Allogeneic stem cell transplantation in the treatment of acute myeloid leukemia: An overview of obstacles and opportunities

As an important treatment for acute myeloid leukemia, allogeneic hematopoietic stem cell transplantation(allo-HSCT) plays an important role in reducing relapse and improving long-term survival. With rapid advancements in basic research in molecular biology and immunology and with deepening understanding of the biological characteristics of hematopoietic stem cells, allo-HSCT has been widely applied in clinical practice. During allo-HSCT, preconditioning, the donor, and the source of stem cells can be tailored to the patient’s conditions, greatly broadening the indications for HSCT, with clear survival benefits. However, the risks associated with allo-HSCT remain high, i.e. hematopoietic reconstitution failure, delayed immune reconstitution, graft-versus-host disease, and posttransplant relapse, which are bottlenecks for further improvements in allo-HSCT efficacy and have become hot topics in the field of HSCT. Other bottlenecks recognized in the current treatment of individuals diagnosed with acute myeloid leukemia and subjected to allo-HSCT include the selection of the most appropriate conditioning regimen and post-transplantation management. In this paper, we reviewed the progress of relevant research regarding these aspects.

Emerging role of the gut microbiome in post-infectious irritable bowel syndrome:A literature review

Post-infectious irritable bowel syndrome(PI-IBS)is a particular type of IBS,with symptom onset after an acute episode of infectious gastroenteritis.Despite infectious disease resolution and clearance of the inciting pathogen agent,10%of patients will develop PI-IBS.In susceptible individuals,the exposure to pathogenic organisms leads to a marked shift in the gut microbiota with prolonged changes in host-microbiota interactions.These changes can affect the gut-brain axis and the visceral sensitivity,disrupting the intestinal barrier,altering neuromuscular function,triggering persistent low inflammation,and sustaining the onset of IBS symptoms.There is no specific treatment strategy for PI-IBS.Different drug classes can be used to treat PI-IBS similar to patients with IBS in general,guided by their clinical symptoms.This review summarizes the current evidence for microbial dysbiosis in PI-IBS and analyzes the available data regarding the role of the microbiome in mediating the central and peripheral dysfunctions that lead to IBS symptoms.It also discusses the current state of evidence on therapies targeting the microbiome in the management of PI-IBS.The results of microbial modulation strategies used in relieving IBS symptomatology are encouraging.Several studies on PI-IBS animal models reported promising results.However,published data that describe the efficacy and safety of microbial targeted therapy in PI-IBS patients are scarce.Future research is required.

Could there be an interplay between periodontal changes and pancreatic malignancies?

The term"periodontal disease"refers to a group of chronic inflammatory illnesses caused by specific microorganisms from subgingival biofilm,that affect the toothsupporting tissues.Recent research has also shown that periodontal infection plays a role in aggravating systemic disease states at distal sites,reinforcing the significance of the oral cavity for general health.Additionally,it has been suggested that gastroenterological malignancies may be promoted by hematogenous,enteral or lymphatic translocation of periopathogens.In the past 25 years,the global burden of pancreatic cancer(PC)has more than doubled,making it one of the major causes of cancer-related mortality.Periodontitis has been linked to at least 50%increased risk of PC and it could be considered a risk factor for this malignancy.A recent study performed on 59000 African American women with a follow up of 21 years showed that participants who had poor dental health had higher chances of PC.The findings,according to researchers,might be related to the inflammation that some oral bacteria trigger.Regarding the mortality of PC,periodontitis considerably raises the chance of dying from PC.Microbiome alterations in the gut,oral cavity and pancreatic tissues of PC patients occur when compared to healthy flora,demonstrating a link between PC and microecology.Inflammation may also contribute to PC development,although the underlying pathway is not yet known.The function of the microbiome in PC risk has drawn more focus over the last decade.Future risk of PC has been linked to the oral microbiome,specifically increased levels of Porphyromonas gingivalis and Aggregatibacter actinomycetemcomitans and decreased relative abundance of Leptotrichia and Fusobacteria,suggesting that it may have an impact on the inflammatory condition by expanding,altering,and regulating the commensal microbiome.Patients who received periodontal treatment had significantly decreased incidence rate ratios for PC.By analyzing patterns in the microbiome composition throughout PC development and establishing strategies to enhance the cancerassociated microbial system,we can increase the efficacy of therapy and eventually find an application for the microbial system.The development of immunogenomics and gut microgenomics in the life sciences will result in a significant advancement in our understanding of how microbial systems and immunotherapy interact,and it may also have intriguing therapeutic implications for extending the lifetime of PC patients.

