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BACKGROUND: Uveal melanoma (UM) is the eye's most common primary malignancy and there are no effective therapies for disseminated disease. It is important to try to know the patient's prognosis. The aim of this study was to reflect genetic variants, studied using NGS, of a series of 69 cases of UM and its correlation with histopathology and clinical progression. METHODS: We performed targeted NGS using a 519-gene panel. RESULTS: There were selected 28 different mutated genes, showing a total of 231 genetic variants that affected the function of the protein. The most common secondary mutations occurred in SF3B1 (in 26%), followed by BAP1 (in 23%), LRP1B (22%) and FGFR4 (20%). BAP1 mutation was associated with a greater likelihood of metastases and with greater presence of epithelioid cells. LRP1B was also associated with presence of epithelioid cells SF3B1 mutation was significantly associated with a spindle morphology. We found variants in the RAD51B, TOP2A, PTPRD, TSC2, DHX9, PDK1 and MTOR that have not been previously reported in consulted databases. The presence of a mutation in: CHEK2, DHX9 and PDK1 was associated with metastases. CONCLUSIONS: BAP1 is the most solid biomarker of a poor prognosis in UM and mutations can be detected using NGS. SF3B1 is associated with the spindle cell subtype of UM, which gives it probably a favourable prognostic value. Our study suggests that mutations in DHX9 and PDK1 can have prognostic value. These potential biomarkers are related to the PI3K/AKT/mTOR pathway and makes them candidates for developing new directed therapies.
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Fosfatidilinositol 3-Quinasas , Neoplasias de la Úvea , Humanos , Fosfatidilinositol 3-Quinasas/genética , Proteínas Proto-Oncogénicas c-akt/genética , Pronóstico , Proteínas Supresoras de Tumor/genética , Análisis Mutacional de ADN , Mutación , Neoplasias de la Úvea/genética , Secuenciación de Nucleótidos de Alto RendimientoRESUMEN
One of the most common food allergies in children is cow's milk allergy (CMA). In breast-fed infants with CMA, the mother is encouraged to avoid dairy products. If this is not possible, or in formula fed infants, use of hypoallergenic replacement formulas such as extensively hydrolyzed formulas (EHF) is recommended. However, in â¼5% of patients EHFs are not tolerated and/or allergy symptoms can persist. When EHFs are ineffective and in severe forms of CMA, amino acid-based formulas (AAF) should be considered. Six pediatric gastroenterologists with extensive experience in food allergy management reviewed scientific publications and international clinical practice guidelines to provide practical recommendations on AAF. The guidelines reviewed had discrepancies and ambiguities around the specific indications for using formulas as a milk substitute. The panel recommends AAFs as the first therapeutic option in anaphylaxis due to CMA, in acute and chronic severe food protein-induced enterocolitis syndrome, in CMA associated with multiple food allergy, and in cases of eosinophilic esophagitis not responding to an extended exclusion diet or not eating solids. The main benefit of AAF is its absence of residual allergenicity, making it a safe treatment option in severe CMA patients who do not tolerate or respond to an EHF.
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Introduction: The COVID-19 pandemic forced a change in the working dynamics of all healthcare professionals, leading to the sudden introduction of telemedicine. Although until that moment telemedicine applications had been described in the paediatric age, their use was anecdotal. Objective: To analyse the experience of Spanish paediatricians after the forced digitization of consultations due to the pandemic. Methods: A cross-sectional survey-type study was designed to obtain information from Spanish paediatricians about the changes that took place in the usual clinical practice. Results: 306 health professionals participated in the study Most of them agreed on the use of the internet and social networks during the pandemic, referring to mail or WhatsApp® as usual channels of communication with their patients' families. There was a great agreement among paediatricians that the evaluation of newborns after hospital discharge and establishing methodologies that allow childhood vaccination and the identification of subsidiary patients for face-to-face evaluation were necessary although the limitations of the lockdown. The idea that telephone and digital consultations have optimized the consultation time and that they will probably continue after the end of the pandemic was generally accepted. No changes in adherence to breastfeeding or the start of complementary feeding were referred to, but an increase in the duration of breastfeeding and the appearance of frequent hoaxes in social networks concerning infant feeding were found. Conclusions: It is necessary to analyse the impact of telemedicine in paediatric consultations during the pandemic to evaluate its effectiveness and quality to maintain it in routine paediatric practice.
