RESUMO
We report a case of adenovirus nephritis (ADVN) in a kidney transplant recipient (KTR) occurring within 8 days post-transplantation. The patient, a 35-year-old male, displayed systemic symptoms, high-grade fever, and acute kidney injury (AKI) without signs of hemorrhagic cystitis (HC). Extensive diagnostic workup revealed widespread necrotizing granulomatous inflammation in the allograft, leading to the identification of adenovirus (ADV) via histopathology and polymerase chain reaction (PCR) testing. The source of ADV transmission remained uncertain, raising questions about the potential donor-derived infection. Unlike typical ADVN cases, the patient exhibited no hematuria or urinary symptoms. The case underscores the atypical presentation of ADVN in KTRs, challenging the conventional understanding of its timeline, transmission routes, and associated clinical features. We discuss the diagnostic challenges, histological findings, and management strategies for ADVN, emphasizing the importance of considering this entity in KTRs with unexplained fever and AKI, even in the absence of classical urinary symptoms or hematuria.
Assuntos
Cistite , Transplante de Rim , Humanos , Masculino , Transplante de Rim/efeitos adversos , Adulto , Cistite/virologia , Nefrite/virologia , Infecções por Adenoviridae , Hemorragia/etiologia , Cistite HemorrágicaRESUMO
INTRODUCTION AND HYPOTHESIS: The objective was to assess PD-L1 expression in nonbacterial chronic cystitis (NCC) and bladder cancer (BC). METHODS: The present study included 20 NCC and 20 BC patients. The degree of inflammation of the bladder wall was assessed on slides stained with H&E. Viral pathogens (herpes simplex virus, Epstein-Barr virus, cytomegalovirus, and high-risk HPVs) were detected using real-time polymerase chain reaction analyses of the bladder specimens. Immunohistochemistry was performed to assess the PD-L1 expression in bladder tissue. RESULTS: Expression of PD-L1 was detected in 40% of NCC patients and 85% of BC patients. Viral pathogens were found in 50% of NCC patients and 60% of BC patients, with EBV being the most common. In NCC patients the immune cell score correlated strongly with the degree of inflammatory infiltration of the bladder wall (r = 0.867, p < 0.001), the presence of lymphoid aggregates in the submucosa (r = 0.804, p < 0.001), koilocytosis (r = 0.620, p = 0.004), and the presence of viral pathogens (r = 0.784, p < 0.001). In BC patients the immune cell score correlated with the degree of inflammatory infiltration of the bladder wall (r = 0.534, p = 0.015) and the presence of viral pathogens (r = 0.626, p = 0.003), but not with the presence of lymphoid aggregates in the submucosa (r = 0.083, p = 0.729), and koilocytosis (r = 0.366, p = 0.112). CONCLUSIONS: Expression of PD-L1 was detected in a cohort of NCC patients, although the PD-L1 positivity rate was lower than that in BC. Our results demonstrate that the degree of PD-L1 expression in bladder tissue is associated with the presence of viral infections and with the degree of inflammatory infiltration of the bladder wall in both NCC and BC.
Assuntos
Antígeno B7-H1 , Cistite , Neoplasias da Bexiga Urinária , Humanos , Antígeno B7-H1/metabolismo , Neoplasias da Bexiga Urinária/virologia , Neoplasias da Bexiga Urinária/metabolismo , Neoplasias da Bexiga Urinária/patologia , Feminino , Pessoa de Meia-Idade , Cistite/virologia , Cistite/metabolismo , Idoso , Masculino , Adulto , Doença Crônica , Bexiga Urinária/patologia , Bexiga Urinária/metabolismo , Bexiga Urinária/virologia , Imuno-Histoquímica , Idoso de 80 Anos ou maisRESUMO
A retrospective cross sectional study was conducted at the Virology Department, Armed Forces Institute of Pathology (AFIP) and Armed Forces Bone Marrow Transplant Centre (AFBMTC), Rawalpindi, from January 2016 to July 2018. Medical records of 193 patients were examined to determine the number of patients developing Haemorrhagic Cystitis associated with BK virus (BKV). BKV PCR testing was done on the patients' urine samples. Cytomegalovirus reactivation was also assessed weekly from day 30 to day 100, by CMV quantitative PCR testing on blood samples. Out of 193 patients, 11 (5.6%) developed haemorrhagic cystitis and all these patients were positive for BKV on urine samples. The maximum number of positive cases, i.e. 5 (2.6%) was in the age group three months to 10 years. Primary disease in seven out of 11 cases was Beta-Thalassemia Major.
