COVID-19 and liver injury:Pathophysiology,risk factors,outcome and management in special populations

The coronavirus disease 2019(COVID-19)caused by severe acute respiratory syndrome coronavirus-2 is an ongoing health concern.In addition to affecting the respiratory system,COVID-19 can potentially damage other systems in the body,leading to extra-pulmonary manifestations.Hepatic manifestations are among the common consequences of COVID-19.Although the precise mechanism of liver injury is still questionable,several mechanisms have been hypothesized,including direct viral effect,cytokine storm,hypoxic-ischemic injury,hypoxiareperfusion injury,ferroptosis,and hepatotoxic medications.Risk factors of COVID-19-induced liver injury include severe COVID-19 infection,male gender,advanced age,obesity,and underlying diseases.The presentations of liver involvement comprise abnormalities in liver enzymes and radiologic findings,which can be utilized to predict the prognosis.Increased gamma-glutamyltransferase,aspartate aminotransferase,and alanine aminotransferase levels with hypoalbuminemia can indicate severe liver injury and anticipate the need for intensive care units’hospitalization.In imaging,a lower liver-to-spleen ratio and liver computed tomography attenuation may indicate a more severe illness.Furthermore,chronic liver disease patients are at a higher risk for severe disease and death from COVID-19.Nonalcoholic fatty liver disease had the highest risk of advanced COVID-19 disease and death,followed by metabolic-associated fatty liver disease and cirrhosis.In addition to COVID-19-induced liver injury,the pandemic has also altered the epidemiology and pattern of some hepatic diseases,such as alcoholic liver disease and hepatitis B.Therefore,it warrants special vigilance and awareness by healthcare professionals to screen and treat COVID-19-associated liver injury accordingly.

Comparison of post-urethroplasty complication rates in pediatric cases with hypospadias using Vicryl or polydioxanone sutures

Objective:Hypospadias is a common congenital problem among male newborns.Both rapid absorbable sutures(polyglactin,Vicryl)and delayed absorbable sutures(polydioxanone,PDO)are used in hypospadias repair based on the surgeon's preference.This study was conducted to compare post-urethroplasty complication rates in pediatric patients with hypospadias using Vicryl or PDO sutures.Methods:This is a retrospective study which was designed and performed on 583 children aged 1-7 years old who had undergone hypospadias repair from January 2012 to December 2018.Required data were obtained from the patients'medical records.Results:Overall,post-surgical complications were observed in 60(10.3%)patients comprising urethro-cutaneous fistula(n=39,6.7%),meatal stenosis(n=10,1.7%),urethral stricture(n=7,1.2%),and glans dehiscence(n=4,0.7%).The mean age of the children with complications was 3.0±1.3 years.According to Kaplan-Meier estimate,the interval between surgery and development of complications was significantly shorter in the Vicryl group(p=0.037).Overall,complications were more prevalent in Vicryl suture than PDO suture(15.1%vs.5.3%,p<0.001).Regression model revealed that in comparison to the distal type,proximal hypospadias(odds ratio[OR]:103.9,95%confidence interval[CI]:32.2-334.9,p<0.001)and mid-shaft hypospadias(OR:82.9,95%CI:25.9-264.6,p<0.001)while using Vicryl suture instead of PDO suture(OR:62.4,95%CI:21.2-183.8,p<0.001)increased the odds of developing post-urethroplasty complications.Conclusion:We suggest PDO suture in the repair of hypospadias due to its lower complication rate,especially in cases of proximal and mid-shaft hypospadias which can get more complicated than the distal type.

CD34^(+)CD38^(-)subpopulation without CD123 and CD44 is responsible for LSC and correlated with imbalance of immune cell subsets in AML

Acute myeloid leukemia(AML)is regarded as a stem cell disease.However,no one unique marker is expressed on leukemia stem cells(LSC)but not on leukemic blasts nor normal hematopoietic stem cells(HSC).CD34^(+)CD38^(-)with or without CD123 or CD44 subpopulations are immunophenotypically defined as putative LSC fractions in AML.Nevertheless,markers that can be effectively and simply held responsible for the intrinsical heterogeneity of LSC is still unclear.In the present study,we examined the frequency of three different LSC subtypes(CD34^(+)CD38^(-),CD34^(+)CD38^(-)CD123^(+),CD34^(+)CD38^(-)CD44^(+))in AML at diagnosis.We then validated their prognostic significance on the relevance of spectral features for diagnostic stratification,immune status,induction therapy response,treatment effect maintenance,and long^(-)term survival.In our findings,high proportions of the above three different LSC subtypes were all significantly characterized with low complete remission(CR)rate,high relapse/refractory rate,poor overall survival(OS),frequent FLT3^(-)ITD mutation,the high level of regulatory T cells(Treg)and monocytic myeloid^(-)derived suppressor cells(M^(-)MDSC).However,there was no significant statistical difference in all kinds of other clinical performance among the three different LSC groups.It was demonstrated that CD34^(+)CD38^(-)subpopulation without CD123 and CD44 might be held responsible for LSC and correlated with an imbalance of immune cell subsets in AML.

