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Background: Liver transplantation (LT) is the best treatment for end-stage liver disease; however, biliary complications (BCs) still pose a significant challenge. Among the post-transplant BC, strictures and biliary fistulas are the most common. Biliary strictures are classified as anastomotic and non-anastomotic. Some previous studies suggest an association between post-transplant biliary strictures and cytomegalovirus (CMV) infection. In this study, we aimed to identify whether there is an association between CMV infection and biliary strictures in patients undergoing LT. Methods: A retrospective study of 175 patients aged ≥18 years undergoing LT at Felicio Rocho Hospital between 2011 and 2017 was conducted. All included patients received grafts perfused with Institut Georges Lopez-1 (IGL-1) solution from brain-dead donors, survived post-transplantation for more than 120 days, and had a minimum follow-up of 12 months after LT. The diagnosis of CMV was made by antigenemia and biliary strictures by magnetic resonance cholangiopancreatography (MRCP). Results: The average age of the recipients was 54 years. Postoperative BCs occurred in 12% of transplants. The most common BC was stricture (9.1%), with a predominance of anastomotic strictures (AS) over non-AS (NAS) (87.5% vs. 12.5%, respectively). CMV infection was confirmed in 22.9% of patients. In the univariate analysis, post-transplant CMV infection correlated with the development of BCs (P=0.01), as well as biliary strictures (P=0.008). In the multivariate analysis, however, only model for end-stage liver disease (MELD) >21 was a risk factor for the development of BCs in general (P=0.02) and biliary strictures (P=0.01). Conclusions: CMV infection was not an independent risk factor for the development of non-anastomotic post-transplant biliary strictures in this study.
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OBJECTIVE: The objective of this study was to assess the role of T-lymphocyte immune responses in newborns with congenital cytomegalovirus (CMV) infection (cCMV) and their potential association with the development of long-term sequelae. STUDY DESIGN: A multicenter, prospective study from 2017 to 2022 was conducted across 8 hospitals in Spain. Blood samples were collected within the first month of life from neonates diagnosed with cCMV. Intracellular cytokine staining was employed to evaluate the presence of CMV-specific interferon-gamma (IFN-γ)-producing CD8+ and CD4+ T lymphocytes (CMV-IFN-γ-CD8+/CD4+) using flow cytometry. The development of sequelae, including hearing loss and neurologic impairment, was assessed during follow-up. RESULTS: In total, 64 newborns were included; 42 infants (65.6%) had symptomatic cCMV. The median age at the last follow-up visit was 25.3 months (IQR 20.1-34.4). Eighteen infants had long-term sequelae (28.1%), predominantly hearing loss (20.3%) and neurologic disorders (15.6%). No relationship was observed between total count or percentage of CMV-specific IFN-γ-CD8+ or CD4+ lymphocytes and long-term sequelae. Multivariable analysis demonstrated an association between lower total lymphocyte count and long-term sequelae (aOR 0.549, 95% CI: 0.323-0.833), which requires further study. CONCLUSIONS: CMV-specific IFN-γ-CD4+ and CD8+ T-lymphocyte responses in neonates with cCMV were not predictive of long-term sequelae.
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Infecções por Citomegalovirus , Humanos , Infecções por Citomegalovirus/imunologia , Infecções por Citomegalovirus/complicações , Recém-Nascido , Estudos Prospectivos , Masculino , Feminino , Linfócitos T CD8-Positivos/imunologia , Linfócitos T CD4-Positivos/imunologia , Espanha , Interferon gama/sangue , Lactente , Seguimentos , Imunidade Celular , Citomegalovirus/imunologia , Perda Auditiva/imunologiaRESUMO
At present, recipients of allogeneic hematopoietic stem-cells are still suffering from recurrent infections after transplantation. Infusion of virus-specific T cells (VST) post-transplant reportedly fights several viruses without increasing the risk of de novo graft-versus-host disease. This study targeted cytomegalovirus (CMV) for the development of an innovative approach for generating a very specific VST product following Good Manufacturing Practices (GMP) guidelines. We used a sterile disposable compartment named the Leukoreduction System Chamber (LRS-chamber) from the apheresis platelet donation kit as the starting material, which has demonstrated high levels of T cells. Using a combination of IL-2 and IL-7 we could improve expansion of CMV-specific T cells. Moreover, by developing and establishing a new product protocol, we were able to stimulate VST proliferation and favors T cell effector memory profile. The expanded VST were enriched in a closed automated system, creating a highly pure anti-CMV product, which was pre-clinically tested for specificity in vitro and for persistence, biodistribution, and toxicity in vivo using NOD scid mice. Our results demonstrated very specific VST, able to secrete high amounts of interferon only in the presence of cells infected by the human CMV strain (AD169), and innocuous to cells partially HLA compatible without viral infection.
