Prevention,diagnostic evaluation,management and prognostic implications of liver disease in critically ill patients with COVID-19

Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2, broke out in December 2019 in Wuhan city of China and spread rapidly worldwide. Therefore, by March 2020, the World Health Organization declared the disease a global pandemic. Apart from the respiratory system, various other organs of the human body are also seriously affected by the virus. Liver injury in patients with a severe form of COVID-19 is estimated to be 14.8%-53.0%. Elevated levels of total bilirubin, aspartate aminotransferase and alanine aminotransferase and low levels of serum albumin and prealbumin are the main laboratory findings. Patients with pre-existing chronic liver disease and cirrhosis are much more prone to develop severe liver injury. This literature review presented the recent scientific findings regarding the pathophysiological mechanisms responsible for liver injury in critically ill patients with COVID-19, the various interactions between drugs used to treat the disease and the function of the liver and the specific tests providing the possibility of early diagnosis of severe liver injury in these patients. Moreover, it highlighted the burden that COVID-19 put on health systems worldwide and its effect on transplant programs and the care provided to critically ill patients in general and particularly to those with chronic liver disease.     

Adipose tissue lipolysis and circulating lipids in acute and subacute critical illness: Effects of shock and treatment

Purpose

The purpose of this study is to assess lipid metabolism at the tissue level in critically ill subjects.

Materials and methods

We studied 182 patients with systemic inflammatory response syndrome/severe sepsis or shock during the acute (day 1) and subacute phase of critical illness (day 6). All subjects had a tissue microdialysis (MD) catheter placed in femoral adipose tissue upon admission to the intensive care unit (ICU). Plasma cholesterol, high-density lipoprotein, low-density lipoprotein, free fatty acids (FFAs), triglyceride, and MD glycerol (GLYC) were measured on days 1 and 6 in the ICU.

Results

On admission, 56% of the patients had increased levels (> 200 μmol/L) of MD GLYC. Patients with shock displayed more pronounced subcutaneous tissue lipolysis and more profound derangements of circulating lipids vs patients without shock (but no appreciable differences in FFA levels). Furthermore, in patients with shock during the acute period, there were positive, albeit weak, correlations of subcutaneous tissue lipolysis (MD GLYC), plasma FFAs (r = 0.260; P = .01), and norepinephrine's dose (r = 0.230; P = .01), whereas during the subacute phase, MD GLY levels were higher in patients receiving glucocorticoids (344.7 ± 276.0 μmol/L vs 252.2 ± 158.4 μmol/L; P = .03).

Conclusions

Subcutaneous tissue lipolysis is only one of the many determinants of plasma FFAs. Routinely applied therapeutic modalities in the ICU interfere with adipose tissue metabolism.     

Angiopoietin-2 is increased in severe sepsis: correlation with inflammatory mediators

OBJECTIVE: Angiopoietin (Ang)-2 is an endothelium-specific growth factor, regulated by proinflammatory stimuli, that destabilizes vascular endothelium and increases vascular leakage; consequently, Ang-2 may contribute to sepsis pathophysiology. We have studied 1) serum Ang-2 levels in critically-ill patients and investigated potential relationships with inflammatory mediators and indices of disease severity and 2) the effect of sepsis-related inflammatory mediators on Ang-2 production by lung endothelium in vitro. DESIGN: Prospective clinical study followed by cell culture studies. SETTING: General intensive care unit and research laboratory of a university hospital. SUBJECTS: Human and bovine lung microvascular endothelial cells and 61 patients (32 men). Patients were grouped according to their septic stage as having: no systemic inflammatory response syndrome (n = 6), systemic inflammatory response syndrome (n = 8), sepsis (n = 16), severe sepsis (n = 18), and septic shock (n = 13). INTERVENTIONS: Cells were exposed to lipopolysaccharide, tumor necrosis factor-alpha, and interleukin-6. MEASUREMENTS AND MAIN RESULTS: Patients' serum Ang-2 levels were significantly increased in severe sepsis as compared with patients with no systemic inflammatory response syndrome or sepsis (p < .05 by analysis of variance). Positive linear relationships were observed with: serum tumor necrosis factor-alpha (rs = 0.654, p < .001), serum interleukin-6 (rs = 0.464, p < .001), Acute Physiology and Chronic Health Evaluation II score (rs = 0.387, p < .001), and Sequential Organ Failure Assessment score (rs = 0.428, p < .001). Multiple regression analysis revealed that serum Ang-2 is mostly related to serum tumor necrosis factor-alpha and severe sepsis. Treatment of human lung microvascular endothelial cells with all mediators resulted in a concentration-dependent Ang-2 reduction. Treatment of bovine lung microvascular endothelial cells with lipopolysaccharide and tumor necrosis factor-alpha increased Ang-2 release, and interleukin-6 reduced basal Ang-2 levels. CONCLUSIONS: First, patients' serum Ang-2 levels are increased during severe sepsis and associated with disease severity. The strong relationship of serum Ang-2 with serum tumor necrosis factor-alpha suggests that the latter may participate in the regulation of Ang-2 production in sepsis. Second, inflammatory mediators reduce Ang-2 release from human lung microvascular endothelial cells, implying that this vascular bed may not be the source of increased Ang-2 in human sepsis.     

