RESUMEN
OBJECTIVES: Nocardia is an opportunistic infection among renal transplant recipients with an incidence of <1% but high mortality. Data from Pakistan are scarce. Our aim was to find the risk factors, clinical and radiographic findings, antimicrobial sensitivity, and outcomes of Nocardia infection among renal transplant recipients in Pakistan. MATERIALS AND METHODS: All adult renal transplant recipients diagnosed with nocardiosis between 2013 and 2020 were included. The cases were matched 1:2 with controls based on sex, age (±1 year), and transplant date (±1 year). Risk factors, clinical features, antibiotic sensitivities and outcomes were analyzed. RESULTS: A total of 48 patients developed nocardiosis. Around 25% of patients presented with disseminated disease. Median time from transplant to disease development was 2.68 years. High-dose methylprednisolone and presence of cytomegalovirus infection within 90 days of disease development were independent risk factors for Nocardia infection. The mortality rate was 20%. Central nervous system disease and cytomegalovirus infection within 90 days were significantly associated with mortality. The most susceptible drugs were co-trimoxazole and linezolid. Imipenem susceptibility was only 20%. CONCLUSIONS: High-dose methylprednisolone and cytomegalovirus infection were independent risk factors for Nocardia infection. Central nervous system disease was associated with mortality. Nocardia species were highly resistant to ceftriaxone and imipenem in our patient population.
Asunto(s)
Antibacterianos , Huésped Inmunocomprometido , Trasplante de Riñón , Nocardiosis , Infecciones Oportunistas , Humanos , Nocardiosis/diagnóstico , Nocardiosis/mortalidad , Nocardiosis/epidemiología , Nocardiosis/tratamiento farmacológico , Nocardiosis/microbiología , Trasplante de Riñón/efectos adversos , Trasplante de Riñón/mortalidad , Factores de Riesgo , Pakistán/epidemiología , Masculino , Femenino , Adulto , Infecciones Oportunistas/mortalidad , Infecciones Oportunistas/inmunología , Infecciones Oportunistas/diagnóstico , Infecciones Oportunistas/microbiología , Infecciones Oportunistas/epidemiología , Infecciones Oportunistas/tratamiento farmacológico , Persona de Mediana Edad , Antibacterianos/uso terapéutico , Resultado del Tratamiento , Factores de Tiempo , Estudios Retrospectivos , Infecciones por Citomegalovirus/diagnóstico , Infecciones por Citomegalovirus/mortalidad , Infecciones por Citomegalovirus/epidemiología , Medición de Riesgo , Metilprednisolona/administración & dosificación , Inmunosupresores/efectos adversosAsunto(s)
Infecciones por Citomegalovirus , Citomegalovirus , Humanos , Infecciones por Citomegalovirus/mortalidad , Infecciones por Citomegalovirus/epidemiología , Estados Unidos/epidemiología , Adulto , Femenino , Masculino , Citomegalovirus/inmunología , Persona de Mediana Edad , Anciano , Estudios Seroepidemiológicos , Adulto Joven , Anticuerpos Antivirales/sangre , Mortalidad , Anciano de 80 o más AñosRESUMEN
Cytomegalovirus (CMV) has long been thought to have an association with glioblastoma multiforme (GBM), although the exact role of CMV and any subsequent implications for treatment have yet to be fully understood. This study addressed whether IGH complementarity determining region-3 (CDR3)-CMV protein chemical complementarity, with IGH CDR3s representing both tumor resident and blood-sourced IGH recombinations, was associated with overall survival (OS) distinctions. IGH recombination sequencing reads were obtained from (a) the Clinical Proteomic Tumor Analysis Consortium, tumor RNAseq files; and (b) the cancer genome atlas, blood exome-derived files. The Adaptive Match web tool was used to calculate chemical complementarity scores (CSs) based on hydrophobic interactions, and those scores were used to group GBM cases and assess survival probabilities. We found a higher OS probability for cases whose hydrophobic IGH CDR3-CMV protein chemical complementarity scores (Hydro CSs) were in the upper 50th percentile for several CMV proteins, including UL99 and UL123, as well as for CSs based on known B cell epitopes representing these proteins. We also identified multiple immune signature genes, including CD79A and TNFRSF17, for which higher RNA expression was associated with higher Hydro CSs. Results were consistent with the idea that stronger immunoglobulin responses to CMV are associated with better OS probabilities for GBM.
