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1.
N Engl J Med ; 378(25): 2376-2385, 2018 Jun 21.
Artigo em Inglês | MEDLINE | ID: mdl-29924955

RESUMO

BACKGROUND: Cisplatin chemotherapy and surgery are effective treatments for children with standard-risk hepatoblastoma but may cause considerable and irreversible hearing loss. This trial compared cisplatin with cisplatin plus delayed administration of sodium thiosulfate, aiming to reduce the incidence and severity of cisplatin-related ototoxic effects without jeopardizing overall and event-free survival. METHODS: We randomly assigned children older than 1 month and younger than 18 years of age who had standard-risk hepatoblastoma (≤3 involved liver sectors, no metastatic disease, and an alpha-fetoprotein level of >100 ng per milliliter) to receive cisplatin alone (at a dose of 80 mg per square meter of body-surface area, administered over a period of 6 hours) or cisplatin plus sodium thiosulfate (at a dose of 20 g per square meter, administered intravenously over a 15-minute period, 6 hours after the discontinuation of cisplatin) for four preoperative and two postoperative courses. The primary end point was the absolute hearing threshold, as measured by pure-tone audiometry, at a minimum age of 3.5 years. Hearing loss was assessed according to the Brock grade (on a scale from 0 to 4, with higher grades indicating greater hearing loss). The main secondary end points were overall survival and event-free survival at 3 years. RESULTS: A total of 109 children were randomly assigned to receive cisplatin plus sodium thiosulfate (57 children) or cisplatin alone (52) and could be evaluated. Sodium thiosulfate was associated with few high-grade toxic effects. The absolute hearing threshold was assessed in 101 children. Hearing loss of grade 1 or higher occurred in 18 of 55 children (33%) in the cisplatin-sodium thiosulfate group, as compared with 29 of 46 (63%) in the cisplatin-alone group, indicating a 48% lower incidence of hearing loss in the cisplatin-sodium thiosulfate group (relative risk, 0.52; 95% confidence interval [CI], 0.33 to 0.81; P=0.002). At a median of 52 months of follow-up, the 3-year rates of event-free survival were 82% (95% CI, 69 to 90) in the cisplatin-sodium thiosulfate group and 79% (95% CI, 65 to 88) in the cisplatin-alone group, and the 3-year rates of overall survival were 98% (95% CI, 88 to 100) and 92% (95% CI, 81 to 97), respectively. CONCLUSIONS: The addition of sodium thiosulfate, administered 6 hours after cisplatin chemotherapy, resulted in a lower incidence of cisplatin-induced hearing loss among children with standard-risk hepatoblastoma, without jeopardizing overall or event-free survival. (Funded by Cancer Research UK and others; SIOPEL 6 ClinicalTrials.gov number, NCT00652132 ; EudraCT number, 2007-002402-21 .).


Assuntos
Cisplatino/efeitos adversos , Perda Auditiva/prevenção & controle , Hepatoblastoma/tratamento farmacológico , Neoplasias Hepáticas/tratamento farmacológico , Tiossulfatos/uso terapêutico , Adolescente , Criança , Pré-Escolar , Cisplatino/administração & dosagem , Doxorrubicina/administração & dosagem , Quimioterapia Combinada , Feminino , Seguimentos , Taxa de Filtração Glomerular , Perda Auditiva/induzido quimicamente , Hepatoblastoma/mortalidade , Humanos , Incidência , Lactente , Neoplasias Hepáticas/mortalidade , Masculino , Método Simples-Cego , Análise de Sobrevida , Tiossulfatos/administração & dosagem , Tiossulfatos/efeitos adversos
2.
J Intern Med ; 289(6): 921-925, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-33372300

