Infective endocarditis in patients with pyogenic spondylodiscitis: implications for diagnosis and therapy.

OBJECTIVEThe incidence of patients with pyogenic spinal infection is increasing. In addition to treatment of the spinal infection, early diagnosis of and therapy for coexisting infections, especially infective endocarditis (IE), is an important issue. The aim of this study was to evaluate the proportion of coexisting IE and the value of routine transesophageal echocardiography (TEE) in the management of these patients.METHODSThe medical history, laboratory data, radiographic findings, treatment modalities, and results of TEE of patients admitted between 2007 and 2017 were analyzed.RESULTSDuring the abovementioned period, 110 of 255 total patients underwent TEE for detection of IE. The detection rate of IE between those patients undergoing and not undergoing TEE was 33% and 3%, respectively (p < 0.0001). Thirty-six percent of patients with IE needed cardiac surgical intervention because of severe valve destruction. Chronic renal failure, heart failure, septic condition at admission, and preexisting heart condition were significantly associated with coexisting IE. The mortality rate in patients with IE was significantly higher than in patients without IE (22% vs 3%, p = 0.002).CONCLUSIONSTEE should be performed routinely in all patients with spondylodiscitis.

Thromboembolic infarction caused by an unknown patent foramen ovale 30 years after VA shunt insertion: a case report and review of the literature.

BACKGROUND: Ventriculoatrial shunt (VA) insertion is one of the possible surgical procedures to treat hydrocephalus. However, it is also associated with several complications such as obstruction and shunt infection as well as life-threatening complications like intraatrial thrombus or thrombosis on the distal catheter. In this case report, we share a rare case of a patient with a VA shunt, who was admitted to our hospital with a stroke. CASE DESCRIPTION: A 56-year-old female patient with suspected acute stroke was admitted to the stroke unit. CT and MRI scans showed multiple cerebral infarctions in both hemispheres. The transesophageal echocardiography (TEE) showed at the tip of the VA shunt catheter, which was implanted about 30 years ago due to aqueduct stenosis, also a thrombotic formation as the reason of stroke. Interestingly, the tip of the catheter was not in the right atrium as expected, but in the left atrium. Further evaluation showed a patent foramen ovale (PFO), through which the catheter migrated from the right to the left side. At first, conservative treatment with anticoagulation was started with the aim to dissolve the thrombotic formation; however, a control TEE showed an unchanged mass at the catheter tip. Therefore, a ventriculoperitoneal shunt was implanted and the proximal shunt catheter was removed with an additional closure of the PFO by our heart surgeons. Postoperatively, the patient was discharged 10 days later in good condition to a rehabilitation center. CONCLUSIONS: Thromboembolic events due to a PFO are rare but possible life-threatening complication after VA shunt insertion. Therefore, preoperative cardiac diagnostic might be clinically relevant prior to a VA shunt implantation to avoid such complications.

High-sensitive troponin is associated with subclinical imaging biosignature of inflammatory cardiovascular involvement in systemic lupus erythematosus.

BACKGROUND: Cardiovascular (CV) involvement in patients with systemic lupus erythematosus (SLE) is presumably subclinical for the major part of its evolution. We evaluated the associations between high-sensitive troponin T (hs-TropT), a sensitive marker of myocardial injury, and CV involvement using cardiac magnetic resonance (CMR). METHODS AND RESULTS: This is a two-centre (London and Frankfurt) CMR imaging study at 3.0 Tesla of consecutive 92 patients with SLE free of cardiac symptoms, undergoing screening for cardiac involvement. Venous samples were drawn and analysed post-hoc for cardiac biomarkers, including hs-TropT, high-sensitive C reactive protein and N-terminal pro brain natriuretic peptide. Compared with age-matched/gender-matched non-SLE controls (n=78), patients had significantly raised cardiac biomarker levels, native T1 and T2, aortic and ventricular stiffness, and reduced global longitudinal strain (p<0.01). In SLE, hs-TropT was significantly and independently associated with native T2, followed by the models including native T1 and aortic stiffness (Χ2 0.462, p<0.01). There were no relationships between hs-TropT and age, gender, CV risk factors, duration of systemic disease, cardiac structure or function, or late gadolinium enhancement. CONCLUSIONS: Patients with SLE have a high prevalence of subclinical myocardial injury as demonstrated by raised high-sensitive troponin levels. CMR with T2 mapping reveals myocardial oedema as the strongest predictor of hs-TropT release, underscoring the inflammatory interstitial remodelling as the main mechanism of injury. Patients without active myocardial inflammation demonstrate diffuse interstitial remodelling and increased vascular stiffness. These findings substantiate the role of CMR in screening of subclinical cardiac involvement. TRIAL REGISTRATION NUMER: NCT02407197; Results.

