Clinical Differences between Posner-Schlossman Syndrome Patients with Intermittent Intraocular Pressure Elevation and Glaucomatous Damage.

INTRODUCTION: Although there is abundant evidence that Posner-Schlossman syndrome (PSS) can lead to secondary glaucoma, data on the clinical differences between PSS patients with secondary glaucoma and those with intermittent intraocular pressure (IOP) elevation are sparse. METHODS: This retrospective observational study included 52 patients (52 eyes) diagnosed with PSS and admitted to Zhongnan Hospital of Wuhan University between January 2019 and February 2022. Demographic characteristics and clinical features were gathered from admission records. Patients were divided into two groups: 27 cases with intermittent IOP elevation (group A) and 25 cases with secondary glaucoma (group B and C). Of the secondary glaucoma cases, 18 were further divided into the topical IOP-lowering medications group (group B) and 7 into the glaucoma surgery group (group C). Clinical characteristics of different groups were compared. RESULTS: Compared to the intermittent IOP elevation group, PSS patients with secondary glaucoma had a longer course of disease, a higher incidence of iris depigmentation, lower best corrected visual acuity, lower endothelial cell density, and higher interferon-γ (IFN-γ) concentration and cytomegalovirus (CMV) deoxyribonucleic acid (DNA) copy number in the aqueous humor (all p < 0.05). Group C presented a higher CMV DNA copy number in the aqueous humor than groups A and B (p < 0.05). Compound trabeculectomy proved effective in group C, with a functional filter bleb and well-controlled IOP without disease progression after 1 year of follow-up. CONCLUSION: Distinctive characteristics existed between PSS patients with secondary glaucoma and those with intermittent IOP elevation. Compound trabeculectomy appears to be an effective treatment option when IOP cannot be controlled through topical medications.

Incidence and antiviral treatment of cytomegalovirus infection in infants with biliary atresia.

PURPOSE: Patients with biliary atresia (BA) and cytomegalovirus (CMV) infection may have poorer outcomes after Kasai portoenterostomy (KPE) than uninfected patients, suggesting a rationale for antiviral treatment (AVT). We aimed to describe the incidence of CMV infection and of AVT in BA patients, and to detect any differences between infected and uninfected patients to conclude if AVT is of use. METHODS: Data on BA patients who underwent KPE 2004-2020 were retrospectively collected, and the outcome was analyzed with regard to CMV status. RESULTS: Fifteen out of forty-six (33%) BA patients had signs of ongoing CMV infection. They did not differ significantly from the CMV-negative patients regarding rate of prematurity, birth weight, or biochemical markers but were slightly older at KPE. All patients received steroids postoperatively and all patients with ongoing CMV infection received AVT with very good effect on viremia and without major side effects. The AVT consisted of oral valganciclovir (10-40 (- 58) mg/kg/d) or intravenous ganciclovir (5.3-11 mg/kg/d). CONCLUSION: Ongoing CMV infection is common in this group of patients. The viremia can effectively be treated with AVT without any major side effects. Larger, randomized studies are needed to clarify the possible effect on clinical outcome.

Treatment of cytomegalovirus anterior segment infection with intravitreal injection of ganciclovir in adjunction with or without oral valganciclovir: a long-term results.

We evaluated the therapeutic outcome of intravitreal injection (IVI) of ganciclovir with/without oral valganciclovir for cytomegalovirus (CMV) anterior segment infection. We enrolled 61 patients (61 eyes) with PCR-proven CMV anterior segment infection. IVI of ganciclovir (2 mg/0.05 mL) was given as a loading dose; subsequent use of oral valganciclovir (900 mg twice daily) was determined according to the severity of anterior chamber inflammation after injection. All eyes had IVI of ganciclovir, and 53 patients received oral valganciclovir as adjunctive therapy with a mean duration of 1.9 months to achieve disease remission. Repeated diagnostic aqueous taps were performed in 37 eyes with suspected recurrence, and CMV DNA was positive in 24 eyes. This therapeutic strategy afforded a median 50% recurrence-free survival time of 47.0 ± 8.12 months. The patients' mean best corrected visual acuity, intraocular pressure and corneal endothelial cell counts stabilized or improved. Corneal transplantation before CMV infection diagnosis was identified as an independent risk factor for recurrence (hazard ratio 6.81, 95% confidence interval 1.21-38.23, P = 0.029). In patients with CMV anterior segment infection, the relative short-term therapeutic strategy, IVI of ganciclovir in adjunction with/without oral valganciclovir, effectively achieved a median recurrence-free survival time of nearly 4 years.

