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Harnessing immunity:Immunomodulatory therapies in COVID-19

World Journal of Virology 2024年第2期13卷 34-47页

作者： Tsvetelina Velikova Hristo Valkov Anita Aleksandrova monika peshevska-sekulovska Metodija Sekulovski Russka Shumnalieva Medical Faculty Sofia University St.Kliment OhridskiSofia 1407Bulgaria Department of Gastroenterology University Hospital“Tsaritsa Yoanna-ISUL”Medical University of SofiaSofia 1527Bulgaria Department of Immunology SMDL RamusSimitli 6000Bulgaria Department of Gastroenterology University Hospital LozenetzSofia 1407Bulgaria Department of Anesthesiology and Intensive Care University Hospital LozenetzSofia 1407Bulgaria Department of Rheumatology Clinic of RheumatologyUniversity Hospital"St.Ivan Rilski"Medical University-SofiaSofia 1612Bulgaria

An overly exuberant immune response,characterized by a cytokine storm and uncontrolled inflammation,has been identified as a significant driver of severe coronavirus disease 2019(COVID-19)***,deciphering the intricacies of immune dysregulation in COVID-19 is imperative to identify specific targets for intervention and *** these delicate dynamics in mind,immunomodulatory therapies have emerged as a promising avenue for miti-gating the challenges posed by *** in manipulating immune pathways presents an opportunity to alter the host response,optimizing antiviral defenses while curbing deleterious *** review article compre-hensively analyzes immunomodulatory interventions in managing *** explore diverse approaches to mitigating the hyperactive immune response and its impact,from corticosteroids and non-steroidal drugs to targeted biologics,including anti-viral drugs,cytokine inhibitors,JAK inhibitors,convalescent plasma,monoclonal antibodies(mAbs)to severe acute respiratory syndrome coronavirus 2,cell-based therapies(i.e.,CAR T,etc.).By summarizing the current evidence,we aim to provide a clear roadmap for clinicians and researchers navigating the complex landscape of immunomodulation in COVID-19 *** Glucocorticoids are among the most widely prescribed drugs with their immune-suppressive and anti-inflammatory effect[84].The current guidelines for the treatment of COVID-19 recommend against the use of dexamethasone or other systemic CS in non-hospitalized patients in the absence of another indication[70].The RECOVERY trial demonstrates the reduced 28-d mortality among hospitalized patients with COVID-19 using dexamethasone compared to the usual standard of care,along with other investigators,such as Ahmed and Hassan[85].The benefit of dexamethasone was seen only among participants receiving either oxygen alone or invasive mechanical ventilation at randomization but not among those receiving no respi

关键词： Immunomodulation COVID-19 SARS-CoV-2 Immunotherapy Antiviral immune response Cytokine storm Adaptive immunity Therapeutic strategies Immune modulators Viral infection Host immune response

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Synchronous manifestation of colorectal cancer and intraductal papillary mucinous neoplasms

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World Journal of Clinical Cases 2023年第15期11卷 3408-3417页

作者： Milko Bozhidarov Mirchev Irina Boeva monika peshevska-sekulovska Veselin Stoitsov Milena Peruhova Department of Gastroenterology Heart and Brain HospitalBurgas 8000Bulgaria Department of Gastroenterology University Hospital LozenetzSofia 1407Bulgaria

High rates of extrapancreatic malignancies,in particular colorectal cancer(CRC),have been detected in patients with intraductal papillary mucinous neoplasm(IPMN).So far,there is no distinct explanation in the literature for the development of secondary or synchronous malignancies in patients with *** the past few years,some data related to common genetic alterations in IPMN and other affiliated cancers have been *** review elucidated the association between IPMN and CRC,shedding light on the most relevant genetic alterations that may explain the possible relationship between these *** keeping with our findings,we suggested that once the diagnosis of IPMN is made,special consideration of CRC should be ***,there are no specific guidelines regarding colorectal screening programs for patients with *** recommend that patients with IPMNs are at high-risk for CRC,and a more rigorous colorectal surveillance program should be implemented.

