Evaluation of the Levels of Selected Cytokines and Their Possible Influence on the Development of Cardiovascular and Pulmonary Complications in Patients after COVID-19.

Background and Objectives: The aim of this study was to evaluate the levels of selected cytokines and their possible influence on the development of cardiovascular and pulmonary complications in patients hospitalized at the Silesian Centre for Heart Disease in Zabrze after having undergone COVID-19. Materials and methods: The study included 76 randomly selected patients from the SILCOVID-19 database. The median time from symptom onset to the study visit was 102 (86-118) days. The median age of the study group was 53 (44-60) years. Assays of a panel of 30 cytokines were carried out in the serum of patients on a Luminex100 platform using the Milliplex MAP kit from Merck KGaA Germany. Results: There were no statistically significant differences in most of the cytokines analyzed between patients with confirmed or excluded lung lesions or cardiac abnormalities. Additionally, no statistically significant differences in cytokine concentrations according to gender, age, comorbidity of diabetes, renal disease, hypertension, increased risk of thrombotic disease, or psychological disorders were demonstrated. There were high concentrations of cytokines such as platelet-derived growth actor-AA (PDGF-AA), monocyte chemoattractant protein-1 (MCP-1), monokine-induced gamma interferon (MIG), and vascular endothelial growth factor-A (VEGF-A). Conclusions: No direct impact of the dependencies between a panel of cytokines and the incidence of cardiovascular and pulmonary complications in patients hospitalized at the Silesian Centre for Heart Disease in Zabrze after having undergone COVID-19 was demonstrated. The demonstration of high levels of certain cytokines (PDGF-AA, VEGF, MIG, and IP10) that are of significance in the development of many lung diseases, as well as cytokines (MCP-1) that influence the aetiopathogenesis of cardiovascular diseases seems to be highly concerning in COVID-19 survivors. This group of patients should receive further monitoring of these cytokine levels and diagnostic imaging in order to detect more severe abnormalities as early as possible and administer appropriate therapy.

Modified Model for End-Stage Liver Disease Is an Indicator of the Ineffectiveness of Sildenafil Treatment in Patients With Advanced Heart Failure and Increased Pulmonary Vascular Resistance.

BACKGROUND: Elevated pulmonary vascular resistance (PVR) is a risk factor for early right ventricular failure and poor prognosis after heart transplantation (HT) as well as an indication for treatment with vasodilators. The aim of the study was to determine the relationship between the baseline values of the modified Model for End-Stage Liver Disease (modMELD) score and the presence of elevated PVR in patients with advanced heart failure (HF) after 6 months of sildenafil treatment. MATERIALS AND METHODS: The study was a retrospective review of 86 adult patients with end-stage HF who were evaluated for HT at our institution between 2015 and 2017. All patients had reversible PVR according to right heart catheterization. They all received sildenafil therapy in the maximum tolerated doses. Before the inclusion of sildenafil, the modMELD scores were calculated based on the serum bilirubin, creatinine, and albumin levels. The study's endpoint was PVR >3 Wood units after 6 months of sildenafil therapy. RESULTS: The median age of the patients was 57 (50-63) years, and 91.9% of them were men. Elevated PVR values (>3 Wood units) after 6 months of sildenafil treatment were found in 36 patients (42%). The area under the ROC curve (AUC) for modMELD was 0.848 (95% CI: 0.768-0.929). The cutoff point for modMELD (>11.1) had a sensitivity of 97% and a specificity of 68%. CONCLUSIONS: The modMELD score may be a useful indicator of the ineffectiveness of sildenafil treatment in patients with advanced HF evaluated for HT.

The role of MMP-12 gene polymorphism - 82 A-to-G (rs2276109) in immunopathology of COPD in polish patients: a case control study.

