RESUMO
BACKGROUND: Low-dose aspirin can cause gastric and duodenal ulceration, hereafter called peptic ulcer disease (PUD). Predisposition is thought to be related to clinical and genetic factors; our aim was to identify genetic risk factors associated with aspirin-induced PUD. METHODS: Patients (n=1478) were recruited from 15 UK hospitals. Cases (n=505) were defined as patients with endoscopically confirmed PUD within 2 weeks of using aspirin and non-aspirin Non-Steroidal Anti-Inflammatory Drugs (NSAIDs). They were compared to two control groups: patients with endoscopically confirmed PUD without any history of NSAID use within 3 months of diagnosis (n=495), and patients with no PUD on endoscopy (n=478). A genome-wide association study (GWAS) of aspirin-induced cases (n=247) was compared to 476 controls. The results were validated by replication in another 84 cases and 162 controls. FINDINGS: The GWAS identified one variant, rs12678747 (p=1·65×10-7) located in the last intron of EYA1 on chromosome 8. The association was replicated in another sample of 84 PUD patients receiving aspirin (p=0·002). Meta-analysis of discovery and replication cohort data for rs12678747, yielded a genome-wide significant association (p=3·12×10-11; OR=2·03; 95% CI 1·65-2·50). Expression of EYA1 was lower at the gastric ulcer edge when compared with the antrum. INTERPRETATION: Genetic variation in an intron of the EYA1 gene increases the risk of endoscopically confirmed aspirin-induced PUD. Reduced EYA1 expression in the upper gastrointestinal epithelium may modulate risk, but the functional basis of this association will need mechanistic evaluation. FUNDING: Department of Health Chair in Pharmacogenetics, MRC Centre for Drug Safety Science and the Barts Cardiovascular NIHR Biomedical Research Centre, British Heart Foundation (BHF).
Assuntos
Aspirina/efeitos adversos , Peptídeos e Proteínas de Sinalização Intracelular/genética , Proteínas Nucleares/genética , Úlcera Péptica/genética , Polimorfismo de Nucleotídeo Único , Proteínas Tirosina Fosfatases/genética , Idoso , Idoso de 80 Anos ou mais , Estudos de Casos e Controles , Regulação para Baixo , Endoscopia Gastrointestinal , Feminino , Predisposição Genética para Doença , Estudo de Associação Genômica Ampla , Humanos , Íntrons , Masculino , Pessoa de Meia-Idade , Úlcera Péptica/induzido quimicamente , Úlcera Péptica/patologia , Reino UnidoAssuntos
Endossonografia , Cisto Pancreático/diagnóstico por imagem , Doença de von Hippel-Lindau/diagnóstico , Adulto , Feminino , Humanos , Cisto Pancreático/etiologia , Cisto Pancreático/terapia , Valor Preditivo dos Testes , Tomografia Computadorizada por Raios X , Doença de von Hippel-Lindau/complicações , Doença de von Hippel-Lindau/terapiaRESUMO
Background. Percutaneous endoscopic gastrostomy (PEG) placement using the "pull" technique is commonly utilized for providing nutritional support in head and neck cancer (HNC) patients, but it may be complicated by peristomal metastasis in up to 3% of patients. Overtube-assisted PEG placement might reduce this risk. However, this technique has not been systemically studied for this purpose to date. Methods. Retrospective analysis of consecutive patients with HNC who underwent overtube-assisted PEG placement at Westmead Hospital, Australia, between June 2011 and December 2013. Data were extracted from patients' endoscopy reports and case notes. We present our technique for PEG insertion and discuss the feasibility and safety of this method. Results. In all 53 patients studied, the PEG tubes were successfully placed using 25 cm long flexible overtubes, in 89% prophylactically (before commencing curative chemoradiotherapy), and in 11% reactively (for treatment of tumor related dysphagia or weight loss). During a median follow-up period of 16 months, 3 (5.7%) patients developed peristomal infection and 3 others developed self-limiting peristomal pain. There were no cases of overtube-related adverse events or overt cutaneous metastases observed. Conclusions. Overtube-assisted PEG placement in patients with HNC is a feasible, simple, and safe technique and might be effective for preventing cutaneous metastasis.