关键词： Colorectal cancer Intraductal papillary mucinous neoplasm Genetic alterations Extrapancreatic malignancies Synchronous neoplasms

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World Journal of Clinical Cases 2023年第9期11卷 1918-1929页

作者： Metodija Sekulovski Simona Bogdanova-Petrova monika peshevska-sekulovska Tsvetelina Velikova Tsvetoslav Georgiev Department of Anesthesiology and Intensive Care University Hospital LozenetzSofia 1407Bulgaria Medical Faculty Sofia University St.Kliment OhridskiSofia 1407Bulgaria First Department of Internal Medicine Medical University-VarnaVarna 9010Bulgaria Clinic of Rheumatology University Hospital“St.Marina”Varna 9010Bulgaria Department of Gastroenterology University Hospital LozenetzSofia 1407Bulgaria Department of Clinical Immunology University Hospital LozenetzSofia 1407Bulgaria

While severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)quickly spread across the globe,our understanding of its pathogenic mechanisms ***,coronavirus disease 2019(COVID-19)is now considered a syndromic multisystem inflammatory disease involving not only the respiratory system but also the cardiovascular,excretory,nervous,musculoskeletal,and gastrointestinal ***,a membrane-bound form of angiotensin-converting enzyme 2,the entry receptor for SARS-CoV-2,is expressed on the surface of cholangiocytes and hepatocytes,suggesting the potential of COVID-19 to involve the *** the widespread distribution of SARS-CoV-2 throughout the population,infection during pregnancy is no longer a rare occurrence;however,little is known about the course of hepatic injuries and related outcomes in pregnant SARS-CoV-2-positive ***,the understudied topic of COVID-related liver disease during pregnancy poses a great challenge for the consulting gynecologist and *** this review,we aim to describe and summarize potential liver injuries in pregnant women with COVID-19.

关键词： COVID-19 Liver injury Pregnancy SARS-CoV-2 Angiotensin-converting enzyme 2 receptors

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Islet transplantation-immunological challenges and current perspectives

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World Journal of Transplantation 2023年第4期13卷 107-121页

作者： Plamena Kabakchieva Yavor Assyov Stavros Gerasoudis Georgi Vasilev monika peshevska-sekulovska Metodija Sekulovski Snezhina Lazova Dimitrina Georgieva Miteva Milena Gulinac Latchezar Tomov Tsvetelina Velikova Clinic of Internal Diseases Naval Hospital-VarnaMilitary Medical AcademyVarna 9010Bulgaria Clinic of Endocrinology Department of Internal DiseasesUniversity Hospital"Alexandrovska"Medical University-SofiaSofia 1434Bulgaria Faculty of Medicine Trakia UniversityStara Zagora 6000Bulgaria Department of Neurology Faculty of MedicineMedical University of PlovdivPlovdiv 4000Bulgaria Department of Gastroenterology University Hospital LozenetzSofia 1407Bulgaria Medical Faculty Sofia University St.Kliment OhridskiSofia 1407Bulgaria Department of Anesthesiology and Intensive Care University hospital LozenetzSofia 1407Bulgaria Department of Pediatric University Hospital"N.I.Pirogov"Sofia 1606Bulgaria Department of Healthcare Faculty of Public Health"Prof.Tsekomir VodenicharovMDDSc"Medical University of SofiaSofia 1527Bulgaria Department of Genetics Sofia University"St.Kliment Ohridski"Sofia 1164Bulgaria Department of General and Clinical Pathology Medical University of PlovdivPlovdiv 4000Bulgaria Department of Informatics New Bulgarian UniversitySofia 1618Bulgaria

Pancreatic islet transplantation is a minimally invasive procedure aiming to reverse the effects of insulin deficiency in patients with type 1 diabetes(T1D)by transplanting pancreatic beta ***,pancreatic islet transplantation has improved to a great extent,and cellular replacement will likely become the mainstay *** review pancreatic islet transplantation as a treatment for T1D and the immunological challenges *** data demonstrated that the time for islet cell transfusion varied between 2 and 10 *** 54%of the patients gained insulin independence at the end of the first year,while only 20%remained insulin-free at the end of the second ***,most transplanted patients return to using some form of exogenous insulin within a few years after the transplantation,which imposed the need to improve immunological factors before *** also discuss the immunosuppressive regimens,apoptotic donor lymphocytes,anti-TIM-1 antibodies,mixed chimerism-based tolerance induction,induction of antigen-specific tolerance utilizing ethylene carbodiimide-fixed splenocytes,pretransplant infusions of donor apoptotic cells,B cell depletion,preconditioning of isolated islets,inducing local immunotolerance,cell encapsulation and immunoisolation,using of biomaterials,immunomodulatory cells,etc.

