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BACKGROUND: The efficacy of continuous antibiotic prophylaxis in preventing urinary tract infection (UTI) in infants with grade III, IV, or V vesicoureteral reflux is controversial. METHODS: In this investigator-initiated, randomized, open-label trial performed in 39 European centers, we randomly assigned infants 1 to 5 months of age with grade III, IV, or V vesicoureteral reflux and no previous UTIs to receive continuous antibiotic prophylaxis (prophylaxis group) or no treatment (untreated group) for 24 months. The primary outcome was the occurrence of the first UTI during the trial period. Secondary outcomes included new kidney scarring and the estimated glomerular filtration rate (GFR) at 24 months. RESULTS: A total of 292 participants underwent randomization (146 per group). Approximately 75% of the participants were male; the median age was 3 months, and 235 participants (80.5%) had grade IV or V vesicoureteral reflux. In the intention-to-treat analysis, a first UTI occurred in 31 participants (21.2%) in the prophylaxis group and in 52 participants (35.6%) in the untreated group (hazard ratio, 0.55; 95% confidence interval [CI], 0.35 to 0.86; P = 0.008); the number needed to treat for 2 years to prevent one UTI was 7 children (95% CI, 4 to 29). Among untreated participants, 64.4% had no UTI during the trial. The incidence of new kidney scars and the estimated GFR at 24 months did not differ substantially between the two groups. Pseudomonas species, other non-Escherichia coli organisms, and antibiotic resistance were more common in UTI isolates obtained from participants in the prophylaxis group than in isolates obtained from those in the untreated group. Serious adverse events were similar in the two groups. CONCLUSIONS: In infants with grade III, IV, or V vesicoureteral reflux and no previous UTIs, continuous antibiotic prophylaxis provided a small but significant benefit in preventing a first UTI despite an increased occurrence of non-E. coli organisms and antibiotic resistance. (Funded by the Italian Ministry of Health and others; PREDICT ClinicalTrials.gov number, NCT02021006; EudraCT number, 2013-000309-21.).
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Antibacterianos , Antibioticoprofilaxia , Infecções Urinárias , Refluxo Vesicoureteral , Feminino , Humanos , Lactente , Masculino , Antibioticoprofilaxia/efeitos adversos , Antibioticoprofilaxia/métodos , Glomerulonefrite , Análise de Intenção de Tratamento , Refluxo Vesicoureteral/complicações , Refluxo Vesicoureteral/tratamento farmacológico , Antibacterianos/administração & dosagem , Antibacterianos/efeitos adversos , Antibacterianos/uso terapêutico , Infecções Urinárias/etiologia , Infecções Urinárias/microbiologia , Infecções Urinárias/prevenção & controle , Farmacorresistência Bacteriana/efeitos dos fármacosRESUMO
BACKGROUND: Molecular imaging is pivotal in staging and response assessment of children with neuroblastoma (NB). [123I]-metaiodobenzylguanidine (mIBG) is the standard imaging method; however, it is characterised by low spatial resolution, time-consuming acquisition procedures and difficult interpretation. Many PET catecholaminergic radiotracers have been proposed as a replacement for [123I]-mIBG, however they have not yet made it into clinical practice. We aimed to review the available literature comparing head-to-head [123I]-mIBG with the most common PET catecholaminergic radiopharmaceuticals. METHODS: We searched the PubMed database for studies performing a head-to-head comparison between [123I]-mIBG and PET radiopharmaceuticals including meta-hydroxyephedrine ([11C]C-HED), 18F-18F-3,4-dihydroxyphenylalanine ([18F]DOPA) [124I]mIBG and Meta-[18F]fluorobenzylguanidine ([18F]mFBG). Review articles, preclinical studies, small case series (< 5 subjects), case reports, and articles not in English were excluded. From each study, the following characteristics were extracted: bibliographic information, technical parameters, and the sensitivity of the procedure according to a patient-based analysis (PBA) and a lesion-based analysis (LBA). RESULTS: Ten studies were selected: two regarding [11C]C-HED, four [18F]DOPA, one [124I]mIBG, and three [18F]mFBG. These studies included 181 patients (range 5-46). For the PBA, the superiority of the PET method was reported in two out of ten studies (both using [18F]DOPA). For LBA, PET detected significantly more lesions than scintigraphy in seven out of ten studies. CONCLUSIONS: PET/CT using catecholaminergic tracers shows superior diagnostic performance than mIBG scintigraphy. However, it is still unknown if such superiority can influence clinical decision-making. Nonetheless, the PET examination appears promising for clinical practice as it offers faster image acquisition, less need for sedation, and a single-day examination.
