Consideration of immunomodulatory actions of morphine in COVID-19 - Short report.

Cytokine storm in COVID-19 is linked to disease severity and mortality. 40% of patients with severe COVID-19 require mechanical ventilation. Analgesia and sedation are used for treatment of pain, facilitation of mechanical ventilation, or management of acute agitation. Herein, we present the immunomodulating actions of morphine that may either improve or worsen the clinical course of COVID-19 once cytokine storm develops. A literature search was performed to find articles on potential immunomodulatory effects of morphine. Taken together, the results of in vitro and in vivo models in non-COVID-19 conditions suggest that morphine could have a beneficial effect by mitigating the cytokine storm in the early stages of severe COVID-19. In contrast, it could be potentially harmful in late stages of severe COVID-19, especially in the presence of septic shock.

Role of Pro-Brain Natriuretic Peptide Serum Concentration in the Detection of Pulmonary Hypertension in Patients With End-Stage Lung Diseases Referred for Lung Transplantation.

BACKGROUND: Serum N-terminal pro-brain natriuretic peptide (NT-proBNP) concentration is elevated in patients with pulmonary hypertension (PH); however, its role in the detection of PH associated with lung disease is not well established. AIM: The aim of this study was to assess the value of NT-proBNP in the detection of PH in patients with end-stage lung disease (esLD) referred for lung transplantation. MATERIALS AND METHODS: The study population consisted of 65 patients: 37 with idiopathic pulmonary fibrosis (IPF), 20 with chronic obstructive pulmonary disease, and 8 patients with other interstitial lung diseases (75% men, mean age 53.3 ± 9.5 years). Serum concentration of NT-proBNP was assessed with an immunoradiometric assay kit. The mean pulmonary artery pressure (mPAP) was measured using a Swan-Ganz catheter. PH was defined as mPAP ≥ 25 mm Hg. RESULTS: Median NT-proBNP concentrations were significantly higher in patients with PH than in patients without PH: 139 (49-1236) pg/mL vs 67 (38-116) pg/mL, respectively; P = .016. Receiver operating characteristic (ROC) analysis revealed that NT-proBNP concentration higher than 131.5 pg/mL was a predictor of PH with good specificity (81%) and positive predictive value (78.9%) but low sensitivity (55.6%) and negative predictive value (58.6%). The area under the ROC curve of serum NT-proBNP concentration for PH was 0.71 (95% confidence interval 0.57-0.85, P = .039). CONCLUSION: Serum concentration of NT-proBNP may be useful in the diagnosis of PH in patients with esLD referred for lung transplantation.

Prognostic Value of Mean, Diastolic, and Systolic Pulmonary Artery Pressure in Patients With End-stage Lung Disease Referred for Lung Transplantation.

BACKGROUND: Pulmonary hypertension (PH) is a common complication in end-stage lung disease (esLD). The aim of this study was to establish the best threshold values for mean, systolic, and diastolic artery pressure (mPAP, dPAP, and sPAP, respectively) to identify patients with esLD referred for lung transplantation and to predict 1-year prognosis. METHODS: Sixty-five patients were enrolled in the study (75% men) with a mean age of 53.3 ± 9.5 years; 31% had chronic obstructive pulmonary disease (COPD), 57% had idiopathic pulmonary fibrosis (IPF), and 12% had interstitial lung diseases (ILDs). The mean period of observation was 14.4 ± 5 months. We assessed invasively mPAP, dPAP, and sPAP, as well as pulmonary capillary wedge pressure (PCWP), using a Swan-Ganz catheter. Receiver-operating characteristic (ROC) curves were constructed to identify the best cutoff points for mPAP, dPAP, and sPAP to predict survival. The study endpoint was defined as 1-year mortality before transplantation. Survival analysis was completed according to the Kaplan-Meier method. RESULTS: During follow-up, 30 (46.1%) patients died and 19 (29%) underwent lung transplantation. Based on ROC curve analysis, we estimated mPAP ≥30 mm Hg, dPAP ≥20 mm Hg, and sPAP ≥44 mm Hg as the best threshold values with the highest sensitivity (70%, 70%, and 73%, respectively) and specificity (76%, 69%, and 72%, respectively) and the acceptable area under curve (0.67, 0.68, and 0.72, respectively). The negative predictive values for mPAP, dPAP, and sPAP were higher than the positive predictive values (79%, 77%, and 81% vs 67%, 61%, and 64%, respectively). We also constructed Kaplan-Meier curves for mPAP, dPAP, and sPAP threshold values. There were significant differences in 1-year survival between patients with and without PH for mPAP, dPAP, and sPAP threshold values (P = .005, P = .035, and P < .001; respectively). CONCLUSION: Elevated mPAP, dPAP, and sPAP are related to worse prognosis in patients with esLD referred for lung transplantation.

Effect of trimetazidine on serum interleukin-6 and C-reactive protein concentrations in patients with stable coronary artery disease.

