Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 19 de 19
Filtrar
Más filtros

Banco de datos
País/Región como asunto
Tipo del documento
Intervalo de año de publicación
1.
Blood ; 143(24): 2504-2516, 2024 Jun 13.
Artículo en Inglés | MEDLINE | ID: mdl-38579284

RESUMEN

ABSTRACT: Wiskott-Aldrich syndrome (WAS) is a multifaceted monogenic disorder with a broad disease spectrum and variable disease severity and a variety of treatment options including allogeneic hematopoietic stem cell transplantation (HSCT) and gene therapy (GT). No reliable biomarker exists to predict disease course and outcome for individual patients. A total of 577 patients with a WAS variant from 26 countries and a median follow-up of 8.9 years (range, 0.3-71.1), totaling 6118 patient-years, were included in this international retrospective study. Overall survival (OS) of the cohort (censored at HSCT or GT) was 82% (95% confidence interval, 78-87) at age 15 years and 70% (61-80) at 30 years. The type of variant was predictive of outcome: patients with a missense variant in exons 1 or 2 or with the intronic hot spot variant c.559+5G>A (class I variants) had a 15-year OS of 93% (89-98) and a 30-year OS of 91% (86-97), compared with 71% (62-81) and 48% (34-68) in patients with any other variant (class II; P < .0001). The cumulative incidence rates of disease-related complications such as severe bleeding (P = .007), life-threatening infection (P < .0001), and autoimmunity (P = .004) occurred significantly later in patients with a class I variant. The cumulative incidence of malignancy (P = .6) was not different between classes I and II. It confirms the spectrum of disease severity and quantifies the risk for specific disease-related complications. The class of the variant is a biomarker to predict the outcome for patients with WAS.


Asunto(s)
Genotipo , Síndrome de Wiskott-Aldrich , Humanos , Adolescente , Niño , Masculino , Síndrome de Wiskott-Aldrich/genética , Síndrome de Wiskott-Aldrich/diagnóstico , Síndrome de Wiskott-Aldrich/terapia , Femenino , Preescolar , Adulto , Estudios Retrospectivos , Lactante , Adulto Joven , Biomarcadores , Trasplante de Células Madre Hematopoyéticas , Índice de Severidad de la Enfermedad , Proteína del Síndrome de Wiskott-Aldrich/genética , Estudios de Seguimiento , Persona de Mediana Edad , Pronóstico , Tasa de Supervivencia
2.
J Clin Immunol ; 42(8): 1748-1765, 2022 11.
Artículo en Inglés | MEDLINE | ID: mdl-35947323

RESUMEN

Warts, hypogammaglobulinemia, infections, and myelokathexis (WHIM) syndrome (WS) is a combined immunodeficiency caused by gain-of-function mutations in the C-X-C chemokine receptor type 4 (CXCR4) gene. We characterize a unique international cohort of 66 patients, including 57 (86%) cases previously unreported, with variable clinical phenotypes. Of 17 distinct CXCR4 genetic variants within our cohort, 11 were novel pathogenic variants affecting 15 individuals (23%). All variants affect the same CXCR4 region and impair CXCR4 internalization resulting in hyperactive signaling. The median age of diagnosis in our cohort (5.5 years) indicates WHIM syndrome can commonly present in childhood, although some patients are not diagnosed until adulthood. The prevalence and mean age of recognition and/or onset of clinical manifestations within our cohort were infections 88%/1.6 years, neutropenia 98%/3.8 years, lymphopenia 88%/5.0 years, and warts 40%/12.1 years. However, we report greater prevalence and variety of autoimmune complications of WHIM syndrome (21.2%) than reported previously. Patients with versus without family history of WHIM syndrome were diagnosed earlier (22%, average age 1.3 years versus 78%, average age 5 years, respectively). Patients with a family history of WHIM syndrome also received earlier treatment, experienced less hospitalization, and had less end-organ damage. This observation reinforces previous reports that early treatment for WHIM syndrome improves outcomes. Only one patient died; death was attributed to complications of hematopoietic stem cell transplantation. The variable expressivity of WHIM syndrome in pediatric patients delays their diagnosis and therapy. Early-onset bacterial infections with severe neutropenia and/or lymphopenia should prompt genetic testing for WHIM syndrome, even in the absence of warts.


Asunto(s)
Agammaglobulinemia , Síndromes de Inmunodeficiencia , Linfopenia , Neutropenia , Verrugas , Humanos , Síndromes de Inmunodeficiencia/diagnóstico , Síndromes de Inmunodeficiencia/epidemiología , Síndromes de Inmunodeficiencia/genética , Verrugas/diagnóstico , Verrugas/epidemiología , Verrugas/genética , Agammaglobulinemia/genética , Receptores CXCR4/genética , Neutropenia/genética , Linfopenia/complicaciones , Progresión de la Enfermedad
3.
Cent Eur J Immunol ; 46(2): 250-257, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34764795

RESUMEN

The J Project is a Central-Eastern European collaborative program in the field of physician education and clinical research aimed at improving the clinical care and diagnosis of primary immunodeficiency disorders (PIDs). Ukraine was one of the first to participate in the project, which allowed us to join the whole European PID community. Since 2004, the country has been holding annual J Project meetings with the involvement of new regions. The spread of the J Project impact has contributed to significantly improved early PID diagnosis in Ukraine. Progress has been made not only in identifying patients but also in arranging the treatment. The assistance in genetic diagnosis made it possible to detect PIDs, study their features, and improve approaches to the management. This also gave an impetus to the development of regional PID centers and participation in scientific research. Of utmost importance is the cooperation with colleagues from Poland, Hungary, and Belarus, who are active members of the J Project.

