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1.
Medicina (Kaunas) ; 57(2)2021 Jan 28.
Artigo em Inglês | MEDLINE | ID: mdl-33525390

RESUMO

Uncertainty analysis is the process of identifying limitations in knowledge and evaluating their implications for scientific conclusions. Uncertainty analysis is a stable component of risk assessment and is increasingly used in decision making on complex health issues. Uncertainties should be identified in a structured way and prioritized according to their likely impact on the outcome of scientific conclusions. Uncertainty is inherent to the rare diseases (RD) area, where research and healthcare have to cope with knowledge gaps due to the rarity of the conditions; yet a systematic approach toward uncertainties is not usually undertaken. The uncertainty issue is particularly relevant to multifactorial RD, whose etiopathogenesis involves environmental factors and genetic predisposition. Three case studies are presented: the newly recognized acute multisystem inflammatory syndrome in children and adolescents associated with SARS-CoV-2 infection; the assessment of risk factors for neural tube defects; and the genotype-phenotype correlation in familial Mediterranean fever. Each case study proposes the initial identification of the main epistemic and sampling uncertainties and their impacts. Uncertainty analysis in RD may present aspects similar to those encountered when conducting risk assessment in data-poor scenarios; therefore, approaches such as expert knowledge elicitation may be considered. The RD community has a main strength in managing uncertainty, as it proactively develops stakeholder involvement, data sharing and open science. The open science approaches can be profitably integrated by structured uncertainty analysis, especially when dealing with multifactorial RD involving environmental and genetic risk factors.


Assuntos
/epidemiologia , Febre Familiar do Mediterrâneo/epidemiologia , Defeitos do Tubo Neural/epidemiologia , Doenças Raras/epidemiologia , Síndrome de Resposta Inflamatória Sistêmica/epidemiologia , Incerteza , Causalidade , Febre Familiar do Mediterrâneo/genética , Genótipo , Humanos , Conhecimento , Fenótipo , Doenças Raras/etiologia , Medição de Risco , Fatores de Risco
2.
Ann R Coll Surg Engl ; 103(2): e50-e52, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33559554

RESUMO

Appendix-associated hernias are extremely rare. They have been described sporadically in the literature, mostly as inguinal hernias. Appendix-associated incisional hernias are even more unusual. High clinical awareness is needed as complications can arise if misdiagnosis or delay occurs. We present an 80-year-old man with acute appendicitis in an incisional hernia. After successful surgery, the patient made a full recovery.


Assuntos
Apendicectomia , Apendicite/diagnóstico , Herniorrafia/efeitos adversos , Hérnia Incisional/diagnóstico , Doenças Raras/diagnóstico , Dor Abdominal/etiologia , Parede Abdominal/cirurgia , Idoso de 80 Anos ou mais , Apendicite/etiologia , Apendicite/cirurgia , Apêndice/diagnóstico por imagem , Apêndice/cirurgia , Hérnia Inguinal/cirurgia , Humanos , Hérnia Incisional/etiologia , Hérnia Incisional/cirurgia , Masculino , Náusea/etiologia , Doenças Raras/etiologia , Doenças Raras/cirurgia , Tomografia Computadorizada por Raios X , Resultado do Tratamento , Vômito/etiologia
4.
Eur J Epidemiol ; 35(10): 937-948, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32681390

RESUMO

Rare cancers together constitute one fourth of cancers. As some rare cancers are caused by occupational exposures, a systematic search for further associations might contribute to future prevention. We undertook a European, multi-center case-control study of occupational risks for cancers of small intestine, bone sarcoma, uveal melanoma, mycosis fungoides, thymus, male biliary tract and breast. Incident cases aged 35-69 years and sex-and age-matched population/colon cancer controls were interviewed, including a complete list of jobs. Associations between occupational exposure and cancer were assessed with unconditional logistic regression controlled for sex, age, country, and known confounders, and reported as odds ratios (OR) with 95% confidence intervals (CI). Interviewed were 1053 cases, 2062 population, and 1084 colon cancer controls. Male biliary tract cancer was associated with exposure to oils with polychlorinated biphenyls; OR 2.8 (95% CI 1.3-5.9); male breast cancer with exposure to trichloroethylene; OR 1.9 (95% CI 1.1-3.3); bone sarcoma with job as a carpenter/joiner; OR 4.3 (95% CI 1.7-10.5); and uveal melanoma with job as a welder/sheet metal worker; OR 1.95 (95% CI 1.08-3.52); and cook; OR 2.4 (95% CI 1.4-4.3). A confirmatory study of printers enhanced suspicion of 1,2-dichloropropane as a risk for biliary tract cancer. Results contributed to evidence for classification of welding and 1,2-dichloropronane as human carcinogens. However, despite efforts across nine countries, for some cancer sites only about 100 cases were interviewed. The Rare Cancer Study illustrated both the strengths and limitations of explorative studies for identification of etiological leads.


