Intrapleural Thrombolytics as First Line Therapy for Complicated Parapneumonic Effusions and Empyema in Patients with Prohibitive Surgical Risk: A Cases Series.

OBJECTIVE: In complicated parapneumonic effusion or Empyema, approximately 25% of patients require surgical intervention which can be associated with a mortality risk of almost 20%. However, the use combination of rt-tPA and DNase in elderly patients with prohibitive surgical risk has improved outcomes. The main goal of our study is to highlight the utility of intrapleural thrombolysis in patients with prohibitive risk for surgery. METHODS: A retrospective record review study of patients (n=23) with complicated parapneumonic pleural effusion or empyema treated with tPA and DNase from January 1st of 2015 to March 18th, 2019 at VACHCS. Data collected to describe the outcome of intrapleural thrombolytics included demographic, pleural fluid analysis, surgical risk assessment, diagnosis and initiation treatment day, doses, chest imaging, drainage rate, chest tube size and average days in place, inflammatory markers, microbiology, antibiotics, and complications. RESULTS: Only 21.7% of patients were considered surgical candidates. Seventy-four percent had a 30-day post-surgical mortality risk of > 2.5% using the National Surgery Office (NSO) risk calculator. Post-operative inpatient stay was 99.7% and estimated post operative ICU stay average was >80%. Primary outcome (pleural drainage improvement) obtained in 73.9%. Most common serious complications included sepsis (52.2%) and nonserious was residual hydropneumothorax (47.8%). CONCLUSION: This study demonstrates that administration of intrapleural thrombolytics through a percutaneous pleural catheter achieved successful drainage safely and without the need for surgical interventions in a selected group of advanced age, elderly patients with pleural infections who were deemed to be high surgical risk.

CD13 is essential for inflammatory trafficking and infarct healing following permanent coronary artery occlusion in mice.

AIMS: To determine the role of CD13 as an adhesion molecule in trafficking of inflammatory cells to the site of injury in vivo and its function in wound healing following myocardial infarction induced by permanent coronary artery occlusion. METHODS AND RESULTS: Seven days post-permanent ligation, hearts from CD13 knockout (CD13(KO)) mice showed significant reductions in cardiac function, suggesting impaired healing in the absence of CD13. Mechanistically, CD13(KO) infarcts showed an increase in small, endothelial-lined luminal structures, but no increase in perfusion, arguing against an angiogenic defect in the absence of CD13. Cardiac myocytes of CD13(KO) mice showed normal basal contractile function, eliminating myocyte dysfunction as a mechanism of adverse remodelling. Conversely, immunohistochemical and flow cytometric analysis of CD13(KO) infarcts demonstrated a dramatic 65% reduction in infiltrating haematopoietic cells, including monocytes, macrophages, dendritic, and T cells, suggesting a critical role for CD13 adhesion in inflammatory trafficking. Accordingly, CD13(KO) infarcts also contained fewer myofibroblasts, consistent with attenuation of fibroblast differentiation resulting from the reduced inflammation, leading to adverse remodelling. CONCLUSION: In the ischaemic heart, while compensatory mechanisms apparently relieve potential angiogenic defects, CD13 is essential for proper trafficking of the inflammatory cells necessary to prime and sustain the reparative response, thus promoting optimal post-infarction healing.

Reversal of cardiac myocyte dysfunction as a unique mechanism of rescue by P2X4 receptors in cardiomyopathy.

Binary cardiac transgenic (Tg) overexpression of P2X(4) receptors (P2X(4)R) improved the survival of the cardiomyopathic calsequestrin (CSQ) mice. Here we studied the mechanism of rescue using binary P2X(4)R/CSQ Tg and CSQ Tg mice as models. Cellular and intact heart properties were determined by simultaneous sarcomere shortening (SS) and Ca(2+) transients in vitro and echocardiography in vivo. Similar to a delay in death, binary mice exhibited a slowed heart failure progression with a greater left ventricular (LV) fractional shortening (FS) and thickness and a concomitant lesser degree of LV dilatation in both systole and diastole at 8 or 12 wk. By 16 wk, binary hearts showed similarly depressed FS and thinned out LV and equal enlargement of LV as did 12-wk-old CSQ hearts. Binary cardiac myocytes showed higher peak basal cell shortening (CS) and SS as well as greater basal rates of shortening and relaxation than did the CSQ myocytes at either 8 or 12 wk. Similar data were obtained in comparing the Ca(2+) transient. At 16 wk, binary myocytes were like the 12-wk-old CSQ myocytes with equally depressed CS, SS, and Ca(2+) transient. CSQ myocytes were longer than myocytes from wild-type and binary mice at 12 wk of age. At 16 wk, the binary myocyte length increased to that of the 12-wk-old CSQ myocyte, parallel to LV dilatation. The data suggest a unique mechanism, which involves a reversal of cardiac myocyte dysfunction and a delay in heart failure progression. It represents an example of targeting the abnormal failing myocyte in treating heart failure.