1,041 results on '"Cytomegalovirus Infections therapy"'
Search Results
202. Effects of Granulocyte and Monocyte Adsorptive Apheresis in Renal Transplantation Recipients With Concomitant Cytomegalovirus Infection.
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Naganuma T, Takemoto Y, Iwai T, Kuwabara N, Uchida J, Nakatani T, Kitamura K, Masuda A, Ohmori K, Matsuura M, and Nakase H
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- Adsorption, Adult, Aged, Combined Modality Therapy, Cytomegalovirus Infections complications, Cytomegalovirus Infections diagnosis, Female, Ganciclovir therapeutic use, Humans, Japan, Kidney Failure, Chronic surgery, Kidney Failure, Chronic virology, Male, Middle Aged, Antiviral Agents therapeutic use, Blood Component Removal, Cytomegalovirus Infections therapy, Granulocytes, Kidney Transplantation, Monocytes
- Abstract
Background: Granulocyte and monocyte adsorptive apheresis (GMAA) is widely used as a treatment for active ulcerative colitis (UC) in Japan. Much attention has been paid to the possibility of GMAA for the treatment and control of cytomegalovirus (CMV) reactivation in patients with refractory UC and concomitant CMV infection. In this study, the effects of the combination of GMAA and antiviral therapy were examined in renal transplant recipients with concomitant CMV infection., Methods: Combination therapy of GMAA and antiviral drugs was performed 9 times in 7 renal transplant recipients with concomitant CMV infection. Four of the cases were positive for CMV-IgG, and 3 were negative. The clinical presentation of CMV infection was viremia in 6 cases and disease (CMV retinitis) in 1 case. CMV infection was diagnosed by using an antigenemia assay (C7-HRP). GMAA session was performed once, and the duration of the session was 120 min. Immediately after the GMAA session, ganciclovir was administered at 5 mg/kg/body weight. CMV infection was monitored based on C7-HRP and CMV-DNA in the peripheral blood samples., Results: All cases became negative for C7-HRP and CMV-DNA within 21 days (median, 14 days; range, 3-21 days) and 17 days (median, 6 days; range, 3-17 days), respectively, after starting the combination therapy. No side effects of GMAA were observed., Conclusions: This case series found that GMAA in combination with antiviral drugs may shorten the duration of treatment against CMV infection in renal transplant recipients. Further studies in a larger number of patients are required to confirm these results., (Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.)
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- 2016
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203. [TORCH syndrome: Rational approach of pre and post natal diagnosis and treatment. Recommendations of the Advisory Committee on Neonatal Infections Sociedad Chilena de Infectología, 2016].
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Cofre F, Delpiano L, Labraña Y, Reyes A, Sandoval A, and Izquierdo G
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- Chagas Disease congenital, Chagas Disease diagnosis, Chagas Disease therapy, Cytomegalovirus Infections congenital, Cytomegalovirus Infections diagnosis, Cytomegalovirus Infections therapy, Female, Fetus, Herpes Simplex congenital, Herpes Simplex diagnosis, Herpes Simplex therapy, Humans, Infant, Newborn, Male, Practice Guidelines as Topic, Pregnancy, Pregnancy Complications, Infectious microbiology, Pregnancy Complications, Infectious parasitology, Pregnancy Complications, Infectious virology, Prenatal Diagnosis, Risk Factors, Rubella congenital, Rubella diagnosis, Rubella therapy, Syndrome, Toxoplasmosis, Congenital diagnosis, Toxoplasmosis, Congenital therapy, Infant, Newborn, Diseases microbiology, Infant, Newborn, Diseases parasitology, Infant, Newborn, Diseases virology
- Abstract
There is a lot of bacterial, viral or parasite infections who are able to be transmitted vertically from the mother to the fetus or newborn which implicates an enormous risk for it. The TORCH acronym is used universally to refer to a fetus or newborn which presents clinical features compatible with a vertically acquired infection and allows a rational diagnostic and therapeutic approach. The traditional "TORCH test" is nowadays considered not appropriate and it has been replaced for specific test for specific pathogens under well defined circumstances. The present document reviews the general characteristics, epidemiology, pathogenesis, diagnostic and therapeutic options for the most frequently involved pathogens in the fetus or newborn with TORCH suspicion.
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- 2016
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204. [Application of Cytotoxic T-Lymphocytes for the Treatment of Cytomegalovirus Infection in Hematopoietic Stem Cell Transplantation].
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Zou BH, Zhang B, and Chen H
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- Adoptive Transfer, Antigen-Presenting Cells cytology, Cytomegalovirus, Humans, Leukocytes, Mononuclear cytology, Cytomegalovirus Infections therapy, Hematopoietic Stem Cell Transplantation adverse effects, T-Lymphocytes, Cytotoxic cytology
- Abstract
Human cytomegalovirus (HCMV) infection, a common complication, remains a major risk factor related with patient death after hematopoietic stem cell transplantation (HSCT). Cytotoxic T lymphocytes (CTL) which is crucial to control HCMV infection, can prevent or treat HCMV infection safely and effectively after adoptive infusion. Many studies have been focussed on exploring different methods for preparation of CTL. The method of using antigen presenting cells to stimulate peripheral blood mononuclear cells is simple to operate, easy to conduct large-scale clinical trials. Isolation of CTL from donor-derived PBMC by peptide-tetramer or INF-γ antibody requires a large volume of peripheral blood and high cost for preparation. Third-party CTL can provide an "off-the-shelf" product, but the problem of HLA-mismatch still would be solved. In addition, the clinical efficacy and safety of different methods also vary. This article reviews and compares the current methods to generate CTL and efficacy of the cells after infusions.
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- 2016
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205. Impact of Cytomegalovirus Infection on Severe Hepatitis C Recurrence in Patients Undergoing Liver Transplantation.
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Caston JJ, Castells L, Varo E, Gomez MA, de la Mata M, Campos-Varela I, Lumbreras C, Gonzalez-Dieguez L, Fabregat J, Herrero I, Salcedo M, Sanchez-Antolín G, and Torre-Cisneros J
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- Adult, Aged, Antiviral Agents therapeutic use, Cytomegalovirus Infections diagnosis, Cytomegalovirus Infections immunology, Cytomegalovirus Infections mortality, Cytomegalovirus Infections therapy, Female, Hepacivirus immunology, Hepatitis C diagnosis, Hepatitis C immunology, Hepatitis C mortality, Hepatitis C therapy, Humans, Immunocompromised Host, Immunosuppressive Agents adverse effects, Kaplan-Meier Estimate, Liver Cirrhosis immunology, Liver Cirrhosis virology, Liver Transplantation mortality, Logistic Models, Male, Middle Aged, Multivariate Analysis, Odds Ratio, Opportunistic Infections diagnosis, Opportunistic Infections immunology, Opportunistic Infections mortality, Opportunistic Infections therapy, Prospective Studies, Recurrence, Reoperation, Risk Factors, Severity of Illness Index, Spain, Time Factors, Treatment Outcome, Viral Load, Cytomegalovirus Infections virology, Hepacivirus pathogenicity, Hepatitis C virology, Liver Transplantation adverse effects, Opportunistic Infections virology, Virus Activation
- Abstract
Background: The influence of cytomegalovirus (CMV) on recurrent hepatitis C virus (HCV) in liver grafts is controversial. Our aim was to investigate the association between CMV infection and disease and severe HCV recurrence (composite variable of presence of stage 3 to 4 fibrosis, need for retransplantation or death due to liver disease) in the first year after transplantation., Methods: An observational, prospective, multicenter study was performed. The CMV replication was monitored by determining CMV viral load weekly during hospitalization after transplantation, twice monthly in the first 3 months after discharge, and at each follow-up visit until month 12. Liver fibrosis was assessed histologically by liver biopsy or transient elastometry. Pretransplant, intraoperative, and posttransplant variables were recorded. Multiple logistic regression was performed to study the impact of CMV on severe HCV recurrence., Results: Ninety-eight patients were included. The CMV infection was detected in 48 patients (49%) in the first year posttransplant, of which 11 patients (22.9%) had CMV disease. Twenty-three patients (23.5%) had severe HCV recurrence. Of these, 17 (73.9%) developed stage 3 to 4 fibrosis, 4 (17.4%) died, and 2 (8.7%) underwent retransplantation. Only 7 of 12 (58.3%) seronegative recipients of a seropositive donor (positive donor/negative recipient [D+/R-]) received universal prophylaxis, and 10 of 12 (83.3%) D+/R- patients developed CMV replication. In the multivariate analysis, the presence of CMV D+/R- serodiscordance (odds ratio, 6.87; 95% confidence interval, 1.89-24.99; P = 0.003), and detection of a higher peak HCV viral load (odds ratio, 3.85; 95% confidence interval, 1.49-9.94; P = 0.005) were associated with severe HCV recurrence., Conclusions: Our results support an association between CMV D+/R- serodiscordance and severe HCV recurrence in patients undergoing liver transplantation for HCV liver disease.
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- 2016
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206. Analysis of memory-like natural killer cells in human cytomegalovirus-infected children undergoing αβ+T and B cell-depleted hematopoietic stem cell transplantation for hematological malignancies.
- Author
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Muccio L, Bertaina A, Falco M, Pende D, Meazza R, Lopez-Botet M, Moretta L, Locatelli F, Moretta A, and Della Chiesa M
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- B-Lymphocytes drug effects, B-Lymphocytes immunology, B-Lymphocytes pathology, CD57 Antigens genetics, CD57 Antigens immunology, Child, Cytomegalovirus immunology, Cytomegalovirus Infections complications, Cytomegalovirus Infections genetics, Cytomegalovirus Infections immunology, Female, Gene Expression Regulation, Hematologic Neoplasms complications, Hematologic Neoplasms genetics, Hematologic Neoplasms immunology, Histocompatibility Testing, Humans, Interleukin-12 pharmacology, Interleukin-18 pharmacology, Killer Cells, Natural drug effects, Killer Cells, Natural pathology, Lymphocyte Depletion, Male, NK Cell Lectin-Like Receptor Subfamily C genetics, NK Cell Lectin-Like Receptor Subfamily C immunology, Primary Cell Culture, Receptors, Antigen, T-Cell, alpha-beta genetics, Receptors, Antigen, T-Cell, alpha-beta immunology, Receptors, KIR genetics, Receptors, KIR immunology, T-Lymphocytes drug effects, T-Lymphocytes immunology, T-Lymphocytes pathology, Transplantation, Homologous, Cytomegalovirus Infections therapy, Hematologic Neoplasms therapy, Hematopoietic Stem Cell Transplantation, Immunologic Memory, Killer Cells, Natural immunology
- Abstract
We analyzed the impact of human cytomegalovirus infection on the development of natural killer cells in 27 pediatric patients affected by hematological malignancies, who had received a HLA-haploidentical hematopoietic stem cell transplantation, depleted of both α/β+ T cells and B cells. In line with previous studies in adult recipients of umbilical cord blood transplantation, we found that human cytomegalovirus reactivation accelerated the emergence of mature natural killer cells. Thus, most children displayed a progressive expansion of a memory-like natural killer cell subset expressing NKG2C, a putative receptor for human cytomegalovirus, and CD57, a marker of terminal natural killer cell differentiation. NKG2C(+)CD57(+) natural killer cells were detectable by month 3 following hematopoietic stem cell transplantation and expanded until at least month 12. These cells were characterized by high killer Ig-like receptors (KIRs) and leukocyte inhibitory receptor 1 (LIR-1) and low Siglec-7, NKG2A and Interleukin-18Rα expression, killed tumor targets and responded to cells expressing HLA-E (a NKG2C ligand). In addition, they were poor Interferon-γ producers in response to Interleukin-12 and Interleukin-18. The impaired response to these cytokines, together with their highly differentiated profile, may reflect their skewing toward an adaptive condition specialized in controlling human cytomegalovirus. In conclusion, in pediatric patients receiving a type of allograft different from umbilical cord blood transplantation, human cytomegalovirus also induced memory-like natural killer cells, possibly contributing to controlling infections and reinforcing anti-leukemia effects., (Copyright© Ferrata Storti Foundation.)
