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Inborn errors of immunity (IEI) are a heterogeneous group of hereditary disorders that affect in number and/or function different components of the immune system, resulting in an increased risk and severity of infections, autoimmune diseases, allergic manifestations, autoinflammation and malignancy. Inactivated vaccines are generally safe in these patients, but may be ineffective in some cases, due to difference in immunogenicity. However, live viral and bacterial vaccines may lead to disease, with high morbidity and mortality, so it is essential a previous immunological work-out. In this document, the Pediatric Immunology Work Group of the Sociedad Argentina de Pediatría summarizes recommendations about immunizations in patients with IEI, their household contacts, as well as in patients under immunosuppressive treatment and hematopoietic stem cell transplant recipients.
Los errores innatos de la inmunidad (EII) constituyen un grupo heterogéneo de enfermedades hereditarias que afectan el número y/o la función de los distintos componentes del sistema inmune, lo que predispone a un incremento de la tasa y gravedad de infecciones, enfermedades autoinmunes, manifestaciones alérgicas, autoinflamación y malignidad. En estos pacientes, la inmunización con vacunas inactivadas es generalmente segura, pero puede no ser efectiva en determinados grupos de EII, sin generar el efecto protector deseado. La aplicación de vacunas vivas atenuadas (virales y bacterianas) puede llevar al desarrollo de enfermedad asociada a la inmunización, con elevada morbimortalidad, por lo que amerita previamente consultar al especialista. El presente informe resume las conclusiones del Grupo de Trabajo de Inmunología de la Sociedad Argentina de Pediatría respecto a la vacunación en pacientes con EII y sus convivientes, en pacientes bajo inmunosupresión farmacológica y en receptores de trasplante de células precursoras hematopoyéticas.
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Human Pegivirus Type 1 (HPgV-1), a ubiquitous commensal virus, has been recently suggested as a marker of immunologic function. There is scarce data for the presence, genotypes, and molecular characteristics of HPgV-1 among kidney transplant recipients. Therefore, the objective of this study was to examine the prevalence and the molecular characteristics (cycle threshold, genotypes) of this viral infection among kidney transplant recipients from the Brasília, Federal District of Brazil. HPgV-1 RNA detection in the plasma was assessed by RT-qPCR. Positive samples were submitted to sequencing and phylogenetic analysis of the 5´-UTR portion of the viral genome. The estimated HPgV-1 prevalence among renal-transplant recipients was 20%. The performed phylogenetic inference revealed that the most frequent genotype among these patients was HPgV-1 genotype 2 (78.9%) presented by its two subgenotypes (2 A and 2B), followed by genotypes 1 and 3 (10.5% each). This study presents new data about the HPgV-1 circulation and molecular characteristics among kidney transplant recipients from the Federal District of Brazil. Further work is fundamental to examine the effect of HPgV-1 among patients with immunological suppression, including kidney transplant recipients.
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Cada vez más pacientes trasplantados hepáticos durante la edad pediátrica alcanzan la adultez debido al aumento en las tasas de sobrevida a largo plazo, por lo que requieren continuar su atención en un centro de adultos. Este pasaje entre centros se asocia con peores resultados clínicos y mayor mala adherencia, debido al momento de vulnerabilidad que representa este momento en la atención médica y por el mismo momento vital atravesado por el paciente adolescente. La mayoría de los centros de trasplantes establecieron programas de transición para mejorar estos resultados. Para que estos programas sean efectivos, deben conocerse las barreras y los facilitadores de adherencia tanto en el paciente como en su entorno. El objetivo de este trabajo es reconocer estos factores de riesgo y su relación con mala adherencia y resultados clínicos, y realizar un seguimiento a corto plazo de los pacientes transferidos a un centro de atención de adultos. Para esto, se realizó una encuesta pre y post derivación a una cohorte de pacientes adolescentes del Hospital Garrahan. Para medir mala adherencia se utilizaron métodos objetivos y subjetivos, cada uno de los cuales correlacionó con distintos factores de riesgo, como presencia de violencia, consumo de sustancias y déficit educativo. Como conclusión, medir la mala adherencia es complejo debido a que su origen es multifactorial. Al parecer, combinar cuestionarios validados con entrevistas no estructuradas es la estrategia más efectiva para detectar mala adherencia en la consulta médica. Luego, las variables psicosociales están cobrando cada vez más relevancia y deben ser consideradas en los programas de transición de los servicios de trasplante si se quiere lograr un seguimiento a largo plazo exitoso (AU)
