Background —Tumor necrosis factor-α (TNF-α) is a multifunctional cytokine that has been detected in several human cardiac-related conditions, including congestive heart failure and septic cardiomyopathy. In these conditions, the origin of TNF-α secretion is, at least in part, cardiac myocytes. Methods and Results —To determine the consequences of TNF-α production by cardiac myocytes in vivo, we developed transgenic mice in which expression of a murine TNF-α coding sequence was driven by the murine α-myosin heavy chain promoter. Four transgenic founders developed an identical illness consisting of tachypnea, decreased activity, and hunched posture. In vivo, ECG-gated MRI of symptomatic transgenic mice documented a severe impairment of cardiac function evidenced by biventricular dilatation and depressed ejection fractions. All transgenic mice died prematurely. Pathological examination of affected animals revealed a globular dilated heart, bilateral pleural effusions, myocyte apoptosis, and transmural myocarditis in both the right and left ventricular free walls, septum, and atrial chambers. In all terminally ill animals, there was significant biventricular fibrosis and atrial thrombosis. Conclusions —This is the first report detailing the effects of tissue-specific production of TNF-α by cardiac myocytes in vivo. These findings indicate that production of TNF-α by cardiac myocytes is sufficient to cause severe cardiac disease and support a causal role for this cytokine in the pathogenesis of human cardiac disease.

Forty-four percent of pediatric patients who failed conventional cardiopulmonary resuscitation from in-hospital cardiopulmonary arrest and who were reported to the National Registry of CardioPulmonary Resuscitation database as treated with extracorporeal cardiopulmonary resuscitation survived to hospital discharge. The majority of survivors with recorded neurologic outcomes were favorable. Patients with cardiac illness category were more likely to survive to hospital discharge after treatment with extracorporeal cardiopulmonary resuscitation. Extracorporeal cardiopulmonary resuscitation should be considered for select pediatric patients refractory to conventional in-hospital resuscitation measures.

Patients who received infusions of fentanyl for at least 5 days were just as likely to complete a low-dose methadone taper as a high-dose methadone taper. Because of the risks of both withdrawal and oversedation with any fixed methadone schedule, the methadone dose must be adjusted according to each patient's response.

Earlier initiation of continuous renal replacement therapy was associated with lower mortality in this cohort of critically ill children. Future studies should focus on early identification of such children who may benefit from early continuous renal replacement therapy initiation.

The presence, severity and duration of early fluid are associated with increased ICU mortality in children admitted to the pediatric ICU in shock states.

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rs12252 was not associated with susceptibility to influenza-related critical illness in children or with critical illness severity. Our data also do not support it being a splice site.

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