Kinase MB Research Articles

Correlation between serum miR-122 and myocardial damage and ventricular function in patients with essential hypertension.

BackgroundMyocardial damage and decreased ventricular function are risk factors leading to a bad prognosis in patients with essential hypertension (EH). MicroRNAs play important roles in myocardial function impairment in patients with hypertension. The purpose of our research was to investigate the correlation between serum miR-122 and myocardial damage and ventricular functions in EH patients.MethodsThe clinic data of EH patients (group A, n=60) and healthy individuals (group B, n=60) from December 2016 to December 2019 in our hospital were collected and analyzed. Serum miR-122, myocardial damage markers [B-type brain natriuretic peptide (BNP), homocysteine (Hcy), cardiac troponin T (cTnT) and creatine kinase MB isoenzyme (CK-MB)] and cardiac function indicators [ejection fraction (EF), left ventricular septal thickness (IVST), left ventricular isovolumic relaxation time (IVRT), left ventricular end-diastolic diameter (LVEDD), left ventricular posterior wall thickness (LVPWT), and left ventricular end-systolic diameter (LVESD)] were assessed in both groups. The correlation between serum miR-122 and myocardial damage markers and ventricular function indicators was analyzed.Results(I) The mean serum miR-122 concentration in group A and group B was 6.86±1.23 and 3.36±1.87 µmol/L, respectively. The serum miR-122 concentration in group A was evidently increased compared with that in group B. (II) The levels of BNP, Hcy, cTnT, and CK-MB in the peripheral blood in group A were evidently increased compared with those in group B (P<0.05). (III) EF and IVRT were evidently decreased in group A compared with that in group B (P<0.05). (IV) Serum miR-122 concentration was positively correlated with the myocardial damage markers BNP, Hcy, cTnT and CK-MB, and serum miR-122 concentration was negatively correlated with the ventricular function indicators EF and IVRT but not significantly correlated with other ventricular function indicators (IVST, LVEDD, LVPWT and LVESD).ConclusionsThe serum miR-122 concentration in EH patients was higher than that in healthy individuals, and miR-122 concentration was positively correlated with myocardial damage markers. Serum miR-122 level was negatively correlated with the ventricular function indicators EF and IVRT but was not significantly correlated with other ventricular function indicators (IVST, LVEDD, LVPWT, and LVESD).

Bone marrow-mesenchymal stem cell-derived exosomal microRNA-141 targets PTEN and activates β-catenin to alleviate myocardial injury in septic mice

Background Mesenchymal stem cells (MSCs) and their derived exosomes have shown potentials in the control of myocardial dysfunction. This study aimed to reveal the function of bone marrow (BM)-MSC-derived exosomes in sepsis-induced myocardial injury and the molecular mechanism. Methods BM-MSC-derived exosomes were obtained and identified. A mouse model with sepsis was induced by cecalligation puncture (CLP) and treated with exosomes. The myocardial function of mice, the production of creatine kinase MB (CK-MB) and lactate dehydrogenase (LDH) in serum, the phosphorylation of a key myocardial contractility-related protein phospholamban (PLB), and the pathological changes in the myocardial tissues were examined. A microRNA (miRNA) microarray analysis was performed to examine the candidate miRNAs carried by the exosomes. Rescue experiments were conducted to validate the involvement of miR-141. Results CLP treatment led to sepsis and notably reduced the myocardial function in mice. Further treatment of BM-MSC-derived exosomes alleviated the CLP-induced myocardial impairment, production of CK-MB and LDH, and inflammatory infiltration and cell apoptosis in mouse myocardial tissues, and restored the PLB phosphorylation. miR-141 was the most upregulated miRNA in the myocardial tissues after exosome treatment. Downregulation of miR-141 blocked the myocardium-protective functions of the exosomes. miR-141 was found to bind to and suppress PTEN expression, which further enhanced the activity of β-catenin. Conclusion This study suggested that BM-MSC derived exosomes ameliorates myocardial injury in septic mice through conveying miRNA-141 and regulating the PTEN/β-catenin axis, and exosomes may serve as promising tools for the management of myocardial injury induced by sepsis or other factors.