关键词： Islet transplantation Type 1 diabetes Diabetes mellitus Immune tolerance Graft rejection T regulatory cells B regulatory cells

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Surveilling Russell body Helicobacter pylori-negative gastritis: A case report and review of literature

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World Journal of Gastroenterology 2020年第33期26卷 5050-5059页

作者： Milena Peruhova monika peshevska-sekulovska Viktoriya Georgieva Gabriela Panayotova Dorian Dikov Department of Gastroenterology University Hospital LozenetzSofia 1407Bulgaria Department of General and Clinical pathology Grand Hôpital de l'Est FrancilienJossigny 77600France

BACKGROUND Russell body gastritis(RBG)is very rare type of chronic inflammation of gastric *** pathologic hallmark of the disease is Russell bodies(RB)which represent accumulation of eosinophilic cytoplasmic inclusions in endoplasmic reticulum of mature plasma cells(Mott cells).Most published cases are associated with Helicobacter pylori(***)infection because of correlation between plasma cell activation and antigenic *** are insufficient data about ***-negative RBG and very little is known about the natural course of the *** SUMMARY A 51-year-old male patient underwent endoscopic screening for mild iron deficiency *** revealed diffuse hyperemia,edema and nodularity of the fundic and corpus *** to non-specific endoscopic findings and iron-deficiency anemia our preliminary diagnosis was diffuse type of gastric carcinoma or gastric *** specimens of gastric mucosa showed inflammatory infiltrate rich in Mott cells,consisting entirely of cytoplasmic *** of nuclear atypia and mitosis of the plasma cells,polyclonal pattern of the Mott cells and negative staining for cytokeratins favored diagnosis of *** patient was treated with proton-pump inhibitor for 8 ***-term clinical and endoscopic surveillance was ***,there was no improvement in endoscopic features of the gastric mucosa in three consecutive gastroscopies,histopathological findings demonstrated that the chronic inflammatory infiltrate in the fundic mucosa is less pronounced,rich in plasma cells,with almost absent RB and Mott *** The prognosis of this entity is uncertain,that is why these patients are subjects of continuous follow up.

关键词： Russell body gastritis Helicobacter pylori-negative Treatment Mature plasma cells Case report

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COVID-19 in patients with gastrointestinal stromal tumors: Recommendations for management and vaccination

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World Journal of Gastrointestinal Pathophysiology 2022年第5期13卷 170-177页

作者： Violeta Snegarova Dimitrina Miteva Milena Gulinac monika peshevska-sekulovska Hristiana Batselova Tsvetelina Velikova Clinic of Internal Diseases Naval Hospital–VarnaMilitary Medical AcademyMedical FacultyMedical UniversityVarna 9000Bulgaria Faculty of Biology Department of GeneticsSofia University"St.Kliment Ohridski"Sofia 1164Bulgaria Department of General and Clinical Pathology Medical FacultyMedical University of PlovdivPlovdiv 4000Bulgaria Department of Gastroenterology University Hospital LozenetzSofia 1407Bulgaria Medical Faculty Sofia University St.Kliment OhridskiSofia 1407OthersBulgaria Department of Epidemiology and Disaster Medicine Medical UniversityPlovdivUniversity Hospital"St George"Plovdiv 6000Bulgaria Department of Clinical Immunology University Hospital LozenetzSofia 1407Bulgaria

The coronavirus disease 2019(COVID-19)pandemic profoundly affected the management and treatment of patients with *** on the progress reported in the literature,we reviewed the recommendations for treatment and vaccination in patients with gastrointestinal stromal tumor(GIST)during *** focus on whether there is a risk and what could be the possible effects of vaccinating patients with GIST/*** the situation is quickly changing,and the health services have been severely disrupted,the diagnosis,treatment and recommendations for vaccination of these patients against COVID-19 are still not *** approval of vaccines in the pandemic gave hope that we would soon be able to return to a more normal ***,the oncology community needs to adapt and provide the most effective treatment and care models for patients with rare cancer,such as *** data on the impact of vaccination in patients with GIST/cancer also will be beneficial in expanding knowledge about the future planning of treatment strategies and optimizing care in the event of a subsequent pandemic.