BACKGROUND: Major symptoms of chronic obstructive pulmonary disease (COPD) are chronic bronchitis and emphysema leading from lung tissue destruction, that is an effect of an imbalance between metalloproteinases (MMPs) and their tissue inhibitors activity. As potential factor involved in this COPD pathogenesis, MMP-12 is considered. We investigated the role of genetic polymorphism and protein level of MMP-12 in the COPD development among Poles. METHODS: We analyzed - 82 A > G SNP in the promoter region of MMP-12 gene (rs2276109) among 335 smoked COPD patients and 309 healthy individuals, including 110 smokers. Additionally, 60 COPD patients and 61 controls (23 smokers) were tested for serum levels of MMP-12 using ELISA. All subjects were analyzed for lung function using spirometry (FEV1% and FEV1/FVC parameters). RESULTS: We observed that -82G allele and -82GG homozygous genotype frequencies of the SNP rs2276109 were significantly lower in COPD patients than in controls (12.5% vs 16.9%, respectively; χ2 = 4.742, p = 0.02 for allele and 0.5% vs 3.9%, respectively; χ2 = 9.0331, p = 0.01 for genotype). Moreover, -82G allele was more frequent in controls smokers than in non-smokers (22.3% vs 14.1%, χ2 = 6.7588, p = 0.01). Serum level of MMP-12 was significantly higher in COPD patients than in controls groups (6.8 ng/ml vs 3.3 ng/ml, respectively; F = 7.433, p < 0.0001), although independently of analyzed gene polymorphisms. Additionally, no correlation between parameters of lung function (FEV1% and FEV1/FVC) and protein level was found. CONCLUSIONS: We found that -82G allele of SNP rs2276109 was associated with reduced risk of COPD, and COPD patients released more MMP-12 than healthy individuals, but independently on this SNP.

MMP-2, MMP-9, and TIMP-4 and Response to Aspirin in Diabetic and Nondiabetic Patients with Stable Coronary Artery Disease: A Pilot Study.

BACKGROUND: High on-aspirin treatment platelets reactivity (HPR) is a significant problem in long-term secondary prevention of cardiovascular events. We hypothesize that imbalance between platelets MMPs/TIMPs results in cardiovascular disorders. We also explored whether chronically elevated blood glucose affects MMP-2/TIMP-4 release from platelets. MATERIALS AND METHODS: Seventy patients with stable coronary artery disease, supplemented with aspirin, participated in this pilot study. The presence of HPR and/or diabetes mellitus was considered as the differentiating factor. Light aggregometry, impedance aggregometry, and ELISA tests for TXB2, MMP-2, MMP-9, and TIMP-4 were performed in serum, plasma, platelet-rich plasma, and platelets-poor plasma, as appropriate. RESULTS: Aspirin-HPR did not affect plasma MMP-2, MMP-9, and TIMP-4. Arachidonic acid-induced aggregation of platelets from aspirin-HPR patients did not lead to increased release of MMP-2, MMP-9, and TIMP-4. Studying patients at the lowest TXB2 serum concentration quartile revealed that high concentration of plasma TIMP-4 and TIMP-4 negatively correlated with TXB2 and platelet aggregation. Diabetics showed an increased plasma MMP-2 as well as an increased MMP-2 in supernatants after platelet aggregation. However, diabetes mellitus did not affect MMP-9 and TIMP-4. CONCLUSION: Aspirin-HPR did not affect the translocation and release of MMPs and TIMP-4 from platelets. TIMP-4 may serve as a marker of TXA2-mediated platelet aggregation. Chronically elevated plasma glucose increases plasma MMP-2, and HPR potentiates this phenomenon.

Monitoring hemostasis parameters in left ventricular assist device recipients - a preliminary report.