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- 2016
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207. Cytomegalovirus Pneumonia in Patients with Rheumatic Diseases After Immunosuppressive Therapy: A Single Center Study in China.
- Author
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Xue Y, Jiang L, Wan WG, Chen YM, Zhang J, and Zhang ZC
- Subjects
- CD4-Positive T-Lymphocytes metabolism, China, Cytomegalovirus Infections genetics, Cytomegalovirus Infections immunology, Humans, Pneumonia genetics, Pneumonia immunology, Polymerase Chain Reaction, Retrospective Studies, Rheumatic Diseases genetics, Rheumatic Diseases immunology, Viral Load, Cytomegalovirus pathogenicity, Cytomegalovirus Infections therapy, Cytomegalovirus Infections virology, Immunosuppression Therapy methods, Pneumonia therapy, Pneumonia virology, Rheumatic Diseases therapy, Rheumatic Diseases virology
- Abstract
Background: Rheumatic diseases involve multiple organs that are affected by immunological mechanisms. Treatment with corticosteroids and immunosuppressive agents may also increase the frequency of infection. Cytomegalovirus (CMV) is a widespread herpes virus and a well-recognized pathogen, which causes an opportunistic and potentially fatal infection in immunocompromised patients. This retrospective study aimed to investigate the clinical and laboratory characteristics of CMV pneumonia in patients with rheumatic diseases after immunosuppressive therapy in a single center in Shanghai, China., Methods: Eight hundred and thirty-four patients with rheumatic diseases who had undergone CMV-DNA viral load tests were included, and the medical records of 142 patients who were positive for CMV-DNA in plasma samples were evaluated. GraphPad Prism version 5.013 (San Diego, CA, USA) was used to conduct statistical analysis. The correlation between CMV-DNA viral loads and lymphocyte counts was assessed using the Spearman rank correlation coefficient test. Significance between qualitative data was analyzed using Pearson's Chi-squared test. The cut-off thresholds for CMV-DNA viral load and lymphocyte count were determined by receiver operating characteristic (ROC) curve analysis., Results: One hundred and forty-two patients had positive CMV viral load tests. Of these 142 patients, 73 patients with CMV pneumonia were regarded as symptomatic, and the other 69 were asymptomatic. The symptomatic group received higher doses of prednisolone (PSL) and more frequently immunosuppressants than the asymptomatic group (P < 0.01). The symptomatic group had lower lymphocyte counts, especially CD4+ T-cells, than the asymptomatic group (P < 0.01). By ROC curve analysis, when CD4+ T-cell count was <0.39 × 109/L, patients with rheumatic diseases were at high risk for symptomatic CMV infection. The CMV-DNA load was significantly higher in the symptomatic patients than that in asymptomatic patients (P < 0.01; threshold viral loads: 1.75 × 104 copies/ml). Seven patients had a fatal outcome, and they had lower peripheral lymphocyte counts (P < 0.01), including CD4+ and CD8+ T-cells (P < 0.01)., Conclusions: When CD4+ T-cell count is <0.39 × 109/L, patients are at high risk for pulmonary CMV infection. Patients are prone to be symptomatic with CMV-DNA load >1.75 × 104 copies/ml. Lymphopenia (especially CD4+ T-cells), presence of symptoms, and other infections, especially fungal infection, are significant risk factors for poor outcome, and a higher PSL dosage combined with immunosuppressants may predict CMV pneumonia.
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- 2016
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208. Successful multidisciplinary treatment of refractory cytomegalovirus infection after living donor liver transplantation using mixed lymphocyte reactions: report of a case.
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Takeda K, Sawada Y, Kumamoto T, Matsuyama R, Tanaka Y, Ohdan H, and Endo I
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- Cytomegalovirus Infections immunology, Drug Administration Schedule, Drug Monitoring methods, Graft Rejection immunology, Graft Rejection prevention & control, Humans, Immunocompromised Host, Immunosuppressive Agents administration & dosage, Immunosuppressive Agents adverse effects, Immunosuppressive Agents therapeutic use, Living Donors, Lymphocyte Culture Test, Mixed methods, Male, Middle Aged, Postoperative Complications immunology, Cytomegalovirus Infections therapy, Liver Transplantation, Postoperative Complications therapy
- Abstract
A 52-year-old Japanese male underwent ABO-incompatible living donor liver transplantation for acute-on-chronic hepatitis B infection. Fifty-one months later, he became feverish and a cytomegalovirus (CMV) infection was diagnosed. A dramatically high CMV pp65 antigen (C10/C11) load (2,412) was measured, which did not respond to ganciclovir and immune globulin treatment, and increased further to 5,353. The next treatment strategy was the reduction of immunosuppressants, but to simply reduce immunosuppressants can lead to graft loss. Therefore, before using this strategy, responses to alloantigens were evaluated using a carboxyfluorescein-diacetate-succimidyl ester-labeled mixed lymphocyte reaction (CFSE-MLR). Only limited CD4(+) and CD8(+) T-cell proliferation was observed, suggesting the patient was hyporesponsive. After reducing tacrolimus levels from 3-4 ng/mL to <1.5-1.8 ng/mL, the fever dropped immediately and C10/C11 disappeared after 2 months. In conclusion, CFSE-MLR could be a useful tool for the treatment of refractory infectious disease after transplantation and, importantly, for checking a patient's immunosuppressive state beyond the perioperative period.
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- 2016
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209. Family Teaching Toolbox. A Parent's Guide to Congenital Cytomegalovirus.
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Mestas E
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- Adult, Female, Humans, Infant, Newborn, Male, Parent-Child Relations, United States, Young Adult, Cytomegalovirus Infections diagnosis, Cytomegalovirus Infections therapy, Parents education
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- 2016
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210. Advances in the prevention and treatment of congenital cytomegalovirus infection.
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James SH and Kimberlin DW
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- Antiviral Agents therapeutic use, Cytomegalovirus Infections transmission, Female, Ganciclovir analogs & derivatives, Ganciclovir therapeutic use, Hearing Loss, Sensorineural prevention & control, Humans, Infant, Newborn, Infectious Disease Transmission, Vertical prevention & control, Pregnancy, Pregnancy Complications, Infectious prevention & control, Prenatal Exposure Delayed Effects prevention & control, Valganciclovir, Cytomegalovirus Infections congenital, Cytomegalovirus Infections therapy
- Abstract
Purpose of Review: Cytomegalovirus (CMV) is the most common cause of congenital infection in the world. Symptomatic infants are at increased risk of developing permanent sequelae, including sensorineural hearing loss and neurodevelopmental delay. Advances in the treatment and prevention of congenital CMV infection are a high priority nationally and globally., Recent Findings: In symptomatic infants, antiviral therapy with 6 months of oral valganciclovir improves hearing and neurodevelopmental outcomes. Strategies to prevent congenital or maternal CMV infections, including the use of CMV hyperimmune globulin and development of a maternal vaccine, have yet to yield positive results., Summary: The clinical significance of congenital CMV infection, developments in antiviral therapy, and efforts to prevent congenital disease are herein reviewed.
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- 2016
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211. Recommendations for the diagnosis and treatment of CMV infections. Polish Society of Epidemiology and Infectious Diseases
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Pokorska-Śpiewak M, Niezgoda A, Gołkowska M, Czech-Kowalska J, Gruszfeld D, Dobrzańska A, Styczyński J, and Marczyńska M
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- Female, Guidelines as Topic, Humans, Immunity, Cellular, Male, Poland epidemiology, Quality Assurance, Health Care standards, Societies, Medical standards, Cytomegalovirus Infections diagnosis, Cytomegalovirus Infections therapy, Disease Outbreaks prevention & control
- Abstract
Cytomegalovirus (CMV) infections are common and their incidence increases with age. In immunocompetent people they are usually asymptomatic or manifest as a mild, self-limiting mononucleosis syndrome. CMV infection in patients with immune deficiency as well as congenital infections may cause a considerable problem. A group of experts designated by the Polish Society of Epidemiology and Infectious Diseases has prepared recommendations on the diagnosis and treatment of CMV infections, with particular emphasis on the management of patients with immunodeficiencies and congenital infections.
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- 2016
212. Haploidentical Haematopoietic Stem Cell Transplantation: Role of NK Cells and Effect of Cytomegalovirus Infections.
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Della Chiesa M, Moretta L, Muccio L, Bertaina A, Moretta F, Locatelli F, and Moretta A
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- Animals, Humans, Transplantation, Homologous, Cytomegalovirus Infections immunology, Cytomegalovirus Infections therapy, Hematopoietic Stem Cell Transplantation, Killer Cells, Natural immunology
- Abstract
Natural killer cells play an important role in the immune responses against cancer and viral infections. In addition, NK cells have been shown to exert a key role in haploidentical hematopoietic stem cell (HSC) transplantation for the therapy of high-risk leukemias. The anti-leukemia effect is mostly related to the presence of "alloreactive" NK cells, i.e., mature KIR(+) NK cells that express inhibitory KIR mismatched with HLA class I (KIR-L) of the patient. In addition, an important role is played by certain activating KIR (primarily, but not only, KIR2DS1) upon interaction with their HLA class I ligand (C2 alleles). In general, the presence of activating KIR correlates with a better prognosis. Beside the infusion of "pure" CD34(+) cells, a novel protocol has been recently developed in which depletion of αβ T cells and CD19(+) B cells makes it possible to infuse into the patient, together with donor CD34(+) HSCs, important effector cells including mature PB NK cells and γδ T cells. Recent studies revealed that cytomegalovirus (CMV) infection/reactivation may induce rapid NK cell maturation and greatly influence the NK receptor repertoire. The remarkable expansion of a subset expressing the activating receptor NKG2C, together with a more efficient virus-specific effector response after rechallenge with CMV (i.e., antigen specificity), and the longevity of the expanded population are all features consistent with an adaptive type of response and support the notion of a memory-like activity of NK cells.
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- 2016
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213. Successful Conservative Treatment of a Cholecystoduodenal Fistula Caused by a Cytomegalovirus-associated Duodenal Ulcer.
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Mori H, Zakimi M, Kato S, Yamada K, Chinen K, Kubota T, Arashiro M, Shinoura S, and Kikuchi K
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- Aged, Biliary Fistula diagnostic imaging, Biliary Fistula etiology, Cholelithiasis diagnostic imaging, Cytomegalovirus, Cytomegalovirus Infections therapy, Duodenal Ulcer diagnostic imaging, Duodenal Ulcer ethnology, Female, Humans, Intestinal Fistula diagnostic imaging, Intestinal Fistula etiology, Intestinal Obstruction diagnostic imaging, Biliary Fistula therapy, Conservative Treatment, Cytomegalovirus Infections complications, Duodenal Ulcer therapy, Intestinal Fistula therapy
- Abstract
An 87-year-old woman on oral prednisolone was diagnosed with a cholecystoduodenal fistula (CDF) caused by a cytomegalovirus-associated duodenal ulcer (DU) and was managed conservatively. A CDF caused by a DU is extremely rare. Although surgical repair is recommended for the treatment of a CDF caused by cholecystolithiasis, appropriate treatment for CDF caused by a DU remains controversial. This case report of a CDF caused by a DU suggests that conservative treatment is feasible in the absence of DU-associated complications, such as an untreatable hemorrhage or obstruction; this finding is compatible with previously reported cases that were conservatively treated.
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- 2016
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214. Cytomegalovirus reactivation in patients with multiple myeloma.
