Hospital de Santa Maria
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Multicentric Genome-Wide Association Study for Primary Spontaneous Pneumothorax
No full textDespite elevated incidence and recurrence rates for Primary Spontaneous Pneumothorax (PSP), little is known about its etiology, and the genetics of idiopathic PSP remains unexplored. To identify genetic variants contributing to sporadic PSP risk, we conducted the first PSP genome-wide association study. Two replicate pools of 92 Portuguese PSP cases and of 129 age- and sex-matched controls were allelotyped in triplicate on the Affymetrix Human SNP Array 6.0 arrays. Markers passing quality control were ranked by relative allele score difference between cases and controls (|RASdiff|), by a novel cluster method and by a combined Z-test. 101 single nucleotide polymorphisms (SNPs) were selected using these three approaches for technical validation by individual genotyping in the discovery dataset. 87 out of 94 successfully tested SNPs were nominally associated in the discovery dataset. Replication of the 87 technically validated SNPs was then carried out in an independent replication dataset of 100 Portuguese cases and 425 controls. The intergenic rs4733649 SNP in chromosome 8 (between LINC00824 and LINC00977) was associated with PSP in the discovery (P = 4.07E-03, ORC[95% CI] = 1.88[1.22-2.89]), replication (P = 1.50E-02, ORC[95% CI] = 1.50[1.08-2.09]) and combined datasets (P = 8.61E-05, ORC[95% CI] = 1.65[1.29-2.13]). This study identified for the first time one genetic risk factor for sporadic PSP, but future studies are warranted to further confirm this finding in other populations and uncover its functional role in PSP pathogenesis
Variations in multiple sclerosis practice within Europe - Is it time for a new treatment guideline?
Get PDFIn the past 5 years, the combination of developments in diagnostic strategy and approval of new disease-modifying therapies has provided an opportunity to achieve dramatic improvements in patient outcomes in multiple sclerosis (MS). However, across Europe there are several factors that may prevent patients from receiving the best therapy at the appropriate time, and there is variation among countries in terms of which of these factors are most relevant. Here, we review current MS clinical practices in a number of countries in the European Union to identify differences regarding initiation of treatment in patients with clinically isolated syndrome or relapsing-remitting MS, and differences in the timing of treatment switch or escalation. While recognizing that policy is not static in any country, we believe that patients' interests would be better served if a European treatment guideline was developed. Such a guideline could both inform and be informed by national policies, facilitating the dissemination of best clinical practice internationally.info:eu-repo/semantics/publishedVersio
Do you know this syndrome? Dyspigmentation along the Blaschko lines caused by trisomy 7 mosaicism
Get PDFDyspigmentation along the Blaschko lines is strongly suggestive of a mosaic skin disorder. We report a 9-year-old male patient who presented with swirls and streaks of both hypo and hyperpigmentation involving the entire body. Additionally, he had hypertrichosis, musculoskeletal and minor neurodevelopment abnormalities but no intellectual disability. Cultured fibroblast displayed trisomy 7 mosaicism, which can explain this pigmentary phenotype. Widespread dyspigmentation associated with involvement of other organs should prompt systemic examination to detect additional anomalies and genetic evaluation should be considered, even with normal fetal karyotype.info:eu-repo/semantics/publishedVersio
Symptomatic bilateral coronary artery fistula to pulmonary artery in elderly patient
No full textWe report the imaging findings of an uncommon coronary vascular termination anomaly, with fistula to the pulmonary artery. This 70 year old female patient presented unstable angina, showing a coronary artery fistula depicted in coronary angiogram from the left coronary to the pulmonary artery, with no significant atherosclerotic pathology. Due to development of ventricular tachycardia in stress echocardiogram examination, she was proposed for coronary fistula closure. Coronary CT was performed for procedure planning and allowed the identification of a second unsuspected fistula from the right coronary to the right pulmonary artery. Congenital coronary anomalies are a possible cause of symptomatic coronary pathology in patients of any age. In older patients, coronary artery fistulas are rare, especially when symptomatic. Adequately performed CT examinations, using its post processing capabilities, with 3D and MIP reconstructions are invaluable in delineating coronary anatomy, essential for further treatment planning.info:eu-repo/semantics/publishedVersio