INTRODUCTION: Mechanical circulatory support (MCS) therapy is associated with the improvement of long-term prognosis in patients with end-stage heart failure. For years it has been used as a bridge to transplant. However, more recently it is even being used as a destination therapy. Recently, clinicians have identified common MCS therapy-associated complications: pump thrombosis, bleeding, and hemolysis. These complications are very challenging with regard to both diagnosis and management. AIM: To determine time-dependant changes of selected hemostasis/coagulation parameters in patients with end-stage heart failure treated with MCS and antithrombotic therapy. MATERIAL AND METHODS: Sixteen patients with end-stage heart failure on left ventricular assist device (LVAD) were followed for 6 weeks (six blood samples for each patient). Every week an extended hemostasis panel was assessed, including activated partial thromboplastin time, prothrombin time, international normalized ratio, von Willebrand factor (vWF) activity, factor VIII activity, fibrinogen level, D-dimer, platelet response to arachidonic acid (ASPI test) and adenosine diphosphate (ADP test), thrombin receptor activating peptide-6 (TRAP test) and collagen (COL test). RESULTS: The study population comprised 16 men. The median time from LVAD implantation was 120 days (100-150 days). During the study period the D-dimer and fibrinogen concentrations were elevated but remained similar throughout all six measurements. Meanwhile factor VIII and vWF activities were elevated in the first two measurements and then subsequently declined. Inhibition of platelet aggregation was greater early after LVAD implantation. During subsequent weeks the inhibition of platelet aggregation was less pronounced. No patient developed any bleeding or thrombo-embolic event during the study period. CONCLUSIONS: Patients on MCS therapy demonstrate significant time-dependant changes in hemostasis parameters (both in the coagulation system and platelet aggregation).

Total Hemoglobin Mass, Aerobic Capacity, and HBB Gene in Polish Road Cyclists.

Malczewska-Lenczowska, J, Orysiak, J, Majorczyk, E, Zdanowicz, R, Szczepanska, B, Starczewski, M, Kaczmarski, J, Dybek, T, Pokrywka, A, Ahmetov, II, and Sitkowski, D. Total hemoglobin mass, aerobic capacity, and the HBB gene in polish road cyclists. J Strength Cond Res 30(12): 3512-3519, 2016-The relationship between genes, amount of hemoglobin, and physical performance are still not clearly defined. The aim of this study was to examine the association between-551C/T and intron 2, +16 C/G polymorphisms in the beta hemoglobin (HBB) gene and total hemoglobin mass (tHbmass) and aerobic capacity in endurance athletes. Total hemoglobin mass and aerobic capacity indices, i.e.,V[Combining Dot Above]O2max, oxygen uptake at anaerobic threshold (V[Combining Dot Above]O2AT), maximal power output (Pmax), and power at anaerobic threshold (PAT) were determined in 89 young road cyclists, female (n = 39) and male (n = 50), who were genotyped for 2 polymorphisms in the HBB gene. The relative values of aerobic capacity indices differed significantly among intron 2, +16 C/G polymorphisms of the HBB gene only in female cyclists; athletes with GG genotype had significantly higher values of V[Combining Dot Above]O2max (p = 0.003), V[Combining Dot Above]O2AT (p = 0.007), PAT (p = 0.015), and Pmax (p = 0.004) than C carriers. No relationships were found between the C-carrier model (CC + CG vs. GG in the case of intron 2, +16 C/G and CC + CT vs. TT for -551 C/T polymorphisms of the HBB gene) and relative values of tHbmass. Our results demonstrated that the HBB gene could be related to aerobic capacity, but it seems that it does not result from an increase in the amount of hemoglobin in the blood.

Relationship between high on aspirin platelet reactivity and oxidative stress in coronary artery by-pass grafted patients.

