Lack of evidence of active lytic replication of Epstein-Barr and cytomegaloviruses in patients with systemic lupus erythematosus

Objectives Systemic lupus erythematosus (SLE) is a multifactorial disease. Environmental factors such as viral infection(s) have been proposed as pathaetiological factors. There are particular interests in studying lymphotropic viruses such as the Epstein-Barr virus (EBV) and cytomegalovirus (CMV). Although previous case reports and in vitro studies suggested that they may have a role, there is no direct evidence that onset of SLE or disease exacerbation is associated with active infection by these viruses. Using the very sensitive polymerase chain reaction (PCR) technique, we tried to find out evidence of active replication of these viruses in patients with SLE. Methods Thirty-four patients with SLE were compared with matched normal controls. Eleven patients were newly diagnosed to have SLE and 18 of the 34 patients had active disease as determined by a SLE Disease Activity Index (SLEDAI) score of ≥10 at the time of study. Results Our results showed no evidence of active replication or reactivation of EBV in the leucocytes amongst the newly diagnosed SLE patients, established SLE patients, patients with SLEDAI ≥10, patients with SLEDAI <10, and control subjects. There was no evidence of CMV infection in any of the subjects studied. The IgG and IgA responses against EBV early antigen (EA) and viral capsid antigen (VCA) were also studied. The IgG and IgA responses against VCA of EBV were increased in patients with SLE when compared with controls. However, there were no differences in these responses among different subgroups of patients. The mechanism of these responses was not apparent but may represent non-specific hyperimmune responses in these patients. There were no differences in the titre of IgG and IgA against EBV EA between the patient groups and controls.Conclusion There is no direct evidence that either EBV or CMV plays a direct role in the onset and/or exacerbation of SLE.

Management strategies for common viral infections in pediatric renal transplant recipients

Viral infections have been considered as a major cause of morbidity and mortality after kidney transplantation in pediatric cohort.Children are at high risk of acquiring virus-related complications due to immunological immaturity and the enhanced alloreactivity risk that led to maintenance of high immunosuppressive regimes.Hence,prevention,early detection,and prompt treatment of such infections are of paramount importance.Among all viral infections,herpes viruses(herpes simplex virus,varicella zoster virus,Epstein-Barr virus,cytomegalovirus),hepatitis B and C viruses,BK polyomavirus,and respiratory viruses(respiratory syncytial virus,parainfluenza virus,influenza virus and adenovirus)are common in kidney transplant recipients.These viruses can cause systemic disease or allograft dysfunction affecting the clinical outcome.Recent advances in technology and antiviral therapy have improved management strategies in screening,monitoring,adoption of prophylactic or preemptive therapy and precise treatment in the immunocompromised host,with significant impact on the outcome.This review discusses the etiology,screening and monitoring,diagnosis,prevention,and treatment of common viral infections in pediatric renal transplant recipients.

Management of cytomegalovirus infection after liver transplantation

Cytomegalovirus(CMV)infection is one of the primary causes of morbidity and mortality following liver transplantation(LT).Based on current worldwide guidelines,the most effective strategies for avoiding post-transplant CMV infection are antiviral prophylaxis and pre-emptive treatment.CMV-IgG serology is the established technique for pretransplant screening of both donors and recipients.The clinical presentation of CMV infection and disease exhibits variability,prompting clinicians to consistently consider this possibility,partic-ularly within the first year post-transplantation or subsequent to heightened immunosuppression.At annual symposia to discuss CMV prevention and how treatment outcomes can be improved,evidence on the incorporation of immune functional tests into clinical practice is presented,and the results of studies with new antiviral treatments are evaluated.Although there are ongoing studies on the use of letermovir and maribavir in solid organ transplantation,a consensus reflected in the guidelines has not been formed.Determining the most appro-priate strategy at the individual level appears to be the key to enhancing out-comes.Although prevention strategies reduce the risk of CMV disease,the disease can still occur in up to 50%of high-risk patients.A balance between the risk of infection and disease development and the use of immunosuppressants must be considered when talking about the proper management of CMV in solid organ transplant recipients.The objective of this study was to establish a compre-hensive framework for the management of CMV in patients who have had LT.