4.
Cancer Immunol Immunother ; 69(6): 983-988, 2020 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-32078017

RESUMEN

BACKGROUND: Hepatitis C virus (HCV) interferes with activation of innate and adaptive immune responses. Theoretically, the efficacy and toxicity of immune checkpoint inhibitors in cancer patients infected with HCV may differ. Nevertheless, HCV was an exclusion criterion in most checkpoint inhibitor trials. We evaluated the efficacy and safety of nivolumab in metastatic renal cell carcinoma (mRCC) patients with or without chronic HCV infection. METHODS: In a matched cohort study, data were collected from 174 patients, retrospectively. All patients had clear-cell mRCC, chronic HCV infection (case study group), no evidence of other malignancy or cirrhosis, and had received nivolumab (3 mg/kg every 2 weeks) until disease progression or unacceptable toxicity. Quantitation of HCV RNA in plasma samples was performed before and during treatment with nivolumab with the automated HCV test (Hoffmann-La Roche, Switzerland). The primary endpoint was overall survival (OS). Secondary endpoints included progression-free survival (PFS), objective response rate (ORR), and rate of grade 3-4 adverse events in study and control cohorts. RESULTS: A total of 44 matched patients were included. Groups were well balanced. HCV-infected patients had significantly longer OS and PFS. Median OS was 27.5 (95% CI 25.3-29.7) and 21.7 (20.3-23.1) in study and control groups, respectively (P = 0.005). Median PFS was 7.5 (5.7-9.3) and 4.9 (4-5.8) (P = 0.013). Despite no differences in ORR between groups (27% vs. 23%, P = 0.7), patients with HCV had significantly more durable responses (P = 0.01). Nivolumab was well tolerated in all HCV-positive patients. No unexpected toxicity was observed. Assessment of viral load during nivolumab therapy was available in 14 of 22 (64%) patients with HCV. Nivolumab did not significantly impact HCV concentration (mean change 210 IU/ml, P = 0.82) in the absence of antiviral therapy. CONCLUSIONS: The efficacy and safety profiles observed in this study support the administration of nivolumab in mRCC patients infected with HCV and warrant further investigation.


Asunto(s)
Antineoplásicos Inmunológicos/uso terapéutico , Carcinoma de Células Renales/tratamiento farmacológico , Hepatitis C Crónica/tratamiento farmacológico , Nivolumab/uso terapéutico , Antineoplásicos Inmunológicos/farmacología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Nivolumab/farmacología , Estudios Retrospectivos
5.
Oncology ; 98(4): 252-258, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-32053815

RESUMEN

BACKGROUND: Very little is known about receptor tyrosine kinase (RTK) expression on peripheral blood mononuclear cells (PBMC) in humans including renal cell carcinoma (RCC) patients. OBJECTIVES: The primary objective of this study was to evaluate expression levels of major RTKs on PBMC and tumor-infiltrating lymphocytes (TIL) isolated from RCC patients. The secondary aim was to compare levels of RTK expression in RCC patients before surgery and on the 180th day after surgery (lymphocyte lifetime) and to compare them with the expression in healthy donors. In addition, we compared RTK and PD-L1 expression in TIL. METHODS: Tumor and blood samples were obtained from 20 patients with primary RCC immediately after surgical resection. Blood samples were collected from 20 healthy donors. Tumors were harvested into RPMI 1640 medium (Gibco) and processed within 4 h. TIL isolation was performed using a modified protocol [Baldan et al. Br J Cancer. 2015;112:1510-18]. Expression of RTKs was evaluated with NovoExpress Software. Twenty tumors from the same patients were stained with PD-L1 IHC assay (clone SP142; Ventana). RESULTS: PBMC and TIL express RTKs in humans. The RTK expression level was significantly lower on peripheral blood cells in patients with RCC (mean 41%, range 27.1-62.6%) as compared with healthy donor PBMC (mean 77.1%, range 72.1-80.1%, all p < 0.05). Furthermore, RTK expression was significantly downregulated on intratumoral cells (mean 40%, range 23.2-52.3%) in comparison with healthy donor PBMC. There was no significant recovery of RTK expression on the 180th day except for VEGFR2. Five of 20 (25%) patients were PD-L1 positive. PD-L1 expression on TIL was strongly associated with downregulated expression of PDGFRα (p = 0.017) and PDGFRß (p = 0.024). CONCLUSIONS: PBMC and TIL had similar low RTK expression levels in RCC patients. PBMC of healthy humans had a significantly higher expression of RTK. PD-L1 and PDGFRα-ß expression could correlate. Comprehensive basic and clinical studies will be needed to define a biological role of RTKs on different lymphocyte subsets and correlations between clinical outcomes and expression levels.