Assuntos
Vírus BK , Cistite , Transplante de Células-Tronco Hematopoéticas , Hemorragia , Humanos , Vírus BK/isolamento & purificação , Estudos Transversais , Cistite/virologia , Países em Desenvolvimento , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Hemorragia/virologia , Estudos Retrospectivos , Urina/virologiaRESUMO
Small-molecule drugs inhibiting BK polyomavirus (BKPyV) represent a significant unmet clinical need in view of polyomavirus-associated nephropathy or hemorrhagic cystitis, which complicate 5% to 25% of kidney and hematopoietic cell transplantations. We characterized the inhibitory activity of acitretin on BKPyV replication in primary human renal proximal tubular epithelial cells (RPTECs). Effective inhibitory concentrations of 50% (EC50) and 90% (EC90) were determined in dilution series measuring BKPyV loads, transcripts, and protein expression, using cell proliferation, metabolic activity, and viability to estimate cytotoxic concentrations and selectivity indices (SI). The acitretin EC50 and EC90 in RPTECs were 0.64 (SI50, 250) and 3.25 µM (SI90, 49.2), respectively. Acitretin effectively inhibited BKPyV replication until 72 h postinfection when added 24 h before infection until 12 h after infection, but decreased to <50% at later time points. Acitretin did not interfere with nuclear delivery of BKPyV genomes, but it decreased large T-antigen transcription and protein expression. Acitretin did not inhibit the initial round of BKPyV replication following transfection of full-length viral genomes, but it affected subsequent rounds of reinfection. Acitretin also inhibited BKPyV replication in human urothelial cells and in Vero cells, but not in COS-7 cells constitutively expressing Simian virus 40 (SV40) large T antigen. Retinoic acid agonists (all-trans retinoic acid, 9-cis retinoic acid [9-cis-RA], 13-cis-RA, bexarotene, and tamibarotene) and the RAR/RXR antagonist RO41-5253 also inhibited BKPyV replication, pointing to an as-yet-undefined mechanism. IMPORTANCE Acitretin selectively inhibits BKPyV replication in primary human cell culture models of nephropathy and hemorrhagic cystitis. Since acitretin is an approved drug in clinical use reaching BKPyV-inhibiting concentrations in systemically treated patients, further studies are warranted to provide data for clinical repurposing of retinoids for treatment and prevention of replicative BKPyV-diseases.
Assuntos
Acitretina/farmacologia , Antivirais/farmacologia , Vírus BK/crescimento & desenvolvimento , Retinoides/farmacologia , Tretinoína/farmacologia , Replicação Viral/efeitos dos fármacos , Animais , Antígenos Virais de Tumores/biossíntese , Antígenos Virais de Tumores/genética , Células COS , Linhagem Celular , Chlorocebus aethiops , Cistite/tratamento farmacológico , Cistite/virologia , Genoma Viral/genética , Células HEK293 , Humanos , Nefropatias/tratamento farmacológico , Nefropatias/virologia , Testes de Sensibilidade Microbiana , Infecções por Polyomavirus/tratamento farmacológico , Tretinoína/análogos & derivados , Infecções Tumorais por Vírus/tratamento farmacológico , Células VeroRESUMO
Although some studies have suggested the effectiveness of hyperbaric oxygen (HBO) therapy for hemorrhagic cystitis (HC) after allogeneic hematopoietic stem cell transplantation (HSCT), the role of HBO has not been established. We compared the treatment outcomes of 8 patients with viral HC (adenovirus [ADV], n = 2; BK virus [BKV], n = 6) treated with HBO (HBO[+]) and 8 patients (ADV, n = 2; BKV, n = 6) treated with conventional therapy (HBO[-]), such as urinary catheterization and intravenous cidofovir. HBO therapy was performed at 2.1 atmospheres for 90 min/day until clinical improvement was achieved. The median number of HBO treatments was 10 (range 8-12). The median duration of HBO treatment was 19.5 days (range 10-23 days). All 8 HBO(+) patients achieved complete remission (CR) at a median of 14.5 days (range 5-25 days). Of the 8 HBO(-) patients, 5 (62.5%) obtained CR and 3 remained symptomatic for 2-6 months. The cumulative incidence of transplant-related mortality at day 100 after allogeneic HSCT was significantly higher in the HBO(-) patients than in the HBO(+) patients (14.2 vs. 0%, P < 0.05). No severe HBO-related adverse effects were observed. In conclusion, HBO is a feasible option for treating viral HC after allogeneic HSCT.
