Sequential treatment of severe pneumonia with respiratory failure and its influence on respiratory mechanical parameters and hemodynamics

BACKGROUND The pathophysiological characteristics of severe pneumonia complicated by respiratory failure comprise pulmonary parenchymal changes leading to ventilation imbalance,alveolar capillary injury,pulmonary edema,refractory hypoxemia,and reduced lung compliance.Prolonged hypoxia can cause acid-base balance disorder,peripheral circulatory failure,blood-pressure reduction,arrhythmia,and other adverse consequences.AIM To investigate sequential mechanical ventilation’s effect on severe pneumonia complicated by respiratory failure.METHODS We selected 108 patients with severe pneumonia complicated by respiratory failure who underwent mechanical ventilation between January 2018 and September 2020 at the Luhe Hospital’s Intensive Care Unit and divided them into sequential and regular groups according to a randomized trial,with each group comprising 54 patients.The sequential group received invasive and non-invasive sequential mechanical ventilation,whereas the regular group received invasive mechanical ventilation.Blood-gas parameters,hemodynamic parameters,respiratory mechanical parameters,inflammatory factors,and treatment outcomes were compared between the two groups before and after mechanical-ventilation treatment.RESULTS The arterial oxygen partial pressure and stroke volume variation values of the sequential group at 24,48,and 72 h of treatment were higher than those of the conventional group(P<0.05).The carbon dioxide partial pressure value of the sequential group at 72 h of treatment and the Raw value of the treatment group at 24 and 48 h were lower than those of the conventional group(P<0.05).The pH value of the sequential group at 24 and 72 h of treatment,the central venous pressure value of the treatment at 24 h,and the Cst value of the treatment at 24 and 48 h were higher than those of the conventional group(P<0.05).The tidal volume in the sequential group at 24 h of treatment was higher than that in the conventional group(P<0.05),the measured values of interleukin-6 and tumor necrosis factor-αin the sequential group at 72 h of treatment were lower than those in the conventional group(P<0.05),and the total time of mechanical ventilation in the sequential group was shorter than that in the conventional group,with a statistically significant difference(P<0.05).CONCLUSION Treating severe pneumonia complicated by respiratory failure with sequential mechanical ventilation is more effective in improving respiratory system compliance,reducing inflammatory response,maintaining hemodynamic stability,and improving patient blood-gas levels;however,from this study’s perspective,it cannot reduce patient mortality.

Pulmonary and tricuspid regurgitation after Tetralogy of Fallot repair: A case report

BACKGROUND Tetralogy of Fallot(TOF)is one of the most common congenital heart defects,and surgery is the primary treatment.There are no precise guidelines on the treatment protocol for tricuspid regurgitation(TR)as a common complication of TOF repair.The timing for treatment in patients presenting with valve regurgitation after TOF repair is often difficult to determine.Here,we report the first case of sequential treatment of pulmonary and TR using interventional therapy.CASE SUMMARY We present the case of a 52-year-old female patient,who had a history of TOF repair at a young age.A few years later,the patient presented with pulmonary and tricuspid regurgitation.The symptoms persisted and TR worsened following percutaneous pulmonary valve implantation.Preoperative testing revealed that the patient’s disease had advanced to an intermediate to advanced stage and that her general health was precarious.Because open-heart surgery was not an option for the patient,transcatheter tricuspid valve replacement was suggested.This procedure was successful,and the patient recovered fully without any adverse effects.This case report may serve as a useful resource for planning future treatments.CONCLUSION Treatment of both valves should be considered in patients with tricuspid and pulmonary regurgitations following TOF repair.The interventional strategy could be an alternative for patients with poor general health.

BRD2 induces drug resistance through activation of the RasGRP1/Ras/ERK signaling pathway in adult T-cell lymphoblastic lymphoma

Background:Adult patients with T-cell lymphoblastic lymphoma(T-LBL)are treated with high-intensity chemotherapy regimens,but the response rate is still unsatisfactory because of frequent drug resistance.We aimed to investigate the potential mechanisms of drug resistance in adults with T-LBL.Methods:Gene expression microarray was used to identify differential mRNA expression profiles between chemotherapy-resistant and chemotherapy-sensitive adult T-LBL tissues.Real-time PCR and immunohistochemistry were performed to detect the expression of bromodomain-containing protein 2(BRD2)and c-Myc in fresh-frozen T-LBL tissues from 85 adult patients.The Ras pull-down assay was performed to monitor Ras activation.Chromatin immunoprecipitation assays were used to analyze the binding of E2F transcription factor 1(E2F1)/BRD2 to the RAS guanyl releasing protein 1(RasGRP1)promoter region.The drug resistance effect and mechanism of BRD2 were determined by both in vivo and in vitro studies.Results:A total of 86 chemotherapy resistance-related genes in adult T-LBL were identified by gene expression microarray.Among them,BRD2 was upregulated in chemotherapy-resistant adult T-LBL tissues and associated with worse progressionfree survival and overall survival of 85 adult T-LBL patients.Furthermore,BRD2 suppressed doxorubicin(Dox)-induced cell apoptosis both in vitro and in vivo.The activation of RasGRP1/Ras/ERK signaling might contribute to the Dox resistance effect of BRD2.Besides,OTX015,a bromodomain and extra-terminal(BET)inhibitor,reversed the Dox resistance effect of BRD2.Patient-derived tumor xenograft demonstrated that the sequential use of OTX015 after Dox showed superior therapeutic effects.Conclusions:Our data showed that BRD2 promotes drug resistance in adult T-LBL through the RasGRP1/Ras/ERK signaling pathway.Targeting BRD2 may be a novel strategy to improve the therapeutic efficacy and prolong survival of adults with TLBL.