Asunto(s)
Donantes de Sangre , Carcinoma de Células Renales/enzimología , Neoplasias Renales/enzimología , Leucocitos Mononucleares/enzimología , Linfocitos Infiltrantes de Tumor/enzimología , Proteínas Tirosina Quinasas Receptoras/sangre , Adulto , Anciano , Antígeno B7-H1/sangre , Femenino , Humanos , Masculino , Persona de Mediana Edad , Proyectos Piloto , Receptores del Factor de Crecimiento Derivado de Plaquetas/sangre
6.
Clin Immunol ; 205: 1-5, 2019 08.
Artículo en Inglés | MEDLINE | ID: mdl-31071452

RESUMEN

Here we describe a 10-year-old girl with combined immunodeficiency presenting as recurring chest infections, lung disease and herpetic skin infections. The patient experienced two hematopoietic stem cell transplantations and despite full chimerism, she developed bone marrow aplasia due to adenovirus infection and died at post-transplant day 86. Immunologic investigation revealed low numbers of TRECs/KRECs, a severe reduction of memory B cells, absence of isohemagglutinins, and low IgG levels. Whole exome sequencing (WES) identified a novel heterozygous mutation in RAC2(c.275A > C, p.N92 T). Flow cytometric investigation of neutrophil migration demonstrated an absence of chemotaxis to fMLP. Cell lines transfected with RAC2 [N92 T] displayed characteristics of active GTP-bound RAC2 including enhanced NADPH oxidase-derived superoxide production both at rest and in response to PMA. Our findings broaden the clinical picture of RAC2 dysfunction, showing that some individuals can present with a combined immunodeficiency later in childhood rather than a congenital neutrophil disease.


Asunto(s)
Inmunodeficiencia Combinada Grave/genética , Proteínas de Unión al GTP rac/genética , Infecciones por Adenovirus Humanos , Linfocitos B , Trastornos de Fallo de la Médula Ósea , Niño , Resultado Fatal , Femenino , Trasplante de Células Madre Hematopoyéticas , Heterocigoto , Humanos , Inmunoglobulinas Intravenosas/uso terapéutico , Factores Inmunológicos/uso terapéutico , Memoria Inmunológica , Linfopenia , Mutación , Recurrencia , Linfocitos T , Virosis , Proteína RCA2 de Unión a GTP
7.
J Clin Immunol ; 38(5): 617-627, 2018 07.
Artículo en Inglés | MEDLINE | ID: mdl-29995221

RESUMEN

PURPOSE: Inborn errors of IFN-γ immunity underlie Mendelian susceptibility to mycobacterial disease (MSMD). Autosomal recessive complete IL-12Rß1 deficiency is the most frequent genetic etiology of MSMD. Only two of the 84 known mutations are copy number variations (CNVs), identified in two of the 213 IL-12Rß1-deficient patients and two of the 164 kindreds reported. These two CNVs are large deletions found in the heterozygous or homozygous state. We searched for novel families with IL-12Rß1 deficiency due to CNVs. METHODS: We studied six MSMD patients from five unrelated kindreds displaying adverse reactions to BCG vaccination. Three of the patients also presented systemic salmonellosis, two had mucocutaneous candidiasis, and one had disseminated histoplasmosis. We searched for CNVs and other variations by IL12RB1-targeted next-generation sequencing (NGS). RESULTS: We identified six new IL-12Rß1-deficient patients with a complete loss of IL-12Rß1 expression on phytohemagglutinin-activated T cells and/or EBV-transformed B cells. The cells of these patients did not respond to IL-12 and IL-23. Five different CNVs encompassing IL12RB1 (four deletions and one duplication) were identified in these patients by NGS coverage analysis, either in the homozygous state (n = 1) or in trans (n = 4) with a single-nucleotide variation (n = 3) or a small indel (n = 1). Seven of the nine mutations are novel. Interestingly, four of the five CNVs were predicted to be driven by nearby Alu elements, as well as the two previously reported large deletions. The IL12RB1 locus is actually enriched in Alu elements (44.7%), when compared with the rest of the genome (10.5%). CONCLUSION: The IL12RB1 locus is Alu-enriched and therefore prone to rearrangements at various positions. CNVs should be considered in the genetic diagnosis of IL-12Rß1 deficiency.


