When sepsis affects the heart: A case report and literature review.

A 59-year-old nursing home patient with Down syndrome was brought to the internal medicine department of our hospital due to fever, cough without expectorate, and dyspnea. A thoracic computed tomography revealed the presence of bilateral basal parenchymal opacities. Her condition deteriorated after admission and troponin reached a peak serum concentration of 16.9 ng/mL. The patient was in cardiogenic shock. In addition to fluid resuscitation, vaso-active amine infusion was administered to achieve hemodynamic stabilization. The differential diagnosis investigated possible pulmonary embolism, myocardial infarction, and myocarditis. Furthermore, a second transthoracic echocardiogram suggested Tako-Tsubo syndrome. This is a septic patient. The purpose of this manuscript is to review studies which formerly examined the possible association between high levels of troponin and mortality to see if it can be considered a positive predictive factor of fatal prognosis as the case of thrombocytopenia, already a positive independent predictive factor of multiple organ failure syndrome, and generally to characterize risk profile in a septic patient.

QT Indexes in Cirrhotic Patients: Relationship with Clinical Variables and Potential Diagnostic Predictive Value.

BACKGROUND AND AIMS: A wide spectrum of cardiovascular changes characterizes cirrhosis, ranging from subclinical alterations to hyperkinetic syndrome. We looked for ECG markers of ventricular repolarization in a population of patients with cirrhosis in comparison to patients without cirrhosis and we investigated the relationship between these and other clinical and laboratory variables. METHODS: In 149 patients with cirrhosis and 152 controls, we measured QT maximum interval (QTmax), QT corrected interval (QTc), QT minimum interval (QTmin), QT dispersion (QTdisp), QT peak and T peak-to-end (TpTe). RESULTS: In subjects with cirrhosis, in comparison with controls, we observed a higher mean QTmax, mean QTc, mean QTmin, mean QTdisp and mean TpTe. At Cox regression analysis, diastolic blood pressure and beta-blocker treatment were significantly associated with mean QTmax, hypertension with mean QTmin and mean QTc, diastolic blood pressure, beta-blockers and ACE-inhibitors/ARBs with QT disp, and beta-blockers with TpTe. Analysis of ROC curves showed a significant area under curve towards cirrhosis diagnosis, respectively, for a cut-off value of > 400 msec of QTmax, > 360 msec of QTmin, > 450 msec of QTc, > 105 msec of TpTe and > 55 msec of QTdisp. CONCLUSIONS: Our study shows that QT indexes are altered in cirrhotic patients and have a potential diagnostic predictive value.

Neuron protection as a therapeutic target in acute ischemic stroke.

Involvement of various neurotransmitters and neuromodulators have been shown to contribute to the ischemic injury and neuronal death associated with stroke Role of excitatory amino acid receptor activation, calcium overload, nitric oxide, and oxidative stress in the pathogenesis of ischemic brain damage is well established. Several new strategies are currently emerging, based on recent advances in our understanding of molecular pathways that could be considered as potential therapeutic targets. For example reactive oxygen species (ROS) are important contributors to the secondary injury cascade following traumatic brain injury (TBI), and ROS inhibition has consistently been shown to be neuroprotective following experimental TBI and brain ischemia. Furthermore, more recently, some authors concluded that nonanticoagulant 3K3A-APC exhibits greater neuroprotective efficacy with no risk for bleeding compared with drotrecogin-alfa activated, a hyperanticoagulant form of APC. Excessive calcium entry into depolarized neurons contributes significantly to cerebral tissue damage after ischemia. Included in the sequence of events leading to neuronal death in ischemic tissue following stroke is an excessive and toxic rise in the intracellular Ca(2+)-concentration, predominantly due to an influx of Ca2+ through nonselective cation-channels as well as Ca(2+)-channels.. Some authros conducted a study to investigate whether the enhancement of GABA receptor activity could inhibit NMDA receptor-mediated nitric oxide (NO) production by neuronal NO synthase (nNOS) in brain ischemic injury. The results showed that both the GABA(A) receptor agonist muscimol and the GABA(B) receptor agonist baclofen had neuroprotective effect, and the combination of two agonists could significantly protect neurons against death induced by ischemia/reperfusion. On this basis we conclude that neuroprotection for ischemic stroke refers to strategies, applied singly or in combination, that antagonize the injurious biochemical and molecular events that eventuate in irreversible ischemic injury. There has been a recent explosion of interest in this field, with over 1000 experimental papers and over 400 clinical articles appearing within the past 6 years. These studies, in turn, are the outgrowth of three decades of investigative work to define the multiple mechanisms and mediators of ischemic brain injury, which constitute potential targets of neuroprotection.

Inflammation as a therapeutic target in acute ischemic stroke treatment.

Animal models of focal ischaemia induced by middle cerebral artery occlusion (MCAO) provide most evidence for cellular inflammatory responses in stroke. Permanent MCAO results in a modest neutrophil infiltration at 24 h after ischaemia, predominantly around arterial vessels at the margins of infarction, whereas MCAO with subsequent reperfusion is associated with substantial infiltration by neutrophils throughout the entire infarct. Several studies show that C-reactive protein (CRP), an inflammatory marker, is associated with stroke outcomes and future vascular events. Several drugs, especially hydroxymethylglutaryl coenzyme A reductase inhibitors (statins), have been demonstrated to reduce hsCRP levels independently of their effects on plasma cholesterol. Various cytokines were shown to be expressed in the injured brain. Recent investigations demonstrated that mRNAs of above cytokines were induced in the ischemic rat brain. TNF-alpha is a pleiotropic cytokine that mediates key roles in many physiological and pathological cellular processes including acute and chronic inflammation, programmed cell death or apoptosis, anti-tumor responses, and infection. Pharmaceutical industry to search a small molecule TNF inhibitor have taken multiple strategies. Significant protection after in vivo oral use of SB-239063 from brain injury and neurological deficits was observed in one study. In the same study significant protection from brain injury and neurological deficits was also demonstrated due to i.v post-stroke treatment with the same compound. Leukocyte-endothelial adhesion process consists of several steps, beginning with rolling of the leukocyte on the endothelial surface until it has slowed down to such a degree that it sticks to the endothelium. Treatment with a murine anti-ICAM-1 antibody (enlimomab) has been investigated in patients with acute ischemic stroke in the Enlimomab Acute Stroke Trial (EAST). Unfortunately, the case fatality rate in this trial was significantly higher in the enlimomab patient group than in the placebo group. Furthermore, experimental data have shown that focal cerebral ischemia induces a time-dependent activation of granulocytes, lymphocytes, and macrophages. Dissipation of ATP by CD39 reduced P2X7 receptor stimulation and thereby suppressed baseline leukocyte alphaMbeta2-integrin expression. As alphaMbeta2-integrin blockade reversed the postischemic, inflammatory phenotype of Cd39-/- mice, these data suggest that phosphohydrolytic activity on the leukocyte surface suppresses cell-cell interactions that would otherwise promote thrombosis or inflammation.