Human Herpesvirus Type Research Articles

Prospective, Cross-Sectional Study Finds No Common Viruses in Cerebrospinal Fluid of Children with Pseudotumor Cerebri

Pseudotumor cerebri (PTC) in children is a rare condition whose underlying cause remains largely unknown. No study has yet systematically examined viral infection as a cause of PTC. The current study aimed to characterize PTC in children and investigate the possible role of acute viral infection of the central nervous system in its pathogenesis. A prospective, cross-sectional study was conducted in three centers in Israel. Participants were 50 children aged 0.5-18 years, of whom 27 had a definitive diagnosis of pseudotumor cerebri (the study group) and 23 comprised a control. Data collected included clinical presentation, imaging, treatment, ophthalmic findings, and cerebrospinal fluid (CSF) analysis. Using the ALLPLEXTM meningitis panel, real-time polymerase chain reaction (PCR) was used to test for the presence of 12 common viruses. PTC patients (mean age 12 ± 4.3 years; 14 males, 13 females) had mean opening pressure of 41.9 ±10.2 mmH2O. All PTC patients had papilledema, and 25 (93%) had PTC symptoms. No viruses were found in the PTC group, while in the control group, one patient tested positive for Epstein-Barr virus and another for human herpesvirus type 6. Overall, in our study, PTC was not found to be associated with the presence of viruses in CSF.

Chemical Characterization of Different Extracts of Justicia secunda Vahl and Determination of Their Anti-Oxidant, Anti-Enzymatic, Anti-Viral, and Cytotoxic Properties.

Justicia secunda Vahl. is a traditional medicinal plant in tropical regions, including West Africa. The present study examined the chemical profiles and biological properties of J. secunda extracts obtained with different solvents (dichloromethane, ethyl acetate, methanolic and aqueous: macerated and infused). Chemical components were characterized by liquid chromatography-mass spectrometry (LC-MS), and over 50 compounds were identified, including flavonoids, phenolic acids, and alkaloids. Antioxidant, enzyme inhibitory, cytotoxic, and antiviral properties were selected as biological properties. Total phenolic and flavonoid contents in methanol (58.07 mg gallic acid equivalent (GAE)/g and 13.07 mg rutin equivalent (RE)/g) and water (infused) (36.34 mg GAE/g and 8.52 mg RE/g) were higher than in other extracts. Consistent with the levels of total bioactive components, the methanol and water extracts exhibited stronger antioxidant abilities. However, the dichloromethane and ethyl acetate extracts were more active on α-amylase and α-glucosidase than other extracts. Aqueous extracts exerted selective anticancer properties toward human pharyngeal cancer cell lines, whereas the methanolic extract decreased the human herpesvirus type-1 (HHV-1) infectious titer by 2.16 log and the viral load by 1.21 log. Overall, J. secunda could be considered a multifunctional bioactive raw material in the preparation of potent applications to manage diseases related to oxidative stress, including cancer, diabetes, and Alzheimer's.

Hunting for mpox (monkeypox) mimickers: Use of the Biofire meningitis/encephalitis panel on lesion swabs to support alternative viral diagnoses

Mpox (formerly monkeypox) is an emerging zoonotic disease of public health concern that presents as a rash mimicking other common viral exanthems. Unlike traditional testing algorithms relying on several assays, the BioFire FilmArray meningitis/encephalitis (ME) panel simultaneously detects common viruses causing rashes; however, Biofire ME is only licensed for testing on cerebral spinal fluid. This study evaluated use of the Biofire ME panel for detection and discrimination of herpes simplex virus types 1 and 2 (HSV-1 and HSV-2), varicella zoster virus (VZV), human herpesviruses type 6 (HHV-6), enteroviruses (EVs), and human paraechoviruses (HPeVs) from a dermal or mucocutaneous swabs collected in universal transport media (UTM). Results of the BioFire ME panel were compared against methods used during clinical testing. Ten-fold serial dilutions in UTM of cultured viruses were used to compare analytical sensitivity, and analytical specificity was assessed using panels of microorganisms in UTM. Clinical sensitivity and specificity were assessed using 20 positive specimens each for HHV-1, HHV-2, HHV-6, VZV, EVs, and HPeV, as well as 35 known negative specimens that included 15 mpox-positive specimens. Biofire ME was as sensitive as comparator methods, and correctly discriminated all HSV-1, HSV-2, VZV, HHV-6, EVs, and HPeVs from mpox and mpox-mimickers. Cross-reaction between EV and rhinoviruses A, B, and C were noted in the specificity panel. Swabs in UTM collected for mpox testing are suitable for use on the Biofire ME panel, allowing more streamlined diagnostic testing for viral exanthems in patients under investigation for mpox infection.