An increasing number of pediatric liver transplant patients reach adulthood due to the increase in long-term survival rates, and therefore require continued care in an adult center. This transition between centers is associated with worse clinical outcomes and poorer adherence, due to the vulnerability that this moment in medical care represents and the same vital moment that the adolescent patient goes through. Most transplant centers have established Transition Programs to improve these outcomes. For these programs to be effective, the barriers and facilitators of adherence in both the patient and their environment should be known. The aim of this study was to identify these risk factors and their relationship with poor adherence and clinical outcomes, and to perform a short-term follow-up of patients transferred to an adult care center. For this purpose, a pre- and post-referral survey was conducted on a cohort of adolescent patients from the Garrahan Hospital. Objective and subjective methods were used to measure poor adherence, each of which correlated with different risk factors, such as the presence of violence, substance use, and educational deficits. In conclusion, measuring poor adherence is complex because its origin is multifactorial. Combining validated questionnaires with unstructured interviews seems to be the most effective strategy for detecting poor adherence in the medical consultation. Therefore, psychosocial variables are becoming increasingly relevant and should be considered in the Transition Programs of transplantation services if a successful longterm follow-up is to be achieved (AU)
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Humanos , Adolescente , Inquéritos e Questionários , Fatores de Risco , Seguimentos , Transplante de Fígado , Transição para Assistência do Adulto/organização & administração , Cooperação e Adesão ao Tratamento , Doença Crônica , Estudos Prospectivos , Estudos de CoortesRESUMO
This study compares the humoral immune response of a cohort of renal transplant recipients (RTRs), in Trinidad & Tobago following two-dose primary immunization with non-mRNA vaccines amidst the COVID-19 pandemic. RTRs along with healthy, age-and gender-matched controls received either the adenoviral vector vaccine, AstraZeneca-Vaxzevria (AZ) or the inactivated vaccine, Beijing CNBG-BBIBP- CorV/Sinopharm (SP). Samples were taken after completion of a two-dose primary immunization during the period November 2021 to December 2021, at a mean interval of 138 days following immunization. 38/72 RTRs (53 %) failed to generate any protective antibody responses, compared with 7/73 participants, approximately 10 % in the healthy, age and gender-matched control group. In the RTRs, there was no significant correlation of their antibody concentration with either the timing of sample collection or the interval since transplantation. The study provides necessary information about the humoral response after two- doses of non-mRNA vaccines in a group of transplant recipients.
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Tacrolimus (TAC) is an immunosuppressant drug that prevents organ rejection after transplantation. This drug is transported from cells via P-glycoprotein (ABCB1) and is a metabolic substrate for cytochrome P450 (CYP) 3A enzymes, particularly CYP3A4 and CYP3A5. Several single-nucleotide polymorphisms (SNPs) have been identified in the genes encoding CYP3A4, CYP3A5, and ABCB1, including CYP3A4-392A/G (rs2740574), CYP3A5 6986A/G (rs776746), and ABCB1 3435C/T (rs1045642). This study aims to evaluate the association among CYP3A4-392A/G, CYP3A5-6986A/G, and ABCB1-3435C/T polymorphisms and TAC, serum concentration, and biochemical parameters that may affect TAC pharmacokinetics in Mexican kidney transplant (KT) patients. METHODS: Forty-six kidney transplant recipients (KTR) receiving immunosuppressive treatment with TAC in different combinations were included. CYP3A4, CYP3A5, and ABCB1 gene polymorphisms were genotyped using qPCR TaqMan. Serum TAC concentration (as measured) and intervening variables were assessed. Logistic regression analyses were performed at baseline and after one month to assess the extent of the association between the polymorphisms, intervening variables, and TAC concentration. RESULTS: The GG genotype of CYP3A5-6986 A/G polymorphism is associated with TAC pharmacokinetic variability OR 4.35 (95%CI: 1.13-21.9; p = 0.0458) at one month of evolution; in multivariate logistic regression, CYP3A5-6986GG genotype OR 9.32 (95%CI: 1.54-93.08; p = 0.028) and the use of medications or drugs that increase serum TAC concentration OR 9.52 (95%CI: 1.79-88.23; p = 0.018) were strongly associated with TAC pharmacokinetic variability. CONCLUSION: The findings of this study of the Mexican population showed that CYP3A5-6986 A/G GG genotype is associated with a four-fold increase in the likelihood of encountering a TAC concentration of more than 15 ng/dL. The co-occurrence of the CYP3A5-6986GG genotype and the use of drugs that increase TAC concentration correlates with a nine-fold increased risk of experiencing a TAC at a level above 15 ng/mL. Therefore, these patients have an increased susceptibility to TAC-associated toxicity.