Cytomegalovirus infection in non-immunocompromised critically ill patients:A management perspective

Critically ill patients are a vulnerable group at high risk of developing secondary infections.High disease severity,prolonged intensive care unit(ICU)stay,sepsis,and multiple drugs with immunosuppressive activity make these patients prone to immuneparesis and increase the risk of various opportunistic infections,including cytomegalovirus(CMV).CMV seroconversion has been reported in up to 33%of ICU patients,but its impact on patient outcomes remains a matter of debate.Even though there are guidelines regarding the management of CMV infection in immunosuppressive patients with human immunodeficiency virus/acquired immuno deficiency syndrome,the need for treatment and therapeutic approaches in immunocompetent critically ill patients is still ambiguous.Even the diagnosis of CMV infection may be challenging in such patients due to non-specific symptoms and multiorgan involvement.Hence,a better understanding of the symptomatology,diagnostics,and treatment options may aid intensive care physicians in ensuring accurate diagnoses and instituting therapeutic interventions.

Destructive effects on endothelial cells of grafts in cytomegalovirus DNA-positive patients after keratoplasty

AIM:To investigate corneal graft survival rate and endothelial cell density(ECD)loss after keratoplasty in cytomegalovirus(CMV)positive patients.METHODS:This was a retrospective cohort study.We analyzed the clinical data of patients who underwent viral DNA detection in aqueous humor/corneal tissue collected during keratoplasty from March 2015 to December 2018 at the Peking University Third Hospital,Beijing,China.To further evaluate the effect of CMV on graft survival rate and ECD loss,patients were divided into three groups:1)CMV DNA positive(CMV+)group;2)viral DNA negative(virus-)group,comprising virus-group eyes pairwise matched to eyes in the CMV+group according to ocular comorbidities;3)control group,comprising virus-group eyes without ocular comorbidities.The follow-up indicators including graft survival rate,ECD,ECD loss,and central corneal thickness(CCT),were analyzed by Tukey honestly significant difference(HSD)test.RESULTS:Each group included 29 cases.The graft survival rate in CMV+group were lowest among the three groups(P=0.000).No significant difference in donor graft ECD was found among three groups(P=0.54).ECD in the CMV+group was lower than the virus-group at 12(P=0.009),and 24mo(P=0.002)after keratoplasties.Furthermore,ECD loss was higher in the CMV+group than in the virus-group in the middle stage(6-12mo)postkeratoplasty(P=0.017),and significantly higher in the early stage(0-6mo)in the virus-group than in the control group(P=0.000).CONCLUSION:CMV reduces the graft survival rate and exerts persistent detrimental effects on the ECD after keratoplasty.The graft ECD loss associate with CMV infection mainly occurrs in the middle stage(6-12mo postoperatively),while ocular comorbidities mainly affects ECD in the early stage(0-6mo postoperatively).

Coexisting cytomegalovirus colitis in an immunocompetent patient with Clostridioides difficile colitis:A case report

BACKGROUND Clostridioides difficile(C.difficile)colitis is one of the most common infections in hospitalized patients,characterized by fever and diarrhea.It usually improves after appropriate antibiotic treatment;if not,comorbidities should be considered.Cytomegalovirus(CMV)colitis is a possible co-existing diagnosis in patients with C.difficile infection with poor treatment response.However,compared with immunocompromised patients,CMV colitis in immunocompetent patients is not well studied.CASE SUMMARY We present an unusual case of co-existing CMV colitis in an immunocompetent patient with C.difficile infection.An 80-year-old female patient was referred to the infectious disease department due to diarrhea,abdominal discomfort,and fever for 1 wk during her hospitalization for surgery.C.difficile toxin B polymerase chain reaction on stool samples was positive.After C.difficile infection was diagnosed,oral vancomycin treatment was administered.Her symptoms including diarrhea,fever and abdominal discomfort improved for ten days.Unfortunately,the symptoms worsened again with bloody diarrhea and fever.Therefore,a sigmoidoscopy was performed for evaluation,showing a longitudinal ulcer on the sigmoid colon.Endoscopic biopsy confirmed CMV colitis,and the clinical symptoms improved after using ganciclovir.CONCLUSION Co-existing CMV colitis should be considered in patients with aggravated C.difficile infection on appropriate treatment,even in immunocompetent hosts.

