Centro Hospitalar do Porto
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Calprotectin and the Magnitude of Antibodies to Infliximab in Clinically-stable Ulcerative Colitis Patients are More Relevant Than Infliximab Trough Levels and Pharmacokinetics for Therapeutic Escalation
Get PDFAlthough infliximab (IFX) is an efficient therapy for ulcerative colitis (UC) patients, a considerably high rate of therapeutic failures still occurs. This study aimed at a better understanding of IFX pharmacokinetics and pharmacodynamics among clinically-asymptomatic UC patients. This was a multicentric and prospective study involving 65 UC patients in the maintenance phase of IFX therapy. There were no significant differences between patients with positive and negative clinical, endoscopic and histological outcomes concerning their IFX trough levels (TLs), area under the IFX concentration vs. time curve (AUC), clearance and antibodies to infliximab (ATI) levels. However, the need to undergo therapeutic escalation later in disease development was significantly associated with higher ATI levels (2.62μg/mL vs. 1.15μg/mL, p=0.028). Moreover, and after adjusting for disease severity, the HR (hazard ratio) for therapeutic escalation was significantly decreased for patients with an ATI concentration below 3μg/mL (HR=0.119, p=0.010), and increased for patients with fecal calprotectin (FC) level above 250μg/g (HR=9.309, p=0.018). In clinically-stable UC patients, IFX pharmacokinetic features cannot predict therapeutic response on a short-term basis. However, high levels of ATIs or FC may be indicative of a future therapeutic escalation.This work was supported by the Portuguese IBD Group (GEDII – Grupo de Estudo da Doença Inflamatória Intestinal). The funder had no role in study design, data collection, data analysis, interpretation and writing of the report.info:eu-repo/semantics/publishedVersio
Hepcidin is regulated by promoter-associated histone acetylation and HDAC3
Get PDFHepcidin regulates systemic iron homeostasis. Suppression of hepcidin expression occurs physiologically in iron deficiency and increased erythropoiesis but is pathologic in thalassemia and hemochromatosis. Here we show that epigenetic events govern hepcidin expression. Erythropoiesis and iron deficiency suppress hepcidin via erythroferrone-dependent and -independent mechanisms, respectively, in vivo, but both involve reversible loss of H3K9ac and H3K4me3 at the hepcidin locus. In vitro, pan-histone deacetylase inhibition elevates hepcidin expression, and in vivo maintains H3K9ac at hepcidin-associated chromatin and abrogates hepcidin suppression by erythropoietin, iron deficiency, thalassemia, and hemochromatosis. Histone deacetylase 3 and its cofactor NCOR1 regulate hepcidin; histone deacetylase 3 binds chromatin at the hepcidin locus, and histone deacetylase 3 knockdown counteracts hepcidin suppression induced either by erythroferrone or by inhibiting bone morphogenetic protein signaling. In iron deficient mice, the histone deacetylase 3 inhibitor RGFP966 increases hepcidin, and RNA sequencing confirms hepcidin is one of the genes most differentially regulated by this drug in vivo. We conclude that suppression of hepcidin expression involves epigenetic regulation by histone deacetylase 3.Hepcidin controls systemic iron levels by inhibiting intestinal iron absorption and iron recycling. Here, Pasricha et al. demonstrate that the hepcidin-chromatin locus displays HDAC3-mediated reversible epigenetic modifications during both erythropoiesis and iron deficiency.We thank Jing Jin (Jenner Institute, Oxford) for assistance with protein production. SP was supported by the NHMRC (Australia), the Haematology Society of Australia and New Zealand, The Bill and Melinda Gates Foundation, and the Cooley’s Anemia Foundation, and received training from the ASH/EHA Translational Training in Hematology Program. H.D., P.J.L., A.E.A., K.A.-H., and K.W. were supported by the Medical Research Council UK and the National Institute for Health Research Biomedical Research Centre Oxford. Production of erythroferrone and K.M. and J.A. were supported by Pfizer Ltd. C.C. and S.R. were supported by NIH-R01 DK095112 and DK090554. S.J.D. is a Jenner Investigator, a Lister Institute Research Prize Fellow and a Wellcome Trust Senior Fellow (106917/Z/15/Z). T.L.D., A.S., and G.P. were supported by Fundação para a Ciência e a Tecnologia/Ministério da Educação e Ciência and COMPETE (FCOMP-01-0124-FEDER-028447, PTDC/BIM-MET/0739/2012, SFRH/BPD/108207/2015), and by Programme NORTE 2020, under the PORTUGAL 2020 Partnership Agreement, through the FEDER (Project Norte-01-0145-FEDER-000012). D.O. was supported by ZonMw (project 11401095001). N.A. was supported by the MRC funded Oxford Consortium for Single-cell Biology (MR/M00919X/1), and the Oxford-Wellcome Trust Institutional Strategic Support Fund.info:eu-repo/semantics/publishedVersio