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Neuroblastoma , Compostos Radiofarmacêuticos , Criança , Humanos , 3-Iodobenzilguanidina , Di-Hidroxifenilalanina , Neuroblastoma/diagnóstico por imagem , Neuroblastoma/patologia , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada/métodos , Tomografia por Emissão de Pósitrons/métodosRESUMO
PURPOSE: This multicentric study aimed to investigate the main prognostic factors associated with treatment response at 1 year after radioactive iodine therapy (RAIT) and the last disease status in pediatric patients affected by differentiated thyroid carcinoma (DTC). MATERIALS AND METHODS: In the period 1990-2020, all consecutive patients ≤ 18 years from six different centers were retrospectively included. Patients were classified as low, intermediate, and high risk for persistence/recurrence. The response to RAIT was evaluated and scored 1 year later according to 2015 ATA guidelines. Moreover, at the last follow-up, the disease status was evaluated and dichotomized as no evidence of disease (NED) or persistent disease. RESULTS: Two hundred and eighty-five patients (197 female, 88 male; mean age 14.4 years) were recruited. All, except nine, underwent near-total thyroidectomy followed by RAIT. One-year after first RAIT, 146/276 (53%) patients had excellent response, 37/276 (14%) indeterminate response, and 91/276 (33%) incomplete response. One-year after RAIT, children with excellent response had significantly lower stimulated thyroglobulin (sTg) compared to not excellent group (median sTg 4.4 ng/ml vs 52.5 ng/ml, p < 0.001). ROC curve showed sTg higher than 27.2 ng/ml as the most accurate to predict 1-year treatment response. After a median follow-up of 133 months, NED was present in 241 cases (87%) while persistent disease in 35 (13%). At multivariate analysis, sTg and 1-year treatment response categories were both significantly associated with the last disease status (p value 0.023 and < 0.001). CONCLUSIONS: In pediatric DTC, sTg is significantly associated with 1-year treatment response and final outcome. However, 1-year response is the principal prognostic factor able to predict pediatric DTCs outcome.
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Adenocarcinoma , Neoplasias da Glândula Tireoide , Adolescente , Criança , Feminino , Humanos , Radioisótopos do Iodo/uso terapêutico , Masculino , Prognóstico , Estudos Retrospectivos , Tireoglobulina , Neoplasias da Glândula Tireoide/radioterapia , Neoplasias da Glândula Tireoide/cirurgia , TireoidectomiaRESUMO
Kidney dysplasia is one of the most frequent causes of chronic kidney failure in children. While dysplasia is a histological diagnosis, the term 'kidney dysplasia' is frequently used in daily clinical life without histopathological confirmation. Clinical parameters of kidney dysplasia have not been clearly defined, leading to imprecise communication amongst healthcare professionals and patients. This lack of consensus hampers precise disease understanding and the development of specific therapies. Based on a structured literature search, we here suggest a common basis for clinical, imaging, genetic, pathological and basic science aspects of non-obstructive kidney dysplasia associated with functional kidney impairment. We propose to accept hallmark sonographic findings as surrogate parameters defining a clinical diagnosis of dysplastic kidneys. We suggest differentiated clinical follow-up plans for children with kidney dysplasia and summarize established monogenic causes for non-obstructive kidney dysplasia. Finally, we point out and discuss research gaps in the field.
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Nefropatias , Insuficiência Renal , Anormalidades Urogenitais , Criança , Humanos , Rim/patologia , Nefropatias/patologia , Insuficiência Renal/patologiaRESUMO
Testicular cancer is relatively uncommon, but at the same time, it is the most common solid tumor in men between the ages of 20 and 34 years. Seminoma represents the most frequently encountered germ cell tumors. Because orchiectomy is usually performed before chemotherapy, little is known about the effect of systemic chemotherapy on primary testicular tumors. Furthermore, the testis has always been considered a sanctuary site, an immune-privileged site in which inadequate exposure of the tumor to chemotherapy may occur. We report the case of a young patient with advanced seminoma with a complete testicular response after four cycles of cisplatin-based chemotherapy. Then, we performed a systematic review of the literature reporting the studies published to date on the topic.