Asunto(s)
Elementos Alu , Variaciones en el Número de Copia de ADN , Estudios de Asociación Genética , Predisposición Genética a la Enfermedad , Sudunidad beta 1 del Receptor de Interleucina-12/deficiencia , Alelos , Secuencia de Bases , Mapeo Cromosómico , Femenino , Expresión Génica , Humanos , Interferón gamma , Masculino , Mutación , Infecciones por Mycobacterium/diagnóstico , Infecciones por Mycobacterium/etiología , Infecciones por Mycobacterium/metabolismo , Linaje , Fenotipo
8.
J Allergy Clin Immunol ; 138(1): 241-248.e3, 2016 07.
Artículo en Inglés | MEDLINE | ID: mdl-26936803

RESUMEN

BACKGROUND: Chronic granulomatous disease (CGD) is a rare primary immunodeficiency caused by inborn errors of the phagocyte nicotinamide adenine dinucleotide phosphate oxidase complex. From the first year of life onward, most affected patients display multiple, severe, and recurrent infections caused by bacteria and fungi. Mycobacterial infections have also been reported in some patients. OBJECTIVE: Our objective was to assess the effect of mycobacterial disease in patients with CGD. METHODS: We analyzed retrospectively the clinical features of mycobacterial disease in 71 patients with CGD. Tuberculosis and BCG disease were diagnosed on the basis of microbiological, pathological, and/or clinical criteria. RESULTS: Thirty-one (44%) patients had tuberculosis, and 53 (75%) presented with adverse effects of BCG vaccination; 13 (18%) had both tuberculosis and BCG infections. None of these patients displayed clinical disease caused by environmental mycobacteria, Mycobacterium leprae, or Mycobacterium ulcerans. Most patients (76%) also had other pyogenic and fungal infections, but 24% presented solely with mycobacterial disease. Most patients presented a single localized episode of mycobacterial disease (37%), but recurrence (18%), disseminated disease (27%), and even death (18%) were also observed. One common feature in these patients was an early age at presentation for BCG disease. Mycobacterial disease was the first clinical manifestation of CGD in 60% of these patients. CONCLUSION: Mycobacterial disease is relatively common in patients with CGD living in countries in which tuberculosis is endemic, BCG vaccine is mandatory, or both. Adverse reactions to BCG and severe forms of tuberculosis should lead to a suspicion of CGD. BCG vaccine is contraindicated in patients with CGD.


Asunto(s)
Enfermedad Granulomatosa Crónica/complicaciones , Infecciones por Mycobacterium/diagnóstico , Infecciones por Mycobacterium/etiología , Vacuna BCG/administración & dosificación , Infecciones Bacterianas/diagnóstico , Infecciones Bacterianas/epidemiología , Infecciones Bacterianas/etiología , Infecciones Bacterianas/mortalidad , Niño , Preescolar , Femenino , Enfermedad Granulomatosa Crónica/epidemiología , Enfermedad Granulomatosa Crónica/mortalidad , Enfermedad Granulomatosa Crónica/terapia , Humanos , Lactante , Masculino , Infecciones por Mycobacterium/epidemiología , Infecciones por Mycobacterium/mortalidad , Micosis/diagnóstico , Micosis/epidemiología , Micosis/etiología , Micosis/mortalidad , Evaluación del Resultado de la Atención al Paciente , Estudios Retrospectivos , Tuberculosis/diagnóstico , Tuberculosis/etiología
9.
J Med Genet ; 50(9): 567-78, 2013 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-23709754

RESUMEN

BACKGROUND: Chronic mucocutaneous candidiasis disease (CMCD) may result from various inborn errors of interleukin (IL)-17-mediated immunity. Twelve of the 13 causal mutations described to date affect the coiled-coil domain (CCD) of STAT1. Several mutations, including R274W in particular, are recurrent, but the underlying mechanism is unclear. OBJECTIVE: To investigate and describe nine patients with CMCD in Eastern and Central Europe, to assess the biochemical impact of STAT1 mutations, to determine cytokines in supernatants of Candida-exposed blood cells, to determine IL-17-producing T cell subsets and to determine STAT1 haplotypes in a family with the c.820C>T (R274W) mutation. RESULTS: The novel c.537C>A (N179K) STAT1 mutation was gain-of-function (GOF) for γ-activated factor (GAF)-dependent cellular responses. In a Russian patient, the cause of CMCD was the newly identified c.854 A>G (Q285R) STAT1 mutation, which was also GOF for GAF-dependent responses. The c.1154C>T (T385M) mutation affecting the DNA-binding domain (DBD) resulted in a gain of STAT1 phosphorylation in a Ukrainian patient. Impaired Candida-induced IL-17A and IL-22 secretion by leucocytes and lower levels of intracellular IL-17 and IL-22 production by T cells were found in several patients. Haplotype studies indicated that the c.820C>T (R274W) mutation was recurrent due to a hotspot rather than a founder effect. Severe clinical phenotypes, including intracranial aneurysm, are presented. CONCLUSIONS: The c.537C>A and c.854A>G mutations affecting the CCD and the c.1154C>T mutation affecting the DBD of STAT1 are GOF. The c.820C>T mutation of STAT1 in patients with CMCD is recurrent due to a hotspot. Patients carrying GOF mutations of STAT1 may develop multiple intracranial aneurysms by hitherto unknown mechanisms.