Invasive aspergillosis in liver transplant recipients, an infectious complication with low incidence but significant mortality

BACKGROUND Infections,including invasive fungal infections(IFIs),are among the leading causes of mortality in liver transplant recipients during the first year posttransplantation.AIM To investigate the epidemiology,clinical manifestations,risk factors,treatment outcomes,and mortality rate of post-liver transplantation invasive aspergillosis(IA).METHODS In this case-control study,22 patients with IA were identified by reviewing the archived and electronic medical records of 850 patients who received liver transplants at the Imam Khomeini Hospital complex in Tehran,Iran,between 2014 and 2019.The control group comprised 38 patients without IA infection matched for age and sex.The information obtained included the baseline characteristics of liver transplant patients,operative reports,post-transplantation characteristics of both groups and information about the fungal infection of the patient group.RESULTS The prevalence rate of IA among liver transplant recipients at Imam Khomeini Hospital was 2.7%.The risk factors of IA among studied patients included high serum creatinine levels before and post-transplant,renal replacement therapy,antithymocyte globulin induction therapy,post-transplant bile leakage,posttransplant hepatic artery thrombosis,repeated surgery within 30 d after the transplant,bacterial pneumonia before the aspergillosis diagnosis,receiving systemic antibiotics before the aspergillus infection,cytomegalovirus infection,and duration of post-transplant hospitalization in the intensive care unit.The most prevalent form of infection was invasive pulmonary aspergillosis,and the most common chest computed tomography scan findings were nodules,pleural effusion,and the halo sign.In the case group,prophylactic antifungal therapy was administered more frequently than in the control group.The antifungal therapy response rate at 12 wk was 63.7%.The 3-and 12-mo mortality rates of the patients with IA were 36.4%and 45.4%,respectively(compared with the mortality rate of the control group in 12 mo,which was zero).CONCLUSION In this study,the prevalence of IA among liver transplant recipients was relatively low.However,it was one of the leading causes of mortality following liver transplantation.Targeted antifungal therapy may be a factor in the low incidence of infections at our facility.Identifying the risk factors of IFIs,maintaining an elevated level of clinical suspicion,and initiating early antifungal treatment may significantly improve the prognosis and reduce the mortality rate of liver transplant recipients.

Pulmonary cytomegalovirus infection:A case report and systematic review

BACKGROUND Cytomegalovirus(CMV)is a common virus that can cause the first infection in childhood or adolescence and reactivate later in life due to immunosuppression.CMV pneumonia is a rare illness in immunocompetent patients but is one of the most significant opportunistic infections in immunocompromised patients.AIM To report a case and review published cases of pulmonary CMV infection in both immunocompromised and immunocompetent patients.METHODS We conducted a systematic search on the MEDLINE(PubMed)database,without date or language restrictions,to identify relevant studies using Medical Subject Headings and Health Science Descriptors.We manually searched the reference lists of the included studies.Simple descriptive analysis was used to summarize the results.RESULTS Our search identified 445 references,and after screening,43 studies reporting 45 cases were included in the final analysis,with 29(64%)patients being immunocompromised and 16(36%)being immunocompetent.Fever(82%)and dyspnea(75%)were the most common clinical findings.Thoracic computed tomography showed bilateral ground-glass opacities,a relevant differential diagnosis for severe acute respiratory syndrome coronavirus 2 infection.The majority of patients(85%)received antiviral therapy,and 89%of patients recovered,while 9%of patients died.CONCLUSION CMV pneumonia should be considered as a differential diagnosis for coronavirus disease 2019 pneumonia,especially in immunocompromised patients.Clinicians should be aware of the clinical presentation,management,and outcomes of CMV pneumonia to guide appropriate treatment decisions.

