The Novel Diagnostic Index Based on HLA-DRB1 Genotype and PD-L1 Expression can Predict Severe irAEs in Patients with Metastatic Melanoma Taking Immune Checkpoint Inhibitors. The Results of the Pilot Study.

Immune-related adverse events (irAEs) occur in up to 50% of patients treated with an anti-CTLA-4 antibody and 30% of patients treated with PD-1/PD-L1 antibodies. Severe forms of toxicity are observed in 3% of patients and require systemic steroid therapy and constant monitoring. One of the considered predictor biomarkers of irAEs development is HLA-genotypes. This research aims to evaluate the diagnostic significance of HLA-DRB1 genotypes and other clinical and laboratory parameters to predict the development of irAEs. The study involved 28 patients with metastatic melanoma taking checkpoint inhibitors therapy [nivo 53.6%, Ipi+nivo 32.1%, other (pembro, prolgo) 14.3%]. The PD-L1 expression and HLA-DRB1 genotype were evaluated. After 2-3 months the development of irAES was assessed. The complications of 3-4 grade or multi-organ damage were termed as severe irAEs. Various IrAEs developed in 57.1% (16/28) of patients, while severe irAEs occurred in 35.7% (10/28). Among all patients, HLA-DRB1 genotypes associated with the risk of autoimmune diseases were found in 78.5% (22/28). The PD-L1 expression was detected in 60.7% (17/28) of individuals. Combination treatment increases the risk of toxicity, p = 0.0028, with a diagnostic sensitivity of 56% and a diagnostic specificity of 100% (RR = 2.71, OR = 31.67). An index based on the parameters studied (HLA-DRB1, absence of PD-L1 expression, and type of treatment) was created. It allows assuming the risk of developing severe irAES (p = 0.0126). When comparing this indicator between irAEs 1-2 and irAEs 3-4, the presence of an index value of more than 2 gives a sensitivity for predicting severe toxicity of 40.00% and a specificity of 83.33%.

Case report of mild form of a new coronavirus infection in patient with idiopathic pulmonary hypertension.

The article presents a clinical case of mild novel coronavirus infection COVID-19 complicated with bilateral interstitial pneumonia in a female patient with idiopathic pulmonary hypertension.

Correlations between clinical and laboratory findings and prognostically unfavorable CMR-based characteristics of acute ST-elevation myocardial infarction.

Aim To evaluate factors associated with unfavorable predictive characteristics of ST-segment elevation acute myocardial infarction (STEMI) as per data of magnetic resonance imaging (MRI).Material and methods The study included 52 patients with STEMI who underwent a primary percutaneous coronary intervention (pPCI). Contrast-enhanced cardiac MRI was performed for all patients on days 3-7. Delayed contrast-enhancement images were used for assessing infarct size, presence of microvascular obstruction (MVO) areas, and heterogeneity zones.Results Multifactorial analysis showed that independent predictors of MVO were type 2 diabetes mellitus (DM) (relative risk (RR) 1.9, confidence interval (CI): 1.1-3.26, р=0.012), increased levels of brain natriuretic peptide (BNP) (RR 2.04, CI: 1.39-2.99, р=0.004) and creatine kinase (CK) (RR 2.06, CI: 0.52-0.80, р=0.02), and infarct size (IS) (RR 2.81; CI: 1.38-5.72, р=0.0004). Construction of ROC curves provided the quantitative values of study indexes, at which the risk of MVO increased. For BNP, this value was ≥276 pg/ml (sensitivity, 95.7 %; specificity, 37.9 %); for CK ≥160 U/l (sensitivity, 74.1 %; specificity, 61.9 %); and for IS ≥18.8 % (sensitivity, 79.3 %; specificity, 69.6 %). Correlation analysis of risk factors for increased size of the heterogeneity zone showed significant correlations of the heterogeneity zone size with older age of patients (r=0.544, р<0.0001), higher concentrations of BNP (r=0.612, р<0.0001), CK (r=0.3, 95 % CI: 0.02-0.5, р=0.03), and C-reactive protein (CRP) (r=0.59, CI: 0.3-0.7, р=0.0001). Increased levels of CK (r=0.53, 95 % CI: 0.29-0.70, р=0.0001) and BNP (r=0.55, 95 % CI: 0.28-0.70, p=0.0003) significantly correlated with increased IS.Conclusion Risk of MVO formation as per MRI data increased in the presence of type 2 DM and IS ≥18.8 % (р<0.05). Formation of MVO in patients with STEMI was associated with increased levels of BNP ≥276 pg/ml and CK ≥160 U/l (р<0.05). Increased levels of BNP, CK, and CRP were associated with a larger size of heterogeneity zone according to data of the correlation analysis. A larger heterogeneity zone was more typical for older patients. Increased levels of CK and BNP were also associated with larger IS. The correlation analysis did not show any significant interactions between the size of heterogeneity zone, IS, and MVO size (р>0.05).