Asunto(s)
Candidiasis Mucocutánea Crónica/genética , Mutación , Factor de Transcripción STAT1/genética , Adolescente , Adulto , Candidiasis Mucocutánea Crónica/inmunología , Niño , Citocinas/metabolismo , Europa Oriental , Predisposición Genética a la Enfermedad , Humanos , Pruebas Inmunológicas , Leucocitos Mononucleares/inmunología , Persona de Mediana Edad , Fosforilación , Estructura Terciaria de Proteína
10.
J Cancer Res Ther ; 20(3): 1036-1038, 2024 Apr 01.
Artículo en Inglés | MEDLINE | ID: mdl-39023613

RESUMEN

ABSTRACT: We assessed the preliminary efficacy and toxicity of intrapleural instillation of nivolumab in patients with large pleural effusion. Patients with metastatic cancers who have a large volume of pleural effusion and required evacuation were eligible. Thoracentesis followed by nivolumab (40 mg, single intrapleural instillation) was performed. The primary endpoint was 3-month recurrence-free survival. A total of 13 patients were enrolled. The study was terminated after stage 1 as no efficacy was observed; 7 patients (54%) had a recurrence of pleural effusion at 3 months. Thirteen (100%) patients had no recurrence, dyspnea, or cough within 1 month, and the median time to recurrence was 1.9 months (95% confidence interval [CI], 1.35-2.5). No adverse events were identified. We concluded that a single intrapleural instillation of the nivolumab at 40 mg was ineffective and well-tolerated in cancer patients with pleural effusion.


Asunto(s)
Nivolumab , Derrame Pleural Maligno , Humanos , Nivolumab/administración & dosificación , Nivolumab/efectos adversos , Nivolumab/uso terapéutico , Femenino , Masculino , Anciano , Persona de Mediana Edad , Derrame Pleural Maligno/tratamiento farmacológico , Derrame Pleural Maligno/patología , Neoplasias/tratamiento farmacológico , Neoplasias/complicaciones , Neoplasias/patología , Toracocentesis/métodos , Anciano de 80 o más Años , Derrame Pleural/etiología , Derrame Pleural/tratamiento farmacológico , Derrame Pleural/patología , Adulto , Resultado del Tratamiento , Antineoplásicos Inmunológicos/uso terapéutico , Antineoplásicos Inmunológicos/efectos adversos , Antineoplásicos Inmunológicos/administración & dosificación
11.
J Pediatr ; 163(1 Suppl): S12-8, 2013 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-23773588

RESUMEN

OBJECTIVE: Haemophilus influenzae type b (Hib) conjugate vaccine was included into the national vaccination schedule of Ukraine in 2006. The objective of this study was to demonstrate the effectiveness of Hib conjugate vaccine against radiologically-confirmed hospitalized pneumonia in children. STUDY DESIGN: Children <2 years old with radiologically confirmed pneumonia admitted to 11 participating hospitals in Kiev and Dnepropetrovsk between April 2007 and June 2009 were included in a case-control evaluation. Four controls were matched to each case by date of birth (within 14 days) and outpatient clinic. We estimated ORs for vaccination and vaccine effectiveness ((1 - OR)*100%) using conditional logistic regression, adjusting for comorbid conditions and contraindications for vaccination. RESULTS: We enrolled 188 case-children and 735 controls. Median age was 16 months (range 4-24 months). Fifty-one percent of cases and 67% of controls received ≥1 doses of Hib conjugate vaccine; 26% of cases and 37% of controls received ≥3 doses. The effectiveness of ≥1 dose Hib conjugate vaccine was estimated at 45% (95% CI 18%-63%). CONCLUSIONS: Our study showed that Hib infections are important causes of hospitalized radiologically confirmed pneumonia in young children in Ukraine.


Asunto(s)
Niño Hospitalizado/estadística & datos numéricos , Infecciones por Haemophilus/epidemiología , Infecciones por Haemophilus/prevención & control , Vacunas contra Haemophilus/administración & dosificación , Haemophilus influenzae tipo b/inmunología , Neumonía Bacteriana/epidemiología , Neumonía Bacteriana/prevención & control , Cápsulas Bacterianas/inmunología , Estudios de Casos y Controles , Preescolar , Femenino , Infecciones por Haemophilus/diagnóstico por imagen , Vacunas contra Haemophilus/inmunología , Humanos , Programas de Inmunización , Lactante , Masculino , Neumonía Bacteriana/diagnóstico por imagen , Radiografía , Ucrania/epidemiología , Vacunas Conjugadas/administración & dosificación , Vacunas Conjugadas/inmunología
12.
Am J Cancer Res ; 13(3): 1103-1106, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37034218

RESUMEN

About 40% of patients with non-small cell lung cancer (NSCLC) developed pleural effusions at some time during the course of their disease. Preliminary results from our Phase 2 multicentre clinical trial (Cohort 1) demonstrated the safety of intrapleural nivolumab in cancer patients. In Cohort 2 we assessed the preliminary efficacy and toxicity of intrapleural instillation of the nivolumab in patients with metastatic NSCLC and large pleural effusion requiring evacuation. Thoracentesis followed by nivolumab (40 mg, single intrapleural instillation) was performed. The primary endpoint was 3-month recurrence-free survival. Simon's two-stage design was used, with 13 patients planned for stage 1. If 11 or more patients did not have a pleural effusion after 3 months, an additional 35 patients were planned to be accrued for a total of 48. A total of 13 patients were enrolled. This study did not meet its primary endpoint and was terminated. Eight patients (61.5%) had a recurrence of pleural effusion at 3 months. The median time to recurrence was 1.84 months (95% CI 1.19-2.49). No adverse events were identified. We concluded that a single intrapleural instillation of the nivolumab at 40 mg was ineffective and well-tolerated in patients with metastatic NSCLC and pleural effusion.

