Use of sirolimus as an adjuvant therapy for kidney transplant recipients with high-risk cutaneous squamous cell carcinomas: a prospective non-randomized controlled study / Uso do sirolimo como terapia adjuvante para receptores de transplante renal com carcinoma espinocelular cutâneo de alto risco: um estudo prospectivo controlado não randomizado

ABSTRACT Introduction: Previous research demonstrated benefits of late conversion to mTOR inhibitors against cutaneous squamous cell carcinomas (cSCC) in kidney transplant recipients (KTR), despite of poor tolerability. This study investigated whether stepwise conversion to sirolimus monotherapy without an attack dose modified the course of disease with improved tolerability. Methods: This prospective exploratory study included non-sensitized KTR with more than 12-months post-transplant, on continuous use of calcineurin inhibitors (CNI)-based therapy, and with poor-prognosis cSCC lesions. Incidence densities of high-risk cSCC over 3-years after conversion to sirolimus-monotherapy were compared to a non-randomized group with high-risk cSCC but unsuitable/not willing for conversion. Results: Forty-four patients were included (83% male, mean age 60 ± 9.7years, 62% with skin type II, mean time after transplantation 9 ± 5.7years). There were 25 patients converted to SRL and 19 individuals kept on CNI. There was a tendency of decreasing density of incidence of all cSCC in the SRL group and increasing in the CNI group (1.49 to 1.00 lesions/patient-year and 1.74 to 2.08 lesions/patient-year, p = 0.141). The density incidence of moderately differentiated decreased significantly in the SRL group while increasing significantly in the CNI group (0.31 to 0.11 lesions/patient-year and 0.25 to 0.62 lesions/patient-year, p = 0.001). In the SRL group, there were no sirolimus discontinuations, no acute rejection episodes, and no de novo DSA formation. Renal function remained stable. Conclusions: This study suggests that sirolimus monotherapy may be useful as adjuvant therapy of high-risk cSCC in kidney transplant recipients. The conversion strategy used was well tolerated and safe regarding key mid-term transplant outcomes.

RESUMO Introdução: Pesquisas anteriores demonstraram benefícios da conversão tardia para inibidores de mTOR contra carcinomas espinocelulares cutâneos (CECs) em receptores de transplante renal (RTR), apesar da baixa tolerabilidade. Este estudo investigou se a conversão gradual para monoterapia com sirolimo sem dose de ataque modificou o curso da doença com melhor tolerabilidade. Métodos: Esse estudo prospectivo exploratório incluiu RTR não sensibilizados com mais de 12 meses pós-transplante, uso contínuo de terapia imunossupressora baseado em inibidor de calcineurina (CNI) associado a micofenolato de sódio ou azatioprina, com lesões de CECs de mau prognóstico. Comparou-se densidades de incidência de CECs de alto risco durante 3 anos após conversão para monoterapia com sirolimo à um grupo não randomizado com CECs classificados conforme os mesmos critérios de gravidade do grupo sirolimo, mas inadequado/não disposto à conversão. Resultados: Foram incluídos 44 pacientes (83% homens, idade média 60 ± 9,7 anos, 62% com fototipo de pele II, tempo médio pós-transplante 9 ± 5,7 anos). 25 pacientes foram convertidos para SRL e 19 indivíduos mantidos em CNI. Foi observado tendência de diminuição da densidade de incidência de todos CECs no grupo SRL e de aumento no grupo CNI (1,49 a 1,00 lesões/paciente-ano; 1,74 a 2,08 lesões/paciente-ano; p = 0,141). A densidade de incidência de lesões moderadamente diferenciadas diminuiu significativamente no grupo SRL enquanto aumentou significativamente no grupo CNI (0,31 a 0,11 lesões/paciente-ano; 0,25 a 0,62 lesões/paciente-ano; p = 0,001). No grupo SRL não houve descontinuação do sirolimo, nenhum episódio de rejeição aguda e nenhuma formação de DSA de novo. Função renal permaneceu estável. Conclusões: Esse estudo sugere que a monoterapia com sirolimo pode ser útil como terapia adjuvante de CECs de alto risco em RTR. A estratégia de conversão usada foi bem tolerada e segura em relação aos principais desfechos do transplante a médio prazo.

Predictive ability of severity scores and outcomes for mortality in kidney transplant recipients with coronavirus disease 2019 admitted to the intensive care unit: results from a Brazilian single-center cohort study / Capacidade preditiva de escores de gravidade e desfechos para mortalidade em receptores de transplante renal com COVID-2019 admitidos em unidade de terapia intensiva: resultados de um estudo de coorte brasileiro de um único centro

