Atrial fibrillation as a contributing factor in the diagnostic algorithm for coronary subclavian steal syndrome and cardiac tamponade following coronary artery bypass graft surgery: a case study

Coronary subclavian steal syndrome (CSSS) is a complication of coronary artery bypass graft (CABG) surgery in patients with coexistent significant subclavian artery stenosis (SAS). It is characterized by a retrograde blood flow through the left internal mammary artery graft from the coronary to subclavian circulation, leading to myocardial ischemia. Current screening for CSSS includes bilateral blood pressure measurement for the detection of a significant inter-arm blood pressure difference. However, the commonly used automated sphygmomanometers have limited accuracy in patients with atrial fibrillation. Consequently, these patients are often underdiagnosed. We present a case of a 73-year-old man with a medical history of atrial fibrillation, peripheral artery disease, and CABG surgery four months before the current event, who came to the emergency department due to progressive dyspnea. The initial diagnostic management showed a large circulatory pericardial effusion, so the patient was admitted to the coronary care unit and underwent pericardial drainage. In the following days, due to a sudden high increase in cardiac troponin, the patient underwent an urgent coronary angiography, which revealed severe left SAS with functional CABG, indicating the occurrence of CSSS. Percutaneous transluminal angioplasty was then performed with an optimal angiographic result. The patient was discharged in good condition with adequate medicament therapy and instructions. This case report highlights atrial fibrillation as a contributing factor for the diagnosis of CSSS and pericardial tamponade after CABG surgery. Furthermore, we suggest a diagnostic approach that can reduce the incidence of both these severe complications.

Coronary subclavian steal syndrome (CSSS) occurs in the presence of subclavian artery stenosis (SAS) or occlusion and represents a reversal of blood flow in the left internal mammary artery (LIMA) bypass graft, which leads to coronary ischemia. It presents as a complication in 2.5–4.5% of patients undergoing coronary artery bypass graft (CABG) surgery. The prevalence is even higher in patients with peripheral artery disease (PAD), who have a 5-fold increased risk of SAS (1,2). It commonly presents as stable angina triggered by left upper extremity activity, but can also manifest as an acute coronary syndrome, acute heart failure, ventricular arrhythmia, or even sudden cardiac death (3). Digital subtraction angiography, the current gold standard in the imaging of CSSS, has lately been increasingly replaced by other diagnostic tools, such as duplex ultrasound (DUS), computed tomography angiography (CTA), and magnetic resonance angiography. The current guidelines recommend the endovascular approach as the first-line treatment of CSSS and vascular surgery as the second option (4).     

Murine cytomegalovirus regulation of NKG2D ligands

Human cytomegalovirus (HCMV) is a ubiquitous pathogen that causes morbidity risk in immunologically suppressed and immunodeficient patients including congenital infections. Approaches to curb the consequences of HCMV infections are restricted by a lack of complete understanding of viral pathogenesis. The infection of mice with murine cytomegalovirus (MCMV) as a model of HCMV infection has been particularly useful in elucidating the role of innate and adaptive immune response mechanisms. A large number of cytomegalovirus genes modulate the innate and the adaptive host immune response. The products of several MCMV genes are involved in subverting the natural killer (NK) cell response by down-modulating cellular ligands for the NKG2D receptor expressed on NK cells and CD8⁺ T cells. Mutant viruses lacking these immunoevasion genes are attenuated with respect to virus growth in vivo. Given the importance of the NKG2D receptor in controlling both NK- and T cell-mediated immunity, it is of tremendous importance to understand the molecular mechanisms and consequences of viral regulation of the NKG2D ligands.     

Engineering of cytomegalovirus genomes for recombinant live herpesvirus vaccines

The advances of sequence knowledge and genetic engineering hold a great promise for a rational approach to vaccine development. Herpesviruses are important pathogens of all vertebrates. They cause acute and chronic infections and persist in their hosts for life. In man there are eight herpesviruses known and most of them can be linked to diseases. To date only one licensed vaccine against a human herpesvirus exists and there is no proven successful concept on rational design for herpesvirus vaccines available. Here, we use new reverse genetic systems, based on the 230-kb mouse cytomegalovirus genome to explore new methods of vaccine delivery and of virus attenuation. With regard to virus delivery, we show that the bacterial transfer of the infectious DNA in vivo is theoretically possible but not yet a practical option. With regard to a rational approach of virus attenuation, we consider a selective deletion of viral genes that modulate the immune response of the host.     

JAK–STAT inhibition impairs K-RAS-driven lung adenocarcinoma progression

Oncogenic K-RAS has been difficult to target and currently there is no K-RAS-based targeted therapy available for patients suffering from K-RAS-driven lung adenocarcinoma (AC). Alternatively, targeting K-RAS-downstream effectors, K-RAS-cooperating signaling pathways or cancer hallmarks, such as tumor-promoting inflammation, has been shown to be a promising therapeutic strategy. Since the JAK–STAT pathway is considered to be a central player in inflammation-mediated tumorigenesis, we investigated here the implication of JAK–STAT signaling and the therapeutic potential of JAK1/2 inhibition in K-RAS-driven lung AC. Our data showed that JAK1 and JAK2 are activated in human lung AC and that increased activation of JAK–STAT signaling correlated with disease progression and K-RAS activity in human lung AC. Accordingly, administration of the JAK1/2 selective tyrosine kinase inhibitor ruxolitinib reduced proliferation of tumor cells and effectively reduced tumor progression in immunodeficient and immunocompetent mouse models of K-RAS-driven lung AC. Notably, JAK1/2 inhibition led to the establishment of an antitumorigenic tumor microenvironment, characterized by decreased levels of tumor-promoting chemokines and cytokines and reduced numbers of infiltrating myeloid derived suppressor cells, thereby impairing tumor growth. Taken together, we identified JAK1/2 inhibition as promising therapy for K-RAS-driven lung AC.     

