月随访,HSS组患者膝关节ROM、HSS评分高于常规组,FJS评分低于常规组,差异有统计学意义（P＜0.05）;术后1年随访,HSS组的HSS评分高于常规组、FJS评分低于常规组,差异有统计学意义（P＜0.05）。步态参数比较：术后6个月随访,HSS组的步数、步长及单足支撑相较常规组高,差异有统计学意义（P＜0.05）;术后1年随访,HSS组的步数、步频、单足支撑相较常规组高,差异有统计学意义（P＜0.05）。结论 HSS膝关节成形术后康复方案在UKA术后早期可显著改善膝关节功能和步态,有利于UKA术后早期康复。     

Impact of the eicosapentaenoic acid to arachidonic acid ratio on plaque characteristics in statin-treated patients with coronary artery disease

BackgroundA low eicosapentaenoic acid (EPA)/arachidonic acid (AA) ratio is associated with an increased risk of cardiovascular events in patients with coronary artery disease (CAD).ObjectiveTo clarify the impact of the EPA/AA ratio on the characteristics of non-culprit coronary plaques in statin-treated patients with CAD.MethodsA total of 370 consecutive stable coronary disease patients treated with statins, who underwent percutaneous coronary intervention for the culprit lesion and optical coherence tomography (OCT) imaging of the non-culprit plaque in a culprit vessel were included. The characteristics of non-culprit plaques assessed using OCT were compared between the lower EPA/AA group (EPA/AA <0.4, n = 255) and the higher EPA/AA group (EPA/AA ≥0.4, n = 115).ResultsThe prevalence of lipid-rich plaque (58.8 vs. 41.7%, p = 0.003) and plaque with macrophages (56.5 vs. 31.3%, p <0.001) was significantly higher in the lower EPA/AA group than in the higher EPA/AA group. This association was observed even if the LDL-C level was <100 mg/dL. The prevalence of thin-cap fibroatheroma was significantly higher in patients with lower EPA/AA and higher LDL-C (≥100 mg/dL) than in those with higher EPA/AA and lower LDL-C (<100 mg/dL) (odds ratio: 2.750, 95% confidence interval: 1.182-6.988, p = 0.024). An EPA/AA <0.4 was independently associated with a higher prevalence of lipid-rich plaque, plaque with macrophages, and cholesterol crystals.ConclusionLower EPA/AA ratio was associated with higher prevalence of vulnerable characteristics in non-culprit plaques. The present results suggest the importance of EPA/AA ratio on the secondary prevention of CAD.     

Clinical manifestations,risk factors and prognosis of patients with Morganella morganii sepsis

BackgroundThere are few studies of Morganella bacteremia. We evaluated risk factors and outcome of patients with Morganella bacteremia.MethodsMedical records of patients with Morganella bacteremia were reviewed (1997–2014). Control group patients with Escherichia coli sepsis were matched by year of diagnosis and infection acquisition site.ResultsThe study group included 136 adult patients. Mean age and gender of study and control groups were similar. Complicated soft tissue infection was more prevalent in the study group (30% versus 3.2%, p < 0.05). The Charlson Comorbidity Index (CCI) was higher in the study group (4.3 ± 2.5 versus 3.4 ± 2.8, p < 0.05). Only 78 (62%) of the study patients versus 101 (83%) of the control group (p < 0.05), received appropriate empirical antibiotic treatment. A significantly higher in-hospital mortality rate (42% versus 25%, p < 0.05) as well as longer length of stay (25 ± 22 versus 14 ± 16 days, p < 0.05) was observed in the study group. Multivariate analysis revealed that a debilitative state, a CCI > 4, septic shock and a clinical syndrome other than UTI were all significant risk factors for mortality (p < 0.05).ConclusionsPatients with Morganella morganii sepsis had more co-morbidities and a worse degree of sepsis. There is an increased risk of inappropriate empirical treatment, longer hospitalization and higher death rate.     

Clinical characteristics and risk factors for children with norovirus gastroenteritis in Taiwan

