Ultrasound features of congenital cytomegalovirus infection in the first trimester:A case report

BACKGROUND Congenital cytomegalovirus(CMV)infection represents a significant public health concern as the most prevalent viral infection in newborns,potentially leading to severe neurological and developmental complications.The majority of cases are asymptomatic and remain undetected during pregnancy due to the absence of effective screening methods.CASE SUMMARY A 27-year-old primigravida presented for early pregnancy ultrasound,which revealed an atypical finding:A normal anechoic thalamus appearing hyperechoic on the mid-sagittal view of the fetal head.Subsequent ultrasound examinations during mid and late gestation demonstrated classic intracranial features sug-gestive of congenital CMV infection.Chromosomal karyotyping and microarray analysis of the fetus yielded no significant abnormalities.Following compre-hensive prenatal counseling regarding potential adverse fetal outcomes,the patient elected to continue her pregnancy.She ultimately underwent cesarean delivery at 42 weeks gestation at another facility,resulting in the birth of a female neonate.At five months of age,the infant presented with epilepsy and significant growth and developmental delays.CONCLUSION Congenital CMV infection occurs during the first trimester may manifest as hyperechoic thalamus which can be revealed by ultrasound in the mid-saggital view of the fetal head.Future research should investigate the correlation between echogenic thalamus and developmental outcomes,as well as explore early sc-reening techniques for suspected congenital CMV infection cases.

Septic shock due to cytomegalovirus colitis associated with rituximab use:A case report

BACKGROUND Cytomegalovirus(CMV)infections can cause significant morbidity and mortality in immunocompromised individuals.CMV targets dysfunctional lymphocytes.Chronic rituximab(RTX)therapy can cause B-lymphocyte dysfunction,increasing CMV risk.Rarely,CMV infections present with critical illness such as septic shock.CASE SUMMARY A 64-year-old African American woman presented with generalized weakness and non-bloody watery diarrhea of 4-6 weeks duration.She did not have nausea,vomiting or,abdominal pain.She had been on monthly RTX infusions for neuromyelitis optica.She was admitted for septic shock due to pancolitis.Blood investigations suggested pancytopenia and serology detected significantly elevated CMV DNA.Valganciclovir treatment led to disease resolution.CONCLUSION This case illustrates an extremely rare case of CMV colitis associated with RTX use presenting with septic shock.High suspicion for rare opportunistic infections is imperative in individuals with long-term RTX use.

DETECTION OF CYTOMEGALOVIRUS(CMV) IMMEDIATE EARLY ANTIGEN IN KIDNEY BIOPSIES AND TRANSPLANT NEPHRECTOMIES

Objective To investigate the relationship between CMV infection and renal allograft rejection. Methods 39 kidney biopsies and transplant nephrectomies were collected and investigated for CMV immediate early antigen by immunohistochemistry. Results In 14 out of 39 tissue specimens CMV immediate early antigen were found. 8 biopsies from normal donor kidneys were negative; only 1 (10%) in 10 tissue specimens with early stage acute rejection was positive; 5(55.6%) in 9 biopsies with late stage acute rejection and 8 (66.7%) in 12 tissue blocks with chronic rejection were positive. Compared with normal kidney tissues, the infections in tissues with early stage acute rejection didn't increase obviously, but increased obviously in kidney tissue specimens with late stage rejection and with chronic rejection (P< 0.05). Conclusion CMV infection appears to contribute to late stage acute rejection and chronic rejection after renal transplantation.

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.

Mycobacterium avium Paratuberculosis (MAP) and Cytomegalovirus (CMV) Are Frequently Detected in the Saliva of Patients Recently Diagnosed with Crohn Disease (CD) Whereas Oral Propionibacterium Acnes (PA) or Methylacetate (MA) in Their Breath Is Rare

We investigated the presence of MAP, CMV, or Epstein-Barr virus (EBV) in the saliva of patients presenting with periodontal disease, gingivitis or oral aphthosis. We also measured methylacetate in their breath and looked for the presence of PA on their tongue. All patients were prospectively enrolled into a two-year cohort study. We compared the group presenting with CD versus the group without CD. 167 patients were enrolled. 24 patients presented with CD. CMV and MAP were found concomitantly in 67% of CD patients (17 patients) whereas only 1 patient (<0.1%;p < 0.001) has these infectious agents in the comparative group. PA was rare in CD (25% versus 70.6%;p < 0.001). MA was low, especially with an empty stomach (0.59 ppm +/? 1.45 versus 5.14 ppm +/? 8.97;p < 0.001). It was concluded that the association MAP + CMV was frequently found in oral lesions of CD at an early stage. Detection of PA, MAP and CMV, as well as breath test could be easily performed and may participate to the early diagnosis of CD.