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BRCA1-associated protein 1 (BAP1)-inactivated melanomas can occur sporadically or in germline contexts, particularly in recently recognized BAP1-tumor predisposition syndrome. Diagnosis represents a clinical and histopathological challenge, requiring comprehensive analysis of morphology and sometimes molecular analysis in addition to immunohistochemistry. We report a BAP1-inactivated cutaneous melanoma initially diagnosed as an atypical Spitz tumor on the auricle in a patient with BAP1-tumor predisposition syndrome. Immunohistochemistry, fluorescence in situ hybridization, and comparative genomic hybridization allowed diagnosis. Cutaneous BAP1-inactivated melanocytic tumors, previously classified as atypical Spitz Nevi, may have a dermal mitotic activity that can resemble melanoma and on the other hand, atypical Spitz tumors are sometimes difficult to differentiate from BAP1-inactivated melanoma. Specific criteria, requiring molecular diagnosis have been proposed in order to support melanoma diagnosis.
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Melanoma , Síndromes Neoplásicos Hereditarios , Nevo Pigmentado , Neoplasias Cutáneas , Humanos , Melanoma/diagnóstico , Melanoma/genética , Melanoma/metabolismo , Neoplasias Cutáneas/diagnóstico , Neoplasias Cutáneas/genética , Neoplasias Cutáneas/metabolismo , Hibridación Genómica Comparativa , Hibridación Fluorescente in Situ , Nevo Pigmentado/patología , Proteínas Supresoras de Tumor/genética , Ubiquitina Tiolesterasa/genética , Melanoma Cutáneo MalignoRESUMEN
INTRODUCTION: Purple Urine Bag Syndrome (PUBS) is a rare disorder seen in elderly persons, wherein the urinary bag and the tubing turn in to purple colour. It is usually seen in patients who are on urinary catheters for a long time. It consists of a change in the colour of the urine that turns purple in a very specific context. CASE REPORT: We report the case of a paediatric female patient with Berdon Syndrome with symptoms consistent with urinary tract infection and purple urine discolouration. Urine test revealed leukocyturia and bacteriuria. DISCUSSION: Several risk factors have been proposed regarding this syndrome. Among them the commonest are female gender, advanced age, kind of diet (increased dietary tryptophan), alkaline urine and diverse situations that leads to urinary retentions which allows bacteria to work on their substrate for a longer time. Although it is a process that is not associated with gravity, recognizing it is important as treatment is simple and can minimize patient and family distress.
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Seudoobstrucción Intestinal , Infecciones Urinarias , Humanos , Femenino , Niño , Anciano , Masculino , Infecciones Urinarias/diagnóstico , Infecciones Urinarias/microbiología , TriptófanoRESUMEN
Numerous cells with very large and irregular nuclei ("monster" cells) have not hitherto been reported in desmoplastic melanoma (DM). Their prognostic significance in melanomas is a matter of debate, although some authors have associated them with more aggressive tumor behavior. We report a mixed DM on the scalp of an 88-year-old woman imitating an atypical fibroxanthoma. Tumor cells stained positive for SOX10, S100, and cyclin D1; BRAF mutation status was negative, and fluorescence in situ hybridization analysis showed copy number gains in 11q13 (cyclin D1) and 6p25 (RREB1), and loss in 6q23 (MYB). Cyclin D1 amplification is associated with poor prognosis in melanoma.