The aim of the study was to assess the responsiveness of blood platelets to acetylsalicylic acid (ASA) in patients following coronary artery bypass grafting (CABG) surgery with relation to oxidative and antioxidative plasma status. The study included 37 patients treated with the CABG procedure. During the first 24 h after CABG patients were given 300 mg of ASA with the following dose of 150 mg daily. The blood was collected before the procedure and 10 days after. Whole blood platelet aggregation induced with arachidonic acid, collagen and adenosine diphosphate (ADP) was performed together with whole blood generation of thromboxane B2 (TxB2). Oxidative stress was measured before and 10 days after CABG with total oxidative plasma status (TOS) and total antioxidative status of the plasma (TAS). TOS/TAS index was calculated. We observed a significant increase in the TOS and TOS/TAS index and ADP-induced aggregation 10 days after CABG in comparison with its level before operation. There was a significant decrease in the arachidonic acid-induced aggregation and serum TxB2 level. Patients with ADP-induced and collagen-induced aggregation in the upper quartile had significantly higher TOS and TOS/TAS index before (ADP) and after the operation (ADP and collagen). There were 19 patients (51%) with high on aspirin platelet reactivity after CABG who had also higher TOS and TOS/TAS index and lower TAS value in comparison with aspirin responders. Despite ASA use, increased oxidative stress after CABG can overcome its antiplatelet effect and increase platelet activation through other pathways.

Low platelet activity predicts 30 days mortality in patients undergoing heart surgery.

Despite advanced techniques and improved clinical outcomes, patient survival following coronary artery bypass grafting (CABG) is still a major concern. Therefore, predicting future CABG mortality represents an unmet medical need and should be carefully explored. The objective of this study is to assess whether pre-CABG platelet activity corresponds with 30 days mortality post-CABG. Retrospective analyses of platelet biomarkers and death at 30 days in 478 heart surgery patients withdrawn from aspirin or/and clopidogrel. Platelet activity was assessed prior to CABG for aspirin (ASPI-test) with arachidonic acid and clopidogrel (ADP-test) utilizing Multiplate impedance aggregometer. Most patients (n = 198) underwent conventional CABG, off-pump (n = 162), minimally invasive (n = 30), artificial valve implantation (n = 48) or valves in combination with CABG (n = 40). There were 22 deaths at 30 days, including 10 in-hospital fatalities. With the cut-off value set below 407 area under curve (AUC) for the ASPI-test, the 30-day mortality was 5.90% for the lower cohort and 2.66% for patients with significantly higher platelet reactivity (P = 0.038). For the ADP-test with a cut-off at 400AUC, the 30-day mortality was 9.68% for the lower cohort and 3.66% for patients with higher platelet reactivity, representing a borderline significant difference (P = 0.046). Aside from the platelet indices, patients who received red blood cell (RBC) concentrate had a highly significant (P < 0.0001) risk of death at 30 days. Both aspirin and clopidogrel tests were useful in predicting 30 days mortality following heart surgery, suggesting the danger of diminished platelet activity prior to CABG in such high-risk patients. These preliminary evidence supports early discontinuation of antiplatelet therapy for elective CABG and requires adequately powered randomized trials to test the hypothesis and potentially improve survival.

Von Willebrand factor in patients on mechanical circulatory support - a double-edged sword between bleeding and thrombosis.

Mechanical circulatory support (MCS) is an umbrella term describing the various technologies used in both short- and long-term management of patients with either end-stage chronic heart failure (HF) or acute HF. Most often, MCS has emerged as a bridge to transplantation, but more recently it is also used as a destination therapy. Mechanical circulatory support includes left ventricular assist device (LVAD) or bi-ventricular assist device (Bi-VAD). Currently, 2- to 3-year survival in carefully selected patients is much better than with medical therapy. However, MCS therapy is hampered by sometimes life-threatening complications including bleeding and device thrombosis. Von Willebrand factor (vWF) has two major functions in haemostasis. First, it plays a crucial role in platelet-subendothelium adhesion and platelet-platelet interactions (aggregation). Second, it is the carrier of factor VIII (FVIII) in plasma. Von Willebrand factor prolongs FVIII half-time by protecting it from proteolytic degradation. It delivers FVIII to the site of vascular injury thus enhancing haemostatic process. On one hand, high plasma levels of vWF have been associated with an increased risk of thrombosis. On the other, defects or deficiencies of vWF underlie the inherited von Willebrand disease or acquired von Willebrand syndrome. Here we review the pathophysiology of thrombosis and bleeding associated with vWF.