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Antineoplásicos/uso terapêutico , Cisplatino/uso terapêutico , Seminoma/tratamento farmacológico , Neoplasias Testiculares/tratamento farmacológico , Adulto , Fumar Cigarros/epidemiologia , Humanos , Masculino , Estadiamento de NeoplasiasRESUMO
BACKGROUND: International guidelines support performing baseline positron emission tomography (PET) in lymphoma. Metabolic tumor volume (MTV) measurement has been proposed as a good measurement of disease burden. We investigated if MTV at baseline PET can be predictive of complete response (CR) to first line standard chemotherapy in diffuse large B-cell lymphoma (DLBCL) and in follicular lymphoma (FL) grade IIIb. METHODS: We retrospectively analyzed data on 54 consecutive patients with DLBCL and FL grade IIIb treated in our institution. Dedicated software automatically estimated the SUV
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Linfoma Folicular/diagnóstico por imagem , Linfoma Difuso de Grandes Células B/diagnóstico por imagem , Tomografia por Emissão de Pósitrons/métodos , Carga Tumoral/efeitos dos fármacos , Adulto , Idoso , Idoso de 80 Anos ou mais , Protocolos de Quimioterapia Combinada Antineoplásica/farmacologia , Ciclofosfamida/farmacologia , Ciclofosfamida/uso terapêutico , Doxorrubicina/farmacologia , Doxorrubicina/uso terapêutico , Feminino , Fluordesoxiglucose F18/química , Seguimentos , Humanos , Linfoma Folicular/tratamento farmacológico , Linfoma Difuso de Grandes Células B/tratamento farmacológico , Masculino , Pessoa de Meia-Idade , Prednisona/farmacologia , Prednisona/uso terapêutico , Prognóstico , Compostos Radiofarmacêuticos/química , Análise de Regressão , Estudos Retrospectivos , Análise de Sobrevida , Vincristina/farmacologia , Vincristina/uso terapêuticoRESUMO
PURPOSE: The Society of Nuclear Medicine and Molecular Imaging (SNMMI) is an international scientific and professional organization founded in 1954 to promote the science, technology, and practical application of nuclear medicine. The European Association of Nuclear Medicine (EANM) is a professional nonprofit medical association that facilitates communication worldwide between individuals pursuing clinical and research excellence in nuclear medicine. The EANM was founded in 1985. SNMMI and EANM members are physicians, technologists, and scientists specializing in the research and practice of nuclear medicine. METHODS: The SNMMI and EANM will periodically define new guidelines for nuclear medicine practice to help advance the science of nuclear medicine and to improve the quality of service to patients throughout the world. Existing practice guidelines will be reviewed for revision or renewal, as appropriate, on their fifth anniversary, or sooner, if indicated. CONCLUSION: Each practice guideline, representing a policy statement by the SNMMI/EANM, has undergone a thorough consensus process in which it has been subjected to extensive review. The SNMMI and EANM recognize that the safe and effective use of diagnostic nuclear medicine imaging requires specific training, skills, and techniques, as described in each document. Reproduction or modification of the published practice guideline by entities not providing these services is not authorized.
