Positive Cytomegalovirus Polymerase Chain Reaction Research Articles

Results of Routine Antenatal Screening for Cytomegalovirus at a Tertiary Center.

Cytomegalovirus (CMV) is the most common viral infection. In this study, we discussed the results of pregnant women who underwent antenatal CMV screening in a tertiary center and the value of CMV antenatal screening. For this retrospective study, the data of pregnant patients with antenatal CMV screening test results between 2019 and 2022 were obtained from hospital records. CMV immunoglobulin M (IgM), CMV IgG, anti-IgG avidity test results, amniocentesis, CMV polymerase chain reaction (PCR), and the outcome of the babies were recorded. A total of 31,912 CMV IgM and 26,969 CMV IgG tests were performed. CMV IgG seropositivity was observed in 78.99% of pregnant women, and 0.09% of the pregnant women were confirmed to have a positive CMV IgM test result. Pregnant women with positive IgM accompanying low avidity were referred to perinatology clinics for detailed ultrasonography and amniocentesis. Only 3 of the 44 pregnant women who underwent amniocentesis were confirmed to have positive CMV PCR testing. CMV screening should be preserved for pregnant women with ultrasonographic findings at high risk of congenital CMV infection.

Colonic cytomegalovirus DNA detection by polymerase chain reaction does not influence outcomes in inflammatory bowel disease and immunosuppressed cohorts.

Cytomegalovirus (CMV) colitis is associated with negative outcomes in inflammatory bowel disease (IBD) and immunosuppressed cohorts and therefore requires timely recognition for appropriate management. We aimed to evaluate the diagnostic tools for CMV colitis and their associations with clinical outcomes. A retrospective cohort study of patients in a metropolitan health service with colonic samples analysed for CMV between 2012 and 2022, stratified into IBD and non-IBD groups, was performed. The main outcome measures were the prevalence of positive and negative results for each CMV test, as well as need for colectomy, use of antiviral and hospital length of stay. Five hundred eighty-two biopsies from 418 patients were included; the median age was 36 years (interquartile range, 24-52 years) and 223 (53.3%) were men. Four hundred sixty-one (79.2%) biopsies were from patients with IBD and 121 (20.8%) were from those without IBD. There were similar proportions of positive CMV histology (IBD 5.9% and non-IBD 7.4%) and tissue CMV polymerase chain reaction (PCR) in the two groups (IBD 5.6% and non-IBD 5.0%), but within each group, results were discordant. Positive CMV histology was significantly associated with need for colectomy in the IBD group, while positive tissue CMV PCR was not. Positive CMV histology, and tissue and serum CMV PCR were all significantly associated with antiviral use. Positive serum CMV PCR was significantly associated with colectomy. Histopathology remains the most predictive tool in assessing CMV colitis, while qualitative tissue CMV PCR was found to have limited utility. Quantitative serum CMV PCR may be useful but requires further evaluation.

Effects of Induction Therapy on Graft Functions in Terms of Immunologic Risk

Advances in immunosuppressive therapies and surgical techniques have led to a significant reduction in the incidence of rejection within 1 year after kidney transplantation. Immunologic risk is an important factor affecting graft functions and guiding the clinician in the selection of induction therapy. The aim of this study was to investigate graft functions based on serum creatinine levels, Chronic Kidney Disease Epidemiology Collaboration (CKD- EPI) and proteinuria levels, frequency of leukopenia, cytomegalovirus (CMV) and BK virus polymerase chain reaction (PCR) positivity in patients with low and high immunologic risk. This retrospective study included 80 renal recipients. Recipients were divided into 2 groups: patients at low immunologic risk who received basiliximab only and those with high immunologic risk who received low-dose (1.5 mg/kg for 3 days) antithymocyte globulin and basiliximab. No significant differences were observed between the 2 risk groups in terms of first, third, sixth, and 12th-month creatinine levels, CKD-EPI, proteinuria levels, leukopenia frequency, and CMV and BK virus PCR positivity. One-year graft survivals did not differ significantly between these 2 treatment modalities. The combined use of low-dose antithymocyte globulin and basiliximab in the induction treatment of patients with high immunologic risk seems promising in terms of graft survival, leukopenia frequency, and CMV and BK virus PCR positivity.

Cytomegalovirus reactivation in ulcerative colitis patients: Early indicators.