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Subfamília B de Transportador de Cassetes de Ligação de ATP , Citocromo P-450 CYP3A , Imunossupressores , Transplante de Rim , Polimorfismo de Nucleotídeo Único , Tacrolimo , Humanos , Citocromo P-450 CYP3A/genética , Transplante de Rim/efeitos adversos , Tacrolimo/sangue , Tacrolimo/farmacocinética , Tacrolimo/administração & dosagem , Subfamília B de Transportador de Cassetes de Ligação de ATP/genética , Feminino , Masculino , Polimorfismo de Nucleotídeo Único/genética , Adulto , México , Imunossupressores/farmacocinética , Imunossupressores/sangue , Imunossupressores/administração & dosagem , Pessoa de Meia-Idade , Genótipo , Rejeição de Enxerto/genéticaRESUMO
OBJECTIVES: To evaluate cost-effective pharmacological treatment in adult kidney transplant recipients from the perspective of the Colombian health system. METHODS: A decision tree model for the induction phase and a Markov model for the maintenance phase were built. A review of the clinical literature was conducted to extract probabilities, and the life-years were used as the outcome. Costs were calculated using the administrative databases. The evaluating treatment schemes are organized by groups of evidence with direct comparisons. RESULTS: In the induction phase, anti-thymocyte immunoglobulin+ methylprednisolone is dominant, more effective, and less expensive, compared with basiliximab+methylprednisolone. In the maintenance phase, azathioprine (AZA) is dominant in contrast to mycophenolate mofetil (MFM) both with cyclosporine (CIC)+ corticosteroids (CE); CIC is dominant relative to sirolimus (SIR) and tacrolimus (TAC) (both with MFM+CE or AZA+CE), and TAC is dominant compared with SIR (in addition with MFM+CE or mycophenolate sodium [MFS]+CE); MFM is dominant in relation to MFS and everolimus, and SIR is more effective MFM but it does not exceed the threshold (in sum with TAC+CE); MFS and MFM are dominant relative to everolimus, and SIR is more effective than MFM, but it does not exceed the threshold (in addiction with CIC+CE); MFM is dominant in relation to TAC (in sum with SIR+CE), and CIC+AZA+CE is dominant in relation to TAC+MFM+CE. CONCLUSIONS: The base-case results for all evidence groups are consistent with the different sensitivity analyses.
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Imunossupressores , Transplante de Rim , Adulto , Humanos , Corticosteroides/uso terapêutico , Corticosteroides/economia , Azatioprina/uso terapêutico , Azatioprina/economia , Colômbia , Análise de Custo-Efetividade , Ciclosporina/uso terapêutico , Ciclosporina/economia , Árvores de Decisões , Rejeição de Enxerto/prevenção & controle , Rejeição de Enxerto/economia , Imunossupressores/economia , Imunossupressores/uso terapêutico , Transplante de Rim/economia , Cadeias de Markov , Ácido Micofenólico/uso terapêutico , Ácido Micofenólico/economia , Sirolimo/uso terapêutico , Sirolimo/economia , Tacrolimo/economia , Tacrolimo/uso terapêutico , Transplantados/estatística & dados numéricosRESUMO
Human Pegivirus Type 1 (HPgV-1), a ubiquitous commensal virus, has been recently suggested as a marker of immunologic function. There is scarce data for the presence, genotypes, and molecular characteristics of HPgV-1 among kidney transplant recipients. Therefore, the objective of this study was to examine the prevalence and the molecular characteristics (cycle threshold, genotypes) of this viral infection among kidney transplant recipients from the Brasília, Federal District of Brazil. HPgV-1 RNA detection in the plasma was assessed by RT-qPCR. Positive samples were submitted to sequencing and phylogenetic analysis of the 5´-UTR portion of the viral genome. The estimated HPgV-1 prevalence among renaltransplant recipients was 20%. The performed phylogenetic inference revealed that the most frequent genotype among these patients was HPgV-1 genotype 2 (78.9%) presented by its two subgenotypes (2 A and 2B), followed by genotypes 1 and 3 (10.5% each). This study presents new data about the HPgV-1 circulation and molecular characteristics among kidney transplant recipients from the Federal District of Brazil. Further work is fundamental to examine the effect of HPgV-1 among patients with immunological suppression, including kidney transplant recipients.