Rapid recruitment of temporally distinct vascular gene sets by estrogen.

Cardiovascular disease is the leading cause of mortality for both men and women in developed countries. The sex steroid hormone estrogen is required for normal vascular physiology. Estrogen functions by binding to intracellular estrogen receptors (ER), ERalpha and ERbeta, ligand-activated transcription factors that are expressed in both vascular endothelial and smooth muscle cells. We recently demonstrated that long-term (8 d) estrogen treatment in vivo in mice recruits distinct vascular gene sets mediated by ERalpha and ERbeta and that the promoters from these gene sets are enriched for binding sites of specific transcription factors, leading to the hypothesis that estrogen initiates a cascade of early transcriptional events that modulate gene expression in the vasculature. Here we test this hypothesis using gene expression profiling to examine initial transcriptional events (2-8 h) mediated by estrogen in blood vessels. Our data reveal that 1) estrogen regulates temporally distinct cascades of vascular gene expression, 2) initially, estrogen-mediated vascular gene repression predominates, 3) the earliest estrogen-recruited gene program is enriched in vascular transcription factors that can interact with binding sites present in estrogen-regulated vascular genes recruited subsequently, and 4) estrogen-regulated genes recruited next have specific functions, including lipid metabolism and cellular growth and proliferation that are potentially important for estrogen's known vascular functions. In summary, estrogen directly and rapidly recruits specific transcriptional factors that then propagate distinct cascades of gene expression. These data define the temporal recruitment of specific vascular genes by estrogen and enable further analysis of the mechanisms by which estrogen directly regulates vascular function.

Competition for Gßγ dimers mediates a specific cross-talk between stimulatory and inhibitory G protein α subunits of the adenylyl cyclase in cardiomyocytes.

Heterotrimeric G proteins are key regulators of signaling pathways in mammalian cells. Beyond G protein-coupled receptors, the amount and mutual ratio of specific G protein α, ß, and γ subunits determine the G protein signaling. However, little is known about mechanisms that regulate the concentration and composition of G protein subunits at the plasma membrane. Here, we show a novel cross-talk between stimulatory and inhibitory G protein α subunits (Gα) that is mediated by G protein ßγ dimers and controls the abundance of specific Gα subunits at the plasma membrane. Firstly, we observed in heart tissue from constitutively Gαi2- and Gαi3-deficient mice that the loss of Gαi2 and Gαi3 was accompanied by a slight increase in the protein content of the nontargeted Gαi isoform. Therefore, we analyzed whether overexpression of selected Gα subunits conversely impairs endogenous G protein α and ß subunit levels in cardiomyocytes. Integration of overexpressed Gαi2 subunits into heterotrimeric G proteins was verified by co-immunoprecipitation. Adenoviral expression of increasing amounts of Gαi2 led to a reduction of Gαi3 (up to 90 %) and Gαs (up to 75 %) protein levels. Likewise, increasing amounts of adenovirally expressed Gαs resulted in a linear 75 % decrease in both Gαi2 and Gαi3 protein levels. In contrast, overexpression of either Gαi or Gαs isoform did not influence the amount of Gαo and Gαq, both of which are not involved in the regulation of adenylyl cyclase activity. The mRNA expression of the disappearing endogenous Gα subunits was not affected, indicating a posttranslational mechanism. Interestingly, the amount of endogenous G protein ßγ dimers was not altered by any Gα overexpression. However, the increase of Gßγ level by adenoviral expression prevented the loss of endogenous Gαs and Gαi3 in Gαi2 overexpressing cardiomyocytes. Thus, our results provide evidence for a novel mechanism cross-regulating adenylyl cyclase-modulating Gαi isoforms and Gαs proteins. The Gα subunits apparently compete for a limited amount of Gßγ dimers, which are required for G protein heterotrimer formation at the plasma membrane.