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Melanoma , Neoplasias Cutáneas , Anciano de 80 o más Años , Ciclina D1/genética , Femenino , Humanos , Hibridación Fluorescente in Situ , Melanoma/patología , Cuero Cabelludo/patología , Neoplasias Cutáneas/patologíaRESUMEN
ABSTRACT: The malignant counterpart of cutaneous clear cell hidradenoma (CCH), hidradenocarcinoma, is an aggressive neoplasm that may have a fatal outcome. However, some cases of benign looking CCH with isolated lymph node involvement and excellent prognosis have been described. "CCH-like neoplasm of uncertain malignant potential" or "atypical hidradenoma" have been proposed as designations for these lesions. We report 3 cases of CCH with lymph node involvement. Ages ranged from 29 to 51 years old. All cases involved the inguinal lymph nodes: 2 of them presented with an isolated lymph node lesion, and the third case had lymph node and cutaneous involvement following the resection of a previous cutaneous lesion. Imaging studies showed no systemic involvement. None of the lesions exhibited histopathologic features of malignancy. All neoplasms were well circumscribed, had cystic spaces, did not display atypia or necrosis, and had less than 4 mitoses per high power field. No recurrence has been observed at follow-up after resection in all cases. All published cases of CCH with lymph node involvement so far affected a single lymph node in the axillary or inguinal regions, lacked features of malignancy, and had excellent long-term prognosis. Some cases previously reported as hidradenocarcinoma probably fit into this category. Our series adds more evidence to this rare phenomenon of "benign metastasis." Aggressive treatment should be avoided in these cases, and a long-term follow-up is warranted.
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Acrospiroma/patología , Metástasis Linfática/patología , Neoplasias de las Glándulas Sudoríparas/patología , Adulto , Humanos , Masculino , Persona de Mediana EdadRESUMEN
Multicenter study conducted in 15 hospitals including 101 COVID-19 pediatric inpatients aiming to describe associated gastrointestinal (GI) manifestations. GI symptoms were present in 57% and were the first manifestation in 14%. Adjusted by confounding factors, those with GI symptoms had higher risk of pediatric intensive care unit admission. GI symptoms are predictive of severity in COVID-19 children admitted to hospitals.
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COVID-19/complicaciones , COVID-19/epidemiología , Enfermedades Gastrointestinales/epidemiología , Enfermedades Gastrointestinales/etiología , Cuidado Intensivo Neonatal , Admisión del Paciente , COVID-19/virología , Niño , Preescolar , Comorbilidad , Femenino , Humanos , Lactante , Unidades de Cuidado Intensivo Pediátrico , Cuidado Intensivo Neonatal/métodos , Cuidado Intensivo Neonatal/estadística & datos numéricos , Masculino , España/epidemiologíaRESUMEN
AIM: to evaluate validity and concordance of Screening Tool for the Assessment of Malnutrition in Pediatrics (STAMP) and Screening Tool for Risk On Nutritional status and Growth (STRONGkids) screening tools for assessment of nutritional risk in pediatric inpatients. METHODS: Prospective longitudinal observational multicenter study in children aged 1 month or older admitted as inpatients. Weight, height, cause of admission, demographic data, length of stay, and nutritional interventions were recorded. STAMP and STRONGkids were applied within the first 72 h of admission. Anthropometric measurements were recorded again 12-18 months after admission. RESULTS: Eighty-one patients with median age of 4.1 years completed the study. Agreement between tools was moderate (κ = 0.47). STAMP had a greater tendency to classify patients as high risk (12.3% vs. 2.5%). Both tools showed very weak correlation with height for age. All undernourished patients at the beginning and the end of the study were classified as medium or high risk by STAMP and STRONGkids (100% sensitivity), although specificity was below 50% in all cases. There were no differences in length of stay based on nutritional risk with any of the tools. CONCLUSIONS: STAMP and STRONGkids demonstrated moderate agreement, with high sensitivity but low specificity for the diagnosis of undernutrition. Further studies are required to analyze cost-effectiveness of these tools and nutritional interventions derived from them.