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Abstract Background: End-stage renal diseases patients have a high risk of postoperative nausea and vomiting (PONV), which is multifactorial and need acute attention after renal transplantation for a successful outcome in term of an uneventful postoperative period. The study was done to compare the efficacy of palonosetron and ondansetron in preventing early and late-onset PONV in live donor renal transplantation recipients (LDRT). Methods: The prospective randomized double-blinded study was done on 112 consecutive patients planned for live donor renal transplantation. Patients of both sexes in the age group of 18-60 years were randomly divided into two groups: Group O (Ondansetron) and Group P (Palonosetron) with 56 patients in each group by computer-generated randomization. The study drug was administered intravenously (IV) slowly over 30 seconds, one hour before extubation. Postoperatively, the patients were accessed for PONV at 6, 24, and 72 hours using the Visual Analogue Scale (VAS) nausea score and PONV intensity scale. Results: The incidence of PONV in the study was found to be 30.35%. There was significant difference in incidence of PONV between Group P and Group O at 6 hours (12.5% vs. 32.1%, p = 0.013) and 72 hours (1.8% vs. 33.9%, p < 0.001), but insignificant difference at 24 hours (1.8% vs. 10.7%, p = 0.113). VAS-nausea score was significantly lower in Group P as compared to Group O at a time point of 24 hours (45.54 ± 12.64 vs. 51.96 ± 14.70, p = 0.015) and 72 hours (39.11 ± 10.32 vs. 45.7 ± 15.12, p = 0.015). Conclusion: Palonosetron is clinically superior to ondansetron in preventing early and delayed onset postoperative nausea and vomiting in live-related renal transplant recipients.
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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.
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COVID-19's severity has been associated with a possible imbalance in the cross-regulation of cytokines and vascular mediators. Since the beginning of the pandemic, kidney transplant recipients (KTRs) have been identified as patients of high vulnerability to more severe diseases. Thus, aiming to describe the patterns of cytokines and vascular mediators and to trace patients' differences according to their KTR status, this prospective study enrolled 67 COVID-19 patients (20 KTRs) and 29 non-COVID-19 controls before vaccination. A panel comprising 17 circulating cytokines and vascular mediators was run on samples collected at different time points. The cytokine and mediator patterns were investigated via principal component analysis (PCA) and correlation-based network (CBN). In both groups, compared to their respective controls, COVID-19 was associated with higher levels of cytokines and vascular mediators. Differentiating between the KTRs and non-KTRs, the number of correlations was much higher in the non-KTRs (44 vs. 14), and the node analysis showed the highest interactions of NGAL and sVCAM-1 in the non-KTRs and KTRs (9 vs. 4), respectively. In the PCA, while the non-KTRs with COVID-19 were differentiated from their controls in their IL-10, IFN-α, and TNF-α, this pattern was marked in the NGAL, sVCAM-1, and IL-8 of the KTRs.