End-inspiratory occlusion maneuver during transesophageal echocardiography for patent foramen ovale detection in intensive care unit patients

Objective Mechanically ventilated patients in the intensive care unit cannot cooperate to perform the Valsalva maneuver during echocardiography for detection of patent foramen ovale. We evaluated the effectiveness of the end-inspiratory occlusion maneuver to enhance detection of patent foramen ovale in this patient population. Design Prospective interventional study. Setting The 40-bed intensive care unit of a university hospital. Patients and participants Twenty five sedated and mechanically ventilated intensive care unit patients referred by their attending physician for bedside transesophageal echocardiography and agitated saline contrast study for detection of patent foramen ovale. Intervention Agitated saline contrast study with end-inspiratory occlusion maneuver. Measurements and results All patients underwent a complete transesophageal echocardiographic study without any complications. Reduction in right atrial cross-sectional area (from 15.80 ± 6.08 cm² to 12.40 ± 4.63 cm²; p < 0.001) and interatrial septum deviation during the maneuver were recorded in all patients. Microbubbles imaged in the left atrium within three cardiac cycles after injection of agitated saline diagnosed patent foramen ovale in three patients. When end-inspiratory occlusion maneuver was added, patent foramen ovale was diagnosed in seven patients (McNemar χ² = 9.33, p = 0.0023). Conclusions The end-inspiratory occlusion maneuver enhances the sensitivity of transesophageal echocardiography with agitated saline contrast study for diagnosing intermittent patent foramen ovale in critically ill mechanically ventilated patients. Electronic supplementary material The online version of this article (doi:) contains supplementary material, which is available to authorized users.     

Abstracts of the 25<Superscript>th</Superscript> Annual Congress of the European Society for Gynaecological Endoscopy (ESGE), 2<Superscript>nd</Superscript>-5<Superscript>th</Superscript> October 2016, Square – Brussels – Belgium

What is the recommended diagnostic work-up of female genital anomalies according to the European Society of Human Reproduction and Embryology (ESHRE)/European Society for Gynaecological Endoscopy (ESGE) system? The ESHRE/ESGE consensus for the diagnosis of female genital anomalies is presented. Accurate diagnosis of congenital anomalies still remains a clinical challenge due to the drawbacks of the previous classification systems and the non-systematic use of diagnostic methods with varying accuracy, with some of them quite inaccurate. Currently, a wide range of non-invasive diagnostic procedures are available, enriching the opportunity to accurately detect the anatomical status of the female genital tract, as well as a new objective and comprehensive classification system with well-described classes and sub-classes. The ESHRE/ESGE Congenital Uterine Anomalies (CONUTA) Working Group established an initiative with the goal of developing a consensus for the diagnosis of female genital anomalies. The CONUTA working group and imaging experts in the field have been appointed to run the project. The consensus is developed based on (1) evaluation of the currently available diagnostic methods and, more specifically, of their characteristics with the use of the experts panel consensus method and of their diagnostic accuracy performing a systematic review of evidence and (2) consensus for (a) the definition of where and how to measure uterine wall thickness and (b) the recommendations for the diagnostic work-up of female genital anomalies, based on the results of the previous evaluation procedure, with the use of the experts panel consensus method. Uterine wall thickness is defined as the distance between interostial line and external uterine profile at the midcoronal plane of the uterus; alternatively, if a coronal plane is not available, the mean anterior and posterior uterine wall thickness at the longitudinal plane could be used. Gynaecological examination and two-dimensional ultrasound (2D US) are recommended for the evaluation of asymptomatic women. Three-dimensional ultrasound (3D US) is recommended for the diagnosis of female genital anomalies in “symptomatic” patients belonging to high-risk groups for the presence of a female genital anomaly and in any asymptomatic woman suspected to have an anomaly from routine avaluation. Magnetic resonance imaging (MRI) and endoscopic evaluation are recommended for the sub-group of patients with suspected complex anomalies or in diagnostic dilemmas. Adolescents with symptoms suggestive for the presence of a female genital anomaly should be thoroughly evaluated with 2D US, 3D US, MRI and endoscopy. The various diagnostic methods should be used in a proper way and evaluated by experts to avoid mis-, over- and underdiagnosis. The role of a combined ultrasound examination and outpatient hysteroscopy should be prospectively evaluated. It is a challenge for further research, based on diagnosis, to objectively evaluate the clinical consequences related to various degrees of uterine deformity.     