Performance of the COMPASS-31 questionnaire with regard to autonomic nervous system testing results and medication use: a prospective study in a real-life setting

The aim of this study was to investigate the performance of the Composite Autonomic System Score-31 (COMPASS-31) questionnaire in a real-life setting in consecutive patients referred to the laboratory for objective testing of the autonomic nervous system (ANS), with the hypothesis that COMPASS-31 results differ depending on medications and findings of the tilt table test results. One hundred seventy-one consecutive patients (125 females, mean age 41.5?±?19.3) referred for testing of the ANS were enrolled. Before testing, all patients completed the recently validated Croatian version of COMPASS-31. The following data were systematically collected for all patients: age, sex, diagnoses, and medications. Results of COMPASS-31 were significantly higher in patients taking medications with a known influence on the ANS (p?<?0.001). Patients with postural orthostatic tachycardia had significantly higher orthostatic intolerance and vasomotor domains of COMPASS-31 (p?=?0.048 and p?=?0.022, respectively). Patients with a cardiovagal score?≥?1 had a significantly higher vasomotor domain of COMPASS-31 compared to patients with normal results of ANS tests (p?=?0.030). These findings suggest the COMPASS-31 might be a valuable screening tool for autonomic dysfunctions, as it is associated with impaired ANS tests, but usage of medications that modify the ANS should always be taken into account.     

孟鲁司特对儿童过敏性紫癜Toll样受体表达的影响及临床疗效观察

目的:探讨孟鲁司特对儿童过敏性紫癜Toll样受体表达的影响及临床疗效。方法:将86例过敏性紫癜(HSP)患儿,按照随机数字法分为治疗组和对照组各43例。对照组采用常规综合治疗,治疗组在对照组治疗基础上加用孟鲁司特,2~6岁4 mg/d,>6岁~14岁5 mg/d,每日一次,睡前服用。比较两组患儿的临床疗效并观察皮疹消退、腹痛缓解及关节肿痛缓解时间;实时荧光定量PCR技术检测外周血单核细胞中TLR2、TLR5及TLR9 mRNA的基因相对表达量,ELISA检测患者血清中IL-6和IL-8浓度。结果:(1)治疗组总有效率97.7%,明显高于对照组的81.4%(P<0.05),治疗组患儿的皮疹消退、腹痛缓解及关节肿痛缓解时间均显著短于对照组(P<0.05);(2)治疗组和对照组治疗后与治疗前比较,外周血单核细胞TLR2、TLR5及TLR9mRNA相对表达量均显著降低(P<0.05),且治疗后观察组外周血单核细胞TLR2、TLR5及TLR9 mRNA相对表达量均明显低于对照组(P<0.05);(3)两组过敏性紫癜患儿治疗后血清中IL-6和IL-8的表达均明显低于治疗前(P<0.05),且治疗后观察组血清中IL-6和IL-8的表达明显低于对照组(P<0.05)。结论:孟鲁司特治疗儿童HSP临床疗效显著,TLR2、TLR5及TLR9活化可能参与了HSP的免疫发病机制,孟鲁司特能影响Toll样受体(TLR2、TLR5及TLR9)以及IL-6和IL-8的蛋白表达,对儿童HSP的治疗发挥积极作用。     

Potential methods for predicting tumor radiocurability

Several predictors of tumor radiocurability are already integrated into clinical practice, for example, tumor size, gross morphology (that is, infiltrative or exophytic), histologic type and grade. These are nonspecific and relatively imprecise. The aim of research into predictive assays is not only to refine the discrimination of existing predictors, but also to suggest specific experimental approaches for overcoming tumor radioresistance in individual patients. Two broad categories of predictive assays can be defined: direct and indirect measurement of tumor cell survival and/or repair capability following irradiation, and measurement of cellular and extracellular parameters affecting radiosensitivity. The ongoing research at The University of Texas M. D. Anderson Hospital is overviewed to illustrate potential methods for predicting radiocurability.     

Innovative Calcium Carbonate-Based Products to Repair Cracked Cement Mortars

The durability of Portland cement mortars is often affected by environmental factors, which can cause physicochemical and mechanical degradation processes. In this study, the performance of three products, calcium acetoacetate and calcium tetrahydrofurfuryloxide dissolved in two different solvents developed and tested as stone consolidants, was evaluated in terms of crack filling or sealing and consolidation. Realistic cracks were induced in quasibrittle cement mortar prisms using a custom-designed test rig. The effectiveness and the performance of the considered treatments, investigated on specimens, were evaluated by optical and scanning electron microscopy, colourimetry, water absorption rate, ultrasonic pulse velocity, and surface hardness measurements. Results revealed that, in the examined conditions, the products were more suitable as surface consolidants than as crack fillers.