Changing therapeutic landscape in advanced Kaposi sarcoma: Current state and future directions.

Kaposi sarcoma is a malignant neoplasm arising from the endothelial cell lining of blood and lymphatic vessels. Herein, we discuss etiopathogenesis, clinical presentation, diagnostic criteria, updated guideline-based approach to its management and newer experimental approaches. Given its efficacy and side effect profile, pegylated doxorubicin is the currently preferred first-line therapy in advanced disease. Paclitaxel remains an alternative first-line option. At the time of relapse, patients can be retreated with the same agents as they often maintain their clinical efficacy. New therapeutic options are on the rise, with pomalidomide being approved in 2020 as a second-line therapy. Optimal control of retroviral infection in human immunodeficiency virus (HIV) positive is instrumental in preventing disease occurrence in most patients. Suppressing human herpes virus type 8 (HHV-8) infection might also play a role in controlling Kaposi sarcoma growth, yet clinical trials are lacking. Unraveling the molecular and genetic intricacies of Kaposi sarcoma's pathogenesis might allow for the emergence of novel and effective therapeutic strategies. Clinical trials are currently underway to establish potential roles for various targeted agents, immune checkpoint inhibitors (ICIs) and experimental agents in the treatment of advanced Kaposi sarcoma.

Cigarette smoking is associated with Herpesviruses in persons with and without serious mental illness.

Herpesviruses are recognized as major causes of human diseases. Following initial infection, Herpesviruses can undergo cycles of reactivation controlled largely by the immune system. Cigarette smoking is an important modulator of the immune system particularly in individuals with serious mental illness where smoking is associated with increased rates of cardiopulmonary diseases and mortality. However, the effect of smoking on Herpesviruses has not been extensively studied. In this nested cohort study, cigarette smoking was assessed in 1323 persons with serious mental illness or without a psychiatric disorder ascertained in a psychiatric health care system and the adjacent community. Participants provided a blood sample from which were measured IgG class antibodies to five human Herpesviruses: Cytomegalovirus (CMV), Epstein Barr Virus (EBV), Herpes Simplex Virus-Type 1 (HSV-1); Varicella Zoster Virus (VZV); and Human Herpes Virus-Type 6 (HHV-6). The associations between smoking variables and antibody levels to the Herpesviruses were analyzed among diagnostic groups in multiple regression models adjusted for age, sex, and race. Current smoking was significantly associated with higher levels of antibodies to CMV (coefficient .183, 95% CI .049, .317, p<.001, q<.007) and the three EBV proteins (EBV NA -(coefficient .088, 95% CI .032, .143, p = .002, q<.014; EBV Virion - coefficient .100, 95% CI .037, .163, p = .002, q<.014; and EBV VCA - coefficient .119, 95% CI .061, .177, p = .00004, q<.0016). The amount of cigarettes smoked was also correlated with higher levels of antibodies to the three EBV proteins. Interaction analyses indicated that the association between cigarette smoking and levels of antibodies to CMV and EBV was independent of diagnostic group. Cigarette smoking was not significantly associated with the level of antibodies to HSV-1, VZV, or HHV-6. Individuals who smoke cigarettes have increased levels of IgG antibodies to CMV and EBV. Cigarette smoking may be a contributory factor in the relationship between CMV, EBV and chronic somatic disorders associated with these viruses.