Takotsubo Cardiomyopathy After mRNA COVID-19 Vaccination

A healthy 63-year-old woman with no cardiovascular risk factors was admitted to the emergency room with new-onset dyspnoea and fever. The symptoms started 1 day after receiving the first of two mRNA-1273 (Moderna, Cambridge, MA, USA) COVID-19 vaccinations. She had no other prior complaints. A retronasal severe acute respiratory syndrome coronavirus 2 polymerase chain reaction test was negative. Laboratory tests revealed normal results for creatinine, creatine kinase, and creatine kinase MB (myocardial type). High-sensitivity troponin T was elevated at 320 ng/L (normal: <14 ng/L), and N-terminal pro-B-type natriuretic peptide was highly elevated at 10,180 pg/mL (normal: <284 pg/mL). C-reactive protein was elevated, but the leucocytes were within the normal range at 8.44 g/L (reference interval [RI]: 3.00–10.5 g/L). Urine and blood cultures were negative. Computed tomography scan of the chest revealed no pulmonary embolism but did show signs of heart failure. An electrocardiogram showed negative T waves over the inferior/anterior leads. Invasive coronary angiography ruled out coronary artery disease, but the ventriculogram (Figure 1) showed mid-ventricular to apical ballooning (asterisk) with preserved basal contraction (blues arrows) and a moderately impaired left ventricular ejection fraction of 40%. Apical ballooning was confirmed by echocardiography and cardiac magnetic resonance imaging (CMR). CMR tissue characterisation further depicted extensive oedema in the mid-ventricular/apical segments (i.e., T2-weighted imaging in the myocardium vs skeletal muscle with a signal intensity ratio of >2.0), elevated T2 mapping at 56 ms (RI: 42–50 ms), elevated T1 mapping at 1,158 ms (RI: 903–1,059 ms), and the extracellular volume fraction was elevated at 35% (RI: 25±4%). There was no late gadolinium enhancement suggesting peri-/myocarditis and no pleural or pericardial effusion. As there were no other stressors that could be determined to be underlying the midventricular/apical oedema and ballooning, the most probable diagnosis of COVID-19 vaccine-induced Takotsubo cardiomyopathy (TCM) was made. Although myocarditis is a possible differential diagnosis after COVID-19 vaccination [[1]Abu Mouch S. Roguin A. Hellou E. Ishai A. Shoshan U. Mahamid L. et al.Myocarditis following COVID-19 mRNA vaccination.Vaccine. 2021; 39: 3790-3793Crossref PubMed Scopus (137) Google Scholar], the clinical and investigative features of this case were strongly suggestive of TCM. There have been rare reports of TCM after influenza vaccination [[2]Singh K. Marinelli T. Horowitz J.D. Takotsubo cardiomyopathy after anti-influenza vaccination: catecholaminergic effects of immune system.Am J Emerg Med. 2013; 31: 1627Abstract Full Text Full Text PDF PubMed Scopus (16) Google Scholar,[3]Santoro F. Ieva R. Ferraretti A. Carpagnano G. Pappalardo I. De Gennaro L. et al.Tako-Tsubo cardiomyopathy after influenza vaccination.Int J Cardiol. 2013; 167: e51-e52Abstract Full Text Full Text PDF PubMed Scopus (8) Google Scholar], with an underlying pathophysiology of systemic inflammatory stress reaction after vaccination with a sympathovagal imbalance towards adrenergic predominance [[4]Lanza G.A. Barone L. Scalone G. Pitocco D. Sgueglia G.A. Mollo R. et al.Inflammation-related effects of adjuvant influenza A vaccination on platelet activation and cardiac autonomic function.J Intern Med. 2011; 269: 118-125Crossref PubMed Scopus (29) Google Scholar]. TCM confirmed by CMR after a COVID-19 vaccination has not yet been reported and may be considered as a differential diagnosis besides myocarditis in this clinical setting. Letter to the Editor Regarding: What Triggers Takotsubo After a SARS-CoV-2 Vaccination? Heart Lung Circ. 2021;30(12):e119–20Heart, Lung and CirculationVol. 31Issue 5PreviewWe read with interest the case report by Boscolo Berto et al. about a 63-year-old female who developed the classical type of Takotsubo cardiomyopathy (TTS) one day after her first jab of the Moderna vaccine [1]. The patient completely recovered without any treatment [1]. The study is appealing but raises several comments and concerns. Full-Text PDF

Upregulation of PCSK9, rho kinase and cardiac troponin by Eucalyptus globulus leaf extract improves fructose-streptozotocin-induced diabetic cardiac dysfunction in rats

Context The effect of Eucalyptus globulus in diabetic cardiac dysfunction and the possible mechanisms involved have not been explored. Objective To evaluate the effect of ethanol leaf extract of E. globulus (NEE) on the cardiac function of fructose/streptozotocin-induced diabetic rats. Materials and methods Type-2 diabetes was induced in rats with 10% fructose feeding for 14 days and an intraperitoneal administration of 40 mg/kg streptozotocin. Diabetic animals were treated with NEE (100–400 mg/kg) or 5 mg/kg glibenclamide orally for 21 days. Biochemical assays, histopathological examination and analyses of PCSK9, Rho kinase and Cardiac troponin expression were performed. Results The untreated diabetic group showed decreased expression of the genes, oxidative stress, dyslipidemia, increased activities of creatine kinase MB and lactate dehydrogenase, reduced nitric oxide level, and depletion of cardiomyocytes, which were reversed in NEE treated groups. Conclusions Eucalyptus globulus ameliorated diabetic cardiac dysfunction through increased PCSK9, Rho kinase and Cardiac troponin expression.