Predicting Bleeding Risk by Platelet Function Testing in Patients Undergoing Heart Surgery.

BACKGROUND: Predicting bleeding events in patients with coronary artery bypass grafting (CABG) represents an unmet medical need that may improve CABG outcomes. HYPOTESIS: To assess the potential link between platelet function testing and bleeding risk in patients undergoing CABG. METHODS: Platelet aggregation and clinical outcomes in 478 patients treated with aspirin and/or clopidogrel were retrospectively analyzed. Platelet activity was assessed prior to CABG with arachidonic acid (ASPI Test), and adenosine diphosphate(ADP Test) utilizing multiple-electrode aggregometry. RESULTS: In the study group of 478 patients, mean age was 65.2±15.2 years; 138 were women. The majority of patients (n = 198) underwent on-pump surgery, with 162 undergoing off-pump and 30 undergoing minimally invasive surgery. Forty-eight patients received artificial valve implantation alone, and 40 received valve implantation in combination with CABG. The analysis of the entire pool revealed that an ASPI test value <407 area under curve per minute (AUC*min) may be useful in predicting postoperative drainage. In CABG patients only, an ASPI test value <271 AUC*min predicted the need for red blood cell concentrate transfusion following surgery. In patients who stopped clopidogrel for up to 5 days before surgery, the ADP test failed to exhibit prognostic utility for predicting bleeding risk. CONCLUSIONS: In patients undergoing heart surgery, an ASPI test value <407 AUC*min may predict higher postoperative drainage, whereas <271 AUC*min may be linked to postoperative use of red blood cell concentrate.

Response to Dual Antiplatelet Therapy Does Not Impact Bleeding Risks in Patients Undergoing Oral Surgery after Acute Coronary Syndromes.

INTRODUCTION: Oral surgery (OS) in patients on antecedent dual antiplatelet therapy (DAPT) may be associated with extra bleeding risks. Monitoring platelet activity in such patients may be beneficial for safety when performing OS. OBJECTIVES: The aim of this study was to assess whether platelet function during DAPT impacted the risk of bleeding following OS in patients with acute coronary syndromes (ACS). PATIENTS AND METHODS: Patients who required OS on top of DAPT with aspirin and clopidogrel (n = 55) for invasively treated ACS were included. The control group (n = 33) consisted of patients who underwent OS with no antiplatelet agent. Platelet aggregation before OS was assessed with a Multiplate® analyzer. Bleeding during OS and at days 1, 3, 7 and 10 after surgery was serially evaluated. RESULTS: All 88 patients completed the study. An incomplete response to aspirin or clopidogrel was observed in 43.6% of the patients. In 11% of the cases, an excessive response to clopidogrel was demonstrated. No excessive bleeding upon OS was exhibited in either group during the entire follow-up. Platelet aggregation values and the use of DAPT did not impact the performance of OS. CONCLUSION: Therapy with clopidogrel and aspirin after ACS does not seem to increase the risk of real-life bleeding following OS, regardless of the platelet activity response to DAPT. © 2015 S. Karger AG, Basel.

Activated Hemostatic Biomarkers in Patients with Implanted Left Ventricle Assist Devices: Are Heparin and/or Clopidogrel Justified?