RESUMO
Endosonography (EUS)-guided drainage of paragastric fluid collections using fully covered self-expanding metal stents (FCSEMS) is now a well-established procedure. Recently, new and specially designed lumen-apposing, fully-covered metal cystgastrostomy stents have been employed for this indication. In this case series, the use of these new stents for the drainage of malignant fluid collections in three symptomatic patients is described. Cases included a large pancreatic pseudocyst, secondary to underlying acute lymphoblastic leukemia, and two large collections of loculated ascites due to metastatic ovarian and cervical cancer, respectively. Technical success in inserting the new stents was achieved in all three patients, and resulted in symptomatic relief. There were no clinically significant complications directly attributed to the stents. These new lumen-apposing cystgastrostomy stents may provide a viable, minimally invasive, and effective alternative for drainage of malignant fluid collections, either for definitive treatment or for palliation of symptoms.
Assuntos
Líquido Ascítico , Carcinoma/complicações , Drenagem/instrumentação , Neoplasias Ovarianas/complicações , Pseudocisto Pancreático/cirurgia , Stents , Neoplasias do Colo do Útero/complicações , Adulto , Idoso , Carcinoma/secundário , Criança , Drenagem/métodos , Endossonografia , Feminino , Humanos , Neoplasias Ovarianas/patologia , Ultrassonografia de Intervenção , Neoplasias do Colo do Útero/patologiaAssuntos
Transplante de Rim , Hepatopatias/diagnóstico , Hepatopatias/etiologia , Tuberculose Miliar/complicações , Tuberculose Miliar/diagnóstico , Biópsia , Osso e Ossos/diagnóstico por imagem , Osso e Ossos/patologia , Histocitoquímica , Humanos , Hospedeiro Imunocomprometido , Fígado/diagnóstico por imagem , Fígado/patologia , Hepatopatias/patologia , Masculino , Microscopia , Pessoa de Meia-Idade , Tomografia por Emissão de Pósitrons , Radiografia , Baço/diagnóstico por imagem , Baço/patologia , Tuberculose Miliar/patologiaAssuntos
Dor Abdominal/etiologia , Cisto do Colédoco/complicações , Febre/etiologia , Icterícia/etiologia , Período Pós-Prandial , Dor Abdominal/diagnóstico , Colangiopancreatografia por Ressonância Magnética , Colangite/complicações , Colangite/diagnóstico , Cisto do Colédoco/diagnóstico , Diagnóstico Diferencial , Febre/diagnóstico , Humanos , Icterícia/diagnóstico , Masculino , Pessoa de Meia-Idade , Pancreatite/complicações , Pancreatite/diagnóstico , Tomografia Computadorizada por Raios XAssuntos
Doença Celíaca/complicações , Varizes Esofágicas e Gástricas/complicações , Hemorragia Gastrointestinal/etiologia , Doença Aguda , Varizes Esofágicas e Gástricas/diagnóstico , Varizes Esofágicas e Gástricas/etiologia , Varizes Esofágicas e Gástricas/cirurgia , Esofagoscopia , Hemorragia Gastrointestinal/diagnóstico , Hemorragia Gastrointestinal/cirurgia , Hemostase Endoscópica/métodos , Humanos , Hipertensão Portal/complicações , Ligadura/métodos , Masculino , Melena/etiologia , Pessoa de Meia-Idade , Resultado do TratamentoAssuntos
Hemorragia Gastrointestinal/etiologia , Veia Porta , Somatostatinoma/diagnóstico por imagem , Neoplasias Vasculares/diagnóstico por imagem , Trombose Venosa/diagnóstico por imagem , Varizes Esofágicas e Gástricas/diagnóstico por imagem , Varizes Esofágicas e Gástricas/etiologia , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias Pancreáticas/patologia , Veia Porta/diagnóstico por imagem , Radiografia , Somatostatinoma/complicações , Somatostatinoma/secundário , Neoplasias Vasculares/complicações , Neoplasias Vasculares/secundário , Trombose Venosa/etiologiaAssuntos