Human cytomegalovirus DNA detection in a recurrent glioblastoma multiforme tumour, but not in whole blood: a case report and discussion about the HCMV latency and therapy perspectives.

In the current study, a 58-year-old male patient presented with recurrent glioblastoma multiforme (GBM). The patient underwent surgical resection, 4 months earlier, followed by radiotherapy and chemotherapy. During the second surgical intervention, tumour tissue and whole blood were sampled and analysed for human cytomegalovirus (HCMV) DNA, immediate early (IE) mRNA and pp65 mRNA. HCMV DNA was detected only in the recurrent tumour tissue but not in the whole blood. Neither IE mRNA nor pp65 mRNA was expressed. Our result suggests HCMV latency in the brain tumour with detectable level of viral DNA. More data are needed to understand the HCMV infection chronology in the brain tumours but our data could be important for further studies of HCMV antigens on the tumour surface and anti-GBM therapy.

The characteristics of Posner-Schlossman syndrome: A comparison in the surgical outcome between cytomegalovirus-positive and cytomegalovirus-negative patients.

This retrospective observational study aims to report the clinical characteristics and surgical results in eyes with Posner-Schlossman syndrome (PSS), and compare these outcomes between cytomegalovirus (CMV)-positive and -negative eyes.We reviewed the medical records of 21 consecutive immunocompetent patients clinically diagnosed with PSS between the years 2010 and 2018. Aqueous humor was collected from all the affected eyes to detect if CMV was present, and polymerase chain reaction (PCR) was performed using the herpesvirus family primers.The average period between the initial PSS attack and aqueous humor sampling at our institute was 9.3 years. Out of the 21 patients, 62% were CMV-positive. Regardless of CMV status, the mean intraocular pressure (IOP), mean deviation (MD), and central corneal endothelium cell (CEC) density, at the initial examination at our institute were already significantly worse in the affected eyes than in the unaffected eyes (all P values < .05). The average visual acuity (VA) was only significantly worse in the CMV-positive group (P = .02). Out of all the patients, those that were CMV-positive had undergone more glaucoma surgeries (P = .056). Fourteen patients underwent either a trabeculectomy (TRAB) or a trabeculotomy (LOT), and their IOP significantly reduced following surgery (P < .001). In 85.7% of those that had surgery, their IOP was successfully lowered to less than 20 mm Hg.Long-lasting PSS causes a decrease in VA, MD, and the CEC density. A prompt diagnosis is required, and an appropriate treatment plan should be formulated. In those patients with PSS that develop uncontrolled glaucoma, both TRAB and LOT may be effective in controlling IOP.

Multimodal techniques failed to detect cytomegalovirus in human glioblastoma samples.

The role of the human cytomegalovirus (HCMV) in gliomagenesis is largely debated. Contradictory data exist regarding the sensitivity and specificity of HCMV detection techniques, including immunohistochemistry (IHC), in situ hybridization (ISH), and RNA and DNA sequencing. The aim of this study is to detect HCMV in glioblastoma (GBM) tumor samples using IHC, ISH, and real-time PCR (qPCR), as well as to correlate the findings with serological status and HCMV DNA load in blood. Forty-seven patients with histopathological diagnosis of GBM and HCMV serological status were retrospectively reviewed. HCMV DNA quantification in whole blood was performed in 31 patients. The detection of HCMV in tumor samples was performed using IHC in 42 cases, ISH in 10 cases, and qPCR in 29 cases. All but two patients were taking high steroid doses at the time of biological testing. HCMV seroprevalence was 68%. Active infection with HCMV DNA detected in blood was diagnosed in 6 out of 21 (28%) seropositive patients. HCMV was not detected in GBM samples using IHC or ISH, while qPCR was positive in one case (also positive for blood HCMV DNA). These data do not support a crucial role of HCMV in GBM tumorigenesis. HCMV might be reactivated in GBM patients, due to steroid treatment.