Human Herpes Virus Type 2 ( HSV2 ), Human Cytomegalovirus (HCMV) in the Male Genital Tract and Fertilization

The possibility of infection of the human male genital tract by human herpes virus type 2 (HSV2) or human cytomegalovirus (HCMV) is well established and their sexual transmission has been the object of many studies. Moreover, medically assisted procreation, which helps in numerous fertility problems, raises the question of new viral risks linked to the application of these new technologies. In this review, we shall consider current knowledge in terms of the presence of HSV 2 and HCMV in the different parts of the genital tract of immunocompetent or immunodepressed men. We shall also consider the possibility of viral transmission by the sexual act or by the various techniques used in medically assisted procreation. We shall describe studies in human beings and in animals.

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.

Comparative analysis of cytomegalovirus retinitis and microvascular retinopathy in patients with acquired immunodeficiency syndrome

AIM：To compare the clinical manifestation of cytomegalovirus（CMV）retinitis and microvascular retinopathy（MVR）in patients with acquired immunodeficiency syndrome（AIDS）in China.METHODS：A total of 93 consecutive patients with AIDS,including 41 cases of CMV retinitis and 52 cases of MVR were retrospectively reviewed.Highly active antiretroviral therapy（HAART）status was recorded.HIV and CMV immunoassay were also tested.CD4＋T-lymphocyte count and blood CMV-DNA test were performed in all patients.Aqueous humor CMV-DNA test was completed in 39patients.Ophthalmological examinations including best corrected visual acuity（BCVA,by International Standard Vision Chart）,intraocular pressure（IOP）,slit-lamp biomicroscopy,indirect ophthalmoscopy were performed.RESULTS：In MVR group,the anterior segment examination was normal in all patients with a mean BCVA of 0.93±0.13.Blood CMV-DNA was 0（0,269 000）and 42 patients（80.77%）did not receive HAART.In CMV retinitis group,13 patients（31.71%）had anterior segment abnormality.The mean BCVA was 0.64±0.35 and blood CMV-DNA was 3470（0,1 450 000）.Nineteen patients（46.34%）had not received HAART.MVR group and CMV retinitis group the positive rates of aqueous CMV-DNA were 0 and 50%,respectively.Two patients with MVR progressed to CMV retinitis during the follow-up period.CONCLUSION：In comparison of CMV,patients with MVR have relatively mild visual function impairment.Careful ophthalmological examination and close follow-up are mandatory,especially for patients who have systemic complications,positive CMV-DNA test and without received HAART.

Long-term follow-up of ulcerative colitis patients treated on the basis of their cytomegalovirus antigen status

AIM:To clarify the impact of cytomegalovirus(CMV)activation and antiviral therapy based on CMV antigen status on the long-term clinical course of ulcerative colitis(UC)patients.METHODS:UC patients with flare-up were divided into CMV-positive and-negative groups according to the CMV antigenemia assay.The main treatment strategy provided for the patients in the CMV-positive group comprised a dose reduction of corticosteroids and administration of ganciclovir.RESULTS:The median number of days to initial remission was significantly greater for the patients in the CMV-positive group(21 d vs 16 d,P=0.009).However,the relapse rate after remission and colectomy rate during more than 30 mo of observation did not differ between the two groups.Multivariate analysis revealed that administration of ganciclovir was the only independent factor for avoiding colectomy in patients of the CMV-positive group.CONCLUSION:CMV antigen status did not significantly affect the long-term prognosis in UC patients under treatment with appropriate antiviral therapy.

