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.     

Thermoelectric Performance of Mechanically Mixed BixSb2-xTe3—ABS Composites

In the current study, polymer-based composites, consisting of Acrylonitrile Butadiene Styrene (ABS) and Bismuth Antimony Telluride (Bi_xSb_2−xTe₃), were produced using mechanical mixing and hot pressing. These composites were investigated regarding their electrical resistivity and Seebeck coefficient, with respect to Bi doping and Bi_xSb_2-xTe₃ loading into the composite. Experimental results showed that their thermoelectric performance is comparable—or even superior, in some cases—to reported thermoelectric polymer composites that have been produced using other complex techniques. Consequently, mechanically mixed polymer-based thermoelectric materials could be an efficient method for low-cost and large-scale production of polymer composites for potential thermoelectric applications.     

SGLT2 inhibitors and cardioprotection: a matter of debate and multiple hypotheses

Sodium-glucose co-transporter 2 (SGLT2) inhibitors inhibit glucose re-absorption in the proximal renal tubules. Two trials have shown significant reductions of cardiovascular (CV) events with empagliflozin and canagliflozin, which could not be attributed solely to their antidiabetic effects. The aim of the review is the critical presentation of suggested mechanisms/hypotheses for the SGLT2 inhibitors' cardioprotection. The search of the literature revealed many possible cardioprotective mechanisms, because SGLT2 inhibitors (i) increase natriuresis and act as diuretics with unique properties leading to a reduction in preload and myocardial stretch (the diuretic hypothesis); (ii) decrease blood pressure and afterload (the blood pressure lowering hypothesis), (iii) favor the production of ketones, which can act as a ‘superfuel’ in the cardiac and renal tissue (the ‘thrifty substrate’ hypothesis), (iv) improve many metabolic variables (the metabolic effects hypothesis), (v) exert many anti-inflammatory effects (the anti-inflammatory effects hypothesis), (vi) can act through the angiotensin II type II receptors in the context of simultaneous renin-angiotensin-aldosterone-system (RAAS) blockade leading to vasodilation and positive inotropic effects (the RAAS hypothesis), (vii) directly decrease the activity of the upregulated in heart failure Na⁺–H⁺ exchanger in myocardial cells leading to restoration of mitochondrial calcium handling in cardiomyocytes (the sodium hypothesis). Additionally, some SGLT2 inhibitors exhibit also SGLT1 inhibitory action possibly resulting in an attenuation of oxidative stress in ischemic myocardium (the SGLT1 inhibition hypothesis). Thus, many mechanisms have been suggested (and possibly act cumulatively) for the cardioprotective effects of SGLT2 inhibitors.     

Pneumothorax-associated pleural eosinophilia is tumour necrosis factor-alpha-dependent and attenuated by steroids

Background and objectives: The pathogenesis and the optimal treatment of eosinophilic pleural effusions are unknown. We aimed to examine whether pneumothorax‐associated pleural eosinophilia in mice is dependent on tumour necrosis factor (TNF)‐alpha, and whether it is affected by systemic administration of corticosteroids. Methods: Mice were injected intrapleurally with 0.4 mL air to create pneumothoraces. Animals were sacrificed 24 or 48 h later, and pleural lavage (PL) was performed. In the first experiment, comparisons were made between wild‐type and TNF‐α knockout mice with pneumothorax. In the second experiment, wild‐type mice were injected intraperitoneally with different doses of dexamethasone (0, 0.25, 0.5 and 1 mg/kg), 5 min before and 24 h after the induction of pneumothorax. Results: After induction of a pneumothorax, TNF‐α knockout mice had significantly fewer total number of cells (P = 0.004), mononuclear cells (P = 0.01), neutrophils (P = 0.017) and eosinophils (P = 0.002) in their PL compared with wild‐type animals. TNF‐α was detected in the PL of most of the control mice but not in TNF‐α knockouts. Dexamethasone induced a significant, dose‐dependent reduction of PL total cells (P < 0.001), eosinophils (P < 0.001), mononuclear cells (P = 0.007) and lymphocytes (P = 0.04) at 48 h, and significantly reduced the number of PL total cells (P = 0.045) and eosinophils (P = 0.005) at 24 h. Furthermore, dexamethasone prevented eosinophil infiltration of lung and pleural tissue. Conclusion: Pneumothorax‐associated pleural eosinophilia in mice is TNF‐α‐dependent and is significantly attenuated by corticosteroid treatment. In addition, both TNF‐α deficiency and dexamethasone treatment were associated with a significant reduction of other types of inflammatory cells in PL.     