RESUMO

BACKGROUND: SARS-CoV-2, the COVID-19 causative agent, has infected millions of people and killed over 1.6 million worldwide. A small percentage of cases persist with prolonged positive RT-PCR on nasopharyngeal swabs. The aim of this study was to determine risk factors for prolonged viral shedding amongst patient's basal clinical conditions. METHODS: We have evaluated all 513 patients attended in our hospital between 1 March and 1 July. We have selected all 18 patients with prolonged viral shedding and compared them with 36 sex-matched randomly selected controls. Demographic, treatment and clinical data were systematically collected. RESULTS: Global median duration of viral clearance was 25.5 days (n = 54; IQR, 22-39.3 days), 48.5 days in cases (IQR 38.7-54.9 days) and 23 days in controls (IQR 20.2-25.7), respectively. There were not observed differences in demographic, symptoms or treatment data between groups. Chronic rhinosinusitis and atopy were more common in patients with prolonged viral shedding (67%) compared with controls (11% and 25% respectively) (P < 0.001 and P = 0.003). The use of inhaled corticosteroids was also more frequent in case group (P = 0.007). Multivariate analysis indicated that CRS (odds ratio [OR], 18.78; 95% confidence interval [95%CI], 3.89-90.59; P < 0.001) was independently associated with prolonged SARS-CoV-2 RNA shedding in URT samples, after adjusting for initial PCR Ct values. CONCLUSION: We found that chronic rhinosinusitis and atopy might be associated with increased risk of prolonged viral shedding. If confirmed in prospective trials, this finding might have clinical implications for quarantine duration due to increased risk of pandemic spread.


Assuntos
COVID-19/virologia , Nasofaringe/virologia , Rinite/virologia , SARS-CoV-2 , Sinusite/virologia , Eliminação de Partículas Virais , Idoso , COVID-19/complicações , Estudos de Casos e Controles , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Rinite/complicações , SARS-CoV-2/fisiologia , Sinusite/complicações
3.
J Investig Allergol Clin Immunol ; 30(2): 101-107, 2020 Apr 24.
Artigo em Inglês | MEDLINE | ID: mdl-31058590

RESUMO

BACKGROUND: The study of perioperative drug reactions remains a major challenge for both diagnosis and therapy. The lack of a standard assessment of allergy to general anesthetics and of data establishing the true value of skin tests for most drugs used in induction and maintenance of anesthesia, as well as the lack of commercially available reagents for in vitro tests, renders the study of these reactions problematic. The aims of this study were to provide a diagnostic protocol for drug challenge testing with general anesthetics, to establish an etiological diagnosis that is as specific as possible, and to determine the predictive value of skin tests. METHODS: Twenty-nine patients with perioperative drug reactions were included in the study from November 2008 to December 2018. RESULTS: We confirmed the high negative predictive value of the tests (96%-100%) in the case of propofol, rocuronium, and fentanyl. To our knowledge, this is the first study to describe drug challenge testing with general anesthetics and, therefore, to establish the true negative predictive value of skin tests, which leads to a definitive diagnosis and safer surgery. CONCLUSIONS: After assessing risks and benefits and considering the importance of this group of drugs, we conclude that drug challenge testing with general anesthetics is necessary. We propose a protocol for perioperative drug reactions that enables us to make a highly accurate etiological diagnosis with minimum risk for the patient.


Assuntos
Anestésicos Gerais/efeitos adversos , Hipersensibilidade a Drogas/diagnóstico , Adulto , Idoso , Idoso de 80 Anos ou mais , Analgésicos Opioides/efeitos adversos , Anestésicos Intravenosos/efeitos adversos , Atracúrio/efeitos adversos , Atracúrio/análogos & derivados , Feminino , Fentanila/efeitos adversos , Humanos , Masculino , Pessoa de Meia-Idade , Bloqueadores Neuromusculares/efeitos adversos , Período Perioperatório , Valor Preditivo dos Testes , Propofol/efeitos adversos , Remifentanil/efeitos adversos , Rocurônio/efeitos adversos , Testes Cutâneos , Sugammadex/efeitos adversos , Adulto Jovem
4.
BMC Oral Health ; 19(1): 196, 2019 08 28.
Artigo em Inglês | MEDLINE | ID: mdl-31462244

RESUMO

BACKGROUND: Recent non-invasive 3D photography method has been applied to facial analysis, offering numerous advantages in orthodontic. The purpose of this study was to analyze the faces of a sample of healthy European adults from southern Spain with normal occlusion in order to establish reference facial soft tissue anthropometric parameters in this specific geographic-ethnic population, as well as to analyze sexual dimorphism. METHODS: A sample of 100 healthy adult volunteers consisting of 50 women (mean age, 22.92 ± 1.56 years) and 50 men (mean age, 22.37 ± 2.12 years) were enrolled in this study. All participants had normal occlusion, skeletal Class I, mesofacial pattern, and healthy body mass index. Three-dimensional photographs of the faces were captured non-invasively using Planmeca ProMax 3D ProFace®. Thirty landmarks related to the face, eyes, nose, and orolabial and chin areas were identified. RESULTS: Male displayed higher values in all vertical and transversal dimensions, with the exception of the lower lip height. Larger differences between sexes were observed in face, mandible, and nose. Male also had higher values in the angular measurements which referred to the nose. No sex differences were found in transverse upper lip prominence or transverse mandibular prominence. No differences were found in the ratio measurements, with the exception of intercantal width/nasal width, which was higher in women than in men. CONCLUSIONS: Reference anthropometric measurements of facial soft tissues have been established in European adults from southern Spain with normal occlusion. Significant sexual dimorphism was found, with remarkable differences in size between sexes.