Asunto(s)
Regiones Determinantes de Complementariedad , Infecciones por Citomegalovirus , Citomegalovirus , Glioblastoma , Proteínas Virales , Humanos , Glioblastoma/mortalidad , Glioblastoma/genética , Glioblastoma/virología , Citomegalovirus/genética , Citomegalovirus/inmunología , Regiones Determinantes de Complementariedad/genética , Regiones Determinantes de Complementariedad/inmunología , Infecciones por Citomegalovirus/mortalidad , Infecciones por Citomegalovirus/inmunología , Infecciones por Citomegalovirus/virología , Proteínas Virales/genética , Proteínas Virales/inmunología , Cadenas Pesadas de Inmunoglobulina/genética , Femenino , Persona de Mediana Edad , Masculino , Análisis de Supervivencia , Anciano , Epítopos de Linfocito B/inmunología , Epítopos de Linfocito B/genéticaRESUMEN
BACKGROUND: Cytomegalovirus (CMV) mismatched, donor IgG-positive/recipient IgG-negative, solid organ transplant recipients (SOTRs) are at high risk of CMV invasive disease. Post-prophylaxis disease is an issue in this population. Some programs employ surveillance after prophylaxis (SAP) to limit the incidence of post-prophylaxis disease. METHODS: This was a single-center retrospective cohort study that included all CMV mismatched SOTRs from 2003 to 2017. Patients underwent SAP with weekly CMV plasma viral load for 12 weeks. The subjects were classified into three post-prophylaxis DNAemia patterns: no DNAemia, one episode of DNAemia, and multiple episodes of DNAemia. We calculated the cumulative incidence of each DNAemia pattern. We also determined 5-year mortality based on DNAemia pattern stratified by organ transplant type. RESULTS: Post-prophylaxis recurrent DNAemia occurred in 63% of lung recipients and 32% of non-lung recipients (p = .003). Tissue invasive CMV disease was diagnosed in 3% of the population and CMV syndrome was diagnosed in 33%. Recurrent DNAemia was not associated with 5-year mortality. CONCLUSION: In this cohort, undergoing SAP tissue invasive disease was uncommon and CMV DNAemia recurrence did not have an impact on long-term mortality.
Asunto(s)
Antivirales , Infecciones por Citomegalovirus , Citomegalovirus , ADN Viral , Receptores de Trasplantes , Carga Viral , Humanos , Infecciones por Citomegalovirus/prevención & control , Infecciones por Citomegalovirus/virología , Infecciones por Citomegalovirus/mortalidad , Estudios Retrospectivos , Femenino , Masculino , Persona de Mediana Edad , Citomegalovirus/genética , Citomegalovirus/inmunología , Antivirales/uso terapéutico , ADN Viral/sangre , Adulto , Receptores de Trasplantes/estadística & datos numéricos , Recurrencia , Trasplante de Órganos/efectos adversos , Anciano , IncidenciaRESUMEN
Background: Sepsis, a life-threatening condition caused by the dysregulated host response to infection, is a major global health concern. Understanding the impact of viral or bacterial pathogens in sepsis is crucial for improving patient outcomes. This study aimed to investigate the human cytomegalovirus (HCMV) seropositivity as a risk factor for development of sepsis in patients with COVID-19. Methods: A multicenter observational study enrolled 95 intensive care patients with COVID-19-induced sepsis and 80 post-surgery individuals as controls. HCMV serostatus was determined using an ELISA test. Comprehensive clinical data, including demographics, comorbidities, and 30-day mortality, were collected. Statistical analyses evaluated the association between HCMV seropositivity and COVID-19 induced sepsis. Results: The prevalence of HCMV seropositivity did not significantly differ between COVID-19-induced sepsis patients (78%) and controls (71%, p = 0.382) in the entire cohort. However, among patients aged ≤60 years, HCMV seropositivity was significantly higher in COVID-19 sepsis patients compared to controls (86% vs 61%, respectively; p = 0.030). Nevertheless, HCMV serostatus did not affect 30-day survival. Discussion: These findings confirm the association between HCMV seropositivity and COVID-19 sepsis in non-geriatric patients. However, the lack of an independent effect on 30-day survival can be explained by the cross-reactivity of HCMV specific CD8+ T-cells towards SARS-CoV-2 peptides, which might confer some protection to HCMV seropositive patients. The inclusion of a post-surgery control group strengthens the generalizability of the findings. Further research is needed to elucidate the underlying mechanisms of this association, explore different patient populations, and identify interventions for optimizing patient management. Conclusion: This study validates the association between HCMV seropositivity and severe COVID-19-induced sepsis in non-geriatric patients, contributing to the growing body of evidence on viral pathogens in sepsis. Although HCMV serostatus did not independently influence 30-day survival, future investigations should focus on unraveling the intricate interplay between HCMV, immune responses, and COVID-19. These insights will aid in risk stratification and the development of targeted interventions for viral sepsis.
