Impact of repaired aortic coarctation in left ventricular myocardial work

AimsMyocardial strain analysis enables more precise assessment of cardiac performance but is relatively load dependent. New tools have been developed with afterload adjustment. Our objective was to assess myocardial work (MW) in patients with repaired aortic coarctation (rACo).MethodsProspective study of consecutive patients with rACo who underwent a routine transthoracic echocardiogram in 2018 and 2019 at our center. Patients with significant aortic valve disease, pacemaker, or other congenital heart diseases (except for mild bicuspid aortic valve disease) were excluded. Global longitudinal strain with two dimensional speckle tracking analysis and MW were obtained (GWI:Global Work Index; GCW: Global Constructive Work; GWW: Global Wasted Work; GWE: Global Work Efficiency). Blood pressure was measured in the patient's right arm.ResultsWe included 42 patients in the analysis, mean age of 37±10 years, 38% males. In this group, 52% had hypertension and 64% had a concomitant bicuspid aortic valve. In comparison to previously published reference values, patients with rACo had significantly lower GWI (1807 vs. 1896 mmHg%) and GCW (2173 vs. 2232 mmHg%) (p<0.001), particularly in males. Systolic blood pressure is an independent predictor for GWI (β=0.432) and for GCW (β=0.534) and GLS an independent predictor of all MW parameters (β>0.594). Neither age nor gender were independent predictors.ConclusionsIn patients with rACo, there are some signs of left ventricular dysfunction with a reduction in GCW and GWI and with preserved GWE, despite normal ejection fraction and strain.     

Coronary Artery Embolism: Two Case Reports and a Review of the Literature

Coronary embolism (CE) is an uncommon and unique cause of acute myocardial infarction. In this report, we review 216 cases of CE including 2 new cases from our institution. The mean patient age was 52.5 years and 62% of the patients were males. Chest pain was the most common presenting symptom followed by dyspnea, and the most commonly affected vessel was the left anterior descending artery. Leading etiologies of the embolus were atrial fibrillation, septic emboli, and iatrogenic causes. Treatment approaches varied with thrombus aspiration being used in 30% of cases. In-hospital mortality rate was 36% and 13% of the cases were complicated by cerebrovascular accident. CE is a unique pathology that leads to acute myocardial infarction. It portends a high mortality rate and requires a high level of suspicion as symptoms may be misleading. Further research is needed in order to improve recognition and management and to lower associated mortality.     

Morphological,Functional, and Tissue Characterization of Silent Myocardial Involvement in Patients With Primary Biliary Cholangitis

1. Download : Download high-res image (419KB)
2. Download : Download full-size image

     

Immunogenicity of next-generation HPV vaccines in non-human primates: Measles-vectored HPV vaccine versus Pichia pastoris recombinant protein vaccine

Human papillomavirus (HPV) infection is the most common sexually transmitted disease worldwide. HPVs are oncogenic small double-stranded DNA viruses that are the primary causal agent of cervical cancer and other types of cancers, including in the anus, oropharynx, vagina, vulva, and penis. Prophylactic vaccination against HPV is an attractive strategy for preventing cervical cancer and some other types of cancers. However, there are few safe and effective vaccines against HPV infections. Current first-generation commercial HPV vaccines are expensive to produce and deliver.The goal of this study was to develop an alternate potent HPV recombinant L1-based vaccines by producing HPV virus-like particles into a vaccine that is currently used worldwide. Live attenuated measles virus (MV) vaccines have a well-established safety and efficacy record, and recombinant MV (rMV) produced by reverse genetics may be useful for generating candidate HPV vaccines to meet the needs of the developing world.We studied in non-human primate rMV-vectored HPV vaccine in parallel with a classical alum adjuvant recombinant HPV16L1 and 18L1 protein vaccine produced in Pichia pastoris. A combined prime-boost approach using both vaccines was evaluated, as well as immune interference due to pre-existing immunity against the MV.The humoral immune response induced by the MV, Pichia-expressed vaccine, and their combination as priming and boosting approaches was found to elicit HPV16L1 and 18L1 specific total IgG and neutralizing antibody titres. Pre-existing antibodies against measles did not prevent the immune response against HPV16L1 and 18L1.     

罗伊氏乳杆菌对轮状病毒感染肠炎患儿免疫功能与肠道菌群及临床疗效的影响

目的探究罗伊氏乳杆菌DSM 17938在治疗轮状病毒感染肠炎患儿中的疗效及对免疫功能、肠道菌群的影响。方法收集于2018年2月-2019年2月在阳光融和医院进行诊治的轮状病毒感染肠炎患儿126例,随机分为试验组(63例)和对照组(63例)。对照组给予常规补液治疗及蒙脱石散和枯草杆菌二联活菌口服治疗,试验组采用常规补液治疗及蒙脱石散和罗伊氏乳杆菌DSM 17938辅助治疗。观察两组患儿的腹泻改善情况,并分析对免疫功能(IgG、IgA、CD4^+/CD8^+水平)及肠道菌群失调的影响。结果在治疗72 h后,试验组患儿的治疗总有效率为92.06%,高于对照组的74.60%(P=0.009);且治疗后两组患儿的IgG、IgA、CD4^+/CD8^+水平均较治疗前有升高(P<0.05),且试验组水平高于对照组(P<0.05)。对患儿肠道菌群进行分析,在治疗1周后,试验组患儿肠道菌群失调程度低于对照组,且试验组的肠道菌群正常比例高于对照组(P<0.05)。结论罗伊氏乳杆菌DSM 17938对于辅助治疗轮状病毒感染肠炎患儿具有良好的疗效,能够提高患儿免疫力,改善肠道菌群失调,减轻患儿腹泻症状,具有一定的临床应用价值。     

Therapeutic strategies for the costimulatory molecule OX40 in T-cell-mediated immunity

The T cell co-stimulatory molecule OX40 and its cognate ligand OX40L have attracted broad research interest as a therapeutic target in T cell-mediated diseases. Accumulating preclinical evidence highlights the therapeutic efficacy of both agonist and blockade of the OX40–OX40L interaction. Despite this progress, many questions about the immuno-modulator roles of OX40 on T cell function remain unanswered. In this review we summarize the impact of the OX40–OX40L interaction on T cell subsets, including Th1, Th2, Th9, Th17, Th22, Treg, Tfh, and CD8⁺ T cells, to gain a comprehensive understanding of anti-OX40 mAb-based therapies. The potential therapeutic application of the OX40–OX40L interaction in autoimmunity diseases and cancer immunotherapy are further discussed; OX40–OX40L blockade may ameliorate autoantigen-specific T cell responses and reduce immune activity in autoimmunity diseases. We also explore the rationale of targeting OX40–OX40L interactions in cancer immunotherapy. Ligation of OX40 with targeted agonist anti-OX40 mAbs conveys activating signals to T cells. When combined with other therapeutic treatments, such as anti-PD-1 or anti-CTLA-4 blockade, cytokines, chemotherapy, or radiotherapy, the anti-tumor activity of agonist anti-OX40 treatment will be further enhanced. These data collectively suggest great potential for OX40-mediated therapies.