Dor Abdominal/etiologia , Ablação por Cateter/efeitos adversos , Quimioembolização Terapêutica/efeitos adversos , Enterococcus faecalis/isolamento & purificação , Febre/etiologia , Infecções por Bactérias Gram-Positivas/diagnóstico , Perfuração Intestinal/diagnóstico por imagem , Idoso , Antibacterianos/uso terapêutico , Bacteriemia/diagnóstico , Bacteriemia/etiologia , Carcinoma Hepatocelular/patologia , Carcinoma Hepatocelular/terapia , Terapia Combinada , Doxorrubicina/administração & dosagem , Duodenite/diagnóstico por imagem , Duodenite/etiologia , Duodenite/terapia , Duodeno/lesões , Evolução Fatal , Infecções por Bactérias Gram-Positivas/etiologia , Humanos , Perfuração Intestinal/etiologia , Cirrose Hepática/complicações , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas/terapia , Masculino , Microesferas , Pancreatite Necrosante Aguda/diagnóstico por imagem , Pancreatite Necrosante Aguda/etiologia , Pancreatite Necrosante Aguda/terapia , Tomografia Computadorizada por Raios XAssuntos
Abdome Agudo/etiologia , Doença Celíaca/complicações , Valva Ileocecal/patologia , Intussuscepção/diagnóstico , Causas de Morte , Feminino , Humanos , Doenças do Íleo/diagnóstico , Doenças do Íleo/etiologia , Doenças do Íleo/patologia , Ileostomia , Íleo/patologia , Íleo/cirurgia , Intussuscepção/etiologia , Intussuscepção/patologia , Pessoa de Meia-Idade , Insuficiência de Múltiplos Órgãos/etiologia , Insuficiência de Múltiplos Órgãos/mortalidade , Osteoporose/complicações , Peritonite/etiologia , Pneumoperitônio/etiologia , Pneumoperitônio/cirurgia , Choque Séptico/etiologia , Choque Séptico/mortalidade , Tomografia Computadorizada por Raios X , Deficiência de Vitamina D/complicaçõesRESUMO
Raised intracranial pressure is a feature of cerebral malaria in children living in Africa. We investigated specific clinical optic disc features of papilledema to establish their prognostic significance in this encephalopathy. We developed a classification of acute papilledema and tested it against disease outcome. Kenyan children admitted with severe falciparum malaria (cerebral or impaired consciousness) underwent dilated fundal examination using direct and indirect ophthalmoscopy. Clinical features of the optic disc were systematically recorded and compared to the child's outcome. Poor outcome defined as death or neurological impairment on discharge was used to construct and test a clinical classification of papilledema. Forty-five children were examined (26 cerebral malaria, 17 severe malaria with an impaired conscious level or prostration) of whom seven had a poor outcome (three died, four had residual neurological impairment). Loss of the optic disc cup and marked optic disc elevation were significantly correlated with a poor outcome (P < 0.05). Increasing severity in the proposed classification of acute papilledema was positively correlated with a poor outcome (P < 0.05, chi-square test for trend). Loss of the optic disc cup and marked elevation of the optic disc head appear to be correlated with poor outcome in children with severe malaria whereas the presence of dilated veins suggests a good outcome. The proposed classification of acute papilledema is useful as a prognostic indicator and may be applicable to other encephalopathies with raised intracranial pressure.
RESUMO
Cerebral malaria is one of the most common nontraumatic encephalopathies in the world. Children living in sub-Saharan Africa bear the brunt of the disease, but cerebral malaria is being seen increasingly in adults throughout the world, including outside malarious areas. There are differences in the clinical presentation and pathophysiology between African children and nonimmune adults from any region. Mortality is high (10-20%). Parenteral antimalarials are the only interventions that have been shown to affect outcome. The cinchona alkaloids (quinine and quinidine) are the mainstay of antimalarial treatment, but the artemisinin derivatives are increasingly being used. Aggressive treatment and prevention of convulsions may be important, particularly in children. Other ancillary treatments that can be used to augment standard antimalarial drugs, such as exchange blood transfusions, osmotic diuretics and pentoxifylline, may improve outcome but have not been subjected to rigorous clinical trials. There is little support for corticosteroids or deferoxamine (desferrioxamine) in cerebral malaria. Other adjuncts have not been adequately tested. Further research is required on drugs that interfere with the pathophysiological processes to prevent neurological complications and death.