The association of. ytomegalovirus (CMV) infection with ulcerative colitis (UC) still remains a controversial topic for the clinicians. Aim: In this study, we aimed to elucidate the CMV infection related parameters in the exacerbation of UC. In this study, 812 UC patients who have admitted to our institution between June 2008 and November 2020 were analyzed retrospectively. CMV infection was diagnosed by the detection of CMV DNA with polymerase chain reaction (PCR) in tissue biopsies with presence of clinical colitis symptoms. CMV negative UC patient group was defined as UC activation group with negative PCR results. A total of 153 patients met the inclusion criteria during the study period, with a median age of 41.8 years. CMV PCR positivity had been detected in tissue biopsy in 43 (28.1%) UC patients. CMV-positive patients had a statistically significant higher frequency of steroid resistance, treatment with azathioprine, longer disease duration, longer remission, and hospitalization day. The mean C-reactive protein (CRP) level, platelet to lymphocyte ratio (PLR) were higher, and mean albumin level was lower in CMV positive patients, with statistically significance. Also, colectomy and anti-tumor necrosis factor-α (TNF-α) therapy were more frequent in CMV-reactivated group in long-term follow-up. In a multivariable model, steroid resistance, treatment with azathioprine, long disease duration, low albumin value was independently associated with colonic CMV infection. Steroid resistance, treatment with azathioprine, long disease duration, low albumin levels were significant risk factors for CMV colitis, among patients with UC activation.

Effectiveness and safety of prenatal valacyclovir for congenital cytomegalovirus infection: systematic review and meta-analysis.

Universal screening for cytomegalovirus (CMV) infection in pregnancy is not recommended in most countries. One of the major deterrents is the lack of effective prenatal therapy. The role of valacyclovir therapy in reducing the risk of vertical transmission, symptomatic congenital CMV infection and adverse outcome is controversial. The main aim of this systematic review and meta-analysis was to investigate the safety and effectiveness of prenatal valacyclovir therapy in pregnancies with maternal CMV infection. MEDLINE, EMBASE and Cochrane databases and ClinicalTrials.gov were searched. The inclusion criteria were pregnancy with confirmed maternal CMV infection, treated or untreated with valacyclovir. The primary outcome was the incidence of congenital CMV infection confirmed by a positive CMV polymerase chain reaction result of the amniotic fluid. The secondary outcomes were symptomatic and asymptomatic infection, perinatal death, termination of pregnancy, anomalies detected on follow-up ultrasound, on fetal magnetic resonance imaging or at birth, severe and mild-to-moderate symptoms due to congenital CMV infection, neurological, visual and hearing symptoms, and adverse events related to valacyclovir. Risk of bias was assessed using the revised Cochrane risk-of-bias tool for randomized trials (RoB 2) or Risk Of Bias In Non-randomized Studies of Interventions (ROBINS-I) tool, as appropriate. Head-to-head meta-analyses were used to compare the risk of each of the explored outcomes according to whether pregnancies with maternal CMV infection were treated with prenatal valacyclovir therapy. Eight studies (620 women) were included. Pregnancies treated with valacyclovir had a significantly lower risk of congenital CMV infection compared with those not receiving valacyclovir (three studies; 325 fetuses; pooled odds ratio (OR), 0.37 (95% CI, 0.21-0.64); I2 = 0%; P < 0.001). When stratifying the analysis according to gestational age at maternal infection, the risk of vertical transmission was significantly lower in pregnancies receiving valacyclovir following first-trimester maternal infection (three studies; 184 fetuses; pooled OR, 0.34 (95% CI, 0.15-0.74); I2 = 20.9%; P = 0.001), while there was no significant difference between the two groups in those acquiring CMV infection in the periconceptional period or in the third trimester of pregnancy. Only one study reported on the risk of vertical transmission in women infected in the second trimester, demonstrating a lower risk of congenital infection in women taking valacyclovir, although this was based on a small number of cases. Pregnancies treated with valacyclovir therapy had an increased likelihood of asymptomatic congenital CMV infection compared with those not receiving valacyclovir (two studies; 132 fetuses; pooled OR, 2.98 (95% CI, 1.18-7.55); I2 = 0%; P = 0.021), while there was no significant difference between the two groups in the risk of perinatal death (P = 0.923), termination of pregnancy (P = 0.089), anomalies detected at follow-up imaging assessment during pregnancy or at birth (P = 0.934) and symptoms due to CMV infection in the newborn (P = 0.092). The occurrence of all adverse events in pregnant individuals taking valacyclovir was 3.17% (95% CI, 1.24-5.93%) (six studies; 210 women), with 1.71% (95% CI, 0.41-3.39%) experiencing acute renal failure, which resolved after discontinuation of the drug. On GRADE assessment, the quality of evidence showing that valacyclovir reduced the risk of congenital CMV infection and adverse perinatal outcome was very low. Prenatal valacyclovir administration in pregnancies with maternal CMV infection reduces the risk of congenital CMV infection. Further evidence is needed to elucidate whether valacyclovir can affect the course of infection in the fetus and the risk of symptomatic fetal or neonatal infection. © 2022 International Society of Ultrasound in Obstetrics and Gynecology.