Assuntos
Neoplasias/etiologia , Doenças Profissionais/etiologia , Exposição Ocupacional/efeitos adversos , Doenças Raras/etiologia , Adulto , Idoso , Estudos de Casos e Controles , Europa (Continente)/epidemiologia , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Neoplasias/epidemiologia , Doenças Profissionais/epidemiologia , Doenças Raras/epidemiologia , Fatores de Risco
5.
Hum Genet ; 139(6-7): 769-776, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32405658

RESUMO

Over the last decade next generation sequencing (NGS) has been extensively used to identify new pathogenic mutations and genes causing rare genetic diseases. The efficient analyses of NGS data is not trivial and requires a technically and biologically rigorous pipeline that addresses data quality control, accurate variant filtration to minimize false positives and false negatives, and prioritization of the remaining genes based on disease genomics and physiological knowledge. This review provides a pipeline including all these steps, describes popular software for each step of the analysis, and proposes a general framework for the identification of causal mutations and genes in individual patients of rare genetic diseases.


Assuntos
Biologia Computacional/métodos , Genes/genética , Doenças Genéticas Inatas/etiologia , Genoma Humano , Mutação , Medicina de Precisão , Doenças Raras/etiologia , Doenças Genéticas Inatas/patologia , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Doenças Raras/patologia , Software
6.
G Chir ; 41(1): 99-102, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32038019

RESUMO

Most diaphragmatic ruptures are due to the traumatic or penetrating injury, while the spontaneous diaphragmatic rupture is considered uncommon. The spontaneous transdiaphragmatic hernia is a consequence of violent coughing, vomiting that increase the thoracoabdominal pressure causing the diaphragmatic rupture. Even rarer is the concomitant prolapse of abdominal viscera into the thoracic subcutis through the chest wall, a condition known as spontaneous transdiaphragmatic intercostal hernia. Herein, we present a rare case of spontaneous transdiaphragmatic intercostal hernia presenting as a thoracoabdominal emergency.


Assuntos
Diafragma/lesões , Hérnia Diafragmática/etiologia , Doenças Raras/etiologia , Parede Torácica/lesões , Prolapso Visceral/etiologia , Tosse/complicações , Humanos , Ruptura Espontânea , Vômito/complicações
7.
Cir Cir ; 88(1): 95-99, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31967610

RESUMO

Bouveret´s syndrome refers to the condition of gastric outlet obstruction caused by the impaction of a large gallstone into the duodenum after passage through a cholecystoduodenal fistula. Many endoscopic and surgical techniques have been described in the management of this syndrome, however the morbidity and mortality are still very high. We present the case of a 67-year-old female patient with Bouveret´s syndrome, with successful resolution with surgical treatment after two failed endoscopic treatments.


Assuntos
Obstrução Duodenal/complicações , Cálculos Biliares/complicações , Obstrução da Saída Gástrica/etiologia , Doenças Raras/etiologia , Idoso , Fístula Biliar/complicações , Obstrução Duodenal/cirurgia , Feminino , Cálculos Biliares/cirurgia , Obstrução da Saída Gástrica/cirurgia , Humanos , Fístula Intestinal/complicações , Doenças Raras/cirurgia , Síndrome
8.
J Pediatr Endocrinol Metab ; 33(1): 165-170, 2020 Jan 28.
Artigo em Inglês | MEDLINE | ID: mdl-31821167