A Case of EBV-Associated Hemophagocytic Lymphohistiocytosis in Adult: Lessons from the Treatment Process

Hemophagocytic lymphohistiocytosis (HLH), which was first described in 1939 by paediatricians Scott and Robb-Smith, is a life-threatening disease. HLH is characterized as cytokine release syndrome which is caused by excessive but non-malignant activation of macrophages and/or histiocytes in bone marrow and other reticuloendothelial systems. EBV-HLH is the most common type of infection-associated HLH, has a high mortality rate without prompt and effective treatment. A previous study showed that the one-year mortality rate of EBV-HLH patients is 75%. Here we report a case of EBV-associated hemophagocytic syndrome in adult, and the lessons from the treatment process. Through this case, we think that for EBV-related HLH, EBV-DNA should also be monitored in addition to hemophagocytosis-related indicators during treatment. In addition, DEP regimen may not be suitable for patients who have received at least partial response, because impaired immunological functioning may lead to EBV and hemophagocytic re-activity.

Loss of Lkb1 impairs Treg function and stability to aggravate graft-versus-host disease after bone marrow transplantation

Accumulating evidence suggests that a reduction in the number of Foxp3^(+) regulatory T cells(Tregs)contributes to the pathogenesis of acute graft-versus-host disease(aGVHD),which is a major adverse complication that can occur after allogeneic hematopoietic stem cell transplantation(allo-HSCT).However,the precise features and mechanism underlying the defects in Tregs remain largely unknown.In this study,we demonstrated that Tregs were more dramatically decreased in bone marrow compared with those in peripheral blood from aGVHD patients and that bone marrow Treg defects were negatively associated with hematopoietic reconstitution.Tregs from aGVHD patients exhibited multiple defects,including the instability of Foxp3 expression,especially in response to IL-12,impaired suppressor function,decreased migratory capacity,and increased apoptosis.Transcriptional profiling revealed the downregulation of Lkb1,a previously identified critical regulator of murine Treg identity and metabolism,and murine Lkb1-regulated genes in Tregs from aGVHD patients.Foxp3 expression in human Tregs could be decreased and increased by the knockdown and overexpression of the Lkb1 gene,respectively.Furthermore,a loss-of-function assay in an aGVHD murine model confirmed that Lkb1 deficiency could impair Tregs and aggravate disease severity.These findings reveal that Lkb1 downregulation contributes to multiple defects in Tregs in human aGVHD and highlight the Lkb1-related pathways that could serve as therapeutic targets that may potentially be manipulated to mitigate aGVHD.

A cross-sectional study of complementary and alternative medicine use in patients with coagulation disorders in Southern Iran

OBJECTIVE：Complementary and alternative medicine（CAM）use has an increasing trend around the world.Despite the wild application of CAM in patients with coagulation disorders,its efficacy is still questioned by many studies.The aim of this study was to determine the frequency and types of CAM usage,and the factors affecting CAM use among patients with bleeding disorders.METHODS：This cross-sectional study investigated the usage of CAM with a standard validated questionnaire in coagulopathic patients who were referred to Dastgheib Hospital,an educational therapeutic center affiliated to the Shiraz University of Medical Sciences in Shiraz,Southern Iran.RESULTS：Between December 2015 and May 2016,75 patients were included in this survey.Severe hemophilia A and rare bleeding disorders were the most frequent among our participants.Overall,nearly half of the studied population（49.3%）used at least one CAM product or practices.The most common products were multivitamin（29.3%）,followed by folic acid（21.3%）and chamomile（12%）.32%of the patients resorted to faith healing.The main reasons of using CAM were reported to be increased general health,correction of anemia and thrombocytopenia and control of bleeding tendency.CONCLUSION：CAM is being used frequently in patients with coagulation disorders like many other chronic illnesses all around the world.Due to emerging concern regarding the safety and possible interaction with the conventional medicine,it is necessary to develop basic data about the hematologic effects of these methods in order to use them more safely.

Mitochondrial DNA sequence diversity in three ethnic populations from the South-west Iran:a preliminary study

To investigate the genetic structure of human populations in the South-west region of Iran,mitochondrial first hypervariable DNA sequences were obtained from 50 individuals representing three different ethnic groups from Khuzestan Province.Studied groups were Shushtari Persians and Chahar Lang Bakhtiyaries from Indo-Europeanspeaking populations and Bani Torof Arabs from Semitic-speaking linguistic families.Genetic analysis of mtDNA data showed high similarity of Chahar Lang Bakhtiyaries with other Iranian Indo-European-speaking populations while Shushtaries and Bani Torofs had a closer affinity with Semitic-speaking groups rather than to other Iranian populations.The relationship of Chahar Lang Bakhtiyaries and Bani Torof Arabs with their neighbor populations can be explained by linguistic and geographic proximity.Whereas,the greater similarity of Shushtari Persians with West Asian Arabs is probably according to high gene flow between them.This article represents a preliminary study of three major ethnic groups of South-west Iran which investigates the potential genetic substructure of the region.