Assuntos
Cistite/terapia , Cistite/virologia , Transplante de Células-Tronco Hematopoéticas , Hemorragia/terapia , Hemorragia/virologia , Oxigenoterapia Hiperbárica , Adenoviridae/isolamento & purificação , Infecções por Adenoviridae/complicações , Adulto , Vírus BK/isolamento & purificação , Cistite/etiologia , Feminino , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Hemorragia/etiologia , Humanos , Oxigenoterapia Hiperbárica/métodos , Masculino , Pessoa de Meia-Idade , Infecções por Polyomavirus/complicações , Transplante Homólogo/efeitos adversos , Resultado do Tratamento , Adulto JovemRESUMO
Adenovirus (ADV)- or BK virus (BKV)-associated hemorrhagic cystitis (HC) is a common complication after allogeneic hematopoietic stem cell transplantation (allo-HSCT). Several risk factors have been previously reported; however, it is unclear whether virus-associated HC can be transmitted. To clarify this point, we performed a retrospective cohort study on 207 consecutive patients who underwent allo-HSCT at Kyoto University Hospital between 2012 and 2018. We evaluated the incidence and risk factors of virus-associated HC and performed a phylogenetic analysis of the ADV partial sequence. The median age at transplantation was 50 (range, 17-68) years. Fifty-eight patients (28%) developed HC. ADVs were detected in 18 cases, BKVs were detected in 51, both were detected in 12, and only John Cunningham virus (JCV) was detected in 1 case. No factor was significantly associated with HC. However, both ADV- and BKV-HC occurred intensively between April 2016 and September 2017, which suggested possible nosocomial transmission of ADV and BKV. Genome sequencing of the hexon, E3, and penton regions of detected ADVs identified 7 cases of ADV type 11, 2 cases of type 35, and 3 cases of a type 79-related strain. A sequence analysis revealed that these strains in each type were almost identical, except for one case of a type 79-related strain. In conclusion, ADV-HCs with possible nosocomial transmission were described based on genotyping of the virus and partial sequencing of the viral genome. Although viral HC after allo-HSCT is thought to mainly be due to reactivation of a latent virus, nosocomial transmission of ADV or BKV should also be considered.
Assuntos
Infecção Hospitalar/etiologia , Cistite/virologia , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Hemorragia/virologia , Viroses/etiologia , Adenoviridae/isolamento & purificação , Adenoviridae/fisiologia , Infecções por Adenoviridae/epidemiologia , Infecções por Adenoviridae/etiologia , Adolescente , Adulto , Idoso , Vírus BK/isolamento & purificação , Vírus BK/fisiologia , Estudos de Coortes , Infecção Hospitalar/epidemiologia , Cistite/epidemiologia , Cistite/etiologia , Feminino , Transplante de Células-Tronco Hematopoéticas/estatística & dados numéricos , Hemorragia/epidemiologia , Hemorragia/etiologia , Humanos , Vírus JC/isolamento & purificação , Vírus JC/fisiologia , Japão/epidemiologia , Masculino , Pessoa de Meia-Idade , Infecções por Polyomavirus/epidemiologia , Infecções por Polyomavirus/etiologia , Estudos Retrospectivos , Fatores de Risco , Transplante Homólogo/efeitos adversos , Transplante Homólogo/estatística & dados numéricos , Infecções Tumorais por Vírus/epidemiologia , Infecções Tumorais por Vírus/etiologia , Infecções Urinárias/epidemiologia , Infecções Urinárias/etiologia , Viroses/epidemiologia , Adulto JovemRESUMO
BK virus (BKV)-hemorrhagic cystitis (HC) is a well-known and rarely fatal complication of hematopoietic stem cell transplantation (HSCT). Treatment for BKV-HC is limited, but virus-specific T-cells (VST) represent a promising therapeutic option feasible for use posttransplant. We report on the case of a 16-year-old male with dedicator of cytokinesis 8 (DOCK8) deficiency who underwent haploidentical HSCT complicated by severe BKV-HC, catastrophic renal hemorrhage, and VST-associated cytokine release syndrome (CRS). Gross hematuria refractory to multiple interventions began with initiation of posttransplant cyclophosphamide (PT/Cy). Complete left renal arterial embolization (day +43) was ultimately indicated to control intractable renal hemorrhage. Subsequent infusion of anti-BK VSTs was complicated by CRS and progressive multiorgan failure, with postmortem analysis confirming diagnosis of hepatic sinusoidal obstruction syndrome (SOS). This case illustrates opportunities for improvement in the management of severe BKV-HC posttransplant while highlighting rare and potentially life-threatening complications of BKV-HC and VST therapy.