Viruses and autism: A Bi-mutual cause and effect

Autism spectrum disorder(ASD)is a group of heterogeneous,multi-factorial,neurodevelopmental disorders resulting from genetic and environmental factors interplay.Infection is a significant trigger of autism,especially during the critical developmental period.There is a strong interplay between the viral infection as a trigger and a result of ASD.We aim to highlight the mutual relationship between autism and viruses.We performed a thorough literature review and included 158 research in this review.Most of the literature agreed on the possible effects of the viral infection during the critical period of development on the risk of developing autism,especially for specific viral infections such as Rubella,Cytomegalovirus,Herpes Simplex virus,Varicella Zoster Virus,Influenza virus,Zika virus,and severe acute respiratory syndrome coronavirus 2.Viral infection directly infects the brain,triggers immune activation,induces epigenetic changes,and raises the risks of having a child with autism.At the same time,there is some evidence of increased risk of infection,including viral infections in children with autism,due to lots of factors.There is an increased risk of developing autism with a specific viral infection during the early developmental period and an increased risk of viral infections in children with autism.In addition,children with autism are at increased risk of infection,including viruses.Every effort should be made to prevent maternal and early-life infections and reduce the risk of autism.Immune modulation of children with autism should be considered to reduce the risk of infection.

猪巨细胞病毒病

猪巨细胞病毒(Porcine Cytomegalovirus,PC-MV)是由疱疹病毒科β疱疹病毒亚科巨细胞病毒属的一种[1]。该病毒遍布全球[2],猪感染该病也是普遍存在,在北美、欧洲和日本,90%以上的猪群曾受到感染。对成年猪只通常只呈现隐性感染,而对3周齡以下仔猪常常诱发致命性的全身感染[3]。

人巨细胞病毒先天性感染胎鼠大脑皮质钙调素基因mRNA表达的研究

目的研究先天性人巨细胞病毒(HCMV)感染致脑损害后钙调素(calmodulin,CaM)基因 mRNA 表达的改变,以探讨先天性 HCMV 感染所致脑损害的机制。方法选用10周龄Balb/c 小鼠,雌雄小鼠腹腔内分别注射1.0ml、0.5ml、0.25ml HCMV 后合笼交配以建立先天性HCMV 中枢神经系统(CNS)感染小鼠模型,对照鼠腹腔注射1.0ml RPMI 1640液。剖腹取21天胎龄小鼠大脑皮质,以自行设计的 CaM cDNA 编码区的一对引物与一条 CaM 特异性探针,分别用逆转录聚合酶链反应(RT-PCR)技术检测 CaM mRNA 相对含量、用原位杂交检测大脑皮质细胞内相应 mRNA 的表达及定位。结果母鼠腹腔内接种 HCMV 量为1.0ml 与0.5ml 的临产胎鼠大脑皮质分离出相应病毒,病理学检查等确认发现了侵袭性脑膜脑炎性病理改变,证实HCMV 可经小鼠宫内传播至胎鼠 CNS。1.0ml 组与0.5ml 组胎鼠 RT-PCR 产物浓度明显高于0.25ml 组及对照组,而1.0ml 组与0.5ml 组间亦有明显差异。电泳结果显示对照组与0.25ml 组胎鼠未见阳性条带,而1.0ml 组胎鼠特异性条带信号强于0.5ml 胎鼠,仅略低于同组母鼠。原位杂交显示 CaM mRNA 不但出现在1.0ml 组胎鼠大脑皮质大神经元胞核及胞浆内,在中小神经元及胶质细胞的胞核及胞浆亦有高密度表达,阳性细胞的突起中亦有弱信号存在。结论提示先天性感染 HCMV 胎鼠大脑皮质内 CaM mRNA 表达量明显增加,且神经元及胶质细胞均有表达,并与感染剂量有依赖关系。提示 CaM mRNA 表达增高可能直接参与了 HCMV 先天性感染脑损害的过程。