Abstract Background: the predictive ability of severity scores for mortality in patients admitted to intensive care units is not well-known among kidney transplanted (KT) patients, especially those diagnosed with coronavirus disease 2019 (COVID-19). The purpose of the present study was to evaluate the predictive ability of severity scores for mortality in KT recipients. Methods: 51 KT recipients with COVID-19 diagnosis were enrolled. The performance of the SOFA, SAPS 3, and APACHE IV tools in predicting mortality after COVID-19 was compared by the area under the ROC curve (AUC-ROC) and univariate Cox regression analysis was performed. Results: The 90-day cumulative incidence of death was 63.4%. Only APACHE IV score differed between survivors and nonsurvivors: 91.2±18.3 vs. 106.5±26.3, P = 0.03. The AUC- ROC of APACHE IV for predicting death was 0.706 (P = 0.04) and 0.656 (P = 0.06) at 7 and 90 days, respectively. Receiving a kidney from a deceased donor (HR = 3.16; P = 0.03), troponin levels at admission (HR for each ng/mL = 1.001; P = 0.03), APACHE IV score (HR for each 1 point = 1.02; P = 0.01), mechanical ventilation (MV) requirement (HR = 3.04; P = 0.002) and vasopressor use on the first day after ICU admission (HR = 3.85; P < 0.001) were associated with the 90-day mortality in the univariate analysis. Conclusion: KT recipients had high mortality, which was associated with type of donor, troponin levels, early use of vasopressors, and MV requirement. The other traditional severity scores investigated could not predict mortality.

RESUMO Introdução: a capacidade preditiva dos escores de gravidade para mortalidade em pacientes admitidos em unidades de terapia intensiva não é bem conhecida entre pacientes transplantados renais (TR), especialmente aqueles diagnosticados com doença coronavírus 2019 (COVID-19). Este estudo avaliou a capacidade preditiva dos escores de gravidade para mortalidade em receptores de TR. Métodos: Foram inscritos 51 receptores de TR diagnosticados com COVID-19. O desempenho das ferramentas SOFA, SAPS 3, APACHE IV em predizer mortalidade após COVID-19 foi comparado pela área sob a curva ROC (AUC-ROC) e realizou-se análise de regressão univariada de Cox. Resultados: A incidência cumulativa de óbito em 90 dias foi 63,4%. Somente APACHE IV diferiu entre sobreviventes e não-sobreviventes: 91,2±18,3 vs. 106,5±26,3; P = 0,03. A AUC-ROC do APACHE IV para predizer óbito foi 0,706 (P = 0,04) e 0,656 (P = 0,06) aos 7 e 90 dias, respectivamente. Receber rim de doador falecido (HR = 3,16; P = 0,03), níveis de troponina na admissão (HR para cada ng/mL = 1,001; P = 0,03), escore APACHE IV (HR para cada 1 ponto = 1,02; P = 0,01), necessidade de ventilação mecânica (VM) (HR = 3,04; P = 0,002), uso de vasopressor no primeiro dia após admissão na UTI (HR = 3,85; P < 0,001) foram associados à mortalidade em 90 dias na análise univariada. Conclusão: Receptores de TR apresentaram alta mortalidade, associada ao tipo de doador, níveis de troponina, uso precoce de vasopressores e necessidade de VM. Os outros escores tradicionais de gravidade investigados não puderam predizer mortalidade.

Effects of Wuzhi capsules on tacrolimus concentration in renal transplant recipients with different CYP3A5 genotypes / 中华泌尿外科杂志