Assuntos
Transferência Adotiva/efeitos adversos , Vírus BK/patogenicidade , Cistite/terapia , Síndrome da Liberação de Citocina/imunologia , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Hemorragia/terapia , Infecções por Polyomavirus/terapia , Linfócitos T/transplante , Infecções Tumorais por Vírus/terapia , Adolescente , Vírus BK/imunologia , Cistite/diagnóstico , Cistite/imunologia , Cistite/virologia , Síndrome da Liberação de Citocina/diagnóstico , Evolução Fatal , Hemorragia/diagnóstico , Hemorragia/imunologia , Hemorragia/virologia , Humanos , Masculino , Insuficiência de Múltiplos Órgãos/etiologia , Infecções por Polyomavirus/diagnóstico , Infecções por Polyomavirus/imunologia , Infecções por Polyomavirus/virologia , Índice de Gravidade de Doença , Linfócitos T/imunologia , Linfócitos T/virologia , Resultado do Tratamento , Infecções Tumorais por Vírus/diagnóstico , Infecções Tumorais por Vírus/imunologia , Infecções Tumorais por Vírus/virologiaRESUMO
The aims were to investigate the incidence of BKV infection and the presence of HC in pediatric patients undergoing HSCT. Twenty-four children patients (M/F: 17/7) undergoing HSCT in a single center over a period of 1 year were included in the study. The presence of BKV DNA was determined by quantitative real-time PCR in plasma and urine samples at the following times: before transplantation, twice a week until engraftment time, and weekly for + 100 days. The mean age of the patients was 7.79 ± 5.03 years, the mean follow-up time was 95.6 ± 25.9 days, and the average number of samples per patient was 15.8 ± 3.2. BKV DNA was detected in at least one urine sample in 91.6% (n: 22) and at least one plasma sample in 75% (n:18) of the patients. The median time to the first BKV DNA positivity in urine and plasma samples was 11 (range: 1-80) and 32 days (range: 2-79), respectively. The median value of BKV DNA copies in urine and plasma were 1.7 × 106 (range: 2.8 × 101 -1.2 × 1014 ) and 1.9 × 103 copies/mL (range: 3-2.1 × 106 ), respectively. Thirteen patients (54.2%) had hematuria with BKV viruria; 8 (33.3%) patients had viremia. The median value of the BKV DNA copies in urine and plasma was 4.4 × 107 (range: 65-1 × 1011 ) and 2.9 × 103 (range: 7-7.8 × 104 ) copies/mL in these patients. Two (15.4%) of the 13 patients with BKV viruria and hematuria were diagnosed with BKV-related HC. BKV DNA viral load monitoring of urine and plasma in pediatric HSCT patients with a high risk for viral infections is valuable for understanding the development of BKV-related HC.
Assuntos
Vírus BK/isolamento & purificação , Cistite/imunologia , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Hospedeiro Imunocomprometido , Imunossupressores/efeitos adversos , Infecções por Polyomavirus/imunologia , Adolescente , Criança , Pré-Escolar , Cistite/diagnóstico , Cistite/epidemiologia , Cistite/virologia , Feminino , Seguimentos , Humanos , Incidência , Masculino , Infecções por Polyomavirus/diagnóstico , Infecções por Polyomavirus/epidemiologia , Infecções por Polyomavirus/metabolismo , Carga Viral , Adulto JovemRESUMO
The current coronavirus disease 2019 (COVID-19) pandemic is a challenge for physicians in triaging patients in emergency rooms. We found a potentially dangerous overlap of classical urinary symptoms and the as yet not fully described symptoms of COVID-19. After a patient was primarily triaged as a urosepsis case and then subsequently diagnosed with COVID-19, we focused on an increase in urinary frequency as a symptom of COVID-19 and identified this in seven males out of 57 patients currently being treated in our COVID-19 wards. In the absence of any other causes, urinary frequency may be secondary to viral cystitis due to underlying COVID-19 disease. We propose consideration of urinary frequency as an anamnestic tool in patients with infective symptoms to increase awareness among urologists during the current COVID-19 pandemic to prevent fatal implications of misinterpreting urological symptoms.