Acute myocardial infarction in myeloproliferative neoplasms

Myeloproliferative neoplasms(MPNs)are a heterogeneous group of hematologic malignancies characterized by an abnormal proliferation of cells of the myeloid lineage.Affected individuals are at increased risk for cardiovascular and thrombotic events.Myocardial infarction(MI)may be one of the earliest clinical manifestations of MPNs or may be a thrombotic complication that develops during the natural course of the disease.In the present review,we examine the epidemiology,pathogenesis,clinical presentation,and management of MI in MPNs based on the available literature.Moreover,we review potential biomarkers that could mediate the MI-MPNs crosstalk,from classical biochemical tests,e.g.,lactate dehydrogenase,creatine kinase and troponins,to pro-inflammatory cytokines,oxidative stress markers,and clonal hematopoiesis.

Budd-Chiari syndrome in myeloproliferative neoplasms:A review of literature

Myeloproliferative neoplasms(MPNs)are defined as clonal disorders of the hematopoietic stem cell in which an exaggerated production of terminally differentiated myeloid cells occurs.Classical,Philadelphia-negative MPNs,i.e.,polycythemia vera,essential thrombocythemia and primary myelofibrosis,exhibit a propensity towards the development of thrombotic complications that can occur in unusual sites,e.g.,portal,splanchnic or hepatic veins,the placenta or cerebral sinuses.The pathogenesis of thrombotic events in MPNs is complex and requires an intricate mechanism involving endothelial injury,stasis,elevated leukocyte adhesion,integrins,neutrophil extracellular traps,somatic mutations(e.g.,the V617F point mutation in the JAK2 gene),microparticles,circulating endothelial cells,and other factors,to name a few.Herein,we review the available data on Budd-Chiari syndrome in Philadelphia-negative MPNs,with a particular focus on its epidemiology,pathogenesis,histopathology,risk factors,classification,clinical presentation,diagnosis,and management.

Toxicity of targeted anticancer treatments on the liver in myeloproliferative neoplasms

The liver has a central role in metabolism,therefore,it is susceptible to harmful effects of ingested medications(drugs,herbs,and nutritional supplements).Druginduced liver injury(DILI)comprises a range of unexpected reactions that occur after exposure to various classes of medication.Even though most cases consist of mild,temporary elevations in liver enzyme markers,DILI can also manifest as acute liver failure in some patients and can be associated with mortality.Herein,we briefly review available data on DILI induced by targeted anticancer agents in managing classical myeloproliferative neoplasms:Chronic myeloid leukemia,polycythemia vera,essential thrombocythemia,and myelofibrosis.

Extrahepatic cholangiocarcinoma:Current status of endoscopic approach and additional therapies

The prognosis of patients with advanced or unresectable extrahepatic cholangiocarcinoma is poor.More than 50%of patients with jaundice are inoperable at the time of first diagnosis.Endoscopic treatment in patients with obstructive jaundice ensures bile duct drainage in preoperative or palliative settings.Relief of symptoms(pain,pruritus,jaundice)and improvement in quality of life are the aims of palliative therapy.Stent implantation by endoscopic retrograde cholangiopancreatography is generally preferred for long-term palliation.There is a vast variety of plastic and metal stents,covered or uncovered.The stent choice depends on the expected length of survival,quality of life,costs and physician expertise.This review will provide the framework for the endoscopic minimally invasive therapy in extrahepatic cholangiocarcinoma.Moreover,additional therapies,such as brachytherapy,photodynamic therapy,radiofrequency ablation,chemotherapy,molecular-targeted therapy and/or immunotherapy by the endoscopic approach,are the nonsurgical methods associated with survival improvement rate and/or local symptom palliation.

Stem/progenitor cells and obstructive sleep apnea syndrome - new insights for clinical applications

Obstructive sleep apnea syndrome(OSAS) is a widespread disorder, characterized by recurrent upper airway obstruction during sleep, mostly as a result of complete or partial pharyngeal obstruction. Due to the occurrence of frequent and regular hypoxic events, patients with OSAS are at increased risk of cardiovascular disease, stroke, metabolic disorders, occupational errors, motor vehicle accidents and even death. Thus, OSAS has severe consequences and represents a significant economic burden. However, some of the consequences, as well as their costs can be reduced with appropriate detection and treatment. In this context, the recent advances that were made in stem cell biology knowledge and stem cell- based technologies hold a great promise for various medical conditions, including respiratory diseases. However, the investigation of the role of stem cells in OSAS is still recent and rather limited, requiring further studies, both in animal models and humans. The goal of this review is to summarize the current state of knowledge regarding both lung resident as well as circulating stem/progenitor cells and discuss existing controversies in the field in order to identify future research directions for clinical applications in OSAS. Also, the paper highlights the requisite for inter-institutional, multi-disciplinary research collaborations in order to achieve breakthrough results in the field.