RESUMO

Background Coenzyme Q10 (CoQ10) serves as a shuttle for electrons from complexes I and II to complex III in the respiratory chain, and has important functions within the mitochondria. Primary CoQ10 deficiency is a mitochondrial disorder which has devastating effects, and which may be partially treated with exogenous CoQ10 supplementation. Case presentation A 9-month-old girl patient was referred to our clinic due to growth retardation, microcephaly and seizures. She was the third child of consanguineous parents (first-degree cousins) of Pakistani origin, born at 38 weeks gestation, weighing 2000 g after an uncomplicated pregnancy, and was hospitalized for 3 days due to respiratory distress. She had sustained clonic seizures when she was 4 months old. Physical examination showed microcephaly, truncal hypotonia and dysmorphic features. Metabolic tests were inconclusive. Abdominal ultrasonography revealed cystic appearance of the kidneys. Non-compaction of the left ventricle was detected in echocardiography. Cranial magnetic resonance imaging (MRI) showed hypoplasia of the cerebellar vermis and brain stem, corpus callosum agenesis, and cortical atrophy. A panel testing of 450 genes involved in inborn errors of metabolism (IEM) was performed that showed a novel frameshift c.384delG (Gly129Valfs*17) homozygous mutation in COQ9. A treatment of 5 mg/kg/day exogenous CoQ10 was started when she was 10 months old, and the dosage was increased to 50 mg/kg/day after the exact diagnosis. No objective neurological improvement could be observed after the adjustment of the drug dosage. Conclusions We report a case of CoQ10 deficiency due to a novel COQ9 gene mutation that adds clinical data from a newly diagnosed patient. Our case also outlines the importance of genetic panels used for specific diseases including IEM.


Assuntos
Ataxia/etiologia , Mitocôndrias/patologia , Doenças Mitocondriais/etiologia , Debilidade Muscular/etiologia , Mutação , Doenças Raras/etiologia , Ubiquinona/deficiência , Ataxia/patologia , Feminino , Humanos , Lactente , Mitocôndrias/genética , Doenças Mitocondriais/patologia , Debilidade Muscular/patologia , Prognóstico , Doenças Raras/patologia , Ubiquinona/genética
9.
J Dermatol ; 47(2): 166-168, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31793058

RESUMO

Hematidrosis is a rare disorder involving spontaneous excretion of sweat contaminated by blood cells. We report the case of a 6-year-old girl with hematidrosis from her palms with no underlying disease or psychotic disorder. Before the onset of this symptom, the patient was given an indoor horizontal exercise bar with which she had been frequently playing. This symptom appeared without apparent triggers and was not associated with subjective symptoms. To examine her hematidrosis, metabolites in the red bodily fluid were analyzed using nuclear magnetic resonance analysis. We found the fluid had a metabolome profile similar to that of eccrine sweat. Pathological analysis revealed no abnormal findings, including expression of the tight junction protein claudin 3. Her symptom decreased after treatment with tap-water iontophoresis. Here, we describe our case and discuss its etiology by reviewing previous reports.


Assuntos
Hemorragia/diagnóstico , Hiperidrose/diagnóstico , Iontoforese/métodos , Doenças Raras/diagnóstico , Suor/química , Suor/citologia , Biópsia , Criança , Feminino , Mãos/patologia , Hemorragia/etiologia , Humanos , Hiperidrose/etiologia , Doenças Raras/etiologia , Pele/patologia , Água/administração & dosagem
10.
Clin. biomed. res ; 40(1): 54-57, 2020.
Artigo em Inglês | LILACS | ID: biblio-1117413

RESUMO

We report the case of a 37-year-old woman investigated for left flank pain 1 year after bariatric surgery (Roux-en-Y gastric bypass). Abdominal computed tomography (CT) revealed a solid intra-abdominal lesion measuring 9.3 × 9.4 × 10.4 cm, compressing adjacent structures with no signs of invasion. Ileocolectomy with partial mesenteric resection was performed. A histopathological and immunohistochemical analysis confirmed the diagnosis of mesenteric desmoid tumor.(AU)


Assuntos
Humanos , Feminino , Adulto , Derivação Gástrica/efeitos adversos , Fibromatose Agressiva/etiologia , Mesentério , Neoplasias Abdominais/etiologia , Neoplasias Peritoneais/diagnóstico , Fibromatose Agressiva/diagnóstico , Doenças Raras/diagnóstico , Doenças Raras/etiologia
12.
World J Surg Oncol ; 17(1): 184, 2019 Nov 09.
Artigo em Inglês | MEDLINE | ID: mdl-31706333