Assuntos
Betacoronavirus/patogenicidade , Infecções por Coronavirus/virologia , Cistite/virologia , Pneumonia Viral/virologia , Incontinência Urinária de Urgência/virologia , Infecções Urinárias/virologia , Micção , Urodinâmica , Idoso , COVID-19 , Teste para COVID-19 , Técnicas de Laboratório Clínico , Infecções por Coronavirus/complicações , Infecções por Coronavirus/diagnóstico , Cistite/diagnóstico , Cistite/fisiopatologia , Interações Hospedeiro-Patógeno , Humanos , Masculino , Pessoa de Meia-Idade , Pandemias , Pneumonia Viral/complicações , Pneumonia Viral/diagnóstico , Estudos Prospectivos , Estudos Retrospectivos , Fatores de Risco , SARS-CoV-2 , Fatores de Tempo , Incontinência Urinária de Urgência/diagnóstico , Incontinência Urinária de Urgência/fisiopatologia , Infecções Urinárias/diagnóstico , Infecções Urinárias/fisiopatologiaRESUMO
Hemorrhagic cystitis (HC) has been reported with increased frequency following post-transplantation cyclophosphamide (PTCy)-based haploidentical hematopoietic cell transplantation (HCT) along with a strong association with BK viruria. We prospectively evaluated the incidence of BK viruria and HC in 115 patients (median age 20 years, 2-65) undergoing PTCy-based haploidentical HCT with (n = 71) or without (n = 44) CTLA4Ig. HC prophylaxis consisted of a continuous infusion of mesna 30 min prior and 48 h post-PTCy. The overall incidence of BK viruria was 65.7%. None with BK viruria < 104 copies/ml developed clinical symptoms (n = 65). The incidence of BK viruria ≥ 104 copies/ml was 7.1% (n = 8) and 75% developed HC. The incidence of HC was 5.4% at a median of 30 days. Both BK viruria ≥ 104 copies/ml and HC were strongly associated with acute GVHD (p < 0.001). A higher NRM was observed in those with BK viruria ≥ 104 copies/ml, related to GVHD and its complications (41.7% vs 12.6%, p = 0.04). The incidences of acute GVHD, vis-à-vis, overall BK viruria, BK viruria ≥ 104 copies/ml, and HC, tended to be lower in patients receiving CTLA4Ig. Thus, extended infusional mesna, coupled with significant reduction in alloreactivity along with possible preservation of antiviral immunity associated with the use of CTLA4Ig, was probably responsible for a much lower incidence of BK viruria and resultant HC than reported previously following PTCy-based haploidentical HCT.
Assuntos
Abatacepte/uso terapêutico , Vírus BK/isolamento & purificação , Ciclofosfamida/efeitos adversos , Cistite/prevenção & controle , Transplante de Células-Tronco Hematopoéticas , Hematúria/prevenção & controle , Imunossupressores/efeitos adversos , Mesna/uso terapêutico , Infecções por Polyomavirus/urina , Transplante Haploidêntico , Infecções Tumorais por Vírus/urina , Abatacepte/administração & dosagem , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Pré-Escolar , Ciclofosfamida/administração & dosagem , Cistite/induzido quimicamente , Cistite/urina , Cistite/virologia , Feminino , Doença Enxerto-Hospedeiro/prevenção & controle , Doenças Hematológicas/complicações , Doenças Hematológicas/terapia , Neoplasias Hematológicas/complicações , Neoplasias Hematológicas/terapia , Hematúria/induzido quimicamente , Hematúria/virologia , Humanos , Imunossupressores/administração & dosagem , Infusões Intravenosas , Estimativa de Kaplan-Meier , Masculino , Mesna/administração & dosagem , Pessoa de Meia-Idade , Infecções por Polyomavirus/complicações , Infecções por Polyomavirus/virologia , Infecções Tumorais por Vírus/complicações , Infecções Tumorais por Vírus/virologia , Urina/virologia , Adulto JovemRESUMO
Background: BK virus hemorrhagic cystitis (BKV-HC) is a common complication following hematopoietic stem cell transplant (HSCT); optimal management remains uncertain. Supportive care (bladder irrigation and blood transfusions) and intravenous and intravesicular cidofovir have all been used with varying success. Objective: The purpose of this study was to determine the safety and effectiveness of intravesicular cidofovir for BKV-HC following HSCT. Methods: A retrospective analysis of all HSCT patients with BKV-HC prescribed intravesicular cidofovir from 2012 to 2017. Results: 33 patients were treated for BKV-HC. The median age was 50 years (range 23-73), and 18 (55%) were male. The median HC symptom severity was 2, with a median BK urine viral load pretreatment of 100,000,000 IU/mL. Patients received a median of 2 intravesicular treatments (range 1-7) at a dosage of 5 mg/kg per instillation. In all, 19 (59%) patients demonstrated complete clinical resolution of symptoms; 9 (28%) had a partial response; and 4 (13%) had no change in symptoms. Patients with a high pretreatment BK viral load (>100 million) and high HC grade (2-4) had a lower frequency of complete remission. The main side effect of intravesicular instillation was severe bladder spasms in 4 patients (12%). Conclusion and Relevance: This is the largest study of intravesicular cidofovir treatment of BKV HC reported to date; 88% of patients with BVK-HC achieved clinical improvement of symptoms with minimal side effects. Clinical trials of intravesicular cidofovir could provide further evidence for this treatment for BKV-HC.