Герпесвирусные инфекции в формировании острой и хронической патологии: обоснование необходимости своевременной терапии

Objective. To determine the frequency and possible clinical significance of herpesvirus DNA detection in various organs. Materials and methods. The study included 168 samples of the cerebral cortex, myocardium, vascular walls, liver, kidneys, and lungs from 28 deceased people. The causes of death were cardiopulmonary insufficiency due to decompensation of atherosclerosis (15 (54%) patients, study group) or intoxication due to septic conditions (13 (46%) patients, comparison group). DNA viruses were detected using the polymerase chain reaction. Results. The most frequently detected virus was human herpes virus type 6 (HHV-6) (82%), less frequently – Epstein-Barr virus (58%), cytomegalovirus and herpes simplex virus type 1 (17% each). In the study group, HHV-6 DNA was more often found in the myocardium (87%), cerebral cortex (47%) and liver (40%). Conclusion. In 87% of cases of death from decompensation of atherosclerotic changes, HHV-6 DNA was found in altered areas of the myocardium. In the brain, liver, kidneys and lungs, HHV-6 was detected less frequently. The association of the presence of HHV-6 DNA with the severity of changes in the heart, brain, liver and kidneys and the presence of other herpesviruses with symptoms of acute respiratory viral infection require the prescription of an antiviral agent with a broad spectrum of action. Inosine pranobex is indicated to prevent the progression of somatic pathology by stopping the activity of herpesvirus infection, which often accompanies or is the main factor in the symptoms of acute respiratory viral infection. Key words: HHV-6, atherosclerosis, human herpes virus type 6, herpes, herpesvirus infection, ARVI, PCR, inosine pranobex

Герпесвирусные инфекции в формировании эпизодов ОРВИ у детей

Aim: to evaluate the detection rate of the herpesvirus activity in children with acute respiratory viral infection (ARVI) signs for determination of the optimal treatment tactics. Patients and Methods: the study included 1120 children aged 3 to 18 years (mean age 7.48±3.91 years) who were observed on an outpatient basis (n=650) or hospitalized (n=379) due to the lack of improvement on the 3rd day after the first ARVI symptoms onset (n=1029) or due to the detected complication (n=91). The herpesvirus DNA was detected in throat swabs by PCR. Enzyme immunoassay was used to evaluate the levels of IgG, IgM, and IgA antibodies. Results: the presence of IgG antibodies to at least one of the herpes viruses was detected in 1097 (97.9%) of patients: in the children group over 6 years old in 723 (100%) patients. The presence of herpesvirus DNA in smears from the posterior pharyngeal wall and tonsils was detected in 234 (20.9%) children: 178 (15.9%) — isolated, 56 (5.0%) — in various combinations. IgM antibodies to Epstein-Barr virus and cytomegalovirus were detected in all cases in the herpesvirus DNA presence in the blood. The herpes simplex virus DNA has not been detected in any case. However, antibodies were detected in 63 (5.6%) children: IgA in 57 (5.1%) and IgM in 6 (0.5%) children. Conclusions: in children with ARVI symptoms, signs of an active infection caused by one or another type of herpes were detected in 26.5% of cases, and in 5% — their combination. The high prevalence of the herpesvirus activity comparable with the detection rate of seasonal respiratory viral infections, along with the adverse effect of herpesvirus infection on the immune system with the severe somatic pathology probability, necessitates the use of a drug with a wide spectrum of antiviral action for the ARVI signs in children — inosine pranobex. In the presence of complications caused by herpesvirus, inosine pranobex does not cause negative trend of antibody activity indicators, inosine pranobex, Groprinosin® KEYWORDS: HHV-6, human herpesvirus type 6, herpes simplex virus, Epstein-Barr virus, herpes, herpesvirus infection, herpes infection, ARVI, cytomegalovirus, inosine pranobex, Groprinosin. FOR CITATION: Ruzhentsova T.A., Popova R.V., Garbuzov A.A., Shushakova E.K., Khalyastov I.N., Meshkova N.A. Herpesvirus infections in ARVI episodes in children. Russian Journal of Woman and Child Health. 2023;6(4):399–404 (in Russ.). DOI: 10.32364/2618-8430- 2023-6-4-12.

FIRES Syndrome in a Preschool Child

Severe epileptic syndromes of childhood are an urgent problem for pediatric neurologists and neuroresuscitators. The article presents a clinical observation of FIRES syndrome in a pediatric patient, which is a form of severe drug-resistant epilepsy in children of preschool and school age, the development of which is caused by hyperthermia, probably associated with herpesvirus (human herpesvirus type 6) infection. The features of the progressive course and the difficulties of diagnostic search are reflected. An empirical approach to etiotropic therapy is described, since the disease manifested itself with respiratory manifestations and fever. The tactic of pathogenetic treatment is described, in which drugs of polyfunctional action, such as Cytoflavin, have a priority, many years of experience in the use of which allows the authors to recommend it as a starting intensive therapy.