13.
Narra J ; 2(2): e83, 2022 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-38449700

RESUMEN

The emergence of acute, severe non hepA-E hepatitis of unknown etiology (ASHUE) has attracted global concern owing to the very young age of the patients and its unknown etiology. Although this condition has been linked to several possible causes, including viral infection, drugs and/or toxin exposure, the exact cause remains unknown; this makes treatment recommendation very difficult. In this review, we summarize recent updates on the clinical manifestations, complemented with laboratory results, case numbers with the global distribution and other epidemiological characteristics, and the possible etiologies. We also provide the proposed actions that could be undertaken to control and prevent further spread of this hepatitis. Since many etiological and pathological aspects of the acute non hepA-E hepatitis remain unclear, further research is needed to minimize the severe impact of this disease.

14.
Front Immunol ; 13: 1032358, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-36605210

RESUMEN

Introduction: The J Project (JP) physician education and clinical research collaboration program was started in 2004 and includes by now 32 countries mostly in Eastern and Central Europe (ECE). Until the end of 2021, 344 inborn errors of immunity (IEI)-focused meetings were organized by the JP to raise awareness and facilitate the diagnosis and treatment of patients with IEI. Results: In this study, meeting profiles and major diagnostic and treatment parameters were studied. JP center leaders reported patients' data from 30 countries representing a total population of 506 567 565. Two countries reported patients from JP centers (Konya, Turkey and Cairo University, Egypt). Diagnostic criteria were based on the 2020 update of classification by the IUIS Expert Committee on IEI. The number of JP meetings increased from 6 per year in 2004 and 2005 to 44 and 63 in 2020 and 2021, respectively. The cumulative number of meetings per country varied from 1 to 59 in various countries reflecting partly but not entirely the population of the respective countries. Altogether, 24,879 patients were reported giving an average prevalence of 4.9. Most of the patients had predominantly antibody deficiency (46,32%) followed by patients with combined immunodeficiencies (14.3%). The percentages of patients with bone marrow failure and phenocopies of IEI were less than 1 each. The number of patients was remarkably higher that those reported to the ESID Registry in 13 countries. Immunoglobulin (IgG) substitution was provided to 7,572 patients (5,693 intravenously) and 1,480 patients received hematopoietic stem cell therapy (HSCT). Searching for basic diagnostic parameters revealed the availability of immunochemistry and flow cytometry in 27 and 28 countries, respectively, and targeted gene sequencing and new generation sequencing was available in 21 and 18 countries. The number of IEI centers and experts in the field were 260 and 690, respectively. We found high correlation between the number of IEI centers and patients treated with intravenous IgG (IVIG) (correlation coefficient, cc, 0,916) and with those who were treated with HSCT (cc, 0,905). Similar correlation was found when the number of experts was compared with those treated with HSCT. However, the number of patients treated with subcutaneous Ig (SCIG) only slightly correlated with the number of experts (cc, 0,489) and no correlation was found between the number of centers and patients on SCIG (cc, 0,174). Conclusions: 1) this is the first study describing major diagnostic and treatment parameters of IEI care in countries of the JP; 2) the data suggest that the JP had tremendous impact on the development of IEI care in ECE; 3) our data help to define major future targets of JP activity in various countries; 4) we suggest that the number of IEI centers and IEI experts closely correlate to the most important treatment parameters; 5) we propose that specialist education among medical professionals plays pivotal role in increasing levels of diagnostics and adequate care of this vulnerable and still highly neglected patient population; 6) this study also provides the basis for further analysis of more specific aspects of IEI care including genetic diagnostics, disease specific prevalence, newborn screening and professional collaboration in JP countries.


Asunto(s)
Inmunoglobulina G , Recién Nacido , Humanos , Administración Intravenosa , Escolaridad , Egipto , Europa (Continente)
15.
Am J Clin Oncol ; 44(4): 137-142, 2021 04 01.
Artículo en Inglés | MEDLINE | ID: mdl-33512910