ACUTE DISSEMINATED ENCEPHALOMYELITIS – A CASE SERIES
Get PDFntrodução: A encefalomielite aguda disseminada (ADEM) é uma doença desmielinizante, tipicamente monofásica, do sistema nervoso central, caracterizada por alterações neurológicas ines-pecíficas e neuroimagem com lesões desmielinizantes multifocais.Objetivos: Descrever dados epidemiológicos, clínicos, labo-ratoriais, imagiológicos, tratamento e evolução de uma coorte pediátrica com diagnóstico inicial de ADEM.Materiais e Métodos: Análise retrospectiva entre 2010-2015 de crianças/adolescentes admitidas em hospital nível II.Resultados: Foram identificados onze casos, com predomí-nio do género masculino e idades entre 8 meses e 16 anos. Sete casos ocorreram no inverno/primavera. Em mais de metade dos casos havia história de patologia infeciosa recente. Sinais neu-rológicos mais frequentes: défices motores, neuropatia craniana e rigidez da nuca. Em todos os casos foram detetadas altera-ções do líquido cefalorraquidiano. Foi estabelecido diagnóstico microbiológico definitivo em duas crianças com vírus Epstein--Barr e diagnóstico provável/possível em duas crianças com infeção prévia por rotavírus e varicela. A ressonância magnética nuclear (RMN) identificou em todos os casos lesões multifocais. Todas as crianças foram submetidas a corticoterapia em altas doses. Em dois casos foi também administrada imunoglobulina humana. Verificou-se ADEM multifásica num caso, após um ano de seguimento. Em dois casos surgiram critérios de esclerose múltipla (EM). A taxa de mortalidade foi nula. Foram constatadas sequelas neurológicas em dois casos. A distinção entre ADEM e EM na altura da sua apresentação inicial permanece, em alguns casos, um desafio.Conclusões: A análise desta série de casos sugere que a pre-sença de infeção esteja associada à etiologia da ADEM. A RMN foi o estudo de escolha para diagnóstico e seguimento. O prognóstico foi excelente. A distinção entre ADEM e EM permanece um desafio.Background: Acute disseminated encephalomyelitis (ADEM) is a demyelinating monophasic disorder of the central nervous system characterized by diffuse neurologic signs and symptoms coupled with multifocal demyelinating lesions on neuroimaging.Aims: To describe the epidemiology, symptoms and signs, laboratory features, neuroimaging, treatment and outcome in a pediatric cohort with the initial diagnosis of ADEM.Methods and Materials: A retrospective review, between 2010-2015, of children/adolescents admitted at a level II hospital.Results: Eleven cases were identified with male predominance and ages between 8 months and 16 years. Seven patients presented in winter/spring. More than half of the cases had a recent infectious disease. Patients presented most often with motor deficits, cranial neuropathy and stiff neck. All patients had spinal fluid abnormalities. A definitive microbiologic diagnosis was established in two children with Epstein-Barr virus disease and probable/possible diagnosis in two children with previous rotavirus disease or varicella. Brain magnetic resonance imaging (MRI) identified multifocal lesions in every case. All patients were treated with corticosteroids, and two were also treated with human immunoglobulin. There was one case with multiphasic ADEM (after one year follow-up) and two cases developed criteria of multiple sclerosis (MS). All patients survived. Two patients had neurologic sequelae. The differential diagnosis between ADEM and MS at first presentaion may be challenging.Conclusions: Our case series suggests that infections are associated with the etiology of ADEM. MRI was the neuroimaging study of choice for diagnosis and follow-up. Prognosis was excellent. It remains difficult to differentiate ADEM and multiple sclerosis.info:eu-repo/semantics/publishedVersio
Reinternamentos Hospitalares num Serviço de Pedopsiquiatria: Taxa de Readmissão e Fatores de Risco
Get PDFINTRODUCTION:
Most mental disorders have a chronic evolution and therefore a certain amount of psychiatric readmissions are inevitable. Several studies indicate that over 25% of child and adolescent inpatients were readmitted within one year of discharge. Several risk factors for psychiatric readmissions have been reported in the literature, but the history of repeated readmissions is the most consistent risk factor. Our aim is to calculate the readmission rates at 30 days and 12 months after discharge and to identify associated risk factors.
