ABSTRACT
Background: The impact of some medical decisions hurriedly taken during the COVID-19 first wave remains unknown. We tried to assess the consequences of one of these precautionary measures, namely the interruption of a 4/6 cyclin D-dependent kinase inhibitor (CDK4/6i) in metastatic patients with clinical benefit (complete response/partial response and patients with stable disease for at least 6 months) on endocrine treatment (ET). The main reason for this interruption was to limit the risk of myelosuppression (assumed as a serious risk factor for COVID-19) and other adverse effects that could overlap with symptoms and clinical signs described in the SARS-CoV-2 infection. Methods: We included 60 patients (median age: 64 years old) in whom the CDK4/6i was stopped during the first COVID-19 outbreak. It was a non-interventional, retrospective, multicentric study. A univariate analysis was performed to assess risk factors associated with disease progression: odds ratios (OR) were estimated along with their confidence intervals (CI). Key patient characteristics, all included in the statistical model, are presented in Table 1. Results: The average duration of a CDK4/6i interruption was 8 weeks. During this therapeutic break, 22 (37 %) patients Shad a radiological and/or clinical progression of the disease. Among them, CDK4/6i were taken back for the majority of patients (n=16/22;73 %) when the sanitary situation improved.For four patients (n=4/22;18 %), a new specific treatment (chemotherapy or targeted therapy) was initiated for rapid or symptomatic tumor progression. Two patients died while CDK4/6i was withdrawn. All the results of the univariate analysis are summarized in Table 2. During the CDK4/6i discontinuation, the risk of disease progression was significantly increased in the presence of liver metastases. This was the only variable with a significant effect in univariate analysis. Although not statistically significant, the risk of disease progression was higher when CDK4/6i withdrawal was longer, when patients had a more aggressive breast cancer (Luminal B) and when the tumor was considered as resistant to ET. Conclusions: The importance of maintaining the cell cycle inhibitor in addition to ET does not seem to be debatable as 36 % of patients progressed during CDK4/6i withdrawal. This is important in clinical practice when the question of CDK4/6i discontinuation arises for other reasons (analgesic radiotherapy or programmed surgery for example). Special attention should be paid to patients with liver metastases for whom stopping such a treatment seems to accelerate the natural course of the disease.
ABSTRACT
Pediatric cardiac surgeries involving aortic arch reconstruction are complex and require long cardiopulmonary bypass (CPB) times with deep hypothermic circulatory arrest (DHCA). Selective perfusion techniques have been developed to prevent the deleterious consequences of DHCA associated hypoperfusion. The effectivity of low body perfusion through cannulation of the femoral artery with an arterial sheath remains to be elucidated. We compared perfusion and inflammation in patients receiving selective antegrade cerebral perfusion (ACP) only to low body perfusion (LBP) in addition to ACP during DHCA for aortic arch reconstruction surgery. There was no difference in patient characteristics, cardiac pathologies, or performed procedures between ACP and LBP groups. Lactate levels increased after cardiac arrest in both groups. However, lactate levels were lower after 1 h reperfusion, at the end of extracorporeal circulation (ECC), and after surgery in LBP group compared to ACP only. Furthermore, creatinine was increased in ACP group on postoperative day 1 compared to LBP group but no acute kidney injury was observed in any group. IL-6 concentration increased in ACP group, while remained unchanged in LBP group compared to pre surgical values and were significantly lower compared to ACP group on postoperative days 1 and 2. LBP via an arterial sheath during cardiac arrest for aortic arch reconstruction surgery in addition to ACP, improves post ECC tissue perfusion as indicated by lower lactate levels and reduces creatinine levels suggesting milder kidney injury. LBP seems to prevent postoperative inflammation through a reduction in procedural duration or enhanced perfusion and thereby improves the outcome after aortic arch reconstruction surgery. © The Author(s) 2021.
ABSTRACT
Clinical manifestations of COVID-19 affect many organs, including the heart. Cardiovascular disease is a dominant comorbidity and prognostic factors predicting risk for critical courses are highly needed. Moreover, immunomechanisms underlying COVID-induced myocardial damage are poorly understood. OBJECTIVE: To elucidate prognostic markers to identify patients at risk. RESULTS: Only patients with pericardial effusion (PE) developed a severe disease course, and those who died could be identified by a high CD8/Treg/monocyte ratio. Ten out of 19 COVID-19 patients presented with PE, 7 (78%) of these had elevated APACHE-II mortality risk-score, requiring mechanical ventilation. At admission, PE patients showed signs of systemic and cardiac inflammation in NMR and impaired cardiac function as detected by transthoracic echocardiography (TTE), whereas parameters of myocardial injury e.g. high sensitive troponin-t (hs-TnT) were not yet increased. During the course of disease, hs-TnT rose in 8 of the PE-patients above 16 ng/l, 7 had to undergo ventilatory therapy and 4 of them died. FACS at admission showed in PE patients elevated frequencies of CD3+CD8+ T cells among all CD3+ T-cells, and lower frequencies of Tregs and CD14+HLA-DR+-monocytes. A high CD8/Treg/monocyte ratio predicted a severe disease course in PE patients, and was associated with high serum levels of antiviral cytokines. By contrast, patients without PE and PE patients with a low CD8/Treg/monocyte ratio neither had to be intubated, nor died. CONCLUSIONS: PE predicts cardiac injury in COVID-19 patients. Therefore, TTE should be performed at admission. Immunological parameters for dysfunctional antiviral immunity, such as the CD8/Treg/monocyte ratio used here, supports risk assessment by predicting poor prognosis.