Objective:To study the effect of Wuzhi capsules on tacrolimus trough concentration in kidney transplant recipients with different CYP3A5 genotypes.Methods:From June 2015 to October 2019, 162 patients who underwent renal transplantation for the first time were retrospectively analyzed. The patients were divided into two groups, combined and uncombined, according to whether combined with Wuzhi capsules. There were 81 cases in the uncombined group (55 males and 26 females), and 81 in the combined group (62 males and 19 females). There was no significant difference between the two groups( P=0.219). The ages of the uncombined group and the combined group were (39.26±11.91) years old and (37.21±10.88) years old ( P=0.103), the weights were (62.39±11.64) kg and (66.18±13.89)kg ( P=0.298), systolic blood pressure were (147.28±20.24) mmHg and (145.00±16.42) mmHg (1 mmHg=0.133 kPa)( P=0.276), diastolic blood pressure were (92.25±13.87) mmHg and (92.20±12.53) mmHg ( P=0.886), alanine aminotransferase were (12.24±8.59) U/L and (17.06±13.11) U/L ( P=0.015), aspartate aminotransferase were (17.76±9.12) U/L and (16.57±8.37) U/L ( P=0.463), fasting blood glucose were (8.70±3.48) mmol/L and (7.18±2.74)mmol/L ( P=0.006), hemoglobin were (98.96±17.53) g/L and (101.05±18.67) g/L ( P=0.789), creatinine were (665.22±296.55) μmol/L and (797.32±279.32) μmol/L ( P=0.007), estimated glomerular filtration rate were (11.47±14.11) ml/(min·1.73m 2) and (8.85±3.71) ml/(min·1.73m 2) ( P=0.130)in the kidney transplant recipients before surgery. Among the 162 cases in this study, there were 86 cases (53.09%) of CYP3A5*1*3 genotype, 17 cases (10.49%) of CYP3A5*1*1 genotype, 59 cases (36.42%) of CYP3A5*3*3 genotype, and the minimum allele frequency of CYP3A5*1 was 37.04%. In the uncombined group, CYP3A5*1*3 genotype 39 cases (48.15%), CYP3A5*1*1 genotype 5 cases (6.17%), and CYP3A5*3*3 genotype 37 cases (45.68%). In the combined group, CYP3A5*1*3 genotype 47 cases (58.02%), CYP3A5*1*1 genotype 12 cases (14.81%), and CYP3A5*3*3 genotype 22 cases (27.16%), with statistically significant differences in the two groups ( P=0.024). The patients were treated with a triple immunosuppressive regimen (tacrolimus+ mycophenolate mofetil+ glucocorticoid) based on tacrolimus [initial dose: 0.15-0.30 mg/(kg·d)], combination of Wuzhi capsules in the combination group (11.25 mg, twice a day). The trough concentration of tacrolimus was detected by enzyme-linked immunosorbent assay, compare the difference in the trough concentration of tacrolimus between the two groups. The relationship between the effect of Wuzhi capsules and CYP3A5 gene polymorphism was compared, and compare the changes before and after the application of CYP3A5 genotype combined with Wuzhi Capsules. The influencing factors of tacrolimus trough concentration were analyzed by multiple linear regression. Results:In the combined with Wuzhi capsules, the dose corrected trough concentration (C 0/D) of tacrolimus was higher than that in patients without Wuzhi capsules, and the extent of increase was related to genotype. The C 0/D of tacrolimus in patients with CYP3A5*3*3 genotype in the combination and non-combination groups were (12.15±2.95) (ng·ml -1/0.1mg·kg -1·d -1) and (9.99±2.33) (ng·ml -1/0.1mg·kg -1·d -1) ( P=0.004), CYP3A5*1*3 genotype were (11.11±3.20) (ng·ml -1/0.1mg·kg -1·d -1) and (6.86±1.62) (ng·ml -1/0.1mg·kg -1·d -1) ( P<0.001), and there were significant difference. However, CYP3A5*1*1 genotype were(8.29±2.64) (ng·ml -1/0.1mg·kg -1·d -1) and (6.16±2.87) (ng·ml -1/0.1mg·kg -1·d -1) ( P=0.160), there was no significant difference. The tacrolimus C 0/D of the combined group before and after the Wuzhi capsule were as follows: CYP3A5*3*3 genotype: (7.18±2.33)(ng·ml -1/0.1mg·kg -1·d -1) and (13.33±3.09) (ng·ml -1/0.1mg·kg -1·d -1) ( P<0.001); CYP3A5*1*3 genotype: (5.14±2.14) (ng·ml -1/0.1mg·kg -1·d -1) and (10.61±3.20) (ng·ml -1/0.1mg·kg -1·d -1) ( P<0.001); CYP3A5*1*1 genotype: (5.17±3.75) (ng·ml -1/0.1mg·kg -1·d -1) and (8.31±2.74) (ng·ml -1/0.1mg·kg -1·d -1)( P=0.002), and the differences were statistically significant. The results of multiple linear regression showed that the combination of Wuzhi capsules (β=0.508, P<0.001) and CYP3A5 genotype(CYP3A5*1*3 and CYP3A5*3*3: β=-0.361, P<0.001; CYP3A5*1*1 and CYP3A5*3*3: β=-0.425, P<0.001)could influence the trough concentration. The sex (β=-0.100, P=0.124) and age (β=-0.003, P=0.967) of renal transplant recipients had no statistical significance to tacrolimus C 0/D. Conclusions:In the renal transplant patients, CYP3A5 genotype and combined use of Wuzhi capsules are the main factors affecting tacrolimus C 0/D. In order to achieve the expected trough concentration as soon as possible, the interaction between CYP3A5 genotypes and drug combination should be considered.

Cytomegalovirus pneumonia presenting as pulmonary nodules

Abstract Cytomegalovirus (CMV) pneumonia is a well-known cause of morbidity and mortality in patients with a history of allogenic hematopoietic stem cell transplant. Radiographically, CMV pneumonia most commonly presents as bilateral ground glass opacities; however, the presentation is non-specific and can be variable, including presenting as areas of air-space consolidation or pulmonary nodules. We report a case of a 70-year-old man who presented with rapidly progressive bilateral pulmonary nodules approximately two months after receiving a bone marrow transplant. No infectious etiology was identified for the pulmonary nodules, and a bronchoscopy was unable to be performed due to a rapid decline in the patient's overall condition and respiratory status. The patient died shortly after the decision was made to transition to palliative care and a limited autopsy was performed to explore the pulmonary findings. Corresponding to premortem imaging were the postmortem gross findings of numerous bilateral pulmonary nodules and a large mass-like area of consolidation in the right upper lobe. Microscopic examination of the nodules demonstrated a necrotizing pneumonia with few foci of viral cytopathologic change consistent with CMV, which was confirmed by immunohistochemistry. While CMV is a common infectious agent in the immunocompromised population, CMV pneumonia continues to be a challenging entity due to difficulty in diagnosis and treatment. Rapidly enlarging pulmonary nodules in an immunosuppressed patient is highly suggestive of an infectious process and careful histologic examination for viral cytopathologic change is essential.