Effects of Danhong Injection () on Peri-Procedural Myocardial Injury and Microcirculatory Resistance in Patients with Unstable Angina Undergoing Elective Percutaneous Coronary Intervention: A Pilot Randomized Study.

To evaluate the effect of Danhong Injection (, DH) on the index of microcirculatory resistance (IMR) and myocardial injury in patients with unstable angina undergoing elective percutaneous coronary intervention (PCI). Seventy-eight patients with unstable angina were randomly divided into DH group (39 cases) and the control group (39 cases) during elective PCI. Randomization was performed using a random-number table. The DH group received DH at a dosage of 40 mL (mixed with 250 mL saline, covered by a light-proof bag, intravenous drip) during PCI and daily for 7 consecutive days, while the control group only received the same dosage of saline. Both groups received standardized treatment. The IMR and fractional flow reserve (FFR) were measured at maximal hyperemia before and after PCI. Myocardial markers, including myoglobin, creatine kinase (CK), creatine kinase MB (CK-MB), and coronary troponin T (cTnT) values were measured at baseline and 24 h after PCI. Among the 78 patients enrolled, the baseline and procedural characteristics were similar between the two groups. There was no significant difference in pre-PCI myocardial markers and coronary physiological indexes between the two groups. However, post-PCI CK and CK-MB levels in the DH group were significantly lower than those in the control group (111.97 ± 80.97 vs. 165.47 ± 102.99, P=0.013; 13.08 ± 6.90 vs. 19.75 ± 15.49, P=0.016). Post-PCI myoglobin and cTNT-positive tend to be lower in the DH group than in the control group but did not reach statistical significance (88.07 ± 52.36 vs. 108.13 ± 90.94, P=0.52; 2.56% vs.7.69%, P=0.065). Compared with the control group, the post-IMR levels of the DH group tended to decrease, but there was no statistical difference (20.73 ± 13.15 vs. 26.37 ± 12.31, P=0.05). There were no statistical differences in post-FFR in both groups. The peri-procedural myocardial injury of the DH group was significantly lower than that of the control group (2.56% vs. 15.38%, P=0.025). During the 30-d follow-up period, no major adverse cardiovascular events occurred in either group. This study demonstrated benefit of DH in reducing myocardial injury and potential preserving microvascular function in patients with unstable angina undergoing elective PCI.

Predictive value of creatine kinase MB for contrast-induced acute kidney injury among myocardial infarction patients

BackgroundPredictive value of creatine kinase MB (CK-MB) for contrast-induced acute kidney injury (CI-AKI) among myocardial infarction (MI) patients has rarely been reported. We aim to evaluate the predictive value of CK-MB for CI-AKI among MI patients.MethodsTotally, 1131 MI patients were included from the REduction of rIsk for Contrast-Induced Nephropathy (REICIN) study. The peak CK-MB before coronary angiography (CAG) was chosen. The study population was divided into two groups by log-transformed CK-MB cut-off point. The association between CK-MB and CI-AKI was tested by multivariable logistic regression. CK-MB was integrated with Age, creatinine and ejection fraction (ACEF) score and Mehran risk score (MRS) to evaluate the additive value of CK-MB. The integrated models were validated internally by the bootstrap method and externally by the PREdictive Value of COntrast voluMe to creatinine Clearance Ratio (PRECOMIN) study data set.ResultsOverall, 62(5.48%) patients developed CI-AKI, patients with CK-MB point > 4.7 displayed a higher incidence of CI-AKI than those without (11.9% vs. 4.0%, p < 0.001). CK-MB point > 4.7 was independently associated with CI-AKI (adjusted OR: 3.40, 95% CI: 1.93–5.98, p < 0.001). The additions of CK-MB to ACEF score, Mehran score A and Mehran score B resulted in increases in C-statistics, which ranged from 0.680 to 0.733 (p = 0.046), 0.694 to 0.727 (p = 0.091), 0.704 to 0.734 (p = 0.102), respectively. Internal validation also showed increases in C-statistics, and external validation performed well in discrimination and calibration.ConclusionsPreprocedural peak CK-MB was a predictor of CI-AKI among MI patients.

The role of adrenergic and muscarinic receptors in stress-induced cardiac injury.

Takotsubo syndrome (TS) is a rare but dangerous disease that can be fatal. The pathogenesis of TS is not well understood because there is no animal model of TS that fully mimics TS. It has now been documented that stress exposure (24h) of rats induced the state which is similar TS in human: contracture damage of myofibrils, elevation of the serum creatine kinase MB level, increased 99mTc-pyrophosphate (99mTc-PYP) accumulation in the heart, QTc interval prolongation, and contractility dysfunction of the heart. Immobilization stress resulted in an increase in coronary blood flow. Emotional stress increased the serum catecholamine level. Blockade of β1-adrenergic receptor (AR) prevented stress-induced cardiac injury (SICI). Blockade of β2-AR aggravated stress-induced cardiac injury. Stimulation of β2-AR increased cardiac tolerance to stress. Inhibition of β3-AR, α1-AR had no effect on SICI. Blockade of peripheral muscarinic receptors or α2-AR aggravated SICI. Pretreatment with the selective β1-AR antagonist atenolol attenuates stress-induced cardiac contractility dysfunction, but recovery of cardiac contractility is not complete. There is indirect evidence that circulating catecholamines play an important role in SICI. Consequently, the activation of β1-AR plays a significant role in SICI. However, there are other receptors which are also involved in SICI and require further investigation.