Cost-effectiveness of a cytomegalovirus screening strategy in neonates born after 34 weeks small for gestational age

IntroductionInfection by cytomegalovirus (CMV) is one of the most common congenital infections, with a global prevalence of 0.3%–2.4%. In Spain, CMV screening is not performed during pregnancy, but rather in neonates with risk factors, and, in many hospitals, in those born small for gestational age (SGA). Screening is usually performed by measurement of the viral load in urine by polymerase chain reaction (PCR) and/or head ultrasound in search of compatible features.The aim of the study was to assess the yield of the CMV PCR test in urine and head ultrasound examination in asymptomatic neonates born SGA after 34 weeks’ gestation. The secondary objective was to assess the cost-effectiveness of this strategy. Design and methodsWe conducted an observational and retrospective study between January and December 2019 in a tertiary care hospital. It included neonates delivered after 34 weeks, SGA and without additional risk factors assessed with a CMV PCR test in urine and/or head ultrasound. ResultsThe sample included 259 patients. It was divided in 2 groups: group 1, patients with a head circumference, weight and length below the 10th percentile (53 patients; 20.5%), and group 2, patients in whom only the weight was below the 10th percentile (206 patients; 79.5%). The incidence of late preterm birth, twin pregnancy, neonatal admission and exposure to illicit drugs during gestation was higher in group 1. A total of 186 urine PCR tests and 223 head ultrasounds were performed overall, and both tests were performed more frequently in group 1 (P=.002). There was only 1 positive CMV PCR test result in the sample (0.54%), corresponding to a patient in group 2 with no abnormal sonographic findings who remained asymptomatic throughout the follow-up. Two head ultrasound examinations yielded abnormal findings, in both cases unrelated to congenital CMV infection. We performed a cost-effectiveness analysis and determined that the cumulative cost of head ultrasound examinations and urine CMV PCR tests in our sample amounted to Є17 000 for the detection of a single asymptomatic positive case. ConclusionIn our population, screening for congenital CMV infection in asymptomatic late preterm and term newborns whose only risk factor is SGA does not seem to be cost effective. It would be necessary to expand the sample to other populations.

Coste efectividad de la estrategia de cribado de citomegalovirus en recién nacidos mayores de 34 semanas de bajo peso para la edad gestacional

IntroductionInfection by cytomegalovirus (CMV) is one of the most common congenital infections, with a global prevalence of 0.3%-2.4%. In Spain, CMV screening is not performed during pregnancy, but rather in neonates with risk factors, and, in many hospitals, in those born small for gestational age (SGA). Screening is usually performed by measurement of the viral load in urine by polymerase chain reaction (PCR) and/or head ultrasound in search of compatible features.The aim of the study was to assess the yield of the CMV PCR test in urine and head ultrasound examination in asymptomatic neonates born SGA after 34 weeks’ gestation. The secondary objective was to assess the cost-effectiveness of this strategy. Design and methodsWe conducted an observational and retrospective study between January and December 2019 in a tertiary care hospital. It included neonates delivered after 34 weeks, SGA and without additional risk factors assessed with a CMV PCR test in urine and/or head ultrasound. ResultsThe sample included 259 patients. It was divided in two groups: group 1, patients with a head circumference, weight and length below the 10th percentile (53 patients; 20.5%), and group 2, patients in whom only the weight was below the 10th percentile (206 patients; 79.5%). The incidence of late preterm birth, twin pregnancy, neonatal admission and exposure to illicit drugs during gestation was higher in group 1. A total of 186 urine PCR tests and 223 head ultrasounds were performed overall, and both tests were performed more frequently in group 1 (P=.002). There was only one positive CMV PCR test result in the sample (0.54%), corresponding to a patient in group 2 with no abnormal sonographic findings who remained asymptomatic throughout the followup. Two head ultrasound examinations yielded abnormal findings, in both cases unrelated to congenital CMV infection. We performed a cost-effectiveness analysis and determined that the cumulative cost of head ultrasound examinations and urine CMV PCR tests in our sample amounted to €17000 for the detection of a single asymptomatic positive case. ConclusionIn our population, screening for congenital CMV infection in asymptomatic late preterm and term newborns whose only risk factor is SGA does not seem to be cost effective. It would be necessary to expand the sample to other populations.