Новые подходы к ведению пациентов с нестойкой ремиссией круглогодичного аллергического ринита на фоне персистирующей хламидийной инфекции

Currently, allergic rhinitis is a global socioeconomic problem. According to current statistics, from 15 to 30% of the world’s population suffers from year-round or seasonal allergic rhinitis. Increasingly, the attention of Russian clinicians is attracted by the problem of year-round allergic rhinitis as there is an increase in the incidence in patients of the central zone of the Russian Federation with this form of rhinitis due to sensitization to house dust mite allergens, epidermal allergens of domestic animals, insect and mold allergens. Despite a timely diagnosis and received basic treatment, patients suffering from year-round allergic rhinitis often fail to achieve stable remission. Therefore, we can conclude that a more thorough diagnosis of the disease is needed, aimed at identifying other factors that affect the course of the disease. Objective. To develop a scheme for diagnosing a possible persistent respiratory chlamydial infection that affects the course of year-round allergic rhinitis in patients with a tendency to transient remissions. Materials and methods. Computed tomography of the paranasal sinuses, nasal swab for flora, PCR scraping of the nasal mucosa for the detection of Epstein–Barr virus (EBV) DNA, determination of viral DNA of cytomegalovirus infection (CMV) (PCR scraping of the nasal mucosa), determination of DNA in the scraping of epithelial cells of the nasal mucosa (PCR scraping) of human herpes virus type 6 (HHV-6 type). Patients who had pathological changes in computed tomography of the paranasal sinuses, deviations from the normal flora during bacteriological culture, and positive results in the PCR study of the above infections were excluded from the study. Then, PCR scraping of the nasopharyngeal mucosa for the detection of chlamydia pneumoniae, a survey of complaints (SNOT-22 questionnaire), data from an objective examination method (examination of ENT organs using video endoscopic technologies), an immunological examination of blood serum for IgG antibodies to chlamydial infection, further avidity of IgG antibodies to chlamydia pneumoniae and serum IL-6. Conclusion. The proposed diagnostic scheme will allow identifying a possible persistent respiratory chlamydial infection, which is the cause of transient remission of year-round allergic rhinitis, and developing a new integrated approach to the management of patients with year-round allergic rhinitis associated with this infection.

Chlorella sp. (UKM8), A Local Microalgae Isolate with Anti-Human Herpes Virus and Antioxidant Properties

Microalgae are an invaluable source of new and safe therapeutics with potential antiviral and free-radical scavenging compounds. This study aimed to investigate the antiviral and antioxidant properties of local microalgae, Chlorella sp. (UKM8). The UKM8 methanol extract (UKM8-ME) was tested for antiviral activity using plaque reduction assay against Human Herpes Virus type 1 (HHV-1). The antioxidant activity of UKM8-ME was evaluated for the radical scavenging activity (RSA) according to the elimination of 1,1-diphenyl-2-pikrilhydrazil (DPPH) radicals and total phenolic content (TPC) by the Folin-Ciocalteu reactions. UKM8-ME effective concentration that inhibits 50% (EC50) of plaque formation was 222.33 ± 24.54 μg/mL. The calculated selective index is 19 indicating potential antiviral activity. In the DPPH assay, the IC50 value of positive control and UKM8-ME were 122.9 ± 29.1 and 198.78 ± 14.35 μg/mL, respectively. The TPC of positive control and UKM8-ME were 263.414 ± 9.6 and 254.793 ± 3.31 mg GAE/g, respectively. Evaluation in RSA and TPC concludes that UKM8-ME has high antioxidant activity. In conclusion, UKM8-ME has two unique properties in anti-HHV-1 and antioxidant activities that can be further evaluated for potential in pharmaceutics and food ingredients.

Utility of renal biopsy in differentiating idiopathic multicentric Castleman disease from IgG4-related disease.