Infection with high-risk genotypes of human papillomavirus and cervical cytological findings among kidney transplant recipients in Kenya: a single centre experience

Background: High-risk human papillomavirus (hrHPV) infection is linked with uterine cervix premalignant lesions and invasive carcinoma of the uterine cervix. Methods: Descriptive cross sectional study carried out among female kidney transplant (KTx) recipients in Kenyatta National Hospital, Nairobi-Kenya. We studied the risk factors for acquisition of hrHPV, examined cervical cytology and assayed for 14 hrHPV DNA using Cervista® HPV HR test and Cervista® MTA (Hologic®) automated platforms. Results: The 14-hrHPV genotypes assayed were 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 66, and 68 and the prevalence rate was 31.25 % (10/32). Abnormal cervical cytology was noted in 4/32 (12.5%) and included low-grade squamous intraepithelial lesion (2/32), atypical squamous cells of undetermined significance (1/32) and atypical glandular cells (1/32). The average age was 41.9years with mean age at first coitus being 20.4 years. Majority of the women 20(62.5%) were married while 8(25%) were single. About 18(56.3%) had only one sexual partner. About 20% of women were nulliparous and 4(12.5%) had a parity of five. Duration sincetransplantation ranged between 1-21 years. Conclusions: The burden of hrHPV and abnormal cervical cytology in our study seemed lower than that reported elsewhere and even in general population. This study may form basis for further studies about HPV infections and carcinoma of the uterine cervix among the kidney allograft recipients in our setting

Características clínicas y microbiológicas de infecciones del torrente sanguíneo en pacientes adultos neutropénicos / Clinical and microbiological characteristics of bloodstream infections in adult neutropenic patients

RESUMEN Las infecciones del torrente sanguíneo (IS) en pacientes oncológicos neutropénicos constituyen una patología de relevancia y se asocian a un aumento de la morbimortalidad. El objetivo de este estudio fue determinar las características epidemiológicas y microbiológicas de los episodios de IS en pacientes adultos neutropénicos con neoplasias hematológicas (NH) y neoplasias sólidas (NS). Se realizó un estudio retrospectivo en dos hospitales de tercer nivel entre 2009 y 2016. Se incluyeron todos los pacientes neutropénicos mayores de 18años con NH y NS que presentaron episodios de IS. Se excluyeron aquellos con neoplasias dermatológicas no melanoma. Se identificaron 143 episodios de IS, de los cuales el 80,4% fueron en personas con NH. El 97,9% de los pacientes tuvieron neutropenia de alto riesgo, sin diferencia entre los grupos NH y NS. Los orígenes más frecuentes de IS fueron bacteriemia primaria (46,9%) e infección asociada a catéter (21%), sin diferencias significativas entre grupos. El 74,1% de los aislamientos fueron bacilos gram negativos yEscherichiacolifue el microorganismo más frecuente (32,1%). El coco gram positivo más frecuentemente aislado fueStaphylococcusaureus(28,1%), seguido del grupo de los estafilococos coagulasa negativos (ECN), sin diferencias entre ambos tipos de neoplasias. El 67,5% de los ECN fueron multirresistentes; solo el 11,1% de los aislamientos deS. aureusfue resistente a la meticilina. El 17,6% de los aislamientos deE. coliy el 27,6% de los deKlebsiellapneumoniaefueron multirresistentes. No hubo diferencias en la frecuencia de aislamientos multirresistentes al comparar entre ambos tipos de neoplasia. Como conclusión, las IS en pacientes neutropénicos fueron más frecuentes en pacientes con NH y las causaron, principalmente, bacilos gram negativos. Se observó una elevada mortalidad en los pacientes neutropénicos con IS.

ABSTRACT Bloodstream infections (BI) are relevant in neutropenic patients because they are associated with an increased number of complications and death. The objective was determinate the epidemiologic and microbiologic features of the BI in neutropenic patients with solid neoplasm (SN) and hematologic neoplasm (HN). Retrospective study in two third level hospitals between 2009 and 2016. They were included all the patients older than 18 years-old with active oncologic disease and neutropenia, who had BI. Patients with dermatologic cancer other than melanoma where excluded. A total of 143 BI in neutropenic were observed, of which 80.4% occurred in HN. Around 97.9% of the patients had a high-risk neutropenia without differences between both groups. The most frequent site of BI was primary bacteremia (46.9%) and catheter-associated infection (21%), without significant differences between the two groups. The gram negatives bacilli (GNB) predominated over the gram positive cocci (GPC) and they represented 74.1% of the isolated bacteria, beingEscherichia colithe most frequent (32.8%). Among the gram positive cocci,Staphylococcus aureus(28.1%) was the most frequent isolated, followed by coagulase-negativeStaphylococci(CNS). There were no differences in microbiological isolates between both groups. With regard to the antimicrobial susceptibility 67.5% of the CNS, 17.6% of theE. coliand 27.6% of theKlebsiella pneumoniaewere multiresistant with no differences between both groups. Only 11.1% of S. aureus isolates were methicillin resistant. In conclusion BI of the neutropenic patients where most frequents within patients with HN, GNB were the main microbiological isolates. High mortality was observed in neutropenic patients with BI.

Research advances in improving the prognosis of recipients of fatty liver transplantation / 临床肝胆病杂志

With the increasing demand for liver donors, more and more marginal donors have been used. How to use fatty liver grafts has become a new issue that physicians in the department of liver transplantation must face. Compared with the normal donor liver, fatty liver grafts have high incidence of postoperative complications and increase the difficulty of clinical cure. This review describes the measures to improve the prognosis of recipients of fatty liver transplantation, and points out that these measures can reduce the risk of fatty liver transplantation and thus increase the utilization of fatty liver grafts.

