Peripheral levels of matrix metalloproteinase-9, interleukin-6, and C-reactive protein are elevated in patients with acute coronary syndromes: correlations with serum troponin I

BACKGROUND: Acute coronary syndromes (ACS) are characterized by activation of systemic and local inflammatory mediators. The interrelation between these soluble inflammatory markers and their association with markers of myocardial necrosis have not been extensively studied. HYPOTHESIS: The study was undertaken to evaluate the association of the systemic levels of matrix metalloproteinase-9 (MMP-9) and the tissue inhibitor of metalloproteinase-1 (TIMP-1), with C-reactive protein (CRP), interleukin-6 (IL-6), and serum troponin-I in patients admitted with ACS. METHODS: Analysis of serum concentrations of the above inflammatory markers was performed in 53 patients with unstable angina (UA) and in 15 with non-ST-segment elevation myocardial infarction (NSTEMI) within 48 h of admission, and 34 patients with stable coronary artery disease. RESULTS: Compared with patients with stable angina, those with ACS had elevated admission levels of MMP-9 (p = 0.04), CRP (p < 0.001), and IL-6 (p = 0.001), but not TIMP-1 (p = 0.55). Compared with patients with UA, those with NSTEMI also had higher levels of IL-6 (p < 0.001), CRP (p = 0.002), and MMP-9 (p = 0.05). CONCLUSIONS: In patients with ACS, the admission levels of inflammatory mediators, including MMP-9, CRP, and IL-6 are significantly elevated, specifically in association with serum troponin I. Systemic and local markers of inflammatory activity may be directly associated with myocardial injury.     

Effects of combined deferiprone and deferoxamine chelation therapy on iron load indices in beta-thalassemia

The benefits of combined deferoxamine (DFO) and deferiprone (L1) chelation therapy, focusing on reducing myocardial iron loading, have been widely reported. Herein, we present the efficacy of combined chelation and its effects on iron load indices. Five thalassemia major (TM) patients who were undergoing chelation monotherapy with DFO were enrolled. Inclusion criteria were magnetic resonance imaging (MRI) T2* values, indicating serious heart and/or liver transfusional hemosiderosis. Combined therapy was started with the same dose of DFO and the addition of L1. The MRI T2* studies were repeated 18 months later. An Echo-Doppler study was performed in order to further evaluate the left ventricular (LV) systolic function. Within the 18 months' follow-up period, there was a significant statical decrease in mean serum ferritin levels. All patients increased their MRI T2* liver values, while two patients with very low MRI T2* also increased their myocardial values. The MRI ejection fraction (EF) and Echo-Doppler study measurements confirmed the improvement of systolic function. No adverse effects were reported. Combined L1 and DFO therapy seems to be effective in reducing iron excess in organ iron overloaded thalassemic patients. Magnetic resonance imaging can accurately quantify iron load, while echocardiography remains a reliable monitoring technology.     

Effect of early application of social distancing interventions on COVID-19 mortality over the first pandemic wave: An analysis of longitudinal data from 37 countries

ObjectivesTo estimate the effect of early application of social distancing interventions on Covid-19 cumulative mortality during the first pandemic wave.MethodsEcological longitudinal study using multivariable negative binomial regression for panel data. Daily numbers of Covid-19 cases and deaths, and data on social distancing interventions, for the 37 member countries of the Organization for Economic Cooperation and Development (OECD) were analysed.ResultsCovid-19 cumulative mortality over the first pandemic wave varied widely across countries (range, 4.16 to 855 deaths per million population). On average, one-day delay in application of mass gatherings ban was associated with an adjusted increase in Covid-19 cumulative mortality by 6.97% (95% CI, 3.45 to 10.5), whilst a one-day delay in school closures was associated with an increase of 4.37% (95% CI, 1.58 to 7.17) over the study period. We estimated that if each country had enacted both interventions one week earlier, Covid-19 cumulative mortality could have been reduced by an average of 44.1% (95% CI, 20.2 to 67.9).ConclusionsEarly application of mass gatherings ban and school closures in outbreak epicentres was associated with an important reduction in Covid-19 cumulative mortality during the first pandemic wave. These findings may support policy decision making.     