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Hasegawa T, Aisa Y, Shimazaki K, Ito C, and Nakazato T
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- Adult, Aged, Aged, 80 and over, Female, Humans, Male, Middle Aged, Retrospective Studies, Antigens, Viral blood, Cytomegalovirus physiology, Cytomegalovirus Infections blood, Cytomegalovirus Infections therapy, Multiple Myeloma blood, Multiple Myeloma therapy, Multiple Myeloma virology, Virus Activation
- Abstract
The introduction of novel antimyeloma agents has improved the outcome of multiple myeloma (MM) dramatically. However, it has also led to an increasing incidence of Herpesviridae family virus infections, including a high incidence of post-transplant cytomegalovirus (CMV) reactivation after treatment with novel agents. We herein retrospectively assessed the CMV reactivation in all 120 newly diagnosed patients with MM consecutively seen and treated at our hospital. CMV antigenemia tests were ordered in 58 patients depending on the clinical context, and the incidence of CMV reactivation and proven/suspected CMV disease requiring antiviral therapy was 20% (24 of 120) and 11% (13 of 120) respectively, including those without stem cell transplantation (SCT). The clinical and laboratory characteristics of these patients were compared with those in 34 CMV antigenemia-negative (CMV-negative) patients. Patients with extramedullary disease or a low absolute lymphocyte count (ALC) had a higher risk of developing CMV reactivation. In addition, the median duration from the time of MM diagnosis to CMV reactivation was 5.0 months. These results suggest that, regardless of whether or not undergoing SCT, elderly patients with MM receiving novel agents should be monitored for CMV reactivation to allow for the timely diagnosis and treatment, especially for those with extramedullary disease., (© 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)
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- 2016
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215. [HUMAN CYTOMEGALOVIRUS INFECTION AND SPONTANEOUS ABORTION IN PREGNANT WOMEN OF I AND II TRIMESTER].
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Cheshik SG and Kisteneva LB
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- Abortion, Habitual immunology, Abortion, Habitual therapy, Abortion, Habitual virology, Acridines therapeutic use, Adult, Chronic Disease, Cytomegalovirus drug effects, Cytomegalovirus immunology, Cytomegalovirus Infections immunology, Cytomegalovirus Infections therapy, Cytomegalovirus Infections virology, Female, Humans, Immunoglobulins therapeutic use, Immunoglobulins, Intravenous, Immunologic Factors therapeutic use, Peptides therapeutic use, Pregnancy, Pregnancy Complications, Infectious immunology, Pregnancy Complications, Infectious therapy, Pregnancy Complications, Infectious virology, Pregnancy Trimester, First, Pregnancy Trimester, Second, Recurrence, Thymus Extracts therapeutic use, Virus Replication drug effects, Abortion, Habitual diagnosis, Antibodies, Viral blood, Antigens, Viral blood, Cytomegalovirus growth & development, Cytomegalovirus Infections diagnosis, Pregnancy Complications, Infectious diagnosis
- Abstract
The goal of this work was the evaluation of the frequency of human CMV infection among the women, whose pregnancy ended in miscarriage, detection of active forms of infection and treatment before pregnancy. Virological and sero-immunological techniques were used. A total of 116 women who had miscarriages before the 28 week of pregnancy were submitted to the CMV test. 109 women (94.0%) demonstrated positive results. 49 women (42.2%) had active form of the cytomegalovirus infection. 13 women (26.5%) had the recurrent form and 36 patients (73.5%) had the persistent form of CMV infection (stage of productive replication). All the women with active CMVI were treated before the next pregnancy. Immunomodulatory therapy for the treatment was used.
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- 2016
216. Cytomegalovirus-targeted immunotherapy and glioblastoma: hype or hope?
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Ferguson SD, Srinivasan VM, Ghali MG, and Heimberger AB
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- Animals, Brain Neoplasms complications, Brain Neoplasms immunology, Cytomegalovirus Infections complications, Cytomegalovirus Infections immunology, Dacarbazine therapeutic use, Glioblastoma complications, Glioblastoma immunology, Humans, Temozolomide, Brain Neoplasms therapy, Cytomegalovirus immunology, Cytomegalovirus Infections therapy, Dacarbazine analogs & derivatives, Glioblastoma therapy, Immunotherapy
- Abstract
Malignant gliomas, including glioblastoma (GBM), are the most common primary brain tumors. Despite extensive research only modest gains have been made in long-term survival. Standard of care involves maximizing safe surgical resection followed by concurrent chemoradiation with temozolomide. Immunotherapy for GBM is an area of intense research in recent years. New immunotherapies, although promising, have not been integrated into standard practice. Human cytomegalovirus (HCMV) is a DNA virus of the family Herpesviridae. Human seroprevalence is approximately 80%, and in most cases, is associated with asymptomatic infection. HCMV may be an important agent in the initiation, promotion and/or progression of tumorigenesis. Regardless of a possible etiologic role in GBM, interest has centered on exploiting this association for development of immunomodulatory therapies.
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- 2016
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217. Optimum treatment of congenital cytomegalovirus infection.
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Leruez-Ville M and Ville Y
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- Cytomegalovirus Infections immunology, Female, Humans, Immunization, Passive, Peripartum Period, Postnatal Care trends, Pregnancy, Pregnancy Complications, Infectious immunology, Prenatal Care trends, Antiviral Agents therapeutic use, Cytomegalovirus Infections congenital, Cytomegalovirus Infections therapy, Pregnancy Complications, Infectious therapy
- Abstract
Congenital cytomegalovirus infection affects 0.7% of live births and is the leading cause of congenital neurological handicaps of infectious origin. However, systematic screening of this infection has not been implemented in pregnancy or at birth in any country. This apparent paradox has been justified by the unavailability of an efficient vaccine and by the scarcity of data available on the treatment of congenital CMV. However, in the last decade interesting new data on the management of this congenital infection has emerged including new results on both neonatal and postnatal treatments. This review provides an update on the potential benefits of antiviral treatment and on passive immunisation both in the neonatal and the antenatal periods. These suggest a benefit to a proactive approach for neonatal and prenatal congenital infections.
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- 2016
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218. Management of Cytomegalovirus Seroconversion during Pregnancy in France.
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Carrara J, N'Diaye DS, Azria E, Launay O, Rozenberg F, Yazpandanah Y, Tsatsaris V, Ayoubi JM, and Picone O
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- Female, France, Humans, Obstetrics standards, Pregnancy, Seroconversion, Surveys and Questionnaires, Cytomegalovirus Infections therapy, Obstetrics statistics & numerical data, Pregnancy Complications, Infectious therapy
- Abstract
Introduction: Guidelines for the management of cytomegalovirus (CMV) infection of the fetus are rare. Our main objective was to evaluate how health care practitioners in France manage cases of CMV seroconversion during pregnancy., Material and Methods: A questionnaire was e-mailed to health care practitioners potentially concerned by CMV seroconversion during pregnancy. They were asked if they would recommend amniocentesis, fetal cerebral MRI examination and fetal blood analysis (FBA), depending on the ultrasound results. They then had to indicate whether they would accept termination of pregnancy (TOP), depending on the results of these examinations., Results: A total of 380 health care practitioners responded, mainly obstetricians (73.9%) and midwives (20.2%). Overall, 57% of respondents recommended amniocentesis in the case of CMV seroconversion during the first trimester of pregnancy, ultrasound findings being normal. In cases of positive amniocentesis and a major ultrasound abnormality, 84.5% of respondents would perform cerebral MRI, and 44.4% would perform FBA. In this case, the rate of acceptance of TOP was not significantly different whether the examinations were normal (337/372, 90.6%) or not performed (339/374, 93.3%; p = 0.17)., Discussion: Amniocentesis is too infrequently used and should be encouraged. The results of MRI and FBA are often not taken into account in the final decision concerning TOP. Guidelines are needed to clarify the management of CMV seroconversion during pregnancy., (© 2015 S. Karger AG, Basel.)
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- 2016
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219. Surgical manifestations of gastrointestinal cytomegalovirus infection in children: Clinical audit and literature review.
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Arnold M, Itzikowitz R, Young B, Machoki SM, Hsiao NY, Pillay K, and Alexander A
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- Age Factors, Child, Child, Preschool, Clinical Audit, Cytomegalovirus, Cytomegalovirus Infections epidemiology, Digestive System Surgical Procedures, Female, Gastrointestinal Diseases epidemiology, HIV Infections complications, Humans, Incidence, Infant, Infant, Newborn, Male, Retrospective Studies, Risk Factors, Cytomegalovirus Infections complications, Cytomegalovirus Infections therapy, Gastrointestinal Diseases therapy, Gastrointestinal Diseases virology
- Abstract
Introduction: Gastrointestinal sequelae of cytomegalovirus are rare, usually associated with significant immune compromise, and carry a high morbidity and mortality. Gastrointestinal disease frequently requires surgical intervention for diagnosis and management., Aim: The aim of the study is to evaluate the incidence, presentation and management of gastrointestinal cytomegalovirus disease in a pediatric population., Method: Between January 2003 and June 2011, a retrospective folder review was conducted of all symptomatic children with proven CMV disease, presenting to the surgical service. Eligible patients were identified using the surgical, histopathology and serology databases., Results: Thirty-eight patients (1.8/1000 surgical admissions) were identified with a median presenting age of 5months (range 3days-12years). Esophagitis (n=18) and small bowel disease (n=16) predominated, but CMV was seen throughout the gastrointestinal tract. Risk factors included HIV infection (n=21, 55%) and recent gastrointestinal surgery or infection (n=10, 26%). Characteristic multiple jejunoileal perforations were seen in six patients. Compared to upper GIT disease, intestinal involvement was associated with younger age and doubled mortality. In HIV-infected children, median CD4 (%) was lower in intestinal compared to upper gastrointestinal disease. Morbidities included anastomotic breakdowns (5), anastomotic strictures (3), relook laparotomies (10), resistant esophageal strictures (5) and prolonged parenteral nutrition (5). Anti-CMV drugs were given in 63%. Overall mortality was 32% (12/38) and was associated with lower GIT disease., Conclusion: Invasive CMV gastrointestinal disease in our children was predominantly HIV-associated, or followed a major lower gastrointestinal inflammatory insult in infants younger than 6months. Successful therapy requires a high index of suspicion of active CMV disease to allow early implementation of CMV viral load control and aggressive treatment of the underlying immune impairment. Multiple surgical interventions are often required for both tissue diagnosis and management of acute and chronic complications. CMV-viral-load-tailored anti-CMV therapy is supported by recent literature., (Copyright © 2015 Elsevier Inc. All rights reserved.)
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- 2015
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220. The immune response to cytomegalovirus in allogeneic hematopoietic stem cell transplant recipients.
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Ciáurriz M, Zabalza A, Beloki L, Mansilla C, Pérez-Valderrama E, Lachén M, Bandrés E, Olavarría E, and Ramírez N
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- Antiviral Agents pharmacology, CD8-Positive T-Lymphocytes virology, Cytokines metabolism, Cytomegalovirus physiology, Cytomegalovirus Infections prevention & control, Humans, Immunocompromised Host immunology, Immunotherapy, Adoptive methods, Killer Cells, Natural immunology, Polymorphism, Genetic, Receptors, CCR5 genetics, Receptors, CCR5 immunology, Tissue Donors, Transplantation Conditioning methods, Transplantation, Homologous, Virus Activation, Cytomegalovirus pathogenicity, Cytomegalovirus Infections immunology, Cytomegalovirus Infections therapy, Hematopoietic Stem Cell Transplantation
- Abstract
Approximately, up to 70 % of the human population is infected with cytomegalovirus (CMV) that persists for life in a latent state. In healthy people, CMV reactivation induces the expansion of CMV-specific T cells up to 10 % of the entire T cell repertoire. On the contrary, CMV infection is a major opportunistic viral pathogen that remains a leading cause of morbidity and mortality after allogeneic hematopoietic stem cell transplantation. Due to the delayed CMV-specific immune recovery, the incidence of CMV reactivation during post-transplant period is very high. Several methods are currently available for the monitoring of CMV-specific responses that help in clinical monitoring. In this review, essential aspects in the immune recovery against CMV are discussed to improve the better understanding of the immune system relying on CMV infection and, thereby, helping the avoidance of CMV disease or reactivation following hematopoietic stem cell transplantation with severe consequences for the transplanted patients.
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- 2015
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221. Cytomegalovirus Encephalitis in a Patient with Severe Combined Immunodeficiency.
