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1.
World J Urol ; 42(1): 499, 2024 Aug 31.
Artículo en Inglés | MEDLINE | ID: mdl-39215768

RESUMEN

PURPOSE: Post-procedural urinary tract infections (ppUTIs) following voiding cystourethrography (VCUG) vary widely, with rates from 0 to 42%, though recent studies suggest rates typically below 5%. Verifying urine sterility before VCUG is traditionally done but questioned. This study assessed the 7-day ppUTI rate post-VCUG without prior urine sterility confirmation and identified associated risk factors. METHODS: A retrospective review of VCUG cases in children under three years at a pediatric hospital over two years was conducted. Exclusions included neuropathic bladder, bladder exstrophy, pre-VCUG urine cultures, and lost-to-follow-up cases. Achieving a ppUTI rate below 5% would support safe VCUG practice without pre-urine culture. RESULTS: Of 318 VCUGs performed on 300 children, 248 (78%) were males (8% circumcised) with a median age of 5 months. Retrograde VCUG was more common than suprapubic cystography (63% vs. 37%). Before the test, 33.6% received antibiotics, mostly prophylactically. Hydronephrosis was present in 66.4%, and 69% had a history of UTI. VCUG results were abnormal in 43% of cases: 85% had vesicoureteral reflux (VUR), 10% had posterior urethral valves (PUV), and 28% had other abnormalities. The 7-day ppUTI rate was 3.8%, with 67% of ppUTI cases having abnormal VCUG results versus 41% without ppUTI (p = 0.06). No significant risk factors for ppUTI were identified. CONCLUSIONS: Omitting systematic urine culture before VCUG was not associated with a high ppUTI rate, even in children with pre-existing urologic conditions or a history of UTI, indicating that VCUG can be safely performed without prior urine sterility confirmation. No risk factors for ppUTI were identified.


Asunto(s)
Cistografía , Infecciones Urinarias , Humanos , Infecciones Urinarias/epidemiología , Infecciones Urinarias/etiología , Estudios Retrospectivos , Masculino , Lactante , Femenino , Incidencia , Preescolar , Fiebre/epidemiología , Fiebre/etiología , Factores de Riesgo , Micción , Uretra/diagnóstico por imagen , Reflujo Vesicoureteral/epidemiología
2.
Pediatr Nephrol ; 2024 Sep 19.
Artículo en Inglés | MEDLINE | ID: mdl-39297957

RESUMEN

BACKGROUND: Neurological complications pose a significant threat in pediatric hemolytic and uremic syndrome (HUS) resulting from infections with Shiga toxin-producing Escherichia coli (STEC), with no established treatment. The involvement of complement activation in the pathogenesis of STEC-HUS is acknowledged, and eculizumab (ECZ), a terminal complement blocker, has been documented in several pediatric series with inconsistent results. Antibody-mediated mechanisms have also been suggested, with IgG-immunoadsorption (IgIA) showing promise in adults with neurological complications. We aimed to assess the benefit of combining IgIA with ECZ in pediatric patients with neurological STEC-HUS compared to patients treated with ECZ alone or supportive care. METHODS: Multicenter retrospective study conducted on pediatric patients (< 18 years) with neurological STEC-HUS treated with IgIA + ECZ or ECZ alone from 2010 to 2020 in France. A historical cohort treated with supportive care served as controls. Primary outcome included survival and neurological evaluation at 1-year follow-up (dichotomized as normal vs. abnormal). RESULTS: A total of 42 children were included: 18 treated with IgIA + ECZ, 24 with ECZ alone, and 27 with supportive care. Although there was no significant difference in survival between groups, three deaths occurred in the control group in the acute phase, while none was reported in both the IgIA + ECZ and ECZ alone groups, despite presenting with more severe neurological symptoms for IgIA + ECZ patients. No significant association was found between treatment group and 1-year neurological evaluation after adjustment for age, sex, and initial neurological presentation. CONCLUSIONS: Systematic association of IgIA + ECZ is not supported for all neurological STEC-HUS pediatric patients; potential rescue therapy for severe cases warrants consideration.