Les marqueurs sériques sont-ils corrélés au caractère invasif de la procédure en arthroplastie primaire de hanche ? Étude prospective randomisée comparant les approches antérieures et latérales directes

BackgroundAdvantages of minimally invasive approaches for total hip arthroplasty are still matter of debate. Serum markers have been assessed as objective method to quantify muscle damage after surgery but in literature ambiguous results have been reported. The aim of this prospective randomized study was to: 1) compare serum markers elevation between a minimally invasive direct anterior approach (DAA) and a direct lateral approach (DLA), 2) to establish a correlation between serum markers increase and other peri-operative variables.Hypothesis A lesser elevation of markers could be found in patients who underwent a minimally invasive DAA. Patients and methodsSeventy patients were enrolled and randomly divided in two groups according to the type of the approach. All patients were treated with the same implant by the same surgeon and received the same rehabilitation protocol. Demographic data, pre-operative Harris Hip Score (HHS) and operative time were recorded. Myoglobin, creatine kinase MB (CK-MB), troponin I, C-reactive protein (CRP), haemoglobin (HB) and pain levels were measured pre- and post-operatively. ResultsMean post-operative rise were 524.9±134.6 and 667.8±409.5 for myoglobin, 4.8±2.5 and 6.6±3.7 for CK-MB, and 16.9±5.3 and 15.4±6.4 for PCR, in DAA and DLA groups respectively. In both groups, post-operatively values were significantly higher than pre-operatively (p<0.05). Comparing the two groups, no significant differences in serum markers elevations were found. A significantly lower post-operative pain was found in DAA group than in DLA group [2,9 vs. 4,2 and 2,7 vs. 3,6 in second and third day, respectively (p<0.05)]. No significant correlation was present between the serum marker elevations and age, BMI, HHS, operative time, HB or pain levels (p>0.05). ConclusionSerum markers of muscle damage and inflammation increased in the post-operative period without significant differences between DAA and DLA, even though overall trend was higher in DLA group. The DAA group had significantly lower levels of post-operative pain. No significant correlation between pain and serum markers levels was found. Level of evidenceI; randomized study.

Selenium mitigated aflatoxin B1-induced cardiotoxicity with potential regulation of 4 selenoproteins and ferroptosis signaling in chicks

The aim of the present study was to explore the underlying mechanism of selenium (Se)-mediated detoxification of aflatoxin B1 (AFB1)-induced cardiotoxicity in chicks. A Se-deficient, corn-soybean meal-basal diet (36 μg Se/kg, BD) and three test diets (BD+1.0 mg AFB1/kg, 0.3 mg Se/kg, or 1.0 mg AFB1/kg+0.3 mg Se/kg) were used in a 3-wk 2 × 2 factorial design trial (n = 30 chicks/group). Dietary AFB1 led to induced (P < 0.05) serum creatine kinase and creatine kinase MB isoenzyme activities and heart histopathologic lesions. However, Se deficiency aggravated most of these alterations induced by AFB1. Moreover, mRNA levels of two ferroptosis activators (solute carrier family 11 Member 2 and transferrin) were upregulated (P < 0.05) in the AFB1-treated groups. Additionally, Se deficiency reduced (P < 0.05) glutathione peroxidase (GPX) 3 and thioredoxin reductase 3 mRNA and GPX activity but increased (P < 0.05) selenoprotein M and selenophosphate synthetase 2 mRNA in the heart in AFB1-administered groups. The in vitro study showed that Se alleviated (P < 0.05) AFB1-reduced cell viability and induced (P < 0.05) ROS and ferroptosis in H9C2 cardiac cells. It also downregulated (P < 0.05) two ferroptosis activators (long-chain acyl-CoA synthetase 4 and solute carrier family 11 Member 2) in the AFB1-treated groups in the H9C2 cells. In conclusion, this study illustrated that Se alleviates AFB1-induced cardiotoxicity and cardiomyocyte damage potentially related to the regulation of redox status, 4 selenoproteins, and ferroptosis-related signaling.

