Case report: Novel TBX5-related pathogenic mechanism of Holt-Oram syndrome.

Introduction: Holt-Oram syndrome (HOS) is a rare genetic disorder characterized by upper limb abnormalities, congenital heart defects, and/or conduction abnormalities. Sequence alteration of T-box transcription factor 5 (TBX5) is correlated with the incidence of HOS. Case description: We present the case of a 24-year-old female with upper limb alterations (congenital dysplasia in the wrist and elbow joints) and an anomalous left main trunk arising from the right coronary sinus. The patient inherited a base T (reference C) at rs883079 from her mother and base C (reference T) at rs10850326 from her father, both of which belong to the 3'-untranslated region (UTR) of the TBX5 gene; no alterations in TBX5 expression or single-nucleotide polymorphisms (SNPs) in other exon areas were found. We explored the effects of TBX5 on cardiomyocytes using the HL-1 cell line and TBX5-knockdown cells. Discussion: Quantitative polymerase chain reaction analysis demonstrated that TEKT2, TEKT4, and SPTB expression decreased after TBX5 knockdown, while chromatin immunoprecipitation analysis further revealed that TBX5 binds to the TEKT2, TEKT4, and SPTB promoter regions to promote gene transcription. Our findings support a novel TBX5-related pathogenic mechanism in HOS.

Anticoagulation with nafamostat mesilate during extracorporeal life support.

Nafamostat mesylate (NM) affects coagulation and fibrinolysis and impedes obesity-associated protein demethylase activity, which regulates Na+/K+ transport properties and the NF-κB signaling pathway. NM significantly decreases macrophage, neutrophil, and T lymphocyte infiltration, thereby reducing inflammation and apoptosis after reperfusion and promoting recovery in patients with severe conditions such as near-fatal asthma and cardiac arrest. Extracorporeal life support (ECLS) devices are used for cardiac and/or pulmonary support as a bridge to recovery, decision, surgery, or transplant in patients with refractory cardio-circulatory or respiratory diseases and provide essential opportunities for organ support and patient survival. However, they can lead to some potential adverse events such as hemorrhage and thrombosis. NM provides a sustained innate immune response of coagulation and anti-inflammation in extracorporeal circuits, principally due to its activation of the contact and complement systems. Heparin is the main anticoagulant used in extracorporeal circuits; however, it may cause massive bleeding and heparin-induced thrombocytopenia. Although no antidote is available, NM has a very short half-life of approximately 8-10 min and might have positive effects on patients who require coagulation and anti-inflammation. NM has been used for anticoagulation in continuous renal replacement therapy, extracorporeal membrane oxygenation, hemodialysis, and left ventricular assist devices. In this review, we focused on the pharmacology, monitoring parameters, and considerations for the special use of NM in patients receiving ECLS. Our findings suggest that systemic anticoagulation with NM during ECLS might be a feasible and safe alternative with several advantages for critically ill patients with high-risk bleeding and might improve their prognosis.

[The use of extracorporeal membrane oxygenation in sustaining pulmonary function patients with influenza A H1N1].

OBJECTIVE: To summarize the clinical method and initial experience of extracorporeal membrane oxygenation (ECMO) supportive treatment in influenza A H1N1 serious patients. METHODS: In 5 critically ill patients with influenza A H1N1, their arterial oxygen saturation was 0.70 to 0.85 with oxygen concentration (FiO(2)) 1.00 under mechanical ventilation. In these 5 patients, 3 males and 2 females, vein-vein mode ECMO bypass (femoral vein-internal jugular vein) was carried out to assist pulmonary function. The ratio between ECMO oxygen flow and blood flow was 2-1:1, FiO(2) was 0.21 to 1.00, FiO(2) for mechanical ventilation was 0.30 to 0.70, and positive end expiratory pressure (PEEP) was 5-10 cm H(2)O (1 cm H(2)O= 0.098 kPa). Activated coagulation time (ACT) was maintained at 160-250 s. When artery oxygen saturation and artery-venous blood gas became normal on discontinuation of ECMO, ECMO was weaned, and venous cannulas were removed. Mechanical ventilation was continued. RESULTS: In 5 patients the assisting time of ECMO was 48-330 hours, the mean duration was 178.2 hours. ECMO assisted flow was 2.4-4.0 L/min. The observation time after stoppage of ECMO was 4-24 hours. Four patients were weaned from ECMO, with continuation of assisted respiration successfully. One patient died because the family member gave up hope and the treatment was stopped. CONCLUSION: Vein-vein mode ECMO bypass through femoral vein-internal jugular vein can offer effective aid to pulmonary function in influenza A H1N1 patients who are critically ill. The strategy can win time for the patients to be able to continue mechanical ventilation treatment.