Asunto(s)
COVID-19 , Infecciones por Citomegalovirus , Citomegalovirus , SARS-CoV-2 , Sepsis , Humanos , COVID-19/inmunología , COVID-19/mortalidad , COVID-19/epidemiología , COVID-19/complicaciones , Masculino , Femenino , Persona de Mediana Edad , Sepsis/inmunología , Sepsis/epidemiología , Sepsis/mortalidad , Citomegalovirus/inmunología , Anciano , Infecciones por Citomegalovirus/inmunología , Infecciones por Citomegalovirus/epidemiología , Infecciones por Citomegalovirus/mortalidad , Infecciones por Citomegalovirus/complicaciones , SARS-CoV-2/inmunología , Factores de Riesgo , Adulto , Anticuerpos Antivirales/sangreAsunto(s)
Infecciones por Citomegalovirus , Trasplante de Células Madre Hematopoyéticas , Leucemia Mieloide Aguda , Ácido Micofenólico , Humanos , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Leucemia Mieloide Aguda/mortalidad , Leucemia Mieloide Aguda/terapia , Leucemia Mieloide Aguda/complicaciones , Leucemia Mieloide Aguda/tratamiento farmacológico , Ácido Micofenólico/uso terapéutico , Ácido Micofenólico/efectos adversos , Ácido Micofenólico/administración & dosificación , Infecciones por Citomegalovirus/mortalidad , Infecciones por Citomegalovirus/tratamiento farmacológico , Infecciones por Citomegalovirus/complicaciones , Masculino , Femenino , Persona de Mediana Edad , Citomegalovirus , Adulto , Anciano , Inmunosupresores/uso terapéuticoRESUMEN
BACKGROUND: Cytomegalovirus (CMV) infection is associated with poor outcome in ICU patients. However, data on immunocompromised patients are scarce. This study aims to describe characteristics and outcomes of critically ill hematological patients and CMV infection. CMV disease characteristics and relationship between CMV viral load, CMV disease, coinfections by other pathogens and outcomes are described. METHODS: Retrospective single center study (Jan 2010-Dec 2017). Adult patients, admitted to the ICU, having underlying hematological malignancy and CMV infection were included. Results are reported as median (interquartile) or n (%). Factors associated with hospital mortality or CMV disease were analysed using logistic regression. RESULTS: 178 patients were included (median age 55y [42-64], 69.1% male). Hospital mortality was 53% (n = 95). Median viral load was 2.7 Log [2.3-3.5]. CMV disease occurred in 44 (24.7%) patients. Coinfections concerned 159 patients (89.3%). After adjustment for confounders, need for vasopressors (OR 2.53; 95%CI 1.11-5.97) and viral load (OR 1.88 per Log; 95%CI 1.29-2.85) were associated with hospital mortality. However, neither CMV disease nor treatment were associated with outcomes. Allogeneic stem cell transplantation (OR 2.55; 95%CI 1.05-6.16), mechanical ventilation (OR 4.11; OR 1.77-10.54) and viral load (OR 1.77 per Log; 95%CI 1.23-2.61) were independently associated with CMV disease. Coinfections were not associated with CMV disease or hospital mortality. CONCLUSION: In critically-ill hematological patients, CMV viral load is independently associated with hospital mortality. Conversely, neither CMV disease nor treatment was associated with outcome suggesting viral load to be a surrogate for immune status rather than a cause of poor outcome.
Asunto(s)
Infecciones por Citomegalovirus , Neoplasias Hematológicas , Mortalidad Hospitalaria , Unidades de Cuidados Intensivos , Carga Viral , Humanos , Masculino , Femenino , Persona de Mediana Edad , Infecciones por Citomegalovirus/mortalidad , Infecciones por Citomegalovirus/epidemiología , Neoplasias Hematológicas/terapia , Neoplasias Hematológicas/mortalidad , Estudios Retrospectivos , Unidades de Cuidados Intensivos/estadística & datos numéricos , Adulto , Enfermedad Crítica , Huésped Inmunocomprometido , Coinfección/epidemiología , Citomegalovirus/aislamiento & purificaciónRESUMEN
BACKGROUND: We aimed to investigate factors associated with cytomegalovirus (CMV) viremia and CMV disease and its impact on post-transplant outcomes including overall survival (OS) following allogeneic hematopoietic stem cell transplantation (Allo-SCT). METHODS: We conducted a single-center retrospective study including 452 Allo-SCT recipients (matched unrelated donor, MUD 61%; haploidentical, haplo 39%) from 2016 to 2021. Data were analyzed using SPSS v28. Descriptive (chi-square and t-test), Kaplan-Meier and regression analyses were conducted. RESULTS: The median age was 57 years. Sixty-one percent were males and 84.3% were Caucasians. CMV serostatus was positive in 59.1% of recipients. The median follow-up was 24.4 months. CMV viremia and CMV disease were observed in 181 (40%) and 32 (7%) patients, respectively. Among CMV seropositive recipients, 65% developed CMV viremia and 11% were noted to have CMV disease compared to 4% and 1% in seronegative recipients, respectively (p < 0.001). Patients with CMV disease had significantly lower OS than those without CMV disease (median 14.1 months vs. not reached, p = 0.024); however, OS was not associated with CMV viremia (median not reached in both groups, p = 0.640). Letermovir prophylaxis was used in 66% (n = 176/267) of CMV seropositive recipients, but no impact was observed on the incidence of CMV viremia or CMV disease and OS. CONCLUSIONS: CMV disease leads to significantly inferior survival after an allogeneic hematopoietic cell transplantation. Recipient CMV seropositive status was associated with the risk of CMV viremia and CMV disease, and this was not abrogated with the use of Letermovir prophylaxis.