Assuntos
Antivirais/uso terapêutico , Vírus BK/efeitos dos fármacos , Cidofovir/uso terapêutico , Cistite/tratamento farmacológico , Hemorragia/tratamento farmacológico , Infecções por Polyomavirus/tratamento farmacológico , Infecções Tumorais por Vírus/tratamento farmacológico , Administração Intravesical , Adolescente , Adulto , Idoso , Antivirais/administração & dosagem , Cidofovir/administração & dosagem , Cistite/etiologia , Cistite/virologia , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/etiologia , Feminino , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Hemorragia/etiologia , Hemorragia/virologia , Humanos , Masculino , Pessoa de Meia-Idade , Infecções por Polyomavirus/etiologia , Infecções por Polyomavirus/virologia , Estudos Retrospectivos , Infecções Tumorais por Vírus/etiologia , Infecções Tumorais por Vírus/virologia , Carga Viral , Adulto JovemRESUMO
We present a patient with virus-associated hemorrhagic cystitis who underwent kidney and allogenic hematopoietic stem cell transplantations (allo-HSCT). Six months post-allo-HSCT, adenovirus hemorrhagic cystitis occurred, which has been in remission after a single dose of intravesical cidofovir. This might cause prolonged neutropenia and nephrotoxicity, suggesting cidofovir absorption in the blood.
Assuntos
Cidofovir/efeitos adversos , Cistite/tratamento farmacológico , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Hematúria/tratamento farmacológico , Transplante de Rim/efeitos adversos , Neutropenia/induzido quimicamente , Administração Intravesical , Aloenxertos/efeitos dos fármacos , Aloenxertos/fisiopatologia , Cidofovir/administração & dosagem , Cidofovir/farmacocinética , Cistite/complicações , Cistite/urina , Cistite/virologia , Hematúria/urina , Hematúria/virologia , Humanos , Rim/efeitos dos fármacos , Rim/fisiopatologia , Masculino , Pessoa de Meia-Idade , Distribuição Tecidual , Transplante Homólogo/efeitos adversos , Bexiga Urinária/efeitos dos fármacos , Bexiga Urinária/virologiaAssuntos
Cistite/virologia , Enfisema/terapia , Herpes Zoster/complicações , Doenças do Sistema Nervoso Periférico/virologia , Bexiga Inativa/virologia , Infecções Urinárias/virologia , Idoso de 80 Anos ou mais , Antivirais/uso terapêutico , Cistite/diagnóstico por imagem , Cistite/terapia , Enfisema/diagnóstico por imagem , Feminino , Febre/virologia , Herpes Zoster/tratamento farmacológico , Herpes Zoster/fisiopatologia , Humanos , Resultado do Tratamento , Infecções Urinárias/tratamento farmacológico , Infecções Urinárias/fisiopatologia , Valaciclovir/uso terapêuticoRESUMO
Human Herpes Virus-8 (HHV-8) may reactivate in immunocompromised patients including recipients of solid organ transplants. Reactivation of HHV-8 may result in Kaposi sarcoma (KS). KS typically occurs with dermatologic involvement but can affect virtually any other organ; most commonly the gastrointestinal tract. We present a diagnostically challenging case of KS in a South American woman 7 months after kidney transplant. She presented with recurrent urinary tract infection manifested by pelvic pain and dysuria. Imaging studies revealed bladder thickening with pelvic lymphadenopathy. Findings on tissue biopsied from the bladder and lymph nodes were consistent with KS. Her skin was not affected. This case illustrates that KS and other HHV-8-related diseases should be on the differential diagnosis as a cause of mass lesions as well as lymphadenopathy in transplant recipients. The case exemplifies the need to pursue a tissue diagnosis in immunocompromised patients when a diagnosis is uncertain.