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Antineoplásicos , Infecções por Citomegalovirus , Transplante de Células-Tronco Hematopoéticas , Animais , Camundongos , Humanos , Linfócitos T Citotóxicos , Transplante de Células-Tronco Hematopoéticas/métodos , Distribuição Tecidual , Citomegalovirus , Infecções por Citomegalovirus/terapia , Imunoterapia Adotiva/métodosRESUMO
Cytomegalovirus (CMV) mutations associated with antiviral resistance have become a major problem related to high mortality in kidney transplant patients. The aim of the study was to investigate mutations in the CMV genes UL97 and UL54 associated with antiviral resistance. A retrospective observational cohort study was carried out at Hospital Ophir Loyola (HOL), a reference in Kidney Transplantation. A total of 81 patients who underwent kidney transplantation were followed up between 2016 and 2018 were monitored for CMV viral load by performing qPCR. Sanger sequencing was performed on 66 patients. All CMV-positive kidney transplant recipients were included. Mutations were observed in 15 samples (22.72%) from patients. Most cases involved UL97 mutations. Mutation in UL54 without mutation in UL97 was detected in only 2 cases. Resistance mutations in UL97 were identified, such as M460V, L595S, H520Q, two co-mutations D465R + Del524 and A594P + D413A and a 3 codon deletion (del598-601). The search for mutations in the CMV genes identified mutations that confer resistance to conventional antivirals, such as ganciclovir and cidofovir, used in the treatment of these patients. Confirmation of the association with increased CMV viral load in transplanted patients, due to mutation in resistance genes, requires phenotypic analysis for confirmation purposes. These were the first findings in patients in northern Brazil that we know of.
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Infecções por Citomegalovirus , Transplante de Rim , Humanos , Antivirais/farmacologia , Citomegalovirus/genética , Infecções por Citomegalovirus/tratamento farmacológico , Infecções por Citomegalovirus/genética , Ganciclovir/farmacologia , Mutação/genética , Estudos RetrospectivosRESUMO
ABSTRACT Introduction: Relapse of acute myeloid leukemia (AML) after allogeneic stem cell transplantation (allo-SCT) leads to dismal outcomes. This study aimed to identify high-risk patients and explore the effects of cytomegalovirus (CMV) reactivation in a high CMV-seropositive population. Methods: The study involved a single-center retrospective cohort in Thailand, analyzing clinical risk factors and CMV-mediated immune responses, correlated with transplant outcomes in AML patients. Results: Eighty-five patients with AML in complete remission (CR) undergoing HLA-matched myeloablative allo-SCT between 2011 and February 2021 were enrolled. The relapse rate was 27.1% with the median time of 7 months after transplantation. The 3-year relapse-free-survival (RFS) and overall-survival (OS) were 72.2% and 80.8%, respectively. The disease status (>CR1) and absence of chronic graft-versus-host disease (cGVHD) were independently significant adverse prognostic factors of RFS and OS. Ninety-two percent of recipient-donor pairs were both CMV seropositive. The CMV reactivation occurred in 54.1% of the patients. The clinically significant CMV infection rate was 49.4%. No CMV syndrome/disease or CMV-related mortality occurred. One-year cumulative incidence of relapse among CMV-reactivation and non-reactivation groups were 14.3% and 25.6%, respectively, without a statistically significant difference. Transplantation-related mortality was 11.1%. Conclusions: The transplantation beyond CR1 and absence of cGVHD are powerful prognostic factors associated with inferior RFS and OS. In a high CMV prevalence country, there appears to be no impact of CMV reactivation on relapse in AML patients undergoing an allo-SCT.