3.
Pediatr Nephrol ; 39(11): 3263-3269, 2024 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-38632123

RESUMEN

BACKGROUND: Between 5 and 50% of atypical hemolytic uremic syndrome (aHUS) cases in children are caused by autoantibodies against complement factor H (CFH). Given the acquired autoimmune nature of the disease, plasma exchange (PE) and various immunosuppressive treatments have been used. More recently, eculizumab has been proposed. METHODS: In this multicenter, retrospective study, we report outcomes of 12 children with anti-FH antibody-associated HUS treated with eculizumab associated with various immunosuppressive regimens. RESULTS: Patients were treated with eculizumab for 15.5 [9.5;23.0] months and 3 received PE or IgG adsorption. Three patients received mycophenolate mofetil (MMF) alone, 1 patient received MMF and steroids, 1 patient received MMF and rituximab, 3 patients received MMF/steroids and rituximab, and 4 patients did not receive any immunosuppression. Anti-FH antibody levels significantly decreased but no difference was observed based on the immunosuppressive regimen. Eculizumab was discontinued in 7/10 patients after 11 [7.5;15.5] months and MMF in 6/8 patients after 36 [35;40] months. Anti-FH titers at MMF discontinuation ranged from 257 to 3425 UI/L. None of these patients relapsed and eGFR at last follow-up was above 70 mL/min/1.73 m2 in all patients. CONCLUSIONS: Eculizumab is effective and safe in inducing and maintaining remission in aHUS secondary to anti-FH antibodies and renders reduction of anti-FH titers less urgent. Anti-FH antibody titers decreased in most patients irrespective of the immunosuppressive treatment chosen, so that a strategy consisting of combining eculizumab with MMF monotherapy seems sufficient at least in non-Indian or less severe forms of anti-FH antibody-associated HUS.


Asunto(s)
Anticuerpos Monoclonales Humanizados , Factor H de Complemento , Inmunosupresores , Intercambio Plasmático , Humanos , Estudios Retrospectivos , Masculino , Femenino , Anticuerpos Monoclonales Humanizados/uso terapéutico , Preescolar , Inmunosupresores/uso terapéutico , Niño , Factor H de Complemento/inmunología , Resultado del Tratamiento , Autoanticuerpos/sangre , Autoanticuerpos/inmunología , Lactante , Síndrome Hemolítico Urémico Atípico/terapia , Síndrome Hemolítico Urémico Atípico/inmunología , Síndrome Hemolítico Urémico Atípico/tratamiento farmacológico , Síndrome Hemolítico Urémico Atípico/sangre , Síndrome Hemolítico Urémico Atípico/diagnóstico , Ácido Micofenólico/uso terapéutico , Síndrome Hemolítico-Urémico/inmunología , Síndrome Hemolítico-Urémico/terapia , Síndrome Hemolítico-Urémico/sangre , Síndrome Hemolítico-Urémico/tratamiento farmacológico , Síndrome Hemolítico-Urémico/diagnóstico , Adolescente , Rituximab/uso terapéutico
4.
Transpl Int ; 36: 11153, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37252612

RESUMEN

In this retrospective cohort study, we analyze the early humoral and cellular response in 64 adolescents KTx recipients, after two or three doses of mRNA vaccine BNT162b2 against different variants of COVID-19. After 2 doses, 77.8% % of children with no history of infection had a positive humoral response with a median anti-S IgG level of 1107 (IQR, 593-2,658) BAU/mL. All the patients with a history of infection responded with a higher median IgG level (3,265 (IQR, 1,492-8,178) BAU/mL). In non-responders after 2 doses, 75% responded after a third dose with a median Ab titer at 355 (IQR, 140-3,865 BAU/mL). Neutralizing activity was significantly lower against the delta and the omicron variants compared to the wild-type strain and did not improve after a 3rd dose, while infection did provide higher levels of neutralizations against the variants. T cell specific response correlated with humoral response and no patient displayed a cellular response without a humoral response. Adolescent KTx recipients exhibit a high seroconversion rate after only two doses. A third injection, induces a response in the majority of the non-responders patients but did not counterbalance the strong decrease in neutralizing antibody activities against variants highlighting the need for boosters with specific vaccines.


Asunto(s)
COVID-19 , Trasplante de Riñón , Adolescente , Humanos , Niño , Vacunas contra la COVID-19 , Vacuna BNT162 , Estudios Retrospectivos , SARS-CoV-2 , COVID-19/prevención & control , Vacunación , ARN Mensajero , Inmunoglobulina G , Anticuerpos Antivirales , Receptores de Trasplantes
5.
Clin Transplant ; 36(3): e14531, 2022 03.
Artículo en Inglés | MEDLINE | ID: mdl-34757651