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COVID-19 , Transplante de Rim , Humanos , Citocinas , Estudos Prospectivos , Lipocalina-2 , TransplantadosRESUMO
OBJECTIVE: This study aimed to investigate whether hysteroscopy plus endometrial fundal incision (EFI) with endoscopic scissors can improve reproductive outcomes in oocyte recipients who have failed in their first egg donation cycle. METHODS: This was a prospective study (2014-2022) conducted in Assisting Nature Centre Reproduction and Genetics, Thessaloniki Greece, IVF Unit. The study population consisted of oocyte recipients with implantation failure in their first embryo transfer (ET) with donor eggs. All the recipients underwent routine evaluation during their early follicular phase, 1-3 months before the start of a new cycle with donor oocytes and were eligible to undergo EFI. RESULTS: During the study period, 218 egg recipients underwent egg donation; 126 out of 218 oocyte recipients (57.8%) did not achieve a live birth at the 1st ET. 109 of them had surplus embryos cryopreserved and underwent a second ET; 50 women consented for EFI. Both groups were similar in terms of age, years of infertility, duration of estrogen replacement protocol and number of transferred blastocysts (p>0.05). In the EFI group, 60% had normal intrauterine cavity, while 40% had minor anomalies. The pregnancy test was positive in 46% (n=23/50) in the EFI group compared with 27.1% (n=16/59) in the control group (p=0.04). Moreover, live birth rates were higher in the EFI group compared to the control group (38.0% vs. 20.3%; p=0.04). CONCLUSIONS: The findings of our study indicate that in oocyte recipients after implantation failure, diagnostic hysteroscopy plus EFI prior to subsequent ETmay increase pregnancy and live birth rates.
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This study aimed to evaluate the effect of luteal blood perfusion and corpus luteum (CL) area on the conception rate and occurrence of pregnancy loss of recipients in a large-scale fixed-time embryo transfer (FTET) program. Multiparous Brangus cows (n = 1700) at 45 days postpartum and body condition scores (BCS) between 2.5 and 4.0 (3.0 ± 0.3) were used in this study. On a random day of the estrous cycle (day -10), the females received progesterone and estradiol based on the FTET protocol. On day 7, 1465 recipients had at least one CL and were evaluated using B-mode ultrasound for the CL area (cm2) and color Doppler for the luteal blood perfusion score (I/low-vascularization area <40% of the CL; II/medium-vascularization >45% to < 50%; and III/high-vascularization >50%). Immediately after CL evaluation, each recipient received a single fresh embryo (blastocyst stage) ipsilateral to the CL, in vitro produced from a commercial laboratory. Pregnancy diagnosis was performed at 30 days and repeated 60 days later to evaluate pregnancy loss (30-90 days). Ultrasound evaluation and embryo transfer were performed by a single technician. For data analysis, in addition to luteal blood perfusion groups, recipients were retrospectively ranked according to CL area into small (<3 cm2; 2.63 ± 0.01), medium (>3 to < 4 cm2; 3.44 ± 0.01), and large (>4 cm2; 4.77 ± 0.03). Data were analyzed using a logistic regression model (P < 0.05). The overall conception rate was 44.2% (648/1465), influenced by the luteal blood perfusion score [P = 0.03; high 48.4%a (134/277), medium 44.6%a (427/958), and low 37.8%b (87/230)] but not by CL area ranking [P = 0.37; large 41.8% (225/538), medium 45.2% (276/610), and small 46.4% (147/317)]. There was no interaction between the luteal blood perfusion score and CL area ranking (P = 0.81), and the BCS did not affect the results of this study (P = 0.51). In terms of pregnancy loss up to 90 days, there was no effect on the CL area ranking (P = 0.77), but the flow score showed an effect [P = 0.03; high 3.6%b (5/139), medium 9.3%a (44/471), and low 10.3%a (10/97)]. The conception rate and occurrence of pregnancy loss in the FTET program in beef cattle are related to luteal blood perfusion but not CL size.