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Citomegalovirus , Leucemia Mieloide AgudaRESUMO
Human herpesviruses are enveloped viruses with double-stranded linear DNA genomes highly prevalent in the human population. These viruses are subdivided into three subfamilies, namely alphaherpesvirinae (herpes simplex virus type 1, HSV-1; herpes simplex virus type 2, HSV-2; and varicella-zoster virus, VZV), betaherpesvirinae (human cytomegalovirus, HCMV; human herpesvirus 6, HHV-6; and human herpesvirus 7, HHV-7) and gammaherpesvirinae (Epstein-Barr virus, EBV; and Kaposi's sarcoma-associated herpesvirus, KSHV). Besides encoding numerous molecular determinants to evade the host antiviral responses, these viruses also modulate cellular metabolic processes to promote their replication. Here, we review and discuss existing studies describing an interplay between carbohydrate metabolism and the replication cycle of herpesviruses, altogether highlighting potentially new molecular targets based on these interactions that could be used to block herpesvirus infections.
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BACKGROUND: CMV remains a frequent complication after liver transplantation. Few studies exist in children reporting the epidemiology and outcomes of CMV after LT with current prevention strategies. Our goal is to report the incidence of CMV infection and disease in pediatric LT recipients under preemptive therapy, identify risk factors, complications, and adverse reactions to treatment. METHODS: All pediatric LT recipients from a single center (1998-2018) were included. Antigenemia pp65 (1998-2003) and QNAT or both were used to inform preemptive therapy. Cutoff value for starting treatment was Agpp65 > 10 + cells/200 000 or QNAT >1500 copies/ml or any value in high-risk recipients (D+/R-). RESULTS: One hundred eighteen LT were analyzed. CMV infection was detected in 67% of patients, only 44 (37%) required treatment, and 5 (4%) developed CMV disease. All patients responded well to treatment, and no graft or patients were lost to CMV effects. There were no differences in mortality, CMV indirect effects, or other complications between those who required treatment and those who did not. Thirty-two percent of the patients who received antivirals developed an adverse hematological reaction. Risk factors associated with CMV infection requiring treatment were D+/R- (OR 13.9, p = .01) and fulminant hepatitis (OR 4.8, p = .02). CONCLUSIONS: Preemptive therapy for CMV in children is safe and effective, yields low CMV infection rates that require treatment, and minimal rates of CMV disease, without increasing CMV-related complications. Using this strategy, 63% of our patients did not receive treatment. Therefore, drug exposure, adverse reactions, and resistance risk were minimized.
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Infecções por Citomegalovirus , Transplante de Fígado , Humanos , Criança , Infecções por Citomegalovirus/epidemiologia , Infecções por Citomegalovirus/etiologia , Infecções por Citomegalovirus/tratamento farmacológico , Antivirais/uso terapêutico , Fatores de Risco , Efeitos Psicossociais da Doença , Ganciclovir/uso terapêuticoRESUMO
INTRODUCTION: Relapse of acute myeloid leukemia (AML) after allogeneic stem cell transplantation (allo-SCT) leads to dismal outcomes. This study aimed to identify high-risk patients and explore the effects of cytomegalovirus (CMV) reactivation in a high CMV-seropositive population. METHODS: The study involved a single-center retrospective cohort in Thailand, analyzing clinical risk factors and CMV-mediated immune responses, correlated with transplant outcomes in AML patients. RESULTS: Eighty-five patients with AML in complete remission (CR) undergoing HLA-matched myeloablative allo-SCT between 2011 and February 2021 were enrolled. The relapse rate was 27.1% with the median time of 7 months after transplantation. The 3-year relapse-free-survival (RFS) and overall-survival (OS) were 72.2% and 80.8%, respectively. The disease status (>CR1) and absence of chronic graft-versus-host disease (cGVHD) were independently significant adverse prognostic factors of RFS and OS. Ninety-two percent of recipient-donor pairs were both CMV seropositive. The CMV reactivation occurred in 54.1% of the patients. The clinically significant CMV infection rate was 49.4%. No CMV syndrome/disease or CMV-related mortality occurred. One-year cumulative incidence of relapse among CMV-reactivation and non-reactivation groups were 14.3% and 25.6%, respectively, without a statistically significant difference. Transplantation-related mortality was 11.1%. CONCLUSIONS: The transplantation beyond CR1 and absence of cGVHD are powerful prognostic factors associated with inferior RFS and OS. In a high CMV prevalence country, there appears to be no impact of CMV reactivation on relapse in AML patients undergoing an allo-SCT.