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Fenómenos Fisiológicos Nutricionales Infantiles , Niño Hospitalizado , Programas de Detección Diagnóstica , Desnutrición/diagnóstico , Evaluación Nutricional , Estado Nutricional , Factores de Edad , Niño , Preescolar , Análisis Costo-Beneficio , Femenino , Humanos , Lactante , Estudios Longitudinales , Masculino , Estudios Prospectivos , Factores de TiempoAsunto(s)
Dermis/patología , Fibrosarcoma/diagnóstico , Neoplasias de los Tejidos Blandos/patología , Anciano , Ciclina D1/metabolismo , Diagnóstico Diferencial , Femenino , Fibrosarcoma/metabolismo , Fibrosarcoma/patología , Fibrosarcoma/cirugía , Estudios de Seguimiento , Antebrazo/patología , Histiocitoma Fibroso Benigno/diagnóstico , Histiocitoma Fibroso Benigno/cirugía , Humanos , PronósticoRESUMEN
OBJECTIVE: To assess the impact of dissected artery occlusion (DAO) on functional outcome and complications in patients with cervical artery dissection (CeAD). METHODS: We analyzed combined individual patient data from 3 multicenter cohorts of consecutive patients with CeAD (the Cervical Artery Dissection and Ischemic Stroke Patients [CADISP]-Plus consortium dataset). Patients with data on DAO and functional outcome were included. We compared patients with DAO to those without DAO. Primary outcome was favorable functional outcome (i.e., modified Rankin Scale [mRS] score 0-1) measured 3-6 months from baseline. Secondary outcomes included delayed cerebral ischemia, major hemorrhage, recurrent CeAD, and death. We performed univariate and multivariable binary logistic regression analyses and calculated odds ratios (OR) with 95% confidence intervals (CI), with adjustment for potential confounders. RESULTS: Of 2,148 patients (median age 45 years [interquartile range (IQR) 38-52], 43.6% women), 728 (33.9%) had DAO. Patients with DAO more frequently presented with cerebral ischemia (84.6% vs 58.5%, p < 0.001). Patients with DAO were less likely to have favorable outcome when compared to patients without DAO (mRS 0-1: 59.6% vs 80.1%, p unadjusted < 0.001). After adjustment for age, sex, and initial stroke severity, DAO was independently associated with less favorable outcome (mRS 0-1: OR 0.65, CI 0.50-0.84, p = 0.001). Delayed cerebral ischemia occurred more frequently in patients with DAO than in patients without DAO (4.5% vs 2.9%, p = 0.059). CONCLUSION: DAO independently predicts less favorable functional outcome in patients with CeAD. Further research on vessel patency, collateral status and effects of revascularization therapies particularly in patients with DAO is warranted.
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Disección Aórtica/patología , Enfermedades Arteriales Cerebrales/patología , Trastornos Cerebrovasculares/patología , Recuperación de la Función , Adulto , Anciano , Femenino , Humanos , Masculino , Persona de Mediana EdadRESUMEN
Resumen Objetivo: Describir los hallazgos en resonancia magnética (RM) de encéfalo en pacientes menores de 65 años que fueron estudiados por Doppler transcraneal (DTC) con contraste de microburbujas, con antecedentes de accidente cerebrovascular (ACV) criptogénico y sospecha de foramen oval permeable (FOP). Materiales y métodos: Este estudio transversal retrospectivo incluyó pacientes de ambos sexos, menores de 65 años. Resultados: Nuestra muestra (n = 47, 47% masculino y 53% femenino, edad media de 42 años) presentó señales transitorias de alta intensidad (HITS, por su sigla en inglés) positivo en el 61,7% y HITS-negativo en el 38,3%. En pacientes HITS-positivo, predominaron las lesiones a nivel de las fibras en U subcorticales, únicas o múltiples con distribución bilateralmente simétrica. En pacientes con HITS moderados, predominaron las lesiones en el territorio vascular de la circulación posterior. Conclusión: En pacientes menores de 65 años con ACV criptogénico y lesiones en fibras en U subcorticales, únicas o múltiples con distribución bilateral y simétrica, debe tenerse en cuenta un FOP como posible causa de dichas lesiones.
Abstract Objectives: To analyze the findings on brain magnetic resonance imaging (MRI) in patients less than 65 years of age with history of cryptogenic stroke and suspected patent foramen ovale (PFO) who were studied with Contrast-Transcranial Doppler. Materials and Methods: This transversal retrospective study included both, men and women less than 65 years of age. Results: Our sample (n = 47, 47% male and 53% female, average age 42 years old) had High Intensity Transient Signals (HITS)-positive in 61.7% and HITS-negative in 38.3%. In HITS-positive patients, lesions were predominantly located on the subcortical U fibers, lone or multiple bilateral symmetric distributions. In patients with moderate-severity HITS, the posterior circulation was the most affected. Conclusion: In patients less than 65 years of age with cryptogenic stroke with lesions affecting the subcortical U fibers, with unique or multiple bilateral symmetric distributions, a PFO should be considered as an underlying cause.