Assuntos
Cefalometria , Oclusão Dentária , Face , Fotografação , Adulto , Antropometria , Feminino , Humanos , Imageamento Tridimensional , Lábio , Masculino , Nariz , Valores de Referência , Espanha , Adulto Jovem
6.
Qual Life Res ; 27(6): 1431-1443, 2018 06.
Artigo em Inglês | MEDLINE | ID: mdl-29372438

RESUMO

PURPOSE: Acute lymphoblastic leukemia (ALL) survivors are the largest group of childhood cancer survivors; however, their risk for late effects is high. Cancer-related late effects have the potential to compromise health-related quality of life (HRQL) long into survivorship. None of the reviews so far have focused on ALL solely, but described HRQL for all childhood cancers. We aimed to identify ALL survivors at risk for poor HRQL and identify possible risk factors. METHOD: Following PRISMA guidelines, we performed a systematic review, searching published literature in Pubmed, PsycInfo, Embase, and the Cochrane database including all publications up to December 16, 2016. Two independent reviewers (JV and ER) screened eligible articles and assessed article quality. RESULTS: We found 31 studies representing 4356 survivors and 901 proxies. Thirteen studies found worse, eight found no difference, and three better, overall HRQL scores compared with healthy controls or norms. ALL survivors typically had better overall HRQL scores than survivors of other childhood cancers. Clinical variables (e.g., treatment received) were not consistently associated with HRQL; however, experiencing worse late effects was associated with lower HRQL. Survivor and parent socio-demographic factors and psychological factors such as resilience and depression were also associated with HRQL. CONCLUSION: ALL survivors appeared to have worse or equivalent HRQL compared with controls, but better HRQL than survivors of other cancer types. However, studies reported a wide variability in HRQL and potential risk factors for poor HRQL. Measuring ALL survivors' HRQL longitudinally and comprehensively assessing potential risk factors might identify future avenues to intervene early.


Assuntos
Sobreviventes de Câncer/psicologia , Leucemia-Linfoma Linfoblástico de Células Precursoras/psicologia , Qualidade de Vida/psicologia , Adolescente , Adulto , Criança , Pré-Escolar , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Leucemia-Linfoma Linfoblástico de Células Precursoras/mortalidade , Adulto Jovem
9.
Pediatr Blood Cancer ; 64(9)2017 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-28266135

RESUMO

Children with acute lymphoblastic leukemia (ALL) undergo intense anticancer treatment. We systematically reviewed 22 studies evaluating 2,073 ALL patients' health-related quality of life (HRQL) and its clinical/demographic correlates during treatment. Overall HRQL was significantly reduced on treatment. Despite HRQL improvements over time, longitudinal studies reported a proportion of children continued to experience reduced HRQL after treatment completion. We found inconsistent associations between clinical/demographic factors and HRQL outcomes. Tentative evidence emerged for worse HRQL being associated with intensive phases of chemotherapy, corticosteroid therapy, experiencing greater toxicity, older age, and female sex. Longitudinal studies are needed to identify children at-risk of reduced HRQL.


Assuntos
Leucemia-Linfoma Linfoblástico de Células Precursoras/complicações , Leucemia-Linfoma Linfoblástico de Células Precursoras/psicologia , Qualidade de Vida , Adolescente , Criança , Pré-Escolar , Feminino , Nível de Saúde , Humanos , Masculino , Leucemia-Linfoma Linfoblástico de Células Precursoras/terapia
11.
Clin Exp Allergy ; 44(4): 579-88, 2014 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-24397754