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Abstract Introduction: Members of the Herpesviridae family have been described in patients with systemic lupus erythematous (SLE), but the clinical impact on renal function is not well known. Methods: HSV1, HSV2, VZV, EBV, CMV, HHV-6, HHV-7, and HHV-8 were evaluated by molecular biology on admission in blood samples from 40 consecutive SLE patients hospitalized for lupus activity. Results: Patients were 90.0% female, 77.5% non-white, with average age of 32.7 ± 13.6 years. We found positivity for EBV (65.0%), CMV (30.0%), HSV-1 (30.0%), HHV-6 (12.5%), and HHV-7 (7.5%). For all viruses, age, SLEDAI, hematological tests, ferritin, LDH, C-reactive protein, and erythrocyte sedimentation rate (ESR) were not significant. However, EBV positivity was a significant factor for higher serum creatinine (3.0 ± 2.8 vs. 0.9 ± 0.8; P = 0.001) and urea (86 ± 51 vs. 50 ± 46; P = 0.03). Moreover, positive cases for EBV only or with combined co-infections (66.7%-CMV; 58.3%-HSV-1) or negative for EBV only were evaluated by Kruskal-Wallis test again showed statistical significance for serum creatinine and urea (both P ≤ 0.01), with posttest also showing statistical differences for renal dysfunction and EBV presence (alone or in combined co-infections). The presence of EBV viral load was also significant for nephrotic-range proteinuria, renal flare, and the need for hemodialysis. Conclusion: Members of the Herpeviridae family (mainly EBV, HSV-1 and CMV) are common on hospital admission of SLE patients, reaching 65% for EBV, which seems to be associated with renal dysfunction and could reflect a previous association or overlapping disease, which is not well understood.
Resumo Introdução: Membros da família Herpesviridae tem sido descritos em pacientes com lúpus eritematoso sistêmico (LES), mas o impacto clínico na função renal não é bem conhecido. Métodos: Avaliou-se HSV1, HSV2, VZV, EBV, CMV, HHV-6, HHV-7, HHV-8 por biologia molecular na admissão em amostras sanguíneas de 40 pacientes com LES consecutivos hospitalizados por atividade lúpica. Resultados: Pacientes 90,0% mulheres, 77,5% não brancos, idade média 32,7 ± 13,6 anos. Encontramos positividade para EBV (65,0%), CMV (30,0%), HSV-1 (30,0%), HHV-6 (12,5%), HHV-7 (7,5%). Para todos os vírus, idade, SLEDAI, exames hematológicos, ferritina, LDH, proteína C reativa, velocidade de hemossedimentação não foram significativos. Entretanto, positividade para EBV foi estatisticamente significativo para creatinina (3,0 ± 2,8 vs. 0,9 ± 0,8; P = 0,001) e ureia (86 ± 51 vs. 50 ± 46; P = 0,03) séricas mais elevadas. Ademais, casos positivos para EBV isolado ou com coinfecções combinadas (66,7%-CMV; 58,3%-HSV-1) ou negativos apenas para EBV foram avaliados pelo teste Kruskal-Wallis e novamente mostraram significância estatística para creatinina e ureia séricas (ambas P ≤ 0,01), com pós-teste mostrando também diferenças estatísticas para disfunção renal e presença de EBV (sozinho ou em coinfecções combinadas). A presença de carga viral do EBV também foi significativa para proteinúria de faixa nefrótica, inflamação aguda, necessidade de hemodiálise. Conclusão: Membros da família Herpeviridae (principalmente EBV, HSV-1, CMV) são comuns na admissão de pacientes com LES, chegando a 65% para EBV, que parece associar-se à disfunção renal podendo refletir associação prévia ou doença sobreposta, o que não é bem compreendido.