Asunto(s)
Infecciones por Citomegalovirus , Citomegalovirus , Trasplante de Células Madre Hematopoyéticas , Trasplante Homólogo , Activación Viral , Humanos , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Masculino , Persona de Mediana Edad , Femenino , Infecciones por Citomegalovirus/mortalidad , Estudios Retrospectivos , Citomegalovirus/fisiología , Adulto , Anciano , Estudios de Seguimiento , Adulto Joven , Viremia/epidemiología , Adolescente , Factores de Riesgo , PronósticoRESUMEN
BACKGROUND: Cytomegalovirus (CMV) reactivation is common after transplantation, and may further augment natural killer (NK) cell activity, which has a protective role through both innate and adaptive immune responses. Bacterial bloodstream infections (BBSIs) are a common cause of morbidity and mortality in patients following allo-HSCT. Therefore, we hypothesized that CMV reactivation might play a role in the outcomes of patients with BBSI after allo-HSCT. OBJECTIVES: We investigated the role of CMV reactivation in the clinical outcomes of patients with BBSI after allo-HSCT. STUDY DESIGN: A total of 101 BBSI patients (45 non-CMV reactivation [NCR] and 56 CMV reactivation [CR]) were included in the study following allo-HSCT. Clinical and laboratory findings were reviewed, and differences were tested using the Chi-square (χ2) test. Multivariate Cox regression analysis was used to calculate hazard ratios for between-group comparisons of clinical outcomes. RESULTS: CMV reactivation had a negative prognostic impact on the clinical outcomes of BBSI patients following allo-HSCT with regard to the 1-year overall survival time (HR, 3.583; 95% CI, 1.347-9.533; P = 0.011). In 56 BBSI patients with CMV reactivation following allo-HSCT, the 1-year mortality among those in whom CMV was reactivated first (CRF) was significantly elevated (56.5% vs. 18.2%, P = 0.003) compared with patients in whom the BBSIs occurred first (BOF). CONCLUSIONS: CMV reactivation in BBSI patients is related to higher mortality 1-year after allo-HSCT. Further studies on a larger cohort are needed to better understanding the mechanism of CMV reactivation influence.
Asunto(s)
Infecciones por Citomegalovirus , Citomegalovirus , Trasplante de Células Madre Hematopoyéticas , Activación Viral , Humanos , Masculino , Femenino , Infecciones por Citomegalovirus/inmunología , Infecciones por Citomegalovirus/mortalidad , Citomegalovirus/fisiología , Citomegalovirus/inmunología , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Adulto , Persona de Mediana Edad , Trasplante Homólogo , Estudios Retrospectivos , Pronóstico , Adulto Joven , Adolescente , Infecciones Bacterianas/inmunología , Infecciones Bacterianas/mortalidad , Bacteriemia/inmunología , Bacteriemia/mortalidadRESUMEN
BACKGROUND: Xenotransplantation, particularly when involving pig donors, presents challenges related to the transmission of porcine cytomegalovirus (pCMV) and its potential impact on recipient outcomes. This study aimed to investigate the relationship between pCMV positivity in both donors and recipients and the survival time of cynomolgus monkey recipients after xenogeneic kidney transplantation. METHODS: We conducted 20 cynomolgus xenotransplants using 18 transgenic pigs. On the surgery day, donor pig blood was sampled, and DNA was extracted from serum and peripheral blood mononuclear cells. Recipient DNA extraction followed the same protocol from pre-transplantation to post-transplantation. Porcine cytomegalovirus detection used real-time polymerase chain reaction (real-time PCR) with the ViroReal kit, achieving a sensitivity of 50 copies/reaction. A Ct value of 37.0 was the pCMV positivity threshold. RESULTS: Of 20 cynomolgus recipients, when donors tested negative for pCMV, recipients also showed negative results in 9 cases. In 4 cases where donors were negative, recipients tested positive. All 5 cases with pCMV-positive donors resulted in positive assessments for recipients. Detection of donor pCMV correlated with shorter recipient survival. Continuous recipient positivity during observation correlated with shorter survival, whereas transient detection showed no significant change in survival rates. However, donor pig phenotypes and transplantation protocols did not significantly impact survival. CONCLUSION: The detection of pCMV in both donors and recipients plays a crucial role in xenotransplantation outcomes. These findings suggest the importance of monitoring and managing pCMV in xenotransplantation to enhance long-term outcomes.