更昔洛韦治疗小儿巨细胞病毒肝炎疗效观察

目的：观察更昔洛韦治疗小儿巨细胞病毒肝炎(CMV肝炎)的疗效。方法：将巨细胞病毒肝炎患儿34例分为更昔洛韦治疗组19例及病毒唑对照组15例进行比较。结果：治疗组和对照组血CMV—IgM或尿CMV—DNA转阴率分别为89．47％和40％，P<0．005；总有效率分别为84．21％和26．67％，P<0．005；且治疗组血清胆红素(SB)及谷丙转氨酶(ALT)恢复正常时间均较对照组缩短。两组治疗过程中均未见明显毒副作用。结论：更昔洛韦治疗小儿CMV肝炎疗效肯定，值得临床推广。

在肝的感染移植接受者

Liver transplantation is a standard life-saving procedure for the treatment of many end-stage liver diseases. The success of this procedure may be limited by infectious complications.In this article,we review the contemporary state of infectious complications during the post-operative period,with particular emphasis on those that occur most commonly during the first 6 mo after liver transplantation.Bacteria,and less commonly Candida infections,remain the predominant pathogens during the immediate post-operative period,especially during the first month,and infections caused by drugresistant strains are emerging.Infections caused by cytomegalovirus and Aspergillus sp.present clinically during the'opportunistic'period characterized by intense immunosuppression.As newer potent immunosuppressive therapies with the major aim of reducing allograft rejection are developed,one potential adverse effect is an increase in certain infections.Hence,it is essential for liver transplant centers to have an effective approach to prevention that is based on predicted infection risk,local antimicrobial resistance patterns,and surveillance.A better understanding of the common and most important infectious complications is anticipated to lead to improvements in quality of life and survival of liver transplant recipients.

Cytomegalovirus and ulcerative colitis:Place of antiviraltherapy

The link between cytomegalovirus(CMV) infection and inflammatory bowel diseases remains an important subject of debate. CMV infection is frequent in ulcerative colitis(UC) and has been shown to be potentially harmful. CMV reactivation needs to be diagnosed using methods that include in situ detection of viral markers by immunohistochemistry or by nucleic acid amplification techniques. Determination of the density of infection using quantitative tools(numbers of infected cells or copies of the genome) is particularly important. Although CMV reactivation can be considered as an innocent bystander in active flareups of refractory UC, an increasing number of studies suggest a deleterious role of CMV in this situation. The presence of colonic CMV infection is possibly linked to a decreased response to steroids and other immunosuppressive agents. Some treatments, notably steroids and cyclosporine A, have been shown to favor CMV reactivation, which seems not to be the case for therapies using anti-tumor necrosis factor drugs. According to these findings, in flare-ups of refractory UC, it is now recommended to look for the presence of CMV reactivation by using quantitative tools in colonic biopsies and to treat them with ganciclovir in cases of high viral load or severe disease.

Specific endoscopic features of ulcerative colitis complicated by cytomegalovirus infection

AIM:To identify specific colonoscopic findings in patients with ulcerative colitis (UC) complicated by cyto-megalovirus (CMV) infection.METHODS: Among UC patients who were hospitalized due to exacerbation of symptoms, colonoscopic findings were compared between 15 CMV-positive patients and 58 CMV-negative patients. CMV infection was determined by blood test for CMV antigenemia. Five aspects of mucosal changes were analyzed (loss of vascular pattern, erythema, mucosal edema, easy bleeding, and mucinous exudates) as well as five aspects of ulcerative change (wide mucosal defect, punched-out ulceration, longitudinal ulceration, irregular ulceration, and cobble-stone-like appearance). Sensitivity, specificity, positive predictive value, and negative predictive value of each finding for CMV positivity were determined.RESULTS: The sensitivity of irregular ulceration for positive CMV was 100%. The specificity of wide mucosal defect was 95%. Punched-out ulceration and lon-gitudinal ulceration exhibited relatively high sensitivity and specificity (more than 70% for each).CONCLUSION:Specific colonoscopic findings in patients with UC complicated by CMV infection were identified. These findings may facilitate the early diagnosis of CMV infection in UC patients.