Resveratrol activates PI3K/AKT to reduce myocardial cell apoptosis and mitochondrial oxidative damage caused by myocardial ischemia/reperfusion injury

Resveratrol is a kind of iPolyphenols widely existing in herbal medicine. Here we aim to investigate whether resveratrol can reduce the degree of myocardial ischemia/reperfusion (IR) injury and inhibit the development of oxidative stress, and elucidate the molecular mechanism of resveratrol in protecting myocardial cells. The primary rat cardiomyocytes were used to establish an ischemia/reperfusion model in vitro, and a series of routine biochemical experiments were conducted to explore the antioxidant and anti-apoptotic effects of resveratrol in myocardial ischemia-reperfusion injury. Compared with that of the simulated ischemia-refusion (SIR) group, cell viability in the SIR and resveratrol co-treatment groups increased significantly (P < 0.001), the release of lactate dehydrogenase (LDH) and creatine kinase MB (CKMB) decreased, the positive rate of reactive oxygen species (ROS) in cardiomyocytes decreased, and the concentration of catalase and glutathione peroxidase increased significantly (P < 0.001). Besides, resveratrol can activate PI3K/AKT signaling pathway. PI3K siRNA can inhibit the PI3K/AKT signaling mediated by resveratrol. The addition of resveratrol can significantly increase the activity of mitochondrial superoxide dismutase (SOD) and reduce the malondialdehyde (MDA), which indicates that the oxidative damage of mitochondria induced by resveratrol was significantly weakened. The mitochondrial functional changes induced by resveratrol can be reversed by PI3K siRNA. In conclusion, our study shows that resveratrol can reduce ROS in cardiomyocytes by PI3K/AKT signaling pathway activation, and effectively inhibit the apoptosis of cardiomyocytes, thus having a direct protective effect on cardiomyocytes under SR.

How Well Do Laboratories Adhere to Recommended Guidelines for Cardiac Biomarkers Management in Europe? The CArdiac MARker Guideline Uptake in Europe (CAMARGUE) Study of the European Federation of Laboratory Medicine Task Group on Cardiac Markers.

The CARdiac MARker Guideline Uptake in Europe (CAMARGUE) program is a multi-country audit of the use of cardiac biomarkers in routine clinical practice. An email link to a web-based questionnaire of 30 multiple-choice questions was distributed via the professional societies in Europe. 374 questionnaires were returned from 39 countries, the majority of which were in northern Europe with a response rate of 8.2%-42.0%. The majority of the respondents were from hospitals with proportionately more responses from central hospitals than district hospitals. Cardiac troponin was the preferred cardiac biomarker, evenly split between cardiac troponin T (cTnT) and cardiac troponin I (cTnI). Aspartate transaminase and lactate dehydrogenase are no longer offered as cardiac biomarkers. Creatine kinase, creatine kinase MB isoenzyme, and myoglobin continue to be offered as part of the cardiac biomarker profile in approximately on 50% of respondents. There is widespread utilization of high sensitivity (hs) troponin assays. The majority of cTnT users measure hs-cTnT. 29.5% of laboratories measure cTnI by a non-hs method but there has been substantial conversion to hs-cTnI. The majority of respondents used ng/L and use the 99th percentile as the upper reference limit (71.9% of respondents). A range of diagnostic protocols are in use. There is widespread utilization of hs troponin methods. A significant minority do not use the 99th percentile as recommended and there is, as yet, little uptake of very rapid diagnostic strategies. Education of laboratory professionals and clinicians remains a priority.

Reactive Hyperglycaemia Connected with Low Glycated Haemoglobin – Risk Factor for Cardiovascular Adverse Events

Introduction: Concomitance of glucose metabolism disturbances and ischemic heart disease is well known and connected to several times higher incidence of cardiovascular events resulted from atherosclerosis. Aim of this study was to assess impact of reactive hyperglycaemia accompanying chronic and not always optimally treated hyperglycaemia assessed with glycated haemoglobin level on cardiovascular prognosis among patient hospitalised in the course of acute myocardial infarction. Methods: 92 patients diagnosed with ST – segment elevation myocardial infarction (STEMI) qualified to primary percutaneous coronary intervention (pPCI) was included in the study. Study population was divided into subgroups, depending glucose level on admission (reactive hyperglycaemia) and HbA1c concentration: subgroup A (HbA1c &lt;6.5%, Glc&lt;7.8 mmol/l: n = 37; 40,2%), subgroup B (HbA1c &lt;6.5%, Glc ≥.,8 mmol/l: n = 27; 29,3%), subgroup C (HbA1c ≥6.5%, Glc ≥7.8 mmol/l: n = 20; 21,7%) and subgroup D (HbA1c ≥6.5% Glc&lt;7.8 mmol/l: n = 8; 8.7%). Level of myocardium damage was assessed on the basis of concentration of myocardial necrosis enzymes: creatine kinase (CK) and creatine kinase MB fraction (CK-MB) in the 0 and 90th minute and thereafter 8, 16, 24 and 48 hours after hospital admission and also echocardiographic examination. Prognosis in long and short term observation was assessed by major adverse cardiovascular events (MACE) such as death, myocardial infarction, stroke, heart failure requiring hospitalisation and repeated revascularisation and level of glucose metabolism disturbances in intrahospital phase, 4 months and 4 years follow up observation. Results: Results in study population revealed significant change of average value of creatine kinase (p&lt;0,001) and its MB fraction (p&lt;0,001) during first 48 hours of hospitalisation in particular subgroups of patients. Mean values of CK and CK-MB assessed in subsequent hours of hospitalisation (1,5, 8, 16 and 48 hours) were significantly higher in subgroup B (CKp=0,034 and CK-MB p=0,01, respectively). It means that area under curve was significantly higher for subgroup B. In 4 months and 4 year follow up observation, statistically significant difference in frequency of MACE in particular subgroups of patients has been shown (p=0,016; p=0,01). Conclusions: Patients with STEMI undergoing pPCI, who were diagnosed with disturbed carbohydrate metabolism, have inferior clinical outcomes in long term follow up observation. Noticeable difference was observed particularly in subgroup B (HbA1c &lt;6.5%, Glc ≥7.8 mmol/l).