Idiopathic multicentric Castleman disease (iMCD) is a subtype of human herpesvirus type 8 (HHV-8)-related Castleman disease that causes multi-organ damage, including kidney damage due to polyclonal lymphoproliferation and interleukin (IL)-6-induced cytokine storm. However, its renal pathological findings are unclear. We report the case of a woman in her 80s who was diagnosed with iMCD based on renal pathological findings. Five years ago, hypergammaglobulinemia was detected, and her renal function declined. Renal biopsy revealed plasma cells infiltrating the stroma. Immunostaining revealed numerous IgG4-positive plasma cells. The serum IgG4 level was high, and she was initially diagnosed with IgG4-related disease (IgG4-RD) and treated with steroids. However, the therapeutic effect was poor. On re-examination, computed tomography revealed lymphadenopathy around the aorta and spleen. Renal histopathology showed numerous IL-6-positive plasma cells. Anemia and C-reactive protein (CRP) positivity persisted despite steroid administration. HHV-8 was negative, and polyneuropathy, organomegaly, endocrinopathy, M-protein, and skin changes syndrome was not suspected. Thus, iMCD was diagnosed. Based on previous reports, there is no significant difference in IgG4 levels between iMCD and IgG4-RD, and IgG4-positive plasma cell infiltrates were observed in iMCD-affected organs. Therefore, it may be difficult to distinguish iMCD from IgG4-RD. In this case, high-serum IL-6 and CRP were observed, which are usually not seen in IgG4-RD but are common findings in iMCD, leading to the diagnosis. Patients with deep lymphadenopathy may be diagnosed with iMCD based on renal pathological findings. Renal biopsy is recommended for patients with suspected iMCD and decreased renal function.

Development of a PCR assay for the detection of human herpes virus type 7.

A PCR assay has been developed to identify the DNA of the human herpes virus type 7. The search and selection of conserved regions was carried out by comparing the whole genome nucleotide sequences of HHV-7. A fragment duplicated in the HHV-7 genomes was chosen as a target for amplification. The performance of the assay was tested on a synthetic matrix and clinical samples. The developed assay has high sensitivity and specificity and showed good efficiency in detecting HHV-7 DNA in clinical samples.

Trends and morphologic variants of Kaposi Sarcoma as seen in Nnewi, Anambra State, Nigeria

Kaposi sarcoma (KS) is a human herpes virus type 8 (HHV-8) driven neoplasm with varying morphologic features and attendant diagnostic dilemma. This study presents the trend of KS in our environment and the different morphologic variants, with a view to arousing awareness and reducing missed and delayed diagnosis. KS accounted for 18.34% and 59.66% of vascular neoplasms and malignant vascular neoplasms, respectively with most KS occurring in the background of human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS). The frequency peaked in 2013 and began to decline with a fairly even sex distribution. There are diverse variants of KS that can pose diagnostic challenges. Hence, there is need for this awareness to enhance prompt and accurate diagnosis.

Incidence of Common Herpesviruses in Colonic Mucosal Biopsies Following Hematopoietic Stem Cell Transplantation.

Intestinal complications are common after allogeneic hematopoietic stem cell transplantation (allo-HSCT). However, only scarce data concern herpesvirus incidence in the colonic mucosa post-HSCT. Our purpose was to assess the frequency and clinical significance of cytomegalovirus (CMV), Epstein-Barr virus (EBV), human herpesvirus type 6 (HHV6), and herpes simplex virus (HSV) in the colonic mucosa post-HSCT. The study group included 119 patients of different ages, mostly with leukemias and lymphomas, subjected to allo-HSCT from haploidentical related (48%) or HLA-compatible donors (52%). In total, 155 forceps biopsies of the colonic mucosa were taken in cases of severe therapy-resistant intestinal syndrome post-HSCT. Most samples were taken from the descending, sigmoid, and transverse colon. Intestinal GVHD or local infections were assessed clinically and by histology. EBV, CMV, HSV, and HHV6 were tested in colonic mucosal lysates with commercial PCR assays. HSV was found in &lt;8% of colonic samples, along with high HHV6 and CMV positivity (up to 62% and 35%, respectively) and a higher EBV incidence at 5-6 months post-HSCT (35%). For CMV and EBV, significant correlations were revealed between their rates of detection in blood and colonic mucosa (r = 0.489 and r = 0.583; p &lt; 0.05). No significant relationships were found between the presence of herpesviruses and most patients' characteristics. EBV positivity in colonic samples was correlated with delayed leukocyte and platelet recovery post-HSCT. Higher EBV frequency in the colonic mucosa was found in deceased patients (56% versus 21%, p = 0.02). The correlations among EBV positivity in the colon, lethality rates and delayed hematopoietic reconstitution suggest some relationship with systemic and local EBV reactivation post-transplant.