RESUMO

BACKGROUND: Traumatic ulcerative granuloma with stromal eosinophilia (TUGSE) is a rare self-limiting condition of the oral mucosa. The lesion manifests as an isolated ulcer that can be either asymptomatic or associated with mild to severe pain, and in most cases, it affects the tongue. TUGSE lesions may mimic malignancy such as squamous cell carcinoma, CD30 positive lymphoproliferative disorder, or infectious diseases such as primary syphilis, tuberculosis, or Epstein-Barr virus mucocutaneous ulcer. Histologically dominating cells are lymphocytes, histiocytes, and eosinophils. CASE PRESENTATION: We describe a TUGSE case of a patient with a solitary ulcer on the lower left retromolar buccal plane. Upon presentation, the patient reported a swelling on the buccal mucosa of the left lower jaw since 1 year with rapid growth over the last days and mild pain while chewing. The diameter of the intraoral lesion on the lower left retromolar buccal plane was approximately 4 × 3 cm; the lesion presented as indurated base with a central superficial ulceration of 2 × 1 cm, indicative for a malignant process. Histologically, the ulceration showed an expanding, infiltrative, and vaguely granulomatous morphology, involving the superficial mucosa and the fatty tissue, and extended between the deep striated muscle fibers. The lesion was rich in lymphocytes, histiocytes, and eosionophils intermingled with activated T-blasts without phenotypic abnormalities. TUGSE was then diagnosed based on the phenotype (especially the lacking expression of CD30, the retained T-cell phenotype, and the absence of Epstein-Barr virus), the clinical presentation, and the morphology. Twenty-six months after diagnosis, no recurrence of the ulceration was seen. CONCLUSIONS: As TUGSE may mimic malignancy or infectious diseases, biopsy is mandatory and should be combined with thorough clinical examination. A screening for infectious diseases (mainly syphilis, Epstein-Barr virus, and HIV infections) must be performed routinely. In most cases, the lesions resolve spontaneously, obviating the need of further actions other than clinical follow-up. The pathogenesis of TUGSE lesions is still under debate, although local traumatic events and a locotypic immune response have been suggested to be major contributing factors.


Assuntos
Granuloma Eosinófilo/diagnóstico , Mucosa Bucal/lesões , Úlceras Orais/diagnóstico , Doenças Raras/diagnóstico , Carcinoma de Células Escamosas/diagnóstico , Diagnóstico Diferencial , Granuloma Eosinófilo/etiologia , Granuloma Eosinófilo/patologia , Infecções por Vírus Epstein-Barr/diagnóstico , Humanos , Masculino , Pessoa de Meia-Idade , Mucosa Bucal/patologia , Neoplasias Bucais/diagnóstico , Úlceras Orais/etiologia , Úlceras Orais/patologia , Doenças Raras/etiologia , Doenças Raras/patologia , Remissão Espontânea , Sífilis/diagnóstico , Tuberculose/diagnóstico
13.
PLoS Med ; 16(11): e1002966, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31751330

RESUMO

BACKGROUND: Rare diseases affect as many as 60 million people in the United States and Europe. However, most rare diseases lack effective therapies and are in critical need of clinical research. Our objective was to determine the frequency of noncompletion and nonpublication of trials studying rare diseases. METHODS AND FINDINGS: We conducted a cross-sectional analysis of randomized clinical trials studying rare diseases as defined by the Genetic and Rare Disease Information Center database that were registered in ClinicalTrials.gov between January 1, 2010, and December 31, 2012, and completed or discontinued by December 31, 2014. Our main outcome measures were the frequency of trial noncompletion and, among completed studies, frequency of trial nonpublication at 2 and 4 years following trial completion. Reasons for discontinuation were extracted from the registry, and trial sponsors were contacted for additional information, as needed. Two independent investigators performed publication searches for each trial in PubMed, EMBASE, and GoogleScholar, allowing for a minimum of 45 months between trial completion and publication. When a publication could not be identified, trial sponsors were contacted to confirm publication status. The impact of funding source on trial noncompletion was assessed with multivariable logistic regression, and the effect on time to publication was examined with Cox proportional hazards regression. Control variables included intervention type, trial phase, masking, enrollment, and study population. We analyzed 659 rare disease trials accounting for 70,305 enrolled patients. Industry was the primary funder for 327 trials (49.6%) and academic institutions for 184 trials (27.9%). There were 79 trials (12.0%) focused on pediatric populations. A total of 199 trials (30.2%) were discontinued. Lack of patient accrual (n = 64, 32.1%) and informative termination (n = 41, 20.6%) were the most common reasons for trial noncompletion. Among completed trials, 306 (66.5%) remained unpublished at 2 years and 142 (31.5%) at 4 years. In multivariable analyses, industry-funded trials were less likely to be discontinued than trials funded by healthcare centers (odds ratio [OR] 2.42; 95% confidence interval [CI] 1.34-4.39, P = 0.003). We found no significant association between funding source and time to publication. A total of 18,148 patients were enrolled in trials that were discontinued or unpublished 4 years after completion. A potential limitation of our study is that certain interventional trials for rare diseases may not have been registered in ClinicalTrials.gov, in particular Phase 0 and Phase I trials, which are not required to be registered. CONCLUSIONS: In this study, over half of clinical trials initiated for rare diseases were either discontinued or not published 4 years after completion, resulting in large numbers of patients with rare diseases exposed to interventions that did not lead to informative findings. Concerted efforts are needed to ensure that participation of patients in rare disease trials advances scientific knowledge and treatments for rare diseases.