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Carotid blowout (CB) is a life-threatening surgical emergency with a mortality rate of up to 60%. CB is commonly seen in head and neck cancer patients after surgical and radiation therapy; other causes include iatrogenic, traumatic, or infectious etiologies. We report an unusual case of spontaneous CB presumed to be caused by cytomegalovirus (CMV) in a chronically immunosuppressed transplant recipient. Given the significant mortality of CB and the prevalence of post-transplant CMV, this case highlights an area of further investigation regarding the association between CMV and carotid pathology, as well as the need to include CB as a potential infectious complication in the immunosuppressed population.
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We investigated the effects of TNF-α, IFN-γ, IL-10 polymorphisms on viral infections (CMV, BKPyV, HHV-6, EBV) after renal transplantation. IFN-γ+874 A > T (lower IFN production) was associated with CMV disease (p = .039) in patients under mycophenolate-based therapy and graft failure (p = .025). This study underscores the role of IFN-γ+874 SNP in CMV infection.
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Infecções por Citomegalovirus , Transplante de Rim , Humanos , Citomegalovirus/genética , Transplante de Rim/efeitos adversos , Citocinas , Infecções por Citomegalovirus/genética , Interferon gama/genéticaRESUMO
Post-transcriptional gene silencing (PTGS) is an evolutionarily conserved plant defense mechanism against viruses. This paper aimed to evaluate a dsDNA construct (77 bp) as a template for in vitro production of virus-derived artificial small hairpin RNAs (shRNAs) and test for their potential to trigger the RNAi mechanism in Nicotiana benthamiana plants against CMV after their foliar infiltration. This approach allowed for the production of significant amounts of shRNAs (60-mers) quickly and easily. The gene silencing was confirmed using polymerase chain reaction (PCR), immunological-based assays, and real-time PCR (qPCR). The highest levels of gene silencing were recorded for mRNAs coding for replication protein (ORF1a), the viral suppressor of RNA silencing (ORF2b), and the capsid protein (ORF3b), with 98, 94, and 70% of total transcript silencing, respectively. This protocol provides an alternative to producing significant shRNAs that can effectively trigger the RNAi mechanism against CMV.
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Cucumovirus , Infecções por Citomegalovirus , Cucumovirus/genética , Cucumovirus/metabolismo , Infecções por Citomegalovirus/genética , Doenças das Plantas/genética , Plantas/metabolismo , Interferência de RNA , RNA Interferente Pequeno/genética , RNA Interferente Pequeno/metabolismo , Nicotiana/metabolismoRESUMO
From 2009-2015 to 2016-2019, the proportion of infants in the US with congenital cytomegalovirus treated with valganciclovir roughly doubled for infants enrolled with employer-sponsored insurance (from 16% to 29%) and Medicaid (from 16% to 36%). The proportion treated with valganciclovir increased for all congenital cytomegalovirus disease severity groups.
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Infecções por Citomegalovirus , Citomegalovirus , Antivirais/uso terapêutico , Infecções por Citomegalovirus/diagnóstico , Infecções por Citomegalovirus/tratamento farmacológico , Humanos , Lactente , Medicaid , Estados Unidos , Valganciclovir/uso terapêuticoRESUMO
INTRODUCTION: Both cytomegalovirus (CMV) infection and CMV disease have been linked with several long-term indirect effects in kidney transplant recipients. Research questions: We conducted a retrospective study to assess the association between cytomegalovirus disease and risks of death, shortterm cardiovascular events and graft loss in a cohort of renal transplant recipients. DESIGN: The associations between CMV disease and death and cardiovascular events were determined using Cox regression models, while the association between viral disease and graft loss risk was analyzed through a competing risks regression according to the Fine and Gray method. Death with a functioning graft was considered as a competing risk event. RESULTS: A total of 865 consecutive renal transplant recipients were included. The prevalence of seropositive donor/seronegative recipient (D+/R-) group was 89.9% with the remaining patients classified as seropositive recipient (R+). After median follow-up time of 24.4 months, CMV disease was not a risk factor for all-causes mortality (HR = 1.75; 95% CI 0.94-3.25), early cardiovascular events (HR = 0.54; 95% CI 0.16-1.82) or graft loss (subhazard ratio [the HR adjusted for competing risk of death with functioning graft] = 0.99; 95% CI 0.53-1.84). CONCLUSIONS: In this cohort with high prevalence of CMV IgG antibodies, we found no association between cytomegalovirus disease and risk of death or graft loss. The relationship between CMV and cardiovascular disease remains to be unraveled and probably corresponds to a multifactorial phenomenon involving individual risk factors and the immune response to infection rather than the virus effect itself.