RESUMEN

The adoption of de novo belatacept in kidney transplant (kTx) recipients was hampered by an increased risk of acute cellular rejection (ACR) with variation in adopted belatacept based immunosuppressive therapies across centers. We used data from the Scientific Registry of Transplant Recipients (SRTR) to evaluate the temporal trends in belatacept use and describe the associated induction and maintenance regimens in US adult kTx recipients transplanted between June 2011 and December 2018. The number of patients receiving de novo-belatacept based immunosuppressive therapy increased from .74% in 2011 to 3.11% in 2016. In 2016, 66/207 centers used de novo belatacept-based regimen with 3.03% using it in over 50% of their patients. The use of T-cell depleting agents increased with time. Since 2012, the rate of calcineurin inhibitor (CNI) use in combination with belatacept remained stable around 50% and ∼30% remained under belatacept/CNI combination at 1-year post-transplantation. The adoption of belatacept as de novo immunosuppressive regimen has been slow and its use remains low in the United States. Various regimens have been used to modulate the risk of ACR. Further studies evaluating the long-term outcomes of these regimens and assessing their safety especially with regard to the risk of infection are needed.


Asunto(s)
Trasplante de Riñón , Receptores de Trasplantes , Abatacept/uso terapéutico , Adulto , Inhibidores de la Calcineurina/uso terapéutico , Rechazo de Injerto/tratamiento farmacológico , Rechazo de Injerto/etiología , Rechazo de Injerto/prevención & control , Supervivencia de Injerto , Humanos , Inmunosupresores/uso terapéutico , Trasplante de Riñón/efectos adversos , Estados Unidos
6.
J Immunol Methods ; 531: 113712, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-38906414

RESUMEN

During SARS-CoV-2 pandemic, the assessment of immune protection of people at risk of severe infection was an important goal. The appearance of VOCs (Variant of Concern) highlighted the limits of evaluating immune protection through the humoral response. While the humoral response partly loses its neutralizing activity, the anti-SARS-CoV-2 memory T cell response strongly cross protects against VOCs becoming an indispensable tool to assess immune protection. We compared two techniques available in laboratory to evaluate anti-SARS-CoV-2 memory T cell response in a cohort of infected or vaccinated patients with different levels of risk to develop a severe disease: the ELISpot assay and the T-Cell Lymphocyte Proliferation Assay respectively exploring IFNγ production and cell proliferation. We showed that the ELISpot assay detected more anti-Spike memory T cell response than the Lymphocyte Proliferation Assay. We next observed that the use of two different suppliers as antigenic source in the ELISpot assay did not affect the detection of anti-Spike memory T cell response. Finally, we explored a new approach for defining the positivity threshold, using unsupervised mixed Gaussian modeling, challenging the traditional ROC curve used by the supplier. That will be helpful in endemic situation where it could be difficult to recruit "negative" patients.


Asunto(s)
COVID-19 , Ensayo de Immunospot Ligado a Enzimas , Células T de Memoria , SARS-CoV-2 , Humanos , COVID-19/inmunología , COVID-19/epidemiología , SARS-CoV-2/inmunología , Células T de Memoria/inmunología , Masculino , Femenino , Persona de Mediana Edad , Proliferación Celular , Anticuerpos Antivirales/sangre , Anticuerpos Antivirales/inmunología , Adulto , Anciano , Interferón gamma/inmunología , Interferón gamma/metabolismo , Glicoproteína de la Espiga del Coronavirus/inmunología , Memoria Inmunológica
7.
Med Sci (Paris) ; 39(3): 281-286, 2023 Mar.
Artículo en Francés | MEDLINE | ID: mdl-36943126

RESUMEN

Kidney transplantation is the preferred treatment for end-stage renal failure in children but remains a rare procedure with only 100 to 120 pediatric kidney transplants per year in France. Although the main principles of kidney transplantation are the same in children and adults, some specificities regarding underlying kidney diseases, surgical technique, immunosuppressive drugs metabolism and the risk of infectious complications require a specific expertise to care for these patients. Similarly, the major morbidity of dialysis in children and the need for repeated transplants during the patient's life justify pediatric specificities in the choice of donors and the allocation of grafts in most kidney allocation systems worldwide. The objectives of this review are to present the history and specificities of pediatric kidney transplantation, to describe the current activity in France and to discuss future developments while emphasizing the need for basic and clinical research focused on the pediatric population.