Characterization and clinical enrichment of HLA-C*07:02-restricted Cytomegalovirus-specific CD8+ T cells.

Human Cytomegalovirus (CMV) reactivation remains a major source of morbidity in patients after solid organ and hematopoietic stem cell transplantation (HSCT). Adoptive T cell therapy (ACT) with CMV-specific T cells is a promising therapeutic approach for HSCT recipients, but might be counteracted by CMV's immune evasion strategies. HLA-C*07:02 is less susceptible to viral immune evasion suggesting HLA-C*07:02-restricted viral epitopes as promising targets for ACT. For a better understanding of HLA-C*07:02-restricted CMV-specific T cells we used recently generated reversible HLA-C*07:02/IE-1 multimers (Streptamers) recognizing a CMV-derived Immediate-Early-1 (IE-1) epitope and analyzed phenotypic and functional T cell characteristics. Initially, we detected very high frequencies of HLA-C*07:02/IE-1 multimer+ T cells (median = 11.35%), as well as robust functional responses after stimulation with IE-1 peptide (IFNγ+; median = 5.02%) in healthy individuals. However, MHC-multimer+ and IFNγ-secreting T cell frequencies showed a relatively weak correlation (r2 = 0.77), which could be attributed to an unexpected contribution of CMV-epitope-independent KIR2DL2/3-binding of HLA-C*07:02/IE-1 multimers. Therefore, we developed a MHC-multimer double-staining approach against a cancer epitope-specific HLA-C*07:02 multimer to identify truly HLA-C*07:02/IE-1 epitope-specific T cells. The frequencies of these truly HLA-C*07:02/IE-1 multimer+ T cells were still high (median = 6.86%) and correlated now strongly (r2 = 0.96) with IFNγ-secretion. Interestingly, HLA-C*07:02/IE-1-restricted T cells contain substantial numbers with a central memory T cell phenotype, indicating high expansion potential e.g. for ACT. In line with that, we developed a clinical enrichment protocol avoiding epitope-independent KIR-binding to make HLA-C*07:02/IE-1-restricted T cells available for ACT. Initial depletion of KIR-expressing CD8+ T cells followed by HLA-C*07:02/IE-1 Streptamer positive selection using paramagnetic labeling techniques allowed to enrich successfully HLA-C*07:02/IE-1-restricted T cells. Such specifically enriched populations of functional HLA-C*07:02/IE-1-restricted T cells with significant central memory T cell content could become a potent source for ACT.

Antiviral Treatment for Colonic Cytomegalovirus Infection in Ulcerative Colitis Patients Significantly Improved Their Surgery Free Survival.

BACKGROUND: The frequency of cytomegalovirus (CMV) colitis in steroid-refractory inflammatory bowel disease has been reported to range from 15.8% to 34.0%. Infected patients are more likely to become hospitalized, have longer lengths of stay, and higher mortality rates. Current data are limited to small scale studies and showed conflicting result regarding the role of antiviral therapy. AIMS: (1) To investigate the role of antiviral treatment in ulcerative colitis (UC) patients with CMV infection. (2) To investigate the role of viremia in the outcomes of these patients. MATERIALS AND METHODS: The Cleveland Clinic pathology database identified 1478 patients who had colon biopsy and were tested for CMV during 1990 to 2013. After inclusion and exclusion, 41 UC patients were selected. Among them, 24 (58.5%) received treatment, 17 (41.5%) did not. A total of 14 demographic data and 4 clinical outcomes (surgery free survival, hospitalization, rehospitalization, and mortality) were compared between treated and nontreated patients. The same outcomes were also compared in patients who received treatment based on their viremia status. RESULTS: All demographic variables are similar between those treated and nontreated groups. Antiviral therapy significantly improved the surgery free survival within 30 days, and lasted 70 months (P<0.01). In contrast, hospitalization, rehospitalization, and mortality were comparable (P>0.05). No significant difference was observed in any of the clinical outcomes based on viremia status. CONCLUSIONS: Our small scale study demonstrates that antiviral treatment for colonic CMV infection significantly improves the surgery free survival short-term and long-term in patients with UC.

Pancreas-preserving duodenectomy after living donor liver transplantation for invasive cytomegalovirus disease.

