QuantiFERON monitor predicts early cytomegalovirus infection and viral burden in allogeneic hematopoietic stem cell transplantation.

INTRODUCTION: Cytomegalovirus (CMV) infection is a major cause of transplantation-related morbidity and mortality. This study assessed the utility of the QuantiFERON monitor (QFM; Qiagen) for the prediction of early CMV infection and viral burden. METHODS: QuantiFERON-CMV (QF-CMV; Qiagen) and QFM were measured at the post-allogeneic hematopoietic stem cell transplantation (HSCT) week 4. CMV DNA was measured at every visit until post-HSCT week 24. The QFM cutoff specific to CMV infection was established. RESULT: At the post-HSCT week 4, the QFM cutoff predicting CMV infection was 86.95 IU/mL. While QF-CMV results at the post-HSCT week 4 were associated with high-level CMV infection (CMV DNA ≥ 5,000 IU/mL) but not with CMV infection (CMV DNA ≥ 500 IU/mL), QFM was associated with both CMV infection and high-level CMV infection. Both indeterminate QF-CMV and nonreactive QFM were associated with increased peak CMV DNA. CONCLUSION: Low QFM is a risk factor for CMV infection and increased CMV viral loads. QFM at post-HSCT week 4 can be utilized as an assay to predict the risk and burden of early CMV infection in HSCT recipients, in conjunction with other risk factors.

Use of letermovir for cytomegalovirus primary prophylaxis in lung transplant recipients.

BACKGROUND: Cytomegalovirus (CMV) is a driver of negative outcomes after lung transplant (LTX) and primary prophylaxis (PPX) with valganciclovir (VGC) is standard-of-care. VGC is associated with myelosuppression, prompting interest in letermovir (LTV). METHODS: Adults receiving LTX between April 1, 2015, and July 30, 2022, at our institution were evaluated. Patients were excluded if low CMV risk (D-/R-), survived <90 days post-LTX, or transferred care before PPX withdrawal. Primary outcomes were leukopenia (white blood cell count [WBC] ≤ 3.0 × 109/L), severe leukopenia (WBC ≤ 2.0 × 109/L), and neutropenia (absolute neutrophil count ≤ 1500 cells/µL) requiring granulocyte-colony stimulating factor (GCSF) on PPX. Secondary outcomes included breakthrough CMV infection and post-PPX CMV infection. RESULTS: 204 patients met inclusion criteria: 175 patients on VGC and 29 patients on LTV (after VGC conversion). Most patients received bilateral LTX (62.7%) with non-lymphocyte-depleting induction (96.6%) and moderate-risk serostatus (D+/R+, 48.5%). Patients transitioned from VGC to LTV after a mean of 178 days (SD 80.8 days) post-transplant. Patients on VGC experienced significantly more leukopenia (82.3% vs. 58.6%, p = 0.008), severe leukopenia (57.1% vs. 31.0%, p = 0.016), and neutropenia requiring GCSF (70.9% vs. 51.7%, p = 0.048). Breakthrough (5.7% vs. 3.4%, p = 0.955) and post-PPX (24.6% vs. 37.9%, p = 0.199) infections were similar. A subgroup analysis of patients with high-risk serostatus showed similar trends, though did not reach statistical significance. CONCLUSIONS: In this single-center study, the incidence of leukopenia and neutropenia requiring GCSF were reduced with LTV compared to VGC. Breakthrough and post-PPX infections were not significantly different. This evidence suggests that LTV has comparable efficacy with reduced myelosuppression compared to VGC in LTX recipients, and may be an appropriate alternative for PPX.

Case report: CMV retinitis following local and systemic immunosuppression.

We report the case of a 71-year-old man who presented 2 years following renal transplantation with diffuse, unilateral cytomegalovirus retinitis five weeks after receiving an intravitreal dexamethasone implant device for the management of central retinal vein occlusion. Examination of the left eye showed diffuse retinal hemorrhages, attenuated and tortuous retinal vessels, and superior retinal whitening. The patient was successfully treated with serial intravitreal foscarnet injections and oral valganciclovir with disease regression observed by 12 weeks after presentation. The patient's visual acuity and examination remained stable at 9-months follow-up.