Vivência do paciente submetido ao transplante hepático na transição do cuidado / The experience of patients undergoing liver transplantation in the transition of care

RESUMO Objetivo compreender a vivência do paciente submetido ao transplante hepático na transição do cuidado entre o hospital e o domicílio. Métodos estudo com abordagem qualitativa, com 20 pacientes submetidos ao transplante hepático e que foram entrevistados por meio de roteiro semiestruturado. A análise de conteúdo foi a técnica selecionada para identificar aspectos inerentes à transição do cuidado. Resultados com base nos dados obtidos, formaram-se quatro categorias temáticas: Percurso marcado por sentimentos e incertezas; Trajetória de idas e vindas à rede de saúde para adquirir insumos; Percurso de aprendizado para desenvolver cuidados domiciliares e: Itinerário entre idealização social e a realidade vivenciada após o transplante. Conclusão perceberam-se as dificuldades de receptores e família após o transplante hepático, em especial, no preparo para a transição do cuidado e no enfrentamento e adaptação às atividades cotidianas.

ABSTRACT Objective to understand the experience of patients undergoing liver transplantation in the transition of care between hospital and home. Methods study with a qualitative approach, with 20 patients undergoing liver transplantation who were interviewed using a semi-structured script. Content analysis was the selected technique to identify aspects inherent to the transition of care. Results based on the data obtained, four thematic categories were formed: Path marked by feelings and uncertainties; Path of comings and goings to the health network to acquire supplies; Learning path to develop home care and: Itinerary between social idealization and the reality experienced after transplantation. Conclusion difficulties of recipients and family after liver transplantation were perceived, especially in the preparation for the transition of care and in coping and adapting to daily activities.

Tratamento farmacológico da estrongiloidíase em pacientes transplantados / Pharmacological treatment of strongilloidiasis in transplanted patients

O objetivo deste artigo foi comparar o uso da ivermectina e do albendazol em pacientes transplantados e relatar os respectivos sucessos terapêuticos nessa população. Foram analisados artigos que abordassem relatos de casos publicados nos últimos 4 anos no PubMed® relacionando os descritores "transplante de órgãos", "estrongiloidíase" e "tratamento". Foram encontrados e analisados dez relatos de caso que abordaram a estrongiloidíase em situa- ção pós-transplante contemplando 13 indivíduos. Desses, cinco (38,5%) utilizaram ambos os medicamentos, dos quais quatro (80%) se curaram, tendo recebido albendazol e ivermectina por via subcutânea (50%) ou albendazol e ivermectina por vias oral/ subcutânea (50%). O paciente que morreu recebeu albendazol e ivermectina por via subcutânea. Sete (53,8%) indivíduos utiliza- ram apenas ivermectina, dos quais três (42,8%) se curaram tendo recebido o medicamento oral (dois pacientes) ou subcutâneo (um paciente); dois (28,6%) morreram recebendo o medicamento via oral, dois (28,6%) usaram profilaticamente via oral e apenas um não manifestou sintomas. Apenas um (7,7%) indivíduo utilizou somente albendazol via oral tendo sobrevivido à infecção. A uti- lização combinada dos medicamentos ivermectina e albendazol parece ter efeito positivo no tratamento da estrongiloidíase. A administração da ivermectina por via subcutânea apresentou resultados promissores, contudo estudos controlados de siner- gia medicamentosa e vias de administração devem ser realizados para efetiva avaliação.

The objective of this article was to compare the use of ivermec- tin and albendazole in transplanted patients and to report the respective therapeutic successes in this population.Articles ad- dressing case reports published in the last 4 years in the PubMed relating the descriptors "organ transplantation", "strongyloidia- sis", and "treatment" were analyzed. Ten case reports addres- sing strongyloidiasis in a post-transplant situation, covering 13 individuals, were found and analyzed. Of these, five (38.5%) used both drugs of which 4 (80%) were cured having received subcu- taneous albendazole and ivermectin (50%) or oral/subcutaneous albendazole and ivermectin (50%). The patient who died received subcutaneous albenzadole and ivermectin. Seven (53.8%) indi- viduals used only ivermectin, of which three (42.8%) were cured having received the oral (2/3) or subcutaneous (1/3) medication, two (28.6%) died receiving the oral medication, and two (28.6%) used oral medication prophylactically, and only one did not show symptoms. Only one (7.7%) individual used only oral albenzadole and survived the infection. The combined use of the drugs iver- mectin and albendazole seems to have a positive effect on the treatment of strongyloidiasis. The administration of subcuta- neous Ivermectin has shown promising results; however, con- trolled studies of drug synergy and administration routes shall be performed for effective evaluation.

Infecção por parvovírus B19 em receptores de transplante renal: série de caso / Parvovirus B19 infection in kidney transplant recipients: a case series

Os receptores de transplante renal são mais suscetíveis a infecções, entre elas o parvovírus B19, que pode ser transmitido por via respiratória, adquirido por meio do enxerto ou por reativação de infecção latente. A anemia normocítica normocrômica, com diminuição dos reticulócitos e resistência ao tratamento com eritropoietina, é a principal forma de apresentação da infecção por parvovírus B19 em transplante renal. O diagnóstico requer alto índice de suspeição clínica e realização de testes diagnósticos selecionados. Tratamento com imunoglobulina e suspensão dos imunossupressores durante a infecção mostraram-se eficazes. Os autores relatam sua experiência com cinco casos de infecção por parvovírus B19 em receptores de transplante renal de um hospital universitário. Os aspectos clínicos, diagnósticos e terapêuticos são revistos.