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Humanos , Masculino , Femenino , Persona de Mediana Edad , Encéfalo , Lesiones Encefálicas , Lesiones Encefálicas/diagnóstico por imagen , Espectroscopía de Resonancia Magnética , Heridas y Lesiones , Imagen por Resonancia Magnética , Causalidad , Estudios Retrospectivos , Ultrasonografía Doppler Transcraneal/métodos , Accidente Cerebrovascular , Foramen Oval PermeableRESUMEN
Non-IgE-mediated cow's milk allergy is a frequent disorder in paediatrics. As patients might be seen by professionals from different specialties and levels of expertise, a great variability in diagnostic procedures and disease monitoring is commonly observed. Therefore, four scientific societies involved in its management have developed a consensus document providing specific recommendations related to its prevention, diagnosis, treatment and follow up.
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Hipersensibilidad a la Leche/terapia , Proteínas de la Leche/inmunología , Pediatría , Niño , Humanos , Hipersensibilidad a la Leche/diagnóstico , Hipersensibilidad a la Leche/prevención & control , EspañaRESUMEN
Background and Purpose- We sought to explore the effect of genetic imbalance on functional outcome after ischemic stroke (IS). Methods- Copy number variation was identified in high-density single-nucleotide polymorphism microarray data of IS patients from the CADISP (Cervical Artery Dissection and Ischemic Stroke Patients) and SiGN (Stroke Genetics Network)/GISCOME (Genetics of Ischaemic Stroke Functional Outcome) networks. Genetic imbalance, defined as total number of protein-coding genes affected by copy number variations in an individual, was compared between patients with favorable (modified Rankin Scale score of 0-2) and unfavorable (modified Rankin Scale score of ≥3) outcome after 3 months. Subgroup analyses were confined to patients with imbalance affecting ohnologs-a class of dose-sensitive genes, or to those with imbalance not affecting ohnologs. The association of imbalance with outcome was analyzed by logistic regression analysis, adjusted for age, sex, stroke subtype, stroke severity, and ancestry. Results- The study sample comprised 816 CADISP patients (age 44.2±10.3 years) and 2498 SiGN/GISCOME patients (age 67.7±14.2 years). Outcome was unfavorable in 122 CADISP and 889 SiGN/GISCOME patients. Multivariate logistic regression analysis revealed that increased genetic imbalance was associated with less favorable outcome in both samples (CADISP: P=0.0007; odds ratio=0.89; 95% CI, 0.82-0.95 and SiGN/GISCOME: P=0.0036; odds ratio=0.94; 95% CI, 0.91-0.98). The association was independent of age, sex, stroke severity on admission, stroke subtype, and ancestry. On subgroup analysis, imbalance affecting ohnologs was associated with outcome (CADISP: odds ratio=0.88; 95% CI, 0.80-0.95 and SiGN/GISCOME: odds ratio=0.93; 95% CI, 0.89-0.98) whereas imbalance without ohnologs lacked such an association. Conclusions- Increased genetic imbalance was associated with poorer functional outcome after IS in both study populations. Subgroup analysis revealed that this association was driven by presence of ohnologs in the respective copy number variations, suggesting a causal role of the deleterious effects of genetic imbalance.
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Isquemia Encefálica/genética , Dosificación de Gen , Adulto , Anciano , Isquemia Encefálica/rehabilitación , Cromosomas Humanos/genética , Estudios de Seguimiento , Duplicación de Gen , Genotipo , Humanos , Persona de Mediana Edad , Polimorfismo de Nucleótido Simple , Recuperación de la Función , Índice de Severidad de la EnfermedadRESUMEN
OBJECTIVE: Acute interstitial pneumonia (AIP) is a severe disease of unknown etiology. Pneumocystis jirovecii is an atypical opportunistic fungus able to colonize patients with chronic pulmonary disease and inducing alveolar macrophage activation. The aim of this study was to evaluate the possible association between Pneumocystis jirovecii and AIP. SUBJECTS AND METHODS: The presence of P. jirovecii in bronchoalveolar lavage fluid in the four confirmed cases of AIP identified in a tertiary-care hospital over a period of nine years was studied using a 2-step nested-PCR protocol assay. RESULTS: P. jirovecii was identified in the four cases. None of them had HIV infection. Two of the patients were treated empirically with trimethoprim-sulfamethoxazole, the only survivor was being one of them. CONCLUSIONS: Our data suggest that Pneumocystis could trigger or favor the development of AIP. Further studies are needed to evaluate the role of the pathogen in the physiopathology of this disease.