Cytomegalovirus-Associated Colitis as a Cause of Lower Gastrointestinal Bleeding in Kidney Transplant Recipients: A Single-Centered Study.

Introduction Cytomegalovirus (CMV) is the most common viral pathogen affecting patients undergoing solid organ transplantation. It is often the most important infection for patients who have undergone kidney transplantation. Clinical presentations of cytomegalovirus infection range from asymptomatic infection to organ-specific involvement. This study aimed to determine the frequency of cytomegalovirus-associated colitis in kidney transplant recipients (KTRs) presenting with lower gastrointestinal bleeding. Methods After the approval of the ethical review committee of the Sindh Institute of Urology and Transplantation (ERC-SIUT), this cross-sectional study was conducted at the Department of Hepatogastroenterology at the Sindh Institute of Urology and Transplantation from January 2021 to December 2021. All the KTRs (six months after the transplantation) of either gender and aged between 18 and 65 years, presenting with lower gastrointestinal (GI) bleeding as per the operational definition, were enrolled in the study. Those patients who were either unfit for the endoscopy or refused to give consent were excluded from the study. Colonic biopsies were reviewed by a consultant histopathologist for the features of CMV infection. Results A total of 95 renal transplant recipients of either gender or age above 18 to 65 years with lower GI bleeding were included in the study. Among them, 84 (88.4%) were males, while 11 (11.6%) were females. The mean age of the patients included in the study was 37±11 years. The most common presenting complaint was fresh bleeding per rectum, which was observed in 73 (76.8%). The most common findings observed on colonoscopy in KTRs with bleeding per rectum were colonic ulcers and erosions noted in 41 (43.1%) and 36 (37.3%) patients, respectively. On histopathology, CMV colitis was noted in 21 (22.1%) patients. On comparison of different baseline variables, the presence of fresh bleeding per rectum and the presence of both ulcers and erosions on colonoscopy were the factors significantly associated with CMV colitis in KTRs. Conclusion CMV colitis is a prevalent condition in KTRs, presenting with lower GI bleeding. Despite the significant occurrence, the levels of CMV viremia were not associated with CMV colitis, suggesting that diagnosis should rely on histopathological confirmation. Prophylaxis during periods of high immunosuppression is crucial to reducing the incidence of CMV infections and improving both graft function and patient survival.

Chronic and Acute Drug-Induced Hypersensitivity Syndrome in a Rural Patient With Cytomegalovirus Infection: A Case Report.

A 50-year-old man presented with fever and a generalized rash, with chronic fatigue and lymphadenopathy for a year and a half. Initial tests ruled out lymphoproliferative disorders, showing reactive hyperplasia and cytomegalovirus. Symptoms worsened after ampicillin treatment, leading to suspected drug-induced hypersensitivity syndrome (DIHS). Upon admission, amoxicillin was discontinued, and prednisolone and antiviral treatment were initiated. The patient's condition improved with this therapy. A drug-induced lymphocyte stimulation test confirmed hypersensitivity to both ampicillin and allopurinol. This case illustrates the diagnostic challenge of chronic and acute DIHS because of the rare presentation. It underscores the need for high suspicion of DIHS in patients with chronic lymphadenopathy and fatigue, particularly with recent drug exposure. Effective management involves recognizing symptoms, withdrawing the offending drug, and using corticosteroids. Viral infections like cytomegalovirus can complicate DIHS diagnosis and treatment, necessitating a comprehensive approach. This case highlights the importance of considering DIHS in differential diagnoses and the complexities of managing it alongside co-infections in rural healthcare settings.

In-vivo confocal microscopy predicts cytomegalovirus as the cause of chronic or recurrent anterior uveitis among Chinese.