Phenotyping GABA transaminase deficiency: a case description and literature review
Get PDFGamma-aminobutyric acid transaminase (GABA-T) deficiency is an autosomal recessive disorder reported in only three unrelated families. It is caused by mutations in the ABAT gene, which encodes 4-aminobutyrate transaminase, an enzyme of GABA catabolism and mitochondrial nucleoside salvage. We report the case of a boy, deceased at 12 months of age, with early-onset epileptic encephalopathy, severe psychomotor retardation, hypotonia, lower-limb hyporeflexia, central hypoventilation, and rapid increase in weight and, to a lesser rate, length and head circumference. He presented signs of premature pubarche, thermal instability, and water-electrolyte imbalance. Serum total testosterone was elevated (43.3 ng/dl; normal range T (p.Gln296His),not previously described. In vitro analysis concluded that this variant is pathogenic. The clinical features of this patient are similar to those reported so far in GABA-T deficiency. However, distinct mutations may have a different effect on enzymatic activity, which potentially could lead to a variable clinical outcome. Clinical investigation aiming for a diagnosis should not end with the patient's death, as it may allow a more precise genetic counselling for the family.info:eu-repo/semantics/publishedVersio
Groove Pancreatitis with Biliary and Duodenal Stricture: An Unusual Cause of Obstructive Jaundice
Get PDFINTRODUCTION:
Groove pancreatitis is an uncommon cause of chronic pancreatitis that affects the groove anatomical area between the head of the pancreas, duodenum, and common bile duct.
CLINICAL CASE:
A 67-year-old man with frequent biliary colic and an alcohol consumption of 30-40 g/day was admitted to the hospital complaining of jaundice and pruritus. Laboratory analysis revealed cholestasis and the ultrasound scan showed intra-hepatic biliary ducts dilatation, middle third cystic dilatation of common bile duct, enlarged Wirsung and pancreatic atrophy. The magnetic resonance cholangiopancreatography showed imaging findings compatible with groove pancreatitis. An esophagogastroduodenoscopy later excluded duodenal neoplasia. He was submitted to a Roux-en-Y cholangiojejunostomy because of common bile duct stricture. Five months later a gastrojejunostomy was performed due to a duodenal stricture. The patient remains asymptomatic during follow-up.
DISCUSSION:
Groove pancreatitis is a benign cause of obstructive jaundice, whose main differential diagnosis is duodenal or pancreatic neoplasia. When this condition causes duodenal or biliary stricture, surgical treatment can be necessary.info:eu-repo/semantics/publishedVersio
Genotype-phenotype correlation in a cohort of Portuguese patients comprising the entire spectrum of VWD types: impact of NGS
Get PDFThe diagnosis of von Willebrand disease (VWD), the most common inherited bleeding disorder, is characterised by a variable bleeding tendency and heterogeneous laboratory phenotype. The sequencing of the entire VWF coding region has not yet become a routine practice in diagnostic laboratories owing to its high costs. Nevertheless, next-generation sequencing (NGS) has emerged as an alternative to overcome this limitation. We aimed to determine the correlation of genotype and phenotype in 92 Portuguese individuals from 60 unrelated families with VWD; therefore, we directly sequenced VWF. We compared the classical Sanger sequencing approach and NGS to assess the value-added effect on the analysis of the mutation distribution in different types of VWD. Sixty-two different VWF mutations were identified, 27 of which had not been previously described. NGS detected 26 additional mutations, contributing to a broad overview of the mutant alleles present in each VWD type. Twenty-nine probands (48.3 %) had two or more mutations; in addition, mutations with pleiotropic effects were detected, and NGS allowed an appropriate classification for seven of them. Furthermore, the differential diagnosis between VWD 2B and platelet type VWD (n = 1), Bernard-Soulier syndrome and VWD 2B (n = 1), and mild haemophilia A and VWD 2N (n = 2) was possible. NGS provided an efficient laboratory workflow for analysing VWF. These findings in our cohort of Portuguese patients support the proposal that improving VWD diagnosis strategies will enhance clinical and laboratory approaches, allowing to establish the most appropriate treatment for each patient
Accelerated age-related olfactory decline among type 1 Usher patients
