Coagulation profiles in patients with sepsis/septic shock identify mixed hypo-hypercoagulation patterns based on rotational thromboelastometry: A prospective observational study.

INTRODUCTION: Sepsis-induced hemostatic disturbances are common and are associated with poor outcomes. Additionally, conventional coagulation tests (CCTs) overdiagnose hypocoagulation and cannot detect hypercoagulation and hyperfibrinolysis. The aim of this study was to describe the coagulation profiles of patients with sepsis/septic shock using rotational thromboelastometry (ROTEM) and to compare coagulation states between sepsis and septic shock groups and between surviving and non-surviving groups. MATERIALS AND METHODS: This prospective, observational, single-center study was conducted in the intensive care unit (ICU) of the University Medical Center Ho Chi Minh City, from 6/2020-12/2021. Patients aged ≥18 years with sepsis or septic shock according to the Sepsis-3 criteria were included. ROTEM and CCTs were concurrently performed within the first 24 h of ICU admission. RESULTS: In total, 161 patients were enrolled. Based on ROTEM, 72.7 % of patients with sepsis/septic shock had coagulation disorders, including 25.5 % hypercoagulation, 54.7 % hypocoagulation, 13.6 % mixed hypo-hypercoagulation patterns, and 18.6 % hyperfibrinolysis. A common mixed disorder subtype was characterized by prolonged initial clotting time (CT) with subsequently increased clot firmness. Fibrinogen levels and maximum clot formation (MCF)-fibtem were strongly correlated (rho = 0.73, p < 0.05). Hypocoagulation was observed more in the septic shock group than in the sepsis group. Compared to survivors, non-survivors had more prolonged CT-extem. CONCLUSIONS: ROTEM could identify hypocoagulability, hypercoagulability, mixed hypo-hypercoagulability patterns, and hyperfibrinolysis in patients with sepsis/septic shock. Elevated MCF-fibtem and elevated fibrinogen levels were notably common and strongly correlated. The septic shock group had more hypocoagulation than the sepsis group. Lastly, non-survivors had more prolonged CT-extem than survivors.

Peripartum Cardiomyopathy-Induced Cardiogenic Shock Causing Hypoxic-Ischemic Encephalopathy in a COVID-19 Patient.

Background: Cardiogenic shock complicating peripartum cardiomyopathy (PPCM) is a rare but lethal syndrome. The etiology of PPCM is not fully elucidated and is probably multifactorial, and viral infection might play some role. It has been documented that the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) directly invades the cardiomyocytes and most commonly damages this vital organ via complex systemic devastating mechanisms. Case presentation. A 28-year-old pregnant female was admitted to a COVID-19 field hospital due to a SARS-CoV-2 infection. She gave birth by spontaneous vaginal delivery at 34 gestational weeks. Six hours after the delivery, she presented signs of hemodynamic collapse and became comatosed, requiring a transfer to the COVID-19 intensive care center. The brain magnetic resonance imaging excluded thromboembolism, intracerebral hemorrhage, and central nervous system infection and revealed a hypoxic-ischemic encephalopathy. Bedside echocardiography documented a dilated left ventricle and severely reduced left ventricular systolic function with an ejection fraction of 24%. The management was aimed at a cardiogenic shock secondary to peripartum cardiomyopathy. The clinical course was favorable: the hemodynamics stabilized, the cognitive function fully recovered, and the patient was extubated on the second day of admission to the intensive care unit. The patient was discharged from the hospital ten days after admission. Neurological and cardiovascular checkups six months after discharge showed full recovery. Conclusion: Peripartum cardiomyopathy-induced cardiogenic shock with severe neurological consequences in COVID-19 patients was rare but did exist. A systemic approach and vigorous efforts to pinpoint the accurate diagnosis played important roles in the prompt and appropriate management.

Hyperglycemia in Severe and Critical COVID-19 Patients: Risk Factors and Outcomes.