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Angiosarcoma (AS) is a malignant mesenchymal neoplasm of endothelial origin with a predominantly lymphatic immunophenotype, which accounts for less than 1% of all sarcomas. Cutaneous AS of the scalp is associated with high rates of local recurrence and a poor prognosis. Histologically, poorly differentiated AS often comprises solid epithelioid cells, although rare variants involving spindle cells have been reported; diagnosis requires immunohistochemical analysis using vascular cell markers. We report on a cutaneous spindle-cell AS of the scalp in a female patient; key features included spontaneous regression after biopsy, local recurrence 2 years later, and aberrant nuclear staining for S100 protein in an area of the tumor not expressing CD34 or D2-40. Tumor cells exhibited positivity for vascular markers CD31, CD34, D2-40, ERG and FLI-1 and were negative for myoid markers (αSMA and desmin), epithelial (EMA and cytokeratin AE1/AE3) and melanocyte markers (HMB45 and melan-A). Cutaneous spindle-cell AS of the scalp is a rare variant with a poor prognosis. Diagnosis of spindle-cell AS was confirmed by immunohistochemical analysis using CD31, CD34, ERG, FLI-1, podoplanin (D2-40), and claudin-5. Although a number of authors have noted aberrant expression of cytokeratins, CD30, CD117 and neuroendocrine markers (synaptophysin and chromogranin A) in AS, intense positive nuclear staining for S100 protein in neoplastic cells has not hitherto been observed. This article reports on a spindle-cell AS of the scalp notable for aberrant expression of S100, spontaneous regression and recurrence 2 years later at the same site and displaying identical histological and immunohistochemical features.
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Hemangiosarcoma/patología , Regresión Neoplásica Espontánea/patología , Proteínas S100/biosíntesis , Cuero Cabelludo/patología , Neoplasias Cutáneas/patología , Anciano de 80 o más Años , Biomarcadores de Tumor/análisis , Femenino , Humanos , Recurrencia Local de Neoplasia/patología , Proteínas S100/análisisRESUMEN
OBJECTIVE: In a cohort of patients diagnosed with cervical artery dissection (CeAD), to determine the proportion of patients aged ≥60 years and compare the frequency of characteristics (presenting symptoms, risk factors, and outcome) in patients aged <60 vs ≥60 years. METHODS: We combined data from 3 large cohorts of consecutive patients diagnosed with CeAD (i.e., Cervical Artery Dissection and Ischemic Stroke Patients-Plus consortium). We dichotomized cases into 2 groups, age ≥60 and <60 years, and compared clinical characteristics, risk factors, vascular features, and 3-month outcome between the groups. First, we performed a combined analysis of pooled individual patient data. Secondary analyses were done within each cohort and across cohorts. Crude and adjusted odds ratios (OR [95% confidence interval]) were calculated. RESULTS: Among 2,391 patients diagnosed with CeAD, we identified 177 patients (7.4%) aged ≥60 years. In this age group, cervical pain (ORadjusted 0.47 [0.33-0.66]), headache (ORadjusted 0.58 [0.42-0.79]), mechanical trigger events (ORadjusted 0.53 [0.36-0.77]), and migraine (ORadjusted 0.58 [0.39-0.85]) were less frequent than in younger patients. In turn, hypercholesterolemia (ORadjusted 1.52 [1.1-2.10]) and hypertension (ORadjusted 3.08 [2.25-4.22]) were more frequent in older patients. Key differences between age groups were confirmed in secondary analyses. In multivariable, adjusted analyses, favorable outcome (i.e., modified Rankin Scale score 0-2) was less frequent in the older age group (ORadjusted 0.45 [0.25, 0.83]). CONCLUSION: In our study population of patients diagnosed with CeAD, 1 in 14 was aged ≥60 years. In these patients, pain and mechanical triggers might be missing, rendering the diagnosis more challenging and increasing the risk of missed CeAD diagnosis in older patients.