Efficacy of HX008 in high microsatellite instability/mismatch repair–defificient (MSI-H/dMMR) solid tumors: Results from a multicenter phase II open-label study.

2572 Background: The subsequent treatment choices are limited for the patients with advanced solid tumors who had failed the standard therapies. PD-1 blockade monotherapy demonstrated robust antitumor activity in patients with MSI-H/dMMR. The aim of this study is to identify the efficacy and safety of HX008, an anti-PD-1 monoclonal antibody, in patients with advanced MSI-H/dMMR solid tumors. Methods: Eligible patients were age ≥18 years with histologically/cytologically confirmed advanced MSI-H/dMMR solid tumors, who have failed at least one line of standard systemic therapy. MSI-H/dMMR status was assessed centrally. Patients received HX008 200 mg once every 3 weeks until disease progression, unacceptable toxicity, or patient withdrawal. Radiologic imaging was performed 9 weeks after the first treatment, then every 6 weeks for the first year of therapy, and every 12 weeks thereafter. The primary end point was objective response rate (ORR) per RECIST1.1. Results: One hundred patients were enrolled from October 2018 to December 2020, with a median age of 53 (range 20-74) years. All of the patients were ≥ second-line patients. The most common cancer types were colorectal cancer (N=74) and gastric cancer (N=10). Median follow-up is 8.97 (range 0.03-25.53) months at the time of data cutoff. Among 86 patients who had reached the initial response evaluation, there were 8 CR, 33 PR, 24 SD, 17 PD and 4 NE. ORR was 47.67% (95%CI 36.79%-58.73%), and DCR was 75.58% (95%CI 65.13%-84.20%). ORR and DCR for the 66 colorectal cancer patients were 50% (95%CI 37.43-62.57%) and 75.76% (95%CI 63.64-85.46%). Median PFS was not reached (95%CI 6.18-NR) for all enrolled patients, while the 6-month and 12-month PFS rates were 62.66% (95%CI 50.98%-72.31%) and 52.70% (95%CI 39.96%-63.94%), respectively. Median OS was not reached. Treatment-related adverse events occurred in 77 patients (77%). Twelve patients (12%) had grade 3 or 4 treatment-related adverse events and there were no grade 5 treatment-related adverse events. The grade 3 or 4 treatment-related adverse events with incidence &gt;1% included anemia (2%) and leukopenia (2%). Immune-related adverse events were observed in 15 patients (15%), including hypothyroidism in 9 patients (all were grade 1-2), and hepatitis, hyperglycemia, myocarditis, creatin kinase/creatin kinase MB increased, hypopigmentation of the vulva, rash, each in 1 patient. Conclusions: HX008 as a ≥second-line therapy showed promising efficacy and a manageable safety profile in patients with MSI-H/dMMR advanced solid tumors. Clinical trial information: NCT03704246.

Aggrecan: a new biomarker for acute type A aortic dissection

Acute type A aortic dissection (ATAAD) constitutes a life-threatening aortic pathology with significant morbidity and mortality. Without surgical intervention the usual mortality rate averages between 1 and 2% per hour. Thus, an early diagnosis of ATAAD is of pivotal importance to direct the affected patients to the appropriate treatment. Preceding tests to find an appropriate biomarker showed among others an increased aggrecan (ACAN) mRNA expression in aortic tissue of ATAAD patients. As a consequence, we investigated whether ACAN is a potential biomarker for diagnosing ATAAD. Mean ACAN protein concentration showed a significantly higher plasma concentration in ATAAD patients (38.59 ng/mL, n = 33) compared to plasma of patients with thoracic aortic aneurysms (4.45 ng/mL, n = 13), patients with myocardial infarction (11.77 ng/mL, n = 18) and healthy volunteers (8.05 ng/mL, n = 12). Cardiac enzymes like creatine kinase MB and cardiac troponin T showed no correlation with ACAN levels in ATAAD patients. Receiver-operator characteristics (ROC) curve analysis for ATAAD patients versus control subjects an optimum discrimination limit of ACAN plasma levels at 14.3 ng/mL with a corresponding sensitivity of 97% and specificity of 81%. According to our findings ACAN is a reliable potential biomarker in plasma samples to detect ATAAD with high sensitivity and specificity.