Cytomegalovirus as a cause of recurrent corneal endotheliitis in the Canadian population

ObjectifPrésenter les manifestations cliniques, la réponse au traitement antiviral et les résultats visuels à long terme de l'endothélite à cytomégalovirus (CMV) au sein d'une cohorte canadienne. NatureÉtude rétrospective d'une série de cas. ParticipantsUn total de 7 patients (9 yeux) atteints d'endothélite cornéenne ont été adressés à une clinique spécialisée dans le traitement des troubles de la cornée intégrée à un important établissement canadien. MéthodesOn a réalisé un examen rétrospectif de tous les patients qui avaient consulté un seul et même chirurgien spécialisé dans les troubles de la cornée en raison d'une endothélite cornéenne. Les patients ont subi une ponction de chambre antérieure et obtenu un résultat positif lors d'un test de dépistage (réaction en chaîne de la polymérase) du CMV. Tous les patients ont reçu le valganciclovir par voie orale pendant un minimum de 3 mois. Les principaux paramètres de mesure comprenaient l'acuité visuelle, la maîtrise de l'hypertension oculaire, la dépendance médicamenteuse et l’état de la cornée. RésultatsLa durée moyenne du suivi a été de 76,4 ± 11,8 mois. Seuls 2 patients présentaient une atteinte bilatérale. On compte 3 types de manifestations de l'endothélite touchant la cornée : les lésions linéaires, disciformes et circinées. La meilleure acuité visuelle corrigée est passée d'une moyenne de 0,48 ± 0,19 logMAR lors de la visite initiale à 0,24 ± 0,11 logMAR lors de la dernière visite de suivi. La pression intraoculaire, pour sa part, est passée d'un maximum de 35 ± 3,1 mm Hg à 14,2 ± 4,3 mm Hg. Le nombre d'antiglaucomateux a diminué, passant de 2,6 ± 0,45 collyres à 0,89 ± 0,29. On a dû procéder à une transplantation endothéliale dans 2 yeux. Le valganciclovir a été bien toléré par l'ensemble des patients; au moment de la dernière visite de suivi, l’état de tous les patients était stable sous l'effet de faibles doses de valganciclovir (dose moyenne hebdomadaire : 1395 mg). ConclusionsLe CMV est une cause peu fréquente, mais cliniquement significative, d'endothélite cornéenne et doit être pris en considération dans le diagnostic différentiel de l'endothélite cornéenne, même au sein d'une population immunocompétente. Nos résultats étayent ceux d’études antérieures selon lesquels le CMV réagit très bien au valganciclovir par voie orale et illustrent pour la première fois l'efficacité d'un traitement antiviral d'entretien faiblement dosé au long cours.

Efficacy of low-dose valganciclovir in Cytomegalovirus R+ lung transplant recipients: a retrospective comparative analysis

BackgroundCytomegalovirus (CMV) infection is extremely common after lung transplant and can be associated with significant morbidity and mortality. Current practice suggests the use of 900 mg daily of valganciclovir for CMV prophylaxis, but there is no literature assessing whether 450 mg daily of valganciclovir is sufficient in intermediate CMV risk lung transplant recipients. Therefore, we sought to assess the role of low-dose valganciclovir (LDV) versus high-dose valganciclovir (HDV) prophylaxis in intermediate-risk (R+) recipients.MethodsWe conducted a retrospective analysis on lung transplant recipients at the Norton Thoracic Institute in Phoenix, Arizona looking at intermediate-risk patients that received either valganciclovir 450 mg per day (LDV) or 900 mg/day (HDV). All patients were followed for 1 year post-transplant for incidence of CMV viremia. The primary outcome was the rate of CMV viremia as determined by a positive CMV polymerase chain reaction ([PCR] >2.7 log copies/mL). Secondary outcomes included rate of adverse events, acute cellular rejection, and mortality.ResultsThe primary analysis included 103 patients (55 in the LDV group, 48 in the HDV group). In the LDV group, 9 patients (16.4%) developed CMV viremia compared to 4 (8.3%) in the HDV group (p=0.221) with no difference observed in adverse event rates between groups.ConclusionThere was no statistical difference between groups for the primary outcome. However, the effect size demonstrated in this analysis may be of clinical relevance and valganciclovir 450 mg daily would not be recommended in intermediate risk lung transplant recipients at this time. To confirm our results, further prospective studies enrolling larger patient populations are necessary.

Cytomegalovirus-Associated Venous and Arterial Thrombotic Disease.