No full textUsher Syndrome (USH) is a rare disease with hearing loss, retinitis pigmentosa and, sometimes, vestibular dysfunction. A phenotype heterogeneity is reported. Recent evidence indicates that USH is likely to belong to an emerging class of sensory ciliopathies. Olfaction has recently been implicated in ciliopathies, but the scarce literature about olfaction in USH show conflicting results. We aim to evaluate olfactory impairment as a possible clinical manifestation of USH. Prospective clinical study that included 65 patients with USH and 65 normal age-gender-smoking-habits pair matched subjects. A cross culturally validated version of the Sniffin' Sticks olfaction test was used. Young patients with USH have significantly better olfactory scores than healthy controls. We observe that USH type 1 have a faster ageing olfactory decrease than what happens in healthy subjects, leading to significantly lower olfactory scores in older USH1 patients. Moreover, USH type 1 patients showed significantly higher olfactory scores than USH type 2, what can help distinguishing them. Olfaction represents an attractive tool for USH type classification and pre diagnostic screening due to the low cost and non-invasive nature of the testing. Olfactory dysfunction should be considered among the spectrum of clinical manifestations of Usher syndrome
Minimally invasive repair of Morgagni hernia - A multicenter case series
Get PDFChildren may benefit from minimally invasive surgery (MIS) in the correction of Morgagni hernia (MH). The present study aims to evaluate the outcome of MIS through a multicenter study. National institutions that use MIS in the treatment of MH were included. Demographic, clinical and operative data were analyzed. Thirteen patients with MH (6 males) were operated using similar MIS technique (percutaneous stitches) at a mean age of 22.2±18.3 months. Six patients had chromosomopathies (46%), five with Down syndrome (39%). Respiratory complaints were the most common presentation (54%). Surgery lasted 95±23min. In none of the patients was the hernia sac removed; prosthesis was never used. In the immediate post-operative period, 4 patients (36%) were admitted to intensive care unit (all with Down syndrome); all patients started enteral feeds within the first 24h. With a mean follow-up of 56±16.6 months, there were two recurrences (18%) at the same institution, one of which was repaired with an absorbable suture; both with Down syndrome. The application of MIS in the MH repair is effective even in the presence of comorbidities such as Down syndrome; the latter influences the immediate postoperative recovery and possibly the recurrence rate. Removal of hernia sac does not seem necessary. Non-absorbable sutures may be more appropriate
Glucose uptake and lipid metabolism are impaired in epicardial adipose tissue from heart failure patients with or without diabetes
Get PDFType 2 diabetes mellitus is a complex metabolic disease, and cardiovascular disease is a leading complication of diabetes. Epicardial adipose tissue surrounding the heart displays biochemical, thermogenic, and cardioprotective properties. However, the metabolic cross-talk between epicardial fat and the myocardium is largely unknown. This study sought to understand epicardial adipose tissue metabolism from heart failure patients with or without diabetes. We aimed to unravel possible differences in glucose and lipid metabolism between human epicardial and subcutaneous adipocytes and elucidate the potential underlying mechanisms involved in heart failure. Insulin-stimulated [(14)C]glucose uptake and isoproterenol-stimulated lipolysis were measured in isolated epicardial and subcutaneous adipocytes. The expression of genes involved in glucose and lipid metabolism was analyzed by reverse transcription-polymerase chain reaction in adipocytes. In addition, epicardial and subcutaneous fatty acid composition was analyzed by high-resolution proton nuclear magnetic resonance spectroscopy. The difference between basal and insulin conditions in glucose uptake was significantly decreased (P= 0.006) in epicardial compared with subcutaneous adipocytes. Moreover, a significant (P< 0.001) decrease in the isoproterenol-stimulated lipolysis was also observed when the two fat depots were compared, and it was strongly correlated with lipolysis, lipid storage, and inflammation-related gene expression. Moreover, the fatty acid composition of these tissues was significantly altered by diabetes. These results emphasize potential metabolic differences between both fat depots in the presence of heart failure and highlight epicardial fat as a possible therapeutic target in situ in the cardiac microenvironment.info:eu-repo/semantics/publishedVersio