Title: Des premières transplantations rénales à la transplantation rénale pédiatrique actuelle. Abstract: La transplantation rénale est le traitement de choix de l'insuffisance rénale terminale chez l'enfant, mais cela reste une procédure rare avec, en France, seulement 100 à 120 transplantations rénales pédiatriques par an. Si les grands principes de la transplantation rénale sont identiques chez l'enfant et chez l'adulte, certaines spécificités en lien avec les maladies rénales sous-jacentes, la technique chirurgicale, le métabolisme des immunosuppresseurs et le risque de complication infectieuse, justifient une prise en charge particulière des jeunes patients. La morbidité de la dialyse, particulière chez l'enfant, et le besoin de transplantations répétées au cours de la vie du patient expliquent des spécificités pédiatriques dans le choix des donneurs et l'allocation des greffons sur la liste d'attente nationale. L'objectif de cette revue est de présenter l'histoire et les spécificités de la transplantation rénale pédiatrique, de décrire l'état actuel de cette activité en France et d'évoquer les perspectives futures en soulignant le besoin de recherches fondamentale et clinique focalisées sur la population pédiatrique.


Asunto(s)
Fallo Renal Crónico , Trasplante de Riñón , Adulto , Niño , Humanos , Trasplante de Riñón/efectos adversos , Inmunosupresores/uso terapéutico , Fallo Renal Crónico/cirugía , Fallo Renal Crónico/tratamiento farmacológico , Francia
8.
Sci Transl Med ; 15(710): eadd1868, 2023 08 23.
Artículo en Inglés | MEDLINE | ID: mdl-37611081

RESUMEN

Checkpoint inhibition using Fc-containing monoclonal antibodies has emerged as a powerful therapeutic approach to augment antitumor immunity. We recently showed that FcγRIIB, the only inhibitory IgG-Fc receptor, is expressed on a population of highly differentiated effector CD8+ T cells in the tumors of mice and humans, raising the possibility that CD8+ T cell responses may be directly modulated by checkpoint inhibitor binding to T cell-expressed FcγRIIB. Here, we show that despite exhibiting strong proliferative and cytokine responses at baseline, human FcγRIIBpos CD8+ T cells exhibited reduced responsiveness to both PD-1 and CTLA-4 checkpoint inhibition as compared with FcγRIIBneg CD8+ T cells in vitro. Moreover, frequencies of FcγRIIBpos CD8+ T cells were reduced after treatment of patients with melanoma with nivolumab in vivo. This reduced responsiveness was FcγRIIB dependent, because conditional genetic deletion of FcγRIIB on tumor-specific CD8+ T cells improved response to checkpoint blockade in B16 and LLC mouse models of cancer. The limited responsiveness of FcγRIIBpos CD8+ T cells was also dependent on an intact Fc region of the checkpoint inhibitor, in that treatment with Fc-devoid anti-PD-1 F(ab) fragments resulted in increased proliferation of FcγRIIBpos CD8+ T cells, without altering the response of FcγRIIBneg CD8+ T cells. Last, the addition of FcγRIIB blockade improved efficacy of PD-1 checkpoint inhibition in mouse models of melanoma, lung, and colon cancer. These results illuminate an FcγRIIB-mediated, cell-autonomous mechanism of CD8+ T cell suppression, which limits the efficacy of checkpoint inhibitors during antitumor immune responses in vivo.


Asunto(s)
Neoplasias del Colon , Melanoma , Animales , Humanos , Anticuerpos Monoclonales/farmacología , Anticuerpos Monoclonales/uso terapéutico , Linfocitos T CD8-positivos , Citocinas , Modelos Animales de Enfermedad , Fragmentos Fc de Inmunoglobulinas , Melanoma/tratamiento farmacológico , Receptores de IgG
9.
Nat Rev Nephrol ; 18(10): 663-676, 2022 10.
Artículo en Inglés | MEDLINE | ID: mdl-35902775

RESUMEN

Transplantation is the only curative treatment for patients with kidney failure but it poses unique immunological challenges that must be overcome to prevent allograft rejection and ensure long-term graft survival. Alloreactive T cells are important contributors to graft rejection, and a clearer understanding of the mechanisms by which these cells recognize donor antigens - through direct, indirect or semi-direct pathways - will facilitate their therapeutic targeting. Post-T cell priming rejection responses can also be modified by targeting pathways that regulate T cell trafficking, survival cytokines or innate immune activation. Moreover, the quantity and quality of donor-reactive memory T cells crucially shape alloimmune responses. Of note, many fundamental concepts in transplant immunology have been derived from models of infection. However, the programmed differentiation of allograft-specific T cell responses is probably distinct from that of pathogen-elicited responses, owing to the dearth of pathogen-derived innate immune activation in the transplantation setting. Understanding the fundamental (and potentially unique) immunological pathways that lead to allograft rejection is therefore a prerequisite for the rational development of therapeutics that promote transplantation tolerance.


Asunto(s)
Trasplante de Órganos , Citocinas , Rechazo de Injerto/prevención & control , Humanos , Activación de Linfocitos , Trasplante Homólogo
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