BACKGROUND: Adequate anticoagulation represents a major problem for left ventricle assist device (LVAD) utilization in patients awaiting heart transplantation as well as for regeneration of the native heart. The proper management of hemostatic abnormalities during LVAD support may improve survival by reducing the incidence of hemorrhagic and/or thromboembolic complications. CASE REPORT: A 40-year-old man with implanted pulsatile LVAD due to dilated cardiomyopathy received aspirin and warfarin. The patient underwent serial weekly monitoring of hemostatic biomarkers including international normalization ratio, prothrombin time, prothrombin activity, activated partial thromboplastin time, fibrinogen, D-dimer, platelet aggregation induced by adenosine diphosphate and arachidonic acid, platelet count, and mean platelet volume. The external pump was exchanged three times - twice because of a clot formation in the blood chamber of the pump, and once according to the standard protocol. RESULTS: LVAD use was consistently associated with enhanced adenosine diphosphate-induced platelet aggregation independent from the timing of clot formation or external pump exchange. Among coagulation indices, increased D-dimer holds predictive value for clot formation. The fibrinogen level peaked before the first pump exchange and was twice as high than the average values. Gradual improvement in exercise capacity was observed 2 years after implantation, after which the patient underwent a controlled stress test in the stop mode of the LVAD and the device was successfully explanted. CONCLUSIONS: Serial assessment of hemostatic biomarkers may benefit and triage LVAD patients. Consistent platelet activation during long-term LVAD may justify the addition of clopidogrel, while high D-dimer and/or elevated fibrinogen may indicate adding heparin to the conventional antithrombotic regimen. Randomized evidence is needed to test such a hypothesis.

Aspirin 'resistance': impact on no-reflow, platelet and inflammatory biomarkers in diabetics after ST-segment elevation myocardial infarction.

BACKGROUND: The no-reflow (NR) phenomenon exists despite percutaneous coronary intervention (PCI), and is especially prevalent in diabetics. The causes(s) of NR are not fully elucidated, but may be associated with impaired residual platelet and inflammatory reactivity during dual-antiplatelet therapy. OBJECTIVE: To assess the relationship between dual-antiplatelet therapy, NR and conventional biomarkers suggestive of platelet and inflammatory response in diabetics following ST-segment elevation myocardial infarction (STEMI) treated with PCI. METHODS: Sixty diabetics with (n = 27) and without NR (n = 33) were prospectively enrolled. All patients were treated with clopidogrel and aspirin. Platelet and inflammatory biomarkers were assessed serially in the peripheral blood and right atrium before and after PCI and then at 24 h, 7 days and 30 days. RESULTS: Arachidonic acid (AA)-induced platelet aggregation and the serum thromboxane B2 level before and after PCI (in the peripheral and right atrium blood) were significantly higher in the NR patients than in those with no NR. AA-induced aggregation >100 (AUC*min) before PCI predicted NR in diabetic patients with 96.2% sensitivity and 38.5% specificity (AUC 0.66; 95% CI 0.52-0.71; p = 0.029). There were no other correlations between NR and platelet reactivity (collagen, adenosine diphosphate, thrombin receptor agonist peptide-induced aggregation, vasodilator-stimulated phosphoprotein platelet reactivity index, soluble P-selectin, soluble CD40 ligand, platelet-derived growth factor AB and the level of platelet-monocyte aggregates) or between NR and inflammatory indices (i.e. high-sensitivity C-reactive protein, interleukin 6 and interleukin 10). CONCLUSION: An inadequate response to aspirin, but not to clopidogrel, may be associated with the occurrence of the NR phenomenon in diabetics with STEMI who have been treated with primary PCI.

Pectus excavatum in relief from Ancient Egypt (dating back to circa 2400 BC).

Pectus excavatum is one of the most common congenital deformities of the chest wall. The aim of the study was to analyse 621 artefacts (reliefs, sculptures, paintings) from Ancient Egypt in terms of anatomical defects of the chest. The team which analysed artefacts consisted of historians of medicine and thoracic surgeons. The researchers found a relief, depicting a man with an abnormal shape of the chest. The relief was from Niankhkhnum and Khnumhotep mastaba and dates back to circa 2400 BC. The authors think it is possible that the relief may represent a pectus excavatum deformity and believe the image will open up debate on the occurrence of this deformity in ancient times.

Thrombin generation and platelet reactivity at hospital discharge and 6-month outcome after the acute coronary syndrome in diabetic and nondiabetic patients.

