Science Letters:A novel way of liver preservation improves rat liver viability upon reperfusion

Background/aim： Currently, the liver is cold-preserved at 0-4 ℃ for experimental and clinical purposes. Here, we investigated whether milder hypothermia during the initial phase of the preservation period was beneficial for liver viability upon reperfusion. Methods： In the first set of experiments, rat livers were preserved either conventionally in clinically used histidine-trypthopan-ketoglutarate （HTK） solution （Group A： 45 min and Group B： 24 h） or by slow cooling HTK solution （from 13 ℃ to 3 ℃） during the initial 45 min of preservation （Group C： 24 h）. In the second set of experiments, additional groups of livers were evaluated： Group BB-preservation according to Group B and Group CC-preservation according to Group C. Further, some livers were preserved at 13 ℃ for 24 h. Livers were then reperfused using a blood-free perfusion model. Results： Bile production was approximately 2-fold greater in Group C compared to Group B. Alanine transaminase （ALT） and aspartate transaminase （AST） release into perfusate were 2-3-fold higher in Group B compared to Group C. No significant differences were found in ALT and AST release between Group C and Group A. Livers in Group CC compared to Group BB exhibited significantly lower portal resistance, greater oxygen consumption and bromosulfophthalein excretion into bile and lower lactate dehydrogenase （LDH） release into perfusate. Histological evaluation of tissue sections in Group BB showed parenchymal dystrophy of hepatocytes, while dystrophy ofhepatocytes was absent in Group CC. Livers preserved at 13 ℃ for 24 h exhibited severe ischemic injury Conclusion： These results suggest that the conventional way of liver preservation is not suitable at least for rat livers and that slow cooling of HTK solution during the initial phase of cold storage can improve liver viability during reperfusion.

Mortality of therapeutic fish Garra rufa caused by Aeromonas sobria

Objective:To investigate a case of mass mortality of Garra rufa(G.rufa)from a fish hatchery farm in Slovakia.Methods:Causative bacterial agent was swabbing out of affected fish skin area and subsequently identified using commercial test system.Antibiotic susceptibility was determined by the disk diffusion method.Results:Infected G.rufa was characterized by abnormal swimming behaviour,bleeding of skin lesions and local haemorrhages.Despite of using recommended aquatic antibiotic treatment no improvement was achieved and Aeromonas sobria{A.sobria)was identified as a causative agent of fish mortality.Due to massive fish mortality,antibiotic susceptibility of pure isolated culture of A.sobria was evaluated employing eight antibiotics against human infections.A.sobria was resistant only against one antibiotic,namely ampicilin.Conclusions:These results indicate that A.sobria can act as a primary pathogen of G.rufa and may be a potential risk factor for immunodeficient or immunoincompetent patients during the ichthyotherapy.

Anti-cytomegalovirus antibodies and other atherosclerosis risk factors in patients with cardiovascular diseases

Objective To determine anti-cytomegalovirus(CMV) antibodies along with anti-Chlamydia pneumoniae(CP) antibodies in comparison with inflammatory markers and other risk factors of atherosclerosis in patients with selected cardiovascular diseases(CVD) . Methods A total of 228 patients with coronary heart disease(CHD) and/or hyperten-sion(HT) ,and those who underwent reconstructive vascular surgery(RVS) on carotids or abdominal aorta were tested for the presence of anti-CMV IgG and IgM antibodies as well as for anti-CP IgA antibodies,C-reactive protein(CRP) ,and interleukin-6(IL-6) . Other risk factors for atherosclerosis,namely age,gender,smoking,hypercholesterolemia,and diabetes mellitus were also analyzed. Results Anti-CMV IgG antibodies were found in 204 patients sera(89.5%) ,compared with 46 positive of 68 sera in the controls(67.6%) ,whereas anti-CMV IgM antibodies were detected in 4 of 54 sera of patients tested(7.4%) ,but not in the controls. The highest proportion of positive sera with not only anti-CMV IgG antibodies(95.6.7%) ,but also anti-CP IgA antibodies(78.3%) ,IL-6(84.8%) and CRP(97.8%) ,was observed in patients with RVS. The results obtained corresponded to age,hypercholesterolemia,and diabetes. Conclusions The presence of anti-CMV antibodies together with antibodies to CP and markers of inflammation(CRP and IL-6) in our study was associated with CVD,primarily in elderly patients who underwent RVS.

Tooth loss caused by displaced elastic during simple preprosthetic orthodontic treatment

The use of elastics to close a diastema or correct tooth malpositions can create unintended consequences if not properly controlled. The American Association of Orthodontists recently issued a consumer alert, warning of "a substantial risk for irreparable damage" from a new trend called "do-it-yourself" orthodontics, consisting of patients autonomously using elastics to correct tooth position. The elastics can work their way below the gums and around the roots of the teeth, causing damage to the periodontium and even resulting in tooth loss. The cost of implants to replace these teeth would well exceed the cost of proper orthodontic care. This damage could also occur in a dental office, when a general dentist tries to perform a simplified orthodontic correction of a minor tooth malposition. The present case report describes a case of tooth loss caused by a displaced intraoral elastic, which occurred during a simple preprosthetic orthodontic treatment.