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Motobayashi M, Shigemura T, Tanaka M, Kurata T, Kobayashi N, Agematsu K, Amano Y, Inaba Y, Koike K, and Nakazawa Y
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- Antibodies, Viral blood, Antigens, Viral metabolism, Cells, Cultured, Cytomegalovirus Infections therapy, DNA, Viral cerebrospinal fluid, Encephalitis therapy, Ganciclovir administration & dosage, Graft vs Host Disease immunology, HLA-DRB1 Chains immunology, Humans, Infant, Interferon-gamma metabolism, Male, Methotrexate administration & dosage, Cord Blood Stem Cell Transplantation, Cytomegalovirus physiology, Cytomegalovirus Infections diagnosis, Encephalitis diagnosis, Graft vs Host Disease prevention & control, Interleukin Receptor Common gamma Subunit genetics, Severe Combined Immunodeficiency diagnosis
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- 2015
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222. Cytomegalovirus Reactivation after Allogeneic Hematopoietic Stem Cell Transplantation is Associated with a Reduced Risk of Relapse in Patients with Acute Myeloid Leukemia Who Survived to Day 100 after Transplantation: The Japan Society for Hematopoietic Cell Transplantation Transplantation-related Complication Working Group.
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Takenaka K, Nishida T, Asano-Mori Y, Oshima K, Ohashi K, Mori T, Kanamori H, Miyamura K, Kato C, Kobayashi N, Uchida N, Nakamae H, Ichinohe T, Morishima Y, Suzuki R, Yamaguchi T, and Fukuda T
- Subjects
- Adolescent, Adult, Aged, Cytomegalovirus immunology, Cytomegalovirus Infections mortality, Cytomegalovirus Infections therapy, Cytomegalovirus Infections virology, Female, Graft vs Host Disease immunology, Graft vs Host Disease mortality, Graft vs Host Disease pathology, Graft vs Host Disease therapy, Humans, Japan, Leukemia, Myelogenous, Chronic, BCR-ABL Positive mortality, Leukemia, Myelogenous, Chronic, BCR-ABL Positive pathology, Leukemia, Myelogenous, Chronic, BCR-ABL Positive therapy, Leukemia, Myeloid, Acute mortality, Leukemia, Myeloid, Acute pathology, Leukemia, Myeloid, Acute therapy, Male, Middle Aged, Myelodysplastic Syndromes mortality, Myelodysplastic Syndromes pathology, Myelodysplastic Syndromes therapy, Precursor Cell Lymphoblastic Leukemia-Lymphoma mortality, Precursor Cell Lymphoblastic Leukemia-Lymphoma pathology, Precursor Cell Lymphoblastic Leukemia-Lymphoma therapy, Proportional Hazards Models, Recurrence, Retrospective Studies, Societies, Medical, Transplantation Conditioning, Transplantation, Homologous, Unrelated Donors, Virus Activation immunology, Cytomegalovirus Infections immunology, Hematopoietic Stem Cell Transplantation, Leukemia, Myelogenous, Chronic, BCR-ABL Positive immunology, Leukemia, Myeloid, Acute immunology, Myeloablative Agonists therapeutic use, Myelodysplastic Syndromes immunology, Precursor Cell Lymphoblastic Leukemia-Lymphoma immunology
- Abstract
Cytomegalovirus (CMV) infection is a major infectious complication after allogeneic hematopoietic cell transplantation (allo-HSCT). Recently, it was reported that CMV reactivation is associated with a decreased risk of relapse in patients with acute myeloid leukemia (AML). The aim of this study was to evaluate the impact of early CMV reactivation on the incidence of disease relapse after allo-HSCT in a large cohort of patients. The Japan Society for Hematopoietic Cell Transplantation's Transplantation-Related Complication Working Group retrospectively surveyed the database of the Transplant Registry Unified Management Program at the Japan Society for Hematopoietic Cell Transplantation. Patients with AML (n = 1836), acute lymphoblastic leukemia (ALL, n = 911), chronic myeloid leukemia (CML, n = 223), and myelodysplastic syndrome (MDS, n = 569) who underwent their first allo-HSCT from HLA-matched related or unrelated donors between 2000 and 2009 and who survived without disease relapse until day 100 after transplantation were analyzed. Patients who received umbilical cord blood transplantation were not included. Patients underwent surveillance by pp65 antigenemia from the time of engraftment, and the beginning of preemptive therapy was defined as CMV reactivation. Cox proportional hazards models were used to evaluate the risk factors of relapse, nonrelapse, and overall mortality. CMV reactivation and acute/chronic graft-versus-host disease (GVHD) were evaluated as time-dependent covariates. CMV reactivation was associated with a decreased incidence of relapse in patients with AML (20.3% versus 26.4%, P = .027), but not in patients with ALL, CML, or MDS. Among 1836 patients with AML, CMV reactivation occurred in 795 patients (43.3%) at a median of 42 days, and 436 patients (23.7%) relapsed at a median of 221 days after allo-HSCT. Acute GVHD grades II to IV developed in 630 patients (34.3%). By multivariate analysis considering competing risk factors, 3 factors were significantly associated with a decreased risk of AML relapse and 1 factor with an increased risk of AML relapse: CMV reactivation (hazard ratio [HR], .77; 95% confidence interval [CI], .59 to .99), unrelated donor compared with related donor (HR, .59; 95% CI, .42 to .84), development of chronic GVHD (HR, .77; 95% CI, .60 to .99), and pretransplantation advanced disease status compared with standard disease status (HR, 1.99; 95% CI, 1.56 to 2.52). However, CMV reactivation was associated with increased nonrelapse mortality (HR, 1.60; 95% CI, 1.18 to 2.17) and overall mortality (HR, 1.37; 95% CI, 1.11 to 1.69). A beneficial effect of CMV reactivation on subsequent risk of relapse was observed in patients with AML but not in those with other hematological malignancies. However, this benefit was nullified by the increased nonrelapse mortality. The underlying mechanism is unclear; however, immunological activation against CMV reactivation plays an essential role in this association. Thus, immune augmentation treatment options, including vaccination and adoptive T cell transfer, may be useful to take advantage of the efficacy of CMV reactivation with minimal increase in nonrelapse mortality., (Copyright © 2015 American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.)
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- 2015
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223. Trabeculectomy ab interno (trabectome): yet another possibility in the treatment of uncontrolled glaucomatocyclitic crisis under systemic valganciclovir therapy?
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Pahlitzsch M, Torun N, Gonnermann J, Maier AK, Pleyer U, Bertelmann E, Joussen A, and Klamann MK
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- Administration, Oral, Adult, Aged, Combined Modality Therapy, Cytomegalovirus genetics, Cytomegalovirus isolation & purification, Cytomegalovirus Infections diagnosis, Cytomegalovirus Infections virology, DNA, Viral genetics, Eye Infections, Viral diagnosis, Eye Infections, Viral virology, Female, Ganciclovir therapeutic use, Glaucoma diagnosis, Glaucoma virology, Humans, Intraocular Pressure, Iridocyclitis diagnosis, Iridocyclitis virology, Male, Middle Aged, Polymerase Chain Reaction, Retrospective Studies, Trabecular Meshwork surgery, Valganciclovir, Antiviral Agents therapeutic use, Cytomegalovirus Infections therapy, Eye Infections, Viral therapy, Ganciclovir analogs & derivatives, Glaucoma therapy, Iridocyclitis therapy, Trabeculectomy methods
- Abstract
Purpose: To assess the outcome of trabectome surgery in the treatment of glaucomatocyclitic crisis (Posner-Schlossman syndrome) in patients with uncontrolled intraocular pressure (IOP)., Patients/methods: Trabectome surgery was performed in seven patients with diagnosed glaucomatocyclitic crisis and uncontrolled IOP where cytomegalovirus DNA was verified by polymerase chain reaction in aqueous humour samples. All patients were treated with oral valganciclovir. After surgery the patients were followed-up for 12 months., Results: Mean IOP before trabectome surgery was 40±10 mm Hg (range 33-58 mm Hg). The mean number of antiglaucoma medication prior to surgery was 3.1±0.4. By the end of the 12 months, IOP in all patients was reduced to normal level (13±1 mm Hg) and their antiglaucoma medication was decreased to 0.8±1.1. No recurring attack of glaucomatocyclitic crisis occurred., Discussion: In addition to oral valganciclovir therapy, trabectome surgery seems to be a reliable and effective tool for the management of glaucomatocyclitic crisis with uncontrolled IOP.
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- 2015
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224. [Toxic megacolon].
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Leppkes M, Ganslmayer M, Strauß R, and Neurath MF
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- Colitis, Ulcerative complications, Colitis, Ulcerative diagnosis, Colitis, Ulcerative therapy, Critical Illness, Cytomegalovirus Infections complications, Cytomegalovirus Infections diagnosis, Cytomegalovirus Infections therapy, Enterocolitis, Pseudomembranous complications, Enterocolitis, Pseudomembranous diagnosis, Enterocolitis, Pseudomembranous therapy, Evidence-Based Medicine, Guideline Adherence, Humans, Interdisciplinary Communication, Intersectoral Collaboration, Megacolon, Toxic diagnosis, Prognosis, Critical Care, Megacolon, Toxic etiology, Megacolon, Toxic therapy
- Abstract
Background: Toxic megacolon constitutes a feared, life-threatening complication of severe intestinal inflammation and is a challenge for interdisciplinary medical care., Objectives: Specific aspects of conservative treatment based on current scientific evidence derived from guidelines, qualified reviews, and scientific studies are presented, which provide a rational approach and maximize therapeutic success., Materials and Methods: This work is based on a selective literature review and the authors' experience of many years in gastroenterology and intensive care., Results: Toxic megacolon requires a rapid interdisciplinary assessment. Depending on the underlying etiology, an individual treatment concept needs to be developed. If an infectious or inflammatory cause is probable, a conservative approach can reduce perioperative morbidity and mortality. A step-wise approach with controlled reevaluations of the response to therapy after 72 h and 7 days avoids uncontrolled delay of surgical options further ensuring patient safety., Conclusion: Despite a decreasing incidence of toxic megacolon, it remains an interdisciplinary therapeutic challenge.
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- 2015
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225. Human antibody technology and the development of antibodies against cytomegalovirus.
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Ohlin M and Söderberg-Nauclér C
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- Antibodies isolation & purification, Antibodies, Monoclonal metabolism, Antibodies, Monoclonal therapeutic use, Antigen-Antibody Complex chemistry, Antigen-Antibody Complex immunology, Antigens, Viral immunology, Antigens, Viral metabolism, Cytomegalovirus metabolism, Cytomegalovirus Infections therapy, Cytomegalovirus Infections virology, Humans, Immunotherapy methods, Models, Molecular, Viral Envelope Proteins immunology, Viral Envelope Proteins metabolism, Antibodies immunology, Antibodies, Monoclonal immunology, Cytomegalovirus immunology, Cytomegalovirus Infections immunology
- Abstract
Cytomegalovirus (CMV) is a virus that causes chronic infections in a large set of the population. It may cause severe disease in immunocompromised individuals, is linked to immunosenescence and implied to play an important role in the pathogenesis of cardiovascular diseases and cancer. Modulation of the immune system's abilities to manage the virus represent a highly viable therapeutic option and passive immunotherapy with polyclonal antibody preparations is already in clinical use. Defined monoclonal antibodies offer many advantages over polyclonal antibodies purified from serum. Human CMV-specific monoclonal antibodies have consequently been thoroughly investigated with respect to their potential in the treatment of diseases caused by CMV. Recent advances in human antibody technology have substantially expanded the breadth of antibodies for such applications. This review summarizes the fundamental basis for treating CMV disease by use of antibodies, the basic technologies to be used to develop such antibodies, and relevant human antibody specificities available to target this virus., (Copyright © 2015 Elsevier Ltd. All rights reserved.)
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- 2015
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226. Combination therapy for multidrug-resistant cytomegalovirus disease.