OBJECTIVES: Increased plasma thrombogenesis and blood platelet reactivity are associated with a worse outcome in patients with the acute coronary syndrome (ACS). The aim of this study was to test the clinical utility of combining a thrombin generation test and platelet aggregation in predicting future ischemic events after ACS. METHODS: The study included patients hospitalized due to ST-elevation myocardial infarction (STEMI) treated with primary percutaneous coronary intervention with stent implantation. Blood for platelet aggregation and thrombin generation was collected at hospital discharge. We performed whole-blood platelet aggregation with arachidonic acid (AA), collagen, adenosine diphosphate and thrombin receptor-activating peptide (TRAP) as agonists and the thrombin generation test using a fluorescence method. Patients were followed for up to 6 months. The combined end point of the study consisted of death, stroke, myocardial infarction or repeated target vessel revascularization. RESULTS: The study enrolled 161 patients. The end point occurred in 30 patients (18.6%). Thrombin generation showed a significantly prolonged lag time, time to thrombogram peak and start of the tail of the thrombogram in diabetic patients who reached the study end point but not in nondiabetics. End point occurrence was not connected with platelet reactivity at hospital discharge in the whole group. In the diabetic subgroup, increased platelet aggregation induced with AA and TRAP at hospital discharge was connected with a more frequent occurrence of the study end point. CONCLUSIONS: In diabetic patients after STEMI, thrombin generation measures as well as TRAP- and AA-induced platelet aggregation at hospital discharge are associated with an ensuing ischemic event during the 6-month follow-up.

Penetrating neck traumas.

AIM OF THE STUDY: Aim of the study is to present our own experiences in the treatment of people suffering from penetrating neck traumas. MATERIAL AND METHODS: In the years 1996-2012, 10 patients with penetrating neck traumas were treated, including 3 women and 7 men. The patients' age ranged from 16 to 55 (the average age being 40.7 years). In 9 cases the wound was caused by cutting or stabbing, while in one case it was inflicted by a gunshot. In 8 patients it was a single cut wound, while one patient suffered from 34 stab wounds to the neck, chest and stomach. Two cut wounds resulted from a suicide attempt. The remaining injuries were the result of a crime. RESULTS: All patients underwent immediate surgery, which involved revision of the neck wounds in 8 cases, one longitudinal sternotomy and one left-sided thoracotomy. The indications for surgery included increased subcutaneous emphysema in 5 patients, bleeding from the wound in 3 patients, and mediastinal hematoma in 2 patients. The damage assessed intraoperatively included tracheal damage in 6 patients, damage to carotid vessels in 3 patients, larynx in 2 patients, thoracic vessels in 2 patients, oesophagus in 1 patient and thyroid gland in 1 patient. In 9 patients, the treatment yielded positive results. The patient with a gunshot wound died during the surgery due to massive bleeding from the aorta. CONCLUSIONS: In patients with penetrating neck wounds, early and rapid diagnostics allows one to determine the indications for surgery and prevent serious fatal complications.

Effect of glycemic control on response to antiplatelet therapy in patients with diabetes mellitus and ST-segment elevation myocardial infarction.

Impaired glycemic control (GC) is a troubling clinical condition with an unclear prognostic value that is frequent in diabetics, especially in the setting of acute coronary syndrome. Residual platelet reactivity can be also affected by GC. We evaluated the relation between response to dual antiplatelet therapy and GC in diabetics with STEMI treated with primary coronary angioplasty (PCI). Sixty diabetic patients were prospectively enrolled in the study. All patients were treated with clopidogrel and aspirin. Platelet reactivity (whole blood aggregation and phosphorylation of vasodilator-stimulated phosphoprotein, VASP) were assessed serially before and 24 hours, 7 days, and 30 days after the PCI. Blood glucose >8.5 mmol/L on admission was an independent predictor of a impaired clopidogrel response measured with platelet reactivity index (PRI) >50% on admission (OR 7.8, 95% CI 1.4-17.7, p<0.02) and 24 hours after PCI (OR 13.1, 95% CI 3.4-28.1, p<0.01). In conclusion, diabetic patients with STEMI and glycemia >8.5 mmol/L on admission is related to a poorer response to clopidogrel. There were no interaction between glycated hemoglobin level or glycemia on admission and platelet reactivity measured with collagen, arachidonic acid or thrombin receptor agonist peptide-induced aggregation. Further clinical studies of the role of GC in the efficacy of antiplatelet agents are warranted.