RESUMO

BACKGROUND: Accurate predictors of natural tolerance development to cooked and uncooked egg are needed in egg-allergic patients. OBJECTIVE: To compare the diagnostic performance of different immunological tests in relation to egg allergy versus tolerance. METHODS: Children aged 5-18 years diagnosed with IgE-mediated egg allergy were prospectively recruited. All followed an egg-free diet. Prick test and specific IgE (sIgE) to ovalbumin, ovomucoid and egg white, ovalbumin-sIgG4 and ovomucoid-sIgG4 were determined. By boiled and raw egg challenges, children were classified as cooked egg allergic (CEA, n = 50) or tolerant (CET, n = 35), and uncooked egg allergic (UEA, n = 64) or tolerant (UET, n = 21). Statistics. Comparative analysis (CEA vs. CET and UEA vs. UET). Multivariate logistic regression. Partial receiver operating characteristic curve analysis of tests in relation to CEA and UEA. Negative decision points were defined as cut-offs with sensitivity 95%. RESULTS: Ovalbumin-sIgG4 resulted an independent protective factor for uncooked egg allergy. To identify patients with high probability of egg tolerance, ovalbumin-sIgE/sIgG4 tended to perform better than sIgE and prick, specifically in children with ovalbumin-sIgE < 1.9 kU/L (for UEA) and ovomucoid-sIgE < 2.12 kU/L (for CEA). The most accurate cut-offs to recommend challenges were ovalbumin-sIgE/sIgG4 below 2.49 for cooked egg and 1.45 for uncooked egg, which associated 89.5% and 80% probability of tolerance (negative likelihood ratios 0.08 and 0.06), respectively. These cut-offs identified correctly as tolerant an additional 23% and 14% of children with negative challenges to cooked and uncooked egg, respectively, in comparison with sIgE negative decision points. Additionally, prick test tended to perform better than sIgE alone in predicting cooked and uncooked egg tolerance for ovomucoid-sIgE < 0.92 kU/L and ovalbumin-sIgE < 1.37 kU/L, respectively. CONCLUSIONS: Ovalbumin-specific IgG4 is an independent predictor of tolerance development to uncooked egg. Ovalbumin-sIgE/sIgG4 ratio, followed by skin prick test (SPT), seems to perform better than sIgE in identifying egg-allergic children with high probability of tolerance to cooked and uncooked egg over follow-up.


Assuntos
Hipersensibilidade a Ovo/diagnóstico , Hipersensibilidade a Ovo/imunologia , Imunoglobulina E/imunologia , Imunoglobulina G/imunologia , Ovalbumina/imunologia , Adolescente , Especificidade de Anticorpos/imunologia , Criança , Pré-Escolar , Feminino , Humanos , Masculino , Prognóstico , Curva ROC , Reprodutibilidade dos Testes , Testes Cutâneos
12.
Clin Exp Allergy ; 44(1): 130-41, 2014 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-24355019

RESUMO

BACKGROUND: Oral immunotherapy (OIT) is a promising treatment for food allergy but dose-related reactions are common. OBJECTIVE: To evaluate safety of egg-OIT. To identify predictors of dose-related reactions. METHODS: Fifty children aged 5-18 underwent egg-OIT after confirming IgE-mediated egg allergy by double-blind placebo-controlled challenge (DBPCFC). All dose-related reactions over a median period of 18 months on-OIT (range: 12-28) were registered. Children were retrospectively divided into three subgroups: (1) children who stopped reacting to OIT-doses over time (RR, Resolved Reactions); (2) children with ongoing dose-related reactions over the whole period on-OIT (PR, Persistent Reactions); (3) children who discontinued OIT within induction phase due to frequent reactions not improved by protocol re-adaptation and medication (ED, Early Discontinuation). Baseline clinical/immunological parameters associated with subgroups were investigated. RESULTS: Reactions occurred in 7.6% of doses. Adrenaline was required in 26% of children. The three subgroups corresponded to three different safety phenotypes: (1) twenty-four children (48%, RR) experienced infrequent and mainly mild reactions that resolved over time. None required adrenaline; (2) seventeen children (34%, PR) experienced more frequent and severe ongoing reactions over time; (3) nine children (18%, ED) discontinued OIT due to very frequent and mainly moderate reactions. Early discontinuation was associated with underlying asthma, higher specific IgE (sIgE) and lower threshold at DBPCFC. In contrast, lower sIgE and less severe reactions at DBPCFC were associated with subgroup RR. sIgE showed excellent performance in predicting belonging to subgroup RR. Levels below the optimal cut-off (ovomucoid-sIgE 8.85 kU/L) indicated 77% probability of belonging to subgroup RR, whereas levels above it indicated 95% probability of early discontinuation or ongoing reactions over time. CONCLUSIONS AND CLINICAL RELEVANCE: Egg-OIT involves substantial risks. However, baseline parameters, particularly sIgE, may help identify children in whom the procedure is more likely to be safe. Egg-OIT safety needs improvement in children with more severe and persistent egg allergy.