Normalizing Glutamine Concentration Causes Mitochondrial Uncoupling in an In Vitro Model of Human Skeletal Muscle

Background: Glutamine has been considered essential for rapidly dividing cells, but its effect on mitochondrial function is unknown. Materials and Methods: Human myoblasts were isolated from skeletal muscle biopsy samples (n = 9) and exposed for 20 days to 6 different glutamine concentrations (0, 100, 200, 300, 500, and 5000 µM). Cells were trypsinized and manually counted every 5 days. Seven days before the end of exposure, half of these cells were allowed to differentiate to myotubes. Afterward, energy metabolism in both myotubes and myoblasts was assessed by extracellular flux analysis (Seahorse Biosciences, Billerica, MA). The protocol for myoblasts was optimized in preliminary experiments. To account for different mitochondrial density or cell count, data were normalized to citrate synthase activity. Results: Fastest myoblast proliferation was observed at 300 µM glutamine, with a significant reduction at 0 and 100 µM. Glutamine did not influence basal oxygen consumption, anaerobic glycolysis or respiratory chain capacity. Glutamine significantly (P = .015) influenced the leak through the inner mitochondrial membrane. Efficiency of respiratory chain was highest at 200–300 µM glutamine (~90% of oxygen used for adenosine triphosphate synthesis). Increased glutamine concentration to 500 or 5000 µM caused mitochondrial uncoupling in myoblasts and myotubes, decreasing the efficiency of the respiratory chain to ~70%. Conclusion: Glutamine concentrations, consistent with moderate clinical hypoglutaminemia (300 µM), bring about an optimal condition of myoblast proliferation and for efficiency of aerobic phosphorylation in an in vitro model of human skeletal muscle. These data support the hypothesis of hypoglutaminemia as an adaptive phenomenon in conditions leading to bioenergetic failure (eg, critical illness).     

“I’ve got somebody there,someone cares”: what support is most valued following a stroke?

Purpose: There is often a need for increased support following a stroke. This study explored what types of support are provided by different network members and what support functions are most valued.

Methods: Adults with first stroke were recruited from a stroke unit and participated in in-depth interviews 8–15 months poststroke. Framework Analysis was used to build thematic and explanatory accounts of the data.

Results: Twenty-nine participants took part. Main themes to emerge were as follows: the spouse was the most important provider of support; children were a relatively stable source of support, although many participants expressed reservations about worrying a child; relatives and friends typically provided social companionship and emotional support rather than on-going practical support. The only universally valued support function was the sense that someone was concerned and cared. Other valued functions were as follows: social companionship including everyday social “chit chat”; practical support provided sensitively; and, for many, sharing worries and sensitive encouragement. The manner and context in which support was provided was important: support was easiest to receive when it communicated concern, and was part of a reciprocal, caring relationship.

Conclusions: As well as measuring supportive acts, researchers and clinicians should consider the manner and context of support.

• Implications for rehabilitation

• The manner in which support was provided mattered: support was easier to receive when it communicated concern.

• The spouse was the most important source of all support functions; children, relatives and friends were important providers of emotional and social companionship support.

• Researchers and clinicians should not only focus on what support is received, but also the context (e.g., contribution, reciprocity, quality of relationship) and manner (e.g., responsiveness, sensitivity) of the support.

     

Pharmacotherapy in complicated parapneumonic pleural effusions and thoracic empyema

Parapneumonic pleural effusions (PPE) and pleural empyema (PE) present a frequently diagnostic and therapeutic challenge in clinical practice. Although pleural diseases have received increased attention during the past decade, there are still many unanswered questions concerning the diagnosis and treatment of PPE and PE. A lack of controlled studies concerning the management of PPE and PE was noted in recent guidelines. The use of fibrinolytics intrapleurally appears to enhance intercostals tube drainage, reducing the requirement for subsequent surgical mechanical debridement. Recently, there has been interest in other intrapleural agents including combination drugs consisting of streptokinase and streptodornase-alpha, Dnase. Factors to be considered in evaluating whether or not intrapleural instillation of fibrinolytics is effective include an assessment of clinical responses. This review discusses the use of fibrinolytic agents as a novel therapeutic options for treating the various stages of parapneumonic effusions and empyemas.     