Cytomegalovirus infection in liver transplant recipients: Updates on clinical management

Cytomegalovirus(CMV) infection is a common complication after liver transplantation, and it is associated with multiple direct and indirect effects. Management of CMV infection and disease has evolved over the years,and clinical guidelines have been recently updated.Universal antiviral prophylaxis and a pre-emptive treatment strategy are options for prevention. A currentlyrecruiting randomized clinical trial is comparing the efficacy and safety of the two prevention strategies in the highest risk D+R- liver recipients. Drug-resistant CMV infection remains uncommon but is now increasing in incidence. This highlights the currently limited therapeutic options, and the need for novel drug discoveries.Immunotherapy and antiviral drugs with novel mechanisms of action are being investigated, including letermovir(AIC246) and brincidofovir(CMX001). This article reviews the current state of CMV management after liver transplantation, including the updated practice guidelines, and summarizes the data on investigational drugs and vaccines in clinical development.

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 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.

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.

Two strategies for prevention of cytomegalovirus infections after liver transplantation

AIM: To analyze differences in patients' clinical course, we compared two regimes of either preemptive therapy or prophylaxis after liver transplantation.METHODS: This retrospective study was reviewed and approved by the institutional review board of the University of Leipzig. Cytomegalovirus(CMV) prophylaxis with valganciclovir hydrochloride for liver transplant recipients was replaced by a preemptive strategy in October 2009. We retrospectively compared liver transplant recipients 2 years before and after October 2009. During the first period, all patients received valganciclovir daily. During the second period all patients included in the analysis were treated following a preemptive strategy. Outcomes included one year survival and therapeutic intervention due to CMV viremia or infection.RESULTS: Between 2007 and 2010 n = 226 patients underwent liver transplantation in our center. n = 55 patients were D^+/R^- high risk recipients and were excluded from further analysis. A further 43 patients had to be excluded since CMV prophylaxis/preemptive strategy was not followed although there was no clinical reason for the deviation. Of the remaining 128 patients whose data were analyzed, 60 receivedprophylaxis and 68 were treated following a preemptive strategy. The difference in overall mortality was not significant, nor was it significant for one-year mortality where it was 10%(95%CI: 8%-28%, P = 0.31) higher for the preemptive group. No significant differences in blood count abnormalities or the incidence of sepsis and infections were observed other than CMV. In total, 19 patients(14.7%) received ganciclovir due to CMV viremia and/or infections. Patients who were treated according to the preemptive algorithm had a significantly higher rate risk of therapeutic intervention with ganciclovir [n = 16(23.5%) vs n = 3(4.9%), P = 0.003)].CONCLUSION: These data suggest that CMV prophylaxis is superior to a preemptive strategy in patients undergoing liver transplantation.

Characteristic endoscopic findings and risk factors for cytomegalovirus-associated colitis in patients with active ulcerative colitis

AIM: To identify characteristic endoscopic findings and risk factors for cytomegalovirus(CMV)-associated colitis in patients with active ulcerative colitis(UC).METHODS: A total of 149 UC patients admitted to the Department of Gastroenterology, Nagoya University Hospital, from January 2004 to December 2013 with exacerbation of UC symptoms were enrolled in this retrospective study. All medical records, including colonoscopy results, were reviewed. CMV infection was determined by the presence of CMV antigen, CMV inclusion bodies in biopsy specimens, or positive specific immunohistochemical staining for CMV. Multivariate analysis was used to identify independent risk factors for CMV colitis.RESULTS: Multivariate analysis indicated independent associations with the extent of disease(pancolitis) anduse of > 400 mg corticosteroids for the previous 4 wk. In contrast, no association was seen with sex, age at UC diagnosis, immunomodulator use, or infliximab use. Punched-out ulceration was also significantly associated with CMV infection in patients with active UC(odds ratio = 12.672, 95%CI: 4.210-38.143).CONCLUSION: Identification of a total corticosteroid dose > 400 mg for 4 wk, extensive colitis and a specific endoscopic finding of punched-out ulcer might facilitate the more rapid diagnosis and timely initiation of antiviral therapy for CMV-associated colitis in patients with active UC.