Background: Cytomegalovirus (CMV) infection has been associated with venous thromboembolism (VTE) and acute coronary syndromes (ACS).Methods: A retrospective study was conducted within the OSF HealthCare System in Peoria, IL. The objectives were to determine the incidence of acute VTE and ACS within one year of CMV testing. The “study group” included patients with positive CMV immunoglobulin M (IgM) or positive CMV polymerase chain reaction (PCR). The “seropositive control” group included patients with positive CMV immunoglobulin G (IgG) and negative IgM. The “seronegative control” group included patients with negative CMV IgG and IgM, or negative PCR.Results: Within one year of CMV infection, 38 of 379 patients (10.0%) developed VTE in the study group compared to 41 of 1334 patients (3.1%) in the seropositive control and 37 of 1249 (3.0%) in the seronegative control. Adjusting for age and gender, both control groups were less likely to have VTE than the study group within one year (seropositive control: odds ratio (OR) = 0.3, 95% confidence interval (CI) 0.2-0.5, p < 0.0001; seronegative control: OR = 0.4, 95% CI 0.2-0.6, p < 0.0001). ACS was more likely to occur in the study group, with the incidence of 7.7% compared to 4.7% (p < 0.0001) in the seropositive control and 1.9% (p <0.0001) in the seronegative control. Adjusting for age and gender, the seronegative control was less likely to develop ACS than the study group within one year (OR = 0.4, 95% CI 0.2-0.7, p = 0.003).Conclusions: This retrospective study demonstrates that CMV infection may be a significant risk factor for VTE and ACS.

Incidental mucocutaneous cytomegalovirus detection and its predictive value for systemic disease

Multiplex polymerase chain reaction (PCR) testing has revolutionised microbiological practice but also increased the number of positive results of uncertain significance. This phenomenon has been seen in the increasing detection of cytomegalovirus (CMV) in mucocutaneous swabs for herpesviruses, the microbiological significance of which is a priori unclear. The aim of our study was to determine if an incidental finding of a positive CMV result represented CMV disease, if it facilitated a timely diagnosis of CMV disease or whether there were any deleterious outcomes. We performed a retrospective review of patients with an incidentally positive PCR result for CMV on external and mucosal swabs, including medical comorbidities and presence of immunosuppression, subsequent investigations, whether a diagnosis of CMV disease was made, and treatment. CMV detection was infrequent, detected in 158 (3.4%) of 4626 herpes multiplex PCR tests performed. The majority (60.4%) of patients were immunocompromised, and amongst these patients a positive swab represented a new diagnosis or already known CMV disease in 14%. In seven patients (5%), all of whom were immunocompromised, the positive CMV PCR on a swab led to further investigation and subsequent diagnosis and treatment of CMV disease. Whilst not recommended for diagnosis of CMV disease, if CMV is detected on a mucocutaneous swab in an immunocompromised patient, further assessment and investigation for CMV disease should be undertaken.

Integration of congenital cytomegalovirus screening within a newborn hearing screening programme.

Targeted screening by a salivary cytomegalovirus (CMV) polymerase chain reaction (PCR) of infants who 'refer' on their newborn hearing screen has been suggested as an easy, reliable and cost-effective approach to identify and treat babies with congenital CMV (cCMV) to improve hearing outcomes. This study aimed to investigate the feasibility and cost-effectiveness of introducing targeted salivary cCMV testing into a newborn hearing screening programme. The study included three tertiary maternity hospitals in Queensland, Australia between August 2014 and April 2016. Infants who 'referred' on the newborn hearing screen were offered a salivary swab for CMV PCR at the point of referral to audiology. Swabs were routinely processed and tested for CMV DNA by real-time quantitative PCR. Parents of babies with a positive CMV PCR were notified, and the babies were medically assessed and, where appropriate, were offered treatment (oral valganciclovir). Of eligible infants, the parents of 83.0% (234/283) consented to the cCMV screen. Of these, 96.6% returned a negative result (226/234), and 3.4% (8/234) returned a positive result (three true positive; five false positive). The prevalence of cCMV for infants with confirmed hearing loss was 3.64% (P = 2/55; confidence interval = 0.44-12.53%). The cost comparison suggests the cost implementation of cCMV screening (and subsequent potential treatment benefits and management over time), compared to non-screening (and subsequent management), to be negligible. Incorporating cCMV testing into Universal Newborn Hearing Screening within Queensland is realistic and achievable, both practically and financially.