Management of cytomegalovirus infection and disease in liver transplant recipients

Cytomegalovirus(CMV) is one of the most common viral pathogens causing clinical disease in liver transplant recipients, and contributing to substantial morbidity and occasional mortality. CMV causes febrile illness often accompanied by bone marrow suppression, and in some cases, invades tissues including the transplanted liver allograft. In addition, CMV has been significantly associated with an increased predisposition to acute and chronic allograft rejection, accelerated hepatitis C recurrence, and other opportunistic infections, as well as reduced overall patient and allograft survival. To negate the adverse effects of CMV infection on transplant outcome, its prevention, whether through antiviral prophylaxis or preemptive therapy, is an essential component to the management of liver transplant recipients. Two recently updated guidelines have suggested that antiviral prophylaxis or preemptive therapy are similarly effective in preventing CMV disease in modest-risk CMV-seropositive liver transplant recipients, while antiviral prophylaxis is the preferredstrategy over preemptive therapy for the prevention of CMV disease in high-risk recipients [CMV-seronegative recipients of liver allografts from CMV-seropositive donors(D+/R-)]. However, antiviral prophylaxis has only delayed the onset of CMV disease in many CMV D+/Rliver transplant recipients, and such occurrence of lateonset CMV disease was significantly associated with increased all-cause and infection-related mortality after liver transplantation. Therefore, a search for better strategies for prevention, such as prolonged duration of antiviral prophylaxis, a hybrid approach(antiviral prophylaxis followed by preemptive therapy), or the use of immunologic measures to guide antiviral prophylaxis has been suggested to prevent late-onset CMV disease. The standard treatment of CMV disease consists of intravenous ganciclovir or oral valganciclovir, and if feasible, reduction in pharmacologic immunosuppression. In one clinical trial, oral valganciclovir was as effective as intravenous ganciclovir for the treatment of mild to moderate CMV disease in solid organ(including liver) transplant recipients. The aim of this article is to provide a state-of-the art review of the epidemiology, diagnosis, prevention, and treatment of CMV infection and disease after liver transplantation.

Design,delivery and efficacy testing of therapeutic nucleic acids used to inhibit hepatitis C virus gene expression in vitro and in vivo

Despite major achievements in the treatment ofchronic hepatitis C with the combination ofinterferons and the nucleoside analog ribavirin themajority of patients with chronic hepatitis C virus(HCV) infection cannot be treated effectively.Toimprove this response rate we used antisensetechnologies to inhibit HCV translation as possibleadditional option for experimental treatment.Antisense oligodeoxynucleotides(ODN) are

IL28B polymorphism and cytomegalovirus predict response to treatment in Egyptian HCV type 4 patients

AIM:To test whether the status of positive cytomegalovirus(CMV) DNA detection adds to the predictive value of IL28B and to further categorize C/T allele carriers.METHODS:This study included 166 chronic hepatitis C(CHC) patients who received combined interferon and ribavirin therapy for 48 wk,84 spontaneous hepatitis C virus(HCV) resolvers who were positive for IgG anti-HCV antibody and negative for HCV RNA,and 100 healthy subjects who were negative for both HCV antibodies and RNA as controls.Genomic DNA from peripheral blood was used for IL28B rs.12979860 single nucleotide polymorphism(SNP) and CMV DNA detection.A 139 bp fragment containing IL28B SNP was amplified in all subjects by polymerase chain reaction using a specifically designed primer.Then the IL28B rs.12979860 SNP was detected by restriction fragment length polymorphism(RFLP) genotyping.The presence of CMV DNA was tested by amplification of the gB1 gene using nested polymerase chain reaction.The role of CMV and IL28B rs.12979860 SNP genotypes in determining the response rate to combined interferon therapy and clinical status of patients were statistically analyzed.RESULTS:Current data showed that 67% of patients carrying the IL28B 12979860 C/C allele had a sustained viral response(SVR) while the genotypes C/T and TT were associated with lower SVR rates,50% and 48%,respectively.SVR rates for the C/C allele were lower than other HCV genotypes and/or other populations.Genotype CC was associated with the response to interferon(P = 0.025).Genotype C/C was reduced from 48% in controls to 14% in CHC patients suggesting its protective role against progression to chronicity.The majority of spontaneously cleared subjects(86%) were C/C,confirming its protective role.The C/T allele was present in 71% of CHC patients compared with 38% of controls,so the use of IL28B SNP genotyping only in these patients may be of little value as a predictor of response.CMV reactivation occurred in 40% of CHC patients.Co-infection with CMV seriously diminished the response to interferon(IFN) therapy,with SVR rates in C/C genotypes 87.5% in CMV-negative patients and 12.5% in CMV-positive patients(P < 0.0001).SVR rates among C/T carriers were reduced to < 50% in patients with positive CMV DNA while the non-response rate doubled.These data indicate that a supplemental assay for CMV viremia adds to the prognostic value of IL28B genotyping.CONCLUSION:The results suggest that both genetic(i.e.,spontaneous) and therapeutic(IFN-based therapy) arms are complementary in the battle against HCV.CMV DNA testing may be of value to better predict the response to IFN,particularly in IL28B C/T carriers.