Screening performance of different methods defining fetal nasal bone hypoplasia as a single and combined marker for the detection of trisomy 21 in the second trimester

Objective: To evaluate different methods of defining fetal nasal bone hypoplasia in the second trimester for the detection of trisomy 21.

Methods: Prospective study in Greek women undergoing anomaly scan between 18?+?0 and 23?+?6 weeks. The following methods of defining nasal bone hypoplasia were evaluated, either as a single marker or in combination with others: (1) BPD to nasal bone length (NBL) ratio; (2) multiples of the median (MoM) of NBL, according to normal curves from a Greek population; (3–4) NBL?<?2.5 percentile according to normal curves (3) commonly used internationally curves and (4) curves from a Greek population.

Results: In total, 1301 singleton fetuses were evaluated???10 with trisomy 21. The best detection rate of trisomy 21 was achieved when the applied method was nasal bone percentiles adjusted to maternal ethnicity, in combination with other markers (<2.5 percentile according to normal curves from a Greek population; p?<?0.001; sensitivity 50%; specificity 94.8%; false-positive rate 5.2%; positive likelihood ratio 9.6).

Conclusion: Screening performance of fetal nasal bone hypoplasia in detecting trisomy 21 varies according to the method applied. The best screening performance is achieved by using percentiles adjusted to maternal ethnicity in combination with other markers of aneuploidy.     

Can ‘high‐risk’ human papillomaviruses (HPVs) be detected in human breast milk?

Aim: Human papillomavirus (HPV) transmission via nonsexual modes in childhood has been proposed by several researchers. The aim of our study was to determine the presence of ‘high‐risk’ HPV DNA in human breast milk. Methods: Using polymerase chain reaction techniques, we evaluated the presence of HPV infection in human breast milk collected from 21 HPV‐positive and 11 HPV‐negative mothers. Results: Of the 32 studied human milk specimens, no ‘high‐risk’ HPV 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58 or 58 DNA was detected. Conclusion: This preliminary case–control study indicates the absence of mucosal ‘high‐risk’ HPV types in human breast milk.     

A life-threatening case of disseminated nocardiosis due to Nocardia brasiliensis

Nocardiosis is a rare disease caused by infection with Nocardia species, aerobic actinomycetes with a worldwide distribution. A rare life-threatening disseminated Nocardia brasiliensis infection is described in an elderly, immunocompromised patient. Microorganism was recovered from bronchial secretions and dermal lesions, and was identified using molecular assays. Prompt, timely diagnosis and appropriate treatment ensured a favorable outcome.     

A voxel-by-voxel parametric fMRI study of motor mental rotation: hemispheric specialization and gender differences in neural processing efficiency

Differences between men and women in brain size, cognitive performance and lateralization of brain activation have been perennial and controversial issues. Here we show that in a motor mental rotation task where women and men performed equally well, the slope of the functional magnetic resonance imaging (fMRI) blood oxygenation level dependent (BOLD) signal per degree of mental rotation was overall 2.4× higher in men than in women. This was attributed to the much more inefficient engagement (i.e. higher slopes) of the right hemisphere by men (mainly the frontal lobe). These findings indicate that women process information much more efficiently than men, which could offset smaller brain size.     

Simvastatin-induced changes in circulating oxidized low-density lipoprotein in different types of dyslipidemia

Beyond lowering lipid levels, 3-hydroxy-3-methyl glutaryl coenzyme A reductase inhibitors (statins) have been shown to possess antioxidant properties, which may explain some of their beneficial effects in reducing atherosclerosis. We sought to determine whether circulating oxidized low-density lipoprotein (ox-LDL) levels differ between subjects with isolated hypercholesterolemia and combined hyperlipidemia, as well as the effect of simvastatin on circulating ox-LDL according to the type of dyslipidemia. Twenty-five subjects with total cholesterol >200 mg/dl and triglycerides <150 mg/dl, and 22 subjects with total cholesterol >200 mg/dl and triglycerides >150 mg/dl were treated with 40 mg simvastatin daily for 3 months. Serum lipids, C-reactive protein, fibrinogen, ox-LDL, and free radicals were measured at baseline and after 3 months of treatment. In both groups studied, simvastatin significantly improved lipids, and reduced C-reactive protein and fibrinogen levels. Free radicals were significantly reduced only in subjects with hypercholesterolemia. Subjects with combined hyperlipidemia had significantly higher baseline levels of ox-LDL compared to those with hypercholesterolemia (64.6 U/l vs 53.5 U/l, P = 0.03). Ox-LDL levels were reduced by 12% in subjects with hypercholesterolemia (P = 0.03) and by 26% in subjects with combined hyperlipidemia (P = 0.001) after simvastatin treatment. In conclusion, subjects with combined hyperlipidemia have increased levels of circulating ox-LDL compared to subjects with isolated hypercholesterolemia. Simvastatin significantly reduced circulating ox-LDL in both groups, but whether this reduction is related to clinical outcomes remains to be shown.