Prophylaxis of Recurrent Cytomegalovirus Uveitis with Topical Ganciclovir

Cytomegalovirus (CMV) can cause recurrent or chronic hypertensive anterior uveitis in immunocompetent patients. Antiviral treatment options include topical ganciclovir or systemic valganciclovir. However, recurrences are common after stopping treatment. We evaluated the efficacy of long-term topical ganciclovir therapy as prophylaxis for recurrent activity. Retrospective analysis of all CMV uveitis patients seen between 2011 and 2018 at Zurich University Hospital. Inclusion criteria were suspected viral anterior uveitis and a positive CMV polymerase chain reaction of the anterior chamber (AC) tap. After diagnosis, topical therapy with ganciclovir gel 5 × daily was started and tapered according to clinical activity. Topical steroids and glaucoma medication were used according to clinical assessment. An active episode was defined as increase in AC inflammatory activity and/or a uveitis-related rise in intraocular pressure (IOP) greater than 25 mmHg. Episodes were analysed before and after initiation of ganciclovir therapy. Six patients, median age 51 (range 24 - 62) years old, were included. All patients had hypertensive unilateral anterior uveitis and presented with small to medium sized endothelial precipitates and with 0.5+ to 2+ AC cells. Median IOP in the affected eye at initial presentation was 43 mmHg (range 36 - 60). Median time from first episode to diagnosis was 19.5 (range 5 - 193) months. Median number of episodes before ganciclovir treatment was 4 (2 - 20), corresponding to a mean of 3.04 episodes per year. Median follow-up time after initiation of ganciclovir medication was 26 (range 4 to 62) months. Median number of episodes under treatment was 1 (range 0 - 6), corresponding to a mean of 0.19 episodes per year (p = 0.04, 2-sided paired t-test). The median (range) for the individually chosen long-term prophylactic dose was ganciclovir gel 2 (0 - 4) times daily, and topical steroids 1 (0 - 2) times daily. Lower doses lead to recurrences in 3 patients (50%). Glaucoma and cataract surgery were performed in 2patients (33%). Although a rare entity in Central Europe, the important feature of CMV uveitis is its hypertensive and recurrent nature. In our cases, topical ganciclovir was found to be an effective treatment. Inflammatory activity was well controlled by using an individually assessed prophylactic dose. Larger studies assessing long-term prophylaxis are desirable.

Detection of Cytomegalovirus in Liver Tissue by Polymerase Chain Reaction in Infants With Neonatal Cholestasis.

Cytomegalovirus (CMV) is associated with neonatal cholestasis (NC). Diagnosis of CMV infection is most often based on either positive blood CMV IgM or CMV blood polymerase chain reaction (PCR). Isolation of CMV in liver tissues in patients with NC has rarely been reported. This study was undertaken to see if CMV is present in liver tissues of patients with NC and evaluate the correlation between positive CMV PCR in liver tissue with the serology and blood PCR. This study was conducted in 31 infants with NC from June 2015 to December 2016. All patients underwent blood CMV IgM, blood CMV PCR and liver CMV PCR. Prevalence of CMV in NC based on positive liver CMV PCR was calculated. Sensitivity and specificity of the serologic markers and blood CMV PCR to identify CMV infection in the liver was determined. CMV IgM was positive in 13 (42%) patients, CMV IgG was positive in 26 (84%) patients and blood CMV PCR was positive in 23 (74%) patients. Liver CMV PCR was positive in 16 (52%) patients. Fifteen (48%) patients had biliary atresia (BA), 10 (32%) patients had neonatal hepatitis, 5 (16%) had paucity of bile ducts and 1 (3%) had ascending cholangitis. Of the 16 patients with positive liver CMV PCR, 8 (50%) had BA, 4 (25%) had neonatal hepatitis, 3 (19%) had paucity of bile ducts and 1 (6%) had ascending cholangitis. Sensitivity of blood CMV IgM in relation to liver CMV PCR was 69% and specificity was 61%. Sensitivity of blood CMV PCR was 61% and specificity was 71% when compared with liver CMV PCR. CMV is present in the liver tissues of more than half the patients with NC. Serology or blood CMV PCR is apparently not an accurate marker of CMV in the liver tissue. Also, CMV infection in children seems to be associated equally with BA or non-BA neonatal hepatitis.