Kidney transplant recipients are more susceptible to infections, including by parvovirus B19, spread through the respiratory tract, acquired through the graft or reactivation of latent infection. Normocytic normochromic anemia, with decreased reticulocytes and resistance to erythropoietin treatment, is the most common presentation of Parvovirus B19 infection in renal transplant. Diagnosis requires a higher clinical suspicion and the performance of selected diagnostic tests. Treatment with immunoglobulin and suspension of immunosuppressive therapy during the infection may be effective. The authors report five cases of PB19 infection in kidney transplant patients at a hospital. The clinical, diagnostic, and treatment features are reviewed.

Quality of life of individuals receiving kidney transplantation in Amazonas State / Qualidade de vida de pessoas receptoras de transplante renal no Amazonas / Calidad de vida de las personas receptoras de trasplante renal en Amazonas

Abstarct Objective: to analyze the quality of life of kidney transplant receivers in the State of Amazonas. Method: a cross-sectional, descriptive study, performed with 222 individuals after renal transplantation registered in a private clinic and in a health public ambulatory. Data collection took place through structured interviews where the quality of life was measured by the Kidney Disease Quality of Life - Short Form. Descriptive statistics were used for data analysis. Results: the quality of life scores found ranged from 36.5 to 83.1. The quality of life domains, specifics of renal disease, have proved to be superior to generic ones. The most compromised were work situation; sleep; physical function and emotional function, with scores of 36.5; 53.7; 52.4; 55.1, respectively, and correlated moderately and significantly with each other. Conclusion: the majority (63.2%) of the quality of life domains obtained high scores and the specific component of renal disease had higher scores than the generic component.

Objetivo: analisar a qualidade de vida de receptores de transplante renal no Estado do Amazonas. Método: estudo transversal, descritivo, realizado com 222 indivíduos pós-transplante renal cadastrados em uma clínica privada e em um ambulatório público de saúde. A coleta de dados deu-se por meio de entrevista estruturada onde a qualidade de vida foi medida pelo Kidney Disease Quality of Life - Short Form. Para a análise dos dados, foi utilizada estatística descritiva. Resultados: os escores de qualidade de vida encontrados variaram de 36,5 a 83,1. Os domínios de qualidade de vida específicos da doença renal mostraram-se superiores aos genéricos. Os mais comprometidos foram Situação de trabalho; Sono; Função física e Função emocional, com escores 36,5; 53,7; 52,4; 55,1, respectivamente, e correlacionados moderada e significativamente entre si. Conclusão: a maioria (63,2%) dos domínios de qualidade de vida obtiveram escores elevados e o componente específico da doença renal teve pontuações superiores ao componente genérico.

Objetivo: analizar la calidad de vida de las personas receptoras de trasplante renal en el Estado de Amazonas. Método: estudio transversal descriptivo, realizado con 222 personas, con posterioridad a la realización de un trasplante renal, inscriptos en una clínica privada y en un hospital público. La recolección de datos se realizó mediante entrevista semiestructurada y se midió la calidad de vida por medio del Kidney Disease Quality of Life - Short Form. En el análisis de datos, se utilizó la estadística descriptiva. Resultados: El puntaje de calidad de vida obtenido osciló de 36,5 a 83,1. Los dominios de calidad de vida propios de la enfermedad renal, tuvieron un puntaje superior al genérico. Los más comprometidos fueron: situación laboral, sueño, función física y función emocional, con puntajes de 36,5; 53,7; 52,4; 55,1, respectivamente, y correlacionados moderada y significativamente entre sí. Conclusión: la mayoría (63,2%) de los dominios relativos a la calidad de vida obtuvieron puntajes elevados y el componente específico de la enfermedad renal obtuvo un puntaje superior al componente genérico.

Detection of cytomegalovirus disease by real-time quantitative PCR targeting immediate early gene (ppUL83) in different samples among post-renal-transplant recipients

Renal transplantation is a treatment option for end-stage renal disease (ESRD). Cytomegalovirus (CMV) infection was analysed among symptomatic and asymptomatic post-renal-transplant recipients (PRTRs). A total of 30 PRTRs were enrolled. DNA was extracted and quantitative real-time PCR for CMV (CMV R-Gene, France) targeting ppUL83 gene was performed on whole blood, urine and saliva. The detection rate of CMV was found to be 27% (n = 8) in different samples, including whole blood, urine and saliva. Among 30 PRTRs, 53% (n = 16) of the PRTRs did not shed virus in saliva. About 7% of CMV was detected only in saliva among PRTRs who were symptomatic.