Trimetazidine is widely used in the treatment of stable coronary artery disease (CAD) and its cytoprotective effect has been confirmed in animal studies and in many clinical trials. Given the inflammatory milieu of CAD and trimetazidine effect on the inflow of neutrophilis to the ischemic area, it is interesting to consider whether trimetazidine actions could be also explained through the inhibition of inflammatory mediators, including cytokines. The aim of this study was to (i) examine the influence of treadmill exercise test (TET) on serum C-reactive protein (CRP) and interleukin-6 (IL-6), and (ii) the influence of three-month trimetazidine therapy on serum CRP and IL-6 concentrations. One hundred and fifty-six patients with stable CAD were included. TET was performed (according to the standard Bruce protocol) twice for all subjects – at baseline and after the three-month trimetazidine treatment. Serum IL-6 and CRP concentrations were determined prior to and after performing each TET. Exercise led to the increase of CRP (2.35 vs 2.81 mg/L, p < 0.05) and IL-6 concentrations (1.64 vs 1.92 pg/ml, p=0.0318) in patients without trimetazidine. Three-month treatment resulted in the increase in the TET duration (378.0s vs 410.9s, p < 0.05) and decrease in serum CRP concentration, both before (2.35 vs 1.51 mg/L, p < 0.05) and after TET (2.81 vs 1.69 mg/L, p < 0.05). There was no significant increase of CRP after the second TET (1.51 vs 1.69 mg/l, p=NS). Three-month trimetazidine treatment increased IL-6 concentrations (1.64 vs 2.23 pg/mL, p < 0.05). TET was not associated with further changes in IL-6 concentrations (2.23 vs 2.18 pg/mL, p=NS). Serum IL-6 and CRP concentrations increase during exercise in patients without trimetazidine. Three-month trimetazidine prolonged the duration of TET. Moreover, it resulted in the reduction of CRP concentration The increase of IL-6 concentration after three-month trimetazidine treatment and the lack of changes of its concentration after TET is associated with yet another mechanism of trimetazidine.

Serum concentration of insulin-like growth factor-I, but not tumor necrosis factor-alpha, measured twelve months after stenting of the infarct-related artery, is associated with in-stent restenosis.

Percutaneous coronary intervention (PCI) has revolutionized the management of and outcomes in patients with ST-segment elevation myocardial infarction (STEMI). The role of insulin-like growth factor-I (IGF-I) and tumor necrosis factor-alpha (TNF-alpha) in restenosis has been intensively studied. We aimed to investigate the power of serum IGF-I and TNF-alpha concentrations to predict restenosis in patients who had previously undergone PCI for STEMI. Thirty-seven patients were enrolled in the study. Twelve months prior to the study they underwent successful PCI with stent placement for STEMI. The patients were divided into two groups: group 1 - patients with in-stent restenosis in the infarct-related artery (N=9); group 2 - patients without in-stent restenosis in the infarct-related artery (N=28). Baseline profile was similar in both groups. The mean diameter and length of placed stents were similar in both groups. Smaller minimal lumen diameter (MLD) and greater lumen loss (LL) were observed in group 1. Median IGF-I concentrations were substantially higher in patients with ISR compared to those without ISR (170 ng/mL vs 115 ng/mL, p=0.004). Strikingly, median TNF-alpha levels were lower in group 1 (2.4 pg/mL vs 4.1 pg/mL, p=0.05). Correlation analysis showed that serum IGF-I levels were significantly associated with diameter stenosis (R=0.29 p=0.05), LL (R=0.37 p=0.02), MLD (R= -0.38 p=0.03), and stent length (R=0.30 p=0.05). The cut-off value to predict restenosis for IGF-I was less than 158 ng/mL (sensitivity 55 percent, specificity 93 percent, positive predictive value 71 percent, negative predictive value 87 percent). IGF-I detected twelve months after stent placement during the acute phase of AMI may be a late determinant of restenosis. High concentrations of IGF-I could play a permissive role in the progression of NIH and subsequently restenosis. It seems that as far as TNF-alpha is concerned, diagnostic value remains inconclusive.

The role of interleukin-6 and transforming growth factor-beta1 in predicting restenosis within stented infarct-related artery.

Despite high efficacy of percutaneous coronary intervention (PCI), in-stent restenosis proves to be a significant problem of therapy. Restenosis concerns around 30 percent of patients. Studies have suggested that restenosis is initiated by cells which participate in intense inflammatory reaction caused by stent implantation. Atherosclerotic plaque rupture during stent implantation and PCI-associated injury of the vessel wall lead to hemorrhage and release of various cytokines. They are probably responsible for quick recurrence of vascular lumen stenosis (restenosis). Interleukin-6 (IL-6) is known as a main pro-inflammatory cytokine, whereas Transformig Growth Factor-beta1 (TGF-beta1) has anti-inflammatory properties. The study population comprised 36 patients with myocardial infarction treated with PCI with stent implantation. They underwent control coronary angiography after 12 months. At this time plasma concentration of IL-6 and TGF-beta was measured in peripheral blood. Serum IL-6 concentration in the analyzed population correlates with lumen loss (p<0.01) and the severity of stenosis (p<0.001). No such correlation was found between serum TGF-beta1 concentration and lumen loss (p=NS) or the severity of stenosis (p=NS). The IL-6 plasma concentration may be a marker of in-stent restenosis in patients after PTCA, while the concentration of TGF-beta1 is not associated with the occurrence of restenosis at one year of follow-up.