MATERIAL AND METHODS:
The authors consulted the clinical files of patients admitted to the Inpatient Unit between 2010 and 2013, in order to calculate the readmission rates at 30 days and at 12 months. The demographic and clinical characteristics of the readmitted patients were analyzed and compared with a second group of patients with no hospital readmissions, in order to investigate possible predictors of readmission.
RESULTS:
A total of 445 patients were admitted to our inpatient unit between 2010 and 2013. Six adolescents were readmitted in a 30 days period (1.3%) and 52 were readmitted in a 12 month period after discharge (11.5%). Duration of the hospitalization and the previous number of mental health admissions were significant predictors of future hospital readmissions (p = 0.04 and p = 0.014).
DISCUSSION:
The low readmission rates may reflect the positive clinical and sociofamilial support being provided after discharge.
CONCLUSION:
Rehospitalisation is considered a fundamental target for intervention concerning prevention and intervention in mental healthcare. Thus, knowledge regarding their minimisation is crucial.Introdução: A maioria das perturbações mentais tem uma evolução crónica pelo que certos reinternamentos são inevitáveis. Vários estudos indicam taxas de reinternamento pedopsiquiátrico superiores a 25%. O nosso objetivo é calcular as taxas de readmissão no internamento pedopsiquiátrico do Centro Hospitalar do Porto a 30 dias e um ano após a alta, e identificar os fatores de risco associa¬dos.
Material e Métodos: A metodologia consistiu na consulta dos processos clínicos dos doentes internados na Unidade de Internamento do Centro Hospitalar do Porto entre 2010 e 2013, a fim de calcular as taxas de readmissão. Foram também recolhidas as característi¬cas demográficas e clínicas dos doentes readmitidos. Finalmente, os resultados do grupo de doentes reinternados foram comparados com um segundo grupo de doentes selecionados aleatoriamente e sem readmissões hospitalares, a fim de investigar possíveis fatores de risco para reinternamentos.
Resultados: Um total de 445 doentes foi admitido entre 2010 e 2013. Seis adolescentes foram readmitidos no período de 30 dias (1,3%) e 52 foram readmitidos nos 12 meses após a alta (11,5%). A análise comparativa revelou que a duração do internamento e o número de internamentos anteriores são preditores significativos (p = 0,04 e p = 0,014) para reinternamento.
Discussão: As baixas taxas de readmissão podem refletir não só a eficácia da intervenção terapêutica durante o internamento como também um bom suporte clínico e sociofamiliar após a alta.
Conclusão: Os reinternamentos são considerados um alvo fundamental quanto à prevenção e intervenção nos cuidados de saúde mental. Assim, o conhecimento sobre a sua minimização é crucial..info:eu-repo/semantics/publishedVersio
Primary vulvar Paget disease - the importance of clinical suspicion
Get PDFExtramammary Paget disease of the vulva is a rare condition that accounts for only 1-2% of vulvar malignancies and represents a frequent cause of misdiagnosis. It is most commonly seen in postmenopausal women. Clinically it is similar to Paget disease of the breast, appearing as red, well-demarcated eczematoid lesions, with slightly raised edges. A high degree of clinical suspicion is very important when evaluating these lesions in order to avoid misdiagnosis and delay of effective treatment. We present a case of vulvar Paget disease treated with vulvectomy.info:eu-repo/semantics/publishedVersio
Mediastinal Mass in a Patient with Colorectal Cancer: A Diagnostic Challenge
Get PDFThe differential diagnosis of mediastinal masses involves many benign and malignant conditions, such as lymphadenopathies and cystic lesions. Metastatic mediastinal adenopathies are usually due to lung, esophagus, and stomach cancer and, rarely, due to colorectal cancer. Gastrointestinal duplication cysts are uncommon inherited lesions usually diagnosed during childhood and may involve the esophagus in 20% of cases. In adults, they are usually asymptomatic and diagnosed incidentally. We report the case of a 54-year-old male who recently underwent sigmoidectomy due to an obstructive colon adenocarcinoma. Staging computed tomography scan showed a hypodense lesion in the posterior mediastinum suggestive of metastatic adenopathy. Endoscopic ultrasound revealed a homogeneous and hypoechogenic lesion with intramural location in the upper esophagus, suggestive of a duplication esophageal cyst. Given the oncologic background and to exclude metastatic disease, endoscopic ultrasound-guided fine needle aspiration was performed, and a mucinous fluid was aspirated. The cytologic examination supported the ultrasonographic diagnostic hypothesis. This case highlights the role of endoscopic ultrasound in the differential diagnosis of mediastinal masses, particularly in oncologic patients, in order to rule out more ominous lesions.info:eu-repo/semantics/publishedVersio
Dermatology case
No full textA esclerose tuberosa é uma síndrome neurocutânea, hereditária, autossómica dominante, caracterizada por manifestações pleomórficas envolvendo múltiplos órgãos, incluindo a pele. O diagnóstico de esclerose tuberosa é clínico. As lesões cutâneas mais comuns nestes doentes são: máculas hipopigmentadas, habitualmente com forma elíptica, os angiofibromas, tipicamente envolvendo a região malar e placas de “shagreen”, mais frequentemente localizadas à região inferior do tronco.