Physical training modulates proinflammatory cytokines and the soluble Fas/soluble Fas ligand system in patients with chronic heart failure

OBJECTIVES: We sought to investigate the effects of physical training on circulating proinflammatory cytokines and the soluble apoptosis mediators Fas (sFas) and Fas ligand (sFasL) in patients with chronic heart failure (CHF). BACKGROUND: Recent investigations have shown an overexpression of circulating proinflammatory cytokines and soluble apoptosis mediators in patients with CHF, which may be related to their exercise intolerance and clinical deterioration. METHODS: Plasma levels of tumor necrosis factor-alpha (TNF-alpha), soluble TNF receptors I and II (sTNF-RI and sTNF-RII, respectively), interleukin-6 (IL-6), soluble IL-6 receptor (sIL-6R), sFas and sFasL were measured in 24 patients with stable CHF (New York Heart Association functional class II/III; left ventricular ejection fraction 23.2 +/- 1.3%) and in 20 normal control subjects before and after a 12-week program of physical training in a randomized, crossover design. Functional status of patients with CHF was evaluated by using a cardiorespiratory exercise test to measure peak oxygen consumption (VO2max). RESULTS: Physical training produced a significant reduction in plasma levels of TNF-alpha (7.5 +/- 1.0 pg/ml vs. 4.6 +/- 0.7 pg/ml, p < 0.001), sTNF-RI (3.3 +/- 0.2 ng/ml vs. 2.7 +/- 0.2 ng/ml, p < 0.005), sTNF-RII (2.6 +/- 0.2 ng/ml vs. 2.3 +/- 0.2 ng/ml, p = 0.06), IL-6 (8.3 +/- 1.2 pg/ml vs. 5.9 +/- 0.8 pg/ml, p < 0.005), sIL-6R (34.0 +/- 3.0 ng/ml vs. 29.2 +/- 3.0 ng/ml, p < 0.01), sFas (5.5 +/- 0.7 ng/ml vs. 4.5 +/- 0.8 ng/ml, p = 0.05) and sFasL (34.9 +/- 5.0 pg/ml vs. 25.2 +/- 4.0 pg/ml, p < 0.05), as well as a significant increase in VO2max (16.3 +/- 0.7 ml/kg per min vs. 18.7 +/- 0.8 ml/kg per min, p < 0.001). Good correlations were found between a training-induced increase in VO2max and a training-induced reduction in levels of the proinflammatory cytokine TNF-alpha (r = -0.54, p < 0.01) and the apoptosis inducer sFasL (r = -0.57, p < 0.005) in patients with CHF. In contrast, no significant difference in circulating cytokines and apoptotic markers was found with physical training in normal subjects. CONCLUSIONS: Physical training reduces plasma levels of proinflammatory cytokines and the sFas/sFasL system in patients with CHF. These immunomodulatory effects may be related to the training-induced improvement in functional status of patients with CHF.     

Deferment of objective assessment of deep vein thrombosis and pulmonary embolism without increased risk of thrombosis: a practical approach based on the pretest clinical model, D-dimer testing, and the use of low-molecular-weight heparins

BACKGROUND: Treatment of patients with suspected deep vein thrombosis (DVT) or pulmonary embolism (PE) is problematic if diagnostic imaging is not immediately available. Pretest clinical probability (PCP) and D-dimer assessment can be used to identify patients for whom empirical protective anticoagulation is indicated. To evaluate whether PCP and D-dimer assessment, together with the use of low-molecular-weight heparins (LMWHs), allow objective appraisal of DVT and PE to be deferred for up to 72 hours, patients with suspected DVT and PE were prospectively examined. METHODS: Patients identified with a high PCP or a moderate PCP with positive D-dimer test results received a protective full-dose treatment of LMWH; the remaining patients were discharged without anticoagulant administration. However, all patients were scheduled to undergo objective tests for DVT or PE within 72 hours. Standard antithrombotic therapy was administered when deferred diagnostic tests confirmed venous thromboembolism. RESULTS: In total, 409 consecutive patients with suspected DVT and 124 with suspected PE were included in this study. A total of 23.8% (95% confidence interval [CI], 20.3%-27.3%) of patients had confirmed venous thromboembolism. At the short-term follow-up (72 hours), only a single thromboembolic event (0.2%; upper 95% CI, 0.6%) had occurred, whereas at the 3-month follow-up, 5 events (1.2%; 95% CI, 0.2%-2.1%) had occurred in patients in whom diagnosis of DVT or PE had previously been ruled out. None of the patients had major bleeding events. Ninety percent of patients were treated as outpatients. CONCLUSION: Our study demonstrates that this approach allows the safe deferral of diagnostic procedures for DVT and PE for up to 72 hours.