BACKGROUND: Hyperglycemia is commonly seen in critically ill patients. This disorder was also seen in coronavirus disease 2019 (COVID-19) patients and was associated with a worse prognosis. The current study determined the prevalence, risk factors, and prognostic implications of hyperglycemia in COVID-19 patients. METHOD: This was a retrospective observational study performed in an intensive care unit for COVID-19 patients. Electronic data of COVID-19 patients admitted to the intensive care unit from August 2nd to October 15th, 2021, were collected. Patients were divided into non-hyperglycemia, hyperglycemia in diabetic patients, and hyperglycemia in non-diabetic patients. Primary outcomes were 28-day and in-hospital mortalities. Multinomial logistic regression and multivariable Cox regression models were used to determine the risk factors for hyperglycemia and mortality, respectively. RESULTS: Hyperglycemia was documented in 65.6% of patients: diabetic patients (44.8%) and new-onset hyperglycemia (20.8%). In-hospital and 28-day mortality rates were 30.2% and 26.1%, respectively. Respiratory failure, corticosteroid therapy, and a higher level of procalcitonin were risk factors for hyperglycemia in diabetic patients, whereas cardiovascular diseases, respiratory failure, and higher aspartate aminotransferase/glutamate aminotransferase ratio were risk factors for hyperglycemia in non-diabetic patients. The risk of the 28-day mortality rate was highest in the new-onset hyperglycemia (hazard ratio [HR] 3.535, 95% confidence interval [CI] 1.338-9.338, p=0.011), which was higher than hyperglycemia in type 2 diabetes mellitus patients (HR 1.408, 95% CI 0.513-3.862, p=0.506). CONCLUSION: Hyperglycemia was common in COVID-19 patients in the intensive care unit. Hyperglycemia reflected the disease severity but was also secondary to therapeutic intervention. New-onset hyperglycemia was associated with poorer outcomes than that in diabetic patients.

Diagnostic Value of hTERT mRNA and in Combination With AFP, AFP-L3%, Des-γ-carboxyprothrombin for Screening of Hepatocellular Carcinoma in Liver Cirrhosis Patients HBV or HCV-Related.

Diagnosis of hepatocellular carcinoma (HCC) in early-stage, to give an effective treatment option and improve quality of life for cancer patients, is an important medical mission globally. Combination of AFP with some biomarkers may be more supportive in both diagnosis and screening of HCC, but the range value of these markers can be applied as daily markers were unclearly. In some studies, human telomerase reverse transcriptase (hTERT mRNA) was reported as an advantage marker to diagnose cancer. The present study identified serum of 340 patients that were infected chronic hepatitis B virus or hepatitis C virus and divided in 2 groups including Hepatocellular carcinoma (HCC) and liver cirrhosis (LC) to measure their values of hTERT mRNA, AFP, AFP-L3%, and DCP, as well as combination of them. As a result, the concentration of hTERT mRNA, AFP, AFP-L3%, and DCP in HCC groups were significantly higher than that in LC group (P < .01). For detecting HCC, hTERT mRNA had sensitivity of 88% and specificity of 96% (at the cutoff value of 31.5 copies/mL), AFP sensitivity of 73% and specificity of 92% (at the cutoff value of 5.1 ng/mL), AFP-L3% sensitivity of 69% and specificity of 90% (at the cutoff value of 1.05%), DCP sensitivity of 82% and specificity of 92% (at the cutoff value of 29.01 mAU/mL). The largest area under the curve (AUC) of combination hTERT mRNA with DCP was 0.932 (sensitivity of 98.2% and specificity of 88.2%). New combination of DCP with hTERT mRNA gave a useful choice for screening of HCC in chronic HBV or HCV patients associated liver cirrhosis.

Cardiogenic Shock Secondary to Dynamic Left Ventricular Outflow Tract Obstruction and Apical Ballooning after Nonmitral Cardiovascular Surgery.

BACKGROUND: The dynamic obstruction of the left ventricular outflow tract (LVOT) is a well-known complication in mitral annuloplasty but rarely seen in nonmitral cardiovascular surgery. The dynamic LVOT obstruction can lead to hemodynamic instability, even shock and the treatment is significantly different from the standard approach. Case Presentation. We reported a case of low cardiac output syndrome (LCOS) with severe mitral regurgitation (MR), dramatically reduced left ventricular ejection fraction (LVEF) after coronary artery bypass grafting in a 72-year-old female requiring an escalation of inotropic support, volume restriction, and mechanical support. The detailed echocardiography combined with lung ultrasound revealed a dynamic systolic anterior movement of the anterior mitral leaflet (SAM), apical ballooning, and no significant lung congestion. Intravenous fluids were given, diuretics withdrawn, inotrope discontinued, and vasopressors uptitrated. The dynamic SAM was rapidly relieved, the hemodynamics was stabilized, and the LVEF was improving. The patient was discharged in good condition without residual LVOT obstruction and trace MR. CONCLUSION: We strongly suggest that a detailed echocardiography should be performed in any patient who presents in shock to rule out a dynamic LVOT obstruction. Lung ultrasound should be a routine examination in addition to echocardiography. Once SAM is detected, treatment should be based on volume expansion, inotrope discontinuation, and a careful afterload increasing.

Percutaneous atrial septal defect closure through femoral and transjugular approaches in patients with interrupted inferior vena cava.