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Rim/diagnóstico por imagem , Medicina Nuclear , Guias de Prática Clínica como Assunto , Cintilografia/métodos , Sociedades Científicas , Adulto , Humanos , Controle de Qualidade , Cintilografia/efeitos adversos , SegurançaAssuntos
Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Linfoma Difuso de Grandes Células B , Carga Tumoral , Adulto , Idoso , Idoso de 80 Anos ou mais , Anticorpos Monoclonais Murinos/administração & dosagem , Anticorpos Monoclonais Murinos/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Ciclofosfamida/administração & dosagem , Ciclofosfamida/efeitos adversos , Intervalo Livre de Doença , Doxorrubicina/administração & dosagem , Doxorrubicina/efeitos adversos , Feminino , Humanos , Linfoma Difuso de Grandes Células B/tratamento farmacológico , Linfoma Difuso de Grandes Células B/mortalidade , Linfoma Difuso de Grandes Células B/patologia , Masculino , Pessoa de Meia-Idade , Prednisona/administração & dosagem , Prednisona/efeitos adversos , Estudos Retrospectivos , Rituximab , Taxa de Sobrevida , Vincristina/administração & dosagem , Vincristina/efeitos adversosRESUMO
Fungi belonging to the genus Pseudogymnoascus have garnered increasing attention in recent years. One of the members of the genus, P. destructans, has been identified as the causal agent of a severe bat disease. Simultaneously, the knowledge of Pseudogymnoascus species has expanded, in parallel with the increased availability of genome sequences. Moreover, Pseudogymnoascus exhibits great potential as a producer of specialized metabolites, displaying a diverse array of biological activities. Despite these significant advancements, the genetic landscape of Pseudogymnoascus remains largely unexplored due to the scarcity of suitable molecular tools for genetic manipulation. In this study, we successfully implemented RNAi-mediated gene silencing and CRISPR/Cas9-mediated disruption in Pseudogymnoascus, using an Antarctic strain of Pseudogymnoascus verrucosus as a model. Both methods were applied to target azpA, a gene involved in red pigment biosynthesis. Silencing of the azpA gene to levels of 90% or higher eliminated red pigment production, resulting in transformants exhibiting a white phenotype. On the other hand, the CRISPR/Cas9 system led to a high percentage (73%) of transformants with a one-nucleotide insertion, thereby inactivating azpA and abolishing red pigment production, resulting in a white phenotype. The successful application of RNAi-mediated gene silencing and CRISPR/Cas9-mediated disruption represents a significant advancement in Pseudogymnoascus research, opening avenues for comprehensive functional genetic investigations within this underexplored fungal genus.
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Urinary tract infections (UTIs) are a common problem in childhood. During the last decade, published papers led to a deep revision in the use and usefulness of imaging tools in children with febrile UTIs. This new body of knowledge was partially endorsed by the guidelines published in 2007 by the UK's National Institute for Clinical Excellence and in 2011 by the American Academy of Pediatrics. Nevertheless, new data continuously arise and the scientific debate always revives. Recommendations of published guidelines and strengths and weaknesses of the available biochemical and imaging tools are here critically analysed for giving to the reader a complete, up-to-date and flexible overview on this hot topic.
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Febre/diagnóstico , Febre/etiologia , Aumento da Imagem/normas , Guias de Prática Clínica como Assunto , Infecções Urinárias/complicações , Infecções Urinárias/diagnóstico por imagem , Imagem Corporal Total/normas , Criança , Humanos , Internacionalidade , CintilografiaRESUMO
Penicillium rubens is a filamentous fungus of great biotechnological importance due to its role as an industrial producer of the antibiotic penicillin. However, despite its significance, our understanding of the regulatory mechanisms governing biological processes in this fungus is still limited. In fungi, zinc finger proteins containing a Zn(II)2Cys6 domain are particularly interesting regulators. Although the P. rubens genome harbors many genes encoding proteins with this domain, only two of them have been investigated thus far. In this study, we employed CRISPR-Cas9 technology to disrupt the pcz1 gene, which encodes a Zn(II)2Cys6 protein in P. rubens. The disruption of pcz1 resulted in a decrease in the production of penicillin in P. rubens. This decrease in penicillin production was accompanied by the downregulation of the expression of pcbAB, pcbC and penDE genes, which form the biosynthetic gene cluster responsible for penicillin production. Moreover, the disruption of pcz1 also impacts on asexual development, leading to decreased growth and conidiation, as well as enhanced conidial germination. Collectively, our results indicate that pcz1 acts as a positive regulator of penicillin production, growth, and conidiation, while functioning as a negative regulator of conidial germination in P. rubens. To the best of our knowledge, this is the first report involving a gene encoding a Zn(II)2Cys6 protein in the regulation of penicillin biosynthesis in P. rubens.