PURPOSE: To evaluate and compare endothelial features by in-vivo confocal microscopy (IVCM) in Chinese eyes with chronic or recurrent anterior uveitis (AU) with and without cytomegalovirus (CMV). METHODS: A double-masked, cross-sectional case-control study at a tertiary eye clinic. RESULTS: Thirty eyes of 30 subjects were analyzed. Fifteen eyes (50%) were CMV positive, while fifteen eyes were negative for herpes simplex virus, varicella zoster virus and CMV. Absence of pseudoguttata was the strongest, independent risk factor for CMV (OR 34.53, 95% CI: 1.84-648.02, p = 0.018), followed by severe iris depigmentation (OR 31.45, 1.02-965.81, p = 0.048) and low corneal endothelial cell density (ECD) (OR 14.79, 1.14-191.30, p = 0.039) on univariable regression. All three remained statistically significant after adjustment. The combination of absence of pseudoguttata and low ECD on IVCM achieved a similar predictive value as iris depigmentation examination. CONCLUSION: Absence of pseudoguttata on IVCM was an independent predictor of positive CMV detection after adjusting for iris depigmentation and corneal endothelial cell density. The addition of this feature to severe iris depigmentation and low corneal ECD can increase the positive predictive value of detecting CMV. IVCM was a useful non-invasive tool to predict CMV in patients with chronic or recurrent AU.

Seroprevalence of human herpes viruses in France, 2018-2022: a multilevel regression and poststratification approach.

BACKGROUND: Information related to herpes simplex virus 1 and 2 (HSV-1 and 2), varicella-zoster virus (VZV), Epstein-Barr virus (EBV), and cytomegalovirus (CMV) seroprevalence in France is either lacking, incomplete, or outdated, despite their public health burden. METHOD: We used routinely collected serological data between 2018 and 2022 to estimate HSV-1, HSV-2, VZV, EBV, and CMV seroprevalence in France. To account for demographic differences between our analytic samples and the French population and get estimates for sparsely sampled districts and age classes, we used a multilevel regression and poststratification approach combined with Bayesian model averaging via stacking weights. RESULTS: The observed seroprevalence (number of positive tests/number of tests) were 64.6% (93,294/144,424), 16.9% (24,316/144,159), 93.0% (141,419/152,084), 83.4% (63,199/75, 781), and 49.0% (23,276/47,525), respectively, for HSV-1, HSV-2, VZV, EBV, and CMV. Between 2018 and 2022, France had a model-based average (equal-tailed interval at 95%) expected seroprevalence equal to 61.1% (60.7,61.5), 14.5% (14.2,14.81), 89.5% (89.3,89.8), 85.6% (85.2,86.0), and 50.5% (49.3,51.7), respectively, for HSV-1, HSV-2, VZV, EBV, and CMV infections. We found an almost certain lower expected seroprevalence in Metropolitan France than in overseas territories for all viruses but VZV, for which it was almost certainly greater. The expected seroprevalences were likely greater among females for all viruses. LIMITATIONS: Our results relied on the assumption that individuals were sampled at random conditionally to variables used to build the poststratification table. IMPLICATIONS: The analysis highlights spatial and demographic patterns in seroprevalence that should be considered for designing tailored public health policies.

Bidirectional transfer of human cytomegalovirus strains in donor and recipient seropositive lung transplant patients.

Donor and recipient human cytomegalovirus (HCMV) seropositive (D+R+) lung transplant recipients (LTRs) often harbor multiple strains of HCMV, likely due to transmitted donor (D) strains and reactivated recipient (R) strains. To date, the extent and timely occurrence of each likely source in shaping the post-transplantation (post-Tx) strain population is unknown. Here, we deciphered the D and R origin of the post-Tx HCMV strain composition in blood, bronchoalveolar lavage (BAL), and CD45+ BAL cell subsets. We investigated either D and/or R formalin-fixed paraffin-embedded blocks or fresh D lung tissue from four D+R+ LTRs obtained before transplantation. HCMV strains were characterized by short amplicon deep sequencing. In two LTRs, we show that the transplanted lung is reseeded by R strains within the first 6 months after transplantation, likely by infiltrating CD14+ CD163+/- alveolar macrophages. In three LTRs, we demonstrate both rapid D-strain dissemination and persistence in the transplanted lung for >1 year post-Tx. Broad inter-host diversity contrasts with intra-host genotype sequence stability upon transmission, during follow-up and across compartments. In D+R+ LTRs, HCMV strains of both, D and R origin can emerge first and dominate long-term in subsequent episodes of infection, indicating replication of both sources despite pre-existing immunity.

Cytomegalovirus infection risk with alemtuzumab therapy in hematological malignancies: a retrospective cohort study in the non-transplant setting.

