Fatal hemophagocytic lymphohistiocytosis-induced multiorgan dysfunction secondary to Burkholderia pseudomallei sepsis: A case report.

BACKGROUND: Burkholderia pseudomallei (B. pseudomallei) is a short, straight, medium-sized Gram-negative bacterium that mostly exists alone, without a capsule or spores, has more than three flagella at one end, and actively moves. B. pseudomallei confers high morbidity and mortality, with frequent granulocytopenia in B. pseudomallei sepsis-related deaths. However, mortality may be related to hemophagocytic lymphohistiocytosis (HLH) secondary to B. pseudomallei infection. CASE SUMMARY: A 12-year-old female was referred from a local hospital to the pediatric intensive care unit with suspected septic shock and fever, cough, dyspnea, and malaise. After admission, supportive symptomatic treatments including fluid resuscitation, anti-infective therapy, mechanical ventilation, and a vasoactive drug maintenance cycle were carefully initiated. The patient became unconscious, her blood pressure could not be maintained even under the exposure of vasoactive drugs, and she experienced cardiorespiratory arrest. The patient died due to ineffective high-quality in-hospital cardiopulmonary resuscitation. A subsequent bone marrow smear examination revealed extensive phagocytosis, and the blood culture was positive for B. pseudomallei. Family history revealed a sibling death from B. pseudomallei sepsis 5 years earlier. CONCLUSION: The higher mortality rate in patients with B. pseudomallei sepsis may be related to secondary HLH after infection, wherein multiorgan dysfunction syndrome may be directly related to infection or immune damage caused by secondary HLH. Patients with B. pseudomallei can be asymptomatic and can become an infective source.

Lysine crotonylation of SERCA2a correlates to cardiac dysfunction and arrhythmia in Sirt1 cardiac-specific knockout mice.

Protein post-translational modifications (PTMs) are important regulators of protein functions and produce proteome complexity. SIRT1 has NAD+-dependent deacylation of acyl-lysine residues. The present study aimed to explore the correlation between lysine crotonylation (Kcr) on cardiac function and rhythm in Sirt1 cardiac-specific knockout (ScKO) mice and related mechanism. Quantitative proteomics and bioinformatics analysis of Kcr were performed in the heart tissue of ScKO mice established with a tamoxifen-inducible Cre-loxP system. The expression and enzyme activity of crotonylated protein were assessed by western blot, co-immunoprecipitation, and cell biology experiment. Echocardiography and electrophysiology were performed to investigate the influence of decrotonylation on cardiac function and rhythm in ScKO mice. The Kcr of SERCA2a was significantly increased on Lys120 (1.973 folds). The activity of SERCA2a decreased due to lower binding energy of crotonylated SERCA2a and ATP. Changes in expression of PPAR-related proteins suggest abnormal energy metabolism in the heart. ScKO mice had cardiac hypertrophy, impaired cardiac function, and abnormal ultrastructure and electrophysiological activities. We conclude that knockout of SIRT1 alters the ultrastructure of cardiac myocytes, induces cardiac hypertrophy and dysfunction, causes arrhythmia, and changes energy metabolism by regulating Kcr of SERCA2a. These findings provide new insight into the role of PTMs in heart diseases.

The role of atria in ventricular fibrillation after continuous-flow left ventricular assist device implantation in ovine model.