Oral manifestation in pre-renal transplant patients in Tertiary Care Hospital in Punjab

The incidence of renal failure is known to be increasing globally. Kidney transplant are considered the most efficient renal replacement therapy for a significant number of patients with end- stage renal disease. Renal failure can give rise to a large spectrum of oral manifestations, affecting overall health of patients with renal disease. End-stage renal disease (ESRD) patients have a plethora of oral findings. The aim of this study was to study oral symptoms and lesions in pre-renal transplant patients. This prospective study was conducted over a 6-month period. A total of 80 individuals (40 pre renal transplant patients and 40 controls) were recruited. Each patient was interviewed individually using questionnaire about oral symptoms. Each patient was examined for oral lesions and documented. For Caries DMFT and for Gingivitis CPITN index was used. In both study and control group majority were males and majority were in age group 21-30 years. In study group knowledge of importance of oral hygiene was more. The most common symptoms were dry mouth (20%), altered taste (52.5%) and bleeding gums (42.5%). Study group showed significantly more oral changes than those in the control group. DMFT index was positive in 60% of study and 80% control group. CPITN index was equally positive (92.5%) in both study and control group. Mucosal pallor, suburral tongue, leukoplakia and hyperplastic gingivitis was seen in 27.5%, 10%, 10% and 2.5% respectively in the study group. Prevalence of oral lesions is significantly higher in renal patients. The potential source of active infective lesions in medically compromised patients with ESRD must be treated before transplant.

Anal dysplasia among solid organ transplant recipients; a cross sectional study / Displasia anal entre receptores de transplantes de órgãos sólidos - um estudo transversal

ABSTRACT Introduction: The incidence of anal cancer in United States has increased over of the last few decades impacting immunosuppressed populations like solid organ transplant recipients, in particular. The aim of this study was to evaluate the prevalence of anal dysplasia among solid organ transplant patients. We also attempted to identify factors that predispose solid organ transplant recipients to developing anal dysplasia. Methods and materials: Patients presenting to transplant office for routine care were recruited to participate in the study. All anal cytology specimens were collected using standard anal pap technique. The results were assessed using Bethesda classification. Information on perceived risk factors for development of anal dysplasia among our subjects was obtained. Results: Among 80 patients approached, 47 agreed to participate in the study. Of all the samples 19.1% had an inadequate amount of specimen to perform any analysis. Dysplastic cells were found in 10.5% of the specimens available for analysis. We were not able to identify any risk factors including age, gender distribution, smoking, and duration of immunosuppression that were statistically significant different between patients with anal dysplasia versus those without anal dysplasia. Conclusions: The rate of anal dysplasia detectable on cytology is high enough to warrant anal dysplasia screening in transplant recipients, which can then be followed up with high-resolution anoscopy with biopsy. Defining a cohort of patients among solid organ transplant recipients who are at an increased risk for the development of anal dysplasia mandating screening continues to be a challenge.

RESUMO Introdução: A incidência de câncer anal nos Estados Unidos aumentou nas últimas décadas, afetando populações imunossuprimidas, especialmente receptores de órgãos sólidos. O objetivo deste estudo foi avaliar a prevalência de displasia anal entre pacientes que receberam transplante de órgãos sólidos. Os autores buscaram identificar fatores que predispõem os receptores de transplante de órgãos sólidos a desenvolverem displasia anal. Métodos e materiais: Pacientes que se apresentaram ao consultório de transplante para acompanhamento de rotina foram recrutados para participar do estudo. Todos os espécimes de citologia foram coletados usando a técnica padrão de Papanicolau anal. Os resultados foram avaliados usando a classificação de Bethesda. Foram coletados dados sobre os fatores de risco percebidos para o desenvolvimento de displasia anal entre os participantes. Resultados: Dos 80 pacientes abordados, 47 concordaram em participar do estudo. Do total de amostras, 19,1% tinham uma quantidade inadequada para realizar qualquer análise. Células displásicas foram encontradas em 10,5% dos espécimes disponíveis para análise. Não foi possível identificar quaisquer fatores de risco, incluindo idade, distribuição de gênero, tabagismo e duração da imunossupressão, que foram estatisticamente diferentes entre pacientes com displasia anal e aqueles sem displasia anal. Conclusões: A taxa de displasia anal detectável na citologia é alta o suficiente para justificar a triagem em receptores de transplante, que pode então ser acompanhada com anuscopia de alta resolução com biópsia. A definição de triagem para uma coorte de pacientes entre os receptores de transplantes de órgãos sólidos que apresentam risco aumentado para o desenvolvimento displasia anal continua a ser um desafio.

Influencing Factors Analysis of 6-Methylmercaptopurine Ribonucleotides (6-MMPR) in Human Red Blood Cell (RBC) in Kidney Transplant Recipients / 中国药学杂志

OBJECTIVE: To monitor and investigate the influencing factors of 6-methylmercaptopurine ribonucleotides (6-MMPR) in human red blood cell (RBC) in Chinese kidney transplant recipients treated with azathiopurine (AZA), and to provide references for clinical personalized medicine. METHODS: In 100 Chinese kidney transplant recipients, the concentration of 6-MMPR in RBC was detected by validated HPLC-UV method. Correlation analysis was performed to analyze the effects of various factors, including patient age, gender, weight, AZA dose and thiopurine S-methyltransferase (TPMT) activity, on the 6-MMPR concentration, and multivariate linear regression analysis was performed using SPSS20.0 software to investigate the influencing factors of 6-MMPR concentration. RESULTS: The concentration of 6-MMPR in 100 Chinese kidney transplant recipients was not normally distributed (P0.05), however, there was a significant positive correlation between TPMT activity and 6-MMPR concentration in RBC (P<0.001). CONCLUSION: TPMT activity in RBC is an independent factor affecting 6-MMPR concentration, which in turn affects the clinical efficacy and toxicity of the drug.