Alemtuzumab is a potent lymphocyte-depleting immunotherapy used in solid organ transplan-tation (SOT), that is increasingly being applied in diverse lymphoproliferative disorders (LPDs). However, a significant toxicity limiting expanded usage is cytomegalovirus (CMV) infection, for which standardized preventive strategies exist in SOT but not in LPDs due to a poor understanding of infection risk in this population, with early LPD studies largely limited to stem cell transplantation. Using one of the most diverse arrays of LPDs studied to date, our retrospective cohort study of non-transplant patients receiving alemtuzumab over a ten-year period at a large regional cancer center examines the incidence and clinical profile of infected patients. Among 24 patients, we identified a composite CMV infection rate of 42% with a symptomatic rate of 21%. We also noted significant variations in preventive strategies, which alongside a high infection rate presents an opportunity to improve outcomes through further work in standardization.

Adaptive natural killer cell expression in response to cytomegalovirus infection in blood and solid cancer.

Natural Killer (NK) cells are conventionally thought to be an indefinite part of innate immunity. However, in a specific subset of NK cells, recent data signify an extension of their "duties" in immune surveillance and response, having characteristics of adaptive immunity, in terms of persistence and cytotoxicity. These cells are known as the adaptive or memory-like NK cells, where human cytomegalovirus (HCMV) infection has been shown to drive the expansion of adaptive NKG2C+ NK cells. HCMV is a ubiquitous pathogen whose prevalence differs worldwide with respect to the socioeconomic status of countries. The adaptive NK cell subpopulation is often characterized by the upregulated expression of NKG2C, CD16, and CD2, and restricted expression of NKG2A, FCεRγ and killer immunoglobulin-like receptors (KIR), although these phenotypes may differ in different disease groups. The reconfiguration of these receptor distributions has been linked to epigenetic factors. Hence, this review attempts to appraise literature reporting markers associated with adaptive or memory-like NK cells post-HCMV infection, in relation to solid cancers and hematological malignancies. Adaptive NK cells, isolated and subjected to ex vivo modifications, have the potential to enhance anti-tumor response which can be a promising strategy for adoptive immunotherapy.

Reactivation of cytomegalovirus and bloodstream infection and its impact on early survival after allogeneic haematopoietic stem cell transplantation: a multicentre retrospective study.

Cytomegalovirus reactivation (CMVr) and bloodstream infections (BSI) are the most common infectious complications in patients after allogeneic haematopoietic stem cell transplantation (allo-HSCT). Both are associated with great high morbidity whilst the BSI is the leading cause of mortality. This retrospective study evaluated the incidence of CMVr and BSI, identified associated risk factors, assessed their impact on survival in allo-HSCT recipients during the first 100 days after transplantation. The study comprised 500 allo-HSCT recipients who were CMV DNA-negative and CMV IgG-positive before allo-HSCT. Amongst them, 400 developed CMVr and 75 experienced BSI within 100 days after allo-HSCT. Multivariate regression revealed that graft failure and acute graft-versus-host disease were significant risk factors for poor prognosis, whereas CMVr or BSI alone were not. Amongst all 500 patients, 56 (14%) developed both CMVr and BSI in the 100 days after HSCT, showing significantly reduced 6-month overall survival (p = 0.003) and long-term survival (p = 0.002). Specifically, in the initial post-transplant phase (within 60 days), BSI significantly elevate mortality risk, However, patients who survive BSI during this critical period subsequently experience a lower mortality risk. Nevertheless, the presence of CMVr in patients with BSI considerably diminishes their long-term survival prospects. This study provides real-world data on the impact of CMVr and BSI following transplantation on survival, particularly in regions such as China, where the prevalence of CMV IgG-positivity is high. The findings underscore the necessity for devising and executing focused prevention and early management strategies for CMVr and BSI to enhance outcomes for allo-HSCT recipients.

Breast milk-transmitted acquired cytomegalovirus infection in an extremely low birth weight infant.

We encountered an extremely low birth weight infant with breast milk-transmitted cytomegalovirus (CMV) infection. To determine the transmission route, we conducted direct sequence analysis of two variable CMV genes, UL139, and UL146. When utilizing breast milk, the possibility of acquired CMV infection should be considered and tested for prompt diagnosis and treatment.

Lissencephaly and Advanced-Stage Congenital Cytomegalovirus Infection in a Neonate.