关键词： Gastrointestinal stromal tumor GIST Cancer COVID-19 vaccination efficacy Treatment strategy Side effects

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Mucosal COVID-19 vaccines:Risks,benefits and control of the pandemic

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World Journal of Virology 2022年第5期11卷 221-236页

作者： Dimitrina Miteva monika peshevska-sekulovska Violeta Snegarova Hristiana Batselova Radostina Alexandrova Tsvetelina Velikova Department of Genetics Sofia University“St.Kliment Ohridski”Faculty of BiologySofia 1164Bulgaria Department of Gastroenterology University Hospital LozenetzSofia 1407Bulgaria Medical Faculty Sofia University St.Kliment OhridskiSofia 1407Bulgaria Clinic of Internal Diseases Naval Hospital-VarnaMilitary Medical AcademyMedical FacultyMedical UniversityVarna 9000Bulgaria Department of Epidemiology and Disaster Medicine Medical UniversityPlovdivUniversity Hospital“St George”Plovdiv 6000Bulgaria Department of Pathology Institute of Experimental MorphologyPathology and Anthropology with MuseumBulgarian Academy of SciencesSofia 1000Bulgaria Department of Clinical Immunology University Hospital LozenetzSofia 1407Bulgaria

Based on mucosal immunization to promote both mucosal and systemic immune responses,next-generation coronavirus disease 2019(COVID-19)vaccines would be administered intranasally or *** goal of severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)vaccines is to provide adequate immune protection and avoid severe disease and *** vaccine candidates for COVID-19 including vector vaccines,recombinant subunit vaccines and live attenuated vaccines are under ***,subunit protein vaccines and virus-vectored vaccines have made substantial progress in preclinical and clinical settings,resulting in SARS-CoV-2 intranasal vaccines based on the previously successfully used nasal *** to their ability to trigger stable,protective immune responses at the sites of pathogenic infection,the development of‘specific’mucosal vaccines targeting coronavirus antigens could be an excellent option for preventing future ***,their efficacy and safety should be confirmed.

关键词： SARS-CoV-2 COVID-19 vaccine Mucosal immunity Intranasal vaccination Oral vaccines Resident memory T cells Vaccine safety Vaxart OraPro-COVID-19 vaccine RPS-vector system platform

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Long-term effectiveness,outcomes and complications of bariatric surgery

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World Journal of Clinical Cases 2023年第19期11卷 4504-4512页

作者： Milena Gulinac Dimitrina Georgieva Miteva monika peshevska-sekulovska Ivan P Novakov Svetozar Antovic Milena Peruhova Violeta Snegarova Plamena Kabakchieva Yavor Assyov Georgi Vasilev Metodija Sekulovski Snezhina Lazova Latchezar Tomov Tsvetelina Velikova Department of General and Clinical Pathology Medical University of PlovdivPlovdiv 4000Bulgaria Department of Genetics Sofia University"St.Kliment Ohridski"Faculty of BiologySofia 1164Bulgaria Department of Gastroenterology University Hospital LozenetzSofia 1407Bulgaria Department of Thoraco-abdominal Surgery Medical University PlovdivPlovdiv 6000Bulgaria University Clinic for Digestive Surgery Medical FacultySkopjeSkopje 1000North Macedonia Department of Gastroenterology Heart and Brain HospitalBurgasBurgas 1000Bulgaria Clinic of Internal Diseases Naval Hospital-VarnaMilitary Medical AcademyMedical FacultyMedical UniversityVarna 9000Bulgaria Clinic of Internal Diseases Naval Hospital-VarnaMilitary Medical AcademyVarna 9010Bulgaria Clinic of Endocrinology University Hospital AlexandrovskaSofia 1431Bulgaria Department of Internal Diseases Medical University–SofiaSofia 1431Bulgaria Clinic of Endocrinology and Metabolic Disorders UMHAT"Sv.Georgi"Plovdiv 4000Bulgaria Department of Anesthesiology and Intensive Care University Hospital LozenetzSofia 1407Bulgaria Medical Faculty Sofia UniversitySt.Kliment OhridskiSofia 1407Bulgaria Department of Pediatric University Hospital"N.I.Pirogov"Sofia 1606Bulgaria Department of Healthcare Faculty of Public Health"Prof.Tsekomir VodenicharovMDDSc"Sofia 1527Bulgaria Department of Informatics New Bulgarian UniversitySofia 1618Bulgaria Medical Faculty Sofia University St.Kliment OhridskiSofia 1407Bulgaria

Dietary imbalance and overeating can lead to an increasingly widespread *** considerations aside,obesity is defined as an excess of adipose tissue that can lead to serious health problems and can predispose to a number of pathological changes and clinical diseases,including diabetes;hypertension;atherosclerosis;coronary artery disease and stroke;obstructive sleep apnea;depression;weight-related arthropathies and endometrial and breast cancer.A body weight 20%above ideal for age,gender and height is a severe health *** surgery is a set of surgical methods to treat morbid obesity when other treatments such as diet,increased physical activity,behavioral changes and drugs have *** two most common procedures currently used are sleeve gastrectomy and gastric *** procedure has gained popularity recently and is generally considered safe and *** current data show that perioperative mortality is low and better control of comorbidities and short-term complications is achieved,more randomized trials are needed to evaluate the long-term outcomes of bariatric *** review aims to synthesize and summarize the growing evidence on the long-term effectiveness,outcomes and complications of bariatric surgery.