RESUMEN

BACKGROUND: Fatigue is one of the most common adverse events of systemic therapy in patients with metastatic renal cell carcinoma (RCC). The aim of multicenter randomized phase 2 study was to determine the efficacy and safety of testosterone in patients with fatigue developed during targeted therapy. PATIENTS AND METHODS: Male patients with metastatic clear-cell RCC, normal prostate-specific antigen level, low testosterone level, and no evidence of hypothyroidism receiving first-line sunitinib or pazopanib with fatigue were randomly assigned (1:1) to either testosterone undecanoate (1000 mg) and targeted therapy or targeted therapy alone. The primary endpoint was the mean change of fatigue from baseline to 28 days according to the Functional Assessment of Chronic Illness Therapy-Fatigue scale. Secondary endpoints were safety, Functional Assessment of Cancer Therapy-Kidney Symptom Index 19, testosterone serum concentrations, red blood cell count, and hemoglobin level. RESULTS: Sixty patients were assigned to receive testosterone and targeted therapy (N=30) or targeted therapy alone (N=30). As of the data cutoff on December 30, 2019, median follow-up was 18.2 months. The study achieved its primary endpoint based on the significant differences at day 28 favoring testosterone over targeted therapy alone regarding the decreased level of fatigue (difference between groups, 22.5 points; 95% confidence interval, 18.4-26.6; P=0.012). Significant changes in scores demonstrating the enhanced quality of life with testosterone compared with targeted therapy were also observed for Functional Assessment of Cancer Therapy-Kidney Symptom Index 19 disease-related symptoms (P=0.01). There were nonsignificant differences in red blood cell count and hemoglobin level between the 2 groups (all P>0.05). CONCLUSION: Male patients with metastatic RCC and hypogonadism receiving testosterone had less fatigue and better symptom control during targeted therapy.


Asunto(s)
Carcinoma de Células Renales/secundario , Fatiga/tratamiento farmacológico , Neoplasias Renales/tratamiento farmacológico , Testosterona/análogos & derivados , Anciano , Antineoplásicos/efectos adversos , Antineoplásicos/uso terapéutico , Carcinoma de Células Renales/complicaciones , Carcinoma de Células Renales/tratamiento farmacológico , Fatiga/etiología , Fatiga/psicología , Estudios de Seguimiento , Humanos , Hipogonadismo/complicaciones , Hipogonadismo/tratamiento farmacológico , Indazoles , Neoplasias Renales/complicaciones , Masculino , Persona de Mediana Edad , Pirimidinas/efectos adversos , Pirimidinas/uso terapéutico , Calidad de Vida , Sulfonamidas/efectos adversos , Sulfonamidas/uso terapéutico , Sunitinib/efectos adversos , Sunitinib/uso terapéutico , Testosterona/efectos adversos , Testosterona/uso terapéutico
16.
Food Chem ; 332: 127467, 2020 Dec 01.
Artículo en Inglés | MEDLINE | ID: mdl-32663755

RESUMEN

The mood pyramid of cocoa, which was previously proposed as a new concept, consists of four levels (flavan-3-ols, methylxanthines, minor compounds and orosensory properties). Roasting is a crucial process for flavor development in cocoa but is likely to have a negative impact on the phytochemicals. We investigated the effect of roasting time (10-50 min) and temperature (110-160 °C) on the potential mood-enhancing compounds corresponding to the distinct mood pyramid levels. Phytochemicals were analyzed using UPLC-HRMS, while the flavor was mapped via aroma (HS-SPME-GC-MS) and generic descriptive analysis (trained panel). Results revealed that roasting at 130 °C for 30 min did not significantly affect the levels of epicatechin, procyanidin B2 and theobromine, while salsolinol significantly increased. Moreover, bitterness and astringency were reduced and the desired cocoa flavor was developed. Thus, through selection of appropriate roasting time and temperature conditions phytochemicals of interest could be retained without comprising the flavor.


Asunto(s)
Cacao/química , Culinaria/métodos , Semillas/química , Biflavonoides/química , Catequina/química , Aromatizantes/química , Cromatografía de Gases y Espectrometría de Masas , Calor , Humanos , Odorantes/análisis , Polifenoles/química , Proantocianidinas/química , Gusto
17.
Am J Trop Med Hyg ; 102(6): 1181-1183, 2020 06.
Artículo en Inglés | MEDLINE | ID: mdl-32323644

RESUMEN

Novel coronavirus disease (COVID-19), named a pandemic by the WHO, is the current global health crisis. National and international collaboration are indispensable for combating COVID-19 and other similar potential outbreaks. International efforts to tackle this complex problem have led to remarkable scientific advances. Yet, as a global society, we can and must take additional measures to fight this pandemic. Undoubtedly, our approach toward COVID-19 was not perfect, and testing has not been deployed fast enough to arrest the epidemic early on. It is critical that we revise our approaches to be more prepared for pandemics as a united body by promoting global cooperation and commitment.