Asunto(s)
Infecciones por Citomegalovirus , Citomegalovirus , Trasplante de Riñón , Macaca fascicularis , Trasplante Heterólogo , Animales , Trasplante Heterólogo/efectos adversos , Porcinos , Citomegalovirus/genética , Infecciones por Citomegalovirus/mortalidad , Infecciones por Citomegalovirus/virología , Trasplante de Riñón/efectos adversos , Supervivencia de Injerto , Donantes de Tejidos , Animales Modificados GenéticamenteRESUMEN
BACKGROUND: Human cytomegalovirus (HCMV) is the most common and serious opportunistic infection after solid organ and hematopoietic stem cell transplantation. In this study, we used whole-genome HCMV data to investigate viral factors associated with the clinical outcome. METHODS: We sequenced HCMV samples from 16 immunocompromised pediatric patients with persistent viremia. Eight of the 16 patients died of complications due to HCMV infection. We also sequenced samples from 35 infected solid organ adult recipients, of whom 1 died with HCMV infection. RESULTS: We showed that samples from both groups have fixed variants at resistance sites and mixed infections. Next-generation sequencing also revealed nonfixed variants at resistance sites in most of the patients who died (6/9). A machine learning approach identified 10 genes with nonfixed variants in these patients. These genes formed a viral signature that discriminated patients with HCMV infection who died from those who survived with high accuracy (area under the curve = 0.96). Lymphocyte numbers for a subset of patients showed no recovery posttransplant in the patients who died. CONCLUSIONS: We hypothesize that the viral signature identified in this study may be a useful biomarker for poor response to antiviral drug treatment and indirectly for poor T-cell function, potentially identifying early those patients requiring nonpharmacological interventions.
Asunto(s)
Infecciones por Citomegalovirus , Citomegalovirus , Huésped Inmunocomprometido , Humanos , Infecciones por Citomegalovirus/virología , Infecciones por Citomegalovirus/inmunología , Infecciones por Citomegalovirus/mortalidad , Citomegalovirus/genética , Niño , Masculino , Femenino , Adulto , Preescolar , Antivirales/uso terapéutico , Adolescente , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Lactante , Trasplante de Órganos/efectos adversos , Secuenciación de Nucleótidos de Alto Rendimiento , Viremia , Genes Virales/genética , Variación Genética , Farmacorresistencia Viral/genética , Adulto Joven , Persona de Mediana EdadRESUMEN
Cytomegalovirus (CMV) causes significant morbidity and mortality in recipients of allogeneic hematopoietic cell transplantation (HCT). Whereas insights gained from mathematical modeling of other chronic viral infections such as HIV, hepatitis C, and herpes simplex virus-2 have aided in optimizing therapy, previous CMV modeling has been hindered by a lack of comprehensive quantitative PCR viral load data from untreated episodes of viremia in HCT recipients. We performed quantitative CMV DNA PCR on stored, frozen serum samples from the placebo group of participants in a historic randomized controlled trial of ganciclovir for the early treatment of CMV infection in bone marrow transplant recipients. We developed four main ordinary differential Equation mathematical models and used model selection theory to choose between 38 competing versions of these models. Models were fit using a population, nonlinear, mixed-effects approach. We found that CMV kinetics from untreated HCT recipients are highly variable. The models that recapitulated the observed patterns most parsimoniously included explicit, dynamic immune cell compartments and did not include dynamic target cell compartments, consistent with the large number of tissue and cell types that CMV infects. In addition, in our best-fitting models, viral clearance was extremely slow, suggesting severe impairment of the immune response after HCT. Parameters from our best model correlated well with participants' clinical risk factors and outcomes from the trial, further validating our model. Our models suggest that CMV dynamics in HCT recipients are determined by host immune response rather than target cell limitation in the absence of antiviral treatment.
Asunto(s)
Infecciones por Citomegalovirus/prevención & control , Citomegalovirus , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Modelos Teóricos , Aloinjertos , Antivirales/administración & dosificación , Infecciones por Citomegalovirus/etiología , Infecciones por Citomegalovirus/mortalidad , Ganciclovir/administración & dosificación , Trasplante de Células Madre Hematopoyéticas/estadística & datos numéricos , Humanos , Carga ViralRESUMEN
Human cytomegalovirus (HCMV) is a highly prevalent herpes virus which persists as a latent infection and has been detected in several different tumor types. HCMV disease is rare but may occur in high-risk settings, often manifesting as a pulmonary infection. To date HCMV has not been investigated in malignant pleural mesothelioma (MPM). In a consecutive case series of 144 MPM patients we evaluated two biomarkers of HCMV: IgG serostatus (defined as positive and negative) and DNAemia (>100 copies/mL of cell free HCMV DNA in serum). Approximately half of the MPM patient population was HCMV IgG seropositive (51%). HCMV DNAemia was highly prevalent (79%) in MPM and independent of IgG serostatus. DNAemia levels consistent with high level current infection (>1000 copies/mL serum) were present in 41% of patients. Neither IgG serostatus nor DNAemia were associated with patient survival. In tissues, we observed that HCMV DNA was present in 48% of tumors (n = 40) and only 29% of normal pleural tissue obtained from individuals without malignancy (n = 21). Our results suggest nearly half of MPM patients have a high level current HCMV infection at the time of treatment and that pleural tissue may be a reservoir for latent HCMV infection. These findings warrant further investigation to determine the full spectrum of pulmonary infections in MPM patients, and whether treatment for high level current HCMV infection may improve patient outcomes.