Assuntos
Dessensibilização Imunológica , Hipersensibilidade a Ovo/imunologia , Hipersensibilidade a Ovo/terapia , Imunoglobulina E/imunologia , Administração Oral , Alérgenos/administração & dosagem , Alérgenos/imunologia , Estudos de Casos e Controles , Criança , Pré-Escolar , Dessensibilização Imunológica/efeitos adversos , Dessensibilização Imunológica/métodos , Hipersensibilidade a Ovo/diagnóstico , Ovos/efeitos adversos , Feminino , Humanos , Imunoglobulina E/sangue , Masculino , Curva ROC , Fatores de Risco , Resultado do Tratamento
13.
Allergy ; 69(10): 1350-6, 2014 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-25040899

RESUMO

BACKGROUND: Egg-sensitized infants who have never eaten egg may react at first ingestion. We sought to determine the association between skin prick test (SPT) and specific IgE (sIgE) to egg proteins (EP) and oral food challenge (OFC) outcomes to find cut-off points which can diagnose egg allergy. METHODS: One hundred and fifty-four infants up to 18 months, with cow's milk allergy (CMA) and/or atopic dermatitis (AD) without previous egg consumption, were recruited. SPT to EP were performed. If it was positive, sIgE was performed. If positive SPT and/or sIgE (n = 94), OFC was performed between 12 and 18 months. Receiver operating characteristic (ROC) curves were plotted, and the outcome of the OFC was related to SPT and sIgE. The cut-off points with the best diagnostic accuracy were found. RESULTS: Ninety-four patients were sensitized to egg (69%) and 60 nonsensitized (31%). Of the sensitized, 27 tolerated cooked (CE) and raw egg (RE) (28.7%). Sixty-seven were allergic (71.3%): 29 reacted to CE, seven to egg yolk (EY) and 22 to egg white (EW) and 38 reacted to RE. 69.2% tolerated CE. EW SPT and ovalbumin (OVA) sIgE have the best area under the curve (AUC). The higher positive predictive values (PPV) were obtained for EW SPT and EW sIgE. CONCLUSIONS: In egg-sensitized infants with EW SPT ≥8 mm and/or EW sIgE ≥8.36 KU/l, egg diagnostic OFC can be avoided as there is 94% probability of becoming positive. In the other patients, OFC should be performed safely and early to avoid unnecessary diets.


Assuntos
Hipersensibilidade a Ovo/diagnóstico , Hipersensibilidade a Ovo/imunologia , Área Sob a Curva , Pré-Escolar , Proteínas Dietéticas do Ovo/efeitos adversos , Proteínas Dietéticas do Ovo/imunologia , Feminino , Humanos , Tolerância Imunológica/imunologia , Imunoglobulina E/sangue , Lactente , Masculino , Hipersensibilidade a Leite/imunologia , Curva ROC , Testes Cutâneos
14.
Heredity (Edinb) ; 112(4): 399-408, 2014 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-24281548

RESUMO

Maternally transmitted associations between endosymbiotic bacteria and insects are diverse and widespread in nature. Owing to imperfect vertical transmission, many heritable microbes have evolved compensational mechanisms to enhance their persistence in host lineages, such as manipulating host reproduction and conferring fitness benefits to host. Symbiont-mediated defense against natural enemies of hosts is increasingly recognized as an important mechanism by which endosymbionts enhance host fitness. Members of the genus Spiroplasma associated with distantly related Drosophila hosts are known to engage in either reproductive parasitism (i.e., male killing) or defense against natural enemies (the parasitic wasp Leptopilina heterotoma and a nematode). A male-killing strain of Spiroplasma (strain Melanogaster Sex Ratio Organism (MSRO)) co-occurs with Wolbachia (strain wMel) in certain wild populations of the model organism Drosophila melanogaster. We examined the effects of Spiroplasma MSRO and Wolbachia wMel on Drosophila survival against parasitism by two common wasps, Leptopilina heterotoma and Leptopilina boulardi, that differ in their host ranges and host evasion strategies. The results indicate that Spiroplasma MSRO prevents successful development of both wasps, and confers a small, albeit significant, increase in larva-to-adult survival of flies subjected to wasp attacks. We modeled the conditions under which defense can contribute to Spiroplasma persistence. Wolbachia also confers a weak, but significant, survival advantage to flies attacked by L. heterotoma. The host protective effects exhibited by Spiroplasma and Wolbachia are additive and may provide the conditions for such cotransmitted symbionts to become mutualists. Occurrence of Spiroplasma-mediated protection against distinct parasitoids in divergent Drosophila hosts suggests a general protection mechanism.