Imbalance of tissue inhibitors of metalloproteinases (TIMP) – 1 and – 4 serum levels,in patients with inflammatory bowel disease

Background  

Tissue inhibitors of metalloproteinases (TIMPs) play a key role in tissue degradation and remodeling. Since chronic inflammation is associated with tissue remodeling in inflammatory bowel disease (IBD), we evaluated serum TIMP-1 and TIMP-4 levels in IBD patients, in comparison with healthy controls (HC).     

Natural course of autoimmune thyroiditis after elimination of iodine deficiency in northwestern Greece.

We have previously reported the elimination of iodine deficiency and increasing prevalence of autoimmune thyroiditis (AIT) among schoolchildren in northwestern Greece. This study followed up 29 children (12-18 years old) with AIT for 5 years to track its course in the postiodination era. At diagnosis, thyroid peroxidase autoantibodies (TPOAbs) were positive in 25 children (86%) and became positive in all children during follow-up. Thyroglobulin autoantibodies (TgAbs) were positive in 17 children at diagnosis (59%) and became positive in 3 more children (69%). Both antibody types increased by the end of the observation period (p < 0.005). Regarding thyroid function, 7 children (24%) at diagnosis had subclinical hypothyroidism that persisted and 4 more children developed subclinical hypothyroidism during the study period (38%). Only 5 of these children (45%) had positive TgAbs. There was an increase in thyrotropin (TSH) so that at the end of the study all children had TSH greater than 2.5 mU/L but none developed overt hypothyroidism. Thyroid hypoechogenicity that increased over time was seen in all children, especially in those with subclinical hypothyroidism. In conclusion, both antibody types increased in frequency and level, but TPOAbs were the predominant autoimmunity marker predictive of impending thyroid failure in children with AIT, as was thyroid hypoechogenicity on ultrasound.     

Pharmacodynamic comparison of low-dose ticagrelor to low-dose prasugrel in patients with prior myocardial infarction: the ALTIC-2 study

Abstract

Given that patients with prior myocardial infarction and features of high ischemic and low bleeding risk may benefit by extending dual antiplatelet therapy beyond 1 year, we aimed of assessing platelet reactivity provided by ticagrelor 60 mg bid versus prasugrel 5 mg od in 20 such patients participating in a randomized, crossover study. The primary end point of platelet reactivity at the end of the two treatment periods (by VerifyNow, in PRU) was significantly lower for ticagrelor (31.9 PRU [95% CI 12.3–51.4]) compared with prasugrel (132.1 PRU [111.9–152.3]) with a least squares mean difference of –100.2 PRU (72.1–128.3, P < .001). This dedicated pharmacodynamic study showed that in post-myocardial infarction patients with high atherothrombotic risk and receiving P2Y₁₂ receptor antagonist beyond 1 year, low-dose ticagrelor results in a significantly lower platelet reactivity compared to low-dose prasugrel.     

Minimal excess risk of cancer and reduced risk of death from cancer in Australian Department of Veterans’ Affairs clients: a record linkage study

Objective: To quantify the risk of incident cancer and cancer‐related mortality in Australian Government Department of Veterans’ Affairs (DVA) clients. Methods: A population‐based record linkage study of 75,482 adult clients residing in New South Wales (NSW) from 2000 to 2007; median age 75 years (interquartile range, 68–79); 57% male. Standardised incidence ratios (SIRs) and mortality ratios (SMRs) for any cancer and by cancer type were calculated, relative to the NSW population. Results: The risk of any cancer was slightly increased for males (SIR 1.07, 95%CI 1.04–1.10) but not females (SIR 1.00, 95%CI 0.96–1.04). Males exhibited a significantly elevated risk of prostate cancer (SIR 1.08), cutaneous melanoma (SIR 1.19), head and neck cancer (SIR 1.27) and connective tissue cancer (SIR 1.52). Females did not exhibit excess risk for any cancer type. Risk of cancer death was significantly reduced for any cancer (male SMR 0.78, 95%CI 0.75–0.81; female SMR 0.80, 95%CI 0.76–0.85) and for a range of haematopoietic and solid neoplasms including prostate (SMR 0.57), breast (SMR 0.62) and colon cancer (male SMR 0.67; female SMR 0.71). Conclusion: Cancer incidence rates are largely similar, and mortality rates moderately lower, for DVA clients compared to the NSW general population. Implications: These risk patterns may reflect service‐related history, a healthy‐survivor effect, competing risk of death, and/or comprehensive health care entitlements with minimal to no co‐payments. Our findings suggest DVA clients are probably accessing cancer screening services. Outcomes after cancer diagnosis are good, most probably due to comprehensive health care entitlements.