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Stuehler C, Stüssi G, Halter J, Nowakowska J, Schibli A, Battegay M, Dirks J, Passweg J, Heim D, Rovo A, Kalberer C, Bucher C, Weisser M, Dumoulin A, Hirsch HH, and Khanna N
- Subjects
- Adoptive Transfer, Antiviral Agents therapeutic use, Combined Modality Therapy, Cytomegalovirus Infections immunology, Drug Therapy, Combination, Humans, Male, Middle Aged, Cytomegalovirus Infections therapy, Drug Resistance, Multiple, Viral, Hematopoietic Stem Cell Transplantation, Immunocompromised Host
- Abstract
Multidrug-resistant (MDR) cytomegalovirus (CMV) emerged after transient responses to ganciclovir, foscarnet, and cidofovir in a CMV-seropositive recipient who underwent allogeneic hematopoietic stem cell transplantation from a CMV-seronegative donor. Experimental treatments using leflunomide and artesunate failed. Re-transplantation from a CMV-seropositive donor supported by adoptive transfer of pp65-specific T cells and maribavir was followed by lasting suppression. This case illustrates that successful MDR CMV therapy may require individualized multidisciplinary approaches., (© 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)
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- 2015
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227. Acute GVHD results in a severe DC defect that prevents T-cell priming and leads to fulminant cytomegalovirus disease in mice.
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Wikstrom ME, Fleming P, Kuns RD, Schuster IS, Voigt V, Miller G, Clouston AD, Tey SK, Andoniou CE, Hill GR, and Degli-Esposti MA
- Subjects
- Adoptive Transfer, Animals, Bone Marrow Transplantation adverse effects, CD8-Positive T-Lymphocytes immunology, CD8-Positive T-Lymphocytes virology, Cells, Cultured, Cytomegalovirus isolation & purification, Cytomegalovirus Infections immunology, Cytomegalovirus Infections pathology, Cytomegalovirus Infections therapy, Dendritic Cells immunology, Dendritic Cells virology, Female, Graft vs Host Disease immunology, Graft vs Host Disease pathology, Graft vs Host Disease therapy, Mice, Mice, Inbred BALB C, Mice, Inbred C57BL, CD8-Positive T-Lymphocytes pathology, Cytomegalovirus immunology, Cytomegalovirus Infections etiology, Dendritic Cells pathology, Graft vs Host Disease complications
- Abstract
Viral infection is a common, life-threatening complication after allogeneic bone marrow transplantation (BMT), particularly in the presence of graft-versus-host disease (GVHD). Using cytomegalovirus (CMV) as the prototypic pathogen, we have delineated the mechanisms responsible for the inability to mount protective antiviral responses in this setting. Although CMV infection was self-limiting after syngeneic BMT, in the presence of GVHD after allogeneic BMT, CMV induced a striking cytopathy resulting in universal mortality in conjunction with a fulminant necrotizing hepatitis. Critically, GVHD induced a profound dendritic cell (DC) defect that led to a failure in the generation of CMV-specific CD8(+) T-cell responses. This was accompanied by a defect in antiviral CD8(+) T cells. In combination, these defects dramatically limited antiviral T-cell responses. The transfer of virus-specific cells circumvented the DC defects and provided protective immunity, despite concurrent GVHD. These data demonstrate the importance of avoiding GVHD when reconstructing antiviral immunity after BMT, and highlight the mechanisms by which the adoptive transfer of virus-specific T cells overcome the endogenous defects in priming invoked by GVHD., (© 2015 by The American Society of Hematology.)
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- 2015
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228. Increased incidence of chronic GvHD and CMV disease in patients with vitamin D deficiency before allogeneic stem cell transplantation.
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von Bahr L, Blennow O, Alm J, Björklund A, Malmberg KJ, Mougiakakos D, Le Blanc A, Oefner PJ, Labopin M, Ljungman P, and Le Blanc K
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- Adult, Allografts, Chronic Disease, Cytomegalovirus Infections etiology, Cytomegalovirus Infections therapy, Female, Graft vs Host Disease etiology, Graft vs Host Disease therapy, Humans, Incidence, Male, Middle Aged, Neoplasms epidemiology, Vitamin D Deficiency complications, Vitamin D Deficiency therapy, Cytomegalovirus, Cytomegalovirus Infections epidemiology, Graft vs Host Disease epidemiology, Hematopoietic Stem Cell Transplantation, Neoplasms therapy, Vitamin D Deficiency epidemiology
- Abstract
Vitamin D has emerged as a central player in the immune system, with its deficiency being implicated in the pathogenesis of several autoimmune diseases, including chronic GvHD. This is a retrospective cohort analysis of 166 patients, who underwent allogeneic hematopoietic stem cell transplantation (HSCT) at the Karolinska University Hospital, evaluating GvHD, graft failure, infectious complications and survival after HSCT in relation to pre-transplantation vitamin D levels. Most of the patients were deficient in vitamin D before HSCT (median 42 nmol/L). In multivariate analysis, vitamin D level before HSCT was identified as a significant independent risk factor for development of cGvHD. The increased incidence of cGvHD was not coupled to better disease-free survival; instead there was a trend towards lower overall survival in the vitamin D-deficient patients. In addition, we found a significant correlation between vitamin D deficiency and incidence of CMV disease, with no case of CMV disease occurring in patients with sufficient levels of vitamin D before HSCT. Our results support a role of vitamin D in immune tolerance following HSCT. These findings could be highly relevant for the care of HSCT patients, and prospective, randomized studies on the effect of vitamin D supplementation are therefore needed.
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- 2015
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229. [Optimization strategies in management of CMV infection in transplant patients].
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Navarro D
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- Antiviral Agents therapeutic use, Cytomegalovirus Infections therapy, Cytomegalovirus Infections virology, Humans, Immunosuppression Therapy adverse effects, Immunosuppressive Agents adverse effects, Cytomegalovirus Infections prevention & control, Organ Transplantation
- Abstract
Currently, two therapeutic strategies are applied for preventing the development of CMV end-organ disease in transplant recipients: universal prophylaxis and preemptive antiviral therapy. Both are potentially optimable. As for the former strategy, precisely identifying patients at greatest risk of viremia would allow for a targeted prophylaxis. In this sense several genotypic, immunological and biological markers have been described that could be ancillary to that purpose. As for the latter strategy, combined monitoring of plasma CMV DNA load and peripheral levels of CMV-specific CD8 + and CD4 + IFN-γ producing T cells would permit a more rationale use of antivirals, thus avoiding overtreatment and derived toxicity.
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- 2015
230. Immunotherapy with Donor T Cells Sensitized with Overlapping Pentadecapeptides for Treatment of Persistent Cytomegalovirus Infection or Viremia.
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Koehne G, Hasan A, Doubrovina E, Prockop S, Tyler E, Wasilewski G, and O'Reilly RJ
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- Aged, Allografts, Child, Female, Graft vs Host Disease immunology, Graft vs Host Disease pathology, Graft vs Host Disease prevention & control, Hematologic Neoplasms immunology, Hematologic Neoplasms pathology, Hematologic Neoplasms therapy, Humans, Male, Middle Aged, Peptides pharmacology, Phosphoproteins pharmacology, Viral Matrix Proteins pharmacology, Cytomegalovirus immunology, Cytomegalovirus Infections immunology, Cytomegalovirus Infections pathology, Cytomegalovirus Infections therapy, Hematopoietic Stem Cell Transplantation, Lymphocyte Transfusion, Peptides immunology, Phosphoproteins immunology, T-Lymphocytes immunology, T-Lymphocytes pathology, T-Lymphocytes transplantation, Tissue Donors, Viral Matrix Proteins immunology, Viremia immunology, Viremia pathology, Viremia therapy
- Abstract
We conducted a phase I trial of allogeneic T cells sensitized in vitro against a pool of pentadecapeptides (15-mer peptides) spanning the sequence of CMVpp65 for adoptive therapy of 17 allogeneic hematopoietic cell transplant recipients with cytomegalovirus (CMV) viremia or clinical infection persisting despite prolonged treatment with antiviral drugs. All but 3 of the patients had received T cell-depleted transplants without graft-versus-host disease (GVHD) prophylaxis with immunosuppressive drugs after transplantation. The CMVpp65-specific T cells (CMVpp65CTLs) generated were oligoclonal and specific for only 1 to 3 epitopes, presented by a limited set of HLA class I or II alleles. T cell infusions were well tolerated without toxicity or GVHD. Of 17 patients treated with transplant donor (n = 16) or third-party (n = 1) CMVpp65CTLs, 15 cleared viremia, including 3 of 5 with overt disease. In responding patients, the CMVpp65CTLs infused consistently proliferated and could be detected by T cell receptor Vβ usage in CMVpp65/HLA tetramer + populations for period of 120 days to up to 2 years after infusion. Thus, CMVpp65CTLs generated in response to synthetic 15-mer peptides of CMVpp65 are safe and can clear persistent CMV infections in the post-transplantation period., (Copyright © 2015 American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.)
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- 2015
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231. Obstructive Gastric Pseudotumor Caused by Cytomegalovirus in an AIDS Patient: A Case Report and Review of Surgical Treatment.
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Boteon YL, Alves IP, da Silva AP, Tercioti Junior V, Coelho Neto Jde S, Lopes LR, Ramos Mde C, and Andreollo NA
- Subjects
- AIDS-Related Opportunistic Infections therapy, Adult, Cytomegalovirus Infections therapy, Gastric Outlet Obstruction diagnosis, Gastric Outlet Obstruction therapy, Humans, Male, AIDS-Related Opportunistic Infections diagnosis, Cytomegalovirus, Cytomegalovirus Infections diagnosis, Gastric Outlet Obstruction virology
- Abstract
Background: Cytomegalovirus (CMV) is a common opportunistic pathogen in patients with HIV. It is also a major cause of gastrointestinal ulcers in patients with acquired immunodeficiency syndrome (AIDS). CMV pseudotumor in the stomach is a rare cause of digestive tract obstruction., Case Report: In this study we report a male patient infected with HIV in 2002. In 2014 he evolved C3 stage AIDS with pre-pyloric gastric ulcer which provoked deformity and pseudotumoral aspect of the gastric outlet. Endoscopic biopsy confirmed CMV infection. He underwent Roux-en-Y gastroenteroanastomosis with good recovery., Conclusions: CMV infection should be considered as an agent in gastric lesions in HIV-infected patients. Roux-en-Y gastroenteroanastomosis is a surgical option for this group of patients, allowing improvements in quality of life and decreasing risks of perioperative complications.
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- 2015
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232. Cytomegalovirus-specific cytokine-induced killer cells: concurrent targeting of leukemia and cytomegalovirus.
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Pfirrmann V, Oelsner S, Rettinger E, Huenecke S, Bonig H, Merker M, Wels WS, Cinatl J, Schubert R, Klingebiel T, and Bader P
- Subjects
- Cell Line, Tumor, Cytokine-Induced Killer Cells cytology, Cytomegalovirus immunology, Cytomegalovirus Infections virology, Cytotoxicity, Immunologic drug effects, Hematopoietic Stem Cell Transplantation adverse effects, Humans, Interferon-gamma pharmacology, Interleukin-15 pharmacology, Interleukin-2 pharmacology, Leukemia pathology, Leukemia therapy, Phosphoproteins immunology, Stem Cell Transplantation, T-Lymphocytes, Cytotoxic immunology, Viral Matrix Proteins immunology, Cell- and Tissue-Based Therapy methods, Cytokine-Induced Killer Cells transplantation, Cytomegalovirus Infections therapy, Immunotherapy methods
- Abstract
Background Aims: Human cytomegalovirus (CMV) infection and reactivation is a leading complication of allogeneic hematopoietic stem cell transplantation (HSCT). In addition to drug treatment, the adoptive transfer of virus-specific T cells to restore cellular immunity has become a standard therapy after allogeneic HSCT. We recently demonstrated potent anti-leukemic activity of interleukin (IL)-15-activated cytokine-induced killer (CIK) cells. With the use of the same expansion protocol, we asked whether concurrent CMV antigen-pulsing might generate CIK cells with anti-leukemic and anti-CMV activity., Methods: CIK cells expanded in the presence of interferon-γ, IL-2, IL-15 and anti-CD3 antibody were pulsed once with CMV(pp65) peptide pool. CMV-specific CIK (CIK(pp65)) and conventional CIK cells were phenotypically and functionally characterized according to their cytokine secretion pattern, degranulation capacity and T-cell receptor (TCR)-mediated and NKG2D-mediated cytotoxicity., Results: We demonstrated that among CIK cells generated from CMV-seropositive donors, a single stimulation with CMV(pp65) protein co-expanded cytotoxic CMV-specific cells without sacrificing anti-tumor reactivity. Cells generated in this fashion lysed CMV(pp65)-loaded target cells and CMV-infected fibroblasts but also leukemic cells. Meanwhile, the alloreactive potential of CIK(pp65) cells remained low. Interestingly, CMV reactivity was TCR-mediated and CMV-specific cells could be found in CD3(+)CD8(+)CD56(+/-) cytotoxic T-cell subpopulations., Conclusions: We provide an efficient method to generate CIK(pp65) cells that may represent a useful cell therapy approach for preemptive immunotherapy in patients who have both an apparent risk of CMV and impending leukemic relapse after allogeneic stem cell transplantation., (Copyright © 2015 International Society for Cellular Therapy. Published by Elsevier Inc. All rights reserved.)