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Basal cell carcinoma (BCC) is the most common malignant tumor of the skin. Despite the indolent nature, metastatic BCC can occur, albeit rarely. Metastasis to the bone is very rare. From its approval, mBCC patients are treated with vismodegib, a selective hedgehog pathway inhibitor. Unfortunately, in recent period, it was demonstrated an emergence of drug resistance, due to Smoothened (SMO) mutation. To date, several groups are studying the effectiveness of immunotherapy in BCC. Clinical trials with Immune Checkpoint Inhibitors are ongoing. We report the rare case of a man with multiple bony metastasis, with a resistance to vismodegib, and we evaluated all manuscripts in literature reporting bone metastasis. Moreover, we review all the manuscripts in literature reporting bone metastasis, and we summarize the main therapeutic strategies, and the further perspectives.
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Fetal lower urinary tract obstruction (LUTO) is associated with high mortality and postnatal morbidity caused by lung hypoplasia and impaired kidney function. Specific diagnostic features that can guide clinical approach and decisions are lacking; thus, the European Reference Network for Rare Kidney Diseases established a work group to develop recommendations regarding the clinical definition, diagnosis and management of prenatally detected LUTO. The work group recommends the use of antero-posterior diameter of renal pelvis as the most reliable parameter for suspecting obstructive uropathies and for suspecting prenatal LUTO in the presence of fetal megacystis. Regarding prenatal and postnatal prognosis of fetuses with LUTO, the risk of fetal and neonatal death depends on the presence of oligohydramnios or anhydramnios before 20 weeks' gestation, whereas the risk of kidney replacement therapy cannot be reliably foreseen before birth. Parents of fetuses with LUTO must be referred to a tertiary obstetric centre with multidisciplinary expertise in prenatal and postnatal management of obstructive uropathies, and vesico-amniotic shunt placement should be offered in selected instances, as it increases perinatal survival of fetuses with LUTO.
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Oligo-Hidrâmnio , Doenças Uretrais , Obstrução Uretral , Consenso , Feminino , Humanos , Recém-Nascido , Masculino , Gravidez , Estudos Retrospectivos , Ultrassonografia Pré-Natal/efeitos adversos , Obstrução Uretral/diagnóstico , Obstrução Uretral/etiologia , Obstrução Uretral/terapia , Bexiga Urinária , Anormalidades Urogenitais , Refluxo VesicoureteralRESUMO
PURPOSE OF THE REPORT: This article aims to explore the prognostic role of 18F-FDG PET/CT metabolic parameters in stage I lung adenocarcinoma patients. PATIENTS AND METHODS: One hundred eighty pathological stage I lung adenocarcinoma patients were retrospectively reviewed. Semiquantitative analysis of FDG tumor uptake was performed with TrueD software on the Siemens Leonardo workstation. SUVmean and MTV were calculated using SUV threshold of 41% of SUVmax; the total lesion glycolysis (TLG) was calculated as the product of SUVmean and MTV. Correlation was evaluated using Spearman correlation coefficient. Maximally selected rank statistics was performed to detect the optimal cutoff used for dichotomizing each PET parameter (6.5 for SUVmean, 9.6 for SUVmax, and 19.1 for TLG). RESULTS: Our main finding was the significant correlation between 18F-FDG PET/CT parameters (SUVmean, SUVmax, and TLG) and disease-free survival in pathologic stage I non-small cell lung cancer. SUVmean has the greatest accuracy in recurrence prediction (integrated area under the curve, 0.803; 95% confidence interval, 0.689-0.918). We run the maximally selected rank statistics to provide the classification of observations in 2 groups by a continuous predictor parameter; the free from recurrence rate was significantly greater in patients with SUVmean ≤6.5, SUVmax ≤9.6, and TLG ≤19.1. CONCLUSIONS: Our research supports the hypothesis that SUVmean, SUVmax, and TLG are well correlated with free from recurrence rate in stage I adenocarcinoma patients, subjected to pulmonary lobectomy. Our findings also indicate these markers as promising prognostic indicators.