No caso descrito, a doente foi referenciada à consulta de dermatologia por uma lesão atípica de localização incomum, que demonstra a importância da observação de toda a pele nesta patologia.Tuberous sclerosis is an inherited neurocutaneous disorder characterized by pleomorphic features involving many organ systems, including the skin. The diagnosis of tuberous sclerosis is clinical. The most common cutaneous lesions are hypopigmented macules, also known as ash-leaf spots, which are usually elliptic in shape, angiofibromas, which typically involve the malar regions of the face, and shagreen patches, most commonly present over the lower trunk.
In the present case, the patient was referred to the dermatology department due to an atypical lesion with an uncommon location, revealing the importance of a whole body examination in patients with this disease.info:eu-repo/semantics/publishedVersio
Chronic granulomatous disease as a risk factor for cutaneous lupus in childhood
Get PDFChronic granulomatous disease (CGD) is a primaryimmunodeficiency disorder that affects the phagocyticcells of the innate immune system. It is characterizedby recurrent or persistent infections with granulomaformation. Lupus-like lesions have been reported incarriers of CGD and less frequently, in patients withCGD. Immunological study in these patients areusually negative. We describe the case of an 8-yearoldboy with CGD who developed chronic and acutecutaneous lupus erythematous with angular cheilitis,oral ulcers, Raynaud phenomenon, and positiveserologies for antinuclear, anticentromere, and anti-Saccharomyces cerevisiae antibodies.info:eu-repo/semantics/publishedVersio
Immune Reconstitution Inflammatory Syndrome: Opening Pandora's Box
Get PDFOne of the purposes of antiretroviral therapy (ART) is to restore the immune system. However, it can sometimes lead to an aberrant inflammatory response and paradoxical clinical worsening known as the immune reconstitution inflammatory syndrome (IRIS). We describe a 23-year-old male, HIV1 infected with a rapid progression phenotype, who started ART with TCD4+ of 53 cells/mm(3) (3,3%) and HIV RNA = 890000 copies/mL (6 log). Four weeks later he was admitted to the intensive care unit with severe sepsis. The diagnostic pathway identified progressive multifocal leukoencephalopathy, digestive Kaposi sarcoma, and P. aeruginosa bacteraemia. Five weeks after starting ART, TCD4+ cell count was 259 cells/mm(3) (15%) and HIV RNA = 3500 copies/mL (4 log). He developed respiratory failure and progressed to septic shock and death. Those complications might justify the outcome but its autopsy opened Pandora's box: cerebral and cardiac toxoplasmosis was identified, as well as hemophagocytic syndrome, systemic candidiasis, and Mycobacterium avium complex infection. IRIS remains a concern and eventually a barrier to ART. Male gender, young age, low TCD4 cell count, and high viral load are risk factors. The high prevalence of subclinical opportunistic diseases highlights the need for new strategies to reduce IRIS incidence.info:eu-repo/semantics/publishedVersio
Pancreas Burkitt primary lymphoma in pediatric age
Get PDFWe present an the case of an eight-year-old Portuguese boy with no history of traveling, admitted with non-specific abdominal pain. An analytic study revealed high levels of lipase and amylase. Ultrasound, abdominal computerized tomography (CT), and an abdominal magnetic resonance imaging (MRI), were performed. The imaging findings are suggestive of a pancreatic tumor which is an extremely rare entity in children. A biopsy was performed by opened surgery and identified a Burkitt lymphoma.info:eu-repo/semantics/publishedVersio