Asunto(s)
Anticuerpos Antivirales/sangre , Citomegalovirus/metabolismo , ADN Viral/sangre , Inmunoglobulina G/sangre , Mesotelioma Maligno , Neoplasias Pleurales , Neumonía Viral , Anciano , Infecciones por Citomegalovirus/sangre , Infecciones por Citomegalovirus/mortalidad , Supervivencia sin Enfermedad , Femenino , Humanos , Masculino , Mesotelioma Maligno/sangre , Mesotelioma Maligno/mortalidad , Mesotelioma Maligno/virología , Persona de Mediana Edad , Neoplasias Pleurales/sangre , Neoplasias Pleurales/mortalidad , Neoplasias Pleurales/virología , Neumonía Viral/sangre , Neumonía Viral/mortalidad , Neumonía Viral/virología , Estudios Retrospectivos , Tasa de SupervivenciaRESUMEN
BACKGROUND: Whether donor (D+) or recipient (R+) cytomegalovirus (CMV) seropositivity is associated with functional impairment in liver transplant recipients is not known. METHODS: Patients included adult liver transplant recipients in the Organ Procurement and Transplantation Network database transplanted over a five-year period from 1 January 2014-31 December 2018. Functional status in the database was assessed using Karnofsky performance scale. A logistic regression model that controlled for potential confounders was used to examine the association of CMV serostatus and functional status. Variables significantly associated with functional status (p < 0.05) were then used to develop propensity score and propensity score matched analysis was conducted where each patient was compared with a matched-control with the same propensity score. RESULTS: Among 30,267 adult liver transplant recipients, D+ or R+ patients had significantly lower functional status at last follow-up than the D-R- cohort (OR 0.88, 95% CI 0.80-0.96, p = 0.007). In propensity score matched model, D+ or R+ patients had significantly lower functional status than matched-controls (p = 0.009). D+ or R+ CMV serostatus (p = 0.018) and low functional level (p < 0.001) were also independently associated with infections as cause-of-death. CONCLUSIONS: D+ or R+ liver transplant recipients had lower functional status and higher risk of deaths due to infections. Future studies are warranted to examine the mechanistic basis of these findings in the setting of transplantation.
Asunto(s)
Infecciones por Citomegalovirus/complicaciones , Citomegalovirus/inmunología , Estado Funcional , Trasplante de Hígado/efectos adversos , Estudios Seroepidemiológicos , Receptores de Trasplantes/estadística & datos numéricos , Adulto , Anciano , Estudios de Cohortes , Citomegalovirus/patogenicidad , Infecciones por Citomegalovirus/inmunología , Infecciones por Citomegalovirus/mortalidad , Infecciones por Citomegalovirus/fisiopatología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Puntaje de Propensión , Donantes de Tejidos/estadística & datos numéricosRESUMEN
BACKGROUND: Primary cytomegalovirus (CMV) infection during pregnancy carries a risk of congenital infection and possible severe sequelae. There is no established intervention for preventing congenital CMV infection. METHODS: In this multicenter, double-blind trial, pregnant women with primary CMV infection diagnosed before 24 weeks' gestation were randomly assigned to receive a monthly infusion of CMV hyperimmune globulin (at a dose of 100 mg per kilogram of body weight) or matching placebo until delivery. The primary outcome was a composite of congenital CMV infection or fetal or neonatal death if CMV testing of the fetus or neonate was not performed. RESULTS: From 2012 to 2018, a total of 206,082 pregnant women were screened for primary CMV infection before 23 weeks of gestation; of the 712 participants (0.35%) who tested positive, 399 (56%) underwent randomization. The trial was stopped early for futility. Data on the primary outcome were available for 394 participants; a primary outcome event occurred in the fetus or neonate of 46 of 203 women (22.7%) in the group that received hyperimmune globulin and of 37 of 191 women (19.4%) in the placebo group (relative risk, 1.17; 95% confidence interval [CI] 0.80 to 1.72; P = 0.42). Death occurred in 4.9% of fetuses or neonates in the hyperimmune globulin group and in 2.6% in the placebo group (relative risk, 1.88; 95% CI, 0.66 to 5.41), preterm birth occurred in 12.2% and 8.3%, respectively (relative risk, 1.47; 95% CI, 0.81 to 2.67), and birth weight below the 5th percentile occurred in 10.3% and 5.4% (relative risk, 1.92; 95% CI, 0.92 to 3.99). One participant in the hyperimmune globulin group had a severe allergic reaction to the first infusion. Participants who received hyperimmune globulin had a higher incidence of headaches and shaking chills while receiving infusions than participants who received placebo. CONCLUSIONS: Among pregnant women, administration of CMV hyperimmune globulin starting before 24 weeks' gestation did not result in a lower incidence of a composite of congenital CMV infection or perinatal death than placebo. (Funded by the Eunice Kennedy Shriver National Institute of Child Health and Human Development and the National Center for Advancing Translational Sciences; ClinicalTrials.gov number, NCT01376778.).