The Effect of Topical Ganciclovir and Corticosteroid on Cytomegalovirus Corneal Endotheliitis in Korean Patients

ABSTRACTPurpose: To report long-term outcomes of topical ganciclovir (GCV) and corticosteroids in Korean patients with cytomegalovirus (CMV) corneal endotheliitis.Methods: This retrospective study included 13 eyes from 13 patients with CMV corneal endotheliitis, with a follow-up period of 24.5 ± 8.2 months. The patients were consistently maintained with topical 2% GCV and 1% prednisolone acetate eyedrop.Results: All patients demonstrated unilateral typical coin-shaped keratic precipitates (KPs) or linear KP, and positive CMV polymerase chain reaction of aqueous humor. After 2 weeks of treatment, all patients showed decrease of clinical signs. During the follow-up, four patients developed mild anterior chamber inflammation with increased intraocular pressure without typical coin-shaped KPs or edema, started to use the initial dose, and resolved the clinical signs. One patient showed recurrence of corneal edema twice, and was administered systemic valgancyclovir for 2 weeks upon second recurrence with resolution of clinical signs.Conclusion: Long-term maintenance therapy with topical GCV and corticosteroids are effective and maintain corneal endothelial function in Korean patients with CMV endotheliitis.

Big Data, Predictive Analytics, and Quality Improvement in Kidney Transplantation: A Proof of Concept.

We sought proof of concept of a Big Data Solution incorporating longitudinal structured and unstructured patient-level data from electronic health records (EHR) to predict graft loss (GL) and mortality. For a quality improvement initiative, GL and mortality prediction models were constructed using baseline and follow-up data (0-90 days posttransplant; structured and unstructured for 1-year models; data up to 1 year for 3-year models) on adult solitary kidney transplant recipients transplanted during 2007-2015 as follows: Model 1: United Network for Organ Sharing (UNOS) data; Model 2: UNOS & Transplant Database (Tx Database) data; Model 3: UNOS, Tx Database & EHR comorbidity data; and Model 4: UNOS, Tx Database, EHR data, Posttransplant trajectory data, and unstructured data. A 10% 3-year GL rate was observed among 891 patients (2007-2015). Layering of data sources improved model performance; Model 1: area under the curve (AUC), 0.66; (95% confidence interval [CI]: 0.60, 0.72); Model 2: AUC, 0.68; (95% CI: 0.61-0.74); Model 3: AUC, 0.72; (95% CI: 0.66-077); Model 4: AUC, 0.84, (95 % CI: 0.79-0.89). One-year GL (AUC, 0.87; Model 4) and 3-year mortality (AUC, 0.84; Model 4) models performed similarly. A Big Data approach significantly adds efficacy to GL and mortality prediction models and is EHR deployable to optimize outcomes.

Long-Term Topical Ganciclovir and Corticosteroids Preserve Corneal Endothelial Function in Cytomegalovirus Corneal Endotheliitis.

To report the long-term outcomes of topical ganciclovir (GCV) and corticosteroids as a maintenance therapy for cytomegalovirus (CMV) corneal endotheliitis. This retrospective study included 10 eyes of 9 patients diagnosed with CMV corneal endotheliitis with a minimum 1-year follow-up at a tertiary referral hospital between 2008 and 2014. CMV corneal endotheliitis was defined by corneal edema associated with typical keratic precipitates (KPs) and a positive CMV polymerase chain reaction from aqueous humor taps. Patients receiving long-term topical 0.5% GCV and topical corticosteroids without discontinuation were included. The final corneal condition and endothelial cell density (ECD) were reported. The mean age was 45.6 ± 11.7 years. The mean follow-up duration was 48 ± 25 months. All patients exhibited typical coin-shaped and/or linear KPs. A significant resolution of corneal edema and decreased KPs were achieved within 1 month in all patients after initiating topical 0.5% GCV every 2 hours and topical corticosteroids twice a day. The dose frequency was gradually tapered to GCV 4 times and corticosteroids once or twice a day as a maintenance therapy. All 10 eyes had a clear graft or corneas at the end of this study. The mean ECD was 1630 ± 699 cells per millimeter square before treatment and 1776 ± 834 cells per millimeter square at the end of the study period. Topical 0.5% GCV and corticosteroids as a maintenance regimen without interruption effectively preserved long-term corneal endothelial function.

Cytomegalovirus reactivation and its clinical impact in patients with solid tumors.