Liver injury associated with the use of selective androgen receptor modulators and post-cycle therapy:Two case reports and literature review

BACKGROUND Muscle growth promoters are being developed for the treatment of diseaseinduced loss of muscle mass.Ligandrol and ostarine are selective androgen receptor modulators(SARMs)with a non-steroidal structure and a presumably more favorable side effect profile.In recent years,these substances with or without“post-cycle therapy”(PCT)are often misused by amateur athletes aiming to promote muscle growth.At the same time,reports on their toxic effects on organ systems are emerging.CASE SUMMARY We report two cases of liver injury in young men who used ligandrol and/or ostarine for a few weeks followed by the use of substances for PCT.Acute liver injury occurred in both cases after stopping SARMs while on PCT.The clinical picture was dominated by jaundice and fatigue.The biochemical pattern showed a mixed type of injury with normal alkaline phosphatase and high concentrations of bilirubin and serum bile acids. Histological evidence showed predominantlycholestatic injury with canalicular bile plugs, ductopenia, and mild hepatocellulardamage without significant fibrosis. The patients recovered from the conditionafter 3 mo. The off target effects of SARMs were likely idiosyncratic, but ourreport highlights the yet unrecognized effects of other toxic substances used forPCT, supra-therapeutic doses, and the complete absence of monitoring foradverse effects.CONCLUSIONAmong muscle-building amateur athletes, SARMs (ligandrol or ostarine) and/orsubstances in PCT may cause cholestatic liver injury with prolonged recovery.

Acute-on-chronic liver failure in patients with severe acute respiratory syndrome coronavirus 2 infection

The coronavirus disease 2019(COVID-19)pandemic caused by the severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)has had a significant impact on the lives of millions of people,especially those with other concomitant diseases,such as chronic liver diseases.To date,seven coronaviruses have been identified to infect humans.The main site of pathological action of these viruses is lung tissue.However,a substantial number of studies have proven that SARSCoV-2 shows affinity towards several organs,including the gastrointestinal tract and the liver.The current state of evidence points to several proposed mechanisms of liver injury in patients with COVID-19 and their combination.Liver impairment is considered to be the result of the direct effect of the virus on the hepatic tissue cells,a systemic reaction consisting of inflammation,hypoxia and cytokine storm,drug-induced liver injury,with the possible contribution of a perturbed gut-liver axis.Reactivation of chronic hepatic disease could be another factor for liver impairment in patients with SARS-CoV-2 infection.Acute-onchronic liver failure(ACLF)is a relatively new syndrome that occurs in 10%–30%of all hospitalized patients with chronic liver disease.It is crucial to recognize high-risk patients due to the increased morbidity and mortality in these cases.Several published studies have reported virus infection as a trigger factor for ACLF.However,to date,there are few relevant studies describing the presence of ACLF in patients with acute SARS-CoV-2 infection.In this minireview we summarize the current state of knowledge regarding the relation between ACLF and acute SARS-CoV-2 infection.

Circulating tumor cells and drug history in primary breast cancer patients

Aim:Different types of chronic medication may affect breast cancer prognosis.Circulating tumor cells(CTCs)play an important role in cancer metastasis formation.There is no evidence of how chronic medication affects CTCs and breast cancer prognosis.The aim of this study was to evaluate association between chronic medication and CTCs in patients with primary breast cancer.Methods:This study involved 414 patients with stage I-III primary breast cancer.Chronic drug history was collected from patients’medical records and included all drugs that were prescribed for patients over at least the last 6 months prior to CTCs evaluation.CTCs were detected using a quantitative real-time polymerase chain reaction(qRT-PCR)-based method at the time of breast surgery.Results:There was no association between CTCs,including their different subpopulations and chronic medication.Chronic medication using angiotensin-converting-enzyme inhibitors(ACEi),metformin,and insulin were associated with inferior disease-free survival(HR=0.49,95%CI 0.26-0.94,P=0.007 for ACEi;HR=0.27,95%CI 0.08-0.91,P<0.001 for metformin;and HR=0.12,95%CI 0.01-2.91,P<0.001 for insulin)and this was most pronounced in patients with epithelial to mesenchymal transition(CTC_EMT)phenotype.In multivariate analysis,chronic administration of metformin and/or insulin was an independent predictor of inferior outcome.Conclusion:Our findings show that there was no association between chronically used medication and CTCs in primary breast cancer patients.However,administration of ACEi,metformin,and/or insulin could negatively affect prognosis of patients with CTC_EMT.