Stromal Herpetic Keratitis with Ulceration Associated with Reactivation of Epstein–Barr Virus and Human Herpes Virus Type 6: Experience of Diagnosis and Therapy

Objective: to study the clinical manifestations of herpetic stromal keratitis with ulceration associated with EBV and HHV-6 reactivation.Patients and methods. 172 patients with anterior ophthalmic herpes were under observation, of which 43 patients had herpetic stromal keratitis with ulceration with an average duration of complaints of more than 60 days. Tear, saliva, blood and urine samples were used as a material for PCR (qualitative and quantitative) for the presence of HSV, VZV, CMV, EBV, HHV-6, HHV-7 DNA. Local therapy of the acute period included instillation of antiviral, anti-inflammatory agents and lubricants. Systemic antiherpetic therapy included oral use of selective nucleoside analogues: valacyclovir and famciclovir in increased daily dosages.Results. 87 cumulative positive results were obtained, of which the proportion of EBV and HHV-6 DNA detection was 23 % and 28 %. Complex local therapy with the inclusion of heparin-containing lubricant and a drug containing 5 % dexpanthenol (“Corneregel”) combined with systemic therapy with nucleoside analogues in increased daily dosages led to complete relief of objective symptoms within 14 to 28 days.Conclusions. EBV and HHV-6 were detected in more than 50 % of cases, which determines systemic antiviral therapy in increased daily dosages and a prolonged course. The pathogenesis of ulcerative defects may be associated with the direct reactivation of HHV-6 and EBV, which requires the use of active reparative therapy from the first days of curation. The phenomenon of a transient viral “surge” detected by PCR during disease course can be observed by adequate systemic therapy and is a normal laboratory pattern indicating the correct tactics.

HUMAN HERPESVIRUS 8 (HHV8)-NEGATIVE MULTICENTRIC CASTLEMAN DISEASE LEADING TO GROUP 1 PULMONARY ARTERY HYPERTENSION AND CLINICALLY SIGNIFICANT RIGHT VENTRICULAR SYSTOLIC DYSFUNCTION

HUMAN HERPESVIRUS 8 (HHV8)-NEGATIVE MULTICENTRIC CASTLEMAN DISEASE LEADING TO GROUP 1 PULMONARY ARTERY HYPERTENSION AND CLINICALLY SIGNIFICANT RIGHT VENTRICULAR SYSTOLIC DYSFUNCTION

Human herpes virus type-6 is associated with central nervous system infections in children in Sudan.

BackgroundHuman herpes virus type-6 (HHV-6) is increasingly recognised as a febrile agent in children. However, less is known in sub-Saharan African countries, including Sudan.ObjectiveWe investigated the involvement of HHV-6 in paediatric central nervous system (CNS) infections in Khartoum, Sudan.MethodsFebrile patients aged up to 15 years with suspected CNS infections at Omdurman Hospital for Children from 01 December 2009 to 01 August 2010 were included. Viral DNA was extracted from leftover cerebrospinal fluid (CSF) specimens and quantitatively amplified by real-time polymerase chain reaction (PCR) at Umeå University in Sweden.ResultsOf 503 CSF specimens, 13 (2.6%) were positive for HHV-6 (33.0% [13/40 of cases with proven infectious meningitis]). The median thermal cycle threshold for all HHV-6-positive specimens was 38 (range: 31.9–40.8). The median number of virus copies was 281.3/PCR run (1 × 105 copies/mL CSF; range: 30–44 × 103 copies/PCR run [12 × 103 – 18 × 106 copies/mL CSF]). All positive patients presented with fever and vomiting; 86.0% had seizures. The male-to-female ratio was 1:1; 50.0% were toddlers, 42.0% infants and 8.0% teenagers. Most (83.0%) were admitted in the dry season and 17.0% in the rainy season. Cerebrospinal fluid leukocytosis was seen in 33.0%, CSF glucose levels were normal in 86.0% and low in 14.0%, and CSF protein levels were low in 14.0% and high in 43.0%.ConclusionAmong children in Sudan with CNS infections, HHV-6 is common. Studies on the existence and spread of HHV-6 chromosomal integration in this population are needed.