Assuntos
Drosophila melanogaster/microbiologia , Drosophila melanogaster/parasitologia , Spiroplasma/fisiologia , Simbiose , Vespas/fisiologia , Animais , Evolução Biológica , Citoplasma/microbiologia , Mecanismos de Defesa , Feminino , Masculino , Análise de Sobrevida , Vespas/microbiologia , Wolbachia
15.
Allergol Immunopathol (Madr) ; 42(2): 136-41, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-23253680

RESUMO

BACKGROUND: The objective of this study was to evaluate safety and efficacy of Privigen®, a 10% intravenous immunoglobulin (IVIG), in a particular group of paediatric patients (highly sensitive to previous IVIG infusion) affected with Primary Immunodeficiencies (PID). MATERIAL AND METHODS: Patients (n=8) from 3 to 17 years old diagnosed of PID who often suffered from adverse events related to the infusion to previous IVIG were switched to Privigen® in an open protocol. Data were prospectively collected regarding Privigen® administration: infusion, safety and efficacy. In parallel, data on safety and tolerance were retrospectively collected from medical charts regarding the previous 10% IVIG product used. RESULTS: 50% of the patients required premedication with previous IVIG. At the end of the study none required premedication with Privigen®. The infusion rate was lower than that recommended by the manufacturer. All patients had suffered through adverse events during previous IVIG infusion being severe in three patients and recurrent in the rest. With Privigen® only three patients suffered from an adverse event (all cases were milder than previous related). Trough levels of IgG remained stable. None suffer from any episode of bacterial infection. CONCLUSION: The present work shows that Privigen® was safe in a group of hypersensitive paediatric patients who did not tolerate the administration of a previous 10% liquid IVIG by using a particular infusion protocol slower than recommended. The number of adverse effects was smaller than published, and all cases were mild. No premedication was needed. Privigen® was also effective in this small group.


Assuntos
Imunoglobulinas Intravenosas/administração & dosagem , Síndromes de Imunodeficiência/tratamento farmacológico , Adolescente , Criança , Pré-Escolar , Hipersensibilidade a Drogas , Feminino , Humanos , Imunoglobulinas Intravenosas/efeitos adversos , Imunoglobulinas Intravenosas/imunologia , Masculino
16.
Blood Cancer J ; 14(1): 74, 2024 Apr 29.
Artigo em Inglês | MEDLINE | ID: mdl-38684670

RESUMO

Smoldering multiple myeloma (SMM) precedes multiple myeloma (MM). The risk of progression of SMM patients is not uniform, thus different progression-risk models have been developed, although they are mainly based on clinical parameters. Recently, genomic predictors of progression have been defined for untreated SMM. However, the usefulness of such markers in the context of clinical trials evaluating upfront treatment in high-risk SMM (HR SMM) has not been explored yet, precluding the identification of baseline genomic alterations leading to drug resistance. For this reason, we carried out next-generation sequencing and fluorescent in-situ hybridization studies on 57 HR and ultra-high risk (UHR) SMM patients treated in the phase II GEM-CESAR clinical trial (NCT02415413). DIS3, FAM46C, and FGFR3 mutations, as well as t(4;14) and 1q alterations, were enriched in HR SMM. TRAF3 mutations were specifically associated with UHR SMM but identified cases with improved outcomes. Importantly, novel potential predictors of treatment resistance were identified: NRAS mutations and the co-occurrence of t(4;14) plus FGFR3 mutations were associated with an increased risk of biological progression. In conclusion, we have carried out for the first time a molecular characterization of HR SMM patients treated with an intensive regimen, identifying genomic predictors of poor outcomes in this setting.