Assuntos
Editoração/tendências , Doenças Raras/etiologia , Projetos de Pesquisa/tendências , Ensaios Clínicos como Assunto , Estudos Transversais , Bases de Dados Factuais , Humanos , Modelos Logísticos , Manuscritos como Assunto , Razão de Chances , Publicações , Sistema de Registros , Estados Unidos
14.
Genes (Basel) ; 10(10)2019 10 12.
Artigo em Inglês | MEDLINE | ID: mdl-31614842

RESUMO

Network biology has the capability to integrate, represent, interpret, and model complex biological systems by collectively accommodating biological omics data, biological interactions and associations, graph theory, statistical measures, and visualizations. Biological networks have recently been shown to be very useful for studies that decipher biological mechanisms and disease etiologies and for studies that predict therapeutic responses, at both the molecular and system levels. In this review, we briefly summarize the general framework of biological network studies, including data resources, network construction methods, statistical measures, network topological properties, and visualization tools. We also introduce several recent biological network applications and methods for the studies of rare diseases.


Assuntos
Biologia Computacional/métodos , Doenças Raras/genética , Software , Algoritmos , Bases de Dados Genéticas , Redes Reguladoras de Genes , Humanos , Modelos Biológicos , Mapas de Interação de Proteínas/genética , Doenças Raras/etiologia , Doenças Raras/imunologia , Doenças Raras/metabolismo
15.
G Ital Nefrol ; 36(5)2019 Sep 24.
Artigo em Inglês | MEDLINE | ID: mdl-31580546

RESUMO

Calcific uremic arteriolopathy (CUA) is a highly morbid condition usually found in ESRD patients that has rarely been reported after renal transplantation and renal function restoration. Furthermore, little is known about the optimal management of CUA in this setting. Herein, we report on the clinical case of AB, a 70-year-old woman who developed CUA after renal transplantation and renal function restoration. However, other risk factors for CUA such as diabetes and warfarin treatment, due to mechanical aortic valve implantation, were present. Thirty-eight months after renal transplantation she developed erythema and livedo reticularis in both legs and a gradually enlarging skin ulcer in the right leg. A skin biopsy of the ulcer showed features compatible with the CUA, such as sub-intimal calcification and luminal obstruction of the small dermal arterioles, tissue ischemia and signs of adipocytes degeneration. A multidisciplinary approach was adopted, including medical and non-medical treatments such as surgical debridement and vacuum-assisted closure therapy. Medical treatments included a five weeks course of once a week intravenous infusion of pamidronate and intravenous sodium thiosulfate (STS) at increasing doses. Four months after beginning the therapy with STS, a complete healing of the ulcer on the right leg and the disappearance of the livedo reticularis on the left leg was noted. In conclusion, although rare CUA may develop also in renal transplanted patients, a timely and combined therapeutic approach is essential for its resolutive treatment. Sodium thiosulfate therapy has proven to be effective and tolerated.