Changing pattern and safety of pretransplant malignancy in kidney transplant recipients

BACKGROUND: Cancer rates are increasing not only in the general population but also in patients with end-stage renal disease. We investigated the changing pattern of pretransplant malignancy in kidney transplant recipients over 5 decades.METHODS: We reviewed 3,748 kidney transplant recipients between 1969 and 2016. We divided patients into three groups (1969–1998, 1999–2006, 2007–2016) based on the era of the cancer screening system used throughout the nation. We analyzed the incidence and pattern of pretransplant malignancy among the three groups. We also evaluated recurrent and de novo malignancy in these patients compared to patients without pretransplant malignancy.RESULTS: A total of 72 patients exhibited pretransplant malignancy (1.9%). There were no cases of pretransplant cancer until 1998, but the rate of pretransplant malignancy gradually increased to 1.1% during 1999–2006 and further increased to 4.3% thereafter. The most frequent types of pretransplant malignancy changed from the bladder, liver, and stomach cancers to thyroid cancer and renal cell carcinoma. There were no de novo cases, but there were three cases of recurrent cancer in patients with pretransplant malignancy; the recurrence rate among kidney transplant recipients with pretransplant malignancy was not significantly different from the incidence rate of de novo malignancy among kidney transplant recipients without pretransplant malignancy (4.2% vs. 6.9%, P = 0.48).CONCLUSION: The incidence of pretransplant malignancy in kidney transplantation candidates is gradually increasing, and recent increases were accompanied by changes in cancer types. Pretransplant malignancy may not be a hindrance to kidney transplantation because of the low incidence of posttransplant recurrence and de novo malignancy.

Nutritional Status of Liver Transplantation Recipients and Factors Influencing Nutritional Status

PURPOSE: This study aimed to investigate the nutritional status of liver transplantation (LT) recipients and explore certain factors that influence nutritional status, including dietary patterns and physical activities. METHODS: This was a cross-sectional, descriptive study. The subjects included 211 LT recipients at a medical center outpatient clinic located in Seoul, Korea. The nutritional status, dietary patterns, and physical activities of each subject were measured using the body mass index (BMI), Mini Dietary Assessment (MDA), and Global Physical Activity Questionnaire. Independent t-test, one-way analysis of variance, and multiple linear regression analysis were used to analyze the data. RESULTS: The percentages of living and deceased donor LTs were 81.0% and 19.0%, respectively. The mean BMIs pre- and post-LT were 23.88 and 23.16 kg/m2, respectively, and the average MDA score was 36.55. More than 60.0% of the subjects had a moderate or high level of physical activity. In multivariate analysis, a higher BMI before LT (β=.72, p<.001), a lower Model for End-stage Liver Disease (MELD) score (β=−.18, p<.001), and being male (β=−.10, p=.024) contributed to better nutritional status post-LT. Patients within six months of LT were less engaged in muscle exercises than those post six months of LT (p=.020). CONCLUSION: LT recipients in Korea have good nutritional status and a good level of physical activity. To improve recipients' post-LT nutritional status, the pre-LT nutritional status should be considered, particularly in those with a higher MELD score. In addition, physical activity including muscle-strengthening exercises should be encouraged from an earlier stage.

Una mirada al origen, funcionamiento y desafíos del nuevo sistema de donación y trasplantes chileno / A peek to the origin, functioning and challenges of the new Chilean transplantation system

Chile made several legal, practical and educational changes to the organ donation and transplant system in recent years, to improve its results. However, studies evaluating these reforms and suggesting further corrections are still pending. Our aim is to assess the new regulations and their reception by both the population and health care providers. Proposals are made to promote the development of a model of Chilean transplantation able to respond to the needs of the population.

Relationship of Transforming Growth Factor-β1 and Arginase-1 Levels with Long-term Survival after Kidney Transplantation / 华中科技大学学报（医学）（英德文版）

In this study,we compared the serum levels of transforming growth factor-β1 (TGF-β1),interleukin-10 (IL-10),and arginase-1 in long-term survival kidney transplant recipients (LTSKTRs) with those in short-term survival kidney transplant recipients (STSKTRs).We then evaluated the relationship between these levels and graft function.Blood samples were collected from 50 adult LTSKTRs and 20 STSKTRs (graft survival approximately 1-3 years post-transplantation).All patients had stable kidney function.The samples were collected at our institution during the patients' follow-up examinations between March 2017 and September 2017.The plasma levels of TGF-β1,IL-10,and arginase-1 were analyzed using enzyme-linked immunosorbent assays (ELISA).The levels of TGF-β1 and arginase-1 were significantly higher in the LTSKTRs than in the STSKTRs.The time elapsed since transplantation was positively correlated with the levels of TGF-β 1 and arginase-1 in the LTSKTRs.The estimated glomerular filtration rate was positively correlated with the TGF-β1 level,and the serum creatinine level was negatively correlated with the TGF-β1 level.Higher serum levels of TGF-β1 and arginase-1 were found in LTSKTRs than in STSKTRs,and we found that TGF-β1 was positively correlated with long-term graft survival and function.Additionally,TGF-β1 and arginase-1 levels were positively correlated with the time elapsed since transplantation.On the basis of these findings,TGF-β1 and arginase-1 may play important roles in determining long-term graft survival.Thus,we propose that TGF-β1 and arginase-1 may potentially be used as predictive markers for evaluating long-term graft survival.