CMV infection plays an important role in the postoperative course following solid organ transplantation. We present the case of an 11-year-old male patient who underwent LDLT due to severe hepatopulmonary syndrome and biliary cirrhosis. Four weeks after LDLT, he developed persistent GI bleeding and was subjected to repeated endoscopic treatment and radiological arterial embolization to stop the bleeding from duodenal ulcers. Diagnostic workup was negative for CMV disease. Because the bleeding persisted, surgical treatment was indicated, and a pancreas-preserving duodenectomy was performed. Immunohistochemical staining of the surgical specimen demonstrated diffuse endothelial infiltration by CMV. Despite ganciclovir treatment, the patient developed new erosions in the jejunal mucosa and melena; ganciclovir was discontinued, and foscarnet was started, resulting in clinical improvement and the cessation of bleeding. This case highlights the technical aspects of performing a complex upper GI resection in a patient recently subjected to LDLT, taking care to avoid injury to the previous liver graft anastomosis and restore GI continuity. Moreover, CMV tissue-invasive disease compartmentalized in the GI tract may be difficult to diagnose, as indicated by the negative results of antigenemia and PCR assays and endoscopic superficial mucosal biopsies.

High prevalence of cytomegalovirus infection in surgical intestinal specimens from infants with necrotizing enterocolitis and spontaneous intestinal perforation: A retrospective observational study.

BACKGROUND: Necrotizing enterocolitis (NEC) is a severe, often fatal gastrointestinal emergency that predominantly affects preterm infants, and there is evidence that neonatal cytomegalovirus (CMV) infection may in some cases contribute to its pathogenesis. OBJECTIVES: This study aimed to evaluate the prevalence of CMV in infants with NEC. STUDY DESIGN: Seventy intestinal specimens from 61 infants with NEC, spontaneous intestinal perforation (SIP), or related surgical complications were collected at Karolinska University Hospital and Uppsala University Hospital, Sweden. Ten specimens from autopsied infants without bowel disease served as controls. Samples were analyzed for CMV immediate-early antigen (IEA), CMV late antigen (LA), 5-lipoxigenase (5LO) and CMV-DNA by immunohistochemistry (IHC) and in situ hybridization (ISH), respectively. In 10 index samples, CMV DNA was analyzed with Taqman PCR after laser capture microdissection (LCM) of cells positive for CMV IEA by IHC. RESULTS: CMV IEA was detected by IHC in 57 (81%) and CMV LA in 45 (64%) of 70 intestinal specimens from index cases; 2 (20%) of 10 control specimens were positive for both antigens. 5LO was detected in intestinal tissue section obtained from all examined index and controls. CMV DNA was detected in 4 of 10 samples (40%) after LCM. By ISH, all 13 IHC-IEA-positive samples were positive for CMV DNA; however, 3 of 5 IHC-IEA-negative samples (60%) were also positive. CONCLUSIONS: CMV-specific antigens and CMV DNA were highly prevalent in intestinal specimens from infants with NEC, SIP, and related surgical complications. Our findings provide further evidence that neonatal CMV infection contributes to the pathogenesis of these diseases and may affect patient outcome.

Descemet Stripping Automated Endothelial Keratoplasty Outcomes in Patients With Cytomegalovirus Endotheliitis.

PURPOSE: There is currently limited information regarding the outcomes of endothelial keratoplasty in eyes with cytomegalovirus (CMV) endotheliitis. We report the results of Descemet stripping automated endothelial keratoplasty (DSAEK) for endothelial failure secondary to CMV. METHODS: This is a retrospective review of 4 eyes of 4 patients with CMV endotheliitis and DSAEK. CMV was confirmed in each case by a positive aqueous tap on qualitative polymerase chain reaction. The clinical characteristics of the patients and postoperative outcomes were studied. RESULTS: The mean age of the 4 patients was 69.6 ± 8.1 years. Two were ethnically Vietnamese, 1 Chinese, and 1 Lebanese. All were immunocompetent. Three eyes had presented with hypertensive uveitis and 1 with bullous keratopathy. Twelve DSAEKs were performed in total in the 4 eyes. Five grafts were performed without any perioperative treatment with oral valganciclovir. All subsequently failed after a mean of 8.0 ± 3.8 months. Seven grafts were managed with oral valganciclovir; 2 of these grafts failed after 18 and 37 months, and 1 graft had primary graft failure. Four grafts are currently surviving, despite an episode of CMV reactivation in 2 grafts. CONCLUSIONS: In cases of unexplained corneal decompensation or early graft failure after uncomplicated DSAEK, a diagnosis of CMV infection must be considered. Subsequent management of DSAEK in such cases remains challenging. The postoperative course can be complicated by CMV reactivation, which may masquerade either as graft rejection or graft failure. Long-term treatment with oral valganciclovir or topical ganciclovir may be required to decrease graft failure rates.