Assuntos
Calciofilaxia/terapia , Transplante de Rim/efeitos adversos , Úlcera da Perna/terapia , Doenças Raras/terapia , Idoso , Anticoagulantes/uso terapêutico , Conservadores da Densidade Óssea/administração & dosagem , Calciofilaxia/etiologia , Quelantes/administração & dosagem , Terapia Combinada/métodos , Diabetes Mellitus , Feminino , Humanos , Úlcera da Perna/etiologia , Livedo Reticular/etiologia , Livedo Reticular/terapia , Pamidronato/administração & dosagem , Doenças Raras/etiologia , Fatores de Risco , Tiossulfatos/administração & dosagem , Varfarina/uso terapêutico
17.
BMC Nephrol ; 20(1): 323, 2019 08 16.
Artigo em Inglês | MEDLINE | ID: mdl-31419960

RESUMO

BACKGROUND: Patients with end-stage renal disease (ESRD) under hemodialysis (HD) are at greater risks of infectious spondylitis (IS), but there is no reliable predictor that facilitate early detection of this relatively rare and insidious disease. METHODS: A retrospective review of the medical records from patients with ESRD under HD over a 12-year period was performed at a tertiary teaching hospital, and those with a first-time diagnosis of IS were identified. A 1:4 propensity score-matched case-control study was carried out, and baseline characteristics, underlying diseases, and laboratory data were compared between the study group and the control group, one month before the date of diagnosis or the index date respectively. RESULTS: A total of 16 patients with IS were compared with 64 controls. After adjustment, recent access operation (odds ratio [OR], 13.27; 95% confidence interval [CI], 3.53 to 49.91; p <  0.001), degenerative spinal disease (OR, 12.87; 95% CI, 1.89 to 87.41; p = 0.009), HD through a tunneled cuffed catheter (OR, 6.75; 95% CI, 1.74 to 26.14; p = 0.006), low serum levels of hemoglobin, albumin, as well as high levels of red blood cell volume distribution width (RDW), alkaline phosphatase (ALP), and high sensitivity C-reactive protein were significant predictors for a IS diagnosis one month later. Receiver operating characteristic curves for hemoglobin, RDW, ALP, and albumin all showed good discrimination. The further multivariate models identified both high serum ALP levels and low serum RDW levels following a recent access intervention in patients with relatively short HD vintages may be indicative of the development of IS. CONCLUSION: Patients under HD with relatively short HD vintages showing either elevated ALP levels or low RDW levels following a recent access intervention should prompt clinical awareness about IS for timely diagnosis.


Assuntos
Infecções Bacterianas/diagnóstico , Falência Renal Crônica/terapia , Doenças Raras/diagnóstico , Diálise Renal/efeitos adversos , Espondilite/diagnóstico , Adulto , Fosfatase Alcalina/sangue , Biomarcadores/sangue , Proteína C-Reativa/análise , Estudos de Casos e Controles , Volume de Eritrócitos , Feminino , Hemoglobina A/análise , Humanos , Masculino , Pessoa de Meia-Idade , Pontuação de Propensão , Curva ROC , Doenças Raras/etiologia , Diálise Renal/instrumentação , Estudos Retrospectivos , Sensibilidade e Especificidade , Espondilite/etiologia
18.
J Am Acad Dermatol ; 81(3): 813-822, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31331726

RESUMO

BACKGROUND: Erythema multiforme (EM) is an acute inflammatory mucocutaneous condition. EM is rarely described in children and infants. OBJECTIVE: To investigate the triggers, clinical manifestations, and treatment of pediatric EM. METHODS: Systematic literature review of pediatric EM. RESULTS: After full-text article review, we included 113 articles, representing 580 patients. The mean age was 5.6 years, ranging 0.1-17 years. Infectious agents were the main triggers: herpes simplex virus (HSV) in 104 patients (17.9%) and Mycoplasma pneumoniae in 91 patients (15.7%). In total, 140 cases (24.1%) were drug-related and 89 cases (15.3%) had other triggers, such as vaccines (19 patients, 3.2%). In total, 229 patients had EM major (39.5%). Treatment was supportive care only (180 patients, 31.1%), systemic corticosteroids (115 patients, 19.8%), antivirals (85 patients, 14.6%), and antibiotics (66 patients, 11.3%), mostly macrolides (45 patients, 7.7%). Long-term sequelae were rare (1.3%). Pediatric EM was reported in 19 infants (3.2%). The main trigger was vaccination (9 patients). Infantile EM was EM major in 2 cases and EM minor in 17. Infants were less prone to develop EM major than older children (P < .01). Pediatric EM was recurrent in 83 cases (14.3%), which was triggered by HSV in 36 patients (61%). Recurrence affected older children. LIMITATIONS: Potential confusion between Steven Johnson syndrome and EM major in addition to publication bias. CONCLUSION: Pediatric EM is a rare disease, mainly triggered by infections. This condition can affect all mucosal surfaces, most commonly the oral mucosae. The diagnosis is clinical, and management relies on supportive care. Vaccines are a particular trigger in infants. Recurrent cases are most commonly linked to HSV. Dermatologists and pediatricians should be aware of this potentially recurrent and severe condition.