775P Treatment of Kaposi sarcoma with immune-checkpoint inhibitors: A systematic review and single-arm meta-analysis

Kaposi sarcoma (KS) is a rare cutaneous tumor of endothelial origin, caused by human herpesvirus type 8. Chemotherapy is the standard treatment for KS patients with extensive cutaneous or visceral disease. However, long-term remission is rare. Early phase studies of immune checkpoint inhibitors (ICI) in KS patientshave demonstrated acceptable safety and efficacy profiles. We conducted a systematic review and meta-analysis of efficacy and safety of ICI in patients with KS.

Relationship between Human Herpes Virus Type 6 and Childhood T-Cell Leukemia-Lymphoma

Background: Previous studies have pointed to the major role of viruses in the pathogenesis of cancers, especially lymphoproliferative cancers. Objectives: The current study investigated the relationship between recent Human Herpesvirus Type 6 (HHV6) infection and childhood leukemia-lymphoma syndrome. Methods: From January 2011 to December 2012, we entered every new case of acute lymphoblastic leukemia, non-Hodgkin lymphoma, acute myeloblastic leukemia, and Hodgkin lymphoma as the case group (n=48); moreover, 60 patients were randomly selected as controls from hospitalized children without infectious agents and myocarditis in the department of pediatric cardiology in Shiraz, Iran. Immunophenotyping of bone marrow or lymph node biopsy was performed for the case group. The DNA was extracted from all collected samples using a DNA extraction kit (Invitek Company, Germany), and a Real-time quantitative polymerase chain reaction (qPCR) for the U38 gene of HHV-6 was performed for the detection of the HHV-6 genome for both groups. Results: In the case group, 48 patients with the age range of 0-18 years were assigned to four subgroups: 1- Acute Lymphoblastic Leukemia, 2- Acute Myeloblastic Leukemia, 3- Hodgkin Lymphoma, and 4- non-Hodgkin Lymphoma. In the case group, there were four positive HHV-6 PCR patients: One in Acute Lymphoblastic Leukemia, one in Non-Hodgkin Lymphoma, and two patients in the Hodgkin Lymphoma subgroup. None of the patients with T-cell leukemia-lymphoma had positive PCR. The frequency of HHV6 PCR positive was not significantly different between the case (8.3%) and control (1.6%) groups (P=0.169). No HHV-6 PCR positive was detected in T-cell leukemia/lymphoma patients. Conclusion: As evidenced by the results of the present study, HHV-6 infection has no significant difference in children with T-Cell leukemia-lymphoma and healthy people.

Metabolite Profiling Analysis and the Correlation with Biological Activity of Betalain-Rich Portulaca grandiflora Hook. Extracts.

The aim of the study was to evaluate the possible correlation between the bioactivity and the phytochemical profile of four betalain-rich extracts from Portulaca grandiflora Hook. The HPLC-DAD-ESI-MS analysis indicated the presence of 19 betaxanthins and two betacyanins. The highest concentrations of betaxanthins (982 mg/100 g DE) and betacyanins (650 mg/100 g DE) were noticed in orange and purple flowers extracts, respectively. The HPLC-DAD-ESI-HRMS/MS analyses revealed the presence of a total of 71 compounds. Fifteen new betaxanthins and fifty other metabolites were identified for the first time. The antioxidant activity of the studied flower extracts increased in the sequence of yellow < orange < purple < red (0.066–0.176 mM TE/g DE). Betalains showed less effect on the antioxidant activity of extracts than other metabolites did. Extracts from yellow and orange flowers were more active against Gram-positive bacteria (MIC = 4–16 mg/L), whereas extracts from red and purple flowers were slightly more active against Gram-negative bacteria (MIC = 16–32 mg/L). All the extracts showed the same activity against yeasts (MIC = 32 mg/L). Betaxanthins were active against Gram-positive bacteria, whereas betacyanins were active against Gram-negative bacteria. Remaining metabolites also exhibited antimicrobial activities. The cytotoxicity assessment showed that the P. grandiflora extracts were non-toxic to normal VERO cells. No significant antiviral activity towards Human Herpesvirus type 1 was observed (62 µg/mL). Among the tested varieties, the purple one showed anticancer selectivity towards colon carcinoma cells (RKO).