Assuntos
Biomarcadores Tumorais , Progressão da Doença , Resistencia a Medicamentos Antineoplásicos , Mutação , Mieloma Múltiplo Latente , Humanos , Masculino , Resistencia a Medicamentos Antineoplásicos/genética , Feminino , Mieloma Múltiplo Latente/genética , Biomarcadores Tumorais/genética , Pessoa de Meia-Idade , Idoso , Sequenciamento de Nucleotídeos em Larga Escala , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico
17.
Clin Exp Allergy ; 43(1): 92-102, 2013 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-23278884

RESUMO

BACKGROUND: Strict avoidance is the only accepted management for cow's milk (CM) allergy. CM oral immunotherapy (CM-OIT) is under investigation. OBJECTIVES: To evaluate long-term safety of CM-OIT. To identify clinical/immunological predictors of adverse events. METHODS: Prospective longitudinal epidemiological intervention study. CM-allergic children aged 5-18 underwent a Spanish-approved CM-OIT protocol without premedication. Clinical data, skin prick test (SPT) and specific IgE (sIgE) at baseline and 1 year after OIT were registered. All dose-related reactions, treatments needed and cofactors involved were recorded. Through survival analysis, we studied the cumulative probability of reactions resolution over time and clinical/immunological risk factors of reactions persistence. RESULTS: 81 children were recruited. Mean follow-up was 25 months. 95% of children suffered reactions, 91% of which affected a single organ. Reactions were heterogeneously distributed: (a) 60 children (75%) had occasional symptoms which ceased over time. 86% of them reached complete desensitization (200 mL). (b) 20 children (25%) suffered frequent (78% of total reactions), more severe and unpredictable reactions, which persisted during follow-up or led to withdrawal (6 cases). Reactions persistence was associated with a higher frequency and severity. Kaplan-Meier estimate revealed a cumulative probability of reactions resolution of 25% at 3 months (95% CI: 1.9-4.1) and 50% (95% CI: 6.1-9.9) at 8 months based on all patients. Cox proportional hazards multivariate regression model identified 3 variables (CM-sIgE ≥ 50 KU L(-1) , CM-SPT ≥ 9 mm and Sampson's severity grades 2, 3 and 4 at baseline food challenge) as independent risk factors of reactions persistence. The combination of 2 or 3 of these factors involved hazard ratios to develop persistent reactions of 2.26 (95% CI: 1.14-4.46; P = 0.019) and 6.06 (95% CI: 2.7-13.7; P < 0.001), respectively. CLINICAL IMPLICATIONS: CM-OIT was insufficiently safe in 25% of children. The above-mentioned clinical and immunological parameters would help clinicians to identify highly reactive patients before CM-OIT. In them, individualized schedules and premedication should be considered.


Assuntos
Dessensibilização Imunológica/efeitos adversos , Hipersensibilidade a Leite/prevenção & controle , Administração Oral , Adolescente , Animais , Bovinos , Criança , Pré-Escolar , Dessensibilização Imunológica/métodos , Feminino , Humanos , Masculino , Testes Cutâneos
18.
Allergy ; 68(10): 1327-32, 2013 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-24004369

RESUMO

The role of specific IgA (sIgA) in oral immunotherapy (OIT) and natural tolerance to foods is poorly understood. We aimed to study serum sIgA in induced and natural tolerance to egg. Children aged 5-16 years diagnosed with IgE-mediated egg allergy were recruited. After egg challenge, patients were classified as transient (TEA) or persistent (PEA) egg-allergic. PEA children were further divided into oral immunotherapy (PEA-OIT) or egg avoidance (PEA-EA). Allergy/tolerance was reassessed 9-12 months later (T1) in PEA-EA. Serum sIgA to ovalbumin and ovomucoid were determined at inclusion in all patients and repeated in PEA at T1. 21 TEA and 52 PEA children were recruited (28 PEA-OIT, 24 PEA-EA). Serum sIgA remained unchanged after OIT. TEA and PEA had similar serum sIgA. No specific trend on serum sIgA was observed in five PEA-EA who developed natural tolerance over follow-up. Thus, serum sIgA seems not to be associated with induced or natural egg tolerance.


Assuntos
Alérgenos/imunologia , Hipersensibilidade a Ovo/imunologia , Ovos/efeitos adversos , Tolerância Imunológica , Imunoglobulina A/imunologia , Adolescente , Especificidade de Anticorpos/imunologia , Criança , Pré-Escolar , Dessensibilização Imunológica , Hipersensibilidade a Ovo/sangue , Hipersensibilidade a Ovo/diagnóstico , Hipersensibilidade a Ovo/terapia , Feminino , Humanos , Imunoglobulina A/sangue , Imunoglobulina E/sangue , Imunoglobulina E/imunologia , Masculino , Ovalbumina/imunologia , Ovomucina/imunologia
19.
Poult Sci ; 92(4): 975-8, 2013 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-23472021