Increased Rates of Clostridium difficile Infection and Poor Outcomes in Patients with IBD with Cytomegalovirus.

BACKGROUND: Clostridium difficile infection (CDI) and Cytomegalovirus (CMV) reactivation are associated with disease exacerbations and poor outcomes in inflammatory bowel disease (IBD). Therefore, we assessed the association between these organisms in patients with IBD and the impact on colectomy. METHODS: A retrospective case-control study was conducted to assess CDI prevalence in patients with IBD with a tissue diagnosis of CMV compared with matched IBD controls without CMV from 2005 to 2011. We also assessed the impact of coinfection on colectomy risk for patients coinfected with CMV and CDI compared with IBD patients with CMV alone (CMV controls) or matched IBD patients with CDI alone (CDI controls). Colectomy-free survival was assessed using Kaplan-Meier methods, and statistical significance was determined using Log-rank analysis for unmatched comparisons and by generalized estimating equations in Cox regression for matched comparisons. RESULTS: CDI was more common in IBD patients with CMV (n = 12/68; 17.6%) than in matched IBD controls (n = 12/144; 8.25%) (P = 0.046). A nonsignificant increase in high-grade disease (5 or more CMV inclusions by immunohistochemistry) was detected in coinfected patients compared with CMV controls (P = 0.15). Colectomy-free survival at 1 year was 30% (95% confidence interval, 12.0-74.7) for coinfected patients and was significantly less compared with 71.5% (95% confidence interval, 58.0-88.2) of CDI controls (P < 0.001) and was numerically less than 57.1% (95% confidence interval, 44.1-74.0) of CMV controls (P = 0.095). CONCLUSIONS: CDI occurs more frequently in IBD patients with CMV reactivation and is associated with poor outcomes. Patients with IBD with CMV should be tested for CDI and managed aggressively.

Is Follow-Up Endoscopy Necessary in Upper Gastrointestinal Cytomegalovirus Disease?

Gastrointestinal (GI) cytomegalovirus (CMV) disease is a major cause of morbidity and mortality in immunocompromised patients. Diagnosis of GI CMV disease mostly relies on endoscopy examination and histopathologic findings. There are limited data on the need for follow-up endoscopy with histopathologic examination in patients with upper gastrointestinal (UGI) CMV disease. All adult patients with confirmed and probable UGI CMV disease at a tertiary hospital over a 16-year period whose follow-up endoscopy was available were enrolled. The patients were classified as endoscopic responders if they showed complete or partial improvement on follow-up endoscopy, and as endoscopic nonresponders if there was no improvement or worsening. CMV tissue clearance was defined as absence of any visible CMV inclusion bodies, negative CMV immunohistochemistry and negative CMV polymerase chain reaction in follow-up biopsy tissues. During the study period, 77 patients with UGI CMV disease were analyzed. The median time to follow-up endoscopy was 19 days (interquartile range, 14-27). Of these 77 patients, 52 (68%) were classified as responders, and the remaining 25 (32%) as nonresponders. GI bleeding was more common in the nonresponders than the responders (36% vs 12%, respectively; P = 0.02). There was no significant difference in CMV tissue clearance between the responders and nonresponders (56% vs 69%, respectively; P = 0.38), median durations of treatment (20 days vs 21 days, respectively; P = 0.48), and relapse rates (10% vs 8%, respectively; P > 0.99). Multivariate analysis showed that the only independent predictive factor for relapse of CMV antigenemia or CMV GI disease was multiorgan CMV disease (odds ratio = 12.4, 95% confidence interval 1.6-97.9; P = 0.02). Endoscopic responses were obtained in about two-thirds of patients with UGI CMV disease 2 or 3 weeks after antiviral therapy. However, these follow-up endoscopic findings neither reflected CMV tissue clearance nor predicted disease relapse. These findings suggest that the routine follow-up endoscopy may not be warranted in patients with UGI CMV disease.