Test Volume Ratio Benchmarking to Identify and Reduce Low-Value Laboratory Utilization.

We analyzed test volume data to identify low-value test utilization. We subsequently tracked the efficacy of interventions to improve test utilization by decreasing low-value testing. Test volume data for analytes included in the Choosing Wisely guidelines were analyzed to identify population outliers. Outliers were defined by test volume ratios of either analyte to sodium or paired analytes to correct for variation in patient volumes at each site. Interventions to improve test utilization were targeted to outlier sites. Relative efficacy in reducing low-value testing was tracked at those sites. After appropriate data cleaning, test volume ratios for 17 analytes paired with sodium and 8 pairs of analytes were acquired from 108 national sites. A site with abnormally high Clostridium difficile/sodium ratio was selected for intervention, leading to a 71% decrease in C difficile tests. Two different interventions to decrease creatine kinase MB isoform (CKMB) testing were performed at two unique sites with abnormally high CKMB/troponin ratios. These interventions decreased CKMB by 11% and 98% at the different sites, showing the efficacy of the different kinds of interventions. Test volume ratio analysis and benchmarking enable identification of low-value test utilization.

The Role of Adrenergic Receptors, Muscarinic Receptors, Glucocorticoids, Reactive Oxygen Species in Stress‐Induced Cardiac Injury

Takotsubo syndrome (TS) is a rare but dangerous disease that can be fatal. The pathogenesis of TS is not well understood because there is no animal model of TS that would be as close as possible to TS. We hypothesized that adrenergic receptors, muscarinic receptors, glucocorticoids, reactive oxygen species (ROS) can be involved in the development of stress-induced cardiac injury (SICI). It was established that immobilization of rats induced the state which is similar TS in human: increased 99mTc-pyrophosphate (99mTc-PP) accumulation in the heart, QTc interval prolongation, contractility dysfunction of the heart, elevation of the serum creatine kinase MB level. Immobilization stress induced an increase in coronary blood flow. Blockade of β1-adrenergic receptor (AR) prevents 99mTc-PP accumulation in the myocardium. Blockade of β2-AR aggravates SICI. Stimulation of β2-AR increased cardiac tolerance to stress. Inhibition of β3-AR, α1-AR, mineralocorticoid receptor and angiotensin AT1 receptor had no effect on SICI. Blockade of peripheral muscarinic receptors or α2-AR aggravates SICI. Inhibition of glucocorticoid receptor attenuated but not abolished SICI. Pretreatment with the selective β1-AR antagonist atenolol attenuates stress-induced cardiac contractility dysfunction but not recover cardiac contractility completely. It was established that ROS are not involved in SICI. It was obtained indirect evidence that circulated in blood catecholamines play an important role in SICI. Consequently, the activation of β1-AR plays an important role in SICI. However, there are other receptors which are also involved in SICI.

Do serum markers correlate with invasiveness of the procedure in THA? A prospective randomized study comparing direct anterior and lateral approaches

BackgroundAdvantages of minimally invasive approaches for total hip arthroplasty are still matter of debate. Serum markers have been assessed as objective method to quantify muscle damage after surgery but in literature ambiguous results have been reported. The aim of this prospective randomized study was to: 1) compare serum markers elevation between a minimally invasive direct anterior approach (DAA) and a direct lateral approach (DLA); 2) to establish a correlation between serum markers increase and other perioperative variables. HypothesisA lesser elevation of markers could be found in patients who underwent a minimally invasive DAA. Patients and methodsSeventy patients were enrolled and randomly divided in two groups according to the type of the approach. All patients were treated with the same implant by the same surgeon and received the same rehabilitation protocol. Demographic data, preoperative Harris Hip Score (HHS) and operative time were recorded. Myoglobin, creatine kinase MB (CK-MB), troponin I, C-reactive protein (CRP), haemoglobin (HB) and pain levels were measured pre- and postoperatively. ResultsMean postoperative rise were 524.9±134.6 and 667.8±409.5 for myoglobin, 4.8±2.5 and 6.6±3.7 for CK-MB, and 16.9±5.3 and 15.4±6.4 for PCR, in DAA and DLA groups, respectively. In both groups, postoperatively values were significantly higher than preoperatively (p<0.05). Comparing the two groups, no significant differences in serum markers elevations were found. A significantly lower postoperative pain was found in DAA group than in DLA group (2.9 vs. 4.2 and 2.7 vs. 3.6 in second and third day, respectively (p<0.05)). No significant correlation was present between the serum marker elevations and age, BMI, HHS, operative time, HB or pain levels (p>0.05). ConclusionSerum markers of muscle damage and inflammation increased in the postoperative period without significant differences between DAA and DLA, even though overall trend was higher in DLA group. The DAA group had significantly lower levels of postoperative pain. No significant correlation between pain and serum markers levels was found. Level of evidenceI; randomized study.