Asunto(s)
Infecciones por Citomegalovirus/congénito , Inmunoglobulinas Intravenosas/uso terapéutico , Complicaciones Infecciosas del Embarazo/tratamiento farmacológico , Adulto , Infecciones por Citomegalovirus/tratamiento farmacológico , Infecciones por Citomegalovirus/mortalidad , Infecciones por Citomegalovirus/prevención & control , Método Doble Ciego , Femenino , Muerte Fetal/etiología , Muerte Fetal/prevención & control , Enfermedades Fetales/prevención & control , Humanos , Incidencia , Lactante , Mortalidad Infantil , Recién Nacido , Transmisión Vertical de Enfermedad Infecciosa/prevención & control , Infusiones Intravenosas , Embarazo , Insuficiencia del TratamientoRESUMEN
BACKGROUND: Reactivation of human cytomegalovirus (CMV) occurs in non-immunocompromised patients with or without specific organ involvement, but it is still unknown whether it has a clinical implication on long-term prognosis or not. METHODS: A retrospective cohort study evaluating non-immunocompromised adult patients with CMV reactivation was conducted during the period between January 2010 and February 2018. Patients were divided into ganciclovir-treated and non-treated groups. Patients who died within 30 days from CMV reactivation were excluded as they died from complex causes of conditions. Survivors were followed for 30-months to evaluate long-term prognosis. RESULTS: A total of 136 patients with CMV reactivation was included, consisting of 66 ganciclovir-treated (48.5%) and 70 non-treated (51.5%) patients. Overall, patients were old-aged (median 70 years old) and most were treated with pneumonia of any cause (91.2%). More patients in ganciclovir-treated group were treated at intensive care unit (43.9% vs 24.3%, respectively) and had higher viral load over 5000 copies/ml (48.5% vs 22.9%) than non-treated group (all P < 0.05). Primary and secondary endpoints including 30-months survival (28.0 vs 38.9%, respectively) and 12-months survival (40.3% vs 49.2%) were not statistically different between the ganciclovir-treated and non-treated groups. In the multivariate analyses, ganciclovir treatment was not associated with 30-months survival (HR 1.307, 95% CI 0.759-2.251) and 12-months survival (HR 1.533, 95% CI 0.895-2.624). CONCLUSION: In a retrospective cohort study evaluating non-immunocompromised patients with CMV reactivation, ganciclovir treatment was not associated with long-term prognosis. Antiviral treatment in this condition would not be necessary unless organ involvement is suspected.
Asunto(s)
Antivirales/uso terapéutico , Infecciones por Citomegalovirus/tratamiento farmacológico , Infecciones por Citomegalovirus/mortalidad , Ganciclovir/uso terapéutico , Anciano , Citomegalovirus/efectos de los fármacos , Citomegalovirus/fisiología , Infecciones por Citomegalovirus/virología , Humanos , Huésped Inmunocomprometido , Masculino , Persona de Mediana Edad , Pronóstico , Estudios Retrospectivos , Resultado del Tratamiento , Carga Viral , Activación Viral/efectos de los fármacosRESUMEN
BACKGROUND: We investigatedthe association between time-averaged area under the curve (AAUC) of cytomegalovirus (CMV) viral load (VL) by day 100 and overall survival (OS) at 1-year after hematopoietic cell transplantation (HCT). METHODS: In a retrospective cohort study, including patients receiving HCT between June 2010 and December 2017 from Memorial Sloan Kettering Cancer Center, AAUC was calculated for patients with detected VL. Patients were categorized into non-controllers (Q4) and controllers (Q1-Q3) using the highest AAUC quartile as cutoff. Cox models were used to estimate the association between AAUC and OS. Patients with non-detected CMV VL were categorized into elite-controllers (recipient+ [R+] or R-/donor+ [D+]) and R-/D-. RESULTS: The study (N = 952) included 282 controllers, 93 non-controllers, 275 elite-controllers, and 302 R-/D-. OS was 80.1% and 58.1% for controllers and non-controllers, respectively. In multivariable models, non-controllers had worse OS versus controllers (adjusted hazard ratio [HR] = 2.65; 95% confidence interval [CI], 1.71-4.12). In landmark analyses, controllers had similar OS as elite-controllers (HR = 1.26; 95% CI, .83-1.91) or R-/D- (HR = 0.98; 95% CI, .64-1.5). CONCLUSIONS: Non-controllers had worse OS 1-year post-HCT. Controllers had similar OS as elite-controllers or R-/D-. Future studies are needed to validate our AAUC cutoff across different cohorts and CMV management strategies.