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- 2015
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233. Pregnancy-related hemophagocytic lymphohistiocytosis associated with cytomegalovirus infection: A diagnostic and therapeutic challenge.
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Tumian NR and Wong CL
- Subjects
- Adult, Cesarean Section methods, Combined Modality Therapy, Cyclosporine administration & dosage, Cytomegalovirus Infections complications, Dexamethasone administration & dosage, Disease Progression, Drug Resistance, Multiple, Drug Therapy, Combination, Fatal Outcome, Female, Humans, Infusions, Intravenous, Lymphohistiocytosis, Hemophagocytic complications, Multiple Organ Failure, Plasma Exchange methods, Pregnancy, Pregnancy Trimester, Third, Severity of Illness Index, Cytomegalovirus Infections diagnosis, Cytomegalovirus Infections therapy, Lymphohistiocytosis, Hemophagocytic diagnosis, Lymphohistiocytosis, Hemophagocytic therapy, Pregnancy Complications, Infectious diagnosis, Pregnancy Complications, Infectious therapy
- Abstract
Objective: Hemophagocytic lymphohistiocytosis (HLH) is a disorder characterized by uncontrolled mature histiocyte proliferation, hemophagocytosis, and hypercytokinemia. We describe a previously healthy pregnant patient who presented in the third trimester of pregnancy with HLH., Case Report: A 35-year-old woman presented at 38 weeks' gestation with pyrexia, jaundice, severe anemia, elevated liver enzymes, and lactate dehydrogenase suggestive of HELLP (hemolysis, elevated liver enzyme, low platelet) syndrome. Unfortunately, her condition deteriorated and she was ventilated in the intensive care unit despite delivery of the baby and administration of dexamethasone. She developed microangiopathic hemolytic anemia, thrombocytopenia, and renal impairment suggestive of thrombotic thrombocytopenic purpura/hemolytic uremic syndrome. However, she was refractory to plasma exchange, intravenous immunoglobulin, and broad-spectrum antibiotics. HLH was eventually diagnosed from biochemical and bone marrow findings. An extensive search for possible causes yielded negative results. She improved significantly with intravenous dexamethasone and cyclosporine A and was transferred out of the intensive care unit. Unfortunately, she developed cytomegalovirus disease 2 weeks later, which improved transiently with intravenous ganciclovir; later, however, she succumbed to multidrug-resistant nosocomial infections, rapidly progressive cytomegalovirus disease, and multiorgan failure., Conclusion: This case highlights the challenges and difficulties involved in the diagnosis and management of pregnancy-related HLH. Immunosuppressive treatment for HLH can precipitate life-threatening opportunistic infections, which need to be promptly diagnosed and treated., (Copyright © 2015. Published by Elsevier B.V.)
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- 2015
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234. Evaluating Human T-Cell Therapy of Cytomegalovirus Organ Disease in HLA-Transgenic Mice.
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Thomas S, Klobuch S, Podlech J, Plachter B, Hoffmann P, Renzaho A, Theobald M, Reddehase MJ, Herr W, and Lemmermann NA
- Subjects
- Animals, Cytomegalovirus Infections immunology, Cytomegalovirus Infections virology, Disease Models, Animal, HLA-A2 Antigen genetics, HLA-A2 Antigen immunology, Humans, Mice, Inbred C57BL, Mice, Inbred NOD, Mice, SCID, Mice, Transgenic, Viral Matrix Proteins immunology, Cell- and Tissue-Based Therapy methods, Cytomegalovirus immunology, Cytomegalovirus Infections therapy, Epitopes, T-Lymphocyte immunology, Viral Load immunology
- Abstract
Reactivation of human cytomegalovirus (HCMV) can cause severe disease in recipients of hematopoietic stem cell transplantation. Although preclinical research in murine models as well as clinical trials have provided 'proof of concept' for infection control by pre-emptive CD8 T-cell immunotherapy, there exists no predictive model to experimentally evaluate parameters that determine antiviral efficacy of human T cells in terms of virus control in functional organs, prevention of organ disease, and host survival benefit. We here introduce a novel mouse model for testing HCMV epitope-specific human T cells. The HCMV UL83/pp65-derived NLV-peptide was presented by transgenic HLA-A2.1 in the context of a lethal infection of NOD/SCID/IL-2rg-/- mice with a chimeric murine CMV, mCMV-NLV. Scenarios of HCMV-seropositive and -seronegative human T-cell donors were modeled by testing peptide-restimulated and T-cell receptor-transduced human T cells, respectively. Upon transfer, the T cells infiltrated host tissues in an epitope-specific manner, confining the infection to nodular inflammatory foci. This resulted in a significant reduction of viral load, diminished organ pathology, and prolonged survival. The model has thus proven its potential for a preclinical testing of the protective antiviral efficacy of HCMV epitope-specific human T cells in the evaluation of new approaches to an immunotherapy of CMV disease.
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- 2015
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235. Cytomegalovirus infection in transplant recipients.
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Azevedo LS, Pierrotti LC, Abdala E, Costa SF, Strabelli TM, Campos SV, Ramos JF, Latif AZ, Litvinov N, Maluf NZ, Caiaffa Filho HH, Pannuti CS, Lopes MH, Santos VA, Linardi Cda C, Yasuda MA, and Marques HH
- Subjects
- Cytomegalovirus, Cytomegalovirus Infections diagnosis, Cytomegalovirus Infections therapy, Graft Rejection etiology, Humans, Cytomegalovirus Infections etiology, Postoperative Complications diagnosis, Postoperative Complications therapy, Transplant Recipients
- Abstract
Cytomegalovirus infection is a frequent complication after transplantation. This infection occurs due to transmission from the transplanted organ, due to reactivation of latent infection, or after a primary infection in seronegative patients and can be defined as follows: latent infection, active infection, viral syndrome or invasive disease. This condition occurs mainly between 30 and 90 days after transplantation. In hematopoietic stem cell transplantation in particular, infection usually occurs within the first 30 days after transplantation and in the presence of graft-versus-host disease. The major risk factors are when the recipient is cytomegalovirus seronegative and the donor is seropositive as well as when lymphocyte-depleting antibodies are used. There are two methods for the diagnosis of cytomegalovirus infection: the pp65 antigenemia assay and polymerase chain reaction. Serology has no value for the diagnosis of active disease, whereas histology of the affected tissue and bronchoalveolar lavage analysis are useful in the diagnosis of invasive disease. Cytomegalovirus disease can be prevented by prophylaxis (the administration of antiviral drugs to all or to a subgroup of patients who are at higher risk of viral replication) or by preemptive therapy (the early diagnosis of viral replication before development of the disease and prescription of antiviral treatment to prevent the appearance of clinical disease). The drug used is intravenous or oral ganciclovir; oral valganciclovir; or, less frequently, valacyclovir. Prophylaxis should continue for 90 to 180 days. Treatment is always indicated in cytomegalovirus disease, and the gold-standard drug is intravenous ganciclovir. Treatment should be given for 2 to 3 weeks and should be continued for an additional 7 days after the first negative result for viremia.
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- 2015
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236. Lymphoma-Like Syndrome: 4 Case Reports About Atypical Presentation of Primary Cytomegalovirus Infection in Immunocompetent Children.
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Vigué MG, Tuaillon E, Makinson A, Bullen GM, Foulongne V, Segondy M, Perre PV, and Jeziorski E
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- Child, Child, Preschool, Cytomegalovirus Infections therapy, Diagnosis, Differential, Female, Humans, Immunocompetence, Male, Retrospective Studies, Cytomegalovirus Infections diagnosis, Lymphoma diagnosis, Pseudolymphoma diagnosis
- Abstract
In immunocompetent persons, primary cytomegalovirus (CMV) infection is self-limited infection. Lymphoma-like syndromes have been sometimes described in adults but have not been described for children.Lymphoma-like syndromes (protracted fever, alteration of the general status, and clinical lymphoproliferative syndrome) were retrospectively recorded in children attending our hospital from 1999 to 2008 for primary CMV infection. Patients with immunodeficiency, coinfection (Epstein-Barr virus, toxoplasmosis, or mycobacterial), or biological criteria of mononucleosis-like syndrome were excluded.We report 4 cases of lymphoma-like syndrome. The median duration of fever was 21.5 days (range 15-27). Tonsillitis and hepatitis are most of the time missing. A probable malignant diagnosis was raised in 3 cases. Clinical outcome was protracted (15-35 days) but favorable.To our knowledge, our study is the first pediatric case series of lymphoma-like syndrome. This clinical presentation is a source of delayed diagnosis due to diagnosis pitfall.
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- 2015
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237. RNase P Ribozymes Inhibit the Replication of Human Cytomegalovirus by Targeting Essential Viral Capsid Proteins.
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Yang Z, Reeves M, Ye J, Trang P, Zhu L, Sheng J, Wang Y, Zen K, Wu J, and Liu F
- Subjects
- Capsid Proteins antagonists & inhibitors, Capsid Proteins genetics, Cytomegalovirus genetics, Cytomegalovirus Infections genetics, Cytomegalovirus Infections therapy, Gene Expression Regulation, Viral, Humans, RNA, Catalytic genetics, Ribonuclease P genetics, Capsid Proteins metabolism, Cytomegalovirus physiology, Cytomegalovirus Infections virology, RNA, Catalytic metabolism, Ribonuclease P metabolism, Virus Replication
- Abstract
An engineered RNase P-based ribozyme variant, which was generated using the in vitro selection procedure, was used to target the overlapping mRNA region of two proteins essential for human cytomegalovirus (HCMV) replication: capsid assembly protein (AP) and protease (PR). In vitro studies showed that the generated variant, V718-A, cleaved the target AP mRNA sequence efficiently and its activity was about 60-fold higher than that of wild type ribozyme M1-A. Furthermore, we observed a reduction of 98%-99% in AP/PR expression and an inhibition of 50,000 fold in viral growth in cells with V718-A, while a 75% reduction in AP/PR expression and a 500-fold inhibition in viral growth was found in cells with M1-A. Examination of the antiviral effects of the generated ribozyme on the HCMV replication cycle suggested that viral DNA encapsidation was inhibited and as a consequence, viral capsid assembly was blocked when the expression of AP and PR was inhibited by the ribozyme. Thus, our study indicates that the generated ribozyme variant is highly effective in inhibiting HCMV gene expression and blocking viral replication, and suggests that engineered RNase P ribozyme can be potentially developed as a promising gene-targeting agent for anti-HCMV therapy.
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- 2015
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238. How understanding immunology contributes to managing CMV disease in immunosuppressed patients: now and in future.