Asunto(s)
Betacoronavirus/patogenicidad , Defensa Civil/organización & administración , Infecciones por Coronavirus/epidemiología , Cooperación Internacional/legislación & jurisprudencia , Pandemias , Neumonía Viral/epidemiología , Antivirales/síntesis química , Antivirales/uso terapéutico , Asia/epidemiología , Betacoronavirus/efectos de los fármacos , COVID-19 , Prueba de COVID-19 , Vacunas contra la COVID-19 , Técnicas de Laboratorio Clínico/normas , Técnicas de Laboratorio Clínico/estadística & datos numéricos , Infecciones por Coronavirus/diagnóstico , Infecciones por Coronavirus/tratamiento farmacológico , Infecciones por Coronavirus/prevención & control , Europa (Continente)/epidemiología , Humanos , Medio Oriente/epidemiología , Pandemias/prevención & control , Neumonía Viral/diagnóstico , Neumonía Viral/tratamiento farmacológico , Neumonía Viral/prevención & control , SARS-CoV-2 , Vacunas Virales/biosíntesis , Vacunas Virales/uso terapéutico
18.
Cancer Rep (Hoboken) ; 2(2): e1142, 2019 04.
Artículo en Inglés | MEDLINE | ID: mdl-32721112

RESUMEN

BACKGROUND: A paraneoplastic syndrome is observed in 5% to 10% of cancer patients. Paraneoplastic vasculitis (PV) in metastatic renal cell carcinoma (mRCC) patients has been poorly investigated. AIMS: In our case series study, we evaluated the incidence and development of PV in patients with mRCC. METHODS AND RESULTS: Patients were required to have previously untreated clear-cell or papillary mRCC and no evidence of autoimmune diseases or venous thrombosis in history. Patients had a careful examination including Doppler ultrasonography of the blood vessels and skin punch biopsy in the presence of suspicious skin rash. Sixteen (8.2%) of 196 patients were diagnosed with PV, which was manifested clinically by leukocytoclastic vasculitis on the lower extremities. Skin biopsy confirmed vasculitis. Progression-free survival and overall survival were significantly better in patients without PV. CONCLUSIONS: PV is not rare paraneoplastic syndrome in mRCC. Leukocytoclastic vasculitis was the most common type of PV in this study.


Asunto(s)
Carcinoma de Células Renales/patología , Neoplasias Renales/patología , Síndromes Paraneoplásicos/patología , Piel/patología , Vasculitis/patología , Adulto , Anciano , Carcinoma de Células Renales/diagnóstico por imagen , Femenino , Humanos , Neoplasias Renales/diagnóstico por imagen , Masculino , Persona de Mediana Edad , Metástasis de la Neoplasia , Síndromes Paraneoplásicos/diagnóstico por imagen , Piel/diagnóstico por imagen , Ultrasonografía/métodos , Vasculitis/diagnóstico por imagen
19.
J Exp Med ; 208(8): 1635-48, 2011 Aug 01.
Artículo en Inglés | MEDLINE | ID: mdl-21727188

RESUMEN

Chronic mucocutaneous candidiasis disease (CMCD) may be caused by autosomal dominant (AD) IL-17F deficiency or autosomal recessive (AR) IL-17RA deficiency. Here, using whole-exome sequencing, we identified heterozygous germline mutations in STAT1 in 47 patients from 20 kindreds with AD CMCD. Previously described heterozygous STAT1 mutant alleles are loss-of-function and cause AD predisposition to mycobacterial disease caused by impaired STAT1-dependent cellular responses to IFN-γ. Other loss-of-function STAT1 alleles cause AR predisposition to intracellular bacterial and viral diseases, caused by impaired STAT1-dependent responses to IFN-α/ß, IFN-γ, IFN-λ, and IL-27. In contrast, the 12 AD CMCD-inducing STAT1 mutant alleles described here are gain-of-function and increase STAT1-dependent cellular responses to these cytokines, and to cytokines that predominantly activate STAT3, such as IL-6 and IL-21. All of these mutations affect the coiled-coil domain and impair the nuclear dephosphorylation of activated STAT1, accounting for their gain-of-function and dominance. Stronger cellular responses to the STAT1-dependent IL-17 inhibitors IFN-α/ß, IFN-γ, and IL-27, and stronger STAT1 activation in response to the STAT3-dependent IL-17 inducers IL-6 and IL-21, hinder the development of T cells producing IL-17A, IL-17F, and IL-22. Gain-of-function STAT1 alleles therefore cause AD CMCD by impairing IL-17 immunity.


Asunto(s)
Candidiasis Mucocutánea Crónica/genética , Candidiasis Mucocutánea Crónica/inmunología , Interleucina-17/inmunología , Modelos Moleculares , Factor de Transcripción STAT1/genética , Linfocitos T/inmunología , Secuencia de Bases , Ensayo de Cambio de Movilidad Electroforética , Ensayo de Inmunoadsorción Enzimática , Femenino , Citometría de Flujo , Técnica del Anticuerpo Fluorescente , Mutación de Línea Germinal/genética , Humanos , Immunoblotting , Interferón gamma/sangre , Interferón gamma/metabolismo , Interferones , Interleucinas/metabolismo , Masculino , Datos de Secuencia Molecular , Linaje , Fosforilación , Receptor de Interferón alfa y beta/inmunología , Factor de Transcripción STAT1/química , Factor de Transcripción STAT1/metabolismo , Alineación de Secuencia , Análisis de Secuencia de ADN
SELECCIÓN DE REFERENCIAS
DETALLE DE LA BÚSQUEDA