Molecular diagnosis in cat allergy

Domestic cats represent one of the most common sources of indoor allergens.All over the world,many households own cats,whose allergens are persistent and widespread.Cat allergy itself is frequent,and its symptoms vary from rhinoconjunctivitis to life-threatening asthma.In vitro diagnosis using precision medicine allergy immunoassays is important because natural cat dander extracts may differ in quality and quantity of some of the individual allergen components and other molecules.In the component-resolved diagnosis of cat allergy,singleplex and multiplex specific immunoglobulin(Ig)E assays include use of the cat-specific major allergen,secretoglobin Fel d 1(as a species-specific molecule),other allergen components(such as lipocalins Fel d 4,cross-reacting with other animal similar molecules,and Fel d 7,present in small quantities in natural extracts),and serum albumin Fel d 2(related to the cat-pork syndrome).IgA Fel d 5 and IgM Fel d 6 are not available as allergen components in the current commercial IgE immunoassays,but they may impair the in vitro diagnostic evaluation of cat allergy because galactose-α1,3-galactose is an IgE-binding epitope of these native feline allergens.The benefits of molecular-based cat allergy diagnosis are continually evaluated,as the role of recombinant allergen components already known is detailed and new other molecules of interest may be discovered in the future.

Occult hepatitis B—the result of the host immune response interaction with different genomic expressions of the virus

With over 40 years of history,occult hepatitis B infection(OBI)continues to remain an important and challenging public health problem.Defined as the presence of replication-competent hepatitis B virus(HBV)DNA(i.e.,episomal HBV covalently closed circular DNA)in the liver and/or HBV DNA in the blood of people who test negative for hepatitis B surface antigen(HBsAg)in currently available assays,OBI is currently diagnosed using polymerase chain reaction(PCR)and real-time PCR assays.However,all efforts should be made to exclude a false negative HBsAg in order to completely follow the definition of OBI.In recent years,significant advances have been made in understanding the HBV lifecycle and the molecular mechanisms that lead to the persistence of the virus in the occult form.These factors are mainly related to the host immune system and,to a smaller proportion,to the virus.Both innate and adaptive immune responses are important in HBV infection management,and epigenetic changes driven by host mechanisms(acetylation,methylation,and microRNA implication)are added to such actions.Although greater genetic variability in the S gene of HBV isolated from OBIs was found compared with overt infection,the mechanisms of OBI are not mainly viral mutations.

High perioperative lactate levels and decreased lactate clearance are associated with increased incidence of posthepatectomy liver failure

To the Editor:Extensive liver resection represents a life-saving intervention in patients with primary or secondary liver tumors.Recent advances made in the field of chemotherapy and surgical techniques have translated into a greater number of patients who are older and with more complex comorbidities presenting for major liver surgery[1]and thus having an increased risk of perioperative mortality.

The Evolution of Disability during the Last Years in Romania and EU Member States

Purpose: People with disabilities represent a major objective, a global public health issue. This disadvantaged category needs protection and integration into society by implementing an improved legislative framework. The effectiveness of the policy making, consolidating the benefit programs and enhancing equity of the social insurance system represent the key of The Governments strategy. Methods: The paper highlights comparable data and research related to disability and social insurance system from Romania and other Member States of the European Union. Internationally, a proper measurement of disability may lead to a successful removal of barriers which increase the vulnerability of people with disability. Results: According to official data, in Romania the number of disabled people decreased gradually one year to another (in the last 5 years). In the EU Member States, musculoskeletal disorders leading to disability were one of the most common compared to Romania where it ranked last. From the point of view of the share in the total number of people with disabilities, according to the degree of disability, both in the EU Member States and in Romania, the number of moderately disabled people was double, respectively triple compared to the number of those with severe disability. Conclusion: The Romania Government promotes social-professional integration of people with disabilities, being responsible for the guidance, vocational counselling and employment. In accordance with our law, “any person with disabilities, fit and included in the labor market in Romania is entitled to a reasonable accommodation of the workplace.”

Vulnerability to Stress and Depression Risk Related to Occupational Exposure to Aluminum

Occupational exposure to aluminum was reported to be associated with various neurotoxic effects including cognitive impairment, depression, anxiety, and also Alzheimer’s disease. The purpose of the present study was to evaluate the level of vulnerability to stress in workers exposed to aluminum. The correlation between vulnerability to stress and depression was also investigated. This was a retrospective study that included 135 participants, 99 were exposed to aluminum, and 36 were not exposed to aluminum. Vulnerability to stress and depression was assessed using a self-rating scale developed in-house. Vulnerability to stress was reported in various degrees in a total of 84 participants, 69 (69.70%) participants from the exposed group and 15 (41.67%) participants from the control group. Out of the 84 participants with vulnerability to stress, 51 had depression also. Excellent resistance to stress was reported in 51 out of 135 participants, 30 (30.30%) in the exposed group and 21 (58.33%) in the control group. Out of the 51 participants with excellent resistance to stress, only 2 participants had depression. The results of the present study suggested that exposure to aluminum is correlated with vulnerability to stress. The level of vulnerability to stress is increasing with the level of exposure to aluminum. Furthermore, since vulnerability to stress is correlated with depression, higher exposure to aluminum might be a risk factor for depression.