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Aborto Animal , Doenças dos Bovinos , Gravidez , Feminino , Bovinos , Animais , Estudos Retrospectivos , Corpo Lúteo , Progesterona , Transferência Embrionária/veterináriaRESUMO
BACKGROUND: Convalescent plasma (CP) became a prominent treatment in the early stages of the SARS-CoV-2 pandemic. In Argentina, a randomized clinical trial was executed to compare the use of CP in inpatients with severe COVID-19 pneumonia versus placebo. No differences in clinical outcomes or overall mortality between groups were observed. We conducted a cohort study in outpatients enrolled in the trial to describe long-term antibody titer variations between CP and placebo recipients. METHODS: Patients' total SARS-CoV-2 IgG antibodies against spike protein were collected 3, 6 and 12 months after hospital discharge from August 2020 to December 2021. In addition, reinfections, deaths and vaccination status were retrieved. Statistical analysis was performed using antibody geometric mean titers (GMT). All estimations were made considering the date of the trial infusion (placebo or CP) as time 0. RESULTS: From the 93 patients included in the follow-up, 64 had received CP and 29 placebo. We excluded all 12-month measurements because they were collected after the patients' vaccination date. At 90 days post-infusion, patients had an antibody GMT of 8.1 (IQR 7.4-8.1) in the CP group and 8.8 (IQR 8.1-9.1) in the placebo group. At 180 days, both groups had a GMT of 8.1 (IQR 7.4-8.1). No statistical differences in GMT were found between CP and placebo groups at 90 days (p = 0.12) and 180 days (p = 0.25). No patients registered a new COVID-19 infection; one died in the CP group from an ischemic stroke. CONCLUSIONS: No differences were observed in long-term antibody titers in unvaccinated patients that received CP or placebo after severe COVID-19 pneumonia.
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COVID-19 , Humanos , COVID-19/terapia , COVID-19/etiologia , SARS-CoV-2 , Estudos de Coortes , Imunização Passiva/efeitos adversos , Soroterapia para COVID-19 , Anticorpos AntiviraisRESUMO
BACKGROUND: Lung transplantation represents the definite treatment for CF patients with advanced-stage pulmonary disease. Recent major developments in the treatment of CF indicate the need for an evaluation of lung transplantation as the current best practice in end-stage disease. This systematic review was performed to evaluate the impact of lung transplantation on health-related quality of life in patients with CF. METHODS: PubMed was searched for studies matching the eligibility criteria between January 2000 and January 2022. OVID (MEDLINE), Google Scholar, and EBSCOhost (EMBASE) as well as bibliographies of included studies were also reviewed. Applying predetermined eligibility criteria, the included studies were selected. Predetermined forms were used to conduct a quality appraisal and implement data tabulation. Results were synthesized by narrative review. This systematic review was prospectively registered in the PROSPERO register (CRD 42022341942). RESULTS: Ten studies (1494 patients) were included. Lung transplantation results in improvements in HRQoL in CF patients relative to their baseline waitlisted state. Up to five years postoperatively CF patients retain their HRQoL at levels similar to the general population. There are several modulating factors that impact HRQoL outcomes in CF patients post-LTx. Compared to lung recipients with other diagnoses CF patients achieve either greater or equal levels of HRQoL. CONCLUSION: Lung transplantation conveys improved HRQoL to CF patients with the advanced-stage pulmonary disease for up to five years, and to levels comparable to the general population and non-waitlisted CF patients. This systematic review quantifies, using current evidence, the improvements in HRQoL gained by CF patients following lung transplantation.
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Fibrose Cística , Transplante de Pulmão , Humanos , Fibrose Cística/cirurgia , Qualidade de Vida , PulmãoRESUMO
Abstract Background: Lung transplantation represents the definite treatment for CF patients with advanced-stage pulmonary disease. Recent major developments in the treatment of CF indicate the need for an evaluation of lung transplantation as the current best practice in end-stage disease. This systematic review was performed to evaluate the impact of lung transplantation on health-related quality of life in patients with CF. Methods: PubMed was searched for studies matching the eligibility criteria between January 2000 and January 2022. OVID (MEDLINE), Google Scholar, and EBSCOhost (EMBASE) as well as bibliographies of included studies were also reviewed. Applying predetermined eligibility criteria, the included studies were selected. Predetermined forms were used to conduct a quality appraisal and implement data tabulation. Results were synthesized by narrative review. This systematic review was prospectively registered in the PROSPERO register (CRD 42022341942). Results: Ten studies (1494 patients) were included. Lung transplantation results in improvements in HRQoL in CF patients relative to their baseline waitlisted state. Up to five years postoperatively CF patients retain their HRQoL at levels similar to the general population. There are several modulating factors that impact HRQoL outcomes in CF patients post-LTx. Compared to lung recipients with other diagnoses CF patients achieve either greater or equal levels of HRQoL. Conclusion: Lung transplantation conveys improved HRQoL to CF patients with the advanced-stage pulmonary disease for up to five years, and to levels comparable to the general population and non-waitlisted CF patients. This systematic review quantifies, using current evidence, the improvements in HRQoL gained by CF patients following lung transplantation.