Epidemiological and clinical presentations of hospitalized COVID-19 patients in Libya: An initial report from Africa

BackgroundThe first case of the novel coronavirus disease 2019 (COVID-19) in Libya was diagnosed in March 2020. We aimed to determine the epidemiological, clinical, and laboratory characteristics of COVID-19 in Libya. MethodIn this retrospective descriptive study, we analyzed the demographics, initial clinical presentation, history, comorbidities, laboratory findings, complications, and outcomes of hospitalized patients with COVID-19 at several centers in the Western part of Libya between March 24, 2020, and December 3, 2020. ResultsThe study included 811 (67.2%) men and 396 (32.8%) women. The median (interquartile range [IQR]) age was 56 (40–64). A total of 173 (14.3%) patients developed respiratory distress syndrome, while 70 (5.8%) developed circulatory shock and hypotension; 190 (15.7%) were admitted to the intensive care unit. Acute cardiac injury occurred in 27 (2.2%) patients, and 45 (3.7%) developed arrhythmia. Acute kidney injury occurred in 44 (3.6%) patients. Of the patients admitted during the study period, 149 (12.3%) died. The predominant comorbidities ordered in a descending manner were as follows; diabetes mellitus, presented 490 (40.6%), hypertension in 414 (34.3%), chronic kidney disease in 114 (9.4%), and lung diseases in 103 (8.5%). The total white blood cell, neutrophil; monocyte; D-dimer; creatinine kinase; creatine kinase–MB; creatinine; total bilirubin; alanine and aspartate aminotransferase; and hypersensitive troponin were increased among non-survivors, whereas lymphocyte and platelet counts were decreased among non-survivors. ConclusionThis is the first report of the clinical presentations and laboratory findings in patients hospitalized with COVID-19 in Libya. Libyan authorities must implement several restrictions to control the pandemic. However, incoming international travelers pose a challenge to the local authorities, especially with the recent discovery of new variants.

Extracorporeal Membrane Oxygenation for Fulminant Myocarditis: Increase of Cardiac Enzyme and SOFA Score Is Associated with High Mortality.

We aimed to evaluate the outcomes of patients with fulminant myocarditis and investigate the factors associated with mortality. This is a retrospective single-center cohort study that included adult and pediatric patients with fulminant myocarditis treated at Samsung Medical Center between September 2004 and December 2019. The primary outcome was in-hospital mortality. Among 100 patients, 71 underwent veno-arterial extracorporeal membrane oxygenation (ECMO) (ECMO group). Comorbidities were not significantly different between the ECMO and non-ECMO groups. Cardiac enzymes, creatinine, and median sequential organ failure assessment (SOFA) score at intensive care unit admission were significantly different between the groups. Twenty patients (28.7%) in the ECMO group and two (6.9%) in the non-ECMO group died in-hospital (p = 0.02). The significant risk factors of in-hospital mortality were creatine kinase MB fraction (CK-MB) and SOFA score (p = 0.009 and p = 0.001, respectively) in the ECMO group. In the receiver-operating characteristic curve analysis, the cutoffs of SOFA score and CK-MB were 12 and 94.74 ng/mL, respectively. The patients with both variables above the cutoffs showed significantly worse outcomes (p < 0.001). ECMO can be an effective treatment option for fulminant myocarditis. SOFA score and CK-MB are significant risk factors for in-hospital mortality.

Antidepressants Relieved Consecutive Chest Pain after Radiofrequency Ablation

Preexcitation symptom presents morbidity of 0.1% to 0.3% in the general population, which could lead to deadly events while accompanying arrhythmia. The classical type is Wolff-Parkinson-White (WPW) syndrome characterized as a shorter PR period, longer QRS duration, and δ wave. Radiofrequency catheter ablation (RCA) takes a vital role in treating WPW and has a high success rate. While some patients complain of consecutive chest pain after RCA, which influence their daily life severely. A 45-year-old man went to a hospital for examination because of uncomfortable palpitation. The electrocardiogram (ECG) presenting WPW syndrome (left free wall accessory pathway), then he was admitted to the hospital and scheduled for RCA. The RCA was very successful and the ECG became normal. However, after ablation, he reported consecutive chest pain, accompanied by insomnia and hypertension. No abnormal elevations of cardiac-Troponin I, myoglobin, cytokeratin, creatine kinase MB were found, and the left ventricular ejection fraction was 60%. His mental status was measured by Patient-Health Questionnaire-9, 7-item Generalized Anxiety Disorder Scale-7, Athens Insomnia Scale, indicating depressive status and anxiety status. The predominant managements involved flupentixol-melitracen and duloxetine. His chest pain, depressive, and anxiety symptoms were gradually relieved after 3-month treatment, and the drugs were slowly tapered in the 1½ years' follow-up period. Ultimately, he recovered and worked as before. This case highlights the importance of evaluating psychological status in patients with unexplained chest pain resulting from RCA and adopting antidepressants in those patients that coexist with definite depression or anxiety.