This case report investigates the management of a 24-week-old neonate with congenital cytomegalovirus (CMV) infection and its sequelae, including severe intrauterine growth restriction, thrombocytopenia, and brain anomalies, ultimately progressing to lissencephaly. The diagnostic challenges included delayed clinical suspicion of congenital CMV, which was not identified until after delivery through CMV DNA polymerase chain reaction, and differentiating its symptoms from other potential causes of the neonate's condition. Aggressive interventions included antibiotics, antiviral therapy with ganciclovir, and supportive measures such as intubation, CPR, respiratory support, blood transfusions, and management of coagulopathy. Despite these efforts, the patient deteriorated due to progressive hypoperfusion, hypoxemic cardiorespiratory failure, and disseminated intravascular coagulopathy. Due to the poor prognosis and extent of multiorgan damage, support was withdrawn per parental consent. This case highlights the complications encountered when managing an advanced-stage neonatal CMV infection and emphasizes the importance of a multidisciplinary and holistic approach to guide diagnosis and treatment.

Relations of optimism and purpose in life to immune markers in aging.

OBJECTIVE: Optimism and purpose in life are associated with improved health outcomes. More information is needed on biological mechanisms, including immunosenescence. We investigated if psychological well-being is associated with healthier immunosenescence-related measures including naïve and terminally differentiated CD4+ and CD8+ T cell percentages, CD4+:CD8+, and cytomegalovirus (CMV) IgG response. METHODS: Participants were adults over age 50 from the Health and Retirement Study. Optimism was measured using the Life Orientation Test Revised. Purpose in life was assessed using the subscale from the Ryff psychological well-being measure. We examined the cross-sectional associations of optimism and purpose in life with measures of T cell subsets using linear regression and with CMV IgG using ordered logit regression, controlling for potential confounding factors. RESULTS: The final analytic sample ranged from 7250 to 7870. After adjusting for sociodemographic factors, a 1-SD increment in optimism was associated with the percentage of naïve CD4+ T cells increasing by 0.6 (95%CI 0.2%, 1.0%). A 1-SD increment in purpose in life was associated with the percentage of naïve CD4+ T cells increasing by 0.9 (95%CI 0.5%, 1.3%) after adjusting for sociodemographic factors and the association was maintained after further adjustments for health conditions, depression, and health behaviors. For naïve CD8+ T cell percentages, CD4:CD8 ratios, and CMV IgG antibodies, associations were seen only in models that adjusted for age. No significant associations were seen in any models for the terminally differentiated CD4+ and CD8+ T cells. CONCLUSIONS: We found associations of optimism and purpose in life with naïve CD4+ T cell percentages.

Characterization of recurrent cytomegalovirus reactivations post allogenic stem cell transplantation in a population with high seropositivity.

OBJECTIVES: This study aimed to characterize incidences of CMV reactivations within one year post-allo-SCT and identify risk factors for CMV second reactivation episode in population with high seropositivity where first CMV reactivation episode deemed to be high. METHODS: This retrospective cohort study analyzed data from 359 allo-SCT patients aged 14 and older admitted to a tertiary academic hospital. Data on demographic and clinical factors, CMV serostatus, conditioning regimens, graft-versus-host disease prophylaxis, engraftment time, and CMV reactivations were collected. RESULTS: First and second CMV reactivations occurred in 88.9% and 18.4% of post-allo-SCT patients respectively. Patients were stratified into two groups based on primary disease necessitating allo-SCT, patients with malignant (Group 1) and non-malignant (Group 2) hematological disease. Factors associated with the second reactivation included cord blood as a stem cell source, human leukocyte antigen mismatch, acute graft-versus-host disease, and hematological malignancies. Patients with non-malignant hematological disease displayed better outcomes, including a higher rate of spontaneous clearance of first CMV reactivation (70% versus 49.4%) and lower rates of second CMV reactivation (9.6% versus 31%) than those with malignant hematological disease. The one-year overall survival rate was 87.7% (95.5% in non-malignant hematological disease and 78.13% in malignant hematological disease). CONCLUSION: Our findings are concordant with previous local study in regard to high rate of first CMV reactivation post-allo-SCT. It appears that patients with nonmalignant hematological disease had better outcomes, such as lower second CMV reactivation and higher survival rates compared to patients with malignant hematological disease. Further investigation is needed to identify other factors affecting recurrent CMV reactivations in allo-SCT in patients with malignant hematological disease.