BackgroundNorovirus is a common acute gastroenteritis (AGE) pathogen across all age groups worldwide, which is difficult to differentiate from other pathogens. This study aimed to understand the clinical characteristics and risk factors of norovirus gastroenteritis among children in Taiwan.MethodsA prospective AGE surveillance study was conducted in children aged ≤5 years who were hospitalized in 10 major hospitals in Taiwan between 2014 and 2017. The non-AGE control group included healthy children who were matched based on age, gender, season, and geographic area.ResultsOverall, 674 norovirus gastroenteritis patients were enrolled. Fever (p < 0.001), mucoid stool (p < 0.001), and bloody stool (p < 0.001) occurred less frequently among norovirus gastroenteritis patients. Norovirus gastroenteritis patients yielded lower CRP values on admission (21.78 ± 36.81 vs. 46.26 ± 58.12 mg/L, p < 0.001) than non-norovirus controls. Norovirus gastroenteritis patients were associated with higher direct contact rates with AGE patients within 1 week (30.5% vs. 0.97%, p < 0.001), lower hand wash rates before meals (21.6% vs. 15.4%, p = 0.001), lower human milk (15.8% vs. 19.8%, p = 0.045) and guava consumption rates (17.8% vs. 24.3%, p = 0.002) than non-AGE participants.ConclusionsBody temperature, stool characteristics, and CRP value can help distinguish the norovirus from other pathogens. The major risk factor of norovirus AGE is contact with AGE patient. Higher frequency of hand wash, human milk, and guava intake may be protective against norovirus gastroenteritis.     

Proprotein convertase subtilisin/kexin type 9 inhibitor utilization and low-density lipoprotein-cholesterol control in familial hypercholesterolemia

BackgroundProprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors were approved in August 2015 as an adjunct to maximally tolerated statin treatment in those with familial hypercholesterolemia (FH).ObjectiveTo assess PCSK9 inhibitor utilization patterns and cholesterol control in the high-risk FH population.MethodsThis study was a retrospective analysis of a large administrative database that includes privately insured and Medicare Advantage patients. Individuals with diagnosis codes for FH from October 2016–September 2019 were identified. Differences in PCSK9 inhibitor utilization between various groups were evaluated using multivariable logistic regression.ResultsDuring the study period, 1:371 people enrolled in medical/pharmacy plans had a diagnosis of FH. While 62.5% (n = 33,649) had medication fills for statins (without PCSK9 inhibitors), only 2.0% (n = 1062) had medication fills for PCSK9 inhibitors (with or without other medications). Compared to men, women were more likely to be untreated (OR 1.23, 95% confidence interval (CI):1.18–1.28, p < 0.01) but more likely to be treated with PCSK9 inhibitors (OR 2.18, 95%CI:1.90–2.49, p < 0.01). Compared to those younger than 55 years of age, older individuals were more likely to be treated (OR 1.64, 95%CI:1.56–1.72, p < 0.01) but less likely to be treated with PCSK9 inhibitors (OR 0.40, 95%CI:0.34–0.47, p < 0.01). Lastly, those with household incomes ≥$40,000 were more likely to be treated with PCSK9 inhibitors than those with lower household incomes (OR 1.69, 95%CI:1.41–2.02, p < 0.01).ConclusionPCSK9 inhibitor utilization in FH remains low. Significant differences exist based on demographic factors. Female sex, higher household incomes, and younger age were associated with increased PCSK9 inhibitor utilization.     

Polymyositis/dermatomyositis and nasopharyngeal carcinoma: The Epstein–Barr virus connection?

BackgroundPolymyositis (PM) and dermatomyositis (DM) are associated with high risk of nasopharyngeal carcinoma (NPC) in Asian countries. Epstein–Barr virus (EBV) might induce autoimmunity and malignancies in susceptible individuals.ObjectivesTo investigate the association of EBV with PM/DM and NPC in PM/DM patients.Study designSerum levels of anti-EBV viral capsid antigens (VCA) and anti-EBV-coded nuclear antigens-1 (EBNA-1) antibodies were measured by ELISA, and EBV DNA loads were determined using real-time PCR for 98 PM/DM patients, 94 systemic lupus erythematosus (SLE) patients and 370 healthy controls (HC). Anti-transfer-RNA synthetase antibodies (ASA) were determined by radioimmunoprecipitation for PM/DM patients.ResultsThirteen (13.3%) of PM/DM patients vs. none of SLE patients had detectable NPC. ASA were detectable in 31.7% of PM/DM without malignancy, while lack of ASA in any PM/DM patient with NPC. IgA anti-EBNA-1 were detectable in 30.6% of PM/DM patients and 31.9% of SLE patients, but only in 4.1% of HC (odds ratio [OR] 10.44 and 11.12 respectively, both p < 0.001). Significantly higher positivity for IgA anti-EBNA-1 were observed in PM/DM with NPC than in those without malignancy (OR 44.7, p < 0.01). Significantly higher positivity for EBV genome were observed in PM/DM with NPC than in those without malignancy (OR 43.9, p < 0.01), in SLE patients (OR 13.2, p < 0.05) and in HC (OR 99.4, p < 0.001). EBV DNA loads were significantly higher in PM/DM with NPC compared with those without malignancy and HC.ConclusionsOur results showed a positive association of EBV with PM/DM and NPC. PM/DM patients who have IgA anti-EBNA-1 or increased EBV DNA loads should be highly suspected to have occult NPC.