RESUMO

The study was carried out under field conditions in a commercial farm, and 1,440 as-hatched Ross-308 broilers were included. Broilers were randomly distributed into 24 experimental 4-m(2) pens (60 broilers/pen). Pens were randomized to the 3 treatment groups: a) tylvalosin 10 mg/kg of live BW during 2 d, b) positive control (tylosin during 2 d), and c) negative control (no treatment). The drugs were provided in the water supply. Mortality, individual BW, and feed intake were assessed. Clostridium presence was assessed in fecal and cecal samples, coccidian oocyst counts were assessed in fecal samples, and bacterial diversity was assessed in ileal content. Live BW at 42 d old was significantly better in the tylvalosin group than in tylosin and no-treatment groups, with tylvalosin-treated broilers reaching 80 to 100 g higher final live weight. Average daily gain results mirrored BW findings. The improvement of feed conversion rate with tylvalosin amounted to 0.13 and to 0.10 versus tylosin and no-treatment, respectively, with mortality being similar in all groups. Significantly reduced sulfite-reducing Clostridium and Clostridium perfringens counts in tylvalosin and tylosin groups versus the no-treatment group were observed in cecum content samples. In conclusion, according to the present study results, tylvalosin, at doses substantially lower than registered for poultry in Europe, has proven effective in controlling the colonization of the cecum by Clostridium ssp. in broilers, improving some productive performances.


Assuntos
Antibacterianos/uso terapêutico , Galinhas/crescimento & desenvolvimento , Infecções por Clostridium/veterinária , Enteropatias/veterinária , Doenças das Aves Domésticas/prevenção & controle , Tilosina/análogos & derivados , Animais , Bactérias/isolamento & purificação , Biodiversidade , Peso Corporal , Ceco/microbiologia , Galinhas/fisiologia , Infecções por Clostridium/microbiologia , Infecções por Clostridium/mortalidade , Infecções por Clostridium/prevenção & controle , Clostridium perfringens/isolamento & purificação , Coccidiose/parasitologia , Coccidiose/veterinária , Contagem de Colônia Microbiana/veterinária , DNA Bacteriano/genética , DNA Bacteriano/metabolismo , Relação Dose-Resposta a Droga , Ingestão de Alimentos , Eimeria/isolamento & purificação , Fezes/microbiologia , Fezes/parasitologia , Comportamento Alimentar , Íleo/microbiologia , Enteropatias/microbiologia , Enteropatias/mortalidade , Enteropatias/prevenção & controle , Contagem de Ovos de Parasitas/veterinária , Reação em Cadeia da Polimerase/veterinária , Polimorfismo de Fragmento de Restrição , Doenças das Aves Domésticas/microbiologia , Doenças das Aves Domésticas/mortalidade , Doenças das Aves Domésticas/parasitologia , RNA Ribossômico 16S/genética , RNA Ribossômico 16S/metabolismo , Tilosina/uso terapêutico
20.
Heliyon ; 9(10): e20942, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37916107

RESUMO

Background and Objective: Unplanned hospital readmissions are a severe and recurrent problem that affects all health systems. Estimating the risk of being readmitted the following days after discharge is difficult since many heterogeneous factors can influence this. The extensive work concerning this problem proposes solutions mostly based on classification machine-learning models. Survival analysis methods could make a better match with the assessment of readmission risk and are yet to become well-established in this field. Methods: We compare different statistical and machine learning survival analysis models trained with right-censored all-cause hospital admission data with covariates available at the moment of discharge. The main focus is on tree-ensemble regression methods based on the assumption of proportional hazards. These models are more thoroughly evaluated at a 30-day time period after discharge, although the actual prediction could be set to any time up to 90 days. Results: The mean performance obtained by each of the proposed survival models ranges from 0.707 to 0.716 C-Index and 0.709 to 0.72 ROC-AUC at a 30-day time period after discharge. The model with the lower performance on both metrics was Cox Proportional Hazards, while the model marking the upper end on both ranges is an XGBoost Regression model with a Cox objective function. Conclusions: Our findings indicate that survival models perform well addressing the hospital readmission problem, machine-learning models getting the edge over statistical methods. There seems to be an improvement over classification models when attempting to predict at a 30-day period since discharge, perhaps due to a better handling of cases nearing the 30-day boundary. Some preprocessing steps, such as limiting the observation period to 90 days after discharge, are also highlighted since they resulted in a performance boost.

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