Cytomegalovirus Colitis in an End-Stage Renal Disease Patient Presenting with Lower Gastrointestinal Bleeding.

The authors report a case of cytomegalovirus colitis which is one of uncommon causes of lower gastrointestinal bleeding in a patient with end-stage renal disease receiving hemodialysis. Our patient presented with recurrent episodes of massive hematochezia within 2 months. He had the underlying end-stage renal disease, ischemic heart disease, cerebrovascular disease, hypertension and gout. Colonoscopy revealed multiple clean base ulcers at rectum and sigmoid colon. An active bleeding lesion was rectal ulcer with non bleeding visible vessel which was successfully treated with hemoclipping. The diagnosis of cytomegalovirus colitis was confirmed by pathology from colonic tissues which showed compatible patterns of cytopathic change. Human immunodeficiency virus serology was negative. He was treated with with ganciclovir intravenously for 1 week after the pathological finding was reported. To our knowledge, cytomegalovirus infection should be considered as causative pathogen of colitis and colonic ulcers in end-stage renal disease patients.

Small bowel transplantation complicated by cytomegalovirus tissue invasive disease without viremia.

We report on a small bowel transplant patient, donor/recipient seropositive (D+/R+) for cytomegalovirus (CMV), with a clinical course complicated by CMV disease. Anti-CMV prophylaxis was given for 100 days. Immunosuppression consisted of alemtuzumab, tacrolimus, mycophenolate mofetil and prednisolone. Five months posttransplant, CMV tissue invasive disease of the upper gastrointestinal tract was evident without the presence of viremia, tested by quantitative polymerase chain reaction (PCR). Complete viral load suppression was achieved with intravenous ganciclovir, followed by valganciclovir for secondary prophylaxis. Mycophenolate mofetil and prednisolone were discontinued. Shortly thereafter the patient presented with recurrent CMV and candida esophagitis. While on ganciclovir and caspofungin, the patient developed CMV tissue invasive disease of the ileal graft, with persistent absence of viremia. Foscarnet and CMV immunoglobulin were added. Viral load declined to undetectable levels; however, clinical improvement did not occur due to occurrence of graft rejection. Despite infliximab and high dose prednisolone, graft rejection was progressive, requiring surgical explantation of the graft. This case highlights the importance of additional diagnostic tools such as endoscopy including PCR analysis of tissue samples. Extension of primary antiviral prophylaxis interval up to 6 months and prolonged retreatment for recurrent CMV disease may be useful to avoid severe CMV-related complications.

Subacute cytomegalovirus appendicitis in a renal transplant recipient.

Cytomegalovirus (CMV) infections in transplant patients is a well-known disease. We describe the first case, to our knowledge, documenting CMV appendicitis in a renal transplant patient, and its clinical presentation, diagnosis, and treatment.

Cytomegalovirus infection-associated fulminant hepatitis in an immunocompetent adult requiring emergency living-donor liver transplantation: report of a case.

Human cytomegalovirus (CMV) infection is usually self-limiting in healthy adults, but it can lead to significant complications. This report presents the case of an immunocompetent adult with fulminant hepatitis caused by a CMV infection requiring emergency living-donor liver transplantation. A 39-year-old female with persistent fever for 6 weeks was referred for fulminant hepatitis, but the underlying etiology was not identified. Rapid deterioration of consciousness led to an emergency living-donor liver transplant using a modified right lobe graft. She showed increasing CMV antigenemia after surgery and the explant liver pathology showed massive hepatic necrosis with positive staining for CMV protein. Treatment with ganciclovir improved the graft liver function and her general condition recovered. This report presents a rare case of CMV-associated fulminant hepatitis which led to emergency liver transplantation. Although CMV is rare, it should be included in the differential diagnosis of patients with severe hepatitis, even immunocompetent patients, after other more common etiologies have been excluded.