Assuntos
Cistite/virologia , Transplante de Rim/efeitos adversos , Sarcoma de Kaposi/diagnóstico , Transplantados , Adulto , Cistite/diagnóstico , Diagnóstico Diferencial , Feminino , Infecções por Herpesviridae/diagnóstico , Herpesvirus Humano 8/patogenicidade , Humanos , Hospedeiro Imunocomprometido , Terapia de Imunossupressão/efeitos adversos , Linfadenopatia/virologia , Bexiga Urinária/patologia , Bexiga Urinária/virologiaRESUMO
BACKGROUND: BK polyomavirus reactivation can occur following allogeneic hematopoietic stem cell transplantation (allo-HSCT) and may lead to hemorrhagic cystitis (BKPyV-HC). We hypothesized that development of BKPyV-HC is associated with increased mortality post allo-HSCT. METHODS: We retrospectively reviewed data on 133 adult patients (≥18 years old) who underwent allo-HSCT from 2007 until 2014 at Hospital Israelita Albert Einstein in São Paulo, Brazil. RESULTS: Thirty-six patients presented with BKPyV-HC after a median time of 42 days, with a 1-year cumulative incidence probability of 28.9% (95% CI 21.5%-36.7%). In a multivariate Cox model, risk factors for development of BKPyV-HC included younger age, male sex, development of grade 2-4 acute graft-versus-host disease and recipients of umbilical cord blood grafts. Development of grade 3-4 BKPyV-HC (but not grade 1-2) was associated with a decreased overall survival (OS) in a multivariate Cox model (hazard ratio [HR] 7.51, P < 0.0001) and an increased risk of TRM (HR 3.66, P < 0.0001). Grade 3-4 BKPyV-HC was also associated with an increased risk of relapse that did not reach statistical significance (HR 3.01, P = 0.07). Median overall survival (OS) post-BKPyV-HC was 4.7 months, and cidofovir had no impact on survival. CONCLUSION: Development of BKPyV-HC appears to be associated with decreased survival following allo-HSCT.
Assuntos
Vírus BK/patogenicidade , Cistite/virologia , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Infecções por Polyomavirus/fisiopatologia , Condicionamento Pré-Transplante , Adolescente , Adulto , Idoso , Cistite/mortalidade , Feminino , Hemorragia/virologia , Humanos , Masculino , Pessoa de Meia-Idade , Infecções por Polyomavirus/mortalidade , Modelos de Riscos Proporcionais , Recidiva , Estudos Retrospectivos , Fatores de Risco , Transplante Homólogo/efeitos adversos , Adulto JovemRESUMO
INTRODUCTION: The human papilloma virus (HPV) belongs to double-stranded, DNA circular viruses which infect the epithelial cells. The highest incidence of HPV is identified in malignant processes which affect the uterine cervix, as well as vulvar, penile, rectal and pharyngeal regions. GOAL OF STUDY: An attempt to find correlations between HPV incidence rates in urine sediment cells and in desquamated epithelial cells of the uterine cervix in a group of patients with frequent, recurrent cystitis. MATERIALS AND METHODS: HPV presence was studied, both in urine sediment cells and in uterine cervix epithelial cells of 77 patients. RESULTS: An analysis of urinary sediments brought a total of twenty (25.97%) positive and 57 (74.03%) negative results. In turn, an evaluation of uterine cervix material samples revealed 17 (22.08%) positive and 60 (77.92%) negative results. CONCLUSIONS: The study enabled a comparison between HPV prevalence rates in urine sediment cells and in uterine cervix epithelial cells of an examined patient. The performed observations are likely to trigger a further analysis of the studied issue; however, the obtained results provide arguments for different natural histories of the infection processes.
Assuntos
Colo do Útero/virologia , Cistite/virologia , Genoma Viral , Genótipo , Papillomaviridae/genética , Infecções por Papillomavirus/virologia , Adulto , Idoso , Cistite/complicações , DNA Viral , Células Epiteliais/virologia , Feminino , Técnicas de Genotipagem , Humanos , Pessoa de Meia-Idade , Infecções por Papillomavirus/complicações , PolôniaAssuntos
Vírus BK , Cistite/terapia , Transplante de Células-Tronco Hematopoéticas , Hemorragia/terapia , Nefropatias/terapia , Transfusão de Linfócitos , Linfoma Folicular/terapia , Infecções por Polyomavirus/terapia , Doadores de Tecidos , Aloenxertos , Cistite/etiologia , Cistite/virologia , Hemorragia/etiologia , Hemorragia/virologia , Humanos , Nefropatias/etiologia , Nefropatias/virologia , Linfoma Folicular/patologia , Linfoma Folicular/virologia , Masculino , Pessoa de Meia-Idade , Infecções por Polyomavirus/etiologiaRESUMO
In a retrospective case-control study, we aimed to assess the utility of plasma BK viral load value to predict hemorrhagic cystitis (HC) symptoms after allogeneic hematopoietic stem cell transplantation (alloHSCT). During first 100 post-transplantation days of all adult AlloHSCT recipients at the University of Nebraska Medical Center from October 1, 2011, to June 30, 2014, 8 unexcluded cases of HC were identified and matched with 88 unexcluded unaffected control cases. Viral loads were determined for archived DNA extracted from plasma collected within 3 weeks before transplantation until â¼100 days after transplantation. Clinical factors, time of onset of BK viremia, and BK viral load were compared between case and control subjects to identify risks for HC. Symptomatic HC occurred in 8/96 (8.3%) of patients at a median of 34 days after transplantation. BK viremia either before or during symptoms was detected in all 8 (100%) HC patients and in 20/88 (22.7%) of control subjects. BK viremia was detected at a median of 8 days before HC clinical symptoms. The log of first positive viral load was not a statistically significant predictor (P = .17) of symptomatic BK. Median BK viral load peak was significantly higher for 8 patients with HC versus 20 viremic patients without HC (6.66 vs 5.06; P < .052). Further study is required to evaluate the predictive value of the BK viral load for HC.