Femoral venous approach is the classic route of percutaneous atrial septal defect (ASD) closure. But in patients with interrupted inferior vena cava (IVC) with azygos continuation the normal connection is lost rendering transcatheter intervention more complicated and innovative approaches should be sought. Transhepatic approach has been used with success but this approach is technically demanding and could lead to major complications. We report successful percutaneous secundum ASD closure in 2 patients with interrupted IVC. Transjugular route was used to close the secundum ASD in a 15-month-old girl. Percutaneous ASD closure through femoral venous route was performed in a 49-year-old woman. We found that both these approaches of percutaneous ASD device occlusion can be performed with success and safety. .

Methods of increasing the performance of radionuclide generators used in nuclear medicine: daughter nuclide build-up optimisation, elution-purification-concentration integration, and effective control of radionuclidic purity.

Methods of increasing the performance of radionuclide generators used in nuclear medicine radiotherapy and SPECT/PET imaging were developed and detailed for 99Mo/99mTc and 68Ge/68Ga radionuclide generators as the cases. Optimisation methods of the daughter nuclide build-up versus stand-by time and/or specific activity using mean progress functions were developed for increasing the performance of radionuclide generators. As a result of this optimisation, the separation of the daughter nuclide from its parent one should be performed at a defined optimal time to avoid the deterioration in specific activity of the daughter nuclide and wasting stand-by time of the generator, while the daughter nuclide yield is maintained to a reasonably high extent. A new characteristic parameter of the formation-decay kinetics of parent/daughter nuclide system was found and effectively used in the practice of the generator production and utilisation. A method of "early elution schedule" was also developed for increasing the daughter nuclide production yield and specific radioactivity, thus saving the cost of the generator and improving the quality of the daughter radionuclide solution. These newly developed optimisation methods in combination with an integrated elution-purification-concentration system of radionuclide generators recently developed is the most suitable way to operate the generator effectively on the basis of economic use and improvement of purposely suitable quality and specific activity of the produced daughter radionuclides. All these features benefit the economic use of the generator, the improved quality of labelling/scan, and the lowered cost of nuclear medicine procedure. Besides, a new method of quality control protocol set-up for post-delivery test of radionuclidic purity has been developed based on the relationship between gamma ray spectrometric detection limit, required limit of impure radionuclide activity and its measurement certainty with respect to optimising decay/measurement time and product sample activity used for QC quality control. The optimisation ensures a certainty of measurement of the specific impure radionuclide and avoids wasting the useful amount of valuable purified/concentrated daughter nuclide product. This process is important for the spectrometric measurement of very low activity of impure radionuclide contamination in the radioisotope products of much higher activity used in medical imaging and targeted radiotherapy.

Uncoupling protein-2 deficient mice are not protected against warm ischemia/reperfusion injury of the liver.

BACKGROUND: Uncoupling protein-2 (UCP2) might play an important role in mediating ischemia/reperfusion (I/R) injury due to its function in uncoupling of oxidative phosphorylation and in the proton leak-associated increase of reactive oxygen species (ROS) production. The aim of this study was to elucidate the role of UCP2 in hepatic I/R injury. MATERIALS AND METHODS: UCP2 wild type and UCP2 deficient mice were subjected to I/R of the left liver lobe. Sham-operated animals without I/R served as controls. Intravital fluorescence microscopy was used for assessing postischemic microcirculatory dysfunction. Indicators of hepatic inflammatory response, oxidative stress, and bioenergetic status as well as histomorphology were investigated. RESULTS: Under sham conditions UCP2-/-mice presented slightly but not significantly higher levels of hepatic ATP and energy charge than wild type mice. In addition, they exhibited higher systemic IL-6 levels and intrahepatic leukocyte adherence. After exposure to I/R, the extent of reperfusion injury did not differ between UCP2+/+ and UCP2-/-mice, as indicated by a comparable loss of sinusoidal perfusion, hepatic ATP, and energy charge levels, as well as rise of transaminases and disintegration of liver structures. Intrahepatic leukocyte adherence and plasma IL-6 levels of postischemic UCP2-/-mice still exceeded those of UCP2+/+mice. CONCLUSIONS: UCP2 appears to be of minor relevance for the manifestation and extent of postischemic reperfusion injury in nondiseased livers with the increased ATP availability being counteracted by the higher pro-inflammatory IL-6 levels in UCP2 deficient mice.

Uncoupling protein-2 deficiency provides protection in a murine model of endotoxemic acute liver failure.