Comparison of intravitreal ganciclovir monotherapy and combination with foscarnet as initial therapy for cytomegalovirus retinitis

AIM：To compare the effectiveness between multiple intravitreal injections of ganciclovir alone and combined with foscarnet as initial treatment for patients with newlyonset cytomegalovirus retinitis （CMVR）.METHODS：The retrospective study observed 37 patients（58 eyes） who suffered from CMVR onset between 2013 and 2015. Among them, 35 eyes underwent 4 weekly intravitreal injections of 3.0 mg ganciclovir, and 23 eyes underwent 4 weekly injections of 3.0 mg ganciclovir combined with 2.4 mg foscarnet. Visual acuity, intraocular pressure and viral load of cytomegalovirus （CMV） in aqueous humor measured by real-time polymerase chain reaction were compared before and after each injection.RESULTS：CMV-DNA copies in aqueous humor decreased remarkably in both groups. The average of CMV-DNA copies in patients’ aqueous decreased from 38.3×10~4 copies/mL at baseline to 2.2×10~4 copies/mL after the 4^（th） injection in patients who were treated with ganciclovir monotherapy,and decreased from 76.9×10~4 copies/mL to 11.3×10~4 copies/mL after 4 continuous injections of ganciclovir combined with foscarnet. No significant difference was found in reduction of viral load, change of visual acuities or intraocular pressures between monotherapy or combined therapy.CONCLUSION：Results of this study show that the initial effectiveness of treating CMVR after 4 weekly intravitreal injections is not significantly different from ganciclovir alone or combined with foscarnet. Continuous injection of ganciclovir alone is sufficient in treating immunosuppressive patients with newly-onset CMVR.

Cytomegalovirus in inflammatory bowel disease： Asystematic review

AIM: To identify definitions of cytomegalovirus(CMV) infection and intestinal disease, in inflammatory bowel disease(IBD), to determine the prevalence associated with these definitions.METHODS: We conducted a systematic review and interrogated Pub Med, EMBASE and Cochrane for literature on prevalence and diagnostics of CMV infection and intestinal disease in IBD patients. As medical headings we used "cytomegalovirus" OR "CMV" OR "cytomegalo virus" AND "inflammatory bowel disease" OR "IBD" OR "ulcerative colitis" OR "colitis ulcerosa" OR "Crohn's disease". Both Me SH-terms and free searches were performed. We included all types of English-language(clinical) trials concerning diagnostics and prevalence of CMV in IBD.RESULTS: The search strategy identified 924 citations, and 52 articles were eligible for inclusion. We identified 21 different definitions for CMV infection, 8 definitions for CMV intestinal disease and 3 definitions for CMV reactivation. Prevalence numbers depend on used definition, studied population and region. The highest prevalence for CMV infection was found when using positive serum PCR as a definition, whereas for CMV intestinal disease this applies to the use of tissue PCR > 10 copies/mg tissue. Most patients with CMV infection and intestinal disease had steroid refractory disease and came from East Asia.CONCLUSION: We detected multiple different definitions used for CMV infection and intestinal disease in IBD patients, which has an effect on prevalence numbers and eventually on outcome in different trials.