Assuntos
Eritema Multiforme/etiologia , Cuidados Paliativos/métodos , Doenças Raras/etiologia , Vacinação/efeitos adversos , Adolescente , Fatores Etários , Antibacterianos/uso terapêutico , Antivirais/uso terapêutico , Criança , Pré-Escolar , Diagnóstico Diferencial , Erupção por Droga/diagnóstico , Erupção por Droga/etiologia , Erupção por Droga/terapia , Eritema Multiforme/diagnóstico , Eritema Multiforme/terapia , Glucocorticoides/uso terapêutico , Herpes Simples/complicações , Herpes Simples/tratamento farmacológico , Humanos , Lactente , Mucosa Bucal/microbiologia , Mucosa Bucal/patologia , Pneumonia por Mycoplasma/complicações , Pneumonia por Mycoplasma/tratamento farmacológico , Doenças Raras/diagnóstico , Doenças Raras/terapia , Recidiva , Índice de Gravidade de Doença
19.
BMC Cancer ; 19(1): 592, 2019 Jun 17.
Artigo em Inglês | MEDLINE | ID: mdl-31208361

RESUMO

BACKGROUND: Pulmonary sarcomatoid carcinoma (SC) consists of both carcinomatous and sarcomatous tumors with high degree of malignancy, rapid progression, and poor prognosis. However, little is known regarding how pulmonary SC develops and progresses. CASE PRESENTATION: A 66-year-old male was initially diagnosed with stage IIIa lung cancer containing both adenocarcinoma (ADC) and SC. Adjuvant chemotherapy was administrated post-surgery, however, recurrence with SC only soon followed. Mutation profiling of the patient's microdissected ADC and SC components of the primary lesion and recurrent tumor was performed by targeted next-generation sequencing (NGS) of 416 cancer-relevant genes. Our data showed that primary SC/ADC and the recurrent SC shared multiple gene mutations including EGFR, NF1, TP53, CDKN2B, and SMARCA4, while both primary and recurrent SCs had a unique TP53 exon 4 splicing mutation frequently observed in sarcoma. Interestingly, a novel PHF20-NTRK1 fusion was acquired in the recurrent SC, which may be a potential driver for SC recurrence. CONCLUSIONS: The molecular genetic characteristics of tumor tissues at different stages reveals a linear tumor evolution model in this case, and support that the primary SC derived from the original lung ADC during the evolution of the tumor. We also identified a novel PHF20-NTRK1 fusion, which may contribute to the disease recurrence, and that can be potentially targeted with NTRK1 inhibitors for treatment.


Assuntos
Adenocarcinoma de Pulmão/complicações , Antígenos de Neoplasias/genética , Biomarcadores Tumorais/genética , Carcinossarcoma/etiologia , Fusão Gênica , Neoplasias Pulmonares/complicações , Doenças Raras/etiologia , Receptor trkA/genética , Adenocarcinoma de Pulmão/tratamento farmacológico , Adenocarcinoma de Pulmão/radioterapia , Adenocarcinoma de Pulmão/cirurgia , Idoso , Carcinogênese , Carcinossarcoma/tratamento farmacológico , Carcinossarcoma/radioterapia , Carcinossarcoma/cirurgia , Quimioterapia Adjuvante , Proteínas de Ligação a DNA , Éxons/genética , Evolução Fatal , Humanos , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/radioterapia , Neoplasias Pulmonares/cirurgia , Masculino , Recidiva Local de Neoplasia , Doenças Raras/tratamento farmacológico , Doenças Raras/radioterapia , Doenças Raras/cirurgia , Fatores de Transcrição
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