OBJECTIVE: Liver injury and cell death are prominent features in the pathogenesis of acute liver failure. Mitochondrial uncoupling protein 2 plays a controversial role in liver cell death through its involvement in the production of reactive oxygen species and adenosine triphosphate. DESIGN: This randomized controlled animal study was designed to investigate the exact role of uncoupling protein 2 in the pathogenesis of endotoxemic acute liver failure. SETTING: Research laboratory of an academic institution. SUBJECTS, INTERVENTIONS, AND MEASUREMENTS: Uncoupling protein 2+/+ and uncoupling protein 2-/- mice were challenged with D-galactosamine (Gal, 720 mg/kg intraperitoneally) and Escherichia coli lipopolysaccharide (10 microg/kg intraperitoneally) and studied 6 hrs thereafter (n = 5 per group). Control mice received physiologic saline (n = 5 per group). Analysis included in vivo fluorescence microscopy of hepatic microcirculation and hepatocellular apoptosis as well as plasma malondialdehyde concentrations as reactive oxygen species-dependent lipid peroxidation product and hepatic adenosine triphosphate levels. MAIN RESULTS: Administration of Gal-lipopolysaccharide in uncoupling protein 2+/+ mice caused systemic cytokine release and malondialdehyde production. Further, it provoked marked hepatic damage, characterized by intrahepatic leukocyte recruitment (10.5 +/- 1.3 n/mm2 vs. 3.3 +/- 0.5 n/mm2), microvascular perfusion failure (33.1% +/- 1.6% vs. 2.3% +/- 0.4%), and adenosine triphosphate depletion (3.4 +/- 0.9 micromol/g vs. 6.4 +/- 0.9 micromol/g). Furthermore, uncoupling protein +/+ mice revealed a huge rise in cell apoptosis, given by high numbers of hepatocytes exhibiting nuclear chromatin fragmentation (44.9 +/- 11.5 n/mm2 vs. 0.0 +/- 0.0 n/mm2) and cleaved caspase-3 expression (1.24 +/- 0.24 vs. 0.06 +/- 0.04). Liver injury was coexistent with enzyme release (alanine aminotransferase 442 +/- 126 U/L vs. 57 +/- 12 U/L) and necrotic cell death. Of interest, Gal-lipopolysaccharide-exposed uncoupling protein 2-/- mice exhibited higher rates of hepatocellular apoptosis (135.6 +/- 46.0 n/mm2) as well as cleaved caspase-3 expression (1.75 +/- 0.25), however, preserved hepatic adenosine triphosphate (6.4 +/- 1.7), milder perfusion failure (24.5 +/- 2.4) and decreased leukocyte recruitment (2.7 +/- 0.2), less necrotic injury, lower transaminase levels (340 +/- 91), and finally better survival rates. CONCLUSION: The higher adenosine triphosphate availability in uncoupling protein 2-deficient mice might allow hepatocytes to undergo apoptosis as an energy-consuming mode of cell death, while at the same time cellular adenosine triphosphate levels seem to increase hepatic resistance against harmful effects upon Gal-lipopolysaccharide exposure. As net result, uncoupling protein 2 deficiency provided protection under endotoxemic stress conditions, underlining the significant role of the bioenergetic status in critical illness.

Attenuation of inflammation and apoptosis by pre- and posttreatment of darbepoetin-alpha in acute liver failure of mice.

In many liver disorders inflammation and apoptosis are important pathogenic components, finally leading to acute liver failure. Erythropoietin and its analogues are known to affect the interaction between apoptosis and inflammation in brain, kidney, and myocardium. The present study aimed to determine whether these pleiotropic actions also exert hepatoprotection in a model of acute liver injury. C57BL/6J mice were challenged with d-galactosamine (Gal) and Escherichia coli lipopolysaccharide (LPS) and studied 6 hours thereafter. Animals were either pretreated (24 hours before Gal-LPS exposure) or posttreated (30 minutes after Gal-LPS exposure) with darbepoetin-alpha (DPO, 10 mug/kg i.v.). Control mice received physiological saline. Administration of Gal-LPS caused systemic cytokine release and provoked marked hepatic damage, characterized by leukocyte recruitment and microvascular perfusion failure, caspase-3 activation, and hepatocellular apoptosis as well as enzyme release and necrotic cell death. DPO-pretreated and -posttreated mice showed diminished systemic cytokine concentrations, intrahepatic leukocyte accumulation, and hepatic perfusion failure. Hepatocellular apoptosis was significantly reduced by 50 to 75% after DPO pretreatment as well as posttreatment. In addition, treatment with DPO also significantly abrogated necrotic cell death and liver enzyme release. In conclusion, these observations may stimulate the evaluation of DPO as hepatoprotective therapy in patients with acute liver injury.