Cytomegalovirus positive ulcerative colitis:A single center experience and literature review

AIM:To compare the clinical outcome of cytomegalovirus(CMV)-positive ulcerative colitis(UC) patients with and without antiviral therapy.METHODS:This was a retrospective case-controlled study.The database of UC patients in our institution was scanned for documented presence of CMV on colonic biopsies.Demographics,clinical data,endoscopy findings and pathology reports were extracted from the patients' charts and electronic records.When available,the data from colonoscopies preceding and following the diagnosis of colonic CMV infection were also ex-tracted.The primary outcomes of the study were colectomy/death during hospitalization and the secondary outcomes were colectomy/death through the course of the follow-up.RESULTS:Thirteen patients were included in the study,7(53.5%) of them were treated with gancyclovir and 6(46.5%) were not.Patients treated with antivirals presented with a more severe disease and 57% of them were treated with cyclosporine or infliximab before initiation of gancyclovir,while none of the patients without antivirals required rescue therapy.One patient died and another patient underwent urgent colectomy during hospitalization,both of them from the gancyclovir-treatment group.For the entire follow-up time(13 ± 13 mo),a total of 3 colectomies and one death occurred,all among the antiviral-treated patients(for colectomy:3/7 vs 0/6 patients,P = 0.19;for combined adverse outcome:4/7 vs 0/6 patients,P = 0.07).In 9/13 patients,immunohistochemistry for CMV was performed on biopsies obtained during a subsequent colonoscopy and was positive in one patient only.CONCLUSION:Gancyclovir-treated patients had a more severe disease and outcome,probably unrelated to antiviral therapy.Immunohistochemistry-CMV-positive patients with mild disease may recover without antiviral therapy.

Current concepts on cytomegalovirus infection after liver transplantation

Cytomegalovirus (CMV) is the most common viral pa- thogen that negatively impacts on the outcome of liver transplantation. CMV cause febrile illness often ac com panied by bone marrow suppression, and in some cases, invades tissues including the transplanted allog raft. In addition, CMV has been signif icantly asso- ciated with an increased predisposition to allograft re- jection, accelerated hepatitis C recurrence, and other opportunistic infections, as well as reduced overall pa tient and allograft survival. To negate the adverse effects of CMV on outcome, its prevention, whether through antiviral prophylaxis or preemptive therapy, is regarded as an essential component to the medical management of liver transplant patients. Two recent guidelines have suggested that antiviral prophylaxis or preemptive therapy are similarly effective in preventing CMV disease in modest-risk CMV-seropositive liver trans plant recipients, while antiviral prophylaxis is the preferred strategy over preemptive therapy for the preven tion of CMV disease in high-risk recipients [CMV-ser o-negative recipients of liver allografts from CMV-seropositive donors (D+/R-)]. However, antiviral prophylax is has only delayed the onset of CMV disease in many CMV D+/R- liver transplant recipients, and at least in one study, such occurrence of late-onset primary CMV disease was significantly associated with increased mortality after liver transplantation. Therefore, optimized strategies for prevention are needed, and aggressive treatment of CMV infection and disease should be pursued. The standard treatment of CMV disease consists of intravenous ganciclovir or oral valganciclovir, and if fea sible, one should also reduce the degree of immuno-suppression. In one recent controlled clinical trial, val ganc iclovir was found to be as effective and safe as intravenous ganciclovir for the treatment of mild to mo d erate CMV disease in solid organ (including liver) tran splant recipients. In this article, the authors review the current state and the future perspectives of prev ention and treatment of CMV disease after liver trans plantation.

Cholestasis, ascites and pancytopenia in an immunocompetent adult with severe cytomegalovirus hepatitis

Human cytomegalovirus(CMV) is a herpesvirus,which establishes lifelong latency after primary infection and leads to severe disease in immunocompromised patients. However,CMV infection in immunocompetent patients is usually asymptomatic and severe organ damage is rarely reported. We report a case of severe CMV hepatitis in an immunocompetent patient presenting with cholestasis,portal hypertensionrelated ascites and pancytopenia. The patient was asymptomatic with normal liver function and negative CMV DNA after two weeks of antiviral therapy. This case is an example of a common infection with an uncommon presentation,and suggests that testing for CMV should be carried out,even in patients with normal immune status,presenting with severe liver damage or cholestasis.

Antiviral therapy in cytomegalovirus-positive ulcerative colitis:A systematic review and meta-analysis

AIM: To evaluate the impact of antiviral treatment on cytomegalovirus (CMV)-positive ulcerative colitis patients.