关键词： Bariatric surgery Long-term outcomes Obesity Roux-en-Y gastric bypass sleeve gastrectomy Effectiveness Safety Quality of life

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What could microRNA expression tell us more about colorectal serrated pathway carcinogenesis?

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World Journal of Gastroenterology 2020年第42期26卷 6556-6571页

作者： Milena Peruhova monika peshevska-sekulovska Boris Krastev Gabriela Panayotova Viktoriya Georgieva Rossitza Konakchieva Georgi Nikolaev Tsvetelina Veselinova Velikova Department of Gastroenterology University Hospital LozenetzSofia 1407Bulgaria Medical Faculty Sofia University St.Kliment OhridskiSofia 1407Bulgaria Department of Clinical Oncology MHAT Hospital for Women Health NadezhdaSofia 1330Bulgaria Faculty of Biology Sofia University St.Kliment OhridskiSofia 1407Bulgaria Department of Clinical Immunology University Hospital LozenetzSofia 1407Bulgaria

In the last two decades,the vision of a unique carcinogenesis model for colorectal carcinoma(CRC)has completely *** addition to the adenoma to carcinoma transition,colorectal carcinogenesis can also occur via the serrated *** non-coding RNA,known as microRNAs(miRNAs),were also shown to be involved in progression towards ***,increased expression of certain miRNAs in premalignant sessile serrated lesions(SSLs)was found,emphasizing their role in the serrated pathway progression towards colon *** miRNAs function as post-transcriptional gene regulators,they have enormous potential to be used as useful biomarkers for CRC and screening in patients with SSLs *** this review,we have summarized the most relevant information about the specific role of miRNAs and their relevant signaling pathways among different serrated lesions and polyps as well as in serrated *** focus is put on the correlation between gut immunity and miRNA expression in the serrated pathway,which remains unstudied.

关键词： MicroRNA Serrated pathway Carcinogenesis Colorectal carcinoma Sessile serrated lesions Adenocarcinoma

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Factors affecting complications development and mortality after single lung transplant

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World Journal of Transplantation 2021年第8期11卷 320-334页

作者： Metodija Sekulovski Bilyana Simonska Milena Peruhova Boris Krastev monika peshevska-sekulovska Lubomir Spassov Tsvetelina Velikova Department of Anesthesiology and Intensive care University Hospital LozenetzSofia 1407Bulgaria Medical Faculty Sofia University St.Kliment OhridskiSofia 1407Bulgaria Department of Gastroenterology University Hospital LozenetzSofia 1407Bulgaria Department of Clinical Oncology MHAT Hospital for Women Health NadezhdaSofia 1330Bulgaria Department of Cardiothoracic Surgery University Hospital LozenetzSofia 1431Bulgaria Department of Clinical Immunology University Hospital LozenetzSofia 1407Bulgaria

Lung transplantation(LT)is a life-saving therapeutic procedure that prolongs survival in patients with end-stage lung ***,as a therapeutic option for high-risk candidates,single LT(SLT)can be feasible because the immediate morbidity and mortality after transplantation are lower compared to sequential single(double)LT(SSLTx).Still,the long-term overall survival is,in general,better for *** the great success over the years,the early post-SLT period remains a perilous time for these *** who undergo SLT are predisposed to evolving early or late postoperative *** review emphasizes factors leading to post-SLT complications in the early and late periods including primary graft dysfunction and chronic lung allograft dysfunction,native lung complications,anastomosis complications,infections,cardiovascular,gastrointestinal,renal,and metabolite complications,and their association with morbidity and mortality in these ***,we discuss the incidence of malignancy after SLT and their correlation with immunosuppression therapy.

关键词： Lung transplantation Single lung transplant Primary graft dysfunction Native lung complications Technical transplant complications Vascular transplant complications Graft rejection De novo malignancy

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