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Doenças Cardiovasculares , Infecções por Citomegalovirus , Transplante de Rim , Antivirais/uso terapêutico , Doenças Cardiovasculares/epidemiologia , Citomegalovirus , Infecções por Citomegalovirus/tratamento farmacológico , Infecções por Citomegalovirus/epidemiologia , Sobrevivência de Enxerto , Humanos , Imunoglobulina G , Estudos Retrospectivos , Fatores de Risco , Estudos Soroepidemiológicos , TransplantadosRESUMO
Coronavirus disease 2019 (COVID-19) is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). COVID-19 has infected over 90 million people worldwide, therefore it is considered a pandemic. SARS-CoV-2 infection can lead to severe pneumonia, acute respiratory distress syndrome (ARDS), septic shock, and/or organ failure. Individuals receiving a heart transplantation (HT) may be at higher risk of adverse outcomes attributable to COVID-19 due to immunosuppressives, as well as concomitant infections that may also influence the prognoses. Herein, we describe the first report of two cases of HT recipients with concomitant infections by SARS-CoV-2, Trypanosoma cruzi, and cytomegalovirus (CMV) dissemination, from the first day of hospitalization due to COVID-19 in the intensive care unit (ICU) until the death of the patients.
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We assessed maternal and infant cytomegalovirus (CMV) infection in Colombia. Maternal serum was tested for CMV immunoglobulin G antibodies at a median of 10 (interquartile range: 8-12) weeks gestation (n = 1501). CMV DNA polymerase chain reaction was performed on infant urine to diagnose congenital (≤21 days of life) and postnatal (>21 days) infection. Maternal CMV seroprevalence was 98.1% (95% confidence interval [CI]: 97.5%-98.8%). Congenital CMV prevalence was 8.4 (95% CI: 3.9%-18.3%; 6/711) per 1000 live births. Among 472 infants without confirmed congenital CMV infection subsequently tested at age 6 months, 258 (54.7%, 95% CI: 50.2%-59.1%) had postnatal infection.
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Anticorpos Antivirais/sangue , Infecções por Citomegalovirus/epidemiologia , Infecções por Citomegalovirus/imunologia , Citomegalovirus/imunologia , Complicações Infecciosas na Gravidez/virologia , Adulto , Pré-Escolar , Colômbia/epidemiologia , Citomegalovirus/genética , Infecções por Citomegalovirus/congênito , Infecções por Citomegalovirus/urina , DNA Viral/urina , Feminino , Idade Gestacional , Humanos , Imunoglobulina G/sangue , Lactente , Mães , Gravidez , Complicações Infecciosas na Gravidez/epidemiologia , Complicações Infecciosas na Gravidez/imunologia , Saliva/virologia , Estudos SoroepidemiológicosRESUMO
Induction therapy with rabbit anti-thymocyte globulin (rATG) in low-risk kidney transplant recipients (KTR) remains controversial, given the associated increased risk of cytomegalovirus (CMV) infection. This natural experiment compared 12-month clinical outcomes in low-risk KTR without CMV prophylaxis (January/3/13-September/16/15) receiving no induction or a single 3 mg/kg dose of rATG. We used logistic regression to characterize delayed graft function (DGF), negative binomial to characterize length of hospital stay (LOS), and Cox regression to characterize acute rejection (AR), CMV infection, graft loss, death, and hospital readmissions. Recipients receiving 3 mg/kg rATG had an 81% lower risk of AR (aHR 0.14 0.190.25 , P < 0.001) but no increased rate of hospital readmissions because of infections (0.68 0.911.21 , P = 0.5). There was no association between 3 mg/kg rATG and CMV infection/disease (aHR 0.86 1.101.40 , P = 0.5), even when the analysis was stratified according to recipient CMV serostatus positive (aHR 0.94 1.251.65 , P = 0.1) and negative (aHR 0.28 0.571.16 , P = 0.1). There was no association between 3 mg/kg rATG and mortality (aHR 0.51 1.253.08 , P = 0.6), and graft loss (aHR 0.34 0.731.55 , P = 0.4). Among low-risk KTR receiving no CMV pharmacological prophylaxis, 3 mg/kg rATG induction was associated with a significant reduction in the incidence of AR without an increased risk of CMV infection, regardless of recipient pretransplant CMV serostatus.