Assuntos
Cistite/virologia , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Infecções por Polyomavirus/virologia , Infecções Tumorais por Vírus/virologia , Adulto , Vírus BK/genética , Estudos de Casos e Controles , Feminino , Hemorragia , Humanos , Masculino , Pessoa de Meia-Idade , Infecções por Polyomavirus/sangue , Estudos Retrospectivos , Transplante Homólogo , Carga Viral , Viremia/virologiaRESUMO
INTRODUCTION: BK polyomavirus can lead to hemorrhagic cystitis (BKPyV-HC) in allogeneic stem cell transplantation and therefore to increased morbidity. No causal therapy has been established yet. Cidofovir (CDV) is a nucleotide analog of cytosine that is active against various DNA viruses and it has been described for therapy of BKPyV-HC using 2 admission routes: intravenous and intravesical. METHODS: We performed a systematic review regarding the comparison of intravenous or intravesical cidofovir in the treatment of BKPyV-HC following adult allogeneic stem cell transplantation. Since there is a lack of randomized controlled trials, we considered all kinds of studies for this review. Due to heterogeneity of the data, we were not able to perform a meta-analysis, so the results are shown descriptively. RESULTS: The literature search for primary studies yielded 232 results. Finally, 9 studies where considered which included a total of 189 adult patients with BKPyV-HC after allogeneic stem cell transplantation. We could only identify retrospective studies for this review. A total of 172 patients received intravenous CDV, 17 patients received intravesical CDV, and 2 patients received CDV in both admission routes. In 68.0% of the cases, a complete response for intravenous CDV was documented and in 88.2% for intravesical CDV. Interestingly, no kidney toxicity was mentioned in intravesical CDV. 9.3% of the intravenously treated patients had renal failure. CONCLUSION: There is only weak evidence for the use of CDV. The intravesical admission route should be further investigated because of a good toxicity profile.
Assuntos
Antivirais/administração & dosagem , Cistite/tratamento farmacológico , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Hemorragia/tratamento farmacológico , Infecções por Polyomavirus/tratamento farmacológico , Infecções Tumorais por Vírus/tratamento farmacológico , Administração Intravenosa , Administração Intravesical , Adulto , Vírus BK/efeitos dos fármacos , Vírus BK/isolamento & purificação , Cidofovir , Cistite/sangue , Cistite/virologia , Citosina/administração & dosagem , Citosina/análogos & derivados , Hemorragia/sangue , Hemorragia/virologia , Humanos , Organofosfonatos/administração & dosagem , Infecções por Polyomavirus/sangue , Infecções por Polyomavirus/virologia , Ensaios Clínicos Controlados Aleatórios como Assunto , Resultado do Tratamento , Infecções Tumorais por Vírus/sangue , Infecções Tumorais por Vírus/virologia , Carga Viral/efeitos dos fármacosRESUMO
The introduction of BCR-ABL-tyrosine kinase inhibitors (TKI) for treatment of hematologic malignancies has made a significant impact on patient outcome. Contingent upon their targeted and off-target activity, therapy-associated infectious complications may occur. We present a case of cytomegalovirus pneumonitis and a case of adenovirus hemorrhagic cystitis in two patients with Philadelphia chromosome-positive acute lymphoblastic leukemia on BCR-ABL TKI treatment and review the literature to summarize the infectious complications based on clinical data. As life-threatening infections may occur, treating physicians should maintain a heightened awareness in patients treated with BCR-ABL TKIs. Based on the frequent reports of hepatitis B virus (HBV) reactivation under the treatment BCR-ABL TKIs, screening for and prophylactic therapy of chronic HBV infection should be considered. Similarly, patients would benefit from screening for and treatment of latent tuberculosis.