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Sissons JG and Wills MR
- Subjects
- Adaptive Immunity, Cytomegalovirus Infections diagnosis, Cytomegalovirus Infections therapy, Disease Management, Humans, Immunity, Innate, Immunotherapy, Adoptive, Myeloid Cells virology, T-Lymphocytes immunology, Virus Activation immunology, Virus Latency immunology, Cytomegalovirus immunology, Cytomegalovirus Infections immunology, Cytomegalovirus Infections virology, Immunocompromised Host
- Abstract
Several decades of research on human cytomegalovirus (HCMV) and the principal mammalian cytomegaloviruses which to varying degrees act as models of HCMV infection, particularly murine, guinea pig and rhesus CMV, have led to the recognition of the CMVs as interesting models of persistent infection with a large and complex DNA virus, which have been highly informative of the immunology and molecular pathogenesis of the virus-host relationship in the normal host. However, it is appropriate to ask how this relative wealth of knowledge has influenced the understanding and management of clinical disease due to HCMV. This article considers the immunology of cytomegalovirus in the normal human host, and the interrelated issue of the sites of HCMV latency and mechanisms of reactivation in the myeloid cell lineage, and in related in vitro model systems. The way in which this site of latency conditions the immune response, and emerging information on the special features of the adaptive immune response to HCMV during latency are also considered. Examples of HCMV disease associated with acquired immunosuppression, principally in the context of transplantation, but also as a consequence of HIV/AIDS and immune reconstitution inflammatory syndrome, are then discussed, with a particular emphasis on how understanding the immunology of persistent infection may contribute to managing CMV disease now and in future.
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- 2015
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239. [Symptomatic cytomegalovirus infection through breastfeeding in a 45 days old boy].
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Sordelli N, Sapia E, Delgado M, Mistchenko A, and Dastugue M
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- Cytomegalovirus Infections diagnosis, Cytomegalovirus Infections therapy, Humans, Infant, Male, Breast Feeding, Cytomegalovirus Infections transmission
- Abstract
Postnatal infection or acquired cytomegalovirus in the newborn is transmitted by maternal cervical secretions at birth, breastfeeding, blood transfusion or biological fluids. Breast milk is the main source of infection. Clinical manifestations depend on the gestational age and birth weight, premature and low birth weight newborn being more vulnerable. Postnatal infection usually resolves spontaneously without antiviral treatment; the risk of long-term sequelae is lower than in congenital infection. We describe the case of a 45 days old male patient, term newborn appropriate for gestational age, with a very rare condition characterized by severe thrombocytopenia secondary to postnatal cytomegalovirus infection. We detail its symptoms, clinical evolution, diagnosis and treatment employed.
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- 2015
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240. Practice bulletin no. 151: Cytomegalovirus, parvovirus B19, varicella zoster, and toxoplasmosis in pregnancy.
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- Chickenpox diagnosis, Chickenpox therapy, Cytomegalovirus Infections diagnosis, Cytomegalovirus Infections therapy, Directive Counseling, Erythema Infectiosum diagnosis, Erythema Infectiosum therapy, Female, Fetal Diseases diagnosis, Humans, Pregnancy, Pregnancy Complications, Infectious diagnosis, Toxoplasmosis diagnosis, Toxoplasmosis therapy, Chickenpox transmission, Cytomegalovirus Infections transmission, Erythema Infectiosum transmission, Fetal Diseases therapy, Infectious Disease Transmission, Vertical prevention & control, Pregnancy Complications, Infectious therapy, Toxoplasmosis transmission
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- 2015
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241. Mycophenolate-based graft versus host disease prophylaxis is not inferior to methotrexate in myeloablative-related donor stem cell transplantation.
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Hamad N, Shanavas M, Michelis FV, Uhm J, Gupta V, Seftel M, Kuruvilla J, Lipton JH, Messner HA, and Kim DD
- Subjects
- Adolescent, Adult, Antibiotics, Antineoplastic therapeutic use, Cyclosporine therapeutic use, Cytomegalovirus immunology, Cytomegalovirus Infections immunology, Cytomegalovirus Infections mortality, Cytomegalovirus Infections pathology, Female, Graft vs Host Disease immunology, Graft vs Host Disease pathology, Graft vs Host Disease prevention & control, Humans, Immunosuppressive Agents therapeutic use, Leukemia, Myeloid, Acute immunology, Leukemia, Myeloid, Acute mortality, Leukemia, Myeloid, Acute pathology, Male, Methotrexate therapeutic use, Middle Aged, Myeloablative Agonists therapeutic use, Precursor Cell Lymphoblastic Leukemia-Lymphoma immunology, Precursor Cell Lymphoblastic Leukemia-Lymphoma mortality, Precursor Cell Lymphoblastic Leukemia-Lymphoma pathology, Recurrence, Retrospective Studies, Survival Analysis, Tissue Donors, Transplantation, Homologous, Cytomegalovirus Infections therapy, Graft vs Host Disease therapy, Hematopoietic Stem Cell Transplantation, Leukemia, Myeloid, Acute therapy, Mycophenolic Acid therapeutic use, Precursor Cell Lymphoblastic Leukemia-Lymphoma therapy, Transplantation Conditioning
- Abstract
We retrospectively reviewed 242 patients who received related donor myeloablative peripheral blood hematopoietic cell transplantation. We compared patients who received mycophenolate (MMF)/cyclosporine (CSA) (n = 71), to historical controls who received methotrexate (MTX)/CSA (n = 172). There were no differences in overall survival, nonrelapse mortality, and relapse. The MMF/CSA group had significantly faster neutrophil and platelet engraftment: medians of 13 versus 18 days and 10 versus 14 days, respectively (P = 0.001). The cumulative incidence of acute graft versus host disease (GVHD) (Grades, 2-4) was significantly lower in the MMF/CSA group (45.1 vs. 74.4%, P < 0.001). The MMF/CSA group showed a lower incidence of skin (51.5 vs. 72.1%, P < 0.001) and liver acute GVHD (11.3 vs. 54.2%, P < 0.001) and a higher incidence of lung (42.2 vs. 19.0%, P = 0.045), eye (59.7 vs. 30.1%, P < 0.001), and mouth (72.8 vs. 56.4%, P = 0.001) chronic GVHD but only eye chronic GVHD was confirmed in propensity score matching (PSM) analysis. The incidence of cytomegalovirus (CMV) viremia was higher in the MMF/CSA group (55.8 vs. 39.6%, P < 0.001) but this was not confirmed in PSM analysis. MMF/CSA was identified as an independent favorable factor for acute GVHD (P < 0.001, hazard ratio, 0.41) but as a possible adverse risk factor for CMV viremia as this was not found to be statistically significant in PSM analysis. MMF/CSA in myeloablative matched related donor peripheral blood stem cell transplant is not inferior as GVHD prophylaxis in comparison with MTX/CSA and is associated with faster engraftment but a potentially higher risk of CMV viremia., (© 2015 Wiley Periodicals, Inc.)
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- 2015
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242. [Cytomegalovirus after renal transplantation - diagnosis, prevention and treatment].
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Kliem V, Sester M, Nitschke M, Tönshoff B, Budde K, Hauser IA, Schmitt M, Höcker B, and Witzke O
- Subjects
- Cytomegalovirus Infections etiology, Evidence-Based Medicine, Germany, Humans, Treatment Outcome, Antiviral Agents administration & dosage, Cytomegalovirus Infections diagnosis, Cytomegalovirus Infections therapy, Infectious Disease Medicine standards, Kidney Transplantation adverse effects, Nephrology standards, Practice Guidelines as Topic
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- 2015
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243. The immunology of human cytomegalovirus latency: could latent infection be cleared by novel immunotherapeutic strategies?
- Author
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Wills MR, Poole E, Lau B, Krishna B, and Sinclair JH
- Subjects
- Animals, Cytomegalovirus Infections virology, Humans, Cytomegalovirus immunology, Cytomegalovirus Infections immunology, Cytomegalovirus Infections therapy, Immunotherapy, Virus Activation, Virus Latency
- Abstract
While the host immune response following primary human cytomegalovirus (HCMV) infection is generally effective at stopping virus replication and dissemination, virus is never cleared by the host and like all herpesviruses, persists for life. At least in part, this persistence is known to be facilitated by the ability of HCMV to establish latency in myeloid cells in which infection is essentially silent with, importantly, a total lack of new virus production. However, although the viral transcription programme during latency is much suppressed, a number of viral genes are expressed during latent infection at the protein level and many of these have been shown to have profound effects on the latent cell and its environment. Intriguingly, many of these latency-associated genes are also expressed during lytic infection. Therefore, why the same potent host immune responses generated during lytic infection to these viral gene products are not recognized during latency, thereby allowing clearance of latently infected cells, is far from clear. Reactivation from latency is also a major cause of HCMV-mediated disease, particularly in the immune compromised and immune naive, and is also likely to be a major source of virus in chronic subclinical HCMV infection which has been suggested to be associated with long-term diseases such as atherosclerosis and some neoplasias. Consequently, understanding latency and why latently infected cells appear to be immunoprivileged is crucial for an understanding of the pathogenesis of HCMV and may help to design strategies to eliminate latent virus reservoirs, at least in certain clinical settings.
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- 2015
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244. Adoptive T cell immunotherapy for treatment of ganciclovir-resistant cytomegalovirus disease in a renal transplant recipient.
- Author
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Macesic N, Langsford D, Nicholls K, Hughes P, Gottlieb DJ, Clancy L, Blyth E, Micklethwaite K, Withers B, Majumdar S, Fleming S, and Sasadeusz J
- Subjects
- Cytomegalovirus Infections drug therapy, Humans, Male, Middle Aged, Antiviral Agents therapeutic use, Cytomegalovirus Infections therapy, Ganciclovir therapeutic use, Immunotherapy, Adoptive, Kidney Transplantation, T-Lymphocytes cytology
- Abstract
Cytomegalovirus (CMV) is a significant cause of morbidity, mortality and graft loss in solid organ transplantation (SOT). Treatment options for ganciclovir-resistant CMV are limited. We describe a case of ganciclovir-resistant CMV disease in a renal transplant recipient manifested by thrombotic microangiopathy-associated glomerulopathy. Adoptive T cell immunotherapy using CMV-specific T cells from a donor bank was used as salvage therapy. This report is a proof-of-concept of the clinical and logistical feasibility of this therapy in SOT recipients., (© Copyright 2015 The American Society of Transplantation and the American Society of Transplant Surgeons.)
- Published
- 2015
- Full Text
- View/download PDF
245. Vaccine therapy for cytomegalovirus in the setting of allogeneic hematopoietic cell transplantation.
- Author
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Kharfan-Dabaja MA and Nishihori T
- Subjects
- Clinical Trials, Phase II as Topic, Clinical Trials, Phase III as Topic, Humans, Immunocompromised Host, Randomized Controlled Trials as Topic, Treatment Outcome, Cytomegalovirus Infections therapy, Hematopoietic Stem Cell Transplantation adverse effects, Immunotherapy, Active methods, Transplantation, Homologous adverse effects
- Abstract
Passive immunization against CMV is desirable to minimize or perhaps eliminate complications related to CMV disease. In allogeneic hematopoietic cell transplantation (allo-HCT), the major challenge facing a successful anti-CMV vaccine is inducing immunity in an immunocompromised host. To date, only one CMV vaccine, ASP0113, has been evaluated in a randomized, placebo-controlled Phase II study. ASP0113 is a bivalent product containing two plasmids that encode CMV glycoprotein B and tegument phosphoprotein 65, respectively. Although there was no significant difference in rate of initiation of anti-CMV therapy, rates of CMV viremia were lower in the ASP0113 group when measured by a central laboratory. Also, time-to-first episode of viremia was longer in subjects receiving ASP0113. These findings paved the way for an ongoing placebo-controlled Phase III study aiming at enrolling 500 subjects. Results of this Phase III trial, especially if it meets clinically meaningful endpoints, will ultimately determine the role of anti-CMV vaccine strategies in allo-HCT.
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- 2015
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246. [HCMV infections after hematopoietic stem cell transplantation--diagnostic methods and importance of viral DNA level monitoring].