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Infecções por Citomegalovirus , Transplante de Rim , Soro Antilinfocitário , Citomegalovirus , Infecções por Citomegalovirus/epidemiologia , Rejeição de Enxerto/prevenção & controle , Humanos , Imunossupressores , Incidência , Transplante de Rim/efeitos adversos , Estudos Retrospectivos , TransplantadosRESUMO
Secondary lymphohistiocytosis is a severe inflammatory condition characterized by uncontrolled inflammatory response hyperactivation of antigen-presenting cells, hemophagocytosis, cytopenias, and multiorgan failure, and is secondary to subjacent pathologies such as cancer, infection, or immune disease. Standard treatment includes chemotherapy; however, this is not always possible or safe. Ruxolitinib, a Janus kinase (JAK) 1/2 inhibitor can reduce inflammation and cytokine activity and has been used in refractory cases and first-line treatment. Here, we present a 35-year-old patient with HIV infection and secondary lymphohistiocytosis due to CMV/EBV infection who was successfully treated with ruxolitinib as first-line therapy. He rapidly showed clinical and biochemical improvement and transfusion independence without complications.
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Infecções por HIV/complicações , Inibidores de Janus Quinases/uso terapêutico , Linfo-Histiocitose Hemofagocítica/tratamento farmacológico , Pirazóis/uso terapêutico , Adulto , Citocinas/metabolismo , Infecções por Citomegalovirus/complicações , Infecções por Vírus Epstein-Barr/complicações , Humanos , Inflamação , Mediadores da Inflamação/metabolismo , Linfo-Histiocitose Hemofagocítica/etiologia , Linfo-Histiocitose Hemofagocítica/metabolismo , Masculino , Nitrilas , Pirimidinas , Resultado do TratamentoRESUMO
Maternal preconceptional cytomegalovirus (CMV) immunity does not protect the fetus from acquiring congenital CMV infection (cCMV). Nonprimary infections due to recurrence of latent infections or reinfection with new virus strains during pregnancy can result in fetal infection. Because the prevalence of cCMV increases with increasing maternal CMV seroprevalence, the vast majority of the cases of cCMV throughout the world follow nonprimary maternal infections and is more common in individuals of lower socioeconomic background. Horizontal exposures to persons shedding virus in bodily secretions (young children, sexual activity, household crowding, low income) probably increase the risk of acquisition of an exogenous nonprimary CMV infection and fetal transmission. In addition, more frequent acquisition of new antibody reactivities in transmitter mothers suggest that maternal reinfection by new viral strains could be a major source of congenital infection in such populations. However, the exact frequency of CMV nonprimary infection in seroimmune women during pregnancy and the rate of intrauterine transmission in these women are yet to be defined. Usually, the birth prevalence of cCMV is high (≥7:1000) in highly seropositive populations. There is increasing evidence that the frequency and severity of the clinical and laboratory abnormalities in infants with congenital CMV infection born to mothers with nonprimary CMV infection are similar to infants born after a primary maternal infection. This is particularly true for sensorineural hearing loss, which contributes to one third of all early-onset hearing loss in seropositive populations. This brief overview will discuss the need for more research to better clarify the natural history of cCMV in highly seropositive populations, which, in almost all populations, remains incompletely defined.