Asunto(s)
Infecciones por Citomegalovirus , Trasplante de Células Madre Hematopoyéticas , Insuficiencia Multiorgánica/mortalidad , Carga Viral , Citomegalovirus , Infecciones por Citomegalovirus/mortalidad , Humanos , Cinética , Insuficiencia Multiorgánica/virología , Estudios Retrospectivos , Tasa de SupervivenciaRESUMEN
Prior studies suggest increased cytomegalovirus (CMV) infection after haploidentical donor transplantation with posttransplant cyclophosphamide (HaploCy). The role of allograft source and posttransplant cyclophosphamide (PTCy) in CMV infection is unclear. We analyzed the effect of graft source and PTCy on incidence of CMV infection, and effects of serostatus and CMV infection on transplant outcomes. We examined patients reported to the Center for International Blood and Marrow Transplantation Research between 2012 and 2017 who had received HaploCy (n = 757), matched related (Sib) with PTCy (SibCy, n = 403), or Sib with calcineurin inhibitor-based prophylaxis (SibCNI, n = 1605). Cumulative incidences of CMV infection by day 180 were 42%, 37%, and 23%, respectively (P < .001). CMV disease was statistically comparable. CMV infection risk was highest for CMV-seropositive recipients (R+), but significantly higher in PTCy recipients regardless of donor (HaploCy [n = 545]: hazard ratio [HR], 50.3; SibCy [n = 279]: HR, 47.7; SibCNI [n = 1065]: HR, 24.4; P < .001). D+/R- patients also had increased risk for CMV infection. Among R+ or those developing CMV infection, HaploCy had worse overall survival and nonrelapse mortality. Relapse was unaffected by CMV infection or serostatus. PTCy was associated with lower chronic graft-versus-host disease (GVHD) overall, but CMV infection in PTCy recipients was associated with higher chronic GVHD (P = .006). PTCy, regardless of donor, is associated with higher incidence of CMV infection, augmenting the risk of seropositivity. Additionally, CMV infection may negate the chronic GVHD protection of PTCy. This study supports aggressive prevention strategies in all receiving PTCy.
Asunto(s)
Ciclofosfamida/efectos adversos , Infecciones por Citomegalovirus , Citomegalovirus , Trasplante de Células Madre Hematopoyéticas , Adolescente , Adulto , Anciano , Aloinjertos , Niño , Preescolar , Enfermedad Crónica , Ciclofosfamida/administración & dosificación , Infecciones por Citomegalovirus/inducido químicamente , Infecciones por Citomegalovirus/mortalidad , Supervivencia sin Enfermedad , Femenino , Enfermedad Injerto contra Huésped/tratamiento farmacológico , Enfermedad Injerto contra Huésped/metabolismo , Humanos , Incidencia , Masculino , Persona de Mediana Edad , Tasa de SupervivenciaRESUMEN
BACKGROUND: Cytomegalovirus (CMV) gastritis is occasionally reported in case reports and limited case series. Up to now, it is the largest and most comprehensive retrospective study of CMV gastritis. METHODS: All patients who were histologically diagnosed with CMV gastritis at Linkou Chang Gung Memorial Hospital between January 2000 and April 2020 were included. Patients were divided into two groups according to immunity. Between-group differences in characteristics, manifestations, endoscopic features, prognostic factors, and outcomes were analyzed. The main endpoint was 3-month mortality. RESULTS: A total of 54 patients (34 immunocompromised, 20 immunocompetent) were enrolled. Common presentations included gastrointestinal bleeding (35.2%), abdominal pain (33.3%) and fever (31.5%). The endoscopic features included ulcer (88.9%) and inflammation (11.1%). The 3-month mortality rate was 20.4% and overall mortality rate was 40.7%. Acute kidney injury was the only independent risk factor for 3-month mortality (OR 53.89, 95%CI 1.56-1861.73, pâ¯=â¯0.027). Anti-viral therapy and host immune status did not affect 3-month mortality. CONCLUSION: Both immunocompromised and immunocompetent patients with CMV gastritis have high mortality rates, without significant between-group differences. Acute kidney injury is the only independent predictive factor for 3-month mortality. Prevention of acute kidney injury may possibly improve the 3-month mortality rate.