Objectives: This study attempted to explore the hemodynamics and potential mechanisms driving pulmonary circulation in status of ventricular fibrillation (VF) following continuous-flow left ventricular assist device (CF-LVAD) implantation. Methods: An ovine CF-LVAD model was built in small-tailed Han sheep, with the pump speed set as 2,400 rpm. VF was induced following ventricular tachycardia using a temporary pacemaker probe to stimulate the right and left ventricular free walls. The central venous pressure (CVP), pump flow (PF), pulmonary artery flow (PAF) and other major indicators were observed and recorded after VF. Results: Low-flow systemic and pulmonary circulation could be sustained for 60 min under VF with sinus atrial rhythm after CF-LVAD implantation. The CVP gradually increased. The mean PF declined from 1.80 to 1.20 L/min, and the mean PAF decreased from 1.62 L/min to 0.87 L/min. Under VF with atrial fibrillation, the systemic and pulmonary circulation couldn't be sustained. The CVP jumped from the 5 mmHg baseline to 12 mmHg, the mean PF rapidly decreased from 3.45 L/min to 0.79 L/min, and the PAF declined from 3.94 L/min to 0.77 L/min. Conclusion: The atrial rhythm and function might be essential for the circulation maintenance in patients with VF after CF-LVAD implantation.

[Effect of angiotensin II and its receptor antagonist on electrophysiology and L-type calcium current in guinea cardiac myocytes].

OBJECTIVE: To evaluate the effect of angiotensin II (Ang II) and its receptor antagonist on action potential duration and L-type calcium current density of cardiac myocytes. METHODS: Single myocyte of the ventricle in guinea was isolated. Action potentials were recorded using a conventional glass microelectrode filled with 3 mol/L KCl solution. Membrane patch clamp whole cell recording technique was used to investigate L-type calcium current maximum in holding potential of -40 mV, length of time 200 ms, command potential 0 mV. RESULTS: Ang II induced arrhythmia of multiple electrophysiologic mechanisms. Action potential amplitude, 90% of action potential duration (APD90), and resting membrane potential (RMP) were significantly decreased or shortened after being perfused Ang II for 1 minute compared with controls. 30% of action potential duration (APD30), 50% of action potential duration (APD50), effective refractory period (ERP) were also shortened significantly after perfused Ang II for 3 minutes compared with controls. Ang II increased the L-type calcium maximum current density after a perfusion of 5 minutes, but losartan perfusion for 1 minute decreased the L-type calcium maximum current density, and it further decreased after perfusion for 3 minutes. However, the current voltage relationship curve was unchanged. CONCLUSION: Ang II could decrease amplitude of monophasic action potential, rest membrane potential, shorten duration of monophasic action potential and effective refractory period, increase maximum current density of voltage dependent L-type calcium, and possess the effect of inducing arrhythmia. Losartan decreased maximum current density of voltage dependent L-type calcium.

[Comparison study on diagnostic and prognostic value of N-terminal pro-brain natriuretic peptide and atrium natriuretic peptide in chronic congestive heart failure].

OBJECTIVE: To investigate the diagnostic and prognostic value of N-terminal pro-brain natriuretic peptide (NT-proBNP) and atrium natriuretic peptide (ANP) in chronic congestive heart failure. METHODS: Seventy-one coronary heart disease patients were enrolled in the study. Among them 58 patients were accompanied by heart failure and 13 with no heart failure. Plasma NT-ProBNP was determined with enzyme linked immunoadsorbent assay method, and plasma ANP was determined with radioimmunoassay method. The results were compared with those of 30 healthy individuals. All patients were followed up accordingly. RESULTS: Compared with patients with no heart failure and healthy individuals, the patients with heart failure had a higher plasma NT-proBNP and ANP contents. Cardiac function grade IV patients had a significantly higher plasma NT-ProBNP than cardiac function grade II and III patients, and their plasma ANP level was significantly higher than that of cardiac function grade III patients, but there was no significantly difference in ANP content between cardiac function grade IV and II. The diagnostic sensitivity of NT-proBNP and ANP was 94.38% and 75.86%, respectively. The diagnostic specificity of NT-proBNP and ANP was 96.67%, 83.33%, respectively. In the heart failure group, after being followed up for (11.35+/-1.69) months, it was found that there was no significant difference in the plasma NT-proBNP and ANP between the deaths and surviving patients. CONCLUSION: The diagnostic value of NT-proBNP in chronic heart failure is higher than that of ANP. According to our follow-up result, the plasma NT-proBNP and ANP can not be relied upon to predict short-term cardiogenic death in heart failure.