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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.
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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.
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Immunocompromised individuals are at high risk of poor coronavirus disease 2019 (COVID-19) outcomes and demonstrate a lower immune response to COVID-19 vaccines, including to the novel mRNA vaccines that have been shown to elicit high neutralizing antibody levels. This review synthesized available data on the immune response to COVID-19 and critically assessed mRNA COVID-19 vaccine immunogenicity in this vulnerable subpopulation. Patients with various immunocompromising conditions exhibit diverse responses to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and COVID-19 severity and mortality, and available vaccines elicit lower immune responses, particularly in solid organ transplant recipients. Strategies to improve vaccine responses in immunocompromised individuals are being implemented in vaccine recommendations, including the use of a third and fourth vaccine dose beyond the two-dose series. Additional doses may enhance vaccine effectiveness and help provide broad coverage against emerging SARS-CoV-2 variants. Continued investigation of vaccines and dosing regimens will help refine approaches to help protect this vulnerable subpopulation from COVID-19.
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A loop-mediated isothermal amplification assay was evaluated as a surrogate marker of treatment failure in Chagas disease (CD). A convenience series of 18 acute or reactivated CD patients who received anti-parasitic treatment with benznidazole was selected-namely, nine orally infected patients: three people living with HIV and CD reactivation, five chronic CD recipients with reactivation after organ transplantation and one seronegative recipient of a kidney and liver transplant from a CD donor. Fifty-four archival samples (venous blood treated with EDTA or guanidinium hydrochloride-EDTA buffer and cerebrospinal fluid) were extracted using a Spin-column manual kit and tested by T. cruzi Loopamp kit (Tc-LAMP, index test) and standardized real-time PCR (qPCR, comparator test). Of them, 23 samples were also extracted using a novel repurposed 3D printer designed for point-of-care DNA extraction (PrintrLab). The agreement between methods was estimated by Cohen's kappa index and Bland-Altman plot analysis. The T. cruzi Loopamp kit was as sensitive as qPCR for detecting parasite DNA in samples with parasite loads higher than 0.5 parasite equivalents/mL and infected with different discrete typing units. The agreement between qPCR and Tc-LAMP (Spin-column) or Tc-LAMP (PrintrLab) was excellent, with a mean difference of 0.02 [CI = -0.58-0.62] and -0.04 [CI = -0.45-0.37] and a Cohen's kappa coefficient of 0.78 [CI = 0.60-0.96] and 0.90 [CI = 0.71 to 1.00], respectively. These findings encourage prospective field studies to validate the use of LAMP as a surrogate marker of treatment failure in CD.
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INTRODUCTION AND OBJECTIVES: Lower antibody (Ab) responses after SARS-CoV-2 vaccination have been reported in liver transplant (LT) recipients and those with chronic liver diseases (CLD). The role of a booster dose in those with poor responses to initial vaccination is not well defined. METHODS: In this prospective study, we determined antibody (Ab) response to spike protein after a booster dose in LT recipients and those with chronic liver diseases (CLD) with and without cirrhosis after they had a poor response to an initial standard regimen. RESULTS: Of the 80 patients enrolled, 45 had LT, and 35 had CLD (18 with cirrhosis). A booster dose was given at a median of 138.5 days after the completion of the standard regimen. After the booster dose, 58 (73%, 31 LT, 27 CLD) had good response (≥250 U/mL), and 22 (28%, 14 LT, and 8 CLD) had poor response (7 undetectable and 15 with low Ab levels). No patient had any serious adverse events. The antibody responses were lower in those who had undetectable Ab (80 U/mL) than those who had low levels of Ab (0.80-249 U/mL) after the standard vaccination regimen (42% vs. 87%, p=0.0001). The antibody responses after homologous and heterologous booster doses were similar. CONCLUSIONS: We have shown that a booster dose will enhance Ab responses in LT recipients and those with CLD who had poor responses after an initial vaccine regimen.