Real-World Experience With Maribavir for Treatment of Cytomegalovirus Infection in High-Risk Solid Organ Transplant Recipients.

We evaluated use of maribavir (MBV) for treatment of 15 episodes of refractory/resistant cytomegalovirus infection in 13 solid organ transplant recipients. Treatment failure due to treatment-emergent MBV resistance or early virological recurrence after MBV discontinuation occurred in 7 (47%) episodes. Sustained viral clearance was achieved in 6 (40%) episodes.

A Case of Adult-Onset Still's Disease With Positive Antinuclear Antibodies and Positive Antineutrophil Cytoplasmic Antibodies.

Adult-onset Still's disease (AOSD) is a rare autoinflammatory disease characterized by nonspecific symptoms such as fever, maculopapular rash, and arthralgias. The exact etiology and pathogenesis remain unclear despite advancements in medical science. Diagnosis is typically established using the Yamaguchi criteria, which include a negative antinuclear antibody (ANA) test as one of the minor criteria. However, some patients with AOSD exhibit positive ANA and even positive antineutrophil cytoplasmic antibodies (ANCA), complicating the diagnostic process. We present the case of a 19-year-old Asian woman of Yakut ethnicity who initially presented with symptoms resembling an upper respiratory tract infection. Laboratory tests revealed the presence of both ANA and ANCA. The diagnosis of AOSD was confirmed based on clinical presentation and the Yamaguchi criteria. Subsequent pulse therapy with prednisolone resulted in significant clinical improvement and a one-year remission. A review of the literature revealed that simultaneous ANCA and ANA positivity in AOSD has not been previously reported. Follow-up over 12 months showed no evidence of other autoimmune or autoinflammatory diseases, suggesting that the positive ANA and ANCA results may be either false positives or atypical laboratory manifestations in AOSD, which should be considered in the diagnosis.

Cytomegalovirus-induced peroxynitrite promotes virus entry and contributes to pathogenesis in a murine model of infection.

There are no licensed vaccines for human cytomegalovirus (HCMV), and current antiviral drugs that target viral proteins are toxic and prone to resistance. Targeting host pathways essential for virus replication provides an alternate strategy that may reduce opportunities for drug resistance to occur. Oxidative stress is triggered by numerous viruses including HCMV. Peroxynitrite is a reactive nitrogen species that is formed during oxidative stress. Herein, we identified that HCMV rapidly induces the generation of intracellular peroxynitrite upon infection in a manner partially dependent upon xanthine oxidase generation. Peroxynitrite promoted HCMV infection in both cell-free and cell-associated infection systems in multiple cell types. Inhibiting peroxynitrite within the first 24 hours of infection prevented HCMV replication and peroxynitrite promoted cell entry and pp65 translocation into the host cell nuclei. Furthermore, using the murine cytomegalovirus model, we demonstrated that antagonizing peroxynitrite significantly reduces cytomegalovirus replication and pathogenesis in vivo. Overall, our study highlights a proviral role for peroxynitrite in CMV infection and implies that RNS and/or the mechanisms that induce their production could be targeted as a novel strategy to inhibit HCMV infection. IMPORTANCE: Human cytomegalovirus (HCMV) causes significant disease in individuals with impaired or immature immune systems, such as transplant patients and after congenital infection. Antiviral drugs that target the virus directly are toxic and are susceptible to antiviral drug resistance due to virus mutations. An alternate strategy is to target processes within host cells that are required by the virus for replication. Herein, we show that HCMV infection triggers a highly reactive molecule, peroxynitrite, during the initial stages of infection. Peroxynitrite was required for the initial entry of the virus into the cell and promotes virus replication in multiple cell types, suggesting a broad pro-viral function. Importantly, targeting peroxynitrite dramatically inhibited cytomegalovirus replication in cells in the laboratory and in mice, suggesting that therapeutic targeting of this molecule and/or the cellular functions it regulates could represent a novel strategy to inhibit HCMV infection.