- Author
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Bocian J and Januszkiewicz-Lewandowska D
- Subjects
- Antigens, Viral blood, Cytomegalovirus Infections therapy, Humans, RNA, Viral blood, Risk Factors, Viral Load, Cytomegalovirus isolation & purification, Cytomegalovirus Infections diagnosis, Cytomegalovirus Infections virology, DNA, Viral blood, Hematopoietic Stem Cell Transplantation adverse effects, Immunocompromised Host, Immunosuppression Therapy adverse effects
- Abstract
HCMV infection is very common. The virus infects 30-90% of population. In immunocompromised patients effective elimination of the virus by immune system is limited by immunosuppressive therapy. Active hCMV infection after HSCT can lead to severe posttransplant complications, graft failure or even death. In addition to direct effects of hCMV infection the virus can cause indirect effects in transplant recipients such as increased immunosuppression or GvHD development/progression. Laboratory diagnostic of hCMV infections after HSCT is now routinely used. Fast and sensitive molecular methods that detect hCMV genetic material are found particularly useful. Quantitative methods, such as R-T PCR, enable identification of patients at high risk of developing hCMV disease and fast employment of appropriate prophylaxis or treatment. Moreover it allows precise monitoring of treatment efficiency and facilitates therapy - related decisions. In last years pre-emptive therapy, which depends on viral load molecular monitoring, significantly reduced morbidity and mortality of active hCMV infections in HSCT recipients. Selective prophylaxis approach enables reduction of patients treated with toxic antiviral therapy which is associated with delayed restoration of virus - specific immune response. Occurrence of symptomatic hCMV disease is still associated with high mortality among HSCT recipients. HCMV infection diagnosis requires further development. Quantitative methods should be unified and optimized.
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- 2015
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247. Human cytomegalovirus and Epstein-Barr virus infection in inflammatory bowel disease: need for mucosal viral load measurement.
- Author
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Ciccocioppo R, Racca F, Paolucci S, Campanini G, Pozzi L, Betti E, Riboni R, Vanoli A, Baldanti F, and Corazza GR
- Subjects
- Adolescent, Adult, Aged, Biopsy, Case-Control Studies, Colonoscopy, Cytomegalovirus genetics, Cytomegalovirus Infections therapy, Cytomegalovirus Infections virology, DNA, Viral isolation & purification, Diagnosis, Differential, Epstein-Barr Virus Infections therapy, Epstein-Barr Virus Infections virology, Female, Herpesvirus 4, Human genetics, Humans, Immunohistochemistry, Inflammatory Bowel Diseases therapy, Inflammatory Bowel Diseases virology, Male, Middle Aged, Opportunistic Infections therapy, Opportunistic Infections virology, Predictive Value of Tests, Prognosis, Prospective Studies, Real-Time Polymerase Chain Reaction, Risk Factors, Viral Load, Young Adult, Colon virology, Cytomegalovirus isolation & purification, Cytomegalovirus Infections diagnosis, Epstein-Barr Virus Infections diagnosis, Herpesvirus 4, Human isolation & purification, Inflammatory Bowel Diseases diagnosis, Intestinal Mucosa virology, Opportunistic Infections diagnosis
- Abstract
Aim: To evaluate the best diagnostic technique and risk factors of the human Cytomegalovirus (HCMV) and Epstein-Barr virus (EBV) infection in inflammatory bowel disease (IBD)., Methods: A cohort of 40 IBD patients (17 refractory) and 40 controls underwent peripheral blood and endoscopic colonic mucosal sample harvest. Viral infection was assessed by quantitative real-time polymerase chain reaction and immunohistochemistry, and correlations with clinical and endoscopic indexes of activity, and risk factors were investigated., Results: All refractory patients carried detectable levels of HCMV and/or EBV mucosal load as compared to 13/23 (56.5%) non-refractory and 13/40 (32.5%) controls. The median DNA value was significantly higher in refractory (HCMV 286 and EBV 5.440 copies/10(5) cells) than in non-refractory (HCMV 0 and EBV 6 copies/10(5) cells; P < 0.05 and < 0.001) IBD patients and controls (HCMV and EBV 0 copies/10(5) cells; P < 0.001 for both). Refractory patients showed DNA peak values ≥ 10(3) copies/10(5) cells in diseased mucosa in comparison to non-diseased mucosa (P < 0.0121 for HCMV and < 0.0004 for EBV), while non-refractory patients and controls invariably displayed levels below this threshold, thus allowing us to differentiate viral colitis from mucosal infection. Moreover, the mucosal load positively correlated with the values found in the peripheral blood, whilst no correlation with the number of positive cells at immunohistochemistry was found. Steroid use was identified as a significant risk factor for both HCMV (P = 0.018) and EBV (P = 0.002) colitis. Finally, a course of specific antiviral therapy with ganciclovir was successful in all refractory patients with HCMV colitis, whilst refractory patients with EBV colitis did not show any improvement despite steroid tapering and discontinuation of the other medications., Conclusion: Viral colitis appeared to contribute to mucosal lesions in refractory IBD, and its correct diagnosis and management require quantitative real-time polymerase chain reaction assay of mucosal specimens.
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- 2015
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248. Modulation of heme oxygenase-1 by metalloporphyrins increases anti-viral T cell responses.
- Author
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Bunse CE, Fortmeier V, Tischer S, Zilian E, Figueiredo C, Witte T, Blasczyk R, Immenschuh S, and Eiz-Vesper B
- Subjects
- Adoptive Transfer, Cytomegalovirus Infections pathology, Cytomegalovirus Infections therapy, Dendritic Cells immunology, Female, Humans, Immunologic Memory, Interferon-gamma immunology, Male, Phosphoproteins immunology, T-Lymphocytes, Regulatory pathology, T-Lymphocytes, Regulatory transplantation, Tumor Necrosis Factor-alpha immunology, Viral Matrix Proteins immunology, Cytomegalovirus immunology, Cytomegalovirus Infections immunology, Heme Oxygenase-1 immunology, Immunity, Cellular, Metalloporphyrins pharmacology, T-Lymphocytes, Regulatory immunology
- Abstract
Heme oxygenase (HO)-1, the inducible isoform of HO, has immunomodulatory functions and is considered a target for therapeutic interventions. In the present study, we investigated whether modulation of HO-1 might have regulatory effects on in-vitro T cell activation. The study examined whether: (i) HO-1 induction by cobalt-protoporphyrin (CoPP) or inhibition by tin-mesoporphyrin (SnMP) can affect expansion and function of virus-specific T cells, (ii) HO-1 modulation might have a functional effect on other cell populations mediating effects on proliferating T cells [e.g. dendritic cells (DCs), regulatory T cells (T(regs)) and natural killer cells] and (iii) HO-1-modulated anti-viral T cells might be suitable for adoptive immunotherapy. Inhibition of HO-1 via SnMP in cytomegalovirus (CMV)pp65-peptide-pulsed peripheral blood mononuclear cells (PBMCs) led to increased anti-viral T cell activation and the generation of a higher proportion of effector memory T cells (CD45RA(-) CD62L(-)) with increased capability to secrete interferon (IFN)-γ and granzyme B. T(reg) depletion and SnMP exposure increased the number of anti-viral T cells 15-fold. To test the possibility that HO-1 modulation might be clinically applicable in conformity with good manufacturing practice (GMP), SnMP was tested in isolated anti-viral T cells using the cytokine secretion assay. Compared to control, SnMP treatment resulted in higher cell counts and purity without negative impact on quality and effector function [CD107a, IFN-γ and tumour necrosis factor (TNF)-α levels were stable]. These results suggest an important role of HO-1 in the modulation of adaptive immune responses. HO-1 inhibition resulted in markedly more effective generation of functionally active T cells suitable for adoptive T cell therapy., (© 2014 British Society for Immunology.)
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- 2015
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249. [Cytomegalovirus specific cytotoxic T lymphocytes for treatment of refractory cytomegalovirus infection in patients following allogeneic hematopoietic stem cell transplantation].
- Author
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Xu Z, Huang X, Sun Y, Wang F, Yan C, Zhang X, Han W, Chen Y, Wang J, Chen H, Wang Y, Zhang Y, Liu K, and Xu L
- Subjects
- Cytomegalovirus Infections complications, Cytomegalovirus Infections immunology, Graft vs Host Disease, Humans, Immunotherapy, Adoptive, Stem Cell Transplantation adverse effects, T-Lymphocytes, Cytotoxic cytology, T-Lymphocytes, Cytotoxic virology, Tissue Donors, Transplantation, Homologous, Treatment Outcome, Viremia, Cytomegalovirus immunology, Cytomegalovirus Infections therapy, Hematopoietic Stem Cell Transplantation adverse effects, T-Lymphocytes, Cytotoxic immunology
- Abstract
Objective: To explore the efficacy and safety of expanding cytomegalovirus specific cytotoxic T lymphocytes (CMV-CTL) in vitro on refractory cytomegalovirus (CMV) infection., Methods: A total of twenty-eight patients with refractory CMV infection following stem cell transplant (SCT) were treated with CMV-specific T cells, of which 19 cases were from hematopoietic stem cell donors and 9 from third-party donors. In the first course, CTL was infused once or twice and the efficacy and adverse effects were evaluated. If CMV infection relapsed after complete remission (CR), the second course would be given., Results: Twenty-one patients with refractory CMV viremia and seven with CMV diseases were eligible for adoptive T-cell transfer. After a median of 76 (39-321) days post-transplant, patients received a median dose of 1.0 (0.5-10.0) × 10(7) CTL infusion in the first course. All twenty-one patients with CMV viremia and four patients with CMV diseases achieved CR after using 9 (3-23) and 7 (4-18) days respecitvely. Six patients with CMV viremia and one with CMV disease received the second course after recurrence. Another four patients with viremia and one with CMV disease had reached CR again. Five patients exhibited graft-versus-host diseases (GVHD), all experiencing mild to moderate skin involvement. Six patients died of CMV infection and 2 of other transplantation-related complications., Conclusion: Our preliminary results have shown that CMV-CTL infusion is effective against refractory cytomegalovirus infection following SCT, but therapeutic schedule still needs to be improved in further study.
- Published
- 2015
250. Synthetic DNA approach to cytomegalovirus vaccine/immune therapy.
- Author
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Wu SJ, Villarreal DO, Shedlock DJ, and Weiner DB
- Subjects
- Adult, Animals, Cytomegalovirus genetics, Cytomegalovirus immunology, Cytomegalovirus Infections genetics, Cytomegalovirus Infections immunology, Cytomegalovirus Vaccines genetics, DNA, Recombinant genetics, DNA, Recombinant therapeutic use, Humans, Vaccines, DNA genetics, Cloning, Molecular methods, Cytomegalovirus Infections therapy, Cytomegalovirus Vaccines therapeutic use, Immunotherapy, Active methods, Vaccines, DNA therapeutic use
- Abstract
There is no licensed vaccine or cure for human cytomegalovirus (CMV), a ubiquitous β-herpes virus that infects 60-95 % of adults worldwide. Infection is a major cause of congenital abnormalities in newborns, contributes to development of childhood cerebral palsy and medulloblastoma, can result in severe disease in immunocompromised patients, and is a major impediment during successful organ transplantation. While CMV has been increasingly associated with numerous inflammatory diseases and cancers, only recently has it been correlated with increased risk of heart disease in adults, the number-one killer in the USA. These data, among others, suggest that subclinical CMV infection, or microinfection, in healthy individuals may play more of a causative role than an epiphenomenon in development of CMV-associated pathologies. Due to the myriad of diseases and complications associated with CMV, an efficacious vaccine would be highly valuable in reducing human morbidity and mortality as well as saving billions of dollars in annual health-care costs and disability adjusted life years (DALY) in the developing world. Therefore, the development of a safe efficacious CMV vaccine or immune therapy is paramount to the public health. This review aims to provide a brief overview on aspects of CMV infection and disease and focuses on current vaccine strategies. The use of new synthetic DNA vaccines might offer one such approach to this difficult problem.
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- 2015
- Full Text
- View/download PDF
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