Cytomegalovirus reactivation can be life threatening. However, little evidence on its incidence in solid cancers is available. Therefore our single center Cytomegalovirus polymerase chain reaction database with altogether 890 CMV positive blood serum samples of mainly hematological and oncological patients was retrospectively analyzed to examine the occurrence of Cytomegalovirus reactivation in patients with solid tumors, resulting in 107 patients tested positive for Cytomegalovirus reactivation. Seventeen patients with solid cancer and a positive CMV-PCR test were identified, of which eight patients had clinically relevant CMV disease and received prompt antiviral treatment. Five patients fully recovered, but despite prompt antiviral treatment three patients died. Among these three patients two had significant co-infections (in one case EBV and in the other case Aspergillus) indicating that that CMV reactivation was at least one factor contributing to sepsis. The patient with the EBV co-infection was treated in an adjuvant therapy setting for breast cancer and died due to Cytomegalovirus and Epstein-Barr virus associated pneumonia despite intensive therapy. The other two patients had progressive disease of an underlying pancreatic cancer at the time of CMV diagnosis. One patient died due to attendant uncontrollable Aspergillus pneumonia, the other patient most likely died independent from CMV disease because of massively progressive underlying disease.Cytomegalovirus reactivation and disease might be underestimated in routine clinical practice. In our retrospective analysis we show that approximately 50 % of our patients suffering from solid cancers with a positive Cytomegalovirus polymerase chain reaction also had clinically relevant Cytomegalovirus disease requiring antiviral therapy.

Prognostic Value of Low PCR Cytomegalovirus Load in Kidney Transplant Recipients.

Cytomegalovirus (CMV) infection after kidney transplantation is associated with significant morbidity and mortality. Use of Polymerase Chain Reaction (PCR) is recommended for diagnosis and/or monitoring of CMV infection. Nevertheless the PCR value threshold to start treatment has not yet been defined. Material and methods: In this retrospective monocentric study, we included all kidney recipients between 05/2012 and 07/2013. CMV PCR (whole blood, detection threshold = 1,79 log, Abbott® RealTime CMV) was performed weekly during the first four months after transplantation and then monthly during one year except for low risk patients (D-/R-). Prophylaxis (valganciclovir) was given for 3 months for R+ and 6 months for D+/R-. All patients with at least one positive PCR were included in our analysis. Curative treatment (ganciclovir iv or oral valganciclovir) was started in case of high CMV load (> 4 log) and/or clinical/biological abnormalities associated with positive CMV load (whatever the level). We assessed indications and incidence of curative treatment. Results were expressed as mean ±SD. Results: During the 14-month period, a first positive CMV PCR occurred in 59 /140 patients after 6,4 ± 5,2 months (5 patients under prophylaxis). Twenty seven (45%) were treated (55,5% D+/R-; 33,3% D-/R+; 11,1% D+/R+). Initial PCR level was similar between treated and non-treated patients (2,9 ± 0,99 log and 2,8 ± 0,96 log respectively). All patients with a PCR level higher than 4 log initially or during the follow-up were treated (n=16, 59%). Thirty two patients (55%) were not treated (50% D+/R+; 40,6% D-/R+; 6,25% D+/R-; 3,12% D-/R-). Interestingly, 26 non-treated patients (81%) had spontaneous undetectable CMV load after two controls and no further positive CMV PCR load was observed during the follow-up. Conclusion: We suggest that a “wait-and-see” attitude may be indicated for patients with low positive CMV load (threshold <4log on whole blood) in the absence of clinical or biological abnormalities.

Cytomegalovirus infection in immunocompetent wheezy infants: the diagnostic value of CMV PCR in bronchoalveolar lavage fluid.

Cytomegalovirus (CMV) pneumonitis in immunocompetent hosts is uncommon but is being recognized more frequently, particularly when presenting as severe viral pneumonia. The objective of this study was to examine lower respiratory tract CMV infection in immunocompetent wheezy infants, based on polymerase chain reaction (PCR) in bronchoalveolar lavage (BAL) fluid, to compare CMV PCR results in BAL and in blood samples and to evaluate the benefits of antiviral ganciclovir therapy in these patients. Retrospective review of the records of patients referred to our tertiary care hospital between January 2000 and July 2010 who had unexplained persistent wheezing and underwent fibreoptic flexible bronchoscopy (FFB). Fibreoptic flexible bronchoscopy was applied to 102 infants with persistent wheezing and diffuse interstitial infiltration on radiological investigations; so CMV PCR in BAL fluid was performed. CMV PCR in BAL fluid was positive in 51 patients. Retrospectively, we had access to the files of 25 of these patients. The mean CMV PCR in BAL fluid was 334840copies/mL. Only eight patients had CMV PCR positivity in their blood samples (mean: 2026·3copies/mL). There was not a relationship between BAL and blood CMV PCR values based on Spearman's correlation analysis (r=-0·008). Fourteen patients had severe respiratory symptoms and received ganciclovir therapy. Twelve of them fully recovered. Bronchoalveolar lavage fluid CMV PCR was superior to blood CMV PCR in diagnosing lower respiratory tract infections caused by CMV in immunocompetent infants. Ganciclovir therapy may be effective in selected immunocompetent wheezy infants with CMV PCR positivity in BAL fluid.