[The State of Vascular Bed, Parenchyma and Perfusion of Lungs in Chronic Thromboembolic Pulmonary Hypertension According to Data of Subtraction Pulmonary Angiography].

AIM: to assess the state of vascular bed, parenchyma, and perfusion of lungs in patients with chronic thromboembolic pulmonary hypertension (CTEPH) using the method of subtraction computed tomography (CT). METHODS: CT pulmonary angiography (CTPA) was performed in 45 patients with verified CTEPH (18 men, 27 women, age 26-79 years) by CT scanner using the "Lung subtraction" standard protocol. Parameters analyzed were characteristics of the state of main pulmonary artery (MPA) and the right ventricle (RV), and calculated CT angiographic (CTA) obstruction and perfusion defect scores. RESULTS: Significant correlation was found between CTA obstruction score and perfusion defect score (r=0.34, p=0.02). Mean pulmonary arterial pressure (mPAP) correlated with MPA diameter (r=0.4, p=0.02), RV wall thickness (r=0.6, p=0.0003) and the ratio of MPA diameter to ascending aortic diameter (r=0.5, p=0.002). Significant correlation was also found between RV wall thickness and pulmonary vascular resistance (PVR) (r=0.4, p=0.04). Neither CTA obstruction score nor perfusion defect score correlated with PVR and mPAP. The data of CT did not correlate with results of 6-minute walk test. CONCLUSION: In patients with CTEPH subtraction CTPA allows carrying out complex diagnostics of the state of vascular bed, parenchyma and perfusion of the lungs.

[Subtraction CT angiopulmonographic assessment of the vascular bed and lung perfusion in patients with chronic thromboembolic pulmonary hypertension: A pilot study]. / Otsenka sosudistogo rusla i perfuzii legkikh u bol'nykh khronicheskoi tromboémbolicheskoi legochnoi gipertenziei s pomoshch'iu subtraktsionnoi KT-angiopul'monografii: rezul'taty predvaritel'nogo issledovaniia.

AIM: To evaluate the vascular bed and lung perfusion in patients with chronic thromboembolic pulmonary hypertension (CTEPH) by computed tomography (CT) and to compare the severity of pulmonary arterial (PA) thrombotic lesions concurrent with parenchymal perfusion disorders with angiopulmonographic findings and clinical and hemodynamic characteristics. SUBJECTS AND METHODS: In the period from November 2015 to May 2016, 22 patients (7 men, 15 women) aged 27 to 67 years with a verified diagnosis of CTEPH were examined using an Aquilion ONE VISION Edition 640 (Toshiba Medical Systems, Japan) CT scanner with a 320-row detector. Perfusion defect in this study was evaluated with the new software allowing one to combine contrast and contrast-free images by a subtraction method. CT data analysis included visual assessment of the vascular bed and lung parenchyma and quantitative assessment with perfusion map construction and semi-automatic determination of the obstruction index (OI) and perfusion defect index (PDI). OI was compared with PDI and mean LA pressure according to the data of right heart catheterization and 6-minute walk test. RESULTS: A statistically significant correlation was found between OI and PDI in patients with CTEPH (Pearson r=0.56; p=0.0065). There were no relationships between mean LA pressure and vascular perfusion indices (OI and PDI) or between vascular perfusion parameters and 6-minute walk test results. CONCLUSION: CT angiopulmonography in conjunction with pulmonary perfusion assessment (within one study) allows evaluation of the severity of vascular lesions and perfusion disorders and determination of the efficiency of treatment in patients with CTEPH.