Effects of platelet and inflammatory system activation on outcomes in diabetic patients with ST segment elevation myocardial infarction treated with primary percutaneous coronary intervention.

BACKGROUND: Recurrent myocardial ischaemia and restenosis are more common in diabetic patients treated with primary percutaneous coronary intervention (PCI) due to an acute coronary syndrome (ACS) compared to patients without diabetes. Diabetes is also associated with increased residual platelet activity during dual antiplatelet treatment. In recent reports, platelet reactivity has been linked to outcomes after ACS. Appropriate platelet inhibition might lead to improved outcomes in this patient population. To this end, newest methods to evaluate platelet function may prove helpful. AIM: To evaluate 6-month outcomes in diabetic patients treated with primary PCI due to ST segment elevation myocardial infarction (STEMI) in relation to platelet reactivity evaluated at discharge. METHODS: The study included 120 diabetic patients treated with primary PCI due to STEMI. Patients received loading doses of acetylsalicylic acid (ASA, 300 mg) and clopidogrel (600 mg) on admission, and later were treated with maintenance doses of 75 mg of ASA and clopidogrel. Blood for platelet aggregation testing was collected at discharge. We used whole blood impedance aggregometry using the Multiplate aggregometer with arachidonic acid (AA), adenosine diphosphate (ADP), collagen, and thrombin receptor peptide agonist (TRAP) as agonists. Six-month follow-up was based on telephone contact and hospital discharge summaries if hospitalisation occurred. The primary combined endpoint included recurrent ACS and restenosis. RESULTS: The primary combined endpoint occurred in 28 (23%) patients. Among patients with the primary endpoint, we found significantly higher platelet reactivity as evaluated by aggregation testing using AA and TRAP at discharge following the initial infarction compared to patients without the primary endpoint (area under aggregation curve 1137.4 ± 198.5 vs 833.5 ± 253.4; p = 0.013 for TRAP-induced aggregation, and 333.0 ± 263.8 vs 186.9 ± 105.4; p = 0.019 for AA-induced aggregation). We found no relationship between ADP- and collagen-induced aggregation at discharge and the occurrence of the primary endpoint. CONCLUSIONS: Increased platelet reactivity evaluated by TRAP-induced aggregation is related to a higher rate of restenosis and recurrent ACS during a 6-month follow-up of diabetic STEMI patients treated with PCI.

Expression of selenoprotein-coding genes SEPP1, SEP15 and hGPX1 in non-small cell lung cancer.

Aim of the study was to investigate the mRNA expression level of selenoprotein P (SEPP1), 15-kDa selenoprotein (SEP15) and glutathione peroxidase 1 (hGPX1) in paired malignant and non-malignant tissue. To achieve this goal, the quantitative real-time PCR technique was utilized in paired tissue samples from 33 non-small cell lung cancer (NSCLC) patients. Simultaneously, the activity of glutathione peroxidases (GPX) and the level of thiobarbituric acid-reactive species (TBARS) in paired tissue specimens and the blood plasma selenium level was measured. We found significant down-regulation of SEPP1 expression level in tumorous lung tissue (2.732-fold; p<0.001). The expression of hGPX1 and SEP15 in tumorous tissue remained unchanged compared to healthy tissue. The level of TBARS in malignant tissue was significantly increased (p<0.005) and negatively correlated with SEPP1 expression level (R(S)=-0.3238; p<0.05). The activity of GPX in malignant tissue was significantly increased compared to the non-malignant one (p<0.005) and negatively correlated with the expression level of SEPP1. It seems possible, that the down-regulation of SEPP1 expression may lead to an increased oxidative stress possibly resulting in lung carcinogenesis. Increased activity of GPX in tumorous lung tissue seems to be a feedback mechanism.