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Carcinoma Pulmonar de Células não Pequenas/diagnóstico por imagem , Carcinoma Pulmonar de Células não Pequenas/cirurgia , Fluordesoxiglucose F18 , Neoplasias Pulmonares/diagnóstico por imagem , Neoplasias Pulmonares/cirurgia , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma Pulmonar de Células não Pequenas/patologia , Intervalo Livre de Doença , Fluordesoxiglucose F18/metabolismo , Glicólise , Humanos , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Prognóstico , Estudos Retrospectivos , Carga TumoralRESUMO
The purpose of these guidelines is to offer nuclear medicine teams a framework that could prove helpful in daily practice. The guidelines include information related to the indications, acquisition, processing and interpretation of bone scans in children, focusing primarily on (99m)Tc-labelled diphosphonate scintigraphy, and also recommendations with regard to the emerging use of PET with (18)F-fluoride.
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Osso e Ossos/diagnóstico por imagem , Fluoretos , Radioisótopos de Flúor , Medicina Nuclear/métodos , Compostos de Organotecnécio , Compostos Radiofarmacêuticos , Criança , Fluoretos/administração & dosagem , Humanos , Processamento de Imagem Assistida por Computador , Injeções , Compostos de Organotecnécio/administração & dosagem , Tomografia por Emissão de Pósitrons , Controle de Qualidade , Doses de Radiação , Compostos Radiofarmacêuticos/administração & dosagem , Tomografia Computadorizada de Emissão de Fóton ÚnicoRESUMO
The optimal imaging strategy for febrile urinary tract infections in children is not yet satisfactorily defined, mainly because of the different clinical scenarios in which these acute illnesses are framed. This is overall true for radionuclide imaging, whose well-known advantages and weaknesses have a weight that can change according to the characteristic of the patients (age, sex, anatomical features, and clinical history). Cortical renal scan with 99mTc-dimercaptosuccinic acid, direct radionuclide cystography, and dynamic renal scan with MAG3 plus indirect radionuclide cystography should be ever taken into account whenever doubts arose during clinical evaluation, mainly looking for their right use in the right child at the right time, having the necessary flexibility in applying published guidelines, being aware of the debate still running about.
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Febre/complicações , Cintilografia/métodos , Infecções Urinárias/complicações , Infecções Urinárias/diagnóstico por imagem , Criança , HumanosRESUMO
BACKGROUND: Thyroglobulin (Tg) measurement following thyrotropin (TSH) stimulation is used in the follow-up of patients with differentiated thyroid carcinoma (DTC). However, high-sensitive assays allow accurate measurement of serum Tg even without TSH stimulation. Here, we prospectively evaluated the impact of unstimulated high-sensitive Tg measurement in early and long-term outcome of patients with DTC. METHODS: One hundred and ninety five patients affected with DTC were evaluated. Six months after thyroid ablation (i.e., thyroidectomy plus radioiodine) serum Tg was measured during TSH-suppressive thyroxine (T4) treatment (onT4-Tg). Patients with undetectable onT4-Tg and negative neck ultrasound (US) were considered disease free and onT4-Tg was measured every 12 months for a mean follow-up of 6.8 (4.7-8.9) years. Patients with an increase in onT4-Tg underwent specific diagnostic work-up and appropriate treatment if necessary. RESULTS: Four patients showed recurrence at first follow-up visit with a corresponding increase in onT4-Tg concentrations (sensitivity 100%). Three patients had false positive onT4-Tg measurement (specificity 98%) with a spontaneous decrease within 3-6 months in all cases (specificity 100%). Three of 188 patients with undetectable serum onT4-Tg at first follow-up showed recurrence later with an increase in onT4-Tg as the first (n=2) or unique (n=1) sign of relapse (sensitivity 100%). Among 185 disease-free patients in a prolonged follow-up, 12 had a transient increase in onT4-Tg (specificity 91.6%). However, a spontaneous reduction within 3-6 months occurred in all cases (specificity 100%). CONCLUSIONS: Undetectable serum onT4-Tg using a high-sensitivity immunoradiometric assay 6 months after thyroid ablation predicts low-risk of DTC recurrence. When onT4-Tg became detectable during follow-up, the evaluation of Tg slope in a 3-6 months period accurately discriminated patients with DTC recurrence from those without recurrence. This helped avoid unnecessary diagnostic or therapeutic procedures.