Clinical characteristics and outcomes of immunocompromised critically ill patients with cytomegalovirus end-organ disease: a multicenter retrospective cohort study.

BACKGROUND: Cytomegalovirus (CMV) infection in patients with cellular immune deficiencies is associated with significant morbidity and mortality. However, data on CMV end-organ disease (CMV-EOD) in critically ill, immunocompromised patients are scarce. Our objective here was to describe the clinical characteristics and outcomes of CMV-EOD in this population. METHODS: We conducted a multicenter, international, retrospective, observational study in adults who had CMV-EOD and were admitted to any of 18 intensive care units (ICUs) in France, Israel, and Spain in January 2010-December 2021. Patients with AIDS were excluded. We collected the clinical characteristics and outcomes of each patient. Survivors and non-survivors were compared, and multivariate analysis was performed to identify risk factors for hospital mortality. RESULTS: We studied 185 patients, including 80 (43.2%) with hematologic malignancies, 55 (29.7%) with solid organ transplantation, 31 (16.8%) on immunosuppressants, 16 (8.6%) with solid malignancies, and 3 (1.6%) with primary immunodeficiencies. The most common CMV-EOD was pneumonia (n = 115, [62.2%] including 55 [47.8%] with a respiratory co-pathogen), followed by CMV gastrointestinal disease (n = 64 [34.6%]). More than one organ was involved in 16 (8.8%) patients. Histopathological evidence was obtained for 10/115 (8.7%) patients with pneumonia and 43/64 (67.2%) with GI disease. Other opportunistic infections were diagnosed in 69 (37.3%) patients. Hospital mortality was 61.4% overall and was significantly higher in the group with hematologic malignancies (75% vs. 51%, P = 0.001). Factors independently associated with higher hospital mortality were hematologic malignancy with active graft-versus-host disease (OR 5.02; 95% CI 1.15-27.30), CMV pneumonia (OR 2.57; 95% CI 1.13-6.03), lymphocytes < 0.30 × 109/L at diagnosis of CMV-EOD (OR 2.40; 95% CI 1.05-5.69), worse SOFA score at ICU admission (OR 1.18; 95% CI 1.04-1.35), and older age (OR 1.04; 95% CI 1.01-1.07). CONCLUSIONS: Mortality was high in critically ill, immunocompromised patients with CMV-EOD and varied considerably with the cause of immunodeficiency and organ involved by CMV. Three of the four independent risk factors identified here are also known to be associated with higher mortality in the absence of CMV-EOD. CMV pneumonia was rarely proven by histopathology and was the most severe CMV-EOD.

Cytomegalovirus Retinitis in an Eye with Unilateral Retinoblastoma: A Case Report.

Introduction: Cytomegalovirus (CMV) retinitis in the setting of pediatric retinoblastoma is exceedingly unusual. Here, we present the first reported case of CMV retinitis in an enucleated eye with retinoblastoma after chemotherapy in the western hemisphere. Case Presentation: A 2-year-old Hispanic male without a family history of retinoblastoma presented with a 3-month history of right eye exotropia and squinting. Clinical examination revealed dense white vitreous opacities in the right eye. Ocular oncology evaluation unveiled an exudative retinal detachment with vitreous seeds, subretinal seeding, and a tumor emanating from the retina in the superonasal quadrant of the right eye. The patient was diagnosed with unilateral Group D retinoblastoma, and RB1 sequencing revealed a pathogenic variant with mosaicism. Treatment involved systemic chemotherapy, intravitreal chemotherapy, and cryotherapy. However, the patient developed a rhegmatogenous retinal detachment with diffuse vitreous hemorrhage and ultimately underwent right eye enucleation. Interestingly, histopathological analysis of the enucleated eye revealed concomitant CMV retinitis alongside retinoblastoma. After consultation with infectious disease, antiviral treatment was not initiated as the patient remained asymptomatic and maintained a recovered immune system. Repeat CMV PCR confirmed viral clearance. The patient received a prosthetic eye and continues to be monitored for retinoblastoma recurrence. Conclusion: Clinicians should be aware of the potential for CMV retinitis to develop in retinoblastoma patients receiving chemotherapy, which may complicate clinical decision-making and management. Timely identification of CMV retinitis in this setting may improve patient ocular outcomes and overall prognosis.